WHEN BREATHING IS a BURDEN Sinonasal Variations and Diseases Affecting the Human Skull in Three Portuguese Identified Osteological Collections (19Th-20Th Centuries)

Bruno Miguel da Silva Magalhães

WHEN BREATHING IS A BURDEN Sinonasal variations and diseases affecting the human skull in three Portuguese identified osteological collections (19th-20th centuries)

Tese de Doutoramento em Antropologia, ramo de especialização em Antropologia Biológica, orientada pela Professora Doutora Ana Luísa Santos e coorientada pelo Doutor Simon Mays e apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra

Junho 2018

Departamento de Ciências da Vida Faculdade de Ciências e Tecnologia Universidade de Coimbra

WHEN BREATHING IS A BURDEN Sinonasal variations and diseases affecting the human skull in three Portuguese identified osteological collections (19th-20th centuries)

Bruno Miguel da Silva Magalhães

Supervisor Professora Doutora Ana Luísa Santos (Universidade de Coimbra, Portugal)

Co-supervisor Dr. Simon Mays (Historic England)

Dissertation submitted to the Faculty of Sciences and Technology, University of Coimbra, in fulfilment of the requirements for the Degree of Doctor in Anthropology, specialisation in Biological Anthropology

Coimbra 2018

Cover image:

Cranium number 780, International Exchange Skull Collection (Department of Life Sciences of the University of Coimbra). Photo: Bruno M. Magalhães.

Funding:

Fundação para a Ciência e a Tecnologia, fellowship SFRH/BD/102980/2014.

Centro de Investigação em Antropologia e Saúde.

Table of contents

List of figures List of tables List of appendices Abstract and keywords Resumo e palavras-chave Acknowledgements

1. Introduction ...... 1 1.1. Sinonasal anatomy and function ...... 3

1.1.1. Nasal anatomy: the piriform aperture and the septum ...... 3 1.1.2. The turbinates, the meatuses, and the ostiomeatal complex ...... 4 1.1.3. The paranasal sinuses ...... 6

1.2. Sinonasal bony pathology ...... 9

1.2.1. Nasal trauma ...... 9 1.2.2. Pathophysiology of rhinosinusitis and rhinitis ...... 10 1.2.2.1. Etiology and predisposing factors for sinonasal inflammation ...... 14 1.2.2.2. Nasal variations and sinonasal pathology ...... 16 1.2.2.3. Sinonasal diseases and variations in Portugal during the 19th and first half of the 20th century ...... 21

1.2.3. Nasal obstruction and craniofacial morphology ...... 25 1.2.4. Other pathologies affecting the sinonasal bony anatomy ...... 27

1.3. Aims ...... 29

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2. Study base ...... 31

2.1. Sampling and study base ...... 35

2.2. Place of residence: rural or urban? ...... 38

3. Methodology ...... 41

3.1. Variations within the nasal cavity ...... 43

3.2. Nasal trauma and maxillary rhinosinusitis ...... 48

3.3. Craniofacial morphology ...... 51

3.4. Nasal variations: review of clinical literature ...... 53

3.5. Anatomical nomenclature and the Istanbul terminological framework ... 54

3.6. Statistical analysis ...... 54

4. Results and discussion ...... 57

4.1. Nasal trauma ...... 59

4.1.1. Results ...... 59

4.1.2. Discussion...... 63

4.2. Nasal osseous variations ...... 71

4.2.1. Results ...... 71

4.2.1.1. Middle turbinates: hypertrophy and paradoxical curvature ...... 71

4.2.1.2. Uncinate process: accessory turbinate ...... 76

4.2.1.3. Nasal septum: deviation and spurs ...... 78

4.2.1.4. Nasal variations and their possible relationship ...... 80

4.2.2. Discussion...... 82

4.3. Nasal cavity and maxillary sinus pathology ...... 94

4.3.1. Results ...... 94

4.3.1.1. Middle turbinate spicules ...... 94

4.3.1.2. Bone formations within the maxillary sinuses ...... 95

4.3.1.3. Testing the hypothesis of association between nasal variations and nasal and sinonasal disease ...... 99

4.3.2. Discussion...... 102

4.4. The role of concha bullosa and maxillary rhinosinusitis on craniofacial morphology ...... 115

4.4.1. Results ...... 115

4.4.2. Discussion...... 116

4.5. Miscellaneous osseous alterations on the anterior surface of the maxillary bones, nasal cavity, and hard palate ...... 121

4.5.1. Results ...... 121

4.5.2. Discussion...... 122

4.5.2.1. The anterior surface of the maxillary bones ...... 122

4.5.2.2. The nasal cavity and hard palate...... 127

5. Conclusion ...... 137

6. References ...... 143

Appendices

List of figures

1. Introduction

Figure 1. Medial (left) and lateral (right) walls of the nasal cavity (from Standring, 2008:548) ...... Plate I

Figure 2. Septum, uncinate processes, and middle and inferior turbinates within the nasal cavity ...... Plate I

Figure 3. Nasal cavity and openings to the paranasal sinuses and nasolacrimal duct ...... Plate II

Figure 4. Nasal cavity, paranasal sinuses, and nasolacrimal duct (from Drake et al., 2010:1015) ...... Plate II

Figure 5. Rhinosinusitis surgeries in the Coimbra University Hospitals between 1913 and 1939 (adapted from Magalhães et al., 2017:14) ...... 24

Figure 6. Advertisements of capsules (top left), tablets (top right), syrups (bottom left), and antiseptics (bottom right) to treat several upper and lower respiratory tract diseases in Portuguese medical journals ...... Plate III

2. Study base

Figure 7. The Medical Schools Skull Collection and the International Exchange Skull Collection are stored at the Department of Life Sciences (University of Coimbra) (top). Example of an individual data record from the Medical Schools Skull Collection (bottom) ...... Plate IV

Figure 8. The Human Identified Skeletal Collection is stored at the National Museum of Natural History and Science (Lisbon) (left). Example of an individual data record from the Human Identified Skeletal Collection (right) ...... Plate IV

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3. Methodology

Figure 9. Nasal cavities demonstrating the methodology adopted to record type 0 (top), type 1 (bottom left), and type 2 (bottom right) paradoxical curvatures of the middle turbinates ...... Plate V

Figure 10. CT scan equipment at the Coimbra Hospital and Universitary Centre (top); post-processing of 3D imaging and 2D multiplanar reformat (bottom) ...... Plate VI

Figure 11. Nasal cavity showing the normal anatomy of the uncinate process (left, arrows) and an accessory turbinate (right, arrows) ...... Plate VII

Figure 12. Nasal cavity demonstrating the septal chord (a) and septal thread length (dotted line) as recommended by Mays (2012) for measuring nasal septal deviation ...... Plate VII

Figure 13. Nasal septal deviation, type 1: unilateral deflection of the perpendicular plate of the ethmoid (PPE); the vomer (V) presents no deviation ...... Plate VIII

Figure 14. Nasal septal deviation, type 2: unilateral deviation of the vomer (V); the perpendicular plate of the ethmoid (PPE) presents no deflection ...... Plate VIII

Figure 15. Nasal septal deviation, type 3: ‘C’ (left) and ‘inverted C’ (middle and right) deviation of the ethmoid (PPE) and vomer (V). The wider deviation is at the level of the ethmoid...... Plate VIII

Figure 16. Nasal septal deviation, type 4: ‘L’ (left) and ‘inverted L’ (middle and right) deviation of the ethmoid (PPE) and vomer (V). The wider deviation is at the level of the ethmoid-vomer fusion ...... Plate IX

Figure 17. Nasal septal deviation, type 5: ‘C-type’ and ‘L-type’ deviation of the ethmoid (PPE) and vomer (V), whether unilateral or bilateral. The deviation of both septal bones presents no continuity ...... Plate IX

Figure 18. Examples of septal spurs on the ethmoid/vomer fusion ...... Plate IX

4. Results and discussion

Figure 19. Nasal trauma by sex and age at death ...... 60

Figure 20. A 70-year-old female (MSSC 173) showing a lateral impact force trauma and fracture of the frontal process of the right maxilla and both nasal bones; the nose is deviated to the left (left). A 90-year-old male (MSSC 300) presenting comminuted trauma of both nasal bones, which are deviated to the right side; the fracture resulted from a blunt impact force on the left side (right) ...... Plate X

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Figure 21. A 57-year-old male (MSSC 551) presenting bilateral trauma of the nasal bones, frontal process of the right maxilla, orbital floor and walls, as well as the displacement of the left zygomatic bone (arrows) ...... Plate X

Figure 22. Hypertrophy of the middle turbinate by sex and age at death ...... 72

Figure 23. Anterior view of the nasal area of a 75-year-old female (IESC 134) presenting a concha bullosa on the right side (left). The diagnosis was confirmed by CT scan (right) ...... Plate XI

Figure 24. Anterior view of a 28-year-old female (IESC 213, left) presenting a bilateral concha bullosa confirmed by CT scan (right) ...... Plate XI

Figure 25. Paradoxical curvature by sex and age at death ...... 75

Figure 26. Accessory turbinate by sex and age at death ...... 77

Figure 27. Septal spurs by sex and age at death ...... 80

Figure 28. Examples of the nasal variations studied ...... Plate XII

Figure 29. Examples of spicules on the middle turbinates ...... Plate XIII

Figure 30. Spicule-type bone formations on the middle turbinates by sex and age at death ...... 95

Figure 31. Bone formations within the maxillary sinuses by sex and age at death ...... 96

Figure 32. Examples of bone formations within the maxillary sinuses ...... Plate XIV

Figure 33. Traditional house in the coastal area of Coimbra with an open fire to cook in the kitchen (Oliveira and Galhano, 2000:198) ...... 109

Figure 34. Statistically significant measurements taken in the present study ...... 118

Figure 35. Bone destruction and formation within the nasal cavity by sex and age at death ...... 122

Figure 36. Bone destruction and formation on the hard palate by sex and age at death ...... 122

Figure 37. A 69-year-old male (MSSC 4; cause of death: senile cachexia) presenting bone destruction and a possible dissection into the nasolacrimal duct ...... Plate XV

Figure 38. A 58-year-old male (IESC 951; cause of death: heart disease) presenting bone destruction on the right nasolacrimal duct...... Plate XV

Figure 40. Examples of possible osteomas within the nasal cavity ...... Plate XVII

Figure 41. A 50-year-old female (MSSC 291; cause of death: neoplastic disease) presenting destruction of the right superior, middle and inferior turbinates, uncinate process, ethmoid bulla, and septum. The same structures on the left side were not affected.…...... Plate XVIII

Figure 42. A 29-year-old female (IESC 264; cause of death: purulent meningitis with suppuration channels) presenting bone destruction on both nasal bones and frontal processes of the maxillae (left), septum and nasal floor /right, arrows) . Plate XVIII

List of tables

1. Introduction

Table 1. Main functions attributed to the paranasal sinuses reviewed by Márquez (2008) and Keir (2009)...... 8

Table 2. Common bony anatomical variations of the sinonasal structures...... 17

Table 3. Examples of treatments for several of the the respiratory symptoms and diseases referred in the first series of the Portuguese journal Coimbra Médica between 1881 and 1901...... 22

Table 4. Alterations associated with nasal blockage and mouth breathing in living patients ...... 26

2. Study base

Table 5. Period of burial of the individuals of the three collections selected for this study...... 34

Table 6. Distribution of the individuals of the three collections studied by decades of birth and death...... 36

Table 7. Individuals selected for the present study by sex and age at death...... 36

Table 8. Individuals of the three collections selected for the current study by the district of birth...... 39

Table 9. Background of the individuals amassed considered for the three collections studied...... 39

3. Methodology

Table 10. List of measurements selected to evaluate craniofacial morphology...... 52

Table 11. Groups of individuals selected for testing the craniofacial morphology...... 52

4. Results and discussion

Table 12. Prevalence of nasal trauma by sex ...... 60

Table 13. Prevalence of nasal trauma by side in the individuals with both nasal bones preserved...... 61

Table 14. Patterns of fracture of the nasal bones ...... 61

Table 15. Fractured bones or anatomical areas of the face ...... 62

Table 16. Mediaeval and Postmediaeval studies reporting prevalence of nasal trauma in palaeopathological literature...... 64

Table 17. Prevalence of middle turbinate hypertrophy by sex...... 71

Table 18. Prevalence of middle turbinate hypertrophy by side and sex ...... 72

Table 19. Prevalence of middle turbinate hypertrophy by side, type, and sex...... 73

Table 20. Concha bullosa by side and type in the 60 individuals who underwent CT scan...... 73

Table 21. Percentages of agreement and κ coefficients of macroscopic and CT scan identifications of concha bullosa in the current work...... 74

Table 22. Standardised widths (mm) of concha bullosa measured by CT scan ...... 74

Table 23. Prevalence of paradoxical curvature by sex ...... 75

Table 24. Prevalence of paradoxical curvature by side and sex, regardless of type...... 76

Table 25. Prevalence of paradoxical curvature by side, type, and sex...... 76

Table 26. Prevalence of accessory turbinate by sex ...... 77

Table 27. Prevalence of accessory turbinates by side and sex ...... 78

Table 28. Mean values for the nasal septal deviation index (NSDI) by sex ...... 78

Table 29. Mean values for nasal septal deviation index (NSDI) by age at death ...... 78

Table 30. Side of nasal septal deviation by sex ...... 79

Table 31. Type of deviation by sex ...... 79

Table 32. Prevalence of septal spurs by sex ...... 80

Table 33. Number of nasal variations per individual ...... 81

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Table 34. Mean values and p-values for the nasal septal deviation index (NSDI) by variation of the middle turbinate ...... 82

Table 35. Synthesis of the results of all the five variations studied in the current work...... 83

Table 36. Reports of variations of the uncinate process in clinical studies ...... 83

Table 37. Reports of paradoxical curvature of the middle turbinate in clinical studies 84

Table 38. Reports of middle turbinate hypertrophy in Palaeopathology ...... 86

Table 39. Reports of concha bullosa of the middle turbinate in clinical studies...... 88

Table 40. Reports of septal spurs in clinical studies...... 92

Table 41. Prevalence of middle turbinate spicules by sex ...... 94

Table 42. Middle turbinate spicules by side and sex in the individuals with both turbinates preserved ...... 95

Table 43. Bone formations within the maxillary sinuses by sex ...... 95

Table 44. New bone formations by side and sex in the individuals with both maxillary sinuses available for examination ...... 97

Table 45. Isolated and combined types of bone changes recorded within the maxillary sinuses ...... 97

Table 46. Degree of bone formations within the maxillary sinuses by side and sex ..... 98

Table 47. Mean age at death by degree of bone formations within the maxillary sinuses ...... 98

Table 48. Contribution of each independent variable to the model tested for the presence of middle turbinate spicules and respective odds ratio ...... 99

Table 49. Contribution of each independent variable to the model tested for the presence of bone formations within the maxillary sinuses and respective odds ratio .. 100

Table 50. Contribution of each independent variable to the model tested for the presence of spicules on the right middle turbinate and respective odds ratio ...... 100

Table 51. Contribution of each independent variable to the model tested for the presence of spicules on the left middle turbinate and respective odds ratio...... 100

Table 52. Contribution of each independent variable to the model tested for the presence of bone formation within the right maxillary sinuses and respective odds ratio ...... 101

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Table 53. Contribution of each independent variable to the model tested for the presence of bone formation within the left maxillary sinuses and respective odds ratio ...... 101

Table 54. Mean values of standardised concha bullosa width by presence of new bone formations and respective statistical significance ...... 102

Table 55. Studies reporting maxillary rhinosinusitis in Portuguese palaeopathological literature ...... 105

Table 56. Reports of prevalence of maxillary rhinosinusitis in palaeopathological literature ...... 106

Table 58. Descriptive statistics and p-values for each measurement and group...... 116

Table 59. Tukey post hoc tests and pairwise comparisons for measurements with significant p-values ...... 117

Table 60. Lesions that may be concurrent with or result from nasal fracture ...... 123

Table 61. Osseous alterations identified in the 1994 nasal cavities and hard palates preserved. Each individual may exhibit more than one lesion ...... 128

Table 62. Osseous alterations on the hard palate comparing the current results and the ones reported by Matos (2009). Lesions consistent with oral pathology are not reported ...... 131

Table 63. Individuals exhibiting nasal and palatal destructions by cause of death. .... 134

Table 64. Nasopalatal perforations by cause of death described by Hackett (1976) in 424 individuals...... 134

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List of appendices

A1. Nasal trauma by side and sex.

A2. Middle turbinate hypertrophy by side and sex.

A3. Type of paradoxical curvature by side and sex.

A4. Accessory turbinate by side and sex.

A5. Middle turbinate spicules by side and sex.

A6. Bone formations within the maxillary sinuses by side and sex.

A7. Degree of bone changes in the individuals presenting at least one maxillary sinus available for examination.

A8. Descriptive statistics for the three groups studied (‘concha bullosa’, ‘maxillary rhinosinusitis’, and ‘control’).

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Abstract

The external nose, nasal cavity, and paranasal sinuses represent key structures whose normal functions may be impaired by several variations and diseases of the upper respiratory tract. Nevertheless, its study in past populations has been neglected. The main aim of the current study is to investigate systematically the osseous changes affecting the sinonasal anatomy of the human skull, as well as its possible impact on craniofacial morphology. Three identified osteological collections from Coimbra and Lisbon comprising 2024 individuals (males=52.7%, females=47.3%; mean age at death=47.81), who lived between 1804 and 1981 were studied. New macroscopic methodologies were structured for recording paradoxical curvatures of the middle turbinate, nasal septal deviations, and spicules on the middle turbinate, whilst computed tomography scanning was used to complement the differential diagnosis. Nasal trauma was recorded in 8.4% (148/1770) of the individuals and the higher frequency in males shows statistically significant differences. The increased age at death also plays a statistical significant role in individuals presenting nasal fracture. A lateral impact force trauma was recorded in 61.5% (91/148) of the individuals, whilst 12.8% (19/148) show other fractures on the facial skeleton. Although the differential diagnosis is limited by the nonspecific location of nasal and facial fractures concerning blows and falls, frequency of lateral impact shows that interpersonal and intimate partner violence may have played an important role in males and females, respectively. The five nasal variations investigated presented prevalence of 38.5% (hypertrophy of the middle turbinates), 50.5% (paradoxical curvature of the middle turbinates), 17.9% (accessory turbinates), 94.8% (septal deviations), and 14.2% (septal spurs), showing that all are fairly common. The nasal septal deviation index and septal spurs present a higher frequency in males, with statistically significant differences. The fact that adult age does not play a significant role in the presence of the nasal variations studied shows that its development may have occurred during early age and is consistent with the hypothesis that genetics may play an important role in their presence. New bone formations on the middle turbinates and within the maxillary sinuses show prevalence of 59.3% and 49.8%, respectively, both showing statistically significant sexual differences with higher frequency in females. Clinical and palaeopathological literature confirm that these osseous alterations are highly consistent with rhinitis and xvii

chronic maxillary rhinosinusitis. The high prevalence of bone formations in both anatomical structures may be related to several reasons, including being the first line of defence against numerous external aggressions, indoor (e.g., smoke due to unprocessed biomass fuels burnt during cooking) and outdoor (e.g., industrialisation) air pollution, insalubrity and lack of hygienic conditions, or mucociliary dysfunction. Clinical studies also state that the nasal anatomical variations may play an important role in sinonasal disease. In the present study, hypertrophy and paradoxical curvature of the middle turbinates are statistically associated with the presence of spicules in the same osseous structure, whilst none of the variations studied are associated with the presence of bone formations within the maxillary sinuses, which is in accordance with most of the clinical literature. Also, although several factors may have played a role on sinonasal disease in the same individual, their relative importance is impossible to study in skeletal remains. The presence of concha bullosa and maxillary rhinosinusitis suggests an effect on craniofacial morphology, since six measurements and two indices revealed a pattern of increased facial breadth in individuals presenting those osseous alterations. This may be related to the development of both concha bullosa and maxillary rhinosinusitis during growth of the facial and cranial bones and anatomical structures, playing a role in its development. Finally, a miscellaneous of osteoblastic and osteoclastic bone alterations was observed on the anatomical structures studied. New cases consistent with leprosy and the first known evidence of possible teaching of modern dacryocystorhinostomy were discussed. The current work brings a new perception of sinonasal morphology and disease in past populations, showing that its presence was frequent in Portugal during the 19th and 20th centuries. Simultaneously, new methodological approaches are expected to facilitate future research understanding sinonasal morphology and disease and its impact on human life.

Keywords: concha bullosa, nasal septal deviation, maxillary rhinosinusitis, rhinitis, craniofacial morphology, miscellaneous osseous alterations.

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Resumo O nariz externo, cavidade nasal e seios paranasais são estruturas chave cujo normal funcionamento pode ser dificultado por diversas variações e doenças do trato respiratório superior. O seu estudo em populações do passado tem sido, no entanto, negligenciado. O presente trabalho tem como objetivo principal o estudo sistemático das alterações ósseas que afetam a anatomia sinonasal do crânio humano, assim como o seu possível impacto na morfologia craniofacial. Três coleções osteológicas identificadas provenientes de Coimbra e Lisboa que incluem 2024 indivíduos (sexo masculino=52,7%, sexo feminino=47,3%; idade à morte média=47,81) que viveram entre 1804 e 1981 foram estudadas. Novas metodologias macroscópicas são descritas para o registo da curvatura paradoxal, do desvio do septo nasal e de espículas ósseas na concha nasal média. Foi também utilizada a tomografia axial computorizada como meio complementar de diagnóstico diferencial. O trauma nasal foi registado em 8,4% (148/1770) dos individuos que fazem parte da base de estudo e a maior frequência no sexo masculino representa diferenças estatísticas significativas, assim como o aumento da idade à morte nos indivíduos que apresentam fratura nasal. A maior parte destes indivíduos (61,5%, 91/148) evidencia o resultado provável de uma força de impacto lateral, enquanto 12,8% (19/148) apresentam outras fraturas no esqueleto facial. Apesar do diagnóstico diferencial destas lesões ser limitado pela localização não específica das fraturas identificadas tendo em conta a sua origem violenta ou não violenta, a frequência da força de impacto lateral mostra que a violência interpessoal e doméstica parecem desempenhar um papel importante nos resultados obtidos. Todas as cinco variações nasais estudadas apresentam prevalências elevadas de 38,5% (hipertrofia das conchas médias), 50,5% (curvatura paradoxal das conchas médias), 18% (concha acessória), 94,8% (desvios septais) e 14,2% (esporões septais). Para além disso, o índex de desvio do septo e os esporões septais apresentam uma maior frequência no sexo masculino com relevância estatística. O facto da idade adulta não desempenhar um papel significativo na presença das variações estudadas mostra que o seu desenvolvimento parece acontecer durante o crescimento e é consistente com a hipótese de que a genética pode desempenhar um papel decisivo na sua presença. As formações ósseas nas conchas médias e no interior dos seios maxilares apresentam uma prevalência de 59,3% e 49,8%, respetivamente, ambas mais elevadas no sexo xix

feminino e com diferenças estatísticas significativas. Os dados clínicos e paleopatológicos confirmam que estas alterações ósseas são altamente altamente consistentes com a presença de rinite e rinossinusite maxilar crónica. A alta prevalência destas formações ósseas parece estar associada a várias razões, incluindo o facto da área sinonasal ser a primeira linha de defesa contra numerosas agressões externas, a poluição do ar interior (e.g., devido ao fumo proveniente da queima de combustíveis não processados ao cozinhar em lareiras abertas) e exterior (e.g., industrialização), insalubridade e falta de condições de higiene ou a disfunção mucociliar. Estudos clínicos mostram também que as variações nasais podem estar na origem da doença sinonasal. No presente estudo, a hipertrofia e a curvatura paradoxal da concha média mostram uma associação estatística significativa com a presença de espículas naquela estrutura óssea, enquanto nenhuma das variações estudadas apresenta associação com as formações ósseas nos seios maxilares, o que está em acordo com a maior parte dos estudos clínicos que se debruçam sobre este tema. Embora vários fatores possam ter desempenhado um papel na doença sinonasal no mesmo indivíduo, a sua importância relativa é impossível de estudar em coleções osteológicas. A concha bolhosa e a rinossinusite maxilar evidenciam também uma associação estatisticamente significativa com o desenvolvimento de um padrão de maior largura da face, muito provavelmente porque ambas se desenvolveram durante o período de crescimento dos ossos e estruturas faciais, desempenhando um papel importante no seu desenvolvimento. Foi ainda registada uma miscelânea de alterações osteoblásticas e osteoclásticas nas estruturas ósseas estudadas. Novos casos consistentes com a presença de lepra ou o primeiro caso conhecido de possível ensino da dacriocistorrinostomia moderna são discutidos. O presente estudo sugere uma nova perceção da morfologia e doença sinonasal em populações do passado, mostrando que a sua presença era já frequente em Portugal durante os séculos XIX e XX. Com a utilização de novas metodologias espera-se facilitar futuros trabalhos científicos na área de forma a ser melhor entendida a morfologia e patologia sinonasal e o seu impacto nos seres humanos.

Palavras-chave: concha bolhosa, desvio do septo nasal, rinossinusite maxilar, rinite, morfologia craniofacial, miscelânea de alterações ósseas.

Acknowledgements This research was supported by a doctoral fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BD/102980/2014) and by the Research Centre for Anthropology and Health (CIAS). I would like to thank to the Department of Life Sciences of the University of Coimbra and to the National Museum of Natural History and Science (NMNHS) in Lisbon for allowing access to the Coimbra and Lisbon collections, particularly to the curators Ana Luísa Santos, Sofia Wasterlain and Susana Garcia, as well as to Judite Alves, coordinator of the Department of Zoology and Anthropology of the NMNHS. Special thanks to Célia Lopes, whose knowledge about the Coimbra collections is of great value, and to Teresa Matos Fernandes (curator of the Identified Skeletal Collection of Évora) and Cláudia Relvado for their help during my stay in Évora.

I also would like to thank to the staff of the Library of the Department of Life Sciences, Library of Health Sciences, General and Central libraries, and Archive, all from the University of Coimbra, and to the staff of the Municipal Library of Porto.

Special thanks are due to Ana Luísa Santos, my thesis advisor, for all the assistance, support, knowledge, and, above all, friendship shared at least during the last four years; to my co-advisor, Simon Mays, for all ideas, improvements, and suggestions throughout the PhD program; to professors Cláudia Umbelino and Ana Maria Silva for all improvements suggested during the defence of the thesis project in 2014; to Deborah Merrett, Kelly Blevins, Samantha Typer, Elina Petersone-Gordina, and Laura González-Garrido, without whom the thesis would not be the same.

Thanks to Zélia Barroso and my friend Cristina Lopes who were decisive helping with the statistical analysis. I owe you. The suggestions of Vítor Matos and Francisco Curate were also very helpful.

Thanks to Anita Fernandes, Fátima Almeida, Calil Makhoul, Marta Roriz, Luís Costa, Daniela Rodrigues, Mariuxi Molina, and Carina Marques for their help and friendship in important moments of the thesis.

Thanks to Doctor Filipe Caseiro Alves, Director of the Medical Imaging Department of the Coimbra Hospital and University Centre, and, particularly, to Rosa Ramos,

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responsible for all CT scans which were performed outside of her working hours. It is not easy to find such a genuinely good friend these days.

Thanks to my brother Hugo Magalhães for all the photography tips, to Eugénia Araújo, to my family, and to all my friends.

Thanks to Inês Leandro and Inês Oliveira-Santos to whom I should thank for a thousand reasons. Thank you both for being a part of my life.

Thanks to Zé and Daniela who are always far but always present. Thank you for all the help in Lisbon and for letting me be a part of your life.

Thanks to Ângela for all the corrections and improvements and for giving me the privilege and pleasure of walking with me through life.

This thesis is dedicated to my brother, mum, and grandpas Mini and David for their encouragement to attend graduate school.

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1. Introduction

«…por que fera impoffivel a os Medicos, e a os Chirurgioens, ainda doutos, e experimentados, curar huâ Epidemia, ou outra qualquer doença , em huâ cidade, adonde ò Ar for corrupto, e o ſeu terreno alagado. Nem a boa dieta, nem os mais acertados conhecimentos neſtas artes produziraô os effeitos dezejados; fem primeiro emmendarfe a malignidade da atmosfera, e impedir os feos eftragos»

António Ribeiro Sanches (1756:vi)

«…because it will be impossible for physicians and surgeons, yet experienced, to cure an epidemic or other disease in a city where the air is corrupted and the land flooded. Neither a good diet nor the best knowledge on these arts will result in the desired effects without first repair the atmospheres’ malignancy and prevent its damage»

António Ribeiro Sanches (1756:vi), free translation of the passage quoted above

During a minute, a human being breathes in about 12 to 24 times, inhaling approximately 10000 litres of air a day (Jones, 2001). The external nose, nasal cavity, and paranasal sinuses represent important structures which perform several functions: olfaction, sensation, immunology, mucociliary clearance, filtration, warming, ventilation, and humidification of air before it enters the lungs (Jones, 2001; Krouse and Stachler, 2006; Gudis et al., 2012). The sinonasal complex is the first contact point for many external insults or aggressions, ranging from trauma or accidents to pollution or complex infectious agents (e.g., Gudis et al., 2012). Each structure, unit, or complex within the sinonasal region plays a role in the defence and protection against those external offences. This work will focus on five main subjects which may affect the osseous anatomy of the sinonasal area and result in possible functional alterations: (1) nasal trauma, (2) nasal variations, (3) new bone formation within the maxillary sinuses and middle turbinates, (4) the possible role of concha bullosa and maxillary rhinosinusitis on craniofacial morphology, and (5) other nonspecific osseous alterations.

1.1. Sinonasal anatomy and function

1.1.1. Nasal anatomy: the piriform aperture and the septum

The anterior bony anatomy of the nose is pyramidal in shape and comprises the nasal bones superiorly (their inferior ends form the top margin of the nasal aperture), and the maxillae laterally and inferiorly, forming, as a whole, the piriform aperture (Jones, 2001; Mondin et al., 2005; Oneal and Beil, 2010; Guyuron, 2012). The nasal 3

bones are wedge-shaped, thin, and rectangular structures placed on either side of the midline of the frontal bone, and usually comprise only a third of the total length of the nose (Jones, 2001; White and Folkens, 2005; Plate I, Figure 1). Their upper portion is thicker and firmly articulates superiorly with the nasal process of the frontal bone, medially with each other, posteriorly with the ethmoid, and laterally with the frontal processes of the maxillae, where they are attached by a strong fibrous attachment (e.g., Jones, 2001; Mondin et al., 2005; White and Folkens, 2005; Oneal and Beil, 2010; Eccles, 2014). The nasal septum (Plate I, Figure 2), composed of both bone and cartilage, forms the midline of the nose and divides the nasal cavity approximately into two equal halves (Jones, 2001; Krouse and Stachler, 2006; Neskey et al., 2009; Guyuron, 2012; Coleman et al., 2013; Walden et al., 2015; Hur et al., 2016). The septal bony segment is formed superiorly by the perpendicular plate of the ethmoid and inferiorly by the vomer, which extends posteriorly to the choanae of the nose (Mygind and Dahl, 1998; Jones, 2001; White and Folkens, 2005; Krouse and Stachler, 2006; Coleman et al., 2013). The ossified perpendicular plate of the septum reaches the vomer usually between 3 to 10 years old, although both only become fully fused between 20 to 30 years old (Scheuer and Black, 2000). Furthermore, the degree of contact between the bony structures of the septum varies according to how much septal cartilage is present between them (Oneal and Beil, 2010; Guyuron, 2012). The vomer attaches inferiorly to the nasal crests of the maxilla and palatine bones (Neskey et al., 2009; Oneal and Beil, 2010), whereas the inferior edge of the septal cartilage is also attached to the anterior nasal spine, the most anterior structure of the maxillae (Oneal and Beil, 2010). The nasal bones, septum, and maxillary bones limit the nasal vestibule, the entrance area to the nose, which is lined by squamous epithelium with hairs and sebaceous glands, and is anteriorly limited by the cartilaginous nasal frame (Jones, 2001; Higuera et al., 2007; Guyuron, 2012).

1.1.2. The turbinates, the meatuses, and the ostiomeatal complex

Three pairs of turbinates usually protrude along the lateral walls of the nasal cavity, the superior and middle projecting from each labyrinth of the ethmoid and the inferior projecting from the maxillary bone (Jones, 2001; Krouse and Stachler, 2006). During the 8th to 10th week of fetal development a series of ridges (or ‘ethmoturbinals’)

form along the lateral nasal wall. These ridges result in the development of the uncinate process, ethmoid bulla, middle, superior, and, rarely, supreme turbinates (Bingham et al., 1991; Braun and Stammberger, 2003). The inferior turbinate derives from the ‘maxilloturbinals’ and the ossification of the bony structures of the lateral nasal wall is completed at 24 weeks of pregnancy (Braun and Stammberger, 2003; Neskey et al., 2009). Each pair of turbinates limits a different air passage known as the superior, middle, and inferior meatuses (Jones, 2001; Krouse and Stachler, 2006; Coleman et al., 2013; Plate I, Figures 1 and 2):

- the superior turbinates limit the underlying superior meatus, which receives drainage from the posterior ethmoid air cells and the sphenoid sinuses through the sphenoethmoidal recess (Krouse and Stachler, 2006; Walden et al., 2015);

- the middle turbinate lays inferomedial to the anterior ethmoid air cells and limits the ostiomeatal complex medially, a term which names the functional unit comprising the final common passageway for drainage and ventilation of the frontal, maxillary, and anterior ethmoid sinuses into the middle meatus, below the middle turbinate (Zinreich et al., 1987; Laine and Smoker, 1992; Stammberger et al., 1995; Scribano et al., 1997; Krouse and Stachler, 2006; Paulsen and Waschke, 2012; Lund et al., 2014; Walden et al., 2015). The ethmoidal infundibulum and the hiatus semilunaris are crucial for the normal drainage from the sinuses to the middle meatus, through several ostia or ducts of variable configurations (e.g., Zinreich et al., 1987; Krouse and Stachler, 2006; Walden et al., 2015). The ethmoidal infundibulum is a curved channel limited laterally by the inferomedial orbit, superiorly by the hiatus semilunaris and ethmoid bulla, medially by the uncinate process (a superior extension or lamella of the lateral nasal wall resembling a hook) and inferiorly by the maxillary sinus (Zinreich et al., 1987). The hiatus semilunaris is a sickle-shaped opening with up to 3mm width, through which the ethmoidal infundibulum can be accessed and thus representing the final segment for drainage from the frontal, maxillary and anterior ethmoid sinuses into the middle meatus (Zinreich et al., 1987; Laine and Smoker, 1992; Stammberger et al., 1995; Daniels et al., 2003; Aygun et al., 2006; Paulsen and Waschke, 2012; Walden et al., 2015);

- the largest pair of turbinates is the inferior, medially limiting the respective meatus, where the nasolacrimal duct opens into the nose and is partially covered by a mucosal fold – the valve of Hasner (Krouse and Stachler, 2006; Walden et al., 2015). The nasolacrimal duct drains the lacrimal fluid/tears from the lacrimal sac into the inferior portion of the nasal cavity (Kakizaki, 2015).

1.1.3. The paranasal sinuses

The nasal cavity is surrounded by the ethmoidal, maxillary, sphenoidal, and frontal sinuses, which are variable in size and shape (Jones, 2001; Krouse and Stachler, 2006; Eccles, 2014), resulting in a complex morphology of this particular area of the upper respiratory tract (Plate II, Figures 3 and 4):

- the ethmoidal sinuses are usually the first to develop and the most mature at birth, undergoing significant growth during the first decade of life (Wise et al., 2012). They are a variable cluster of 8 to 18 cells divided in anatomical regions by thin septa, generally forming the labyrinths of the ethmoid and divided in the anterior and posterior ethmoid air cells by the basal lamella of the middle turbinate (Stammberger et al., 1995; Jones, 2001; Walden et al., 2015). The most anterior includes the agger nasi cells and the ethmoidal bulla, the former are usually the most numerous and smaller, and the latter the most nonvariant air cells in the anterior ethmoid complex; both communicate with the nose in the middle meatus through the ostiomeatal complex (Stammberger et al., 1995; Jones, 2001; White and Folkens, 2005; Krouse and Stachler, 2006). The posterior ethmoidal cells are less numerous, larger, and communicate with the nose through the sphenoethmoidal recess in the superior meatus (Jones, 2001; White and Folkens, 2005; Krouse and Stachler, 2006). Ultimately, the morphology of all ethmoidal cells is variable and dependent of the pneumatisation occurring during early development (Krouse and Stachler, 2006);

- the maxillary sinuses (or antra of Highmore) are the largest of the paranasal sinuses and are bilateral and pyramidal in shape, forming the dominant projection of the anterior face (Jones, 2001; Krouse and Stachler, 2006). By the

Plate I

Figure 1. Medial (left) and lateral (right) walls of the nasal cavity (from Standring, 2008:548).

Septum . Perpendicular plate of the ethmoid . Vomer

Uncinate processes Middle turbinates Inferior turbinates

Figure 2. Septum, uncinate processes, and middle and inferior turbinates within the nasal cavity. Plate II

Figure 3. Nasal cavity and openings to the paranasal sinuses and nasolacrimal duct. Openings to the (1) frontal sinus, (2) nasolacrimal duct, (3) anterior ethmoidal cells, (4) maxillary sinus, (5) posterior ethmoidal cells, and (6) sphenoidal sinus (from Paulsen and Waschke, 2012:60).

Figure 4. Nasal cavity, paranasal sinuses, and nasolacrimal duct (from Drake et al., 2010:1015). 17th to the 18th week of pregnancy, an air space is already observed laterally to the developing uncinate process and the sinuses are perfectly individualised and growing at birth (Scheuer and Black, 2000). The roots of the second premolar and molar teeth are separated from the sinus by a thin bony layer or only by sinusoidal mucosa, which is frequently reported to facilitate infection from dental disease to spread into the sinuses (e.g., Scheuer and Black, 2000; Lund et al., 2014). Also, drainage within the sinus is hampered by the position of the ostia high above the floor of the sinus (Scheuer and Black, 2000) and accessory ostia can occur in about 30% of individuals (Jones, 2001). The roof of the sinus forms the most part of the orbital floor, also containing the infraorbital canal which opens on the anterior surface of the maxilla at the infra-orbital foramen (Lund et al., 2014);

- the sphenoid sinuses are usually the last sinuses to completely pneumatise; they are separated by an intersphenoidal septum and located within the midportion of the most complex bone of the cranium (White and Folkens, 2005; Krouse and Stachler, 2006). Its development begins in the third to fourth month of fetal age, whilst pneumatisation begins at age one until early adult age (Wolf et al., 1993; Shah et al., 2003; Wise et al., 2012). The sphenoid is composed of a body, two wings (greater and lesser), and two plates (lateral and medial pterygoid), forming the major portion of the central skull base and parts of the orbit and lateral skull. Since it is very thin, it is never found intact in skeletal assemblages (White and Folkens, 2005; Krouse and Stachler, 2006). The sphenoid sinuses communicate bilaterally with the nasal cavity through the sphenoethmoidal recess, where the ostia are located near the superior aspect of the sinus, in the inferomedial edge of the superior turbinate (Krouse and Stachler, 2006; Lund et al., 2014);

- the frontal sinuses are the last to begin and complete development (Wise et al., 2012). Usually, they are not visible at birth and develop mostly from the first or second year of life, acquiring its final shape during or after adolescence (Krouse and Stachler, 2006; Wise et al., 2012). When fully developed, extend for a variable distance between the inner and outer tables of the frontal bone, forming the roof of the orbits and completing the roof of the ethmoidal complex (Krouse 7

and Stachler, 2006; Lund et al., 2014). Variable in size and development, they are absent in up to 10% of the individuals (Aygun et al., 2006; Krouse and Stachler, 2006). Its connection to the nasal cavity is found inferomedially in the frontal recess located in the ostiomeatal complex (Krouse and Stachler, 2006; Lund et al., 2014).

The physiological role of the human paranasal sinuses is not yet fully understood (Lundberg, 2008; Keir, 2009; Phillips et al., 2011; Eccles, 2014). In two reviews of the literature, Márquez (2008) and Keir (2009) identified and discussed several of the hypothesised functions ascribed for the paranasal sinuses. Márquez (2008) grouped them into architectural, physiological, and nonfunctional categories, as presented in Table 1.

Table 1. Main functions attributed to the paranasal sinuses reviewed by Márquez (2008) and Keir (2009). Category Theoretical function . Skull lightening to maintain equipoise of the head; . Assist in facial growth and anatomy; Architectural . Part of normal skull pneumatisation; . Functional as pillars for dispersal of masticatory forces; . Provide thermal insulation and protection for the brain; . Humidifying and warming inspired air; . Imparts resonance to the voice; Physiological . Assists in regulating intranasal pressure; . Assisted in flotation at some point in its phylogenetic heritage; . Aiding nasal cavity immune defence producing nitric oxide gas; Nonfunctional . Evolutionary remnants of useless air spaces;

Currently, almost all hypotheses are subjected to doubts, resulting in controversy and lack of scientific support (Keir, 2009). The production of nitric oxide is currently understood as the most significant function of the paranasal sinuses, although its benefits, which supposedly include contributions for local host defence and reinforcement of viral and bacterial growth inhibition, are still under debate (Lundberg, 2008; Keir, 2009; Phillips et al., 2011; Eccles, 2014; Jankowski et al., 2016). Lundberg (2008) states that the role of nitric oxide is likely to enhance local defence mechanisms, directly inhibiting pathogen growth and stimulating mucociliary activity. In patients with primary ciliary dyskinesia and cystic fibrosis, nasal nitric oxide is extremely low when compared to healthy patients (Lundberg et al., 1994; 1996; Lundberg, 2008), and the same was found by Deja et al. (2003) in patients with maxillary rhinosinusitis. Nonetheless, an extensive literature review by Phillips et al. (2011) found no studies

correlating nasal nitric oxide levels with any clinical, biochemical, or pathological measure of sinus mucosal inflammation. Moreover, although the production of nitric oxide within the paranasal sinuses also seems to be associated with ciliary beat frequency, a key factor in the defence of the airways, it is still unclear if this is a cause or effect of rhinological disease (Keir, 2009; Phillips et al., 2011; Jankowski et al., 2016). It has also been suggested that nitric oxide plays a role in warming and humidifying inhaled air (Holden et al., 1999; Jankowski et al., 2016). Holden et al. (1999) showed that, by dilating the nasal wall vessels, nitric oxide increases their capacitance, thus regulating intranasal temperature. Other authors argue that the paranasal sinuses may act as air insulators and protectors of the brain by cooling with the inspiration of cold air, although the possible coexistence of more than one of the abovementioned functions cannot be ruled out in the current state of investigation (Keir, 2009; Eccles, 2014).

1.2. Sinonasal bony pathology

1.2.1. Nasal trauma

The nose can be easily fractured and nasal trauma is usually described as the most common type of fracture of the facial bones, either by itself or associated with other facial fractures (Lloyd, 1988; Higuera et al., 2007; Chan and Most, 2008; Lee et al., 2010; Baek et al., 2013; Jeon et al., 2013; Galloway and Wedel, 2014). Its most common causes are violence, falls, sports, and motor vehicle and work related accidents (Hussain et al., 1994; Lovell, 1997; Gassner et al., 2003; Hwang et al., 2006; Higuera et al., 2007; Lee et al., 2010; Hashemi and Beshkar, 2011; Baek et al., 2013; Jeon et al., 2013; Boffano et al., 2014; Galloway and Wedel, 2014; Park et al., 2014). Literature shows that, regardless of chronology or environment (e.g., rural/urban), craniofacial injuries, particularly to the face, are the most common in both sexes inflicted by fists, feet, or blunt objects (e.g., Brink et al., 1998; Brickley and Smith, 2006; Galloway and Wedel, 2014; Redfern, 2017). Nevertheless, the differentiation between accidental and intentional injuries in skeletal assemblages is problematic, essentially because their causal distinction was irretrievably lost (Walker, 2001). The way bone respond to injuries reflects the extrinsic shape, area, mass, speed, and direction of the instrument that was applied as the external force, as well as the

intrinsic strength, anatomy, thickness, mineral content, and health of the bone, collectively determining the susceptibility to fracture (Martin and McCulloch, 1987; Passalacqua and Fenton, 2012; Smith et al., 2016). High-velocity impacts (e.g., gunshots) deliver energy in such a way that the bone reacts like a brittle material and shatters, whereas lower energy impacts and bending forces (resulting in blunt force trauma) distributes a gradual rate of loading, causing the bone to react as a ductile material and showing plastic deformation (Smith et al., 2016). Hydroxyapatite crystals and calcium salts represent the stiff, unyielding, and brittle constituent of the bone, whilst the collagen matrix characterises the elastic, yielding, and ductile section; together, they are responsible for bone hardness and resistance (Martin and McCulloch, 1987; Junqueira and Carneiro, 2008; Smith et al., 2016). Three predictable and consecutive stages represent the biomechanical reaction of a bone when subjected to blunt force: stress (the result of the force applied to the bone), strain (elastic or plastic deformation, forces passing though the bending bone or bending the bone with permanent deformation, respectively), and failure of the structure during separation (the fracture of the bone) (Martin and McCulloch, 1987; Passalacqua and Fenton, 2012; Smith et al., 2016). Depending on its structure, the bone bends and is able to resist to low rates of compression and tension stresses (Smith et al., 2016). During the elastic stage, the bone is able to reacquire its natural shape if the force is removed; however, if the pressure increases, the bone enters the deformation phase and it is not able to reacquire its natural shape (Smith et al., 2016). Consequently, fracture will occur when extrinsic factors exceed the resisting strength of the bone (Smith et al., 2016). The time elapsed until bone fracture usually differentiates slow-loading trauma (e.g., blunt force trauma) from high-loading trauma, characterised by minimal bone deformation (e.g., gunshots and blast injury) (Passalacqua and Fenton, 2012).

1.2.2. Pathophysiology of rhinosinusitis and rhinitis

A recent hypothesis argued that rhinosinusitis, like otitis media, may be a primarily human disease, secondary to consequences of evolution (adaptations to bipedalism, speech, and loss of prognathism) and incompatible with animal survival in their natural environment (Bluestone et al., 2012). Whether or not it is exclusively human, rhinosinusitis is a common heterogeneous group of diseases characterised by the inflammation of the nose and paranasal sinuses, which can be generally defined as

acute (<12 weeks symptoms) or chronic (≥ 12 weeks symptoms) (e.g., Jackman and Kennedy, 2006; Timperley et al., 2010; Magryś et al., 2011; Meltzer and Hamilos, 2011; Fokkens et al., 2012; Orlandi et al., 2016). Acute rhinosinusitis is divided in ‘acute viral rhinosinusitis’ and ‘acute post-viral rhinosinusitis’. The latter term indicates that viruses are the primary cause of acute rhinosinusitis and only 0.5 to 2% of the patients develop acute bacterial rhinosinusitis secondary to a viral infection (Lloyd, 1988; Meltzer and Hamilos, 2011; Fokkens et al., 2012). Moreover, the two main types of chronic rhinosinusitis are currently differentiated by the presence or absence of nasal polyps (e.g., Bernstein, 2006; Fokkens et al., 2012). Recently, the International Consensus Group on Allergy and Rhinology (Orlandi et al., 2016) has defined chronic rhinosinusitis as a syndrome with different phenotypes and endotypes rather than a disease, showing the difficulty to differentiate etiologic factors responsible for its development in a single patient. The true prevalence of rhinosinusitis is actually unclear, due to the inconsistencies in its definition and also because not all individuals seek care (File Jr., 2006). Nevertheless, recent studies show that the disease may affect between 5% and 15% of the general population, both in Europe and the United States (e.g., Hastan et al., 2011; Fokkens et al., 2012; Orlandi et al., 2016). In a recent study conducted in 19 centres from 12 European countries, Coimbra was the one presenting higher prevalence (27.1%; 95% CI 25.0-29.3%) of chronic rhinosinusitis in a total of 2162 questionnaire responses, whilst the mean prevalence of the 57128 individuals of all centres was 10.9% (95% CI 10.6-11.2%) (Hastan et al., 2011). The authors found no justification for such differences. Its symptoms can be disabling and lead to significant impairment of quality of life, reduced productivity at the workplace, and high medical treatment costs (e.g., Van Crombruggen et al., 2010; Orlandi et al., 2016). The major symptoms associated with the diagnosis of chronic rhinosinusitis are facial pain and pressure, facial congestion, nasal obstruction and discharge, hyposmia or fever; on the other hand, minor factors include headache, halitosis, fatigue, ear and dental pain or cough (e.g., Clement, 2006; Caroline et al., 2011; Desrosiers et al., 2011; Schalek, 2011; Fokkens et al., 2012). Rhinosinusitis may include several complications, such as orbital cellulitis and abscess, meningitis, intracranial abscess, thrombophlebitis and cavernous sinus thrombosis or

perivascular spread of infection (e.g., Lloyd, 1988; Madani and Beale, 2009; Witterick and Vescan, 2012). The presence of periosteal thickening, woven bone formation, and fibrosis associated with sinus inflammation is a mechanism currently defined as ‘osteitis’ in clinical practice, which is regarded as part of the pathophysiological process associated with chronic rhinosinusitis (Fokkens et al., 2012) and represents the response to an aggression through inflammatory reaction across the nasal and sinonasal mucosa into the underlying bone (Bolger et al., 1997; Videler et al., 2011; Georgalas, 2013; Leung et al., 2016). These histopathological changes have been demonstrated since the 1990s through analysis of induced sinus infection in rabbits (Westrin et al., 1992; Bolger et al., 1997; Perloff et al., 2000; Khalid et al., 2002), resulting in appositional bone remodelling comprising osteoclasis, appositional bone formation, or intramembranous bone formation just four to 28 days after the inoculation of Pseudomonas aeruginosa within the maxillary sinuses, a bacteria associated with rhinosinusitis in humans (Bolger et al., 1997). Although clinical studies are still limited, bony alterations are similarly observed in human patients, where increased osteoclastic and osteoblastic activity was shown through the disarrangement of organised lamellar bone and consequent deposition of new woven bone (e.g., Kennedy et al., 1998; Giacchi et al., 2001; Lee et al., 2006; Mutijima et al., 2014). Giacchi et al. (2001) demonstrated that 18 out of 19 patients presenting chronic rhinosinusitis also exhibited some degree of bone alteration. Lee et al. (2006) found concurrent osteitis in 36% to 53% of patients with chronic rhinosinusitis. Similarly, Mutijima et al. (2014) demonstrated the presence of osteitis in a group of 51 patients suffering of allergic and non-allergic chronic rhinosinusitis. Three comprehensive reviews by Videler et al. (2011), Georgalas (2013), and Leung et al. (2016) have confirmed and highlighted the relationship between chronic rhinosinusitis and the presence of increased bone density, periosteal and irregular thickening, woven bone formation, bone resorption, fibrosis, and inflammatory cell infiltrate, in different clinical studies. New bone formation is recurrent in patients with chronic rhinosinusitis in all studies reviewed by Leung et al. (2016). Moreover, the inability to treat the underlying bone within the maxillary sinuses may contribute to localised persistent mucosal inflammation and to the difficulty in managing chronic rhinosinusitis (Chiu, 2005; Videler et al., 2011). This recent body of evidence confirming the relationship between chronic rhinosinusitis and osseous

alterations has also resulted in a variety of grading systems to classify osteitis usually based on CT scan observations, which appears as a thickened, irregular, heterogeneous layer of the sinus walls (Biedlingmaier et al., 1996; Lee et al., 2006; Videler et al., 2011; Leung et al., 2016). Nevertheless, the role of osteitis in the pathogenesis of chronic rhinosinusitis, although considered important, is still unclear (Videler et al., 2011; Fokkens et al., 2012) and staging systems for chronic rhinosinusitis continue to focus on the degree of opacification of the sinuses and obstruction of the ostiomeatal complex (Videler et al., 2011). Rhinitis is also a heterogeneous group of nasal disorders associated with the symptomatic inflammation of the inner lining of the nose resulting in nasal obstruction, rhinorrhoea, sneezing, or nasal/ocular itch (Dykewicz, 2003; Tran et al., 2011; Hellings et al., 2017). The presence of at least two of these symptoms during a minimum of 12 weeks defines chronic rhinitis, although the patient’s clinical history and the differential diagnosis are important clinical steps in the correct identification of the disease (e.g., Rodrigues, 1998; Loureiro et al., 2004; Hellings et al., 2017). Infectious, allergic, and nonallergic noninfectious rhinitis represent the current major subgroups of the disease (Hellings et al., 2017). Its etiopathogenesis is usually associated with the action of virus, bacteria, aeroallergens (dust mites, mould spores, pollens), food allergens, occupation, or pollutants (e.g., Castel-Branco, 1997; Loureiro et al., 2004; Hellings et al., 2017). Allergic rhinitis is the most frequent allergic airway disease causing disabilities and respiratory impairment in social life, sleep, school, and work (Mygind and Dahl, 1998; Corriveau and Bachert, 2012; Toskala, 2012). For the past decades, clinical literature has demonstrated a very close relation between sinusitis and rhinitis, which are currently studied as the expression of one disease entity (Van Crombruggen et al., 2010; Desrosiers et al., 2011). The recent nomenclature of ‘rhinosinusitis’ was adopted based on the fact that sinus inflammation is almost always accompanied by concomitant inflammation of the contiguous nasal mucosa and rarely occurs in the absence of rhinitis (Lund and Kennedy, 1995; Lanza and Kennedy, 1997; Meltzer et al., 2004; 2006; Dykewicz and Hamilos, 2010; Van Crombruggen et al., 2010; Desrosiers et al., 2011; Meltzer and Hamilos, 2011; Fokkens et al., 2012). Additionally, rhinosinusitis usually involves both the nasal passages and the paranasal sinuses whose mucous membrane represents contiguous structures with shared vascular, neuronal, and interconnecting anatomic pathways (e.g., Lund and

Kennedy, 1995; Dykewicz and Hamilos, 2010; Desrosiers et al., 2011; Meltzer and Hamilos, 2011). Van Crombruggen and co-authors (2010) have shown that similar inflammatory mediators were present in ethmoidal and nasal mucosa of chronic rhinosinusitis patients. Milbrath et al. (1994), Busaba et al. (2006), and Naeimi et al. (2013), although with a limited number of 25, 22, and 15 patients studied, respectively, founded that middle turbinate inflammation correlated with inflammation of ipsilateral ethmoid sinus. Although further investigation is needed to corroborate this hypothesis, these studies suggest the importance of the role of nasal inflammation in the inflammatory process of the sinuses. In fact, the presence of osteitis as a consequence of middle turbinate inflammation was also described by Biedlingmaier et al. (1996) in all 38 partial middle concha resections from 20 patients. In a small percentage of individuals, the inflammation of the maxillary sinuses may also have a dental or iatrogenic origin and, in such circumstances, the pathway of the disease is reversed from the sinus cavity to secondary nasal inflammation; nevertheless, the terminology is currently accepted as the same (Fokkens et al., 2012).

1.2.2.1. Etiology and predisposing factors for sinonasal inflammation

Currently, rhinosinusitis is one of the diseases that most commonly affect the respiratory tract and one of the most prevalent chronic health conditions (Abuzaid and Thaler, 2008; Hamilos, 2011; Meltzer and Hamilos, 2011; Fokkens et al., 2012). The sinonasal inflammation that defines chronic rhinosinusitis occurs at the interface with the external environment and the disease can have multiple etiologies, predisposing factors, and/or comorbidities (Bernstein, 2006; Fokkens et al., 2012; Han and Wold, 2012). Current clinical literature describes bacteria, fungi, allergens, viruses, or environmental toxins as potential primary inflammatory triggers or etiologic agents (e.g., Bernstein, 2006; Epstein and Lanza, 2012; Fokkens et al., 2012; Lane and Turner, 2012; Orlandi et al., 2016) and Staphylococcus aureus is the most common bacterial pathogen associated with chronic rhinosinusitis in western countries (Fokkens et al., 2012). Nevertheless, in healthy individuals some of these external entities are cleared without tissue injury or chronic disease and clinicians have proposed that, rather than the action of environmental or microbial agents, the alterations in the host mucosal immune response may represent the primary etiologic factor in chronic rhinosinusitis

pathogenesis (Fokkens et al., 2012; Lane and Turner, 2012). These so-called systemic host factors include a defective mucociliary function and problems with the innate or acquired/adaptive immune response, particularly with sinonasal epithelial cells, dendritic cells, macrophages, eosinophils, neutrophils, mast cells, mucosal immunoglobulin secretion, T Cells, or cytokine patterns (Bernstein, 2006; Fokkens et al., 2012; Lane and Turner, 2012; De Schryver et al., 2013; Desrosiers and Kilty, 2013; Kawauchi, 2013; Kern and Decker, 2013; Ponikau et al., 2013; Saito, 2013; Shimizu, 2013). Laryngopharyngeal reflux, aspirin intolerance, iatrogenic factors, pregnancy, genetics, immunodeficiency, environmental factors, odontogenic disease, and nasal anatomical variations have also been proposed and discussed as predisposing to chronic sinonasal inflammation (e.g., Bernstein, 2006; Hamilos, 2011; Fokkens et al., 2012; Lane and Turner, 2012). Indoor and outdoor air quality is currently amongst the main environmental factors for respiratory disease. The World Health Organization estimates that 36% of lower respiratory infections worldwide are attributable to solid fuel use, whilst 1% of all respiratory infections are associated with outdoor air pollution (Prüss-Üstün and Corvalán, 2006). Indoor dampness and mould exposure (Koskinen et al., 1999; Fisk et al., 2007; Jaakkola et al., 2013), poor housing conditions (Oudin et al., 2016), active and second-hand cigarette smoking (Reh et al., 2009; Tammemagi et al., 2010; Higgins and Reh, 2012) were also associated with sinonasal inflammation. Two studies carried out in Portuguese schools located in Porto (N=1607) and Coimbra (N=1019) reported an association between high concentrations of carbon dioxide and greater respiratory symptomatology (e.g., sneezing, rales, wheezing, irritation of mucous membranes, rhinitis, and asthma) (Fraga et al., 2008; Ferreira and Cardoso, 2014). Specific components of air pollution (carbon monoxide, nitrogen dioxide, sulphur compounds, and particulate matter) have also been associated with sinonasal disease (Marttila et al., 1994; Andersson et al., 2002; Bhattacharyya, 2009). Freitas et al. (2010) found a statistically significant association between high levels of several atmospheric pollutants (airborne particles with aerodynamic diameter below 10 μm, sulphur dioxide, nitrogen dioxide, and ozone) and daily admissions in 12 hospitals from Lisbon due to respiratory disease. Alves et al. (2010) also established in Lisbon significant positive associations between markers of traffic-related pollution (carbon monoxide and nitrogen dioxide) and cardiocirculatory diseases in all age groups and increased childhood emergency

admissions for respiratory illness due to sulphur dioxide levels from industrial activities. In a literature review concerning several atmospheric pollutants and its impact on public health in Portugal, Torres et al. (2017) confirmed that the Lisbon metropolitan area is currently the most problematic Portuguese region. Recently, Timperley et al. (2010) have emphasised a model of interaction between the abovementioned etiologies for chronic rhinosinusitis as the key factor for the progression of the disease, particularly differentiating three types of trigger interactions: (1) intrinsic mucosal inflammation, (2) local microbial community, and (3) mucociliary dysfunction, a triangle of pathologic mechanisms leading to the unregulated proinflammatory mucosal response (Timperley et al., 2010). The authors stated that the individual’s physiology represents a central contribution as the driving pathology only in the first factor of the proposed model, whereas the other two are subsequent and only disease modifying. Ostial obstruction caused by nasal variations of the ostiomeatal complex would be considered as a factor impeding mucociliary clearance (Timperley et al., 2010). This kind of approach may be useful to create a different and specific understanding for each chronic patient presenting the disease (Timperley et al., 2010).

1.2.2.2. Nasal variations and sinonasal pathology

With the advent of functional endoscopic sinus surgery and the advances in the understanding of the sinonasal pathophysiology, attention has been directed since the 1980s towards its analysis through computed tomography (CT) scan imaging, which is still the best technique for evaluating the nasal cavity and paranasal sinuses (Zinreich et al., 1987; Bolger et al., 1991; Lloyd et al., 1991; Laine and Smoker, 1992; Willner et al., 1997; Badia et al., 2005; Wani et al., 2009). CT scan has dramatically improved sinonasal imaging thanks to its ability to show both the soft tissue inflammatory lesions and alterations of sinonasal bony structures (Willner et al., 1997; Jones, 2002; Badia et al., 2005; Tezer et al., 2006; Mazza et al., 2007). As a result, several new nasal variations were identified, whilst several others were more appropriately described (Stammberger and Posawetz, 1990; Tezer et al., 2006). Earwaker (1993), for instance, has identified 52 nasal variations in sinonasal CT scans of 800 patients from Australia, whilst Dasar and Gokce (2016) observed 39 variations in 400 Turkish individuals and Shpilberg et al. (2015) described at least 20 in 192 North Americans. Moreover, Earwaker (1993) reported that 93% of the patients had one or more variants and

Shpilberg et al. (2015) showed that all patients developed at least one variation. Table 2 presents several of the most frequent osseous anatomical variations described in clinical literature over the past decades.

Table 2. Common bony anatomical variations of the sinonasal structures. Anatomical structure Variation Deviation; Septum Pneumatisation (septum bullosa); Unilateral spur in the ethmoid-vomer fusion; Superior turbinate Pneumatisation/hypertrophy (concha bullosa); Pneumatisation/hypertrophy (concha bullosa);

Paradoxical curvature; Middle turbinate Secondary; Hypoplasia; Inferior turbinate Pneumatisation/hypertrophy (concha bullosa);

Pneumatisation; Uncinate process Accessory turbinate; Pterygoid process

Crista galli Pneumatisation; Anterior clinoid process Hard palate Lamina papyracea Dehiscence; Supraorbital cell; Sphenoethmoidal (Onodi) cells; Agger nasi cells;

Paranasal sinuses Infraorbital ethmoidal (Haller) cell; Prominent ethmoidal bulla; Maxillary sinus septa; Frontal, sphenoidal, or maxillary hypoplasia; Frontal, sphenoidal, or maxillary agenesis;

Most of the anatomical variations comprise the pneumatisation or incorrect development of the anatomical structures of the sinonasal cavity. Nonetheless, many of these variations do not compromise the major drainage pathways and, consequently, are less likely to contribute to sinonasal pathology (Earwaker, 1993). The communication between the paranasal sinuses and the nasal cavity takes place through small ostia from 2 to 6mm in diameter, resulting in a very small exchange of air (Stammberger, 1986; Stammberger and Posawetz, 1990; Krouse and Stachler, 2006). When normal ventilation and drainage of the sinuses is compromised and the ostia or recesses are blocked, it is possible that an inflammatory process occur within the sinuses (Stammberger, 1986; Stammberger and Posawetz, 1990; Krouse and Stachler, 2006). The nasal structures of the middle meatus and ostiomeatal complex are more frequently associated with such pathological processes, either for its anatomical and physiological complexity or for comprising most of the drainage pathways to the paranasal sinuses. 17

The frontal, maxillary and anterior ethmoidal sinuses communicate with the nasal cavity through a system of very narrow clefts containing mucosal areas with ciliated respiratory epithelium and those aerated structures may be infected if blocked (Stammberger and Posawetz, 1990; Jones, 2002). Over the past decades clinical literature has reported diverse results regarding the contribution of anatomical variations of the ostiomeatal complex to paranasal sinus disease through narrowing or completely obstruct the middle meatus (e.g., Bolger et al., 1991; Earwaker, 1993; Jones et al., 1997; Tosun et al., 2000; Pérez-Piñas et al., 2000; Jones, 2002; Kantarci et al., 2004; Beale et al., 2009; Orlandi, 2010; Smith et al., 2010; Han and Wold, 2012; Tunçyürek et al., 2013). The association between nasal anatomic variations and chronic rhinosinusitis is controversial, since several studies reported a positive association (e.g., Calhoun et al., 1991; Elahi and Frenkiel, 2000; Caughey et al., 2005; Fadda et al., 2012), while others showed no relationship (e.g., Bolger et al., 1991; Earwaker, 1993; Smith et al., 2010; Shpilberg et al., 2015). The main anatomic variations studied include concha bullosa and paradoxical curvature of the middle turbinates and several variations of the uncinate processes, structures which are intrinsic to the ostiomeatal complex, or variations of the nasal septum, which is extrinsic, but may also interact with the middle meatus. The first description of the hypertrophy of the middle turbinate is traditionally attributed to the Venetian physician and anatomist Jo Dominici Santorini in 1724 (Santorini, 1724). Concha bullosa is clinically described as an air-filled cavity, pneumatisation, or hypertrophy of the middle nasal concha (e.g., Bolger et al., 1991; Hatipoglu et al., 2005; Koo et al., 2017), although concha bullosa of the inferior and superior turbinates have also been reported in literature (e.g., Kantarci et al., 2004; Pittore et al., 2011; Roozbahany and Nasri, 2013; Onwuchekwa and Alazigha, 2017). Several clinical studies found a prevalence of concha bullosa between 9.6% (Milczuk et al., 1993) and 67.5% (Dasar and Gokce, 2016), which is usually pointed out as the most frequent variation of the lateral nasal wall (e.g., Tunçyürek et al., 2013). The clinical treatment of concha bullosa is indicated when symptomatic (Pittore et al., 2011), with patients presenting rhinorrhoea, nasal breathing difficulties, headache and diplopia (Erkan et al., 2006; Cukurova et al., 2010; 2012; Pittore et al., 2011). Paradoxical curvature of the middle turbinate is described as its lateral rather than medial convexity and is not associated with changes in the normal turbinate attachments

(e.g., Lloyd, 1990; Earwaker, 1993; Arslan et al., 1999). Prevalence of paradoxical turbinates in clinical reports varies widely between 0.7% (Nouraei et al., 2009) and 1.8% (Onwuchekwa and Alazigha, 2017) to 40.4% (Earwaker, 1993) and 51.5% (Sadr et al., 2012). Several authors state that small paradoxical turbinates are not usually significant and only large ones may obstruct the drainage pathways of the ostiomeatal complex (e.g., Lloyd, 1990; Earwaker, 1993; Tonai and Baba, 1996). Partial resections are sometimes described in clinical practice as effective in managing symptomatic paradoxical middle turbinates (Wolf and Biedlingmaier, 2001). Several variations are also described for the uncinate process. The pneumatisation of this structure, for instance, was fairly characterised over the past decades by several clinical studies (e.g., Bolger et al., 1990; 1991; Riello and Boasquevisque, 2008; Tuli et al., 2013). Nevertheless, Emil Zuckerkandl has shown an outstanding anatomical knowledge in the last quarter of the 19th century describing eight different volumes and shapes of the uncinate process (Zuckerkandl, 1893) and several other authors have more recently reported inconsistent consensus about its various anatomical configurations (Al-Qudah, 2015). Earwaker (1993), for instance, classified six different types of ostiomeatal complex configurations associated with different orientations of the uncinate process and size of the ethmoid bulla. Isobe et al. (1998) also detailed nine different shapes of the uncinate process. But a particular shape of this osseous structure has emerged as a central factor that may hamper the normal function of the middle meatus: the accessory turbinate, a medially bent and anterior folded outline, appearing as a ‘false’ middle turbinate (Aksungur et al., 1999; Lin et al., 2006; El-Shazly et al., 2012; Al-Qudah, 2015). Nasal septal deviation represents a divergence of the septum from the midline of the nose, which can involve the quadrilateral cartilage, the bony portion, or both structures (e.g., Earwaker, 1993; Guyuron and Behmand, 2003; Neskey et al., 2009). It is usually reported as the most common variation within the nasal cavity (e.g., Earwaker, 1993; Uygur et al., 2003; Jin et al., 2007; Yigit et al., 2010; Fadda et al., 2012; Shpilberg et al., 2015). Zuckerkandl (1893) described and discussed several types of septal deviations in the late 19th century, but the clinical study of this anatomical variation is still problematic, mainly because of the use of unstandardised classification methods (Mladina, 1987; Guyuron et al., 1999; Stallman et al., 2004; Jin et al., 2007; Orlandi, 2010; Smith et al., 2010; Reitzen et al., 2011; Holton et al., 2013; Gregurić et

al., 2016; Koo et al., 2017). The prevalence of nasal septal deviation appears to increase with age in childhood and adolescence (e.g., Subarić and Mladina, 2002; Zielnik- Jurkiewicz and Olszewska-Sosińska, 2006; Reitzen et al., 2011; Wee et al., 2012) and may arise both early or late in development (often from a combination of etiological sources) due to failure at embryonic stage, prolonged pressure during the intrauterine phase, genetics or environmental causes, infections, neoplasia or trauma (Kawalski and Spiewak, 1998; Aktas et al., 2003; Neskey et al., 2009; Reitzen et al., 2011; Koo et al., 2017). Also, Kawalski and Spiewak (1998) showed that caesarean section is associated with reduced nasal septal deviation, contrasting with injury during births from spontaneous delivery. However, septal straightening during the first days of life was usual and the most anterior nasal deviations were not considered a clinical problem (Kawalski and Spiewak, 1998). Nevertheless, particularly during growth and adulthood, nasal septal deviation may have consequences in the alteration of the airflow in the nasal cavity, which can result in a localised dry effect inhibiting the formation of mucous and ciliary depuration, inflammatory changes, sleep apnoea, nosebleeds, nasal obstruction, postnasal drip, or even in the aesthetic appearance of the nose and face (e.g., Wee et al., 2012; Teixeira et al., 2016). The methodology developed by Ranko Mladina in 1987, for instance, summarises seven types of nasal deviation related to different clinical implications. Spurs in the ethmoid-vomer fusion are unilateral defects in the form of horizontal crests (e.g., Mladina, 2012; Mladina et al., 2015) and are described at least since the late 19th century (Zuckerkandl, 1893). Currently, they are studied as an isolated variation (e.g., Earwaker, 1993; Shpilberg et al., 2015) or included in the classification of nasal septal deviations (e.g., Mladina, 1987; Koo et al., 2017). The concomitant presence of septal spurs, septal deviation and/or concha bullosa, are usually suggested to cause rhinogenic contact point headache (e.g., Stammberger and Posawetz, 1990; Chow, 1994; Mehle and Schreiber, 2005; IHS, 2013; Peric et al., 2016; Swain et al., 2016). Septal spur resection is often recommended in patients undergoing unsuccessful medical treatment (Stammberger and Posawetz, 1990; Chow, 1994; Mehle and Schreiber, 2005; Peric et al., 2016; Swain et al., 2016).

1.2.2.3. Sinonasal diseases and variations in Portugal during the 19th and first half of the 20th century

In 1825 AD the Royal Medical Schools (or Medical and Surgical Schools) were founded in Lisbon and Porto and, along with the University of Coimbra, became the three schools teaching medicine in Portugal (Clode, 2010). From then on, hundreds of theses were presented to the Lisbon, Porto, and Coimbra schools by their students at the end of the course and, lately, its importance has been emphasised as a historical source (e.g., Costa and Vieira, 2011). In the theses presented to the Porto Medical School1 between 1827 and 1908 AD, for instance, the study of the sinus anatomy or pathology is only referred since the end of the 19th century. The thesis “Resection of the maxilla”, presented by Pedro Nunes de Sousa in 1888, presents an exhaustive description of the maxillary bone and sinus, as well as of different types of inflammation (osteitis, periostitis, osteoperiostitis) and neoplastic diseases that could have led to the resection of the maxillary bone. Four years later, Castro (1892) described ten patients diagnosed with coryza, nasal polyps, chronic rhinitis, or hypertrophy of the middle and inferior turbinates. This is probably one of the earliest clinical studies in Portugal describing such nasal diseases and variations. Moreover, the first series of the Portuguese medical journal Coimbra Médica (1881-1901) does not refer to ‘sinusitis’, but published different therapeutics for nasopharyngeal catarrh, mucosal hypertrophy (Revista de jornaes, 1882), coryza2 (Revista de jornaes, 1884; Da atropina na coryza, 1885; Formulario, 1887; Therapeutica, 1890; Therapeutica, 1891; Therapeutica, 1892b, 1892c, 1892d; Therapeutica, 1893a, 1893b; Vieira, 1893; Therapeutica, 1895b, 1895b), ozena2 (Neves, 1889; Therapeutica, 1889a; Therapeutica, 1900b), rhinitis (Therapeutica, 1889c; Therapeutica, 1900a), constipation (Therapeutica, 1889a; Therapeutica, 1892a; Vieira, 1895), epistaxis (Revista de jornaes, 1885), and suppuration and bacterial infections of the nose (Therapeutica, 1896) (Table 3).

1 The references of the theses were published by Lima (1908) and most of them are fully available at https://repositorio-aberto.up.pt/

2 According to the ‘Dictionary of medical terms’ (Costa, 2012) coryza and ozena currently mean: Coryza: “Acute catarrhal disease of the nasal mucosa accompanied of abundant mucous or mucopurulent discharge. Synonymous of rhinitis” (Costa, 2012:289); Ozena: “Chronic and atrophic inflammation of the nasal mucosa characterised by the formation of fetid crusts that may invade the external wall of the nasal cavity and, rarely, the paranasal sinuses, Eustachian tube, or middle ear” (Costa, 2012:893). 21

Table 3. Examples of treatments for several of the respiratory symptoms and diseases referred in the first series of the Portuguese journal Coimbra Médica between 1881 and 1901. Symptom/disease Therapeutic Reference Nasopharyngeal catarrh .Extreme . Sprays and nasal injections with the Dobell’s solution: Phenic acid (6g.), borax (8g.), sodium bicarbonate (8g.), glycerine

(60g.), water (1000g.) Revista de .Simple . Zinc sulphate, iron sulphate, potassium chloride, tannin in the jornaes ratio of 1 to 30, silver nitrate, zinc chloride in the ratio of 1 to 100 (1882:43-44) . In cases of dry atrophia, cauterization. Stimulation of the mucosa Mucosal hypertrophy with a solution of iodine or 5/10 drops of a solution of: iodine (1g.), potassium iodide (2g.), and water (23g.) . Insufflations of iodine powder Cozzolino recommendations:

. Salol (5,4g.), boric acid (2,7g.), salicylic acid (0,45g.), thymol Ozena Therapeutica (0,18g.), talc powder (7,5g.) (1889a:94) . Mercuric chloride (0,09g.), resorcinol (1,35g.), benzoic acid (1,80g.), boric acid (11,25g.)

Revista de Dobson treatment: jornaes . Aspirations of camphora (4g.) in boiling water (1884:188) Baretoux treatment: Formulario

. Cocaine chlorhydrate (1g.), water (10g.), glycerine (10g.) (1887:226) Coryza Rabow recommendations to inhale: Therapeutica . Menthol (2g.), roasted coffee (50g.), sugar (50g.) (1890:13) . Sodium Salicylate (15g.), orange peel syrup (15g.), peppermint Therapeutica water (90g.) (1891:297) . Cocaine chlorhydrate (0.6g), eucalyptus essence (0,18g.), iodine Therapeutica (4,5g), milk sugar (39g) (1892b:126) Constipation . Ammonia iron citrate (1,8g.), Stearns’ aromatic cascara (30g.), Therapeutic water (30g.) (1892a:45) Chronic constipation . Aloin, nux vomica extract, iron sulphate, ipecacuanha powder, Therapeutica myrrha powder, saponaria powder (0.03g. each) (1889a:93) Rhinitis .Scrupulous . Zinc sulphophenate (0,30g.), bismuth salicylate (4g.), iodol (3g.),

zinc tannate (3g.), talc powder, (10g.) Therapeutica .Chronic catarrhal . Alum powder (2g.), borax powder (2g.), menthol (0,2g.), zinc (1889c:207) tannate (3g.), bismuth tannate (3g.); lycopodium (8g.) . Zinc salicylate (4g.), bismuth tannate (4g.), borax powder (2g.), salol (1,5g.), talc powder (8g.) Nasal cavities

.Suppurations . Alumnol (one part), boric acid (three parts); Therapeutica .Bacterial infections . Menthol (0.16 parts), camphora (100 parts). The same mixtures (1896:31) can be made with ammonium chloride/cocaine and lycopodium/camphora.

These recommendations are either summarised from foreign articles or recommended by the journal itself in unsigned therapeutic forms. Although many of these problems may have been the result of the presence of what is currently defined as rhinitis or rhinosinusitis, it is evident that clear clinical definitions for each one of these diseases were somehow absent. The therapeutics frequently focused on isolated symptoms and some of the diagnoses may have resulted in different names for the same 22

diseases, as it is evident when Baetta Neves described the treatment of a 15-year-old female diagnosed with “…chronic nasopharyngeal coryza, commonly designated as ozena…” (Neves, 1889:88) or when Vieira (1895) recognised that constipation was the common designation for mucosal acute catarrhs of the nose, pharynx, larynx, trachea, or bronchi. This problem was also recognised by Garcia (1897), when the author referred that sphenoidal sinusitis may be confused with nasopharyngeal catarrh. This last article is, at the same time, the first known clear reference to ‘sinusitis’ in clinical Portuguese literature, when C. Garcia presented several treatments for the affection of the ethmoid, frontal, and sphenoidal sinuses in the journal A Medicina Contemporanea, summarizing the results from the 12th International Medical Congress that took place in Moscow. A real change in the perception of sinonasal disease is only apparent at the beginning of the 20th century, when an increasing number of articles and theses have shown that sinusitis was already clearly discussed as a clinical entity. The thesis entitled Highmore antrum and Highmorian sinusitis, presented in 1902 by José António Batista to the Porto Medical School, shows a very detailed knowledge of the history, embryology, anatomy, physiology, etiology, and surgical treatment of maxillary sinusitis (Baptista, 1902). Maximo Rodrigues presented in 1906 the thesis Indications for surgical interventions to frontal sinusitis to the Lisbon Medical School, stating that the medical treatment for patients evidencing less severe cases of rhinosinusitis included inhalations of menthol alcohol vapours, catheterization, nasal washes, and aspiration of the purulent material. Surgical drainage was indicated in very painful crises, orbital complications, or intracranial accidents (Rodrigues, 1906). According to this author, the resection of the middle turbinate was recommended for easing the drainage of the purulent material. When endonasal surgery was not enough, external surgery through the anterior wall of the frontal sinus was proposed (Rodrigues, 1906). Baptista (1902) also mentioned several different surgical techniques for maxillary sinusitis and discussed an interesting case study of a 39-year-old female presented to the Santo António Hospital (Porto), subjected to different treatments during the development of the disease (thermal inhalations during 15 days, perforation through the tooth socket to drain the pus, and, finally, bilateral trepanation of the maxillary sinuses).

Over the years, medical literature has shown an increasing knowledge regarding sinonasal disease. In the early 1920s, Bissaia-Barreto (1922) has described several options for frontal and maxillary sinusitis surgery performed at the Coimbra University Hospitals (CUH). Magalhães et al. (2017) have discussed exhaustively several of those approaches observed in the crania of two individuals who died in 1927 and 1933 and are currently amassed in the International Exchanges Skull Collection (Coimbra). Similar surgical approaches were performed in other Portuguese hospitals, as described, for instance, by d’Azevedo (1931) in two surgical cases of maxillary sinusitis in the Otorhinolaryngology Clinic of the Faculty of Medicine of the University of Lisbon. Actually, the Lisbon and Coimbra hospital records show that the medical treatment of sinonasal respiratory problems was fairly common during the first half of the 20th century. Lobato (1931) refers that 54 patients were observed due to rhinitis complaints and 38 due to sinusitis (of whom 27 underwent sinus surgery) between November, 1929, and November, 1930, at the Hospital School of the University of Lisbon. During the same period, eight other patients were observed due to chronic dacryocystitis, three due to concha bullosa, and 165 due to nasal septal deviation (of whom 34 underwent surgery) (Lobato, 1931). This growing concern with sinonasal respiratory diseases was also a reality at the Coimbra University Hospitals where, between 1913 and 1939, 179 patients (aged from 15 months to 73 years, x̅ =36.16) underwent sinus surgery (Magalhães et al., 2017; Figure 5).

25 24

20 15 N 15 13 12 12 11 11 11 10 10 10 9 7 7 6 5 5 5 3 2 2 2 1 1 0 0 0 0 0 0 1913 1915 1917 1919 1921 1923 1925 1927 1929 1931 1933 1935 1937 1939 Year Figure 5. Rhinosinusitis surgeries at the Coimbra University Hospitals between 1913 and 1939 (adapted from Magalhães et al., 2017:14).

In addition to clinical literature, advertising to capsules, throat lozenges, syrups, or antiseptics to treat respiratory diseases (Plate III, Figure 6) also shows that an increased importance was being given to people who were affected by such diseases. It is also interesting to note that plastic surgery for aesthetic purposes and functional correction of the nasal septum was a concern during the 1930s. Mello (1931), for instance, discussed the social problem concerning aesthetics resulting from septal deviations and two detailed case studies were described by Melo (1932).

1.2.3. Nasal obstruction and craniofacial morphology

Normal nasal breathing allows proper development of craniofacial morphology, also interacting with other functions such as normal mastication and swallowing (Lessa et al., 2005). On the contrary, nasal blockage and mouth breathing during growth may have significant consequences in craniofacial morphology, particularly in an excessive vertical facial growth (Lessa et al., 2005; Bansal et al., 2015). Clinical literature has more commonly named the syndrome resulting in these alterations as ‘long face syndrome’ or ‘long face pattern’ (e.g., Capelozza Filho et al., 2007; D’Ascanio et al., 2010; Cardoso et al., 2011; 2013), although several other names have been proposed (see Cardoso et al., 2011 and Bansal et al., 2015). The presence of a lower position of the tongue and mandible, half-opened lips, and reduced orofacial muscle tonicity to compensate the decrease in nasal airflow and facilitate respiration is usually observed (e.g., Vig, 1998; Faria et al., 2002; Lopatiene and Babarskas, 2002; Lessa et al., 2005; Harari et al., 2010; Bakor et al., 2011). These morphological changes may result in an elongated face, particularly in an increased anterior facial height and vertical excess of the lower facial third (Lopatiene and Babarskas, 2002; Arun et al., 2003; Jefferson, 2010; van Spronsen, 2010; Cardoso et al., 2011; 2013; Gallego-Romero et al., 2012). Table 4 show the major morphological alterations that are currently associated with nasal blockage and mouth breathing based on recent literature (Vig, 1998; Lessa et al., 2005; Capelozza Filho et al., 2007; Van Spronsen, 2010; D’Ascanio et al., 2010; Harari et al., 2010; Jefferson, 2010; Bakor et al., 2011; Cardoso et al., 2011; 2013; Agostinho et al., 2015; Bansal et al., 2015).

Table 4. Alterations associated with nasal blockage and mouth breathing in living patients. Anatomical area Alteration

. Alterations in the position of the head in relation to the neck Cranium . Dolichocephalic cranium . Increased total, upper, and lower anterior facial height . Deficiency may be present in the zygomatic prominence . Long nose and narrow nostrils . Marked nasolabial depression

. Lip apart posture with excessive maxillary incisor exposure Face . Excessive vermillion of the lower lip display at rest . Retrognathic position of the maxilla and mandible . Reduced size of mandible muscles . Extreme vertical condylar growth . Deficiency of the chin contour . More oval or tapered facial appearance . Enlarged adenoids . Narrow nasopharynx, maxillary arch, and intermolar width Intraorally . Increased palatal height . Lower position of the tongue and mandible . Dental malocclusion

Studies addressing the prevalence of long face pattern are scarce, but a recent study with 5020 Brazilian individuals, aged from 10 to 17 years old, shows values of 34.9% of any type of change in vertical relationship and 14.1% of a specific pattern of elongated face (Cardoso et al., 2011). Also, Bailey et al. (2001) found a prevalence of 22.4% of long face pattern in 2074 individuals from the United States seeking surgical- orthodontic treatment. Nevertheless, the effect of nasal blockage in craniofacial morphology is still under debate, with clinicians seeking answers to questions such as how much nasal obstruction is significant, at what age the onset of nasal blockage is critical, and how long the nasal obstruction has to be effective to result in a practical morphological alteration (Vig, 1998). Clinically, this is not dissociated from the lack of objective criteria used to define mouth breathing, although methodologies of cephalometric classification have been proposed (e.g., Lessa et al., 2005; Capelozza Filho et al., 2007). A strong genetic determination of craniofacial growth, particularly vertical measurements, has been proposed as one of its main backgrounds after several twin studies have been conducted (e.g., Lundström and McWilliam, 1987; Manfredi et al., 1997; Savoye et al., 1998; Carels et al., 2001; Šešelj et al., 2015; Djordjevic et al., 2016). Nevertheless, a comprehensive perception of the causes that can trigger these cranial, facial, and oral growth patterns still remain uncertain, although a complex multifactorial etiology involving genetic, environmental, and epigenetic regulation is under debate (e.g., Vig, 1998; van Spronsen, 2010; Bansal et al., 2015).

Plate III

Advertisements (1887a:no page).

Advertisements (1887b:no page).

Advertisements (1889:no page). Advertisements (1925:no page).

In addition to the pathologies and variations referred in the previous sections, the bony anatomy of the nose and maxillary sinuses may be affected by several other diseases. Leprosy is known to cause severe skeletal lesions, although skeletal involvement is thought to be present in 5 to 10% percent of the infected individuals with the Mycobacterium leprae (Ortner, 2003; 2008). In lepromatous leprosy, the most aggressive and malignant type of the disease, the bacillus spreads throughout the whole organism and the primary sites of infection are the skin, peripheral nerves, eyes, nasal and oral mucosa, larynx, pharynx, and the upper and lower extremities (Andersen et al., 1994; Aufderheide and Rodríguez-Martín, 2011; Lynnerup and Boldsen, 2012). Particularly in the nose, sequels of leprosy may result in epistaxis, destruction of the nasal mucosa, necrosis of the nasal septum, and the development of the so-called saddle nose deformity, resulting from the destruction of the nasal skeleton and causing functional difficulties and severe aesthetic problems (Menger et al., 2007; Aufderheide and Rodríguez-Martín, 2011). Nasopalatal alterations are a well-known consequence of lepromatous or near lepromatous leprosy (e.g., Møller-Christensen et al., 1952; Møller- Christensen, 1967; Møller-Christensen and Weiss, 1971), and the features associated with the ‘rhinomaxillary syndrome’ in leprosy were defined by Andersen and Manchester (1992) as follows:

- Resorption of the alveolar process of the maxilla, from the prosthion to the incisors; - Surface pitting, loss of cortical bone, and, at the end of the process, total loss of the anterior nasal spine; - Resorption and bilaterally symmetrical resorption and remodelling of the lateral and inferior margins of the piriform aperture; - Fine pitting, new bone formation, and erosive lesions along the nasal surface of the alveolar process of the maxilla; - Presence of pitting on both sides of the septum, particularly on the vomer, possibly exhibiting perforation; - Coarse pitting or destruction of the turbinates (particularly the inferior); - Empty cavity appearance resulting from the destruction of the nasal structures;

- The palatine processes may present small discrete erosive pits along the palatine suture, coalescent pitting, erosive lesion, or porous perforation.

Although the concomitant presence of these bony alterations are usually accepted as pathognomonic of leprosy (e.g., Andersen and Manchester, 1992; Andersen et al., 1994; Lynnerup and Boldsen, 2012), this assumption may not be this clear-cut (e.g., Waldron, 2009). Despite being frequently associated with leprosy, similar nasopalatal alterations may also be observed in treponematosis and tuberculosis (lupus vulgaris), and more rarely in leishmaniosis, actinomycosis, mucomycosis, and neoplastic disease (e.g., Brothwell, 1967; Møller-Christensen, 1967; Hackett, 1976; Manchester, 1994; Ortner, 2003). Particularly in the tertiary phase of syphilis, the tibia, cranial vault, and nasal cavity are usually the primarily affected areas, although only the presence of caries sicca is currently considered pathognomonic of treponematosis (Hackett, 1976; Waldron, 2009; Aufderheide and Rodríguez-Martín, 2011). Considering the facial bony anatomy, the nasal bones, nasal septum, hard palate, turbinates, and lateral walls of the maxillary antrum are the most often affected by tertiary syphilis (Ortner, 2003). These osseous alterations are reported to be more extensive and rapidly progressive than in leprosy (Hackett, 1976; Manchester, 1994), but its differentiation may be challenging. Moreover, in tertiary syphilis, the frontal bone is usually involved and the anterior nasal spine may be spared, unlike what happens in leprosy (Ortner, 2003). The walls of the nasal cavity may also be affected in tuberculosis of the facial bones (e.g., chronic tuberculosis of the zygomatic arch) by extension of mucosal tuberculosis (Ortner, 2003). Tuberculosis of the facial skin and soft tissues also may lead to the destruction of the nasal bones and piriform aperture (Ortner, 2003). During the 19th century, syphilis and leprosy were actually two of the most serious clinical problems in Portugal (Barbosa, 1856; Rocha, 1897; Carvalho, 1932; Matos, 2009; Lopes, 2014). Nevertheless, case reports of syphilis in Portuguese skeletal assemblages are extremely rare, and only a 28-year-old female extensively affected by caries sicca from the Medical School Collection (Coimbra) was presented by Lopes and colleagues in 2010. Also, few cases of leprosy from archaeological collections have been reported so far in Portugal (Antunes-Ferreira et al., 2013; Ferreira et al., 2013; Garcia et al., 2016).

Primary and secondary tumours may also affect the sinonasal tract. A tumour may be benign, if the growth comprises well-differentiated mature tissue and remains localised, or malignant, if the tumour consists of poorly differentiated immature tissue, continues to grow unchecked, and has the potential to involve other parts of the body through blood and/or lymphatic vessels (Ortner, 2003). Very few examples of nasal or sinonasal tumours were reported on skeletal remains (e.g., Campillo, 2005; Smith, 2010; Kendall et al., 2015), but clinical studies show that all structures in the nasal cavity may be involved (e.g., Ziari et al., 2006; Momeni et al., 2007; Lund, 2012; Seiberling and Wormald, 2012; Magnano et al., 2015). Other pathologies like Paget’s disease of bone (e.g., Mirra et al., 1995; Mays, 2010), fibrous dysplasia (e.g., Kruse et al., 2009; Cheng et al., 2012), several other types of dysplasia (e.g., Ihde et al., 2011; Boulet et al., 2016), and Crohn’s disease (e.g., Sari et al., 2007) may also affect the sinonasal bony anatomy, although are known to be very rare both in clinical patients and past populations.

1.3. Aims

The main objective of this study is to investigate, discuss, and contribute to the knowledge of several diseases and variations of the sinonasal anatomy of the human skull that may affect bone and hamper the normal functions of the upper respiratory tract. In this regard, three Portuguese identified osteological collections (19th and 20th centuries) are studied. This aim is fivefold and may be summarised as follows:

- To study and discuss the prevalence of nasal trauma in the context of the 19th and 20th centuries and to understand to what extent it is possible to differentiate between accidental or violent fractures;

- To investigate the prevalence of five nasal variations (concha bullosa and paradoxical curvature of the middle turbinate, accessory turbinate of the uncinate process, and deviation and spurs of the nasal septum) which are usually associated with the obstruction of the ostiomeatal complex and impairment of normal breathing. It is also intended to study the best use of computed tomography imaging for the differential diagnosis of the pneumatisation of the middle turbinate in skeletal remains, testing the assumption of its requirement for a conclusive diagnosis; 29

- To study the presence of new bone formations on the middle turbinates and within the maxillary sinuses, as well as to discuss its possible etiologies. In this regard, the hypothesis of association between the presence of nasal variations and sinonasal inflammation will also be tested as a central subject matter. This type of study using skeletal remains is rare and the few existent works use small, unidentified, and poorly preserved skulls;

- To test the possible influence of concha bullosa and maxillary rhinosinusitis on craniofacial morphology;

- To identify and discuss the prevalence of other nonspecific bone destructions, as well as to make the differential diagnosis of the most interesting cases.

2. Study base

The study base used in the present work comprises three Portuguese reference collections: the Medical Schools Skull Collection (MSSC) and the International Exchange Skull Collection (IESC), both curated by the University of Coimbra, and the Human Identified Skeletal Collection (HISC), curated by the Museu Bocage (National Natural History Museum, University of Lisbon). A reference collection should not be perceived as a population or a sample, since it is not a living group of people or randomly selected from those who were once living (Waldron, 2007). Because reference collections are the result of several factors that acted since each individual died until the moment the collection was amassed, almost everything about it is not random (Albanese, 2003; Cardoso, 2003-2004; Hoppa, 1996; Jackes, 2011; Palkovich, 2001; Waldron, 1994; 2007). Wood et al. (1992) referred to this as ‘the osteological paradox’, stating that palaeodemographic inferences from skeletal assemblages do not reflect the demographic profile of the once living population. Deaths are often the consequence of age-specific diseases, accidents, and conflict associated with young males, or reproductive hazards in young females, frequently resulting in over or underrepresentation of specific age groups (Jackes, 2011). For instance, the younger individuals represented in an osteological collection are only the ones who died prematurely and are often underrepresented in osteological assemblages (Cardoso, 2003-2004; 2005; Pinhasi and Bourbou, 2007). Several other biological, cultural, environmental, chemical, or methodological factors can also bias the differences between the total dead population and the proportion amassed in a reference collection, clearly showing that researchers have no control over the selection

of human osteological assemblages (Wood et al., 1992; Nawrocki, 1995; Hoppa, 1996; Cardoso, 2005; Pinhasi and Bourbou, 2007; Waldron, 2007; Jackes, 2011). As a result, the recommendations of Waldron (2007) are followed and the term ‘study base’, widely used in epidemiology, is applied throughout the current work. Moreover, biotic (e.g., fungi, bacteria, plant activity) and abiotic environmental factors (e.g., soil pH, exposure to water, temperature) are among the most important causes influencing the differential preservation of skeletal remains (e.g., Hoppa, 1996; Nawrocki, 1995; Nielsen-Marsh et al., 2007). The choice for reference collections also aims to somehow mitigate this taphonomic action. The cranial bones, particularly the anatomical structures within the nasal cavity, are extremely fragile and usually poorly preserved in archaeological assemblages, and those factors affecting the recovery of human bones may theoretically be lessen in skeletal remains that were buried for shorter periods of time or not buried at all (Table 5).

Table 5. Period of burial of the individuals of the three collections selected for this study. Collection Place of collection Date of death Collection amassed Burial time span Anatomical Museum of

Coimbra University; MSSC 1895-19021 1896-19031 Not buried Medical Schools of Lisbon and Porto IESC Cemetery of Conchada 1904-19371 1932-19421 Maximum of 38 years

Cemeteries of São João, HISC 1898-19812 1981-19912 Maximum of 93 years Benfica and Prazeres MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection; 1Fernandes (1985) and Rocha (1995); 2Cardoso (2006).

The recognition that reference collections should not be understood as ‘populations’ or ‘samples’ of the living population is far from invalidating the data collected, but leads interpretations to take into account its relative level of representativeness; whether the Coimbra and Lisbon skeletal collections are representative of the once living population (e.g., the total number of individuals living in Portugal during the same period of time) cannot be evaluated (e.g., Moleson, 1995). Nevertheless, the biases of reference collections can be exploited, improved, and made more consistent for answering research questions (Albanese, 2003), as well as be the best approach to generate diagnostic criteria in Palaeopathology (e.g. Mays, 2018). Therefore, the study of these individuals does not aim to know the reality of a ‘theoretical population’ in the sense given by Marôco (2014), but to recognise patterns

of disease and variation in a specific set of individuals who lived between 1804-1981 using their biographical data to reinforce knowledge of their past lives.

2.1. Sampling and study base

The study base comprises 2024 individuals from the Medical Schools Skull Collection (MSSC, N=540), the International Exchange Skull Collection (IESC, N=1117), and the Human Identified Skeletal Collection (HISC, N=367) who were born in Portugal and have most of the biographical data detailed. For the HISC collection this study was also limited to a smaller number of individuals whose biographical data was accessible at the Bocage Museum. All individuals who were undoubtedly misidentified were excluded from this work3. The MSSC collection is the oldest stored at the University of Coimbra (Plate IV, Figure 7) and was amassed between 1896 and 1903 together with the individuals’ biographical data (Fernandes, 1985; Rocha, 1995). Later, this data was compiled in two record books detailing birth and death places, sex, age at death, occupation, marital status, name, parents’ names, and location of the burial in the cemetery. The collection originally comprised 585 skulls (Rocha, 1995); nevertheless, birth place is unknown for thirty-four4 individuals and nine crania5 were missing during the periods of observation. In addition, individuals number 39 and 170 were misidentified as nonadults, resulting in a total of 540 individuals studied in the current work (Tables 6 and 7). Of these, 303 (303/540, 56.1%) came from the Medical School of Lisbon, 142 (142/540, 26.3%) from the Anatomical Museum of the University of Coimbra, and 95 (95/540, 17.6%) from the Medical School of Porto. Five hundred and twenty-eight (528/540, 97.8%) individuals were born6 between 1804 and 1891 and for twelve the date of birth is unknown. Five hundred and thirty-seven (537/540, 99.4%) died between 1895 and 1902, and for three

3 In this regard, we have to thanks for the help of Susana Garcia, curator of the Human Identified Skeletal Collection of Lisbon, who shared data detailing several misidentifications in the collection.

4 Individuals number 10, 31, 71, 277, 281, 294, 297, 305, 321, 322, 330, 331, 333, 337, 349, 350, 354, 357, 358, 374, 388, 390, 393, 394, 401, 402, 420, 425, 442, 443, 471, 540, 555, and 558.

5 Crania number 18, 105, 264, 312, 397, 404, 497, 511, and 569.

6 The date of birth is absent for the individuals of the three collection studied; nevertheless, it was calculated subtracting the age at death (plus one year) to the year of death.

the date of death is absent. Three hundred and thirty-six (336/540, 62.2%) are males and 204 (204/540, 37.8%) females, with age at death between 11 and 95 years old (x̄ =48.84; SD=17.87). The mean age at death is higher in females (x̅ =49.00; SD=19.44) than in males (x̅ =48.74; SD=16.86).

Table 6. Distribution of the individuals of the three collections studied by decades of birth and death.

MSSC N=540 IESC N=1117 HISC N=367 Total N=2024 Decades Birth Death Birth Death Birth Death Birth Death [1804]-1809 4 - - - - - 4 - 1810-1819 14 - 1 - - - 15 - 1820-1829 47 - 1 - - - 48 - 1830-1839 73 - 10 - 3 - 86 - 1840-1849 93 - 55 - 8 - 156 - 1850-1859 115 - 113 - 18 - 246 - 1860-1869 89 - 123 - 35 - 247 - 1870-1879 80 - 140 - 57 - 277 - 1880-1889 12 - 163 - 61 - 236 - 1890-1899 1 273 156 - 37 1 194 274 1900-1909 - 264 176 2 48 7 224 273 1910-1919 - - 140 14 27 15 167 29 1920-1929 - - 39 421 41 33 80 454 1930-1939 - - - 680 17 63 17 743 1940-1949 - - - - 7 106 7 106 1950-1959 - - - - 2 130 2 130 1960-1969 - - - - - 7 - 7 1980-[1981] - - - - - 1 - 1 Unknown 12 3 - - 6 4 18 7 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Table 7. Individuals selected for the present study by sex and age at death.

Age at death (years) Collection Sex N % Minimum Maximum x̄ SD

Male 336 62.2 11 92 48.74 16.86 Medical Schools Skull Female 204 37.8 14 95 49.00 19.44 Collection (MSSC) Total 540 100 11 95 48.84 17.87

Male 551 49.3 6 100 43.23 20.30 International Exchange Skull Female 566 50.7 7 109 49.24 22.93 Collection (IESC) Total 1117 100 6 109 46.28 21.87

Male 179 48.8 1 88 47.24 22.27 Human Identified Skeletal Female 188 51.2 2 94 54.66 24.44 Collection (HISC) Total 367 100 1 94 51.01 23.66 Male 1066 52.7 1 100 45.62 19.81 Total Female 958 47.3 2 109 50.24 22.63 Total 2024 100 1 109 47.81 21.31

The IESC collection was originally accumulated between 1932 and 1942 (together with the individuals’ biographical data) with the purpose of being exchanged for skulls from other international institutions, which has never happened (Fernandes, 1985;

Plate IV

Rocha, 1995). The biographical information is currently compiled in four record books, similar to those of the MSSC collection and with the same biographical information available. Fernandes (1985) and Rocha (1995) stated that the collection was originally composed of 1075 identified skulls, but a recent study showed that there are actually a total of 1144 (Lopes, 2014). Nevertheless, several of them were not considered in this work due to several issues:

 Lopes (2014) observed the misidentifications of individuals number 754 and 771, who were identified as nonadults, but are actually adults;

 The skulls 699 and 700, as well as 711 and 712 are also misidentified. It is possible that their documental identification was switched by mistake when the collection was amassed or before being labelled;

 Fourteen individuals7 were excluded from analysis because they were born outside of Portugal;

 The birth place was unknown for individuals number 149 and 160;

 Five8 crania/skulls were missing during the periods of observation of this work.

Thereby, 1117 skulls were studied (Table 7), 551 males (551/1117, 49.4%) and 566 females (566/1117, 50.6%), with age-at-death between 6 to 109 years old (x̄ =46.28; SD=21.87). The mean age-at-death is higher in females (x̅ =49.24; SD=22.93) than in males (x̅ =43.23; SD=20.30). All individuals were born between 1819 and 1926, died between 1904 and 1937 (Table 6), and were buried at the Municipal Cemetery of Conchada, Coimbra (Lopes, 2014). The HISC collection of the Bocage Museum was amassed between 1981 and 1991 and comprises 1767 individuals (Cardoso, 2006), 699 of whom with biographical parameters (age at death, place of birth and residence, occupation, and date and cause of death) available at the Bocage Museum through copies of the original records (Plate IV, Figure 8) and detailed in a digital database. The study base for this work was selected

7 Individuals numbers 25, 279, 285, 388, 391, 396, 473, 538, 648, 746, 828, 890, 980 and 1101.

8 Crania numbers 120, 390, 600, 770 and 1133.

among the individuals with the skull preserved and whose biographical information was most complete. Three hundred and sixty-seven individuals were selected, 179 (179/367, 48.8%) of whom are males and 188 (188/367, 51.2%) females (Table 7). Three hundred and sixty-one individuals were born between 1833 and 1951, and for six this information is missing. Three hundred and sixty-three (363/367, 98.9%) died between 1898 and 1981, and for four this information is absent. Age at death ranges between 1 and 94 years old (x̅ =51.01; SD=23.66) and mean age at death is higher in females (x̅ =54.66; SD=24.44) than in males (x̅ =47.24; SD=22.27). All individuals were buried in three of the Lisbon cemeteries (Alto de S. João, Prazeres and Benfica), corresponding to the remains that were destined for its communal graves, due to having been abandoned/neglected by their relatives or because they could not afford for an individual burial (Cardoso, 2005). Overall, 2024 individuals from the three collections were studied in this work, 52.7% (1066/2024) males and 47.3% (958/2024) females, who were born between 1804 and 1951, and died between 1895 and 1981. Mean age at death ranges between 1 and 109 years old (x̅ =47.81; SD=21.31) and is higher in females (n=952; x̅ =50.24; SD=22.63) than in males (n=1059; 45.62; SD=19.81). Almost half of the individuals of the three collections were born in the Coimbra district (947/2024, 46.8%), 17.3% (351/2024) were born in the Lisbon district, and the remaining 35.9% (726/2024) were born in other continental and insular Portuguese districts (Table 8).

2.2. Place of residence: rural or urban?

In the present study the Lisbon collection (HISC) was considered of urban background (Table 9), since 90.7% of the 367 individuals were residents in the Portuguese capital at the moment of death, 1.9% (n=7) in the Lisbon suburbs, 1.4% (n=5) in other districts, and for 6% (n=22) the place of residence was not stated. On the other hand, both the Coimbra collections (IESC and MSSC) were considered from rural to urban backgrounds, although the place of residence is sometimes vague and very incomplete, or most of the times non-existent.

Table 8. Individuals of the three collections selected for the current study by the district of birth. Collection District MSSC IESC HISC Total n % n % n % n % Aveiro 18 3.3 25 2.2 9 2.5 52 2.6 Beja 9 1.7 - - 11 3 20 1 Braga 14 2.6 6 0.5 4 1.1 24 1.2 Bragança 3 0.6 1 0.1 3 0.8 7 0.3 Castelo Branco 10 1.9 14 1.3 9 2.5 33 1.6 Coimbra 130 24.1 795 71.2 22 6 947 46.7 Évora 11 2 3 0.3 6 1.6 20 1 Faro 11 2 5 0.4 8 2.2 24 1.2 Guarda 17 3.1 55 4.9 12 3.3 84 4.1 Leiria 36 6.7 62 5.6 11 3 109 5.4 Lisbon 144 26.7 14 1.3 193 52.6 351 17.3 Funchal 2 0.4 1 0.1 3 0.8 6 0.3 Minho province 1 0.2 - - - - 1 0.05 Ponta Delgada - - 1 0.1 - - 1 0.05 Portalegre 2 0.4 10 0.9 9 2.5 21 1 Porto 58 10.7 13 1.2 7 1.9 78 3.8 Santarém 18 3.3 23 2.1 22 6 63 3.1 Setúbal - - 1 0.1 15 4.1 16 0.8 Viana do Castelo 11 2 2 0.2 4 1.1 17 0.8 Vila Real 9 1.7 13 1.2 6 1.6 28 1.4 Viseu 36 6.7 73 6.5 13 3.5 122 6 Total 540 100 1117 100 367 100 2024 100 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Table 9. Background of the individuals amassed considered for the three collections studied. Collection Background Medical Schools Skull Collection (MSSC) Rural to urban International Exchange Skull Collection (IESC) Rural to urban Human Identified Skeletal Collection (HISC) Urban

In the IESC collection 17.2% (n=192) of the individuals were residents in one of the parishes of the city of Coimbra at the time of their death, 10.1% (n=113) lived in other rural areas of the same district, 13.9% (n=155) lived in other districts (usually also from rural places) and died in the Coimbra University Hospitals, and for 58.8% (n=657) the place of residence is absent. The place of residence of all individuals amassed in the MSSC collection is also missing. Instead, the place of birth was searched, showing a sparse occupation across urban and rural areas, whilst the cities of Lisbon, Porto, and Coimbra are presented as the places of death.

3. Methodology

The facial bones and the nasal cavity were macroscopically examined with the help of artificial light (a desk lamp and a small light), a magnifying glass, and a mouth mirror. The observations were made without the previous knowledge of the individuals’ identification. Taking into consideration that this was, to a certain extent, an exploratory study, mainly because several of the nasal variations studied were not yet subjected to a replicable methodology for skeletal remains, a first group of 200 crania was observed with the purpose of understanding the most suitable methodology to describe and record each bone change. A second observation of this first group was then carried out. The pathological analysis and the definition of different types of bone reaction followed the recommendations of Ortner (2003), Waldron (2009), and Aufderheide and Rodríguez-Martín (2011). The specific observation of the different osseous alterations within the nasal cavity and maxillary sinuses were recorded as described below.

3.1. Variations within the nasal cavity

The middle nasal turbinates were carefully inspected and paradoxical and hypertrophic turbinates were recorded by side and degree of development. Several clinical studies state that small paradoxical turbinates are not significant for health but, if large, may impair access to the ostiomeatal complex (e.g., Tonai and Baba, 1996; Beale et al., 2009), although no specific methodology has been proposed to differentiate both. Also, the method developed by Keast et al. (2008) is only suitable for imaging purposes. In this regard, a new method to record paradoxical curvatures of the middle turbinates is proposed as follows (Plate V, Figure 9):

- Type 0, no paradoxical turn: the most anterior and inferior portion of the middle turbinate is bent towards the ostiomeatal complex or is vertically directed towards the inferior nasal concha of the same side;

- Type 1, small paradoxical turn: the most anterior and inferior portion of the middle turbinate is bent paradoxically towards the nasal septum, but not at the same level or undertaking its lamellar (or most superior and anterior) portion when a vertical line is drawn with the cranium placed in norma frontalis;

- Type 2, large paradoxical turn: the most anterior and inferior portion of the middle turbinate is bent paradoxically towards the nasal septum, at the same level or beyond its lamellar or most superior and anterior part when a vertical line is drawn with the cranium placed in norma frontalis.

Hypertrophies of the middle nasal turbinates were scored for presence, side, and type, the last following the recommendations of Bolger et al. (1991) distinguishing between the pneumatisation of its superior portion (lamellar concha bullosa), inferior portion (bulbous concha bullosa), or both the lamellar and bulbous portions (extensive concha bullosa). Nevertheless, the macroscopic characterisation of a hypertrophy of the middle turbinate can be challenging, because such hypertrophies may be the result of different etiologies. Computed tomography (CT) is the suitable medical imaging option to support the differential diagnosis (e.g., Laine and Smoker, 1992; Mazza et al., 2007; Wani et al., 2009): the presence of an internal empty space defines a concha bullosa, whereas an internal bony structure is in agreement with the diagnosis of a haemangioma or a fibrous-osseous lesion (e.g., Galvan et al., 2007; Goff et al., 2015). Also, clinical literature suggests the association between the size of the concha bullosa and sinonasal pathology (e.g., Uygur et al., 2003; Stallman et al., 2004; Hatipoglu et al., 2005; Yigit et al., 2010). These premises entailed the use of CT imaging, which was performed in 60 crania selected within the group where middle turbinate hypertrophy appeared hypertrophied on gross examination in the Coimbra International Exchange Collection. CT scans were performed at the Coimbra Hospital and Universitary Centre (CHUC) using a Siemens Somatom Emotion 16 CT scanner with study protocol for imaging the paranasal sinuses, field of view (FOV) for head with kernel H50, and associated bone window. Several other technical parameter were kept constant (16x0.75mm collimation, pitch of 1.0, a 0.5 second rotation time, and constant tube voltage of 80kV with care 44

Plate V

Figure 9. Nasal cavities demonstrating the methodology adopted to record type 0 (top), type 1 (bottom left), and type 2 (bottom right) paradoxical curvatures of the middle turbinates. Dotted line – Anterior contour of the middle turbinate (MT); a – The most medial point of the lamellar portion of the MT; b – the most medial and inferior point of the bulbous portion of the MT; S – Septum; IT – Inferior turbinate.

dose system) and the range of the scanned area was adapted to the area of interest (Plate VI, Figure 10). All scans were reconstructed in axial plane with an effective thickness of 0.75mm and incremental reconstruction of 0.5mm. The study was completed with post-processing of 3D volume rendering and 2D multiplanar reformat with a thickness of 1.0mm in axial, coronal, and sagittal planes. The 60 crania were first subjected to gross examination and later the results of these observations were compared to the results of the CT scans for presence, side, and type to test the reliability of macroscopic diagnosis of concha bullosa. As recommended by Mays et al. (2012), those that appeared grossly rather large but turned out not to be pneumatised were considered as normal size variation. The maximum medio-lateral width of the concha bullosa was measured directly on a previously selected slice of the CT scan using image software analysis ImageJ9 (Ferreira and Rasband, 2012). The measure was taken perpendicular to a straight line drawn between the crista galli and the intermaxillary suture, as recommended by Mays et al. (2014). The measurement was then standardised by dividing it by the width across the entire nasal passage (from the nasal septum to the lateral wall on the same slice and at the same location) and the result is the extent to which the bullous concha obstructs the respective nasal passage (Mays et al., 2014). Clinical literature describes an accessory turbinate as a medially bent and anteriorly folded uncinate process, a curvature which results in a bony structure nearly perpendicular to the lateral nasal wall (Aksungur et al., 1999; Lin et al., 2006; El- Shazly et al., 2012; Al-Qudah, 2015). As stated by Aksungur et al. (1999), the medial curvature may involve the entire uncinate process or only part of it. This is one of the most frequent variations of the uncinate process and studied as a potential cause for the obstruction of the middle meatus and occlusion of the ostium into the maxillary sinus (Isobe et al., 1998; El-Shazly et al., 2012). In the current work, accessory turbinates were scored using a binary classification (presence or absence) (Plate VII, Figure 11). For the past decades clinical literature presented several different types of classification of nasal septal deviation which became one of the main problems to establish comparative approaches. Several clinical studies adopted binary (presence/absence) or subjective classifications (e.g., Aktas et al., 2003; Stallman et al.,

9 The software is available for free download at https://imagej.nih.gov/ij/

2004; Smith et al., 2010; Sevinc et al., 2013; Kucybała et al., 2017; Santos and Prado, 2017) and perhaps the morphological classification most widely used was first introduced by Ranko Mladina in 1987 (Mladina, 1987) and continuously described by the author in the following decades (Subarić and Mladina, 2002; Mladina et al., 2008; 2015; 2017; Mladina, 2012). This approach emphasises seven different types of septal deformities and its clinical consequences. In addition, several other morphological approaches were proposed during the last decades (e.g., Guyuron et al., 1999; Baumann and Baumann, 2007; Jin et al., 2007) and recently reviewed by Teixeira and colleagues (2016). Several other clinical studies used quantitative approaches for measuring nasal septal deviation (Uygur et al., 2003; Holton et al., 2012; Mohebbi et al., 2012; Kapusuz Gencer et al., 2013; Javadrashid et al., 2014; Lin et al., 2014; Gregurić et al., 2016) on CT scan. Nevertheless, all these classifications are based on the nasal septum as a whole (bony and cartilaginous framework), whilst the perpendicular plate of the ethmoid and the vomer are the only structures preserved in skeletal collections. In the present work, the tortuosity of the nasal septum was measured following the recommendations of Mays (2012), only when its anterior osseous structure was entirely preserved. Each cranium was photographed in norma frontalis with the internasal suture, nasal septum, anterior nasal spine, and the intermaxillary suture positioned centrally in the grid line of the image. Two landmarks were placed on the anterior margin of the bony septum using ImageJ: the first on the most superior part of the septum visible in the photograph and the second at the intermaxillary suture on the anterior nasal spine (Mays, 2012; Plate VII, Figure 12). The chord and thread lengths were measured on the image between these two landmarks, and the nasal septal deviation index (NSDI) was given by:

NSDI = (100 × thread length / chord length) – 100

Moreover, since the cartilaginous portion of the nasal septum is absent, a new approach adapted to skeletal remains was necessary regarding the morphological characterisation of nasal septal deviation. Five types of deflection were recorded observing the septum in norma frontalis. The differentiation between each type is based on the septal bone that is deviated (the perpendicular plate of the ethmoid, the vomer, or both) and the different forms that each deflection can assume (Plates VIII and IX, Figures 13 to 17): 46

Plate VI

Figure 10. CT scan equipment at the Coimbra Hospital and Universitary Centre (top); post-processing of 3D imaging and 2D multiplanar reformat (bottom). Plate VII

Figure 11. Nasal cavity showing the normal anatomy of the uncinate process (left, arrows) and an accessory turbinate (right, arrows). MT – Middle turbinate; IT – Inferior turbinate; S – Septum.

Figure 12. Nasal cavity demonstrating the septal chord (a) and septal thread length (dotted line) as recommended by Mays (2012) for measuring nasal septal deviation. MT – Middle turbinate. Plate VIII

PPE PPE PPE

V V V

Figure 13. Nasal septal deviation, type 1: unilateral deflection of the perpendicular plate of the ethmoid (PPE); the vomer (V) presents no deviation.

PPE PPE PPE

V V V

Figure 14. Nasal septal deviation, type 2: unilateral no deviation. deviation of the vomer (V); the perpendicular plate of the ethmoid (PPE) presents no deflection.

PPE PPE PPE

V V V

PPE PPE PPE

V V V

PPE PPE PPE

V V V

Figure 18. Examples of septal spurs on the ethmoid/vomer fusion. MT – Middle turbinate; IT – Inferior turbinate; S – Septum. - Type 1, isolated deviation of the ethmoid: the perpendicular plate of the ethmoid is unilaterally deviated, whilst the vomer presents no deviation;

- Type 2, isolated deviation of the vomer: the vomer is unilaterally deviated, whereas the ethmoid shows no deflection;

- Type 3, ‘C-type’ deviation of the ethmoid and vomer: the deflection originated on the ethmoid bone and represents the deviation of both the ethmoid and the vomer. This type of deviation usually means a ‘C’ or ‘inverted C’ appearance of the septum, depending on the side of deviation. The point of maximum deflection in type 3 can be observed along the perpendicular plate of the ethmoid bone;

- Type 4, ‘L-type’ deviation of the ethmoid and vomer: unlike type 3, the deflection originated on the vomer, but also represents the deviation of both the septal bones. It is distinguished from type 3 because results in an ‘L’ or ‘inverted L’ appearance, depending on the side of deflection, which means that the point of maximum deviation in type 4 is in the ethmoid/vomer fusion;

- Type 5, ‘C-type’ and ‘L-type’ deviation of the ethmoid and vomer: this type of nasal septal deviation is the result of the presence of types 3 and 4, whether deviated to the same or to opposite sides.

For each type of deviation the direction of the perpendicular plate of the ethmoid and/or the vomer was recorded by the convexity of its curvature. Although the bones of the nasal septum fuse between 20 and 30 years of age, the ossification of the perpendicular plate of the ethmoid towards the vomer and the fusion of the edges of the vomerine groove happens roughly until 20 years old (Scheuer and Black, 2000; White and Folkens, 2005). Kim et al. (2008) also state that the total dorsal length of the nasal septum increases until the age of twenty, showing that these structures are already developed at this age. In this regard, only the preserved septa of individuals with at least twenty years old were studied. Septal spurs were recorded when a horizontal crest or ‘tilt’ was present in the ethmoid/vomer fusion (EVF) of the nasal septum, following the clinical definitions of Guyuron et al. (1999) and Mladina and colleagues (2015) (Plate IX, Figure 18).

3.2. Nasal trauma and maxillary rhinosinusitis

The nasal bones were considered present when completely preserved, since nasal bone trauma may only affect its most anterior portion. As there is not yet a detailed methodological approach to record nasal trauma in skeletal remains, an adaptation of the clinical recommendations of Stranc and Robertson (1979), Murray et al. (1986), and Han et al. (2011) was defined for the osseous anatomy of the nose. Nasal trauma was classified according to five characteristics:

- Nasal trauma definition: the piriform aperture comprises the nasal bones superiorly, and the maxillae laterally and inferiorly. Nasal trauma was considered, not only when the nasal bones were fractured, but also the frontal processes of the maxillae and/or any of the internal osseous structures of the nose;

- Side of deviation: the side of deviation of the nasal bones/frontal processes of the maxillae was recorded adapting the recommendations of Stranc and Robertson (1979), for whom the presence of a lateral deviation of the nasal bones/frontal processes of the maxillae is associated with a lateral force impact;

- Pattern: the pattern of fracture of the nasal bones was adapted from the clinical literature abovementioned, as well as from the recommendations of Lovell (1997) and Ortner (2003) for trauma analysis of the long bones. Five patterns were considered: ‘transverse’, ‘longitudinal’, or ‘oblique’ (with reference to the internasal suture – the suture joining the nasal bones), ‘comminuted’ (when at least one nasal bone was fractured in two or more pieces), and ‘doubtful’;

- Other facial fractures: fractures in the frontal, zygomatic, and orbital bones, as well as in the zygomatic processes of the temporal bones and mandible were recorded, although it is impossible to identify if other facial fractures are temporally concurrent with nasal trauma;

- Side: the presence of trauma was recorded according to the side (right, left, bilateral);

- Bone remodelling: nasal fractures were classified as ‘remodelled’, ‘remodelling’, or ‘no remodelling’;

The maxillary sinuses were subjected to gross examination searching for new bone formation on the sinus floor and walls. When necessary, observations were aided by a dental mirror. In case of complete sinuses an endoscope (Cartull Professional, external diameter of 4.9 mm) was used (if possible), as recommended in literature (e.g., Boocock et al., 1995a; Lewis et al., 1995; Merrett and Pfeiffer, 2000; Roberts, 2007). This non-invasive technique uses natural openings, usually through the middle meatus, in the lateral wall of both nasal cavities. The maxillary hiatus or nasal fontanelles are large natural openings in the lateral nasal wall of the disarticulated maxillary bone which are covered by mucosa and connective tissue (e.g., Stammberger et al., 1995; Lund et al., 2014). The absence of these structures in skeletal remains allows the insertion of an endoscope, which is why the maxillary sinuses are usually the only ones accessible for inspection. No authorisations were obtained to clean the antra or to drill into the maxillary sinus, as suggested in other studies (e.g., Boocock et al., 1995a; Lewis et al., 1995; Sundman and Kjellström, 2013a). The unaffected appearance of the dry maxillary antrum surface is smooth and regular (Lewis et al., 1995). Bone changes related to rhinosinusitis are suggested to be similar to the ones caused by the inflammatory response in other parts of the body (Boocock et al., 1995a; Merrett and Pfeiffer, 2000). Wells (1977) was probably the first to systematically study different osseous alterations (spicules, excrescences, rough ‘mini’ exostoses, and pits) associated with maxillary rhinosinusitis. Nevertheless, only in the 1990s Boocock and colleagues (1995a) have published a methodology which has been the basis for sinusitis investigation in skeletal remains since then. In the current work, the method to record bone changes in the floor and walls of the maxillary antra was adapted from Boocock et al. (1995a) and Merrett and Pfeiffer (2000) and categorized as follows:

- Spicule-type bone formation: spicules are described as a continuum of bone deposition that appear to have been applied on its surface (Boocock et al., 1995a; Merrett and Pfeiffer, 2000);

- Remodelling spicules: spicules that appear to be remodelling into the walls of the sinus, merging and becoming plaque-like, or merging together as molten wax-like appearance, as proposed in Boocock et al. (1995a) and Sundman and Kjellström (2013a);

- Lobules of white bone: rounded masses of bone on the surface of the sinus, which are stated in literature as active new bone formation at the time of death (e.g., Boocock et al., 1995a; Merrett and Pfeiffer, 2000);

- Plaque: plaque may vary in the texture of the surface, and the thickness of the bony reaction; its surface can appear as smooth and dense or porous (Merrett and Pfeiffer, 2000).

The recording of the extent and severity of bone formations within the maxillary sinuses was adapted from Sundman and Kjellström (2013a), as previously suggested by Magalhães et al. (2017) for sinuses where it is not possible to measure the size of the bone formations: degree 0 (no alterations), degree 1 (isolated alterations, maximum of three isolated spicules), degree 2 (isolated alterations to half of the sinus), and degree 3 (more than half of the sinus shows alterations). When different osseous alterations were present in the same sinus they were also recorded according to their extent and severity. Furthermore, pitting and white pitted bone were also taken into account within the maxillary antra, but recorded separately. The posterior teeth have a close relationship with the sinus floor, which is subject to remodelling during teeth development and/or loss, making it difficult to differentiate between its physiological or pathological origin (e.g., Lewis et al., 1995; Krenz-Niedbała and Łukasik, 2016). Pits and white pitted bone, as defined by Boocock et al. (1995a), were thus recorded and the biological profile of the individuals presenting these osseous alterations was compared to the ones showing new bone formations. Also, oroantral fistulae connecting the teeth to the maxillary sinuses were carefully searched to avoid confusion with postmortem damage and differentiated as suggested by Sundman and Kjellström (2013a): (1) fistula presenting rounded and smooth edges or (2) fistula surrounded by a ‘chimney-like’ new bone formation. Oroantral root protrusions without bone remodelling were distinguished from fistulae when the respective tooth was present and signs of possible inflammation on the edges of the oroantral connection were absent.

Finally, four types of alterations were considered on the hard palate (palatine processes and bones), following the recommendations of Matos (2009): (1) reactive aspect of the bone along the median palatine suture, always coexisting with macroporosity (>1mm), coalescing or not; (2) small perforations (one or more micro or macropores) through the palatine processes into the nasal floor; (3) osteolytic lesions, including coalescing porosities with >1mm of diameter; (4) new bone formations.

3.3. Craniofacial morphology

The measurements selected in the present work to study craniofacial morphology have been systematically used since the 19th century by anthropologists and anatomists like Anders Retzius (1846), Paul Broca (1875; 1879; 1883), and Paul Topinard (1876). In 1906, an international congress took place in Monaco attempting to unify and standardise craniometric and cephalometric measurements (Papillault, 1919), whereas several other lists were defined throughout the 20th century (e.g., Buxton and Morant, 1933; Montagu, 1951; Vallois, 1965). Twenty measurements and six indices were used in the current work to access craniofacial morphology based on the definitions compiled by Howells (1973), Brothwell (1981), Bass (1995), and Langley et al. (2016) (Table 10). Priority was given to the measurements of the facial skeleton that were tested in clinical studies to differentiate between nasal and oral breathing individuals (e.g., Harari et al., 2010; Bakor et al., 2011; Gallego-Romero et al., 2012). Nevertheless, the selected measurements and indices describe overall skull and facial morphology. Also, several measurements with alveolar landmarks (e.g., maxillo-alveolar breadth, palate breadth, and palatal length) were excluded, because of the high prevalence of alveolar resorption due to antemortem tooth loss, which increases with age at death in the individuals of the Coimbra collections, as demonstrated by Wasterlain (2006). All measurements were recorded in millimetres using the spreading and sliding callipers on the left side (for bilateral measurements of the skull), except when damaged, in whose cases the right side was used. In order to test craniofacial morphological variability, three groups of individuals (‘group 1=concha bullosa’, ‘group 2=maxillary rhinosinusitis’, and ‘group 3=control’) with similar number of male and female individuals were chosen (Table 11). Also, since the development of the cranial bones generally ends just before early adulthood 51

(Scheuer and Black, 2000), only adults (20 years old or more) were selected, 164 (164/174, 94.3%) from the International Exchange Skull Collection (IESC) and ten (10/174, 5.7%) from the Medical Schools Skull Collection (MSSC).

Table 10. List of measurements selected to evaluate craniofacial morphology. Measurement Abbreviation Instrument Reference Glabello-occipital length GOL Basion-nasion length BNL

Basion-bregma height BBH Spreading calliper Howells (1973) Maximum cranial breadth MCB Bizygomatic breadth ZYB Basion-prosthion length BPL Nasion-prosthion height NPH Nasal height NLH Cranium Orbital height OBH

Orbital breadth OBB

Nasal breadth NLB Sliding calliper Howells (1973) Bimaxillary breadth ZMB Bifrontal breadth FMB Interorbital breadth DKB Simotic chord WNB Nasion-bregma chord FRC Zygoorbitale breadth ZOB Sliding calliper Langley et al. (2016) Intercondylar width W1 Mandible Bigonial breadth Go-Go Sliding calliper Brothwell (1981) Symphysial height H1 Cranial index CI Cranial length-height CHI

Cranial breadth-height BHI Indices – Bass (1995) Upper facial UFI Orbital index OI Nasal index NI

Table 11. Groups of individuals selected for testing the craniofacial morphology.

Age at death Group Sex n % Range (years) x̅ Male 27 48.2 21 – 73 45.22 Concha bullosa Female 29 51.8 22 – 87 48.59 Total 56 100 21 – 87 46.96

Male 29 50 20 – 80 48.14 Maxillary Female 29 50 23 – 84 51.66 rhinosinusitis Total 58 100 20 – 84 49.90 Male 30 50 23 – 83 45.80 Control Female 30 50 22 – 82 47.77 Total 60 100 22 – 83 46.78

The group ‘concha bullosa’ comprises 56 individuals (age at death between 21 and 87 years old, X̅ =46.96) in whom the presence of concha bullosa was confirmed by CT scan. Twenty-seven (27/56, 48.2%) are males and 29 (29/56, 51.8%) are females.

The group ‘maxillary rhinosinusitis’ includes 58 individuals (age at death between 20 and 84 years old, X̅ =49.90) where the most severe cases of bone formations within the maxillary sinuses (types 2 or 3) were recorded. Twenty-nine are males (29/58, 50%) and 29 (29/58, 50%) are females. The ‘control’ group comprises 60 individuals (age at death between 22 and 83 years old, X̅ =46.78) in whom concha bullosa and bone formation within the maxillary sinuses are absent. Thirty are males (30/60, 50%) and 30 (30/60, 50%) are females.

3.4. Nasal variations: review of clinical literature

A review of the literature found in PubMed, Mendeley, and Web of Science was conducted on documents reporting the prevalence of concha bullosa, paradoxical curvature, accessory turbinate, nasal septal deviation, and septal spurs. The criteria to screen for relevant articles included:

- Articles written in English, French, Portuguese, or Spanish; - The use of computed tomography (CT) scan or cone beam computed tomography as imaging techniques used for diagnosis; - At least 100 patients included; - When different groups were compared in the same study each group had to present at least 80 individuals.

Furthermore, for the specific study of concha bullosa, the following criteria were also included:

- Prevalence of concha bullosa of the middle turbinate detailed separately concerning superior and inferior pneumatisations; - Definition of concha bullosa regardless of the size.

These two criteria were used to mitigate factors that can originate discrepancy in prevalence analysis, such as differences in criteria for pneumatisation and in the method of analysis (e.g., Bolger et al., 1991; Stallman et al., 2004). ‘Related citations’ and ‘cited by’ were also reviewed for relevant articles and references cited within each one of the selected articles were similarly scrutinised.

3.5. Anatomical nomenclature and the Istanbul terminological framework

Despite the advances in knowledge since the 1980s regarding the anatomical structures and pathophysiology of the sinonasal region, its correct terminology and nomenclature is still prone to confusion (Stammberger et al., 1995; Lund et al., 2014). In this regard, the ‘European Position Paper on the Anatomical Terminology of the Internal Nose and Paranasal Sinuses’ (Lund et al., 2014) will be used as a basis in this work. The text was an attempt to reconsider the aspects of nomenclature first done by Stammberger and colleagues in 1995 and describes thoroughly all the structures encountered in the nasal cavity, paranasal sinuses, and at the interface with the orbit and skull base. The term ‘rhinosinusitis’ was also adopted, following the recommendations of several clinical guidelines and position papers published since the 1990s (e.g., Lund and Kennedy, 1995; Lanza and Kennedy, 1997; Benninger et al., 2003; Meltzer et al., 2004; Fokkens et al., 2005; 2007; 2012; Dykewicz and Hamilos, 2010; Desrosiers et al., 2011; Meltzer and Hamilos, 2011; Orlandi et al., 2016). Finally, the Istanbul terminological framework to increase confidence in palaeopathological diagnosis (Appleby et al., 2015) was also followed and the recommendations of Buikstra and colleagues (2017) for scientific rigor in Palaeopathology were taken into account.

3.6. Statistical analysis

All data were analysed using the Statistical Package for the Social Sciences (SPSS), version 21.0. Concerning categorical variables, Chi-Square testing was used to determine if independent groups are different concerning a given characteristic. The normal distribution of the parametric variables was evaluated using the Shapiro-Wilk (for variables with groups presenting 50 or less cases) and Kolmogorov-Smirnov (for variables with groups presenting more than 50 cases) tests, as recommended by Marôco (2014), whilst the Levene’s test was performed to fulfil the assumption of homogeneity of variances. Nevertheless, literature shows that formal normality tests may be unreliable for large samples (e.g., Field, 2009; Ghasemi and Zahediasl, 2012; Kim, 2013). Particularly both the independent samples t-test (Student t Test) and the one-way analysis of variance (one-way ANOVA) may be robust to the violation of the assumption of normality, not only if distributions are not extremely biased or flattened, but also if the dimensions of the samples are not to small

(e.g., Schmider et al., 2010; Kline, 2011; Marôco, 2014; Ross, 2014). Indeed, the central limit theorem (CLT) shows that, as the sample size increases, its mean is increasingly close around the population mean with a decrease in variance (Murteira et al., 2002; Elliot and Woodward, 2007; Field, 2009; Howell, 2014; Marôco, 2014; Kwak and Kim, 2017). The CLT ensures that the sum of n independent random variables, all with the same mean and finite variance, present approximate distribution, N(0,1), after standardisation and for n sufficiently large (Murteira et al., 2002; Elliot and Woodward, 2007; Tabachnick and Fidell, 2007; Howell, 2014; Marôco, 2014; Kwak and Kim, 2017). The CLT is one of the most important theorems in statistics (Howell, 2014; Kwak and Kim, 2017) which specifies the nature of the sample distribution of the mean and is defined by Howell (2014:297) as follows:

“Given a population with mean µ and variance σ2, the sampling distribution of the mean (the distribution of sample means) will have a mean equal to µ (i.e., 휇x = 휇) and a variance (휎 ) equal to 휎/푁 (and standard deviation, 휎x = σ/√푁). The distribution will approach the normal distribution as N, the sample size, increases”.

As a result, variables presenting each group with at least 100 cases were accepted for both independent samples t-test and one-way analysis of variance. Linear regression was performed after testing if residuals (errors) followed a normal distribution, if its variance was constant, and if they were independent. Inference for the model of linear regression is only valid when these assumptions are fulfilled (e.g. Marôco, 2014). The presence of significant outliers was also checked. When the dependent variable was binary, a binomial logistic regression was calculated to estimate the probability of a binary response on several predictors or independent variables. P-values equal to or less than 0.05 were accepted as significant for all tests performed.

4. Results and discussion

The results and discussion of the diseases and variations affecting the nasal cavity and maxillary sinuses will be presented in five main chapters: (4.1.) nasal trauma, (4.2.) anatomical variations within the nasal cavity, (4.3.) bone formations on the middle turbinates and within the maxillary sinuses and its possible association with nasal variations, (4.4.) the possible influence of concha bullosa and maxillary rhinosinusitis on craniofacial morphology, and (4.5.) a miscellaneous of other bony alterations.

4.1. Nasal trauma

4.1.1. Results

Of the 1770 individuals with at least one nasal bone preserved, 148 (148/1770, 8.4%) exhibit nasal trauma. The International Exchange Skull Collection (IESC) (53/986, 5.4%) present significantly fewer occurrences (Pearson χ2=26.303; d.f.=2; p<0.001) compared to the Medical School Skull Collection (MSSC) (64/509, 12.6%) and the Human Identified Skeletal Collection (HISC) (31/275, 11.3%) (Table 12). Overall, male individuals account for the higher frequency in the study base (males=101/970, 10.4% vs females=47/800, 5.9%), with significant differences (Pearson χ2=11.780; d.f.=1; p=0.001). The youngest individual showing nasal trauma was a 23-year-old female, whilst the oldest was a 95-year-old female. When the three collections were pooled, the individuals exhibiting nasal trauma show higher mean age at death (absence X̅ =46.67, SD=20.85 vs presence X̅ =54.79, SD=16.79), showing statistical significant differences (Student’s t= -4.563; d.f.=1756; p<0.001) (Figure 19).

The increased age also results in significant differences in both sexes (males Mann-Whitney U=53811.5, p<0.001; females Mann-Whitney U=21589.0, p=0.004). The 148 individuals presenting nasal trauma were born between 1804 and 1921 and died between 1895 and 1969.

Table 12. Prevalence of nasal trauma by sex.

Male Female Total Collection N n % N n % N n % MSSC 322 48 14.9 187 16 8.6 509 64 12.6 IESC 510 35 6.9 476 18 3.8 986 53 5.4 HISC 138 18 13 137 13 9.5 275 31 11.3 Total 970 101 10.4 800 47 5.9 1770 148 8.4 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Males Females

20 17,5 18 16 14,7

14 12,3 12 12 10 9,1 % 8,1 7,9 8 5,8 5,6 6 5,3 4 3,4 1,9 2 0 0 0 <=19 yo 20-29yo 30-39yo 40-49yo 50-59yo 60-69yo => 70yo

Figure 19. Nasal trauma by sex and age at death.

Of the 1636 individuals with both nasal bones preserved, 35 (35/1634, 2.1%) show trauma on the right side, 17 (17/1634, 1%) on the left side, and 90 (90/1634, 5.5%) bilateral fracture of the nasal bones (Table 13; Appendix A1). The higher frequency of bilateral trauma presents significant differences (Pearson χ2=5.297; d.f.=1; p=0.021), as well as the higher frequency of unilateral trauma on the right side (Pearson χ2=6.667; d.f.=1; p=0.010). The type of impact force, pattern, and presence of other facial fractures were also recorded. Ninety-one (91/148, 61.5%) individuals show a lateral impact force fracture, 52 (52/91, 57.1%) of whom with the nasal bones deviated to the right and 39 (39/91, 42.9%) to the left (Plate X, Figure 20). Ninety-one (91/148, 61.5%) individuals exhibit a transverse pattern of fracture, in 11 (11/148, 7.4%) the pattern was oblique, and in 60

Plate X

A 90-year-old male (MSSC 300) presenting comminuted trauma of both nasal bones, which are deviated to the Figure. A 90right-year side;-old themale fracture (MSSC resulted 300) presenting from a blun comminutedt impact force tra umaon the of leftboth side nasal (right). bones which are deviated to the right side. The fracture resulted from a blunt impact force on the left side.

four (4/148, 2.7%) parallel, whilst in eight individuals (8/148, 5.4%) more than one pattern of fracture was identified. In 26 (26/148, 17.6%) individuals a comminuted pattern was recorded and in one (1/148, 0.7%) the pattern was doubtful. Finally, trauma of the nasal bones was absent in seven individuals (7/148, 4.7%), although at least one of the frontal processes of the maxillae was fractured (Table 14).

Table 13. Prevalence of nasal trauma by side in the individuals with both nasal bones preserved.

Male N=911 Female N=723 Total N=1634 Side n % n % n % Right 23 2.5 12 1.7 35 2.1

Left 11 1.2 6 0.8 17 1 Bilateral 62 6.8 28 3.9 90 5.5 Total 96 10.5 46 6.4 142 8.7

Table 14. Patterns of fracture of the nasal bones. Pattern of fracture N=1481 n % Transverse 91 61.5 Right 27 - Left 9 - Bilateral 51 - One nasal bone NP 4 - Oblique 11 7.4 Right 4 - Left 2 - Bilateral 3 - One nasal bone NP 2 - Parallel 4 2.7 Right 2 - Left 2 - Bilateral - - Comminuted 26 17.6 Right 2 - Left - - Bilateral 24 - Oblique+transverse 4 2.7 Transverse+oblique 3 2 Parallel+transverse 1 0.7 Doubtful 1 0.7 NP=Not preserved; 1Seven of the 148 fractures only present trauma of the frontal processes of the maxillae.

Of the 148 individuals exhibiting nasal trauma, a total of 349 nasal and other facial fractures were recorded, representing a mean of 2.4 fractures per individual. All fractured bones or anatomical areas of the face are listed in Table 15.

Table 15. Fractured bones or anatomical areas of the face.

Collection Fractured bone MSSC N=64 IESC N=53 HISC N=31 N=148 n % n % n % n % Frontal bone 2 3.1 - - 1 3.2 3 2.0 Nasal bone Right 55 85.9 48 90.6 22 71 125 84.5 Left 49 76.6 35 66 19 61.3 103 69.6 Lacrimal bone 1 1.6 - - - - 1 0.7 Sphenoid bone 1 1.6 - - - - 1 0.7 1 FPM Right 21 32.8 18 34 11 35.5 50 33.8 Left 11 17.2 9 17 8 25.8 28 18.9 Septum 3 4.7 - - 7 22.6 10 6.8 Maxilla Right 1 1.6 - - - - 1 0.7 Left 2 3.1 1 1.9 2 6.5 5 3.4 Zygomatic bone Right 1 1.6 1 1.9 - - 2 1.4 Left 2 3.1 4 7.5 3 9.7 9 6.1 2 ZPTB Right 2 3.1 3 5.7 - - 5 3.4 Left 3 4.7 1 1.9 2 6.5 6 4.1 Mandible ------

Total 154 - 120 - 75 - 349 - MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection. 1FPM=Frontal process of the maxilla; 2ZPTB=Zygomatic process of the temporal bone.

Overall, 129 (129/148, 87.2%) individuals show isolated nasal trauma, about twice as much in males (87 males, 43 females), and 19 (19/148, 12.8%) individuals show other facial fractures (fourteen males and five females): twelve individuals present one other facial fracture, three exhibit two other fractures, two individuals three other fractures, one show four other facial fractures, and also one present five other fractures. Moreover, 98.6% (146/148) of the individuals present complete bone remodelling, whereas in 1.4% (2/148) the fractures appear to be remodelling. Of the 19 individuals exhibiting other facial fractures, three adult males present traumatic injury of the frontal bone. An adult male of unknown age and cause of death (MSSC 392), shows bilateral trauma of the nasal bones and fracture of the frontal bone, which may also have resulted in the fracture of the right frontal sinus. A 42-year-old male, whose documented cause of death was pulmonary tuberculosis (MSSC 29), also presents fracture of both nasal bones, frontal bone and, probably, right frontal sinus. Finally, a 71-year-old male, who died of cerebral haemorrhage (HISC 464), also

exhibits trauma in the upper periorbital region and right nasal bone and frontal process of the maxilla. Three other individuals (two males, one female) exhibit periorbital fractures. A 60-year-old female, who died of bronchopneumonia (MSSC 159), presents a comminuted trauma of both nasal bones and the fracture of the frontal process of both maxillae, as well as a line of remodelled trauma between the piriform aperture and the orbital floor. The orbital floor also shows a marked depression resulting from the traumatic impact. The second individual, a 57-year-old male who died of heart disease (MSSC 551), shows bilateral trauma of both nasal bones and the fracture of the frontal process of the right maxilla. Anteriorly, the left maxilla presents several lines of remodelled trauma and both the lacrimal and sphenoid bones, within the left orbit, exhibit bone remodelling and lytic lesions. The individual also presents a diastatic fracture on the same side, with the displacement of the zygomatic bone on the frontozygomatic, zygomaticomaxillary, and zygomaticotemporal sutures (Plate X, Figure 21). The third individual, a 36-year-old male, who died of pulmonary tuberculosis (IESC 999), also shows a comminuted trauma of both nasal bones and fracture of the left maxilla, zygomatic bone, and left zygomatic process of the temporal bone. New bone formation is present on the anterior surface of the left maxilla and zygomatic bone.

4.1.2. Discussion

The current work shows a prevalence of 8.4% (148/1770) of nasal trauma. Reports of prevalence of nasal fracture in skeletal assemblages for Mediaeval and Postmediaeval periods are not abundant and are detailed in Table 16. Prevalence is fairly variable, resulting from the very different contexts of the collections studied. Djurić et al. (2006) reported a prevalence of 0.4% (1/237) of nasal bone fracture in individuals from 11th to 19th century AD cemeteries from Serbia, whereas Krakowka (2017) presented a prevalence of 10% (5/50) in a 1350-1540 AD skeletal assemblage. De la Cova (2012) reported significant differences of nasal trauma between Euro-American (16.7%) and African-American (31.2%) females from the Terry collection (1800-1877 AD) and Walker (1997) reported a prevalence between 0% to 33.3% in eight collections from Mediaeval age to the early 20th century AD.

Table 16. Mediaeval and Postmediaeval studies reporting prevalence of nasal trauma in palaeopathological literature. Bones / Reference Location Date Anatomical Prevalence area Krakowka (2017) London 1350-1540 AD Nasal bones 10% (5/50)

Born between 16.7% (23/138) de la Cova (2012) USA Nose 1800-1877 AD 31.2% (34/109) Djurić et al. (2006) Serbia 11th-19th centuries AD Nasal bones 0.4% (1/237) Russia 18th to early 20th century AD 33.3% (6/18) Spain 7th-11th centuries AD 5.5% (3/55) Spain 16th-18th centuries AD 0% (0/17)

Scotland 16th-19th centuries AD Nasal area 3.5% (2/57) Walker (1997) London 17th to mid-19th century AD 2.9% (1/34) London Mid-18th to 19th century AD 8.2% (5/61) USA Late 19th century AD 4.2% (3/71) USA Early 20th century AD 27.8% (62/223)

Although few studies with skeletal assemblages include a systematic approach to nasal and facial trauma, clinical literature gives a broader understanding of its prevalence and etiology. For instance, in an extensive clinical literature research, Brickley and Smith (2006) found relative higher proportions of facial trauma related to violence in European and American studies compared to Asian and African ones. Brink et al. (1998) reported that 69% of all injuries in 1481 individuals who attended the Department of Forensic Medicine in Aarhus (Denmark) were on the head, neck, or face, and nasal fractures were the most common. Male victims were significantly more often injured by kicks, head-butts or broken drinking glasses and females were predominantly exposed to blunt violence; blows with the fist caused 53.7% of all fractures (Brink et al., 1998). Ribeiro et al. (2016) found that road traffic accidents (52%) and interpersonal violence (34%) were the two most common causes of facial fractures in 1989 Brazilian patients. According to the study Crime in Lisbon: 1850 and 1910, interpersonal violence was very frequent in the Portuguese capital during the second half of the 19th and much of the 20th century and its report to authorities was mostly associated with men, both as aggressors and victims, although women were also sporadically reported (Vaz, 2014). According to this study, fights frequently took place between neighbours, co-workers, friends, or relatives, and less frequently between strangers. Episodes of interpersonal violence comprising small occurrences of ‘body offences’, ‘aggression’, or ‘injury’ are amongst the most common causes of detention by the Civil Police of Lisbon in 1871, 1874, 1880, and 1912-1913 (Vaz, 2014). Between 1886 and 1892, for instance, 43.5% 64

of 34.823 detentions of the Civil Police were due to crimes against people (Vaz, 2014). Also, between 1858 and 1918 in Coimbra, Montemor-o-Velho, and Penacova the reality was similar and approximately 72% of the offences were due to crimes against other people (Vaquinhas, 1992). The author also emphasises that much of this crime was associated with increased consumption of alcoholic beverages. Indeed, interpersonal violence is usually pointed out as one of the most common causes of facial trauma (e.g., Lee et al., 2007; Schneider et al., 2015) and alcohol often plays an important role in it (e.g., Lee et al., 2007; Laverick et al., 2008; Lee, 2009; Elledge et al., 2011; Redfern, 2017). Schneider et al. (2015), for instance, reported that a significant percentage of the maxillofacial fractures of 409 German patients were caused by interpersonal violence, and the majority of the patients who were treated had consumed alcohol. In a retrospective study of 2581 patients, Lee (2009) found a higher frequency of midfacial trauma with associated alcohol consumption in 87% of the fractures related to interpersonal violence. These factors may have also played an important role in the present results. Intimate partner violence (IPV) is often suggested as a major cause for trauma in the middle third of the face, particularly nasal fracture, in females (e.g., Berrios and Grady, 1991; Le et al., 2001; Lau et al., 2008; Lee et al., 2010; Saddki et al., 2010; Hashemi and Beshkar, 2011; Dourado and Noronha, 2015; Redfern, 2017). Le and colleagues (2001) noted a significant presence of left nasal fracture in women victims of IPV and pointed out two factors that might have contributed for it. Firstly, this can reflect the fact that the fists were the most common mechanism in IPV and more than 90% of the population is more skilful at using the right hand. Secondly, it is suggested that hemispheric cerebral dominance leads the victim to turn to the right in a reflex trying to avoid being punched. In the current work, twenty-five females show nasal bone fractures laterally deviated, 14 to the right (impact force on the left side) and 11 to the left (impact force on the right side). Following Le and colleagues (2001) hypothesis, these results show that IPV may have played a role in the present results, although not decisive. Juarez and Hughes (2014) stated that, although documented in intimate partner violence, no statistical association was found with fracture of the nasal bones and, so, this supposed relationship has to be taken with caution, because no fracture or fracture pattern is exclusive of IPV (Wu et al., 2010; Juarez and Hughes, 2014). After an extensive literature search, Redfern (2017) linked orbital, zygomatic, and nasal bone

fractures primarily to accidental and assault injuries, but also to IPV. Although not exclusively, Juarez and Hughes (2014) also statistically correlated periorbital fractures, zygomatic fractures, and intracranial injuries with IPV. In fact, domestic violence during the 19th and beginning of the 20th century has been generally accepted in Portugal, on the one hand, because there had to be a complaint of the victim for the police to take action and, on the other hand, the arrest of the offender (usually the man) commonly resulted in the aggravation of the survival conditions of his family (Vaz, 2014). Although domestic violence may have been more common during the studied period, formal complaints to the police were far from being amongst the most frequent (Vaz, 2014). It is also important to highlight that several clinical studies have also shown that IPV is not exclusively committed against women (e.g., Archer, 2000; Tjaden and Thoennes, 2000; Machado and Matos, 2014; Machado et al., 2016) and men cannot be excluded as victims. Falls and stumbling accidents may have also played a role in the overall results. Falls may occur in a variety of circumstances (e.g., unconsciousness due to diseases, loss of control during working hours) (Zandi et al., 2011). A study from several European departments of maxillofacial surgery showed that assault and falls were the most frequent causes of maxillofacial injury in 3396 patients (Boffano et al., 2015). Facial fractures are frequently the result of falling accidents, and several studies report nasal trauma as its most common consequence (Brink et al., 1998; Zandi et al., 2011). Also, as people age, the importance of falls on midface fractures also increases (Iida et al., 2003; Yamamoto et al., 2010) and this factor may have played a role in the present work, since nasal trauma is statistically related to the increased age at death. Indeed, Zandi et al. (2011) have shown that the nose is a preferential area for trauma in stumbling accidents, which are usually more frequent in males and may occur at any age. In the current study, 87.2% (129/148) of the individuals presented isolated nasal trauma, whilst other facial fractures present higher frequency in both zygomatic bones (11/148, 7.4%) and zygomatic processes of the temporal bones (11/148, 7.4%), maxillae (6/148, 4.1%), frontal bone (3/148, 2%), lacrimal bone (1/148, 0.7%), and sphenoid bone (1/148, 0.7%). The absence of mandible fractures is in accordance with the hypothesis of a marked influence of interpersonal violence in the results. Galloway and Wedel (2014), for instance, refer that direct trauma to the face usually focus on the

frontonasal region or laterally to the frontozygomatic area. Nevertheless, the frequency of other facial fractures shows differences to clinical studies. In a retrospective study of 186 patients, Park et al. (2014) stated that orbital blowout fractures (32/186, 17.2%) accounted for the highest proportion of other facial fractures, followed by fractures of the zygomaticomaxillary complex and mandible. Baek et al. (2013) reported that most of other facial fractures were in the orbit (19/108, 17.6%), maxilla (4/108, 3.7%), zygomatic bone (3/108, 2.8%), and mandible (3/108, 2.8%). Mohammadi and Ghasemi-Rad (2011) refer that 21 of 87 patients (24%) had other facial fractures mostly in the orbital wall and zygomatic bone. In a group of 125 patients, Han et al. (2011) reported that nasal bone fractures alone were present in 52% of the individuals, concurrent nasal septal fractures in 30.4%, and other facial fractures (such as in the orbital wall or in the maxilla) in 24%. The fact that fewer traumas of other facial bones were recorded in the current study may be associated with the reduced presence of one of the most current common causes of high force trauma to the face: motor vehicle accidents. The impact force resulting from motor vehicle accidents is often transmitted through the nasal bones to the underlying ethmoid sinuses and orbit, whilst other etiologies (e.g., falls, fist trauma) are often limited to the nose (Fraioli et al., 2008). In 1960, for instance, the first year for which data is available in Portugal, 12.537 road accidents officially occurred in the country, whilst 14.336 individuals were injured and 641 died10. Rallis et al. (2015) also stated that between 1960 and 1984 road traffic accidents accounted for 2228 (57%) of the individuals with maxillofacial trauma in Greece. Actually, Vaz (2014) reported that the intense movement of animal carts, cars, and trams have caused several accidents in Lisbon at least since the end of the 19th century, showing that traffic accidents may have also played a role in nasal fracture. The current results show statistically significant higher frequency of nasal trauma in males, a tendency that is also common in other palaeopathological studies (e.g., Walker, 1997; Brickley and Smith, 2006), as well as in clinical literature (e.g., Gassner et al., 2003; Hwang et al., 2006; Lee, 2009; Boffano et al., 2014; 2015; Park et al., 2014; Schneider et al., 2015). Cahn (2016) found a significantly higher frequency of nasal trauma in males of the Grant collection (Canada) when compared to males from the Human Identified Skeletal Collection (HISC) from Lisbon (which is also part of the

10 http://www.pordata.pt/DB/Portugal/Ambiente+de+Consulta/Tabela (consulted in 24/10/2017).

present study base). The author referred that these results were consistent with the boxing hypothesis discussed by Walker (1997), linking the higher frequency of nasal fractures in Canadian males to the popularity of boxing and prize-fighting in populations of British descendants. Although sports should not be ruled out as a possible etiology, it seems indeed probable that other causes, as discussed above, have most likely originated such injuries in the individuals studied. Blunt force trauma is the result of injury inflicted through a number of different forces (Zephro and Galloway, 2014). Depending on the biomechanical properties of the injured bone and on the nature of the applied loading force, blunt force trauma may evidence a wide range of fracture patterns (Zephro and Galloway, 2014). All nasal fractures recorded in the current study base are in accordance with the result of a blunt force, which is by definition the consequence of low-velocity impact from a blunt object or the low-velocity impact of a body with a blunt surface (SWGANTH, 2011; Passalacqua and Fenton, 2012; Zephro and Galloway, 2014). Although many factors may affect direction and shape of bone fractures, blunt-force injuries may be better understood when examined in terms of compression/tension for directionality of trauma (Passalacqua and Fenton, 2012). Of the 148 individuals presenting nasal trauma, 61.5% (91/148) show a clear deviation of the nasal bones to the opposite side of the impact force. This is in accordance with the results detailed by Stranc and Robertson (1979), which stated that lateral impact fractures are usually more frequent. The degree of bone disruption in lateral force fractures varies from a slight depression of a single nasal bone to full lateral displacement of other bones or anatomical structures (Stranc and Robertson, 1979), and this variation was also observed in the current study base. Galloway and Wedel (2014) refer that a broken nose from a typical assault usually involves a low-energy lateral impact, which is why lateral force fractures may be a good indicator of interpersonal violence (either between the same or different sexes). High-force incidents more commonly result in frontal impacts (Stranc and Robertson, 1979; Galloway and Wedel, 2014), but they are often difficult to distinguish from lateral impact fractures in skeletal remains. The overall strength of the bone depends on its composition, organisation, and geometry (Wescott, 2017). The strength of the bone is usually defined as its ability to withstand load (Wescott, 2017) and nasal bones require less force to fracture than any other facial bone (Mondin et al., 2005). They are most commonly fractured distally,

where they are broader and thinner (Galloway and Wedel, 2014), and are frequently the result of even minimal force (Higuera et al., 2007). Also, Walker (1997) stated that the result of the impact force on the superior bridge of the nose is usually a transverse fracture passing across one or both nasal bones. An exclusive transverse fracture was identified in 61.1% of the individuals presenting any type of nasal bone fracture. Different types of fracture patterns may be associated with different types of trajectory, impact forces, or the use of different types of blunt objects. The increased severity and force of the blow may also lead to the presence of linear fractures in the lateral borders of the nasal apertures (Walker, 1997). Fractures of the frontal processes of the maxillae (unilateral or bilateral), structures which outline the medial contour of the piriform aperture, were the most common finding after nasal bones fractures, either isolated or associated with other facial traumas. This is associated with the fact that this thin medial portion of the anterior skeletal anatomy of the nose is also very liable to fracture (Mondin et al., 2005). On the other hand, frontal, maxillary, zygomatic, and sphenoid bones (and their strong attachments to one another) represent a large portion of the buttress system of the midface (Linnau et al., 2003; Fraioli et al., 2008). The fracture of these thicker bones or anatomical areas requires a higher impact force because they provide structure and absorb the forces applied to the face (Fraioli et al., 2008). The frontal bone, for instance, is the strongest of the facial bones, requiring a large amount of force to fracture (Fraioli et al., 2008). The type of force necessary for zygomatic-maxillary fractures is more difficult to access, since the central portion of the zygomatic bone is robust, but its projections by which articulates with the surrounding facial bones are weaker (Fraioli et al., 2008). Unfortunately, the study of facial fractures in skeletal assemblages present several limitations:

- as stated by Walker (1989), well healed fractures of the nasal bones without deformation are very difficult to identify and, consequently, several may have been missed in the current work. Additionally, trauma is very difficult to identify in fragile bones. Fractures of the septum, for instance, are extremely difficult to identify and characterise due to two main reasons: postmortem damage and the irregularity and thin aspect of the perpendicular plate of the ethmoid and vomer.

In the present study ten fractures of the septum were identified, but others may have been missed;

- the fact that no nasal trauma was documented in nonadult individuals is probably related to the fact that traumatic injuries of the nose are seldom fatal (Brickley and Smith, 2006; Pollak and Saukko, 2017). In the current work, only age at death is available (not at what age trauma occurred) and several of the nasal fractures may have occurred during the individuals’ early life. Accordingly, non-fatal injuries during early age may act like a bias when analysing the influence of age using skeletal collections;

- it is impossible to understand if other facial fractures are temporally concurrent with nasal bone trauma. Although the same level of remodelling may be present, the differential diagnosis has to highlight that it is not possible to understand if the fractures occurred at the same time or during the same traumatic episode. Also, although clinical studies may be very useful to help finding possible etiologic factors for trauma and to identify particular forms of violence in the past, these comparisons should be discussed very carefully, because its etiology depends on several factors subjected to interpretation that may also be a potential source of bias (Redfern, 2017).

4.2. Nasal osseous variations

4.2.1. Results

Five nasal osseous variations will be studied in this chapter, three on the ostiomeatal complex (hypertrophy and paradoxical curvature of the middle turbinates and accessory turbinate of the uncinate processes) and two on the nasal septum (deviation and spurs). The concurrence of these variations in the same individual, as well as their possible relationship, will also be discussed.

4.2.1.1. Middle turbinates: hypertrophy and paradoxical curvature

Of the 1684 individuals with at least one middle turbinate intact for examination, 38.5% (648/1684) present at least one hypertrophy (Table 17). Of the three collection studied, the Lisbon collection (HISC) accounts for the highest percentage (42.7%, 129/302), although no statistically significant differences were found (Pearson χ2=3.876; d.f.=2; p=0.144).

Table 17. Prevalence of middle turbinate hypertrophy by sex.

Male Female Total Collection N n % N n % N n % MSSC 303 125 41.3 179 65 36.3 482 190 39.4 IESC 433 153 35.3 467 176 37.7 900 329 36.6 HISC 145 59 40.7 157 70 44.6 302 129 42.7 Total 881 337 38.3 803 311 38.7 1684 648 38.5 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Females present a slightly higher frequency (females=311/803, 38.7%; males=337/881, 38.3%) without significant differences (Pearson χ2=0.042; d.f.=1; p=0.838). The youngest individual exhibiting hypertrophy of the middle turbinate is five years old and the oldest is 100. Age at death also does not play a significant role in the presence of hypertrophy (Student’s t=0.674; d.f.=1672; p=0.501; absence n=1030, x̅ =46.96, s.d.=21.36 vs presence n=644, x̅ =46.24, s.d.=21.02) (Figure 22). Of the 1471 individuals with both middle turbinates preserved, unilateral hypertrophies present higher frequency (unilateral=342/1471, 23.2% vs bilateral=259/1471, 17.6%), with statistically significant differences (Pearson χ2=11.463; d.f.=1; p=0.001) (Table 18; Appendix 2). Within the unilateral cases, the

side of the hypertrophy shows no significant differences (Pearson χ2=0.292; d.f.=1; p=0.589).

Males Females

44,4 45 43,2 41,2 40,1 39,3 39,2 39,8 40 38,4 37 37,3 % 35,2 34,5 35 33,3

30,9 30

25 <=19 yo 20-29yo 30-39yo 40-49yo 50-59yo 60-69yo => 70yo Figure 22. Hypertrophy of the middle turbinate by sex and age at death.

Table 18. Prevalence of middle turbinate hypertrophy by side and sex.

Male N=767 Female N=704 Total N=1471 Side n % n % n % Right 92 12 84 11.9 176 12 Left 88 11.5 78 11.1 166 11.3 Bilateral 132 17.2 127 18 259 17.6 Total 312 40.7 289 41.1 601 40.9

Of the 1684 individuals with at least one middle turbinate preserved, the right is preserved in 93.8% (1579/1684) and the left in 93.6% (1576/1684) the left. The bulbous type of hypertrophy is the most frequent on both sides (right=253/1579, 16%; left=227/1576, 14.5%), followed by the extensive (right=140/1579, 8.9%; left=159/1576, 10.1%) and lamellar (right=68/1579, 4.3%; left=60/1576, 3.8%) types (Table 19). Moreover, in 9.9% (64/648) of the individuals presenting a pneumatisation, at least one was broken postmortem and a hollow space within the turbinate was observed on gross examination. Sixty crania (28 males, 32 females; x̅ =46.63, s.d.=16.93) from the International Exchange Skull Collection presenting macroscopic hypertrophy of the middle turbinate were examined by CT scan (Plate XI, Figures 23 and 24). Of the total 120 middle turbinates, 16.6% (20/120) showed the hypertrophy of the lamellar portion, 24.1% (29/120) of the bulbous part, 36.7% (44/120) of both, in 20% (24/120) the pneumatisation was absent, and 2.5% (3/120) of the turbinates were not preserved 72

Plate XI

Figure 23. Anterior view of the nasal area of a 75-year-old female (IESC 134) presenting a concha bullosa on the right side (left). The diagnosis was confirmed by CT scan (right).

Figure 24. Anterior view of a 28-year-old female (IESC 213, left) presenting a bilateral concha bullosa confirmed by CT scan (right).

(Table 20). All the 93 hypertrophies of the middle turbinate presented the appearance of an internal empty space (an air-filled cavity) and none of them showed an internal osseous structure.

Table 19. Prevalence of middle turbinate hypertrophy by side, type, and sex.

Right N=823 Left N=825 Total N=1648 Sex Type n % n % n % Lamellar 33 4 32 3.9 65 3.9 Male Bulbous 137 16.6 123 14.9 261 15.8 Extensive 67 8.1 77 9.3 144 8.7 N=756 N=751 N=1507 Lamellar 35 4.6 28 3.7 63 4.2 Female Bulbous 116 15.3 104 13.8 221 14.7 Extensive 73 9.7 82 10.9 156 10.4 N=1579 N=1576 N=3155 Lamellar 68 4.3 60 3.8 128 4.1 Total Bulbous 253 16 227 14.4 482 15.3 Extensive 140 8.9 159 10.1 300 9.5

Table 20. Concha bullosa by side and type in the 60 individuals who underwent CT scan.

Right Left Sex Type n % n % Lamellar 4 14.3 3 10.7

Bulbous 10 35.7 6 21.4 Male Extensive 10 35.7 12 42.9 N=28 Absent 4 14.3 4 14.3 Not preserved - - 3 10.7 Lamellar 6 18.8 7 21.9

Bulbous 3 9.4 10 31.3 Female Extensive 12 37.5 10 31.3 N=32 Absent 11 34.4 5 15.6 Not preserved - - - - Lamellar 10 16.7 10 16.7

Bulbous 13 21.7 16 26.6 Total Extensive 22 36.7 22 36.7 N=60 Absent 15 25 9 15 Not preserved - - 3 5

A Cohen’s kappa (κ) was run to determine the agreement between macroscopic and CT scan observations. Table 21 presents the error, percentage of agreement, and Cohen’s κ for the presence of concha bullosa per individual, side, and type. The percentage of agreement considering the presence/absence of concha bullosa per individual is 96.7% (58/60), whilst the agreement by side shows a value of 88.3% (53/60; κ=0.81), which is indicative of an almost perfect reliability of macroscopic 73

observations, following the interpretation of the κ values suggested by Landis and Koch (1977). The type of concha bullosa shows a moderate (right side, 38/60, 63.3%, κ=0.50) and fair (left side, 32/60, 53.3%, κ=0.37) coefficients of agreement, following the recommendations of the same authors.

Table 21. Percentages of agreement and κ coefficients of macroscopic and CT scan identifications of concha bullosa in the current work.

Error Agreement Cohen’s N n % N % Kappa (κ) Reliability Presence/absence 60 2 96.7 58 96.7 0/0a a Side 60 7 11.7 53 88.3 0.81 Almost perfect

Type Right side 60 22 36.7 38 63.3 0.50 Moderate Left side 60 28 46.7 32 53.3 0.37 Fair κ is statistically significantly different from zero (p <0.001) in all four categories; a indeterminate (no statistics were computed because macroscopic observations of concha bullosa were a constant for ‘presence’ in the 60 individuals).

The means for the standardised widths of bullous conchae in the 60 individuals who underwent CT scan are presented on Table 22. Overall, the total standardised widths represent higher means on the right side with statistical significance (Student’s t=2.597, d.f.=51, p=0.012). Male individuals also show higher means, both on the right and left sides, although without statistical significant differences (Student’s t=0.402, d.f.=18, p=0.692 and Student’s t=1.376, d.f.=28, p=0.180, respectively). When analysing the standardised width of the larger concha bullosa, male individuals exhibit a higher mean, with significant differences (Student’s t=2.385, d.f.=35, p=0.023).

Table 22. Standardised widths (mm) of concha bullosa measured by CT scan.

Male Female Total Concha bullosa n Mean SD n Mean SD n Mean SD

Right 13 63.9 11 9 61 5.3 22 62.7 9.1 Side Left 16 57.9 13.7 15 51.2 10.3 31 54.6 12.5 Dominant 20 65.1 11.1 17 56.5 10.7 37 61.2 11.6

A simple linear regression was calculated to predict standardised dominant concha bullosa width based on age and no association was found (Linear regression F[1,35]=0.356, p=0.554). Of the 1684 individuals with at least one middle turbinate preserved, 50.5% (851/1684) show at least one paradoxical curvature (types 1 or 2) (Table 23). Of the three collections studied, the individuals from the Medical Schools Skull Collection (MSSC) exhibit higher occurrences, although without significant differences (Pearson

χ2=4.737; d.f.=2; p=0.094). Males show a higher percentage of paradoxical curvature, without statistical significant differences (Pearson χ2=1.324; d.f.=1; p=0.250). The youngest individual presenting a paradoxical curvature is a one-year-old male and the oldest is a 97-year-old-female. The increased age at death plays a statistically significant role on the absence of paradoxical curvature of the middle turbinate (Student’s t=5.192, d.f.=1672, p<0.001; absence n=828, x̅ =49.39, s.d.=21.15, presence n=846, x̅ =44.04, s.d.=20.98) (Figure 25).

Table 23. Prevalence of paradoxical curvature by sex.

Male Female Total Collection N n % N n % N n % MSSC 303 174 57.4 179 86 48 482 260 53.9 IESC 433 211 48.7 467 222 47.5 900 433 48.1 HISC 145 72 49.7 157 86 54.8 302 158 52.3 Total 881 457 51.9 803 394 49.1 1684 851 50.5 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Males Females

70 65,5 65 62,9 60 57 57,3 55,1 % 55 52,4 50 50 47,3 47,2 47 46,4 45 43 43,3 40 40 35 <=19 yo 20-29yo 30-39yo 40-49yo 50-59yo 60-69yo => 70yo Figure 25. Paradoxical curvature by sex and age at death.

The 1471 individuals with both middle turbinates preserved show a higher frequency of bilateral paradoxical curvatures (Table 24; unilateral=319/1471, 21.7%; bilateral=467/1471, 31.7%) with statistically significant differences (Pearson χ2=27.189; d.f.=1; p<0.001). Unilateral cases show higher frequency on the left side, although without significant differences (Pearson χ2=0.705; d.f.=1; p=0.401).

Table 24. Prevalence of paradoxical curvature by side and sex, regardless of type.

Male N=767 Female N=704 Total N=1471 Side n % N % n % Right 79 10.3 73 10.4 152 10.3 Left 90 11.7 77 10.9 167 11.4 Bilateral 254 33.1 211 30 467 31.7 Total 423 55.1 361 51.3 786 53.4

Of the 93.8% (1579/1684) right middle turbinates preserved, 34.5% (545/1579) show a type 1 paradoxical curvature and 6.7% (106/1579) show a type 2 (Table 25; Appendix 3). Of the 93.6% (1576/1684) left middle turbinates preserved, 32.8% (517/1576) present a type 1 paradoxical curvature and 9.4% (148/1576) exhibit a type 2. Both types are not influenced by sex on both sides (right Pearson χ2=1.197; d.f.=2; p=0.550; left Pearson χ2=2488; d.f.=2; p=0.288).

Table 25. Prevalence of paradoxical curvature by side, type, and sex.

Male Female Total Side Type N=823 % N=756 % N=1579 % 1 293 35.6 252 33.3 545 34.5 Right 2 57 6.9 49 6.5 106 6.7 Total 350 42.5 301 39.8 651 41.2 N=825 % N=751 % N=1576 % 1 276 33.5 241 32.1 517 32.8 Left 2 85 10.3 63 8.4 148 9.4 Total 361 43.8 304 40.5 665 42.2 N=1648 % N=1507 % N=3155 %

1 569 34.5 495 32.8 1064 33.7 Total 2 142 8.6 112 7.4 254 8.1 Total 711 43.1 607 40.3 1318 41.8

Overall, 12.8% (216/1684) individuals exhibit at least one middle turbinate with the most extreme type of curvature (type 2). Males present a higher frequency, without significant differences (Pearson χ2=0.955; d.f.=1; p=0.328; males=118/881, 13.4%; females=98/803, 12.2%).

4.2.1.2. Uncinate process: accessory turbinate

Of the 1400 individuals with at least one uncinate process preserved, 17.9% (251/1400) present at least one accessory turbinate (Table 26). Of the three collections studied, the individuals from the Medical Schools Skull Collection (MSSC) show a higher percentage, although without significant differences (Pearson χ2=4.633; d.f.=2; 76

p=0.099). Both sexes present similar occurrences (males=129/721, 17.9%; females=122/679, 18%) and no significant differences were found (Pearson χ2=0.001; d.f.=1; p=0.971). The youngest individual presenting an accessory turbinate is a two-year-old male and the oldest is a 98-year-old female. Age at death does not play a major role in the presence of accessory turbinate (Student’s t= -0.232, d.f.=1390, p=0.817; absence n=1143, x̅ =46.28, s.d.=21.05; presence n=249, x̅ =46.63, s.d.=21.54) (Figure 26).

Table 26. Prevalence of accessory turbinate by sex.

Male Female Total Collection N n % N n % N n % MSSC 263 50 19 165 38 23 428 88 20.6 IESC 339 57 16.8 377 70 18.6 716 127 17.7 HISC 119 22 18.5 137 14 10.2 256 36 14.1 Total 721 129 17.9 679 122 18 1400 251 17.9 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Males Females

25 23,7 23,3 23 21,8

21 18,3 18,1 19 17,6 16,7 16,9 16,8 17 15,9 17 15,8 15,7 % 15 13,3 13

11 9 7

5 <=19 yo 20-29yo 30-39yo 40-49yo 50-59yo 60-69yo => 70yo

Figure 26. Accessory turbinate by sex and age at death.

Of the 1126 individuals with both uncinate processes preserved, 10% (113/1126) present a unilateral accessory turbinate and 7.6% (86/1126) show a bilateral variation (Table 27; Appendix A4), without significant differences (Pearson χ2=3.663; d.f.=1; p=0.056). The side of the unilateral cases (right=60/1126, 5.3%; left=53/1126, 4.7%) also does not represent significant differences (Pearson χ2=0.434; d.f.=1; p=0.510).

Table 27. Prevalence of accessory turbinates by side and sex.

Male N=582 Female N=544 Total N=1126 Side n % n % N % Right 37 6.4 23 4.2 60 5.3 Left 21 3.6 32 5.9 53 4.7 Bilateral 50 8.6 36 6.6 86 7.6 Total 108 18.6 91 16.7 199 17.7

4.2.1.3. Nasal septum: deviation and spurs

The 726 individuals of the three collections with the septum preserved show a mean and standard deviation of 3.6 and 3.3, respectively, for the nasal septal deviation index (NSDI). Males present a statistically significant higher mean (Student’s t=5.876, d.f.=705.2, p<0.001) (Table 28). A Kruskal-Wallis H test shows no significant differences for the NSDI between age groups (Kruskal-Wallis H=6.131; d.f.=5; p=0.294) (Table 29).

Table 28. Mean values for the nasal septal deviation index (NSDI) by sex.

Male Female Total Collection N x̄ SD N x̄ SD N x̄ SD MSSC 156 4.4 3.4 89 3.3 3.1 245 4 3.3 IESC 165 4.2 3.7 198 2.8 2.7 363 3.5 3.3 HISC 51 4.5 3.6 67 2.6 3 118 3.4 3.4 Total 372 4.3 3.6 354 2.9 2.9 726 3.6 3.3 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Table 29. Mean values for nasal septal deviation index (NSDI) by age at death. Age groups (years old) n x̅ s.d. < 30 137 3.1 2.7 30-39 98 4.0 3.7 40-49 130 3.7 3.4 50-59 116 4.0 3.3 60-69 112 3.6 3.3 >69 133 3.5 3.5

Of the 726 individuals with the septum preserved, 5.2% (38/726) present no deviation when observed on gross examination, 40.5% (294/726) show a deviation to the right side, 38.4% (279/726) to the left and 15.8% (115/726) show a bilateral deviation (Table 30) – the ethmoid is deviated to the right and the vomer to the left in 58.3% (67/115) individuals, whilst the opposite happens in 41.7% (48/115). The higher frequency of unilateral cases (unilateral=573/726, 78.9%; bilateral=115/726, 15.8%) presents significant differences (Pearson χ2=304.890; d.f.=1; p<0.001), whereas no

significant differences (Pearson χ2=0.393; d.f.=1; p=0.531) were found between sides. Moreover, the frequency of all types of septal deviation are detailed in Table 31.

Table 30. Side of nasal septal deviation by sex.

Male N=372 Female N=354 Total N=726 Side n % n % N % No deviation 10 2.7 28 7.9 38 5.2 Right 160 43 134 36 294 40.5 Left 133 35.8 146 39.2 279 38.4 Bilateral 69 18.5 46 12.4 115 15.8

Table 31. Type of deviation by sex.

Male N=372 Female N=354 Total N=726 Type n % n % N % No deviation 10 2.7 28 7.9 38 5.2 1 35 9.4 48 13.6 83 11.4 2 1 0.3 7 2 8 1.1 3 70 18.8 94 26.6 164 22.6 4 128 34.4 83 23.4 211 29.1 5 128 34.4 94 26.6 222 30.6

Of the individuals presenting type 5, 48.2% (107/222) show a ‘C’ and ‘L’ deviation of the ethmoid and vomer to the same side, whilst 51.8% (115/222) present a bilateral deviation. Overall, the presence of deviation is statistically higher in males (Pearson χ2=9.970; d.f.=1; p=0.002). The mean differences between sexes for the NSDI is in accordance with the sexual occurrences within each type of deviation: types 1 (x̄ =2.3, s.d.=2.4), 2 (x̄ =1.9, s.d.=1.1), and 3 (x̄ =2.7, s.d.=2.5) present lower means of deviation and show higher frequency in females, whereas types 4 (x̄ =4, s.d.=3.6) and 5 (x̄ =5.0, s.d.=3.5) present higher means of deviation and show higher frequency in males. Of the 1814 individuals with the ethmoid-vomer fusion (EVF) preserved, 14.2% (258/1814) exhibit a spur. Of the three collection studied, the individuals from the Human Identified Skeletal Collection (HISC) show higher percentage, although without significant differences (Pearson χ2=2.194; d.f.=2; p=0.334) (Table 32). Male individuals present higher frequency of EVF spurs (males=185/966, 19.2% vs females 73/848, 8.6%), with statistically significant differences between sexes (Pearson χ2=41.150; d.f.=1; p<0.001). The youngest individual presenting an EVF spur is a 13-year-old male and the oldest are two 92-year-olds (one male, one female). The increased age at death is statistically associated with the presence of septal spurs (Student’s t=2.411, d.f.=1801, p=0.016; absence n=1546, x̄ =46.93, s.d.=21.04 vs presence n=257, x̄ =50.30,

s.d.=18.90), which are less frequent in the first three decades of life (Figure 27). Left sided spurs present higher frequency (right=118/258, 45.7% vs left=140/258, 54.3%), without showing statistical significance (Pearson χ2=1.876; d.f.=1; p=0.171).

Table 32. Prevalence of septal spurs by sex.

Male Female Total Collection N n % N n % N n % MSSC 319 55 17.2 194 18 9.3 513 73 14.2 IESC 510 98 19.2 501 38 7.6 1011 136 13.5 HISC 137 32 23.4 153 17 11.1 290 49 16.9 Total 966 185 19.2 848 73 8.6 1814 258 14.2 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Males Females

25 23,4 22,2 21,5 21,7 20,5 20

14 % 15 11,4 10 10,1 8,2 10 7,1 7,9 4,1 5,6 5

0 <=19 yo 20-29yo 30-39yo 40-49yo 50-59yo 60-69yo => 70yo

Figure 27. Septal spurs by sex and age at death.

4.2.1.4. Nasal variations and their possible relationship Of the 483 individuals with the uncinate processes, middle turbinates, and nasal septum preserved, only in 1.7% (8/483) all five variations are absent, whilst 98.3% (475/483) show at least one11. Around one-fifth (20.3%, 98/483) present one nasal variation, 46% (222/483) two concurrent variations, 25.1% (121/483) three variations, 6.6% (32/483) show four variations, and 0.4% (2/483) individuals exhibit all five variations studied (Table 33; Plate XII, Figure 28).

11 These results include the morphological methodology used to characterise nasal septal deviation in the present study (see section 3).

Plate XII

. Male, 34 years old (MSSC 361) . Female, 49 years old (IESC 28) . Nasal septal deviation: . Nasal septal deviation:

Type 5, Index=12.2 Type 3, Index=2.8 . Bilateral hypertrophy . Bilateral hypertrophy

. Left paradoxical turbinate (type 1) . Absence of paradoxical curvature (type 0), . A bsence of accessory turbinate, and septal spur accessory turbinate, and septal spur

. Male, 24 years old (IESC 178) . Male, 35 years old (IESC 1099) . Nasal septal deviation: . Nasal septal deviation: Type 1, Index=4.5 Type 5, Index=11.7 . Right hypertrophy . Left hypertrophy . Bilateral paradoxical curvature (type 1) . Absence of paradoxical curvature (type 0), . A bsence of accessory turbinate, and septal spur accessory turbinate, and septal spur

Figure 28. Examples of the nasal variations studied. Table 33. Number of nasal variations per individual.

Individuals N=483 Nasal variation(s) n % 0 - 8 1.7 CB 4 0.8 1 PC 5 1 NSD 89 18.4 Total 98 20.3 AT+NSD 28 5.8

CB+PC 2 0.4 2 CB+NSD 63 13 PC+NSD 113 23.4 SS+NSD 16 3.3 Total 222 46 AT+CB+NSD 14 2.9 AT+PC+NSD 18 3.7

AT+SS+NSD 2 0.4 3 CB+SS+NSD 8 1.7 PC+SS-NSD 8 1.7 CB+PC+NSD 71 14.7 Total 121 25.1 AT+CB-PC+NSD 11 2.3

AT+PC+SS+NSD 4 0.8 4 AT+CB+SS+NSD 2 0.4 PC+CB+SS+NSD 15 3.1 Total 32 6.6 5 AT+CB+PC+SS+NSD 2 0.4 AT=accessory turbinate; CB=concha bullosa; PC=paradoxical curvature; NSD=nasal septal deviation; SS=septal spur.

Nasal septal deviation (NSD) is statistically associated with contralateral presence of pneumatisation (Pearson χ2=23.696; d.f.=1; p<0.001) and paradoxical curvature (Pearson χ2=5.048; d.f.=1; p=0.025) of the middle turbinates. Moreover, although unilateral concha bullosa and paradoxical curvature increase the means of the contralateral nasal septal deviation index (NSDI), only the presence of right unilateral concha bullosa shows statistically significant differences (Table 34). Concha bullosa is statistically associated with the types of septal deviation comprising the deflection of the perpendicular plate of the ethmoid (Pearson χ2=4.758; d.f.=1; p=0.029; pooled types 1+3+5 vs pooled types 2+4). On the contrary, paradoxical curvature (Pearson χ2=0.255; d.f.=1; p=0.614) and accessory turbinate (Pearson χ2=0.010; d.f.=1; p=0.922) show no statistical relationship with none of the pooled types of septal deflection.

Table 34. Mean values and p-values for the nasal septal deviation index (NSDI) by variation of the middle turbinate.

Septal Concha NSDI Mann-Whitney deviation bullosa N x̅ s.d.

Right 21 2.2 1.6 Right U=303.0; p=0.020 Left 45 4.6 3.9

Right 40 3.8 3.9 Left U=193.0; p=0.307 Left 12 2.5 1.8

Septal Paradoxical NSDI Mann-Whitney deviation curvature N x̅ s.d.

Right 18 3.0 3.0 Right U=248.0; p=0.208 Left 35 3.7 2.7

Right 29 4.1 4.4 Left U=330.0; p=0.949 Left 23 3.5 2.8

One hundred and nine individuals (60 right sided, 49 left sided) present a septal spur and the septum completely preserved. Of the 60 right septal spurs, 41 show ipsilateral septal deviation, eight contralateral, and 11 bilateral. Of the 49 left septal spurs, 36 present ipsilateral septal deviations, four contralateral, seven bilateral, and two present no deviation. The presence of septal spurs is associated with the ipsilateral deviation of the nasal septum (Pearson χ2=50.534; d.f.=3; p<0.001), as well as with the NSDI (Student’s t=5.568, d.f.=724, p<0.001; absence n=617, x̄ =3.3, s.d.=3.2 vs presence n=109, x̄ =5.2, s.d.=3.8).

4.2.2. Discussion

The present results show that nasal septal deviation is the most frequent variation within the nasal cavity, followed by paradoxical curvature (50.5%) and hypertrophy (38.5%) of the middle turbinates, accessory turbinates (17.9%), and septal spurs in the ethmoid/vomer fusion (14.2%) (Table 35). The current work reports the first examples of accessory turbinates in Portuguese palaeopathological literature. Clinically, this variation has been described at least since 1991 by Khanobthamchai and colleagues but, as noted by Al-Qudah (2015), its definition in literature is still confusing and unclear. Only few isolated examples were reported (Bae and Lim, 2010; El-Shazly et al., 2012; Jung et al., 2012; Choi, 2013; Lee et al., 2013; Muthiyan et al., 2014; Al-Qudah, 2015; Chang et al., 2016), and the study of Ozcan et al. (2008) is the only detailing its systematic occurrence (6.8%, 26/384), although prevalence is also reported for several other variations of the uncinate process, including its medial deviation (Wani et al., 2009; Fadda et al., 2012; Tuli et al., 2013), horizontal bent (Lloyd et al., 1991;

Earwaker, 1993), and retroflexed (Keast et al., 2008), or C-shaped (Milczuk et al., 1993) positions. These are similar variations of the uncinate process, representing its medial or anterior curvature. Table 36 presents prevalence reports of variations of the uncinate process in clinical studies.

Table 35. Synthesis of the results of all the five variations studied in the current work. Variation Prevalence Sex U/B Left/Right Age

M=38.3% U=23.2% R=12% Hypertrophy of the Student’s T 38.5% F=38.7% B=17.6% L=11.3% middle turbinate p=0.674 p=0.838 p=0.001 p=0.627

M=51.9% U=21.7% R=10.3% Paradoxical curvature Student’s T 50.5% F=49.1% B=31.7% L=11.4% of the middle turbinate p<0.001 p=0.250 p<0.001 p=0.401

M=17.9% U=10% R=5.3% Student’s T Accessory turbinate 17.9% F=18% B=7.6% L=4.7% p=0.817 p=0.971 p=0.056 p=0.510

M=97.2% U=78.9% R=40.5% Kruskal-Wallis Nasal septal deviation 94.8% F=92.7% B=15.8% L=38.4% p=0.294 p=0.004 p<0.001 p=0.531

M=19.2% R=6.5% Student’s T Septal spur 14.2% F=8.6% - L=7.7% p<0.016 p<0.001 p=0.171 M=Males, F=Females; U=Unilateral, B=Bilateral.

Table 36. Reports of variations of the uncinate process in clinical studies. Reference Location Prevalence Variation Lloyd et al. (1991) USA . 21% (21/100) Horizontal bent Earwaker (1993) Australia . 19% (152/800) Horizontal bent Milczuk et al. (1993) USA . 9.6% (11/114) C-shaped Keast et al. (2008) New Zealand . 1.1% (2/180) Retroflexed (pooled results) Ozcan et al. (2008) Turkey . 6.8% (26/384) Accessory turbinate Wani et al. (2009) India . 11.3% (17/150) Medial deviation Fadda et al. (2012) Italy . 22.9% (32/140) Medial deviation Tuli et al. (2013) India . 24% (24/100) Medial deviation

A similar distribution between sexes was observed in the current study base, whilst Tuli et al. (2013) found a significantly higher frequency of medial deviation in males in a study of Indian patients. Also, the higher frequency of unilateral cases without statistical significance is in accordance with the results reported by Ozcan et al. (2008). The same study reported a similar higher frequency of right accessory turbinates in unilateral cases. Paradoxical curvature was the second most common variation recorded in the current work. Lothrop reported in 1903 the only known reference to a paradoxical curvature in skeletal assemblages, describing it as “...a true internal concavity rather than a convexity” (Lothrop, 1903:239). Just one example was reported in all the 1000 83

individuals composing the collection from the dissecting room of the Harvard Medical School (USA), although its prevalence in 31 clinical studies searched ranges from 0.7% (Nouraei et al., 2009) to 40.4% (Earwaker, 1993) (Table 37).

Table 37. Reports of paradoxical curvature of the middle turbinate in clinical studies. Reference Location Prevalence Reason for CT scan Kennedy and Zinreich (1988) USA . 15% (n=230) Rhinosinusitis symptoms Lloyd (1990) USA . 16% (16/100) Orbital tumour

. 27.1% (n=166) Chronic sinus Bolger et al. (1991) USA . 22.3% (n=36) Nonsinus

. 12.2% (10/82) Orbital disease Calhoun et al. (1991) USA . 12% (12/100) Sinus disease Lloyd et al. (1991) England . 15% (15/100) Sinus complaints Earwaker (1993) Australia . 40.4% (323/800) Evaluation before sinus surgery

. 16% (16/100) Control Jones et al. (1997) Austria . 7% (7/100) Proven rhinosinusitis Arslan et al. (1999) Turkey . 3% (6/200) Chronic rhinosinusitis

. 7.3% (6/82) Nonsinus disease Kayalioglu et al. (2000) Turkey . 12.2% (11/90) Sinus disease Pérez-Piñas et al. (2000) Spain . 10% (11/110) Inflammatory sinus disease Kim et al. (2006) South Korea . 19.5% (22/113) Chronic rhinosinusitis

. 8.9% (19/213) Allergic rhinosinusitis Tezer et al. (2006) Turkey . 11.1% (14/126) Non-allergic rhinosinusitis Mazza et al. (2007) Italy . 11% (11/100) Sinus CT scan Keast et al. (2008) New Zealand . 32.2% (58/180) Sinus CT scan (pooled results) Ozcan et al. (2008) Turkey . 9.1.% (35/384) Nasal complaints Riello and Boasquevisque (2008) Brazil . 29% (58/200) Sinus complaints Nouraei et al. (2009) England . 0.7% (2/278) Rhinosinusitis symptoms Wani et al. (2009) India . 9.3% (14/150) Sinonasal disease Cabezón A et al. (2010) Chile . 9.9.% (14/142) Sinus CT scan Al-Qudah (2010) Jordan . 18% (20/110) Sinonasal symptoms

. 11.7% (14/120) Chronic rhinosinusitis Azila et al. (2011) Malaysia . 22.5% (27/120) Controls Fadda et al. (2012) Italy . 6.4% (9/140) Persistent rhinosinusitis symptoms

. 37.9% (33/87) Chronic rhinosinusitis Sadr et al. (2012) Iran . 51.5% (53/103) Controls Al-Abri et al. (2014) Oman . 12.5% (45/360) Chronic sinonasal symptoms Chaitanya et al. (2015) India . 11% (11/100) Complaints of sinonasal pathology Shpilberg et al. (2015) USA . 15.6%(30/192) Rhinosinusitis symptoms Dasar and Gokce (2016) Turkey . 15.8% (63/400) Sinonasal pathology Roman et al. (2016) Romania . 8% (n=130) Rhinosinusitis symptoms Sarkar et al. (2016) India . 6.8% (21/310) Rhinosinusitis Çalışkan et al. (2017) Turkey . 21.8% (70/322) Facial disease Onwuchekwa and Alazigha (2017) Nigeria . 1.8% (2/110) Sinonasal symptoms

The differences between clinical reports and the present study (50.5%) may be associated with the use of different methodological approaches, and this may be an important limitation for comparison with clinical literature. Nevertheless, if only the 84

most pronounced curvatures (type 2) were taken into account, the total prevalence would be 12.8% (216/1684), which is much more in accordance with clinical literature showing that, of the 31 studies consulted, 18 detailed a prevalence of 12.8%±5% (Kennedy and Zinreich, 1988; Lloyd, 1990; Calhoun et al., 1991; Lloyd et al., 1991; Jones et al., 1997; Kayalioglu et al., 2000; Pérez-Piñas et al., 2000; Tezer et al., 2006; Mazza et al., 2007; Ozcan et al., 2008; Wani et al., 2009; Cabezón et al., 2010; Azila et al., 2011; Al-Abri et al., 2014; Chaitanya et al., 2015; Shpilberg et al., 2015; Dasar and Gokce, 2016; Roman et al., 2016). Also, males show a higher frequency of paradoxical curvature without statistical significance, which is in accordance with the results of Kayalioglu et al. (2000) and Narendrakumar and Subramanian (2016). Moreover, a statistically higher frequency of bilateral cases was found, disagreeing with several clinical studies presenting a higher frequency of unilateral paradoxical curvatures (Pérez-Piñas et al., 2000; Kim et al., 2006; Ozcan et al., 2008; Wani et al., 2009; Al- Qudah, 2010; Fadda et al., 2012; Narendrakumar and Subramanian, 2016). Concerning the unilateral cases, only the patients studied by Al-Qudah (2010) exhibit a higher frequency on the left side, whereas the ones studied by Pérez-Piñas et al. (2000), Kim et al. (2006), Ozcan et al. (2008), Fadda et al. (2012), and Narendrakumar and Subramanian (2016) show a higher frequency on the right side. Unfortunately, none of the cited studies detailed statistical analysis. It is also important to refer that, in most of the clinical studies presented in the Table 37, patients underwent CT scan precisely for evaluation of symptoms related to nasal or sinonasal diseases and, thus, those pathologies might have been the consequence of nasal variations (e.g., Stallman et al., 2004; Balikci et al., 2016). This is a valid argument for all variations studied and should be understood as a limitation for comparison with clinical reports (see also Tables 39 and 40), because the current study base was amassed with very different purposes. The hypertrophy of the middle turbinate shows a prevalence of 38.6%. Few isolated cases have been reported in Palaeopathology and only two studies presented a prevalence of 6.3% (2/32) (Gawlikowska-Sroka et al., 2016b), and 37.8% (17/45) (Mays et al., 2014) (Table 38), showing that its systematic observation has been neglected in past populations. Also, Santos and Prado (2017) reported a prevalence of 54.3% (25/46) in a modern forensic collection of 46 individuals from Brazil. In Portugal, only an adult female presenting a right middle turbinate hypertrophy was

reported by Magalhães (2013), which is the only known reference in Portuguese literature to all five variations studied.

Table 38. Reports of middle turbinate hypertrophy in Palaeopathology.

Individuals/prevalence, Reference Location Date sex, and age at death Burton (1922) Peru Prehistory Five individuals Krogman (1940) Tepe Hissar, Iran 3500-3000 BC One female Gregg and Gregg (1987) South Dakota, USA 1650-1700 AD One female, 35 y.o. Brothwell and Browne York, England 1177-1290 AD One adult female (1994) Marchi and Tarli (2002) Montescaglioso, Italy 7th-3rd centuries BC One female

Isidro and Malgosa Mallorca, Spain Prior to the 9th century AD One mature adult female (2003); Cuesta (2008) Campillo (2005) Barcelona, Spain Mediaeval One female, ±20 y.o. Cuesta (2008) Navarra, Spain Bronze Age One young female Cuesta (2008) Vallès Ocidental, Spain 14th-15th centuries AD One adult male Kwiatkowska et al. (2011) Glogow, Poland 13th-14th centuries AD One adult male Mays et al. (2011) Huntingdon, England 8th-17th centuries AD One adult female, +50 y.o. Powers (2011) London, England 19th century AD One male, 34 y.o.

Two young adult females Reina and Roca (2011) El-Bahnasa, Egipt Roman One mature adult

Three females, one 20-25 Hincak et al. (2013) East Slavonia, Croatia Early Bronze Age y.o., two 45-55 y.o.

Magalhães (2013) Évora, Portugal 16th-17th centuries AD One adult female Booth (2014) Dorchester, England 240-430 AD One male, 30-40 y.o.

Wharrem Percy, 37.8% (17/54); ten males, Mays et al. (2014) 11th-14th centuries AD England seven females

Gawlikowska-Sroka et al. Beginning of the 20th Prędocice, Poland 6.3% (2/32); two females (2016b) century AD Santos and Prado (2017) Salvador, Brazil Modern, forensic 54.3% (25/46)

The diagnosis of concha bullosa using CT scan was first introduced in Palaeopathology by Campillo (2005) in an adult female from Mediaeval Spain. Since then, only five other studies (Kwiatkowska et al., 2011; Mays et al., 2011; 2014; Hincak et al., 2013; Gawlikowska-Sroka et al., 2016b) have used the same imaging support to confirm the differential diagnosis. Indeed, the study of the pneumatisation of the middle turbinate using CT scan is rare, mainly due to the costs involved. Nevertheless, even when this resource is available, only turbinates that appear grossly to be hypertrophied are examined by CT scan. This is what has happened in the two studies that have investigated the prevalence of concha bullosa in skeletal assemblages in Mediaeval England (Mays et al., 2014) and early 20th century Poland (Gawlikowska-Sroka et al., 2016b), as well as with 60 crania in the current work. It is thus possible that minor cases of hypertrophy were missed, as stated by Mays et al. (2014), although this methodology is essential in Anthropology, since it is impossible to perform CT scans in all

individuals from an archaeological assemblage or identified collection. In such cases, the results of the Cohen’s kappa showed that the percentage of agreement for ‘presence’ and ‘side’ is almost perfect, but the reliability for ‘type’ (lamellar, bulbous, or extensive) is moderate to fair. Consequently, the diagnosis of concha bullosa based on its macroscopic observation is highly consistent for presence and side, but unreliable for type. Nevertheless, hypertrophy may arise owning to a variety of pathologies, including haemangioma or fibro-osseous lesions (fibrous dysplasia and ossifying fibroma). Intraosseous haemangiomas of the middle turbinate are extremely rare and characterised by thin internal ‘honeycomb’ bone trabeculations seen on CT scan (Akiyama et al., 2011; Goff et al., 2015). Fibro-osseous lesions are rare, benign tumours in the sinonasal region (Caylakli et al., 2004; Galvan et al., 2007; Gozeler et al., 2016) with well-defined hyperdense bone masses which are sometimes difficult to differentiate even in clinical analysis (Galvan et al., 2007). Mays et al. (2011) refer the formation of fibrous bone as characteristic of fibrous dysplasia, which was not identified in any of the hypertrophies subjected to gross examination in the individuals studied. In fact, the presence of other pathologies that can result in osseous alterations on the middle turbinates is very rare and the use of direct light is usually very helpful to distinguish bone masses from hollow pneumatisations. Nevertheless, when the turbinate is completely preserved, the definitive confirmation of concha bullosa requires the support of CT scan, because normal variation in size should be expected. Despite the few reports of concha bullosa in skeletal assemblages, many have been detailed in clinical practice for the past 30 years. In a review of 43 clinical studies (Table 39), the prevalence of concha bullosa ranges from 9.6% (Milczuk et al., 1993) to 67.5% (Dasar and Gokce, 2016) and 21 of the 43 studies have report a prevalence of 38.6%±10% (Kennedy and Zinreich, 1988; Arslan et al., 1999; Maru and Gupta, 1999; Kinsui et al., 2002; Aktas et al., 2003; Uygur et al., 2003; Kim et al., 2006; Tezer et al., 2006; Ozcan et al., 2008; Riello and Boasquevisque, 2008; Nouraei et al., 2009; Wani et al., 2009; Cabezón et al., 2010; Azila et al., 2011; Javadrashid et al., 2014; Chaitanya et al., 2015; Göçmen et al., 2015; Balikci et al., 2016; Roman et al., 2016; Sarkar et al., 2016; Onwuchekwa and Alazigha, 2017). The wide range of prevalence shows that this is a fairly common anatomical variation, whatever is the background of each group (controls, nasal symptoms, diagnosed rhinosinusitis, or skeletal assemblages) and the prevalence found in the current study is within the expected range.

Table 39. Reports of concha bullosa of the middle turbinate in clinical studies. Reference Location Prevalence Symptoms/complaints Kennedy and Zinreich (1988) USA . 36% (n=230) Rhinosinusitis symptoms

. 33% (27/82) Rhinitis and rhinosinusitis Clark et al. (1989) USA . 11% (13/116) Controls Lloyd (1990) USA . 14% (14/100) Orbital tumour

. 15.9% (13/82) Orbital disease Calhoun et al. (1991) USA . 29% (29/100) Sinus disease Lloyd et al. (1991) England . 24% (24/100) Sinus complaints

88 with sinusitis/nasal polyposis, six Meloni et al. (1992) Italy . 21% (22/106) normal subjects, 12 had tumours Milczuk et al. (1993)a USA . 9.6% (11/114) Chronic rhinosinusitis Earwaker (1993) Australia . 55% (443/800) Evaluation before sinus surgery Nadas et al. (1995) Switzerland . 53% (164/308) Chronic rhinosinusitis

. 23% (23/100) Control Jones et al. (1997) Austria . 18% (18/100) Proven rhinosinusitis Arslan et al. (1999) Turkey . 30% (60/200) Chronic rhinosinusitis Maru and Gupta (1999) India . 41.3% (62/150) Proven chronic rhinosinusitis

. 28.9% (26/90) Sinus disease Kayalioglu et al. (2000) Turkey . 26.8% (22/82) Nonsinus disease Kinsui et al. (2002) Brazil . 33% (49/150) Sinus disease Aktas et al. (2003) Turkey . 38% (54/142) Chronic or recurrent rhinosinusitis Uygur et al. (2003) Turkey . 35% (35/100) Nasal obstruction/nasal septal deviation Subramanian et al. (2005) Malaysia . 49.5% (50/101) Chronic rhinosinusitis Kim et al. (2006)a South Korea . 32.7% (37/113) Chronic rhinosinusitis

. 33.3% (71/213) Allergic rhinosinusitis Tezer et al. (2006) Turkey . 42.1% (53/126) Non-allergic rhinosinusitis Mazza et al. (2007) Italy . 20% (20/100) Sinus CT scan Keast et al. (2008) New Zealand . 60.6% (109/180) Sinus CT scan (pooled results) Ozcan et al. (2008) Turkey . 48.2% (185/384) Nasal complaints Riello and Boasquevisque (2008) Brazil . 42.5% (85/200) Sinus complaints Nouraei et al. (2009) England . 35.3% (98/278) Rhinosinusitis symptoms Wani et al. (2009) India . 30% (45/150) Sinonasal disease Al-Qudah (2010) Jordan . 62% (68/110) Sinonasal symptoms Cabezón A et al. (2010) Chile . 30.3% (43/142) Sinus CT scan Vincent and Gendeh (2010) Malaysia . 25.5% (35/137) Chronic rhinosinusitis

. 40.8% (49/120) Chronic rhinosinusitis Azila et al. (2011) Malaysia . 47.8% (57/120) Controls Fadda et al. (2012) Italy . 49.3% (69/140) Persistent rhinosinusitis symptoms

. 55.2% (48/87) Chronic rhinosinusitis Sadr et al. (2012) Iran . 47.6% (49/103) Controls Al-Abri et al. (2014) Oman . 49% (177/360) Chronic sinonasal symptoms Javadrashid et al. (2014) Iran . 35% (72/206) Sinonasal complaints Chaitanya et al. (2015) India . 47% (47/100) Complaints of sinonasal pathology Göçmen et al. (2015) Turkey . 44.3% (133/300) Sinonasal complaints Shpilberg et al. (2015) USA . 26% (50/192) Rhinosinusitis symptoms Balikci et al. (2016) Turkey . 44.6% (132/296) Facial and sinonasal symptoms Dasar and Gokce (2016) Turkey . 67.5% (270/400) Sinonasal pathology Roman et al. (2016) Romania . 35.4% (46/130) Rhinosinusitis symptoms Sarkar et al. (2016) India . 32.9% (102/310) Rhinosinusitis Koo et al. (2017) South Korea . 53.7% (319/594) Nasal septal deviation Onwuchekwa and Alazigha (2017) Nigeria . 32.7% (36/110) Sinonasal symptoms Avsever et al. (2018) Turkey . 14.6% (101/691) Implant planning or impacted teeth

Although a slightly higher frequency of pneumatisation was found in females, no significant differences were observed between sexes. This is in accordance with the results of Göçmen et al. (2015), but not with the studies of Vincent and Gendeh (2010) and Subramanian et al. (2005), who found a higher frequency with statistical significance in male and female patients, respectively. Narendrakumar and Subramanian (2016) and Koo et al. (2017) report a higher frequency in females and Kayalioglu et al. (2000) in males, but no statistical analysis was detailed. The current results also provide evidence that the pneumatisation of the middle turbinate present statistically higher number of unilateral cases. Mays et al. (2014) report similar results, whereas several clinical studies show higher occurrence of unilateral cases (e.g., Clark et al., 1989; Nadas et al., 1995; Kayalioglu et al., 2000; Riello and Boasquevisque, 2008; Vincent and Gendeh, 2010; Balikci et al., 2016) and others of bilateral pneumatisation (e.g., Uygur et al., 2003; Ozcan et al., 2008; Anazy, 2011; Koo et al., 2017; Avsever et al., 2018). Again, none of the studies provided statistical analysis for this parameter. Nasal septal deviation is the most frequent nasal variation in the current work and there are few examples of its study in skeletal assemblages. Steele et al. (1965) and Titche (1977) reported a prevalence of 52.3% (191/365) and 62% (44/71) of nasal deviations in Prehistoric North American Indians. Gregg and Gregg (1987) detailed a prevalence of 10% (13/129), 7.7% (4/90), 12.4% (3/24), and 39.5% (181/458) in four aboriginal skeletal archaeological collections. More recently, Mays (2012) found that all septa of 32 individuals from Mediaeval England presented deviation. Nevertheless, comparisons with other studies have to be interpreted with caution. Firstly, there is still little consensus regarding the best methodology to record nasal deviation, and several different classifications have been used over the past decades (e.g., Guyuron et al., 1999; Baumann and Baumann, 2007; Jin et al., 2007; Orlandi, 2010; Aziz et al., 2014; Lin et al., 2014; Teixeira et al., 2016). Secondly, several of these methods are based on the clinical or surgical consequences of septal deviations (e.g., Mladina, 1987), making it impossible to adapt for skeletal remains. Finally, clinical morphological approaches always take into account the septum as a whole (both the cartilaginous and osseous portions) and it is impossible to compare and understand the true extent of all deviations in skeletal assemblages, especially the caudal or most anterior deviations of the septum (e.g., Guyuron and Behmand, 2003; Haack and Papel, 2009). Moreover, the fact that the

bony septum may present different deviations depending on the septal bone that is deflected has been noticed before in clinical literature (e.g., Guyuron et al., 1999; Mladina et al., 2008; Beale et al., 2009), with investigators describing its inferior deviation, at the chondrovomeral junction, or a more superior broad-based deviation; nevertheless the subject has not yet been thoroughly studied, both clinically or in archaeological collections. Several clinical studies using the morphological classification proposed by Mladina (1987), the most extensively used in clinical practice, report a prevalence of any type of deviation in 95% (Prasad et al., 2013), 91.3% (Poje et al., 2014), 89.2% (Mladina et al., 2008), 89.1% (Mariño-Sánchez et al., 2017), and 50.3% (Wee et al., 2012) of the individuals studied. Although this approach cannot be adapted for skeletal assemblages, the overall results are in accordance with the high prevalence recorded in this study. These and other clinical studies also acknowledge the high frequencies and clinical importance of C- and S- shape deviations (e.g., Guyuron et al., 1999; Wee et al., 2012; Prasad et al., 2013; Sarafoleanu and Negrila-Mezei, 2014; Mladina et al., 2015; Mariño-Sánchez et al., 2017). This was also noted by Gawlikowska-Sroka and colleagues (2013), who stated that C- and S- shaped deflections were the most common findings in a 12th to 17th century skeletal assemblage of 110 individuals. C-shaped deviations are usually the most frequent in clinical practice (e.g., Mladina, 1987; Guyuron et al., 1999) and were also one of the most frequent types of deviation in the present study. It is usually associated with an abnormal mucociliary clearance system, opening the door for bacterial and viral invasion (e.g., Mladina et al., 2015). S-shape (or bilateral) septal deviations are clinically the most variable, but also reported as one of the most common types of deviation (Mladina et al., 2015). These deviations present similarities to the type 5 described in the current work, when the deviation of the ethmoid is associated with the contralateral deflection of the vomer (recorded in 15.8% of the individuals). S-type deviations are usually associated with the most severe cases of impaired nasal breathing (Mladina et al., 2015). Furthermore, a statistically higher frequency of septal deviation was found in males, which is in accordance with the results of Göçmen et al. (2015), although other clinical studies have found no significant differences between sexes (Subarić and Mladina, 2002; Yildirim and Okur, 2003; Smith et al., 2010; Mariño-Sánchez et al., 2017).

Concha bullosa is usually associated with the types of septal deviation comprising the deflection of the perpendicular plate of the ethmoid, especially with C-type deviations (Guyuron et al., 1999; Uygur et al., 2003; Stallman et al., 2004; Mladina et al., 2008; 2015; Beale et al., 2009; Mladina, 2012; Balikci et al., 2016; Koo et al., 2017; Kucybała et al., 2017; Özdoğan et al., 2017; Santos and Prado, 2017). The origin of the association of the broad-based C- type septal deviations and contralateral concha bullosa has been discussed over the past decades, especially focusing on both the congenital and compensatory hypotheses for the pneumatisation of the middle turbinates. Several authors denote that the enlargement of the middle nasal concha may be determined by genetic factors, whereas others refer that, after the formation of septal deviation, the unfilled space on the contralateral side leads to the development of concha bullosa, mechanism which was termed as compensatory (e.g., Uzun et al., 2012). Theoretically, concha bullosa would be greater in size as the nasal septal deviation increases, and this has been also hypothesised for skeletal remains (Gregg and Gregg, 1987). Nadas et al. (1995) refer that their results might support the compensatory hypothesis. Uygur et al. (2003) suggest that septal deviation does not originate concha bullosa, but increases its contralateral pneumatisation, depending on the degree and angle of deviation. Uzun et al. (2012) report findings that are not consistent with the compensatory theory, showing that the degree of hypertrophy of the contralateral side of deviation was independent of age and severity of deviation, proposing a genetic origin for concha bullosa. The study of Chaiyasate et al. (2007) with monozygotic and dizygotic twins also suggests a genetic influence. The present results show that, not only the occurrence of concha bullosa, but also of paradoxical curvature is statistically associated with contralateral septal deviation, whilst the size of the concha bullosa does not predict the NSDI. Moreover, all five variations studied in the current work show a lack of association with adult age at death. These results seem to be related to the fact that all variations develop mostly during early age, when bones are growing, and is consistent with the hypothesis that genetics may play an important role in their presence, as suggested in literature (e.g. Lam et al., 1996; Chaiyasate et al., 2007; Neskey et al., 2009; Vincent and Gendeh, 2010). The present study is in accordance with the hypothesis that septal deviations may also present the same genetic basis of development but, particularly the deviation of the perpendicular plate of the ethmoid (or ‘C’ shape deflections), may be increased during development by other

variations of the ostiomeatal complex. On the other hand, L-shape deviations and isolated deflections of the vomer are more likely to be associated with genetics or developmental problems, not only in the vomer, but probably also in the maxillary and palatine bone crests, which are the base axis of the nasal septum. This may be an important line of investigation in future studies. Clinical literature also highlight several anomalies that may occur during pregnancy and hypothetically result in nasal deviation, when the foetus is subjected to various torsions and pressures (e.g., Braun and Stammberger, 2003; Kim et al., 2006; Chaiyasate et al., 2007; Neskey et al., 2009). Once displaced, these bones would continue to grow in their altered alignment (Neskey et al., 2009). In the current work, the NSDI resulted in values higher than zero for all individuals (726/726, 100%), whereas the morphological methodology showed the macroscopic absence of deviation in 5.2% (38/726) individuals. The apparent paradox of these 38 individuals is related to the fact that their deviation is so tenuous that is indiscernible to the human eye, but perceptible when the ImageJ software was used to measure the septal thread length. The current results show that individuals without macroscopic septal deviation present a NSDI between 0.08 and 0.79. Septal spurs were recorded in 14.2% (258/1814) of the individuals studied, in accordance with clinical studies presenting a prevalence between 1.2% (Koo et al., 2017) and 45% (Grazia K. et al., 2014) (Table 40). Male individuals exhibit twice as much septal spurs than females, with statistically significant differences. Madani et al. (2013) and Koo et al. (2017) also reported a higher frequency in males, whilst Avsever et al. (2018) found a higher frequency in females.

Table 40. Reports of septal spurs in clinical studies. Reference Location Prevalence Symptoms/complaints Pérez-Piñas et al. (2000) Spain . 13.6% (15/110) Inflammatory sinus disease Cabezón A et al. (2010) Chile . 34.5% (49/142) Sinus CT scan Madani et al. (2013) Iran . 3.9% (8/206) Chronic rhinosinusitis symptoms Grazia K et al. (2014) Chile . 45% (45/100) Sinonasal pathology Shpilberg et al. (2015) USA . 32.3% (62/192) Rhinosinusitis symptoms Dasar and Gokce (2016) Turkey . 42.3% (169/400) Sinonasal pathology Koo et al. (2017) South Korea . 1.2% (7/594) Nasal septal deviation Avsever et al. (2018) Turkey . 7.8% (54/691) Implant planning or impacted teeth

The present work also show no significant differences between sides, which is in accordance with Saedi et al. (2015), but not with Guyuron et al. (1999), who found a higher frequency of left sided spurs. Clinically, septal spurs are associated with 92

unilateral impairment of nasal breathing and sometimes to ipsilateral sudden attacks of diffuse pain in one half of the head (typical hemicrania or Sluder’s headache) followed by edema and secretion of the nasal mucosa (Mladina, 2012; Mladina et al., 2015). Moreover, the relationship between spurs and the development of the nasal septum seems to be very close, since septal spurs are statistically associated with higher values of NSDI as well as with ipsilateral septal deviation. This is in accordance with Saedi et al. (2015) who described thirty patients who underwent septorhinoplasty due to the presence of septal spurs, all presenting ipsilateral septal deviation. Nevertheless, Guyuron et al. (1999) described divergent septal directions in 93 patients. The current results show a general high prevalence of nasal variations, which are absent only in eight (8/483, 1.7%) individuals. This may be partially explained by the methodology used, especially for nasal septal deviation, but also for paradoxical curvature and concha bullosa, where all variations were recorded regardless of the curvature, size, or type. Unfortunately, there are few studies based on skeletal collections addressing nasal variations; nevertheless, as discussed above, clinical studies detail solid results confirming a high prevalence of each one of the nasal variations studied. Shpilberg et al. (2015), for instance, found at least one nasal or paranasal variation in all 192 patients studied, whilst 191 presented at least two variations. Earwaker (1993) also found at least one nasal variation in 92.9% (743/800) of the patients studied. The current work seems to corroborate the high prevalence reported for nasal variations in clinical studies for the past 30 years, although there is still lack of detail, for instance, reporting sexual frequencies or statistical analysis.

4.3. Nasal cavity and maxillary sinus pathology

This chapter will discuss the presence of new bone formations on the middle turbinates and within the maxillary sinuses and its possible association with the nasal variations studied in chapter 4.2.

4.3.1. Results

4.3.1.1. Middle turbinate spicules Of the 1684 individuals with at least one middle turbinate preserved, 59.3% (999/1684) present spicules on the middle turbinates (Table 41; Plate XIII, Figure 29). Of the three collections studied, the Medical Schools Skull Collection (MSSC) shows the lowest percentage (49%, 236/482), with statistically significant differences (Pearson χ2=30.047; d.f.=2; p<0.001).

Table 41. Prevalence of middle turbinate spicules by sex.

Male Female Total Collection N n % N n % N n % MSSC 303 130 42.9 179 106 59.2 482 236 49 IESC 433 225 52 467 347 74.3 900 572 63.6 HISC 145 76 52.4 157 115 73.2 302 191 63.2 Total 881 431 48.9 803 568 70.7 1684 999 59.3 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Females present higher frequency (males=48.9%, 431/881; females=70.7%, 568/803), with statistically significant differences (Pearson χ2=82.834; d.f.=1; p<0.001). The youngest individual presenting STBF is a 2-year-old male and the oldest is a 109-year-old female. The increased age at death is statistically associated with the absence of spicules in males (Student’s t=4.583, d.f.=873, p<0.001; absence n=445, x̅ =47.22, s.d.=18.59 vs presence n=430, x̅ =41.21, s.d.=20.22), but not in females (Student’s t=1.385, d.f.=452, p=0.167; absence n=234, x̅ =51.02, s.d.=21.90 vs presence n=565, x̅ =48.63, s.d.=22.82) (Figure 30). Of the 1473 individuals with both turbinates preserved, 17.3% (254/1471) exhibit unilateral and 44.7% (658/1471) bilateral spicules (Table 42; Appendix A5). The higher frequency of bilateral cases is statistically significant (Pearson χ2=178.965; d.f.=1; p<0.001), whilst unilateral spicules do not resulted in significant differences between sides (Pearson χ2=2.268; d.f.=1; p=0.132). 94

Plate XIII

Female, 82 years old (MSSC 560). Female, 55 years old (IESC 328).

Female, 65 years old (IESC 984). Female, 27 years old (HISC 276).

Figure 29. Examples of spicules on the middle turbinates. Males Females

90 82,1 80 74,2 73,8 70,6 69,5 69 69,3 70 64,3

% 60 52,5 53 50 47,3 44 42,7 40 37,6

30 <=19 yo 20-29yo 30-39yo 40-49yo 50-59yo 60-69yo => 70yo

Figure 30. Spicule-type bone formations on the middle turbinates by sex and age at death.

Table 42. Middle turbinate spicules by side and sex in the individuals with both turbinates preserved.

Male N=767 Female N=704 Total N=1471 Side n % n % n % Right 67 8.7 72 10.2 139 9.4 60 7.8 55 7.8 115 7.8 Left Bilateral 266 34.7 392 55.7 658 44.7 Total 393 51.2 519 73.7 912 62

4.3.1.2. Bone formation within the maxillary sinuses

Of the 873 individuals with at least one maxillary sinus available for examination, 49.8% (435/873) had evidence of bone formation within the sinuses, without significant differences between the three collections studied (χ2=1.305; d.f.=2; p=0.521) (Table 43).

Table 43. Bone formations within the maxillary sinuses by sex. Collection Male Female Total N n % N n % N n % MSSC 109 45 41.3 89 60 67.4 198 105 53 IESC 250 112 44.8 263 136 51.7 513 248 48.3 HISC 85 43 50.5 77 39 50.6 162 82 50.6 Total 444 200 45 429 235 54.8 873 435 49.8 MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection.

Females present higher frequency (males=45%, 200/444; females=54.8%, 235/429) of bone formations, with statistically significant differences (Pearson χ2=8.269; d.f.=1; p=0.004). The youngest individual presenting bone formations is a

4-year-old male and the oldest is a 109-year-old female. The increased age at death is associated with bone formations within the maxillary sinuses in females (Student’s t= -3.124, d.f.=403, p=0.002; absence n=193, x̅ =44.77, s.d.=23.47 vs presence n=234, x̅ =51.78, s.d.=22.64), but not in males (Student’s t=0.761, d.f.=421, p=0.447; absence n=244, x̅ =46.02, s.d.=21.06 vs presence n=199, x̅ =44.48, s.d.=21.34) (Figure 31).

Males Females

80 75 73,5 70 65 60,2 % 60 53,8 53,7 55 52,7 52,5 51,1 49,2 50 48,3

45 42,5 43,3 43,5 40 34,7 36,5 35 30 <=19 yo 20-29yo 30-39yo 40-49yo 50-59yo 60-69yo => 70yo

Figure 31. Bone formations within the maxillary sinuses by sex and age at death.

Of the 506 individuals with both maxillary sinuses available for inspection, bilateral cases present higher frequency (unilateral=18.8%, 95/506; bilateral=35.8%, 181/506), with statistically significant differences (Pearson χ2=26.797; d.f.=1; p<0.001) (Table 44; Appendix A6). Regarding the unilateral cases, 10.1% (51/506) are on the right side and 8.7% (44/506) on the left, without significant differences (Pearson χ2=0.516; d.f.=1; p=0.516). Of the 616 maxillary sinuses presenting bone formations, 83.3% (513/616) show isolated spicule-type bone formations (STBF), 2.3% (14/616) remodelled spicules (ReS), 1.9% (12/616) lobules of white bone (LWB), 0.5% (3/616) plaque, and in 12% (74/616, side: right=38, left=36) more than one alteration was recorded (Table 45; Plate XIV, Figure 32).

Plate XIV

. Female, 23 years old (MSSC 30) . Male, 66 years old (IESC 110) . L obule of white bone and spicule-type bone . Spicule-type bone formations within the right formations within the left maxillary sinus maxillary sinus

. Male, 64 years old (IESC 168) . Female, 58 years old (IESC 265) . Spicule -type bone formations within the left . Plaque bone formation and spicules within the right maxillary sinus maxillary sinus

. Female, 6 years old (HISC 521) . Male, 29 years old (IESC 725) . Remodelling spicules within the left maxillary . Spicule-type bone formations surrounding a sinus ‘chimney-like’ oroantral fistula within the right maxillary sinus.

Figure 32. Examples of bone formations within the maxillary sinuses. Table 44. New bone formations by side and sex in the individuals with both maxillary sinuses available for examination.

Male N=269 Female N=237 Total N=506 Side n % n % n % Right 27 10 24 10.1 51 10.1 Left 24 8.9 20 8.4 44 8.7 Bilateral 78 29 103 43.5 181 35.8 Total 129 48 147 62 276 54.5

Table 45. Isolated and combined types of bone changes recorded within the maxillary sinuses.

Male Total Female Total Type of Right Left N=713 Right Left N=666 bone change N=360 N=353 N=335 N=331 n % n % N % n % n % n % Absent 215 59.7 220 62.3 435 61 163 48.7 165 49.8 328 49.2 STBF 128 35.6 111 31.4 239 33.5 136 40.6 138 41.7 274 41.1 ReS 1 0.3 2 0.6 3 0.4 7 2.1 4 1.2 11 1.7 LWB 3 0.8 3 0.8 6 0.8 1 0.3 5 1.5 6 0.9 Plaque 2 0.6 - - 2 0.3 1 0.3 - - 1 0.2

More than 11 3.1 17 4.8 28 3.9 27 8.1 19 5.7 46 6.9 one type STBF=Spicule-type bone formation; ReS=Remodelled spicules; WPB=White pitted bone; LWB=Lobules of white bone.

Males present a higher frequency of isolated changes, whilst females present a higher frequency of more than one type of alteration, with significant differences (Pearson χ2=4.906; d.f.=1; p=0.027). STBF, LWB, and plaque show a higher frequency in males, whereas ReS represent higher values in females, although none of them show statistically significant differences (STBF Pearson χ2=0.906; d.f.=1; p=0.341; ReS Pearson χ2=0.645; d.f.=1; p=0.422; LWB Pearson χ2=1.145; d.f.=1; p=0.285; Plaque Fisher’s Exact Test p=0.601). Pits and/or white pitted bone were also recorded in 41 individuals with both maxillary sinuses available for examination, showing a lower mean age at death (n=41, x̅ =40.07, s.d.=27.11) compared to individuals presenting new bone formations (n=433, x̅ =48.43, s.d.=22.33). These differences do not show statistically significant differences (Mann-Whitney U=7072.0; p=0.055). Regarding the degree of osseous changes, of the 616 maxillary sinuses presenting bone formations, degree 1 was recorded in 34.7% (214/616) individuals, degree 2 in 50.3% (310/616), and degree 3 in 14.9% (92/616) (Table 46; Appendix A7). All degrees present a higher frequency in females, without significant differences between sexes on both sides (right Pearson χ2=2.709; d.f.=2; p=0.258; left Pearson χ2=2.596; d.f.=2; p=0.273).

Table 46. Degree of bone formations within the maxillary sinuses by side and sex. Male Total Female Total Degree Right N=360 Left N=353 N=713 Right N=335 Left N=331 N=666 n % n % n % n % n % n % 1 55 15.3 51 14.4 106 14.9 52 15.5 56 16.9 108 16.2 2 71 19.7 68 19.3 139 19.5 89 26.6 82 24.8 171 25.7 3 19 5.3 14 4 33 4.6 31 9.2 28 8.5 59 8.9 Total 145 40.3 133 37.7 278 39 172 51.3 166 50.2 338 50.8

Moreover, a Kruskal-Wallis H test shows that there is no statistical relationship between the degree of bone formation and age at death (Kruskal-Wallis H=2.637; d.f.=3; p=0.451) (Table 47).

Table 47. Mean age at death by degree of bone formations within the maxillary sinuses. Degree n x̅ s.d. 0 230 45.8 22.7 1 78 48.0 22.4 2 149 47.8 23.7 3 48 51.4 21.0

Of the 873 individuals with at least one maxillary sinus available for inspection, 1.7% (15/873) present oroantral fistulae with bone remodelling, nine (9/15, 60%) on the right side and six (6/15, 40%) on the left; ten (10/15, 66.7%) of individuals are males and five (5/15, 33.3%) are females, without significant differences between sexes (Pearson χ2=1.134; d.f.=1; p=0.287). Of the 15 fistulae, 53.3% (8/15) show smooth remodelled edges, 33.3% (5/15) present a ‘chimney-like’ bone formation, whilst in 13.3% (2/15) postmortem damage does not allow its proper classification. All oroantral fistulae were identified on molar tooth sockets (six first molars, six second molars, and three third molars). Nine tooth sockets exhibit antemortem tooth loss, two show postmortem tooth loss, in two teeth pathology is absent, one tooth presents one carious lesion, and one is not observable. Overall, 83.3% (10/12) of the preserved teeth/tooth sockets also present pathological alterations. Oroantral root protrusions without bone remodelling into the sinus floor were recorded in 4.5% (39/873) of the individuals, 43.6% (17/39) on the right side, 48.7% (19/39) on the left, and 7.7% (3/39) bilaterally, totalising 42 root protrusions. Twenty-one (23/39, 59%) individuals are males, and 16 (16/39, 41%) are females, without statistically significant differences between sexes (Pearson χ2=0.199; d.f.=1; p=0.656). Forty protrusions without bone remodelling were recorded on molar teeth (12

first molars, 23 second molars, and five third molars) and two in the second premolars. Twenty-eight teeth are present in the sockets without pathological alterations, seven show carious lesions, three were lost antemortem, one was lost postmortem, two tooth sockets exhibit periodontal disease, and one is not observable. Overall, 30% (12/40) of the preserved teeth/tooth sockets present pathological alterations.

4.3.1.3. Testing the hypothesis of association between nasal variations and nasal and sinonasal disease

Two models of logistic regression were performed to ascertain the effects of sex, age at death, concha bullosa, paradoxical curvature, accessory turbinate, and nasal septal deviation index (NSDI) on the likelihood that individuals present spicules in the middle turbinates or bone formations within the maxillary sinuses. The model tested for 2 the presence of middle turbinate spicules is statistically significant (χ [6d.f.]=68.065, p<0.001), indicating an association with females, which are approximately 3.5 times more likely than males to exhibit middle turbinate spicules, and the presence of concha bullosa, and paradoxical curvature, which increase on 1.7 and 1.6 times, respectively, the likelihood of presenting spicules. The coefficients, Wald statistic, odds ratio, and p- values for all variables tested in the equation are shown in Table 48.

1 Table 48. Contribution of each independent variable to the model tested for the presence of middle turbinate spicules and respective odds ratio. Middle turbinate spicules B Wald p-value OR 95% CI Sex 1.259 44.895 <0.001 3.523 2.437-5.092 Age at death -0.005 1.042 0.307 0.995 0.986-1.004 Concha bullosa 0.505 7.413 0.006 1.657 1.152-2.385 Paradoxical curvature 0.461 6.518 0.011 1.585 1.113-2.257 Accessory turbinate -0.239 1.007 0.316 0.788 0.494-1.255 Nasal septal deviation index -0.022 0.632 0.427 0.978 0.427-0.978

The model performed for the presence of bone formation within the maxillary 2 sinuses is not statistically significant (χ (6d.f.)=7.345, p=0.290) and only presents statistical association with female individuals, which are approximately two times more likely than males to exhibit bone formation within the maxillary sinuses. The coefficients, Wald statistic, odds ratio, and p-values for all variables tested in the equation are shown in the Table 49.

Table 49. Contribution of each independent variable to the model tested for the presence of bone formations within the maxillary sinuses and respective odds ratio. Bone formation within the right maxillary sinus B Wald p-value OR 95% CI Sex 0.688 4.347 0.037 1.990 1.042-3.801 Age at death -0.002 0.066 0.797 0.998 0.982-1.014 Concha bullosa -0.375 1.249 0.264 1.456 0.754-2.811 Paradoxical curvature 0.420 1.641 0.200 0.657 0.346-1.249 Accessory turbinate 0.190 0.215 0.643 0.827 0.370-1.848 Nasal septal deviation index 0.017 0.117 0.733 1.018 0.921-1.125

Four logistic regressions were also performed to assess the possible association between the presence of middle turbinate spicules or bone formations within the maxillary sinuses and ipsilateral nasal variations. Concerning the presence of spicules on the middle turbinate, the models of logistic regression were statistically significant 2 2 (right side χ (6d.f.)=65.574, p<0.001; left side χ (6d.f.)=56.694, p<0.001), confirming that females, concha bullosa, and paradoxical curvature increase the likelihood of presence of spicules on the middle turbinate on both sides. The coefficients, Wald statistic, p-values, and odds ratio for all variables tested in the equation are shown in Tables 50 and 51.

Table 50. Contribution of each independent variable to the model tested for the presence of spicules on the right middle turbinate and respective odds ratio. Right middle turbinate spicules B Wald p-value OR 95% CI Sex 1.171 39.360 <0.001 3.226 2.238-4.652 Age at death -0.001 0.054 0.816 0.999 0.989-1.009 Ipsilateral variations: - - - - - Concha bullosa 0.582 7.789 0.005 1.790 1.189-2.694 Paradoxical curvature 0.601 9.946 0.002 1.823 1.255-2.648 Accessory turbinate -0.463 2.875 0.090 0.629 0.369-1.075 Septal deviation -0.111 0.352 0.553 0.895 0.620-1.291

Table 51. Contribution of each independent variable to the model tested for the presence of spicules on the left middle turbinate and respective odds ratio. Left middle turbinate spicules B Wald p-value OR 95% CI Sex 1.230 42.084 <0.001 3.423 2.360-4.964 Age at death -0.008 2.423 0.120 0.992 0.983-1.002 Ipsilateral variations: - - - - - Concha bullosa 0.498 5.670 0.017 1.645 1.092-2.479 Paradoxical curvature 0.417 4.967 0.026 1.518 1.052-2.190 Accessory turbinate 0.121 0.173 0.678 1.129 0.638-1.996 Septal deviation -0.330 2.972 0.085 0.719 0.494-1.046

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Concerning the presence of bone formation within the maxillary sinuses, the model of logistic regression for the right side was not statistically significant 2 2 (χ (6d.f.)=4.925, p=0.553), whilst the one for the left side was (χ (6d.f.)=15.441, p=0.017). The model for the left side showed that females are approximately two times more likely than males to exhibit bone formation within the maxillary sinuses. Nevertheless, the presence of paradoxical turbinate is statistically associated with a decrease in likelihood of exhibiting spicules on the left middle turbinate (OR=3.868, 95% C.I.: 1.514-9.884). The coefficients, Wald statistic, p-values, and odds ratio for all variables tested in the equation are shown in Tables 52 and 53.

Table 52. Contribution of each independent variable to the model tested for the presence of bone formation within the right maxillary sinuses and respective odds ratio. Bone formation within the right maxillary sinus B Wald p-value OR 95% CI Sex 0.681 2.411 0.120 1.976 0.836-4.667 Age at death -0.007 0.477 0.490 0.993 0.973-1.013 Ipsilateral variations: - - - - - Concha bullosa 0.486 1.032 0.310 1.626 0.637-4.152 Paradoxical curvature 0.205 0.214 0.644 1.228 0.515-2.926 Accessory turbinate -0.028 0.002 0.962 1.028 0.328-3.219 Septal deviation -0.090 0.362 0.548 1.094 0.816-1.466

Table 53. Contribution of each independent variable to the model tested for the presence of bone formation within the left maxillary sinuses and respective odds ratio. Bone formation within the left maxillary sinus B Wald p-value OR 95% CI Sex 1.333 7.910 0.005 1.976 0.836-4.667 Age at death -0.007 0.348 0.555 0.993 0.972-1.016 Ipsilateral variations: - - - - - Concha bullosa 0.066 0.016 0.899 1.068 0.385-2.964 Paradoxical curvature -1.353 7.985 0.005 3.868 1.514-9.884 Accessory turbinate 0.471 0.536 0.464 1.602 0.454-5.653 Septal deviation -0.245 0.038 0.614 0.783 0.303-2.025

Moreover, the concurrence of several variations (hypertrophy, curvature, accessory turbinate, and septal deviation) was tested in 113 individuals to determine its possible influence on the occurrence of bone formations within the maxillary sinuses and no statistically significant differences were found (Pearson χ2=0.719; d.f.=2; p=0.698). Also, the most extreme type of paradoxical curvature (type 2) is statistically associated with the presence of bone formations within the right maxillary sinuses (Pearson χ2=5.359; d.f.=1; p=0.021), but not within the left ones (Pearson χ2=0.200; d.f.=1; p=0.655).

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The standardised concha bullosa width of the 60 individuals who underwent CT scan is not associated with middle turbinate or maxillary sinus bone formations by side or dominant concha bullosa (Table 54). When the type of concha bullosa is tested, bulbous/extensive types are not statistically associated with bone formations within the maxillary sinuses on both sides (right Pearson χ2=0.072; d.f.=1; p=0.788; left Pearson χ2=2.182; d.f.=1; p=0.140).

Table 54. Mean values of standardised concha bullosa width by presence of new bone formations and respective statistical significance.

Bone formations within the maxillary Middle turbinate spicules Concha bullosa sinuses N x̅ SD Student’s T N x̅ SD Student’s T

A1 7 64.9 9.1 t=1.392; d.f.=18; A 7 62.6 11.6 t=0.459; d.f.=14;

Right P2 13 59.8 7.0 p=0.181 P 9 60.6 5.3 p=0.654

Side

A 13 54.2 13.0 t= -0.276; d.f.=28; A 7 48.7 9.5 t= -1.113; d.f.=19 Left P 17 55.5 12.5 p=0.784 P 14 55.0 13.3 p=0.280

A 10 64.8 9.3 t=1.164; d.f.=35; A 13 61.0 11.0 t=0.139; d.f.=33; Dominant P 27 59.8 12.3 p=0.252 P 22 60.5 11.6 p=0.890 1Absent; 2Present.

The concurrence of paradoxical curvature and concha bullosa on the same side is statistically associated with the ipsilateral presence of middle turbinate spicules (right Pearson χ2=15.939; d.f.=1; p<0.001; left Pearson χ2=6.113; d.f.=1; p=0.013), although it is not statistically associated with ipsilateral bone formations within the maxillary sinuses (right Pearson χ2=0.035; d.f.=1; p=0.852; left Pearson χ2=3.249; d.f.=1; p=0.071). Finally, the presence of new bone formation within the maxillary sinuses is not associated with the presence of spicules on the middle turbinates on both sides (right Pearson χ2=0.151; d.f.=1; p=0.697; left Pearson χ2=0.155; d.f.=1; p=0.694). Nevertheless, the most extreme types (2 and 3) of bone formations within the maxillary sinuses are statistically associated with ipsilateral middle turbinate spicules on the right side (Pearson χ2=4.433; d.f.=1; p=0.035), but not on the left (Pearson χ2=0.148; d.f.=1; p=0.700).

4.3.2. Discussion

Overall, a prevalence of 59.3% and 49.8% of bone formations on the middle turbinates and within the maxillary sinuses, respectively, was recorded in the current work. The mechanisms through which new bone is formed within the maxillary sinuses 102

have been studied more intensively over the past two decades. The presence of ‘osteitis’ have been associated with the disruption of the organised collagen pattern of the lamellar bone and new unorganised woven bone formation (e.g., Giacchi et al., 2001; Leung et al., 2016). Initial changes occur in the soft tissues, reflecting the prolonged inflammatory response of the nasal and sinus mucosa and the fluid within the sinuses, but also producing changes in the underlying bone (e.g., Norlander et al., 1994; Khalid et al., 2002; Slavin et al., 2005; Roberts, 2007). Investigators have shown that there is a periosteal reaction within the maxillary sinuses in cases of chronic rhinosinusitis, which was first observed in experimentally infected animals and subsequently in humans (e.g., Norlander et al., 1994; Kennedy et al., 1998; Mutijima et al., 2014; Sethi, 2015). In fact, recent clinical studies have suggested that the bone may play a more significant role than previously thought in rhinosinusitis, where chronic infection can also spread through the bony structures and both mucosal and bone changes are not limited to the initial focus of the disease, but also to the contralateral maxillary sinus, after the inflammation spreads through the Haversian canal system within the bone (Perloff et al., 2000; Khalid et al., 2002). The ostiomeatal complex is an intricate anatomical area and the pathophysiological mechanisms of the mucosa and underlying bone associated with rhinosinusitis may be also described for the inflammation of the nasal mucosa, particularly of the middle turbinates, resulting in the formation of similar spicules of new bone. As stated before, the mucous membrane of both the nasal passages and paranasal sinuses represent contiguous structures, sharing vascular, neuronal, and interconnecting anatomical pathways, and similar inflammatory mediators are present in both diseased structures (e.g. Lund and Kennedy, 1995; Van Crombruggen et al., 2010; Naeimi et al., 2013). Accordingly, rhinitis may be hypothesised as one of the most probable causes of middle turbinate spicules as a consequence of the swelling of the mucous membranes. The clinical concept of the presence of osteitis on the middle turbinates, wherein new bone is formed as a response of body tissues to harmful stimuli, was described by Biedlingmaier et al. (1996), in 38 partial middle turbinate resections due to complications of anosmia, bleeding, and crusting. This histopathological study, not only confirmed the presence of mucosal changes which were previously seen on CT scan, but also showed changes on the underlying bone of the middle turbinates. The changes were most prominent in patients who were diagnosed with the most severe clinical and imaging consequences (Biedlingmaier et al., 1996), and the authors

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highlighted the idea of osteitis on the middle nasal turbinates as a source of recurrent infection and a focus of pathologic changes (Biedlingmaier et al., 1996; Wolf and Biedlingmaier, 2001). Clinical literature describes the relation between rhinitis and sinusitis (e.g., Dykewicz, 2003; Fokkens et al., 2005; Van Crombruggen et al., 2011; Sedaghat et al., 2012), which has been highlighted by the abovementioned use of the term ‘rhinosinusitis’. This clinical assumption recognises that sinusitis without rhinitis is rare and that the mucosa of the nose and sinuses are contiguous and related to one another (e.g., Dykewicz, 2003). Nevertheless, the current results show an overall lack of statistical association between new bone formations on the maxillary sinus and middle turbinate on both sides and only a partial statistical association was confirmed between the most extreme types (2 and 3) of bone formations within the maxillary sinuses and ipsilateral middle turbinate spicules on the right side. This may be related to the fact that rhinosinusitis may affect all the human sinuses, whereas in the present study only the maxillary sinuses were considered. Also, different pathophysiological mechanisms may underlie different patterns of new bone formation, due to the differences between both anatomical frameworks. Unfortunately, these mechanisms are badly understood even in clinical practice. Moreover, the presence of bone formations on both anatomical structures show a lack of association with increased age at death, excepting higher frequency of maxillary rhinosinusitis with older age in females. This seems to be related to the occurrence of these bone formations since early age, mainly on the middle turbinate, but, to a certain extent, also within the maxillary sinuses. Clinical studies estimate that 5-40% of the general population suffers from rhinitis (Spector, 2001; Dykewicz and Hamilos, 2010) and state that the global prevalence of both rhinitis and rhinosinusitis has increased over the past decades (Spector, 2001; Meltzer et al., 2004; Fokkens et al., 2012) Particularly in Portugal, a cross-sectional, population-based study including 6859 questionnaire responses performed by Todo-Bom et al. (2007) estimated a prevalence of 26% of rhinitis in the Portuguese population. Falcão et al. (2008) reported a prevalence of 32% in 2161 Portuguese children, whilst Morais-Almeida et al. (2013) found a prevalence of 43.4% in 5030 Portuguese children with 3-5 years old. Also, recent epidemiological studies of rhinosinusitis have reported a prevalence of 13.7% and 27% in Portuguese individuals (Barros et al., 2008; Todo-Bom et al., 2012), which represent lower prevalence for both

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diseases compared to the current work. Moreover, no studies were found discussing how rhinitis has affected past populations, but few isolated cases were reported in Portuguese literature for maxillary rhinosinusitis and three studies including small archaeological collections reported a prevalence of 20% (Neto, 2005), 20.5% (Garcia, 2007), and 60% (Lopes, 2001) (Table 55). Two case studies were reported for the Neolithic/Chalcolithic periods, whilst a few more were reported for Mediaeval and Postmediaeval periods, showing that the search for evidence of maxillary rhinosinusitis has been neglected in Portuguese archaeological collections. Several other studies, mainly from Europe and North America, reported a prevalence of maxillary rhinosinusitis between 4.9%, in several pooled skeletal assemblages from England (Wells, 1977), and 95.1%, in an early Mediaeval assemblage from Sweden (Sundman and Kjellström, 2013b) (Table 56).

Table 55. Studies reporting maxillary rhinosinusitis in Portuguese palaeopathological literature. Reference Location Date Sex and age at death Silva (1993) Cascais Neolithic/Chalcolithic Unknown Cunha (1994) Coimbra 11th-14th centuries AD Adult male (40-50 y.o.)

Three adults females (two with Cardoso (1997) Coimbra 14th-17th centuries AD >49 y.o.; one with 30-39 y.o.) Matos (1999) Foz Côa 5th-9th centuries AD Adult male Silva (1999) Santarém - Male adult (>40 y.o.) Silva (2002) Leiria 4640±90 BP Unknown Costa (2003) Miranda do Corvo 16th-19th centuries AD Unknown (ossuary) Santos and Ferreira (2004) Alcobaça - Unknown (ossuary) Antunes (2006) Santarém Mediaeval? Unknown (ossuary) Godinho (2008) Lisbon 16th-18th centuries AD Adult male (20-29 y.o.) Pinto (2012) Figueira da Foz 17th-19th centuries AD Unknown (ossuary) Magalhães (2013) Évora 16th-17th centuries AD Adult Serafim (2017) Lisbon 12th-14th centuries AD Adult male Prevalence n N % Lopes (2001) Coimbra 14th-17th centuries AD 6 10 60 Neto (2005) Almada 16th-18th centuries AD 3 15 20

Non-adults 3 22 13.6 Garcia (2007) Leiria 12th-16th centuries AD Adults 5 17 29.4 y.o.=years old

These wide differences reported in prevalence are frequently associated with environmental issues. Lewis et al. (1995) found higher prevalence proved to be significant in individuals living in an urban environment, suggesting an influence of industrial air pollution in the Mediaeval city of York (England). Sundman and Kjellström (2013b) have also found significant differences between the urban population of Sigtuna and the rural sites of the Mälaren Valley and Birka in Sweden.

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Roberts (2007) found an overall higher prevalence of maxillary rhinosinusitis in urban agricultural sites compared to rural ones, although with somehow similar results (48.5% vs 45%).

Table 56. Reports of prevalence of maxillary rhinosinusitis in palaeopathological literature.

Prevalence Reference Location Date n N %

From Bronze to Mediaeval ages Wells (1977) Several locations, England 19 387 4.9 (pooled collections) Brothwell and Browne (1994) York, England 1177-1290 AD 28 90 31.1 Boocock et al. (1995a) Chichester, England 1118-1148 AD 73 133 54.9

Wharram Percy, England 950-1500 AD 106 268 39.6 Lewis et al. (1995) St. Helen-on-the-Walls, England 950-1550 AD 134 245 54.7 Boschsraat, Netherlands 600-800 AD 7 28 25.0 Panhuysen et al. (1997) Servaas, Netherlands 450-950 AD 29 67 43.3 Nunnery, Netherlands 1250-1600 AD 13 31 41.9 Merrett and Pfeiffer (2000) Ontario, Canada 1410-1483 AD 103 207 49.8 Merrett (2003) Ontario, Canada Ca. 1300 AD 44 74 59.5 Aleutian Islanders 1599-1600 AD 15 35 42.9 Kentucky, USA 1550-1675 AD 17 33 51.5 Kentucky, USA 4570±75 to 3500±60 37 96 38.5 Roberts (2007) Illinois, USA 800-1100 AD 27 70 38.6 South Dakota, USA Late 1500s to early 1800s AD 15 87 17.2 Kulubnarti, Sudan 50-1700 AD 22 101 21.8 London, England 18th-19th centuries AD 71 394 18.0 Schultz et al. (2007) Grasshopper , USA Pre-Columbian 65 129 50.5 Iron Age 43 57 75.4 Roman Period (pooled collections) 54 162 33.3 Bernofsky (2010) Several locations, England Early Mediaeval (pooled collections) 89 186 47.8 Late Mediaeval (pooled collections) 219 363 60.3 Postmediaeval (pooled collections) 138 334 41.3 Liebe-Harkort (2012) Ostergotland, Sweden 150 BC to 260 AD 46 65 70.8 Sundman and Kjellström Birka, Sweden 750-960 AD 28 34 82.3 (2013b) The Malaren Valley, Sweden 750-1200 AD 14 20 70.0 Sigtuna, Sweden 970-1100 AD 39 41 95.1 Teul et al. (2013) Rurka and Chwarszczny, Poland 13th-15th centuries AD 69 96 75.0 Mushrif-Tripathy (2014) Several locations, India 2000 BC to 17th century AD 9 74 12.2

Krenz-Niedbała and Łukasik Cedynia, Poland 18 100 18 10th-14th centuries AD (2016) Slaboszewo, Poland 2 28 7.1

Concerning the present work, the classification of rural or urban background of individuals presenting incomplete data is always open to debate and subjectivity. The amount of years that an individual actually lived in a given place (urban or rural) is unknown and only the last place of residence is referred in the identification. This is also a limitation for the interpretation of the results, but intrinsic to the study of skeletal assemblages with limited data of identification. Although the individuals from the Human Identified Skeletal Collection (HISC) show a more marked urban background, no significant differences for the presence of maxillary rhinosinusitis were found between the three collections studied. Nevertheless, industrialisation and the lack of 106

sanitary and hygienic conditions during the 19th and 20th centuries may help to explain the general high prevalence of sinonasal bone formations in the current work. Indoor and outdoor air quality are usually reported as two of the main environmental causes influencing respiratory disease (e.g., Prüss-Üstün and Corvalán, 2006; Jaakkola et al., 2013; Oudin et al., 2016) and recent studies developed in Lisbon, Porto, and Coimbra have confirmed that factors like poor housing conditions, high levels of atmospheric pollutants, or different markers of traffic-related pollution play an important role in sinonasal inflammation and respiratory illness (Fraga et al., 2008; Alves et al., 2010; Freitas et al., 2010; Ferreira and Cardoso, 2014; Torres et al., 2017). Environmental concerns were reported before the Industrial Revolution in Portugal, when the physician António Ribeiro Sanches discussed in 1756 the nature and importance of air quality and public hygiene in the Treaty on the conservation of the people’s health. With the advent of the Industrial Revolution, which had a rapid growth in Portugal since the 1870s (Castro, 1978; Reis, 1987), these concerns increased and became central throughout the following decades (Ferreira, 1990). Indeed, several risk factors for health came along with industrialisation, mainly from three different reasons: (1) toxicity and insalubrity leading to professional diseases, (2) improvised housing for workers without hygienic conditions and prone to the spread of disease, and (3) the insufficient feeding of workers, deprived of various nutrients (Ferreira, 1990). The defence of the public health was thus focused on preventive strategies through the enactment of hygiene-sanitary laws (Cosme, 2006). Nevertheless, the Portuguese population increased from 3.829.618 to 8.255.414 individuals between 1864 and 1960 (Cosme, 2006), which has aggravated insalubrious conditions in factories, private dwellings, and urban buildings, as well as problems concerning the lack of hygiene of food products and drinking water (Ferreira, 1990; Cosme, 2006; Vaquinhas and Guimarães, 2011). The sanitary crisis between 1856 and 1858 in Lisbon, for instance, resulted in epidemic outbreaks of cholera, yellow fever, and diphtheria (Gonçalves, 2008). The plague outbreak declared in 1899 in Porto was also the consequence of the miserable sanitary and hygienic conditions in the city (Almeida, 2014). With such conditions and the recurrent presence in everyday life of so many other diseases like pulmonary tuberculosis, whopping cough, or diphtheria (Vaquinhas, 2011; Almeida, 2014) it is not difficult to recognize that the sinonasal mucosa, the first line of defence against external offences to the respiratory tract, may have been primarily affected by a

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variety of factors associated with poor housing conditions, dampness or mould exposures, or atmospheric pollutants, which are all currently proven to be associated with sinonasal inflammation. Furthermore, the fact that not all new bone formations within the maxillary sinuses may have been symptomatic, may also have played a role in the overall high prevalence of rhinosinusitis. Several imaging studies confirmed the identification of incidental mucosal sinus findings without the presence of clinical symptoms (e.g., Havas et al., 1988; Bolger et al., 1991; Kinsui et al., 2002; Abreu, 2007; Nazri et al., 2013). Havas et al. (1988) found 23.6% of incidental maxillary sinus findings in 666 patients; Nazri et al. (2013) found 6.4% to 47.5% of incidental maxillary sinus abnormalities in 115 patients with non-sinus related diagnoses. Although the presence of new bone formation within the maxillary sinuses is usually associated with the chronic cases of rhinosinusitis, it is possible that some of these mucosal asymptomatic cases may correspond similarly to asymptomatic bone formations on the maxillary walls. Current estimates of prevalence of rhinosinusitis do not include accidental findings, and its diagnosis is associated with characteristic symptomatology. Unfortunately, as stated by the European Position Group on Rhinosinusitis in 2012 (Fokkens et al., 2012), the role of new bone formation on the pathogenesis of paranasal inflammation, although assumed as important, is not yet fully understood. The present results also show a relationship between females and the occurrence of maxillary rhinosinusitis. Similar differences were also identified in clinical studies (Chen et al., 2003; Hastan et al., 2011; Schiller et al., 2012), whilst in the study of skeletal assemblages these differences are not so clear (Lewis et al., 1995; Merrett and Pfeiffer, 2000; Liebe-Harkort, 2012; Sundman and Kjellström, 2013b; DiGangi and Sirianni, 2017). Roberts (2007) found a tendency for higher frequency in female occurrences in fifteen sites, but only two presented significant differences. These differences were noted in rural agricultural societies, whilst sexual results are generally comparable in urban populations (Roberts, 2007). Panhuysen et al. (1997) and Merrett (2003) also reported higher frequency in females, the former pointing out female exposure to smoke fires or to infected children as possible etiologies. Sundman and Kjellström (2013a) found a statistically higher frequency in males from Mediaeval Sigtuna (Sweden), which was associated with male exposure to pollution in local industries (e.g., tannery and lime kiln).

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Exposure to indoor smoke and air pollution has been identified as a possible trigger to rhinosinusitis, both in living (e.g., Bruce et al., 2002) and past populations (e.g., Panhuysen et al., 1997; Merrett, 2003; Roberts, 2007). Particularly women were more vulnerable to indoor smoke due to unprocessed biomass fuels burnt (particularly wood and charcoal) during cooking and several ethnographic studies show that this may also have been a reality in Portugal. D Indeed, during the 19th and most part of the 20th century the daily use of open fireplaces was very common in the Portuguese kitchens (Pina-Cabral, 1986; Oliveira and Galhano, 2000; Lino, 2001; Vaquinhas and Guimarães, 2011) (Figure 33). In such cases, women and young children are usually more vulnerable to smoke because they spend more time indoors, the former cooking or doing other household activities and the latter accompanying their mothers (Bruce et al., 2002).

Figure 33. Traditional house in the coastal area of Coimbra with an open fire to cook in the kitchen (Oliveira and Galhano, 2000:198).

No association was found between sex and type or degree of bone change within the maxillary sinuses, which is in accordance with the results of Sundman and Kjellström (2013a), but isolated changes were statistically associated with males, while the presence of more than one type of alteration was statistically associated with females. Sundman and Kjellström (2013a) also found significant differences between the most severe degrees of maxillary rhinosinusitis and increased age at death, which were not confirmed in the current work. Spicule-type new bone formation was the most common lesion within the antra and this is in accordance with palaeopathological literature (Boocock et al., 1995a;b; Merrett and Pfeiffer, 2000; Sundman and Kjellström, 2013a; Krenz-Niedbała and Łukasik, 2016). This type of alteration is 109

believed to be the early stage of the disease, subsequently remodelling to form compact bone (Boocock et al., 1995a; Lewis et al., 1995). The current results show that they are transversal to almost all individuals and independent of age, showing that, more than an early stage, they may be associated with an active stage of the disease at the moment of death. Calvin Wells (1964) was one of the first authors to associate new bone formation within the maxillary sinuses to rhinosinusitis in archaeological collections, describing the sinus of a Mediaeval individual from England where a “…rough area of chronic osteitis covers the entire antral floor…” (Wells, 1964:320). Nevertheless, only in 1995 Boocock and colleagues have published their seminal methodology, which is still a reference today. The authors suggested to record bone depositions (spicule-type bone formation, remodelling spicules, and lobules of white bone) and resorptions (pitting and white pitted bone) within the maxillary sinuses. In the same year, Mary Lewis and two of the co-authors of the Boocock's article published a slightly different methodology where pits were not recorded, because their presence may also be the result of bone expansion to accommodate larger teeth during growth or the consequence of its loss during adulthood, with resultant remodelling of the teeth sockets (Lewis et al., 1995). The literature published thereafter resulted in the use of different methodologies based in recording (e.g., Merrett and Pfeiffer, 2000; Roberts, 2007; Sundman and Kjellström, 2013a; DiGangi and Sirianni, 2017) or not recording (e.g., Panhuysen et al., 1997; Krenz-Niedbała and Łukasik, 2016) pitting and white pitted bone as evidence of the disease. The current results show that age at death in individuals presenting pitting and/or white pitted bone within the maxillary sinuses, although not statistically significant (Mann-Whitney U=7072.0; p=0.055), is much lower than the mean age at death in individuals presenting bone formations (Pits/white pitted bone n=41, x̅ =40.07, s.d.=27.11 vs bone formations n=433, x̅ =48.43, s.d.=22.33). These results are in accordance with the concerns of Lewis et al. (1995), showing that a considerable amount of individuals may exhibit pits due to anterior tooth eruption. Consequently, pits and/or white pitted bone within the maxillary sinuses should not be recorded as evidence of sinus disease until a proper differentiation of developmental and pathological pits is described. This is also in accordance with clinical literature that analysed fragments of bone from patients showing evidence of rhinosinusitis, and has

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only identified the deposition of new bone formation within the paranasal sinuses as a result of the disease (e.g., Tovi et al., 1992; Giacchi et al., 2001; Mutijima et al., 2014). The logistic regressions which were performed have also shown an association between spicules on the middle turbinates and the presence of concha bullosa and paradoxical curvature. These results underline the hypothesis that the presence of nasal variations in the middle meatus plays an important role and may predispose to disease on the ostiomeatal complex. Unfortunately, no studies were found discussing this possible association. On the contrary, the etiological role of nasal variations in rhinosinusitis has been widely discussed and subject of controversy at least since the 1980’s. Of the 31 clinical studies searched investigating the possible association between concha bullosa and sinus disease, nine have reported its statistical association, whereas in 22 no relationship was found (Table 57). The present work is in accordance with the majority of the studies that found no relationship between concha bullosa and rhinosinusitis, including all studies involving more than 300 patients (Earwaker, 1993; Nadas et al., 1995; Stallman et al., 2004; Ozcan et al., 2008; Smith et al., 2010; Anazy, 2011). Bolger and colleagues suggested in 1991 that only the bulbous and extensive types of hypertrophy of the middle turbinate may be associated with rhinosinusitis and several studies have reported results that supported this hypothesis (Maru and Gupta, 1999; Aktas et al., 2003; Balikci et al., 2016). In the current work, the type of concha bullosa observed in the 60 individuals who underwent CT scan does not increase the likelihood of presence of bone formation within the maxillary sinuses. Also, the increased standardised width of the concha bullosa is not associated with the presence of maxillary bone formations, which is in accordance with the results obtained by Mays and colleagues (2014) for 45 crania from a English Mediaeval collection. Moreover, of the 12 clinical studies searched analysing the possible association between sinus disease and paradoxical curvature of the middle turbinate, only Azila and colleagues (2011) reported a relationship. All other 11 studies found no association between paradoxical curvature and rhinosinusitis, which is in accordance with the overall lack of statistical association in the current work. Azila et al. (2011) also stated that the degree of convexity of the middle nasal concha is the most important factor obstructing the middle meatus, eventually resulting in rhinosinusitis. This is partially in accordance with the results of this study, which showed an association between sinus

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disease and the most extreme type of paradoxical curvature (type 2) on the right side, but not on the left.

Table 57. Clinical studies analysing the possible association between rhinosinusitis and concha bullosa, paradoxical curvature, variations of the uncinate process, and nasal septal deviation. Association with Reference Concha Paradoxical Uncinate Nasal septal bullosa curvature process deviation Clark et al. (1989) Yes - - - Lloyd (1990) Yes No No - Bolger et al. (1991) No - - - Calhoun et al. (1991) Yes No - Yes Lloyd et al. (1991) No No No - Earwaker (1993) No No - No Nadas et al. (1995) No - - - Lam et al. (1996) No - - - Jones et al. (1997) No No No No Maru and Gupta (1999) No - - - Elahi and Frenkiel (2000) - - - Yes Kinsui et al. (2002) No - - No Aktas et al. (2003) No - - - Harar et al. (2004) - - - No Stallman et al. (2004) No - - No Caughey et al. (2005) Yes - - - Subramanian et al. (2005) No - - - Yasan et al. (2005) - - - Yes Kim et al. (2006) No No - No Ozcan et al. (2008) No No - - Nouraei et al. (2009) No - - - Smith et al. (2010) No - - No Vincent and Gendeh (2010) Yes - - No Anazy (2011) No - - - Azila et al. (2011) No Yes - No Fadda et al. (2012) Yes No Yes Yes Sadr et al. (2012) No No - No Prasad et al. (2013) - - - No Tunçyürek et al. (2013) Yes - - No Javadrashid et al. (2014) No - - Yes Shpilberg et al. (2015) No No - - Balikci et al. (2016) No - - No Gregurić et al. (2016) - - - No Roman et al. (2016) Yes No Yes - Sarkar et al. (2016) Yes - - Yes Kucybała et al. (2017) No - - Yes

Considering the uncinate process, the test of association between accessory turbinate and rhinosinusitis is absent in clinical literature. Nevertheless, five articles were found testing different deviations of the uncinate process and sinus disease and two of them found a positive association. Fadda et al. (2012) describe a relationship between right and bilateral medial uncinate process deviation and right and bilateral anterior ethmoid rhinosinusitis. Roman et al. (2016) also found an association between

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the presence of variations of the uncinate process and rhinosinusitis. Three other studies found no association with the increase likelihood of sinus disease (Lloyd, 1990; Lloyd et al., 1991; Jones et al., 1997). In the present work no association was found between accessory turbinate and ipsilateral maxillary bone formation. Furthermore, no association was found between the nasal septal deviation index (NSDI) and maxillary sinus disease, nor between nasal septal deviation (NSD) and ipsilateral maxillary rhinosinusitis. Of the 21 studies searched investigating this possible association, 14 found no relationship between septal deviation and sinus disease, whereas seven reported statistically significant results. Calhoun et al. (1991) found a relationship between nasal septal deviation, ostiomeatal complex disease, and anterior and posterior ethmoid disease, whilst Javadrashid et al. (2014) found an association between nasal septal deviation and frontal, maxillary, ethmoid and sphenoid rhinosinusitis. Fadda et al. (2012) reported a statistical association between left septal deviation and ipsilateral maxillary rhinosinusitis. Elahi and Frenkiel (2000) and Kucybała and colleagues (2017) observed a higher frequency of bilateral maxillary rhinosinusitis in patients with septal deviation. Nevertheless, comparisons with clinical studies should be approached cautiously because the methodology used to record nasal septal deviation is far from being standardised and, in several studies, is not even specified (e.g., Jones et al., 1997; Kim et al., 2006; Fadda et al., 2012) or objective (e.g., Calhoun et al., 1991; Earwaker, 1993; Kinsui et al., 2002; Javadrashid et al., 2014). The variations studied in the present work show a general lack of association with maxillary rhinosinusitis, which is in accordance with the majority of the literature consulted. The concurrence of these anatomical variations also does not seem to compromise drainage between the maxillary sinuses and the ostiomeatal complex. Clinical literature has identified and analysed several other sinonasal variations (e.g., Pérez-Piñas et al., 2000; Jones, 2002; Tezer et al., 2006; Fadda et al., 2012; Roozbahany and Nasri, 2013). Sarna et al. (2002) and Shpilberg et al. (2015), for instance, studied more than 20 different variations and Earwaker (1993) identified 52 in 800 patients. Nevertheless, there is still a lack of clinical investigation of the pathological consequences resulting from the concurrence and possible interaction of several nasal variations, since its significance has been systematically tested alone. Unfortunately, most of these nasal variations are only seen on CT scan, and thus

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impossible to be identified on gross examination in skeletal remains. In the present study, several tests were performed to ascertains the effects of isolated and concurrent nasal variations of the ostiomeatal complex on the likelihood that individuals present sinus disease, without significant results. The model of interaction between different etiologies (intrinsic mucosal inflammation, local microbial community, and mucociliary dysfunction) recently proposed by Timperley et al. (2010) may help to explain the lack of association between paranasal disease and nasal variations in the current work. These variations may only be a part of a bigger picture that unfortunately cannot be accessed and understood when studying skeletal remains. Dental disease is usually seen as a risk factor for maxillary rhinosinusitis development due to the close proximity between the anterior maxillary teeth and the maxillary sinus floor (e.g., Boocock et al., 1995a; Lewis et al., 1995; Merrett, 2003; Hoskison et al., 2012), but its roots often protrude into the maxillary sinuses not causing sinus pathology (Lewis et al., 1995). Maxillary rhinosinusitis and fistulation may also develop independently or a fistula may occur into an actually inflamed sinus (Lewis et al., 1995; Merrett and Pfeiffer, 2000; Roberts, 2007; Sundman and Kjellström, 2013a). In the current work, oroantral root protrusions without bone remodelling on the sinus floor were recorded in 39 (39/873, 4.5%) individuals and only 15 (15/873, 1.7%) exhibited fistulae with bone remodelling. In Mediaeval Sweden, a prevalence of 4.2% (4/95, 4.2%) and 9.6% (15/157) of oroantral fistulae with bone remodelling was found in individuals with at least one complete antral floor (Sundman and Kjellström, 2013a;b). DiGangi and Sirianni (2017) reported a prevalence of 5.1% (5/99) in American individuals from the 19th century. The current results present lower prevalence and are in accordance with Roberts (2007), who reported the rare occurrence of oroantral fistulae in several skeletal assemblages. Although there is usually a very thin bony layer between the tooth socket and the maxillary antrum, it is possible that its complete absence increases the likelihood of developing maxillary rhinosinusitis compared to those not presenting this type of direct protrusion (Merrett, 2003; Sundman and Kjellström, 2013a).

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4.4. The role of concha bullosa and maxillary rhinosinusitis on craniofacial morphology

4.4.1. Results

In this chapter three different groups (‘concha bullosa’, ‘maxillary rhinosinusitis’ [types 2 and 3], and ‘control’) are tested for possible association with the development of different patterns of craniofacial morphology. A one-way ANOVA was performed to test ten measurements and four indices and statistical significant differences were found between groups in bifrontal breadth (FMB) (Anova F=3.691; d.f.=2; p=0.027) and zygoorbitale breadth (ZOB) (Anova F=5.194; d.f.=2; p=0.007) (Tables 58 and 59; Appendix A8). A Kruskal-Wallis H test was also run to test the mean values of ten measurements and two indices. Statistically significant differences were found between groups in orbital breadth (OBB) (Kruskal-Wallis H=17.157; d.f.=2; p<0.001), nasal breadth (NLB) (Kruskal-Wallis H=10.053; d.f.=2; p=0.007), bimaxillary breadth (ZMB) (Kruskal-Wallis H=7.361; d.f.=2; p=0.025), and interorbital breadth (DKB) (Kruskal- Wallis H=8.286; d.f.=2; p=0.016). The cranial (Kruskal-Wallis H=8.185; d.f.=2; p=0.017) and nasal (Kruskal-Wallis H=6.851; d.f.=2; p=0.033) indices also showed statistically significant differences (Tables 58 and 59; Appendix A8). Overall, of the 20 craniofacial measurements and six indices, eight resulted in statistically significant differences. The descriptive statistics and p-values are presented in Table 58. Tukey post hoc tests were run to identify statistical significant differences within groups in FMB and ZOB measurements and pairwise comparisons were performed to ascertain which groups show significant values in OBB, NLB, DKB, WNB, and both cranial and nasal indices. The results are presented in Table 59. All six measurements with statistical significant p-values represent differences within groups in the breadth of the face (Figure 34). Five measurements (FMB, ZOB, OBB, NLB, and DKB) have shown statistically significantly higher means in the concha bullosa group, whilst three measurements (ZOB, OBB, and ZMB) have shown statistically significantly higher means in the maxillary rhinosinusitis group. The concha bullosa group has also shown statistically significantly higher means in both cranial and nasal indices.

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Table 58. Descriptive statistics and p-values for each measurement and group.

Maxillary Concha bullosa Control Anova Measurement rhinosinusitis n x̅ ±SD n x̅ ±SD n x̅ ±SD F d.f. p-value BBH 53 130.26 5.85 56 129.76 5.75 56 129.91 4.55 0.119 2 0.888 BPL 39 95.21 5.92 38 93.16 6.11 40 93.74 5.59 1.249 2 0.291 NPH 40 69.98 4.65 38 67.82 4.23 41 68.35 4.25 2.589 2 0.079 NLH 53 50.71 3.94 54 50.21 3.71 58 50.08 3.64 0.424 2 0.655 OBH 56 33.57 2.02 58 33.56 1.94 60 33.23 1.70 0.643 2 0.527 FMB 56 101.20 4.28 57 99.99 4.29 60 99.14 3.67 3.691 2 0.027 FRC 53 110.65 5.29 56 109.16 5.12 58 109.36 4.61 1.413 2 0.246 ZOB 50 52.61 5.14 50 53.01 6.28 55 49.96 4.39 5.194 2 0.007

W1 37 114.32 7.08 41 112.95 6.92 37 112.97 4.64 0.537 2 0.586

H1 42 30.12 3.20 37 29.97 3.33 39 29.46 2.81 0.487 2 0.616 CLHI 52 70.98 3.01 56 71.36 3.10 56 71.19 3.09 0.202 2 0.818 CBHI 49 96.78 4.52 55 95.63 4.16 53 95.67 4.10 1.200 2 0.304 UFI 37 87.57 8.73 37 83.82 7.64 39 85.31 7.59 2.066 2 0.132 OI 56 84.47 5.88 57 83.10 5.27 60 85.31 4.83 2.549 2 0.081

Kruskal-Wallis H d.f. p-value GOL 54 183.76 7.71 58 181.84 7.24 59 182.29 7.42 2.522 2 0.283 BNL 56 99.40 5.38 58 98.35 4.94 59 97.44 4.63 2.816 2 0.245 MCB 51 134.77 5.67 57 135.64 4.49 57 135.70 5.20 2.074 2 0.354 ZYB 50 124.54 6.41 56 124.26 5.85 54 124.16 4.90 0.079 2 0.961 OBB 56 39.81 1.90 57 40.45 1.74 60 39.00 1.77 17.157 2 <0.001 NLB 42 23.82 1.67 44 23.52 2.04 52 22.74 1.49 10.053 2 0.007 ZMB 55 88.97 4.69 55 89.31 5.49 59 87.06 4.52 7.361 2 0.025 DKB 56 20.67 2.51 57 19.47 2.22 60 19.68 2.36 8.286 2 0.016 WNB 53 9.52 1.61 58 8.92 1.88 60 9.05 1.76 5.467 2 0.065 CI 51 73.29 3.08 57 74.60 2.78 56 74.55 2.97 8.185 2 0.017 NI 42 12.14 1.30 42 11.81 1.36 51 11.44 1.09 6.851 2 0.033 BBH=Basion-bregma height; BPL=Basion-prosthion length; NPH=Nasion-prosthion height; NLH=Nasal height; OBH=Orbital height; FMB=Bifrontal breadth; FRC=Nasion-bregma chord; ZOB=Zygoorbitale

breadth; W1-Intercondylar width; H1-Symphysial height; CLHI-cranial length-height index; CBHI=Cranial breadth-height index; UFI=Upper facial index; OI=Orbital index; GOL=Glabello-occipital length; BNL=Basion-nasion length; MCB=Maximum cranial breadth; ZYB=Bizygomatic breadth; OBB=Orbital breadth; NLB=Nasal breadth; ZMB=Bimaxillary breadth; DKB=Interorbital breadth; WNB=Simotic chord; CI=Cranial index; NI=Nasal index.

4.4.2. Discussion

Inadequate breathing patterns can occur during growth with possible consequences in the normal development of the facial bones (Bakor et al., 2011). Nevertheless, this subject is still widely debated after almost a century of controversy (e.g., McNamara, 1981; Fields et al., 1991; Vig, 1998; D’Ascanio et al., 2010; Harari et al., 2010). Theoretically, normal nasal respiratory activity influences the normal growth of craniofacial structures, whereas chronic nasal obstruction may lead to oral breathing 116

as an adaptive resource to changes in nasal pathways (Bakor et al., 2011). Concha bullosa and chronic maxillary rhinosinusitis are recognised as two causes for inadequate nasal breathing and the current results shows that craniofacial morphology may develop with different patterns of facial breadth compared to individuals where both are absent. This is in accordance with the hypothesis that concha bullosa and maxillary rhinosinusitis have developed during the growth period of the facial and cranial bones, since early age.

Table 59. Tukey post hoc tests and pairwise comparisons for measurements with significant p-values. Measurement Group comparisons p-value

Concha bullosa – MRS* 0.262 Bifrontal Tukey post hoc test Concha bullosa – Control 0.020 breadth (FMB) MRS – Control 0.500

Concha bullosa – MRS 0.924 Zygoorbitale Tukey post hoc test Concha bullosa – Control 0.031 breadth (ZOB) MRS – Control 0.010

Concha bullosa – MRS 0.322 Orbital Pairwise comparison Concha bullosa – Control 0.042 breadth (OBB) MRS – Control <0.001

Concha bullosa – MRS 1.000 Nasal Pairwise comparison Concha bullosa – Control 0.008 breadth (NLB) MRS – Control 0.067

Concha bullosa – MRS 1.000 Bimaxillary Pairwise comparison Concha bullosa – Control 0.224 breadth (ZMB) MRS – Control 0.024

Concha bullosa – MRS 0.024 Interorbital Pairwise comparison Concha bullosa – Control 0.062 breadth (DKB) MRS – Control 1.000 Concha bullosa – MRS 0.024 Cranial index(CI) Pairwise comparison Concha bullosa – Control 0.065 MRS – Control 1.000 Concha bullosa – MRS 0.817 Nasal index(NI) Pairwise comparison Concha bullosa – Control 0.028 MRS – Control 0.442 *Maxillary rhinosinusitis.

Variance in craniofacial morphology is usually studied in medical literature through the comparison between nasal- and oral-breathing individuals, or short- and long-faced subjects. In a study of 30 patients, for instance, Bakor and colleagues (2011) reported lower means of maxillary, mandibular, and facial widths in oral breading non-adults, with statistically significant differences. The authors suggested that this may be associated with a greater electrical activity for the masseter muscles and lesser for the suprahyoid muscles in the nasal-breathing group compared to oral-breathing individuals. In fact, several studies show that individuals presenting mouth breathing due to nasal pathology tend to have a higher mandibular inclination and a more 117

vertically positioned anterior facial morphology, which are closely related to the size and strength of the masticatory musculature (e.g., Blanchette et al., 1996; Lessa et al., 2005; Juliano et al., 2009; D’Ascanio et al., 2010; Harari et al., 2010; van Spronsen, 2010; Muñoz and Orta, 2014; Agostinho et al., 2015; Chambi-Rocha et al., 2018). Van Spronsen (2010), for instance, found that the masticatory muscles associated with jaw closing are up to 33% smaller in long-faced subjects compared to individuals presenting normal craniofacial growth. Agostinho et al. (2015) reported, in a group of 70 patients (35 with allergic rhinitis and mouth breathing and 35 controls) from Santa Maria University Hospital (Lisbon, Portugal), that children presenting allergic rhinitis and mouth breathing have more vertical faces with an open bite tendency, shorter maxillae and mandibles, and a narrowed pharyngeal airway space.

Figure 34. Statistically significant measurements taken in the present study. 1-Bifrontal breadth (FMB); 2-Interorbital breadth (DKB); 3-Orbital breadth (OBB); 4-Zygoorbitale breadth (ZOB) 5-Nasal breadth; 6-Bimaxillary breadth (ZMB) (figure adapted from chapter 2: Attachment 6a in Buikstra and Ubelaker, 1994).

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In the current work, no comparisons were made between nasal- and oral-breathing individuals since it is impossible to confirm if concha bullosa and maxillary rhinosinusitis (types 2 and 3) have resulted in nasal obstruction and consequent mouth breathing; it is also impossible to measure the anterior facial height ratio to assess if a short-, long-face, or normal morphologies are present. Still, no association was found between concha bullosa or maxillary rhinosinusitis and the vertical measures concerning the height of the face (orbital, nasal, symphysial, and nasion-prosthion height). Nevertheless, there is a pattern showing that those nasal and sinonasal osseous alterations have contributed to the development of the surrounding structures, resulting in an increased facial breadth. Concha bullosa is a highly frequent nasal variation, but may be asymptomatic or does not completely block nasal breathing (e.g., Cukurova et al., 2012; Kucybała et al., 2017); nevertheless, the enlargement of the middle turbinates during growth appear to have resulted in a different pattern of development of the closest anatomical bony structures. This is also in accordance with the lack of statistical significance between age at death and concha bullosa, denoting that its development since early age may be an important factor to take into account on facial growth. Clinically, the study of the association between concha bullosa and craniofacial morphology is rare. Kajan et al. (2016), for instance, found that the concurrence of concha bullosa and septal deviation influence the depth and curve of the palatal bone, but no reports are known studying its possible influence on the anterior facial morphology. Also, Mays and colleagues (2012) have found a significant association between nasal septal deviation and reduced measures of anterior facial height in 45 individuals from Mediaeval England, but no results were reported for concha bullosa. Maxillary rhinosinusitis also seems to play an important role on craniofacial growth, resulting in higher means of facial breadth in three measurements (zygoorbitale, orbital, and bimaxillary breadths) compared to controls, with significant differences. Maxillary rhinosinusitis seems to represent an important mechanism influencing craniofacial morphology when developing from early age, at least early enough to influencing upper facial growth breadth. Lawson et al. (2008) refer that pathology within the maxillary sinuses may lead to compensatory marrow proliferation or sclerotic new bone formation, ultimately resulting in maxillary enlargement. Fernández et al. (2000) also found greater volume in maxillary sinusitis patients, which was explained by the effect of the inflammatory process in the sinus walls. Several recent studies

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found statistically higher values of bone thickness in diseased maxillary sinuses compared to normal controls (e.g., Kim et al., 2008; Cho et al., 2010; Deeb et al., 2011), and several other works have pointed out the importance of osseous alterations when sinusitis is present (e.g., Perloff et al., 2000; Khalid et al., 2002). Nevertheless, the importance of these changes occurring during growth and the consequent mechanisms of impact in sinus volumes and facial morphology are not yet fully understood, since other clinical studies found that maxillary sinus volume significantly decrease in patients with chronic sinusitis (Kim et al., 2008; Cho et al., 2010).

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4.5. Miscellaneous osseous alterations on the anterior surface of the maxillary bones, nasal cavity, and hard palate

4.5.1. Results

This chapter describes and discusses several other lesions recorded on the anterior surface of the maxillary bones, nasal cavity, and hard palate. Firstly, the lesions are quantified and, when relevant, statistical analysis for sex and age at death is presented. Secondly, lesions on the anterior surface of the maxillary bones are discussed, with particular emphasis on complications that may be concurrent with or result from nasal trauma and the problematic differential diagnosis of nasolacrimal duct lesions. The differential diagnosis of several of the most uncommon case studies is also discussed. Finally, lesions within the nasal cavity and hard palate are discussed and several unusual case studies highlighted. Of the 1994 individuals with the maxillary bones, nasal cavities, and hard palate preserved, 18 (18/1994, 0.9%) show one or more osseous alterations on the anterior surface of the maxillary bones (lesions due to oral pathology are not reported). Of these, nine (9/18, 50%) present osteolytic lesions, six (6/18, 33.3%) new bone formations, and three (3/18, 16.7%) both lesions. The presence of one or more osseous alterations within the nasal cavity (other than the ones referred in chapters 4.1. to 4.3.), was recorded in 99 (99/1994, 5%) individuals, 82 (82/99, 82.8%) presenting one osseous alteration, 15 (15/99, 15.2%) showing two bony changes, and two (2/99, 2%) exhibiting three alterations, totalling 118 changes. Fifty-six (56/99, 56.6%) individuals exhibit new bone formation, 45 (45/99, 45.5%) osteolytic lesions, and 17 (17/99, 17.2%) porous perforations on the nasal floor and hard palate. Male individuals exhibit higher frequency of lesions (males=62/1057, 5.9%; females=37/937, 3.9%), with statistical significant differences (Pearson χ2=3.868; d.f.=1; p=0.049). The presence of osseous alterations is statistically associated with increased age at death (Mann-Whitney U=114912.5 p<0.001; absence n=1883, x̅ =47.19, s.d.=21.28; presence n=98, x̅ =55.91, s.d.=19.05) (Figure 35). Bony alterations on the palatine processes and bones were observed in 196 (196/1994, 9.8%) individuals, 153 (153/196, 78.1%) of whom showing one alteration, 35 (35/196, 17.9%) presenting two, and eight (8/196, 4.1%) showing three alterations, totalling 247 osseous alterations. Regarding the type of alteration, 116 (116/196, 59.2%)

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individuals show osteolytic lesions, 98 (98/196, 50%) new bone formation, 17 (17/196, 8.7%) nasopalatal porous perforations, and 16 (16/196, 8.2%) reactive bone along the palatine suture associated with at least one macropore (>1mm). Sex does not play a major role in the presence of osseous alteration on the hard palate (Pearson χ2=0.219; d.f.=1; p=0.640; males=107/1057, 10.1%; females=89/937, 9.5%), whilst the presence of osseous changes is statistically associated with increased age at death (Student’s t= - 6.021; d.f.=1979; p<0.001; absence n=1786, x̅ =46.71, s.d.=21.14; presence n=195, x̅ =56.02, s.d.=20.43) (Figure 36).

Males Females 20 17 15 15 12 12 10 N 10 7 6 5 5 4 4 4 2 0 0 0 <=19 yo 20-29yo 30-39yo 40-49yo 50-59yo 60-69yo => 70yo Figure 35. Bone destruction and formation within the nasal cavity by sex and age at death.

Males Females 40 38

29 30 24

17 17 N 20 12 12 10 7 7 8 10 4 5 5

0 <=19 yo 20-29yo 30-39yo 40-49yo 50-59yo 60-69yo => 70yo Figure 36. Bone destruction and formation on the hard palate by sex and age at death.

4.5.2. Discussion

4.5.2.1. The anterior surface of the maxillary bones

The etiology of bony lesions on the anterior surface of the maxillary bones is usually difficult to understand, particularly when these changes are isolated and nonspecific. As mentioned in chapter 4.1., trauma on the facial skeleton is seldom fatal, but several other lesions may be concurrent with or result from it. Although nasal 122

trauma is considered a minor condition, it may also result in significant complications (Rohrich and Adams, 2000; Jeon et al., 2013). Untreated nasal bone fracture can lead to complications in the upper airway, including severe nasal deformity, intranasal dysfunction, hyposmia, hypoesthesia, or obstruction (e.g., Rohrich and Adams, 2000; Jeon et al., 2013; Park et al., 2014). Of the 148 individuals presenting nasal trauma, 11 (7.4%, 11/148) also exhibit other alterations in the anterior maxilla, nasal cavity, and/or hard palate that may be concurrent with or result from nasal trauma (Table 60).

Table 60. Lesions that may be concurrent with or result from nasal fracture.

Age at death Individual Sex Lesions (years) . Comminuted trauma of both nasal bones and frontal process of

the right maxilla (Plate XV, Figure 37) MSSC 4* Male 69 . Lytic lesion and possible dissection on the right nasolacrimal duct and orbital floor . Trauma of both nasal bones, frontal process of the right

maxilla, and septum MSSC 14 Male 30 . Fusion between the left middle turbinate and the septum . New bone formation in the left upper portion of the nasal cavity

. Trauma of both nasal bones MSSC 65 Male 57 . Possible osteoma on the right nasal wall . Trauma of both nasal bones and septum . Anterior septal destruction/remodelled trauma MSSC 75* Female 26 . Remodelling of the lateral margins of the piriform aperture and nasopalatal porous perforations, lytic lesions, and new bone formation (Plate XVI, Figure 39) . Trauma on the left nasal bone and frontal process of the maxilla MSSC 247 Male 78 . Circular erosion and osteolytic lesion on the left maxilla (⌀=ca.16mm) . Trauma on the left nasal bone MSSC 508 Male 40 . Destructive lesion and new bone formation on the floor of the left nasal cavity and both palatine processes . Trauma on the left nasal bone MSSC 528 Male 47 . Reactive bone on the nasolacrimal duct entrance . Possible osteoma above the left inferior turbinate (ca. 4x7mm) . Trauma of both nasal bones . Destructive lesion of the septum IESC 367* Male 66 . Reactive bone and macroporosity along the intermaxillary suture, and new bone formation and bone destruction on the left palatine bone IESC 951 Male 58 . Trauma of both nasal bones . Destructive lesion on the right nasolacrimal duct (ca. 3.5x4.5mm) (Plate XV, Figure 38) IESC 1005 Male 67 . Trauma of both nasal bones . Bone formation (⌀= ca. 7.5mm) and destruction (⌀=ca. 4,5mm) on the left maxillary fossa HISC 381 Female 85 .Trauma of both nasal bones . New bone formation on the lamellar portion of both middle turbinates and uncinate processes MSSC=Medical Schools Skull Collection; IESC=International Exchange Skull Collection; HISC=Human Identified Skeletal Collection. *The differential diagnosis of these three individuals is discussed below in the dashed boxes.

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Four of these individuals, for instance, exhibit lesions on the nasolacrimal duct (MSSC 4, 528; IESC 951, 1005) (Plate XV, Figures 37 and 38), whilst a 78-year-old male (MSSC 247) presents an osteolytic lesion (⌀=ca.16mm) on the left canine fossa. Also, a 67-year-old male (IESC 1005) presents new bone formation (⌀= ca. 7.5mm) and bone destruction (⌀=ca. 4,5mm) on the left maxillary fossa.

Case study

MSSC 4

69-year-old male; occupation: beggar; cause of death: senile cachexia; provenance and

date of death: Lisbon Medical School, 1896 AD

This individual presents a comminuted trauma of both nasal bones and frontal

process of the right maxilla, as well as an osteolytic lesion (ca.10x10mm) between the

right nasolacrimal duct entrance, the infraorbital foramen, and the frontal process of the

maxilla. The duct entrance and its inner surface also presents destruction. This lesion is

consistent with primary or secondary obstruction of the nasolacrimal duct (Plate XV,

Figure 37), possibly associated with the traumatic injury of the nose. Moreover, the

anterior surface of the maxilla shows a square-shaped hole (1.5mm) into the nasolacrimal

duct, in the center of the lytic lesion, without evidence of bone remodelling. The shape of

the hole and the lack of bone remodelling on its margins are consistent with dissection, probably with the purpose of teaching how to drain the diseased nasolacrimal duct. Nevertheless, the hypothesis of perimortem surgery cannot be ruled out, although it is unclear which pathological process may have led to the individual’s death. His occupation is also in accordance with the use of cadavers of the poor for dissection, which was

officially allowed in Portugal only in 1913 by the Ordinance Number 40, and stating that unclaimed bodies within twelve hours after death were available to the faculties of medicine for dissection (Magalhães et al., 2017). This is the first known evidence of possible teaching of modern dacryocystorhinostomy to drain the lacrimal sac, which was first attempted in the 18th century with the extirpation of the lacrimal sac, perforation of bone, and placement of a drain (Yakopson et al., 2011; Ali, 2015). Only in 1893 George Caldwell first described the endonasal approach to nasolacrimal obstructions (Savino et al., 2014; Ali, 2015). Both facial surgery and dissection were very frequent during the first half of the 20th century in Coimbra (Magalhães et al., 2017).

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Plate XV

Figure 37. A 69-year-old male (MSSC 4; cause of death: senile cachexia) presenting bone destruction and a possible dissection into the nasolacrimal duct.

Figure 38. A 58-year-old male (IESC 951; cause of death: heart disease) presenting bone destruction on the right nasolacrimal duct. Plate XVI

NBF NBF

DL DL

Figure 39. A 26-year-old female (MSSC 75; cause of death: tuberculosis) presenting comminuted trauma of the nasal bones (top left), possible trauma of the nasal septum, and possible remodelling of the lateral margins of the piriform aperture (top right), as well as new bone formations (NBF) and destructive lesions (DL) on the palatine processes and bones (bottom, arrows). Also, the nasopalatal lesions exhibited by the individuals MSSC 75 and IESC 367 are also two good examples of bone changes that should be included in a broad differential diagnosis when lesions are nonspecific.

Case studies MSSC 75

26-year-old female; occupation: housewife; cause of death: tuberculosis; provenance and date of death: Lisbon Medical School, 1896 AD

This individual shows bilateral comminuted trauma of the nasal bones and

nasopalatal osteolytic lesions and new bone formations (Plate XVI, Figure 39), as well as

an irregular new bone formation anteriorly on the floor of the right nasal cavity. The nasal

septum also exhibits trauma and remodelling, possibly concurrent with the fracture of the

nasal bones. Remodelling of the lateral margins of the piriform aperture seems to be also

present, although without atrophy of the anterior nasal spine or resorption of the alveolar process. The differential diagnosis should include complications resulting from nasal trauma, although the type of nasal and palatal lesions are usually associated with leprosy, syphilis, cancer, or tuberculosis (e.g., Ortner, 2003; Matos, 2009; Lopes, 2014). Literature shows that leprosy and syphilis, for instance, were very common in Portugal during the 19th and first half of the 20th century (e.g., Barbosa, 1856; Carvalho, 1932). The lesions may also be consistent with the result of different pathological processes occurring during the individual’s life. The fact that the postcranium is absent makes the differential diagnosis much more difficult and broad.

IESC 367

66-year-old male; occupation: locksmith; cause of death: pulmonary tuberculosis; local and date of death: Coimbra, 1929AD

This individual presents trauma of both nasal bones and bone destruction of the

vomer and perpendicular plate of the ethmoid. The hard palate presents reactive bone and

macropores surrounding the intermaxillary suture, as well as a circular lamellar bone

formation (⌀=ca.7.5mm) on the left palatine process, which presents partial destruction. This new bone formation is similar to the one observed in a 24-year-old male amassed in the same collection (IESC 1009) and both may be rare examples of osteomas on the hard

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palate. The distribution of the osseous lesions is not enlightening for the differential

diagnosis and may result from nasal trauma and/or from a nonspecific pathological process affecting the nasopalatal area. This individual show the limitations underlying the differential diagnosis of such nonspecific lesions in skeletal remains.

The basis of the septum (particularly the vomer and the nasal crests of the maxillary and palatine bones) is extremely fragile and directly associated with the intermaxillary and median palatine sutures and the fracture of the septal bones may also play a role in nasopalatal pathology. Several other lesions may be concurrent with or result from nasal trauma. A 30-year-old male (MSSC 14), who died in Lisbon and whose documented cause of death is ‘typhoid fever’, shows extensive new bone formation in the left upper portion of the nasal cavity, probably as a consequence of the trauma of both nasal bones, frontal process of the right maxilla, septum, and the left middle turbinate (Table 60). Also, an 85-year-old female (HISC 381), who died in Lisbon and whose documented cause of death is ‘pulmonary embolism’, presents fracture of both nasal bones and new bone formation on the lamellar portion of both middle turbinates and uncinate processes. Two adult male individuals (MSSC 65 and 528) presenting ‘urine infiltration’ and ‘heart disease’ as causes of death, show small, irregular lamellar bone formations on the upper portion of the lateral wall of the nasal cavity (ca.6x3mm and ca.7x4mm, respectively), both anterior to the middle turbinate. Moreover, of the 18 (18/1994, 0.9%) individuals showing lesions on the anterior surface of the maxillary bone, 14 do not exhibit nasal fracture. For instance, a 44-year-old male (IESC 192), who died in Coimbra and whose documented cause of death is ‘pulmonary congestion’, presents an irregular destruction (maximum width of ca.21x21mm) in the canine fossa with a fistula into the right maxillary sinus, which may be the result of a diseased maxillary antra (which was not available for examination). Also, a 78-year-old female (IESC 583), who died in Coimbra and whose documented cause of death was ‘flu/cardiac syncope’, shows an isolated destructive lesion under the infraorbital foramen.

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The differential diagnosis of lesions of the nasolacrimal duct and anterior maxillary bone, whether nasal trauma is present or not, should include primary or secondary nasolacrimal duct obstructions, complications from rhinosinusitis, disturbances of the infraorbital nerve, osteomyelitis, or bone tumours. The obstruction of the nasolacrimal duct may be either primary or secondary (e.g., Lee-Wing and Ashenhurst, 2001; Kamal and Ali, 2015). Primary nasolacrimal obstructions are a common disorder resulting from a localised inflammatory infiltrate, edema, and dense fibrosis of periductal tissues, whilst secondary obstructions may result from infection, inflammation, trauma, or neoplasia (e.g., Lee-Wing and Ashenhurst, 2001; Kamal and Ali, 2015). Although uncommon, lesions on the nasolacrimal system may occur with fracture of the naso-orbital-ethmoid region (Gruss et al., 1985; Sundar, 2015). Nevertheless, even in the most severe facial traumas, the nasolacrimal system frequently escapes injury (Gruss et al., 1985). For instance, in a retrospective study of 587 American patients, Woog (2007) noted the presence of nasolacrimal obstructions as a result of facial fracture in 3.1% (18/587), whereas hypertension (241/587, 41.1%), cigarette smoking (155/587, 26.4%), neoplasms (110/587, 18.8%), and diabetes (64/587, 10.9%) were detailed as the most common causes for nasolacrimal obstruction. Francisco and colleagues (2007) also reported that epiphora was the most common cause for examination in 97.9% (277/283) Brazilian individuals suspected of obstruction of the lacrimal duct. Nasolacrimal obstructions may also result from rhinosinusitis (Woog, 2007). In the current study, of the 873 individuals with at least one maxillary sinus available for inspection, none exhibit both new bone formation within the antrum and nasolacrimal bony lesions.

4.5.2.2. The nasal cavity and hard palate

The nasopalatal anatomy shows a diversity of isolated or combined new bone formations, osteolytic lesions, and porous perforations which may differ in location, type, and size. Table 61 presents the nasopalatal alterations and differential diagnosis of the lesions recorded in the present study.

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Table 61. Osseous alterations identified in the 1994 nasal cavities and hard palates preserved. Each individual may exhibit more than one lesion. Anatomical area Osseous alterations n % New bone formation Due to nasal trauma 2 0.1 Due to oral pathology 2 0.1

Possible osteoma 20 1 Nasal cavity Nonspecific 32 1.6

Osteolytic

Due to oral pathology 12 0.6 Nonspecific 33 1.7 Nasopalatal porous perforations 17 0.9 New bone formation Due to oral pathology 17 0.9 Possible osteoma 2 0.1

Nonspecific 79 4 Hard palate Osteolytic

Due to oral pathology 73 3.7

Nonspecific 43 2.2

Reactive bone+macropores 16 0.8

New bone formations within the nasal cavity were observed in 56 (2.8%, 56/1994) individuals, two of them highly consistent with the result of nasal trauma (MSSC 14, HISC 381, Table 60), two consistent with the result of oral pathology, and 20 consistent with the diagnosis of osteoma (Plate XVII, Figure 40). The remaining 32 represent nonspecific, localised growths or irregular formations, mainly located on the nasal floor or, anteriorly, on the lateral nasal wall. The differential diagnosis between osteomas and nonspecific bone growths within the nasal cavity is challenging, due to the presence of several irregular and curved bones and anatomical structures. Osteomas are dense, dome-shaped, well-delineated protrusions of well-organised lamellar bone which are mostly solitary (e.g., Eshed et al., 2002; Kaplan et al., 2012). In the current work, all lesions consistent with osteomas were found isolated. Although according to literature they occur primarily on the outer table of the skull, particularly in the frontal and parietal bones (e.g., Capasso, 1997; Eshed et al., 2002; Larrea-Oyarbide et al., 2007; Aufderheide and Rodríguez-Martín, 2011), there have been reports of osteomas in the facial skeleton and sinonasal and palatal anatomy, both in skeletal assemblages (Campillo, 2005; Premužić et al., 2013; Charlier et al., 2014; Gawlikowska-Sroka et al., 2016a; Odes et al., 2018; Riccomi et al., 2018) and clinical practice (e.g., Sayan et al., 2002; Larrea-Oyarbide et al., 2007; Boffano et al., 2012; Janovic et al., 2013). In the current work, the mean age at death for its occurrence is 52.95 years old (minimum=12 years old; maximum=87 years old)

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Plate XVII

Male, 47 years old (MSSC 133). Female, 56 years old (MSSC 318).

Male, 77 years old (IESC 5). Male, 15 years old (IESC 127).

Figure 40. Examples of possible osteomas within the nasal cavity. and 16 were observed in males and four in females, with significant differences (Fisher’s Exact Test p=0.022). Although the study of osteomas within the nasal cavity is rare, Eshed et al. (2002) reported similar occurrences of cranial osteomas between sexes in 585 individuals from the Hamann-Todd Osteological Collection (United States). Janovic and colleagues (2013) also found a similar occurrence of osteomas in the sinuses in 2820 patients from Serbia. Boffano et al. (2012) reported higher frequency of craniofacial osteomas in females in 43 patients from Italy, whereas Sayan et al. (2002) and Larrea-Oyarbide and colleagues (2007) found a predilection of craniofacial and maxillofacial osteomas in males from Turkey and Spain, respectively. Furthermore, osteolytic lesions associated with new bone formations within the nasal cavity were observed in nine individuals (MSSC 208, 291, 416, 469; IESC 264, 269, 593, 1000, 1086). Although all lesions are nonspecific, three adult females (MSSC 291; IESC 264, 593) present the most severe cases, as described below.

Case studies

MSSC 291

50-year-old female; occupation: housewife; cause of death: neoplastic disease; provenance and date of death: Lisbon Medical School, 1900 AD

The individual shows destruction of the right superior, middle, and inferior turbinates, right uncinate process and ethmoid bulla, and septum, as well as extensive bone formations on the floor and walls of the right nasal cavity and maxillary sinus (Plate XVIII, Figure 41). The inner surface of the right maxillary antrum shows type 3 spicule-type bone formation (the left antrum was not available for examination). The septum is markedly deviated to the left side and a small bone formation is visible anteriorly

on the perpendicular plate of the ethmoid. Alterations are absent in all the remaining

structures on the left side. Particularly the lytic lesions are highly consistent with the

individual’s cause of death (e.g., Ortner, 2003; Marques et al., 2018), although the

concomitant presence of bone remodelling/new bone formation may also be consistent with leprosy, syphilis, or tuberculosis (e.g., Hackett, 1976; Manchester, 1994; Ortner, 2003; Marques et al., 2018).

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IESC 264

29-year-old female; occupation: housewife; cause of death: purulent meningitis with suppuration channels; local and date of death: Coimbra, 1923 AD

This individual shows lytic lesions in both nasal bones and frontal processes of the maxillae, septum, and, posteriorly, on the nasal floor (left palatine process and both palatine bones) (Plate XVIII, Figure 42), whilst the lateral margins of the piriform aperture seem to be in an early stage of remodelling. Unfortunately, the nasal cavity presents

postmortem damage and the remaining nasal structures are not preserved. The hard palate

does not exhibit pathological changes. The lesions are nonspecific and the differential diagnosis should include complications resulting from nasal trauma or neoplastic or infectious disease. The last may be consistent with the individual’s cause of death. Although nasal symptoms are not usually associated with purulent meningitis (Geiseler et al., 1980; Arda et al., 2008), Geiseler et al. (1980) found, in a study of 1316 Americans, that patients with meningitis caused by Staphylococcus aureus or various streptococci commonly presented associated suppurative foci and the highest fatality rate.

IESC 593

82-year-old female; occupation: housewife; cause of death: chronic myocarditis; local

and date of death: Coimbra, 1925 AD

The individual shows general destruction of the osseous structures within the nasal

cavity, particularly of both superior and inferior turbinates, left middle turbinate, both uncinate processes, and septum, the last presenting complete destruction (Plate XIX, Figure 43). New bone formation is also present on the remaining nasal structures, whilst the nasal floor shows a thin layer of new bone formation that appear to have been applied to the original bone surface. The hard palate also shows coalescent macroporosity, lytic

lesions, and new bone formation. The piriform aperture does not seem to have been affected. Again, the type and distribution of the lesions are consistent with neoplasia, leprosy, syphilis, or tuberculosis, particularly with infectious disease (e.g., Hackett, 1976;

Manchester, 1994; Ortner, 2003; Marques et al., 2018).

Concerning the hard palate, 90 lesions are consistent with oral pathology (17 new bone formations and 73 osteolytic lesions), the most common cause for the presence of lytic lesions on the palatine processes and bones (Table 61). The severity of 12 of the 73

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Plate XVIII

Figure 43. An 82-year-old female (IESC 593; cause of death: chronic myocarditis) presenting destruction of both superior and inferior turbinates, left middle turbinates, both uncinate processes, and septum (top). The nasal floor presents a thin layer of new bone formation (middle), whilst the hard palate shows bone destruction and formation (bottom right, arrows). lesions resulted in nasopalatal perforations (MSSC 9, 193, 253, 519, 536; IESC 103, 287, 747, 957, 1112; HISC 300, 332). Furthermore, of the 43 nonspecific lytic lesions on the hard palate, eight resulted in the most severe cases – three affecting both palatine processes (MSSC 144; IESC 168, 1086), three affecting both palatine bones (MSSC 75, 532; IESC 269), one affecting the right palatine process and bone (HISC 408) and one affecting all four bony structures (MSSC 573). Nasopalatal destructions are often associated with leprosy (e.g., Ortner, 2003; Matos, 2009; Aufderheide and Rodríguez- Martín, 2011) and the methodology to record bony alterations on the hard palate in the current study followed the suggestions proposed by Matos (2009). The author studied a skeletal assemblage from the christian cemetery of the St. Jørgensgård hospital (Odense, Denmark), which was used between 1270/1280 AD and 1625 AD to bury deceased individuals, most of whom had suffered from leprosy. The comparison between the results of both studies concerning osseous alterations on the hard palate is presented in Table 62.

Table 62. Osseous alterations on the hard palate comparing the current results and the ones reported by Matos (2009). Lesions consistent with oral pathology are not reported.

Present study N=1994 Matos (2009) N=191 Osseous alteration n % n % Nasopalatal porous perforations 17 0.9 9 4.7 New bone formations 79 4 5 2.6 Osteolytic lesions 43 2.2 19 9.9 Reactive bone+macropores 16 0.8 26 13.6

Both studies show different results concerning each osseous alteration. New bone formation is more common in the current work, whereas a much higher occurrence of porous perforations, osteolytic lesions, and reactive bone/macropores was reported by Matos (2009), confirming that these alterations may be consistent with leprosy. Nonetheless, these isolated lesions are not pathognomonic of Hansen’s disease and the differential diagnosis shoud include other etiologies (Andersen and Manchester, 1992; Roberts, 2002; Matos, 2009; Aufderheide and Rodríguez-Martín, 2011). Moreover, of the individuals presenting nasopalatal lytic lesions, only two males (IESC 168, see case study, page 132; MSSC 416, see case study, page 133) and two females (IESC 264, see case study, page 130; MSSC 75, see case study, page 125) present remodelling on the lateral margins of the piriform aperture and only the first one shows atrophy of the anterior nasal spine and alveolar process.

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Case study

IESC 168

64-year-old male; occupation: merchant; cause of death: Bright disease; local and date

of death: Coimbra, 1928 AD

The individual shows nasopalatal lytic lesions, particularly in both palatine processes, and destruction of the vomer. New bone formation is also observed anteriorly on the hard palate and all the upper teeth were lost antemortem (Plate XX, Figure 44). The incisive foramen assumed the shape of a fistula-like structure (⌀=6.5mm) and characteristic

remodelling is present in the margins of the piriform aperture. The anterior nasal spine

presents atrophy, although also shows postmortem destruction, and the alveolar process of

the maxilla exhibits characteristic bone resorption. These lesions are highly consistent with

the rhinomaxillary syndrome associated with leprosy (e.g., Andersen and Manchester, 1992; Ortner, 2003; Matos, 2009; Matos and Santos, 2013), as well as with the destructive lesions described for the palatine processes in the advanced stages of the disease (e.g., Aufderheide and Rodríguez-Martín, 2011). Similar lesions are also described for other Portuguese cases of leprosy from archaeological skeletal remains (Antunes-Ferreira et al., 2013; Ferreira et al., 2013).

Furthermore, biographical data from reference collections may be very informative, but documented causes of death resulted from the limited medical knowledge available at the time (Mitchell; 2011, 2017; Marques et al., 2013; Mays, 2018). The distinction between cause of death and cause of lesion usually difficult the differential diagnosis and, ultimately, can lead to a misdiagnosis in Palaeopathology (e.g. Mays, 2018). These problems have been particularly addressed over the past few years and several examples were discussed concerning the reference collections housed in Coimbra (e.g. Umbelino et al., 2012; Marques et al., 2013). Still, a few causes of death may be helpful for the differential diagnosis. Leprosy, for instance, may be very useful to recognise, because of its characteristic changes in the face, hands, and feet. Of the three collections studied, three adult males present ‘leprosy’ as cause of death: (1) a 47-year-old amassed in Human Identified Skeletal Collection (HISC 35), who was previously described by Garcia et al. (2016) and Matos et al. (2017), showing

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Plate XX

Figure 44. A 64-year-old male (IESC 168; cause of death: Bright disease) presenting possible resorption and remodelling of the piriform aperture, atrophy of the anterior nasal spine (top), nasopalatal lytic destructions on both palatine processes, and destruction of the vomer (bottom). A fistula-like structure is present anteriorly on the incisive foramen (arrow). pathological alterations on two hand phalanges, tibiae, fibulae, and foot bones, but not in the skull; (2) a 60-year-old male amassed in the International Exchange Skull Collection (IESC 545) who presents nonspecific woven bone formation anteriorly on both palatine processes; and (3) an adult male amassed in the Medical Schools Skull Collection (MSSC 416) whose bony alterations are described below.

Case study

MSSC 416 Adult male; occupation: worker; cause of death: leprosy; provenance and date of death:

Lisbon Medical School, 1900 AD

The individual exhibits remodelling of the piriform aperture and a slight depression on the basis of the right nasal cavity. Woven bone is present on both sides of the nasal floor and along the most inferior portions of the lateral nasal walls, coexisting with osteolytic lesions on the left nasal cavity. The nasal septum shows severe bone destruction, both in the perpendicular plate of the ethmoid and vomer, which is also present in the left

uncinate process. New bone formation is also visible superiorly on the nasal septum and nasal bones, within the nasal cavity. The individual also presents woven bone along the sutures of the palatine processes and bones. This set of lesions is also described for other

cases of leprosy (e.g., Andersen and Manchester, 1992; Ortner, 2003; Matos, 2009; Matos

and Santos, 2013) and is highly consistent with the individual’s cause of death. He died in 1900, when the presence of leprosy seemed to be increasing in Portugal (Rocha, 1897; Carvalho, 1932).

Nevertheless, the presence of nasopalatal destruction is not pathognomonic and vary widely among several of the most common causes of death of the 19th and 20th centuries in Portugal. Table 63 groups the causes of death documented for all individuals exhibiting nasopalatal destruction in the three collections studied. Palaeopathological literature confirms that similar nasopalatal alterations may be associated with treponematosis or tuberculosis (lupus vulgaris), and, more rarely, leishmaniosis, actinomycosis, or neoplastic disease (e.g., Hackett, 1976; Manchester, 1994; Ortner, 2003). Table 64 shows the nasopalatal perforations by cause of death detailed by Hackett (1976) in 424 individuals from several identified anatomical/medical collections.

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Table 63. Individuals exhibiting nasal and palatal destructions by cause of death. Isolated Nasopalatal porous Isolated Cause of death destructions within and/or osteolytic destruction on the nasal cavity lesions the hard palate Lower respiratory tract disease 3 2 6 Heart disease 1 2 1 Neoplastic disease/tumour 3 1 3 Pulmonary tuberculosis 3 5 9 Senile cachexia 1 2 6 Cerebral haemorrhage - 1 3 Meningitis 2 - 1 Kidney disease - 2 2 Leprosy 1 - - Other 3 2 3 Not stated 3 4 5 Total 20 21 39

Table 64. Nasopalatal perforations by cause of death described by Hackett (1976) in 424 individuals.

Presenting nasopalatal destruction Cause of death N n % Syphilis 281 29 10.3 Osteomyelitis 16 - - Tuberculosis (lupus vulgaris) 8 1 12.5 Neoplastic disease 40 8 20 Leprosy 4 4 100

The results reported by Hackett (1976) are also in accordance with the lack of specificity of nasopalatal destructions concerning their etiology and differential diagnosis, which is emphasised by several other investigators (e.g., Manchester, 1994; Brothwell, 2005; Matos, 2009). Moreover, no cranial lesions consistent with caries sicca were found in the individuals presenting nasopalatal perforations in the current study. Lopes (2014) studied the hospital records of 55 individuals who were treated for syphilis at the Coimbra University Hospitals amassed in two identified collections from Coimbra and only four (4/55, 7.3%) exhibit nasopalatal destruction and new bone formation, whilst Caries sicca was absent in all 55 patients. This study has also demonstrated the difficulty of association between syphilis and nasopalatal destructions, as well as the problematic identification of syphilis when caries sicca is absent. Palatal and septal perforations are also associated with long term cocaine consumption (e.g., Bains and Hosseini-Ardehali, 2005; Valencia and Castillo, 2008; Silvestre et al., 2010). Cocaine was used during the 19th century in several Portuguese hospitals as a local anaesthetic for nasal and dental problems (e.g., Vieira, 1890; Castro, 1892) and its recreational use must also be taken into account for the differential

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diagnosis. Crohn’s disease (Sari et al., 2007), iatrogenic factors, and chemical irritants (Kridel, 2004) are also possible etiologies for septal perforations. Also, Kridel (2004) refers that septal perforations may be asymptomatic and this is more likely to happen if they are located posteriorly within the nose.

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5. Conclusion

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138

The study of sinonasal variations and diseases affecting the human skull in past populations is still subject of several doubts, including proper methodological approaches and definitions, prevalence, or differential diagnosis. The main objective of this work, whose study base comprised 2024 individuals who lived in Portugal between 1804 and 1981, was to study several of these sinonasal osseous alterations and take a step forward on the issue. Regarding the analysis of nasal trauma, its proper definition (as well as the differentiation between nasal trauma and other facial fractures) is essential for the methodological standardisation, replication, and interpretation of the results. Males present a higher frequency in the current work, with statistically significant differences. Most of the lesions are the result of a lateral impact force fracture, which may mean that interpersonal and intimate partner violence may have played an important role in the etiology of the fractures. Concerning the variations and diseases affecting the nasal cavity and maxillary sinuses, all were very common and the general high prevalence should be particularly emphasised. Moreover, the definitive diagnosis of concha bullosa should only be achieved by using CT scan, which is most of the times restrictive due to the limited access to this imaging technique and to its inherent costs. Nevertheless, agreement between macroscopic observations and CT scans of the 60 crania resulted in the reliable and consistent macroscopic observation of concha bullosa, both for presence and side. Concerning the type of concha bullosa, the results turned out to be unreliable for analytical purposes.

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The sinonasal anatomical area is usually neglected when studying skeletal assemblages and the present work intended to provide tools to better understand what shoud be considered a normal variation, a variation that might result in pathology, or the different expressions of disease. Nasal septal deviation is probably the most difficult nasal variation to study, which is shown by the wide variety of morphologic and metric methodologies described in clinical studies. This study proposes a new morphologic method for dry bone analysis, dividing five different types of deviation according to the presence of the deflection of the perpendicular plate of the ethmoid or/and the vomer. One of the main hypotheses underlying the current study relies in the possible association between the presence of nasal variations and sinonasal pathology. In fact, concha bullosa and paradoxical curvature play a role in the presence of new bone formations on the middle turbinate. Nevertheless, no association seems to be present in the current work between nasal variations and maxillary rhinosinusitis and other factors may have played a more important role in the high prevalence of sinonasal disease. As it is currently hypothesised in clinical studies, factors like intrinsic mucosal inflammation, local microbial community, or mucociliary dysfunction may have played a role in the same individual and their relative importance in the etiology of sinonasal disease is impossible to understand when studying skeletal assemblages. Moreover, the current results do not recommend to record pits and white pitted bone when searching for evidence of maxillary rhinosinusitis because it is not possible to differentiate between pathological and physiological porosities within the maxillary sinuses. This study also highlights, for the first time, that the presence of spicules of bone formation on the middle turbinate are highly consistent with rhinitis as the nasal mucosa and the middle meatus, particularly the middle turbinates, are the first line of defence against external aggressions. Concha bullosa and maxillary rhinosinustis also play a role on craniofacial morphology. Indeed, a pattern of increased facial breadth was found in the present study, most probably because both have developed during early age. These findings may be important for future investigations concerning the study of the influence of sinonasal anatomy on craniofacial morphology. The individuals of the Coimbra and Lisbon collections also showed wide variety of osseous alterations on the anterior wall of the maxillary sinuses, nasal cavity, and/or

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hard palate. Several examples highly consistent with leprosy were described, as well as the first know evidence of possible teaching of modern dacryocystorhinostomy. This was a pioneer research using skeletal collections, both regarding to sample size and to the study of the possible association between some of the most common sinonasal variations and diseases, and craniofacial morphology. This work intended to contribute to the knowledge of disease in Portuguese individuals and how life conditions of an increasingly urban population may impair the normal function of the upper respiratory tract, as well as a step forward for future studies to use, compare, and discuss results and methodological approaches. Only time will tell if this ultimate objective will be fulfiled.

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6. References

143

Abreu, J. L. N. 2007. Os estudos anatômicos e cirúrgicos na medicina portuguesa do século XVIII. Revista da Sociedade Brasileira da História da Ciência, 5(2): 149–172.

Abuzaid, W.; Thaler, E. R. 2008. Etiology and impact of rhinosinusitis. In: Thaler, E. R.; Kennedy, D. W. (eds.) Rhinosinusitis: a guide for diagnosis and management. New York, Springer: 1–15.

Advertisements, 1887a. Coimbra Médica, 7(1): no page.

Advertisements, 1887b. Coimbra Médica, 7(3): no page.

Advertisements, 1889. Coimbra Médica, 9(5): no page.

Advertisements, 1925. Lisboa Médica, 11(8/9): no page.

Agostinho, H. A.; Furtado, I. Ã.; Silva, F. S.; Ustrell Torrent, J. 2015. Cephalometric evaluation of children with allergic rhinitis and mouth breathing. Acta Médica Portuguesa, 28(3): 316–321.

Akiyama, K.; Karaki, M.; Osaki, Y.; Takeda, J.; Mori, N. 2011. Intraosseous cavernous hemangioma of the middle turbinate. Auris Nasus Larynx, 38(4): 516–518.

Aksungur, E. H.; Biçakçi, K.; Inal, M.; Akgül, E.; Binokay, F.; Aydogan, B.; Oguz, M. 1999. CT demonstration of accessory nasal turbinates: secondary middle turbinate and bifid inferior turbinate. European Journal of Radiology, 31(3): 174–176.

Aktas, D.; Kalcioglu, M. T.; Kutlu, R.; Ozturan, O.; Oncel, S. 2003. The relationship between the concha bullosa, nasal septal deviation and sinusitis. Rhinology, 41(2): 103– 106.

Al-Abri, R.; Bhargava, D.; Al-Bassam, W.; Al-Badaai, Y.; Sawhney, S. 2014. Clinically significant anatomical variants of the paranasal sinuses. Oman Medical Journal, 29(2): 110–113.

Albanese, J. 2003. Identified skeletal reference collections and the study of human variation. Doctoral dissertation. Hamilton, McMaster University.

Ali, M. J. 2015. Lacrimal disorders and surgery: historical perspectives. In: Ali, M. J. (ed.) Principles and practice of lacrimal surgery. New Delhi, Springer India: 1–8.

144

Almeida, M. A. P. 2014. As epidemias nas notícias em Portugal: cólera, peste, tifo, gripe e varíola, 1854-1918. História, Ciências, Saúde-Manguinhos, 21(2): 687–708.

Al-Qudah, M. A. 2010. Anatomical variations in sino-nasal region: a computed tomography (CT) study. Jordan Medical Journal, 44(3): 290–297.

Al-Qudah, M. A. 2015. Extra middle turbinate lamellas: a suggested new classification. Surgical and Radiologic Anatomy, 37(8): 941–945.

Alves, C. A.; Scotto, M. G.; Freitas, M. C. 2010. Air pollution and emergency admissions for cardiorespiratory diseases in Lisbon (Portugal). Química Nova, 33(2): 337–344.

Anazy, F. H. A. 2011. The incidence of concha bullosa and its association with chronic rhinosinusitis deviated nasal septum and osteomeatal complex obstruction. Bahrain Medical Bulletin, 33(4): 188–191.

Andersen, J. G.; Manchester, K. 1992. The rhinomaxillary syndrome in leprosy: a clinical, radiological and palaeopathological study. International Journal of Osteoarchaeology, 2(2): 121–129.

Andersen, J. G.; Manchester, K.; Roberts, C. 1994. Septic bone changes in leprosy: a clinical, radiological and palaeopathological review. International Journal of Osteoarchaeology, 4(1): 21–30.

Andersson, J. A.; Uddman, R.; Cardell, L. O. 2002. Increased carbon monoxide levels in the nasal airways of subjects with a history of seasonal allergic rhinitis and in patients with upper respiratory tract infection. Clinical and Experimental Allergy, 32(2): 224– 227.

Antunes, M. C. J. C. 2006. Mortos sem voz: à descoberta do seu passado Medieval. Master dissertation. Coimbra, University of Coimbra.

Antunes-Ferreira, N.; Matos, V. M. J.; Santos, A. L. 2013. Leprosy in individuals unearthed near the Ermida de Santo André and Leprosarium of Beja, Portugal. Anthropological Science, 121(3): 149–159.

Appleby, J.; Thomas, R.; Buikstra, J. 2015. Increasing confidence in paleopathological

145

diagnosis – Application of the Istanbul terminological framework. International Journal of Paleopathology, 8: 19–21.

Archer, J. 2000. Sex differences in aggression between heterosexual partners: a meta- analytic review. Psychological Bulletin, 126(5): 651–680.

Arda, B.; Sipahi, O. R.; Atalay, S.; Ulusoy, S. 2008. Pooled analysis of 2,408 cases of acute adult purulent meningitis from Turkey. Medical Principles and Practice, 17(1): 76–79.

Arslan, H.; Aydınlıoğlu, A.; Bozkurt, M.; Egeli, E. 1999. Anatomic variations of the paranasal sinuses: CT examination for endoscopic sinus surgery. Auris Nasus Larynx, 26(1): 39–48.

Arun, T.; Isik, F.; Sayinsu, K. 2003. Vertical growth changes after adenoidectomy. The Angle Orthodontist, 73(2): 146–150.

Aufderheide, A. C.; Rodríguez-Martín, C. 2011. The Cambridge encyclopedia of human paleopathology. 4th edition. Cambridge, Cambridge University Press.

Avsever, H.; Gunduz, K.; Karakoç, O.; Akyol, M.; Orhan, K. 2018. Incidental findings on cone-beam computed tomographic images: paranasal sinus findings and nasal septum variations. Oral Radiology, 34(1): 40–48.

Aygun, N.; Uzunes, O.; Zinreich, S. J. 2006. Imaging sinusitis. In: Brook, I. (ed.) Sinusitis: from microbiology to management. New York, Taylor & Francis: 145–178.

Azila, A.; Irfan, M.; Rohaizan, Y.; Shamim, A. K. 2011. The prevalence of anatomical variations in osteomeatal unit in patients with chronic rhinosinusitis. The Medical Journal of Malaysia, 66(3): 191–194.

Aziz, T.; Biron, V. L.; Ansari, K.; Flores-Mir, C. 2014. Measurement tools for the diagnosis of nasal septal deviation: a systematic review. Journal of Otolaryngology - Head & Neck Surgery [Online], 43(1):11. DOI: 10.1186/1916-0216-43-11.

Badia, L.; Lund, V. J.; Wei, W.; Ho, W. K. 2005. Ethnic variation in sinonasal anatomy on CT-scanning. Rhinology, 43(3): 210–214.

Bae, S.-H.; Lim, S.-C. 2010. Accessory middle turbinate. Otolaryngology-Head and 146

Neck Surgery, 142(5): 770–771.

Baek, H. J.; Kim, D. W.; Ryu, J. H.; Lee, Y. J. 2013. Identification of nasal bone fractures on conventional radiography and facial CT: comparison of the diagnostic accuracy in different imaging modalities and analysis of interobserver reliability. Iranian Journal of Radiology, 10(3): 140–147.

Bailey, L. J.; Haltiwanger, L. H.; Blakey, G. H.; Proffit, W. R. 2001. Who seeks surgical-orthodontic treatment: a current review. The International Journal of Adult Orthodontics and Orthognathic Surgery, 16(4): 280–292.

Bains, M. K.; Hosseini-Ardehali, M. 2005. Palatal perforations: past and present. Two case reports and a literature review. British Dental Journal, 199(5): 267–269.

Bakor, S. F.; Enlow, D. H.; Pontes, P.; De Biase, N. G. 2011. Craniofacial growth variations in nasal-breathing, oral-breathing, and tracheotomized children. American Journal of Orthodontics and Dentofacial Orthopedics, 140(4): 486–492.

Balikci, H. H.; Gurdal, M. M.; Celebi, S.; Ozbay, I.; Karakas, M. 2016. Relationships among concha bullosa, nasal septal deviation, and sinusitis: retrospective analysis of 296 cases. Ear, Nose, & Throat Journal, 95(12): 487–491.

Bansal, A. K.; Sharma, M.; Kumar, P.; Nehra, K.; Kumar, S. 2015. Long face syndrome: a literature review. Journal of Dental Health, Oral Disorders & Therapy [Online], 2(6): 71. DOI: 10.15406/jdhodt.2015.02.00071.

Baptista, J. A. 1902. Antro d’Highmoro e sinusite Highmorianna (breve estudo): dissertação inaugural apresentada á Escola Medico-Cirurgica do Porto. Porto, Typographia Central.

Barbosa, A. M. 1856. Memoria sobre as principaes causas de mortalidade do Hospital de S. José e meios de as attenuar. Lisboa, Imprensa de Francisco Xavier de Sousa.

Barros, E.; Monteiro, L.; Prata, J. B.; Vieira, A. S.; Tomé, P.; Gonçalves, P.; Santos, A.; Mota, M.; Macedo, A. 2008. Avaliação da prevalência e caracterização da rinossinusite em Portugal – Estudo epidemiológico. Revista Portuguesa de Otorrinolaringologia e Cirurgia Cérvico-Facial, 46(4): 243–250.

147

Bass, W. M. 1995. Human osteology: a laboratory and field manual. 4th edition. Columbia, Missouri Archeological Society.

Baumann, I.; Baumann, H. 2007. A new classification of septal deviations. Rhinology, 45(3): 220–223.

Beale, T. J.; Madani, G.; Morley, S. J. 2009. Imaging of the paranasal sinuses and nasal cavity: normal anatomy and clinically relevant anatomical variants. Seminars in Ultrasound, CT and MRI, 30(1): 2–16.

Benninger, M. S.; Ferguson, B. J.; Hadley, J. A.; Hamilos, D. L.; Jacobs, M.; Kennedy, D. W.; Lanza, D. C.; Marple, B. F.; Osguthorpe, J. D.; Stankiewicz, J. A.; Anon, J.; Denneny, J.; Emanuel, I.; Levine, H. 2003. Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology. Otolaryngology-Head and Neck Surgery, 129(3 Suppl.): S1–S32.

Bernofsky, K. S. 2010. Respiratory health in the past: a bioarchaeological study of chronic maxillary sinusitis and rib periostitis from the Iron Age to the Post Medieval Period in Southern England. Doctoral dissertation. Durham, Durham University.

Bernstein, J. M. 2006. Chronic rhinosinusitis with and without nasal polyposis. In: Brook, I. (ed.) Sinusitis: from microbiology to management. New York, Taylor & Francis: 371–402.

Berrios, D. C.; Grady, D. 1991. Domestic violence. Risk factors and outcomes. The Western Journal of Medicine, 155(2): 133–135.

Bhattacharyya, N. 2009. Air quality influences the prevalence of hay fever and sinusitis. The Laryngoscope, 119(3): 429–433.

Biedlingmaier, J. F.; Whelan, P.; Zoarski, G.; Rothman, M. 1996. Histopathology and CT analysis of partially resected middle turbinates. The Laryngoscope, 106(1): 102– 104.

Bingham, B.; Wang, R.-G.; Hawke, M.; Kwok, P. 1991. The embryonic development of the lateral nasal wall from 8 to 24 weeks. The Laryngoscope, 101(9): 992–997.

Bissaia-Barreto. 1922. O ensino da técnica operatória e patologia cirúrgica em

148

Coimbra (920-921). Coimbra, Imprensa da Universidade.

Blanchette, M. E.; Nanda, R. S.; Currier, G. F.; Ghosh, J.; Nanda, S. K. 1996. A longitudinal cephalometric study of the soft tissue profile of short- and long face syndromes from 7 to 17 years. American Journal of Orthodontics and Dentofacial Orthopedics, 109(2): 116–131.

Bluestone, C. D.; Pagano, A. S.; Swarts, J. D.; Laitman, J. T. 2012. Consequences of evolution: is rhinosinusitis, like otitis media, a unique disease of humans? Otolaryngology-Head and Neck Surgery, 147(6): 986–991.

Boffano, P.; Kommers, S. C.; Karagozoglu, K. H.; Forouzanfar, T. 2014. Aetiology of maxillofacial fractures: a review of published studies during the last 30 years. British Journal of Oral and Maxillofacial Surgery, 52(10): 901–906.

Boffano, P.; Roccia, F.; Campisi, P.; Gallesio, C. 2012. Review of 43 osteomas of the craniomaxillofacial region. Journal of Oral and Maxillofacial Surgery, 70(5): 1093– 1095.

Boffano, P.; Roccia, F.; Zavattero, E.; Dediol, E.; Uglešić, V.; Kovačič, Ž.; Vesnaver, A.; Konstantinović, V. S.; Petrović, M.; Stephens, J.; Kanzaria, A.; Bhatti, N.; Holmes, S.; Pechalova, P. F.; Bakardjiev, A. G.; Malanchuk, V. A.; Kopchak, A. V.; Galteland, P.; Mjøen, E.; Skjelbred, P.; Grimaud, F.; Fauvel, F.; Longis, J.; Corre, P.; Løes, S.; Lekven, N.; Laverick, S.; Gordon, P.; Tamme, T.; Akermann, S.; Karagozoglu, K. H.; Kommers, S. C.; Meijer, B.; Forouzanfar, T. 2015. European maxillofacial trauma (EURMAT) in children: a multicenter and prospective study. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 119(5): 499–504.

Bolger, W. E.; Butzin, C. A.; Parsons, D. S. 1991. Paranasal sinus bony anatomic variations and mucosal abnormalities. The Laryngoscope, 101(1): 56–64.

Bolger, W. E.; Leonard, D.; Dick, E. J.; Stierna, P. 1997. Gram negative sinusitis: a bacteriologic and histologic study in rabbits. American Journal of Rhinology, 11(1): 15– 25.

Bolger, W. E.; Woodruff, W.; Parsons, D. S. 1990. CT demonstration of pneumatization of the uncinate process. American Journal of Neuroradiology, 11(3): 552.

149

Boocock, P.; Roberts, C. A.; Manchester, K. 1995a. Maxillary sinusitis in Medieval Chichester, England. American Journal of Physical Anthropology, 98(4): 483–495.

Boocock, P.; Roberts, C. A.; Manchester, K. 1995b. Prevalence of maxillary sinusitis in leprous individuals from a Medieval leprosy hospital. International Journal of Leprosy and other Mycobacterial Diseases, 63(2): 265–268.

Booth, P. 2014. A Late Roman military burial from the Dyke Hills, Dorchester on Thames, Oxfordshire. Britannia, 45: 243–273.

Boulet, C.; Madani, H.; Lenchik, L.; Vanhoenacker, F.; Amalnath, D. S.; de Mey, J.; De Maeseneer, M. 2016. Sclerosing bone dysplasias: genetic, clinical and radiology update of hereditary and non-hereditary disorders. The British Journal of Radiology [Online], 89(1062): 20150349. DOI: 10.1259/bjr.20150349.

Braun, H.; Stammberger, H. 2003. Pneumatization of turbinates. The Laryngoscope, 113(4): 668–672.

Brickley, M.; Smith, M. 2006. Culturally determined patterns of violence: biological anthropological investigations at a historic urban cemetery. American Anthropologist, 108(1): 163–177.

Brink, O.; Vesterby, A.; Jensen, J. 1998. Pattern of injuries due to interpersonal violence. Injury, 29(9): 705–709.

Broca, P. 1875. Instructions craniométriques: notions complémentaires sur l’ostéologie du crâne. Détermination et dénomination nouvelles de certains points de repère. Nomenclature craniologique. Bulletins de la Société d’Anthropologie de Paris, 10(1): 337–367.

Broca, P. 1879. Instructions générales pour les recherches anthropologiques à faire sur le vivant. 2nd edition. Paris, G. Masson.

Broca, P. 1883. Mémoires d’Anthropologie. Tome Quatrième. Paris, C. Reinwald.

Brothwell, D. 1967. The evidence of neoplasms. In: Brothwell, D.; Sandison, A. T.; Dawson, W. R. (eds.) Diseases in antiquity. Springfield, Charles C Thomas: 320–345.

Brothwell, D. R. 1981. Digging up bones: the excavation, treatment, and study of 150

human skeletal remains. New York, Cornell University Press.

Brothwell, D. R. 2005. North American treponematosis against the bigger world picture. In: Powell, M. L.; Cook, D. C. (eds.) The myth of syphilis: the natural history of treponematosis in North America. Gainesville, University Press of Florida: 480–496.

Brothwell, D. R.; Browne, S. 1994. Pathology. In: Lilley, J. M.; Stroud, G.; Brothwell, D. R.; Williamson, M. H. (eds.) The Jewish burial ground at Jewbury. The archaeology of York. The Medieval cemeteries 12/3. York, Council of British Archaeology: 457–494.

Bruce, N.; Perez-Padilla, R.; Albalak, R. 2002. The health effects of indoor air pollution exposure in developing countries. Geneva, World Health Organization.

Buikstra, J. E.; Cook, D. C.; Bolhofner, K. L. 2017. Introduction: scientific rigor in paleopathology. International Journal of Paleopathology, 19: 80–87.

Buikstra, J. E.; Ubelaker, D. H. 1994. Standards for data collection from human skeletal remains. Arkansas Archeological Survey Research Series Number 44. Arkansas, Arkansas Archeological Survey.

Busaba, N. Y.; Shin, H. J.; Faquin, W. C. 2006. Correlation between middle turbinate and ipsilateral ethmoid histopathology in chronic rhinosinusitis. Otolaryngology-Head and Neck Surgery, 134(2): 250–254.

Buxton, L. H. D.; Morant, G. M. 1933. The essential craniological technique. The Journal of the Royal Anthropological Institute of Great Britain and Ireland, 63: 19–47.

Cabezón, A. R.; Vaidés, S. R.; Breinbauer, K. H.; Ramírez, R. C.; Grau, L. C.; Iñíguez, C. R. 2010. Variantes anatómicas relevantes en tomografía computarizada de cavidades perinasales. Revista de Otorrinolaringología y Cirugía de Cabeza y Cuello, 70(3): 223– 230.

Cahn, J. N. 2016. Bone-years: accounting for differences in preservation and age distribution when comparing lesion prevalence between skeletal collections. Poster presented at the 85th Annual Meeting of the American Association of Physical Anthropologists; Atlanta, USA; 13-16 September 2016.

Calhoun, K. H.; Waggenspack, G. A.; Simpson, C. B.; Hokanson, J. A.; Bailey, B. J.

151

1991. CT evaluation of the paranasal sinuses in symptomatic and asymptomatic populations. Otolaryngology-Head and Neck Surgery, 104(4): 480–483.

Çalışkan, A.; Sumer, A. P.; Bulut, E. 2017. Evaluation of anatomical variations of the nasal cavity and ethmoidal complex on cone-beam computed tomography. Oral Radiology, 33(1): 51–59.

Campillo, D. 2005. Paleoradiology III: neoplastic conditions. Journal of Paleopathology, 17(3): 93–135.

Capasso, L. 1997. Osteoma: Palaeopathology and phylogeny. International Journal of Osteoarchaeology, 7(6): 615–620.

Capelozza Filho, L.; Cardoso, M. A.; Li An, T.; Lauris, J. R. P. 2007. Proposta para classificação, segundo a severidade, dos indivíduos portadores de más oclusões do Padrão Face Longa. Revista Dental Press de Ortodontia e Ortopedia Facial, 12(4): 124–158.

Cardoso, F. A. 1997. Reviver o passado em Aeminium: estudo paleodemográfico e paleopatológico duma amostra antropológica do Convento de Santa Clara-a-Velha. Research report in Human Sciences. Coimbra, University of Coimbra.

Cardoso, H. F. V. 2003/2004. Onde estão as crianças? Representatividade de esqueletos infantis em populações arqueológicas e implicações para a paleodemografia. Antropologia Portuguesa, 20/21: 237–266.

Cardoso, H. F. V. 2005. Patterns of growth and development of the human skeleton and dentition in relation to environmental quality: a biocultural analysis of a sample of 20th century portuguese subadult documented skeletons. Doctoral dissertation. Hamilton, McMaster University.

Cardoso, H. F. V. 2006. Brief communication: the collection of identified human skeletons housed at the Bocage Museum (National Museum of Natural History), Lisboa, Portugal. American Journal of Physical Anthropology, 129(2): 173–176.

Cardoso, M. A.; Capelozza Filho, L.; Li An, T.; Lauris, J. R. P. 2011. Epidemiologia do Padrão Face Longa em escolares do ensino fundamental do município de Bauru – SP. Dental Press Journal of Orthodontics, 16(2): 108–119. 152

Cardoso, M. A.; Castro, R. C. F. R.; Li An, T.; Normando, D.; Garib, D. G.; Capelozza Filho, L. 2013. Prevalence of long face pattern in Brazilian individuals of different ethnic backgrounds. Journal of Applied Oral Science, 21(2): 150–156.

Carels, C.; Van Cauwenberghe, N.; Savoye, I.; Willems, G.; Loos, R.; Derom, C.; Vlietinck, R. 2001. A quantitative genetic study of cephalometric variables in twins. Clinical Orthodontics and Research, 4(3): 130–140.

Caroline, H.; Franceschi, D.; Philippe, R. 2011. Chronic rhinosinusitis and olfactory dysfunction. In: Marseglia, G. L.; Caimmi, D. P. (eds.) Peculiar aspects of rhinosinusitis. Ryjeka, InTech: 39–52.

Carvalho, A. S. 1932. História da lepra em Portugal. Porto, Oficinas Gráficas da Sociedade de Papelaria, Lda.

Castel-Branco, M. G. 1997. Redefinindo a rinite. Revista Portuguesa de Imunoalergologia, 5(1): 51–54.

Castro, A. 1978. A revolução industrial em Portugal no século XIX. 4th edition. Porto, Limiar – Actividades Gráficas, Lda.

Castro, Q. E. 1892. Nevroses reflexas de origem nasal: dissertação inaugural apresentada á Escola Medico-Cirurgica do Porto. Porto, Typographia Empreza Litteraria.

Caughey, R. J.; Jameson, M. J.; Gross, C. W.; Han, J. K. 2005. Anatomic risk factors for sinus disease: fact or fiction? American Journal of Rhinology, 19(4): 334–339.

Caylakli, F.; Buyuklu, F.; Cakmak, O.; Ozdemir, H.; Ozluoglu, L. 2004. Ossifying fibroma of the middle turbinate: a case report. American Journal of Otolaryngology, 25(5): 377–378.

Chaitanya, D. K.; Suseelamma, D.; Singh, V. 2015. Anatomical variations of paranasal air sinuses – A CT scan study. Journal of the Anatomical Society of India, 64(1): 87–90.

Chaiyasate, S.; Baron, I.; Clement, P. 2007. Analysis of paranasal sinus development and anatomical variations: a CT genetic study in twins. Clinical Otolaryngology, 32(2): 93–97.

153

Chambi-Rocha, A.; Cabrera-Domínguez, M. E.; Domínguez-Reyes, A. 2018. Breathing mode influence on craniofacial development and head posture. Jornal de Pediatria, 94(2): 123–130.

Chan, J.; Most, S. P. 2008. Diagnosis and management of nasal fractures. Operative Techniques in Otolaryngology-Head and Neck Surgery, 19(4): 263–266.

Chang, A.; Ulualp, S. O.; Koral, K.; Veling, M. 2016. A rare nasal cavity mass in a child: accessory middle turbinate. SAGE Open Medical Case Reports [Online], 4. DOI: 10.1177/2050313X16672152.

Charlier, P.; Froesch, P.; Benmoussa, N.; Froment, A.; Shorto, R.; Huynh-Charlier, I. 2014. Did René Descartes have a giant ethmoidal sinus osteoma? The Lancet, 384(9951): 1348.

Chen, Y.; Dales, R.; Lin, M. 2003. The epidemiology of chronic rhinosinusitis in Canadians. The Laryngoscope, 113(7): 1199–1205.

Cheng, J.; Wang, Y.; Yu, H.; Wang, D.; Ye, J.; Jiang, H.; Wu, Y.; Shen, G. 2012. An epidemiological and clinical analysis of craniomaxillofacial fibrous dysplasia in a Chinese population. Orphanet Journal of Rare Diseases [Online], 7: 80. DOI: 10.1186/1750-1172-7-80.

Chiu, A. G. 2005. Osteitis in chronic rhinosinusitis. Otolaryngologic Clinics of North America, 38(6): 1237–1242.

Cho, S. H.; Kim, T. H.; Kim, K. R.; Lee, J.-M.; Lee, D.-K.; Kim, J.-H.; Im, J.-J.; Park, C.-J.; Hwang, K.-G. 2010. Factors for maxillary sinus volume and craniofacial anatomical features in adults with chronic rhinosinusitis. Archives of Otolaryngology– Head & Neck Surgery, 136(6): 610–615.

Choi, J. H. 2013. Frontal sinusitis caused by first and second secondary middle turbinates co-existing with an accessory middle turbinate. Japanese Journal of Radiology, 31(5): 352–356.

Chow, J. M. 1994. Rhinologic headaches. Otolaryngology-Head and Neck Surgery, 111(3): 211–218.

154

Clark, S. T.; Babin, R. W.; Salazar, J. 1989. The incidence of concha bullosa and its relationship to chronic sinonasal disease. American Journal of Rhinology, 3(1): 11–12.

Clement, P. A. R. 2006. Classifications of rhinosinusitis. In: Brook, I. (ed.) Sinusitis: from microbiology to management. New York, Taylor & Francis Group: 15–38.

Clode, J. J. P. E. 2010. A otorrinolaringologia em Portugal. Queluz, Círculo Médico - Comunicação e Design, Lda.

Coleman, L.; Zakowsky, M.; Gold, J. A.; Ramanathan, S. 2013. Functional anatomy of the airway. In: Hagberg, C. A.; Artime, C. A.; Aziz, M. F. (eds.) Hagberg and Benumof’s airway management. 3rd edition. Philadelphia, Elsevier: 3–20.

Corriveau, M.-N.; Bachert, C. 2012. Allergic and nonallergic rhinitis. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 82–91.

Cosme, J. 2006. As preocupações higio-sanitárias em Portugal (2ª metade do século XIX e princípios do XX). Revista da Faculdade de Letras. História, 7(3): 181–195.

Costa, H. G. A. 2003. Testemunhos fiéis: contribuição para o estudo bioantropológico do espólio osteológico exumado da Igreja do Mosteiro Beneditino de Santa Maria de Semide datado dos séculos XVI-XIX. Undergraduate dissertation in Human Sciences. Coimbra, University of Coimbra.

Costa, M. F. 2012. Dicionário de termos médicos. Porto, Porto Editora.

Costa, R. M. P.; Vieira, I. C. 2011. O trabalho académico como fonte histórica: as teses inaugurais da Escola Médico-Cirúrgica do Porto (1827-1910). CEM/Cultura, Espaço & Memória, 3: 251–260.

Crichton, N. 2000. Information point: prevalence and incidence. Journal of Clinical Nursing, 9(2): 188.

Cuesta, M. 2008. Patologia nasosinusal i oral. In: Campillo, D. (ed.) Quaranta anys de paleopatologia en el Museu d’Arqueologia de Catalunya. Barcelona, Museu d’Arqueologia de Catalunya: 217–244.

Cukurova, I.; Demirhan, E.; Arslan, I. B.; Cumurcu, S. 2010. Cholesteatoma of the 155

concha bullosa: a case report. Journal of Medical Case Reports [Online], 4: 407. DOI: 10.1186/1752-1947-4-407.

Cukurova, I.; Yaz, A.; Gumussoy, M.; Yigitbasi, O. G.; Karaman, Y. 2012. A patient presenting with concha bullosa in another concha bullosa: a case report. Journal of Medical Case Reports [Online], 6: 87. DOI: 10.1186/1752-1947-6-87.

Cunha, E. 1994. Paleobiologia das populações Medievais portuguesas: os casos de Fão e S. João de Almedina. Doctoral dissertation. Coimbra, University of Coimbra.

D’Ascanio, L.; Lancione, C.; Pompa, G.; Rebuffini, E.; Mansi, N.; Manzini, M. 2010. Craniofacial growth in children with nasal septum deviation: a cephalometric comparative study. International Journal of Pediatric Otorhinolaryngology, 74(10): 1180–1183.

D’Azevedo, L. C. C. 1931. Dois casos de sinusite maxilar crónica latente. Lisboa Médica, 11(8 Suppl.): S1–S4.

Da atropina na coryza. 1885. Coimbra Médica, 5(8): 142.

Daniel, W. W. 2005. Biostatistics: a foundation for analysis in the health sciences. 8th edition. Hoboken, John Wiley & Sons, Inc.

Daniels, D. L.; Mafee, M. F.; Smith, M. M.; Smith, T. L.; Naidich, T. P.; Brown, W. D.; Bolger, W. E.; Mark, L. P.; Ulmer, J. L.; Hacein-Bey, L.; Strottmann, J. M. 2003. The frontal sinus drainage pathway and related structures. American Journal of Neuroradiology, 24(8): 1618–1627.

Dasar, U.; Gokce, E. 2016. Evaluation of variations in sinonasal region with computed tomography. World Journal of Radiology, 8(1): 98–108. de la Cova, C. 2012. Patterns of trauma and violence in 19th-century-born African American and Euro-American females. International Journal of Paleopathology, 2(2– 3): 61–68.

De Schryver, E.; Calus, L.; Derycke, L.; Bachert, C.; Gevaert, P. 2013. Local nasal inflammation: T cells and B cells. In: Önerci, T. M. (ed.) Nasal physiology and pathophysiology of nasal disorders. New York, Springer: 47–67.

156

Deeb, R.; Malani, P. N.; Gil, B.; Jafari-Khouzani, K.; Soltanian-Zadeh, H.; Patel, S.; Zacharek, M. A. 2011. Three-dimensional volumetric measurements and analysis of the maxillary sinus. American Journal of Rhinology and Allergy, 25(3): 152–156.

Deja, M.; Busch, T.; Bachmann, S.; Riskowski, K.; Câmpean, V.; Wiedmann, B.; Schwabe, M.; Hell, B.; Pfeilschifter, J.; Falke, K. J.; Lewandowski, K. 2003. Reduced nitric oxide in sinus epithelium of patients with radiologic maxillary sinusitis and sepsis. American Journal of Respiratory and Critical Care Medicine, 168(3): 281–286.

Desrosiers, M.; Evans, G. A.; Keith, P. K.; Wright, E. D.; Kaplan, A.; Bouchard, J.; Ciavarella, A.; Doyle, P. W.; Javer, A. R.; Leith, E. S.; Mukherji, A.; Schellenberg, R. R.; Small, P.; Witterick, I. J. 2011. Canadian clinical practice guidelines for acute and chronic rhinosinusitis. Allergy, Asthma & Clinical Immunology [Online], 7: 2. DOI: 10.1186/1710-1492-7-2.

Desrosiers, M.; Kilty, S. J. 2013. The neutrophil and chronic rhinosinusitis. In: Önerci, T. M. (ed.) Nasal physiology and pathophysiology of nasal disorders. New York, Springer: 89–93.

DiGangi, E. A.; Sirianni, J. E. 2017. Maxillary sinus infection in a 19th-century almshouse skeletal sample. International Journal of Osteoarchaeology, 27(2): 155–166.

Djordjevic, J.; Zhurov, A. I.; Richmond, S.; Consortium, V. 2016. Genetic and environmental contributions to facial morphological variation: a 3D population-based twin study. PLOS ONE [Online], 11(10): e0162250. DOI: 10.1371/journal.pone.0162250.

Djurić, M. P.; Roberts, C. A.; Rakočević, Z. B.; Djonić, D. D.; Lešić, A. R. 2006. Fractures in late Medieval skeletal populations from Serbia. American Journal of Physical Anthropology, 130(2): 167–178.

Dourado, S. M.; Noronha, C. V. 2015. Marcas visíveis e invisíveis: danos ao rosto feminino em episódios de violência conjugal. Ciência & Saúde Coletiva, 20(9): 2911– 2920.

Drake, R. L.; Vogl, W.; Mitchell, A. W. M. 2010. Gray's anatomy for students. 2nd edition. Canada, Churchill Livingstone.

157

Dykewicz, M. S. 2003. Rhinitis and sinusitis. Journal of Allergy and Clinical Immunology, 111(2 Suppl.): S520–S529.

Dykewicz, M. S.; Hamilos, D. L. 2010. Rhinitis and sinusitis. Journal of Allergy and Clinical Immunology, 125(2 Suppl. 2): S103–S115.

Earwaker, J. 1993. Anatomic variants in sinonasal CT. Radiographics, 13(2): 381–415.

Eccles, R. 2014. The nose and control of nasal airflow. In: Adkinson, N. F.; Bochner, B. S.; Burks, A. W.; Busse, W. W.; Holgate, S. T.; Lemanske, R. F.; O’Hehir, R. E. (eds.) Middleton’s allergy: principles and practice. Philadelphia, Elsevier: 640–651.

Elahi, M. M.; Frenkiel, S. 2000. Septal deviation and chronic sinus disease. American Journal of Rhinology, 14(3): 175–179.

Elledge, R. O. C.; Elledge, R.; Aquilina, P.; Hodson, J.; Dover, S. 2011. The role of alcohol in maxillofacial trauma: a comparative retrospective audit between the two centers. Alcohol, 45(3): 239–243.

Elliot, A. C.; Woodward, W. A. 2007. Statistical analysis quick reference guidebook with SPSS examples. Thousand Oaks, Sage Publications, Inc.

El-Shazly, A. E.; Poirrier, A.-L.; Cabay, J.; Lefebvre, P. P. 2012. Anatomical variations of the lateral nasal wall: the secondary and accessory middle turbinates. Clinical Anatomy, 25(3): 340–346.

Epstein, V. A.; Lanza, D. C. 2012. The diagnosis of rhinosinusitis. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 110–125.

Erkan, A. N.; Canbolat, T.; Ozer, C.; Yilmaz, I.; Ozluoglu, L. N. 2006. Polyp in concha bullosa: a case report and review of the literature. Head & Face Medicine [Online], 2: 11. DOI: 10.1186/1746-160X-2-11.

Eshed, V.; Latimer, B.; Greenwald, C. M.; Jellema, L. M.; Rothschild, B. M.; Wish- Baratz, S.; Hershkovitz, I. 2002. Button osteoma: its etiology and pathophysiology. American Journal of Physical Anthropology, 118(3): 217–230.

Fadda, G. L.; Rosso, S.; Aversa, S.; Petrelli, A.; Ondolo, C.; Succo, G. 2012. 158

Multiparametric statistical correlations between paranasal sinus anatomic variations and chronic rhinosinusitis. Acta Otorhinolaryngologica Italica, 32(4): 244–251.

Falcão, H.; Ramos, E.; Marques, A.; Barros, H. 2008. Prevalence of asthma and rhinitis in 13 year old adolescents in Porto, Portugal. Revista Portuguesa de Pneumologia, 14(6): 747–768.

Faria, P. T. M.; de Oliveira Ruellas, A. C.; Matsumoto, M. A. N.; Anselmo-Lima, W. T.; Pereira, F. C. 2002. Dentofacial morphology of mouth breathing children. Brazilian Dental Journal, 13(2): 129–132.

Fernandes, M. T. M. 1985. Coleções osteológicas. In: Museu e Laboratório Antropológico da Universidade de Coimbra (ed.) 100 anos de Antropologia em Coimbra 1885-1985. Coimbra, Imprensa da Universidade de Coimbra: 77–81.

Fernández, J. M. S.; Escudero, J. A. A.; Del Rey, A. S.; Montoya, F. S. 2000. Morphometric study of the paranasal sinuses in normal and pathological conditions. Acta Oto-Laryngologica, 120(2): 273–278.

Ferreira, A. M. C.; Cardoso, M. 2014. Indoor air quality and health in schools. Jornal Brasileiro de Pneumologia, 40(3): 259–268.

Ferreira, F. A. G. 1990. História da saúde e dos serviços de saúde em Portugal. Lisboa, Fundação Calouste Gulbenkian.

Ferreira, M. T.; Neves, M. J.; Wasterlain, S. N. 2013. Lagos leprosarium (Portugal): evidences of disease. Journal of Archaeological Science, 40(5): 2298–2307.

Ferreira, T.; Rasband, W. 2012. ImageJ user guide. ImageJ/Fiji 1.46. [Online]. [accessed June 05, 2017]. Available at: https://imagej.nih.gov/ij/.

Field, A. 2009. Discoverinf statistics using SPSS. 3rd edition. London, Sage Publications Ltd.

Fields, H. W.; Warren, D. W.; Black, K.; Phillips, C. L. 1991. Relationship between vertical dentofacial morphology and respiration in adolescents. American Journal of Orthodontics and Dentofacial Orthopedics, 99(2): 147–154.

File Jr., T. M. 2006. Sinusitis: epidemiology. In: Brook, I. (ed.) Sinusitis: from 159

microbiology to management. New York, Taylor & Francis Group: 1–14.

Fisk, W. J.; Lei-Gomez, Q.; Mendell, M. J. 2007. Meta-analyses of the associations of respiratory health effects with dampness and mold in homes. Indoor Air, 17(4): 284– 296.

Fokkens, W.; Lund, V.; Bachert, C.; Clement, P.; Helllings, P.; Holmstrom, M.; Jones, N.; Kalogjera, L.; Kennedy, D.; Kowalski, M.; Malmberg, H.; Mullol, J.; Passali, D.; Stammberger, H.; Stierna, P. 2005. EAACI position paper on rhinosinusitis and nasal polyps executive summary. European Journal of Allergy and Clinical Immunogy, 60(5): 583–601.

Fokkens, W.; Lund, V.; Mullol, J.; Bachert, C.; Alobid, I.; Baroody, F.; Cohen, N.; Cervin, A.; Douglas, R.; Gevaert, P.; Georgalas, C.; Goossens, H.; Harvey, R.; Hellings, P.; Hopkins, C.; Jones, N.; Joos, G.; Kalogjera, L.; Kern, B.; Kowalski, M.; Price, D.; Riechelmann, H.; Schlosser, R.; Senior, B.; Thomas, M.; Toskala, E.; Voegels, R.; Wang, D. Y.; Wormald, P. J. 2012. European position paper on rhinosinusitis and nasal polyps 2012. Rhinology, 50(23 Suppl.): S1–S298.

Fokkens, W.; Lund, V.; Mullol, J.; Bachert, C.; Cohen, N.; Cobo, R.; Desrosiers, M.; Hellings, P.; Holmstrom, M.; Hytönen, M.; Jones, N.; Kalogjera, L.; Kennedy, D.; Klossek, J. M.; Kowalski, M.; Meltzer, E.; Naclerio, B.; Passali, D.; Price, D.; Riechelmann, H.; Scadding, G.; Stammberger, H.; Thomas, M.; Voegels, R.; Wang, D.- Y. 2007. European position paper on rhinosinusitis and nasal polyps 2007. Rhinology, 20(Suppl.): S1–S136.

Formulario: Contra a coryza. 1887. Coimbra Médica, 7(14): 226.

Fraga, S.; Ramos, E.; Martins, A.; Samúdio, M. J.; Silva, G.; Guedes, J.; Fernandes, E. O.; Barros, H. 2008. Qualidade do ar interior e sintomas respiratórios em escolas do Porto. Revista Portuguesa de Pneumologia, 14(4): 487–507.

Fraioli, R. E.; Branstetter, B. F.; Deleyiannis, F. W.-B. 2008. Facial fractures: beyond le fort. Otolaryngologic Clinics of North America, 41(1): 51–76.

Francisco, F. C.; Carvalho, A. C. P.; Francisco, V. F. M.; Francisco, M. C.; Neto, G. T. 2007. Evaluation of 1000 lacrimal ducts by dacryocystography. The British Journal of

160

Ophthalmology, 91(1): 43–46.

Freitas, M. C.; Pacheco, A. M. G.; Verburg, T. G.; Wolterbeek, H. T. 2010. Effect of particulate matter, atmospheric gases, temperature, and humidity on respiratory and circulatory diseases’ trends in Lisbon, Portugal. Environmental Monitoring and Assessment, 162(1–4): 113–121.

Gallego-Romero, D.; Llamas-Carrera, J. M.; Torres-Lagares, D.; Paredes, V.; Espinar, E.; Guevara, E.; Gutierrez-Perez, J. L. 2012. Long-term stability of surgical-orthodontic correction of class III malocclusions with long-face syndrome. Medecina Oral, Patología Oral y Cirugía Bucal [Online], 17(3): e435-e441. DOI: 10.4317/medoral.17647.

Galloway, A.; Wedel, V. L. 2014. Bones of the skull, the dentition, and osseous structures of the throat. In: Wedel, V. L.; Galloway, A. (eds.) Broken bones: anthropological analysis of blunt force trauma. 2nd edition. Springfield, Charles C Thomas: 133–160.

Galvan, O.; Gassner, E. M.; Neher, A.; Gunkel, A. R. 2007. Fibro-osseous lesion of the middle turbinate: ossifying fibroma or fibrous dysplasia? The Journal of Laryngology & Otology, 121(12): 1201–1203.

Garcia, C. 1897. Revista extrangeira: XII Congresso Internacional de Medicina em Moscou de 19 a 26 d’agosto de 1897. Secção de laryngologia e rhinologia. A Medicina Contemporanea, 15(44): 357–361, 369–370, 373–378.

Garcia, M. S. J. 2007. Maleitas do corpo em tempos medievais: indicadores paleodemográficos, de stresse e paleopatológicos numa série osteológica urbana de Leiria. Doctoral dissertation. Coimbra, University of Coimbra.

Garcia, S.; Magno, G.; Amoroso, A.; Matos, V. 2016. A case study of leprosy from the Luís Lopes collection, National Museum of Natural History and Science, Lisbon. Poster presented at the V Jornadas Portuguesas de Paleopatologia; Coimbra, Portugal; 25-26 Novembro 2016.

Gassner, R.; Tuli, T.; Hächl, O.; Rudisch, A.; Ulmer, H. 2003. Cranio-maxillofacial trauma: a 10 year review of 9,543 cases with 21,067 injuries. Journal of Cranio-

161

Maxillofacial Surgery, 31(1): 51–61.

Gawlikowska-Sroka, A.; Kwiatkowska, B.; Dąbrowski, P.; Dzięciołowska-Baran, E.; Szczurowski, J.; Nowakowski, D. 2013. Respiratory diseases in the late middle ages. Respiratory Physiology & Neurobiology, 187(1): 123–127.

Gawlikowska-Sroka, A.; Kwiatkowska, B.; Szczurowski, J.; Gronkiewicz, S.; Dąbrowski, P. 2016a. Two cases of osteoid osteoma in skulls dating from the 13–14th centuries from St. Elisabeth’s Church in Wrocław, Poland. Anthropological Review, 79(1): 87–94.

Gawlikowska-Sroka, A.; Szczurowski, J.; Kwiatkowska, B.; Konczewski, P.; Dzieciołowska-Baran, E.; Donotek, M.; Walecka, A.; Nowakowski, D. 2016b. Concha bullosa in paleoanthropological material. In: Pokorski, M. (ed.) Advances in experimental medicine and biology. Cham, Springer International Publishing: 65–73.

Geiseler, P. J.; Nelson, K. E.; Levin, S.; Reddi, K. T.; Moses, V. K. 1980. Community- acquired purulent meningitis: a review of 1,316 cases during the antibiotic era, 1954- 1976. Reviews of Infectious Diseases, 2(5): 725–745.

Georgalas, C. 2013. Osteitis and paranasal sinus inflammation: what we know and what we do not. Current Opinion in Otolaryngology & Head and Neck Surgery, 21(1): 45– 49.

Ghasemi, A.; Zahediasl, S. 2012. Normality tests for statistical analysis: a guide for non-statisticians. International Journal of Endocrinology and Metabolism, 10(2): 486– 489.

Giacchi, R. J.; Lebowitz, R. A.; Yee, H. T.; Light, J. P.; Jacobs, J. B. 2001. Histopathologic evaluation of the ethmoid bone in chronic sinusitis. American Journal of Rhinology, 15(3): 193–197.

Göçmen, G.; Borahan, M. O.; Aktop, S.; Dumlu, A.; Pekiner, F. N.; Göker, K. 2015. Effect of septal deviation, concha bullosa and haller’s cell on maxillary sinus’s inferior pneumatization; a retrospective study. The Open Dentistry Journal, 9: 282–286.

Godinho, R. M. 2008. Vestígios de um império passado: a necrópole de Santo Antão-o- Novo e a Lisboa dos séculos XVI-XVIII. Master dissertation. Coimbra, University of 162

Coimbra.

Goff, R.; Weindling, S.; Gupta, V.; Nassar, A. 2015. Intraosseous hemangioma of the middle turbinate: a case report of a rare entity and literature review. The Neuroradiology Journal, 28(2): 148–151.

Gonçalves, G. R. 2008. Para que servem as ruas? A acção do Estado na transformação dos usos do espaço público urbano (séc. XIX – XX). Ponto Urbe [Online], 2. DOI: 10.4000/pontourbe.1906.

Gozeler, M. S.; Kilic, K.; Sakat, M. S.; Ucuncu, H. 2016. A rare location for fibrous dysplasia. The middle turbinate. European Annals of Otorhinolaryngology, Head and Neck Diseases, 133(5): 371–372.

Grazia, K. J. A.; Miranda, G. G.; Walker, J. K.; Aguirre, V. S. 2014. Prevaléncia de variantes anatómicas naso-sinusales: importancia en el informe radiológico y en la cirugía endoscópica funcional. Revista Chilena de Radiología, 20(1): 5–12.

Gregg, J. B.; Gregg, P. S. 1987. Dry bones, Dakota Territory reflected: an illustrated descriptive analysis of the health and well being of previous people and cultures as is mirrored in their remnants. Sioux Falls, Sioux Printing.

Gregurić, T.; Baudoin, T.; Tomljenović, D.; Grgić, M.; Štefanović, M.; Kalogjera, L. 2016. Relationship between nasal septal deformity, symptoms and disease severity in chronic rhinosinusitis. European Archives of Oto-Rhino-Laryngology, 273(3): 671–677.

Gruss, J. S.; Hurwitz, J. J.; Nik, N. A.; Kassel, E. E. 1985. The pattern and incidence of nasolacrimal injury in naso-orbital-ethmoid fractures: the role of delayed assessment and dacryocystorhinostomy. British Journal of Plastic Surgery, 38(1): 116–121.

Gudis, D. A.; Woodworth, B. A.; Cohen, N. A. 2012. Sinonasal physiology. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 21–31.

Guyuron, B. 2012. Surgical anatomy and physiology of the nose. In: Guyuron, B. (ed.) Rhinoplasty. New York, Elsevier: 1–26.

Guyuron, B.; Behmand, R. A. 2003. Caudal nasal deviation. Plastic and Reconstructive

163

Surgery, 111(7): 2449–2457.

Guyuron, B.; Uzzo, C. D.; Scull, H. 1999. A practical classification of septonasal deviation and an effective guide to septal surgery. Plastic and Reconstructive Surgery, 104(7): 2202–2209.

Haack, J.; Papel, I. D. 2009. Caudal septal deviation. Otolaryngologic Clinics of North America, 42(3): 427–436.

Hackett, C. J. 1976. Diagnostic criteria of syphilis, yaws and treponarid (treponematoses) and of some other diseases in dry bones (for use in osteoarchaeology). Berlin, Springer-Verlag.

Hamilos, D. L. 2011. Chronic rhinosinusitis: epidemiology and medical management. Journal of Allergy and Clinical Immunology, 128(4): 693–707.

Han, D. S. Y.; Han, Y. S.; Park, J. H. 2011. A new approach to the treatment of nasal bone fracture: radiologic classification of nasal bone fractures and its clinical application. Journal of Oral and Maxillofacial Surgery, 69(11): 2841–2847.

Han, J. K.; Wold, S. M. 2012. Acute rhinosinusitis. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 164–170.

Harar, R. P. S.; Chadha, N. K.; Rogers, G. 2004. The role of septal deviation in adult chronic rhinosinusitis: a study of 500 patients. Rhinology, 42(3): 126–130.

Harari, D.; Redlich, M.; Miri, S.; Hamud, T.; Gross, M. 2010. The effect of mouth breathing versus nasal breathing on dentofacial and craniofacial development in orthodontic patients. Laryngoscope, 120(10): 2089–2093.

Hashemi, H. M.; Beshkar, M. 2011. The prevalence of maxillofacial fractures due to domestic violence – A retrospective study in a hospital in Tehran, Iran. Dental Traumatology, 27(5): 385–388.

Hastan, D.; Fokkens, W. J.; Bachert, C.; Newson, R. B.; Bislimovska, J.; Bockelbrink, A.; Bousquet, P. J.; Brozek, G.; Bruno, A.; Dahlén, S. E.; Forsberg, B.; Gunnbjörnsdóttir, M.; Kasper, L.; Krämer, U.; Kowalski, M. L.; Lange, B.; Lundbäck,

164

B.; Salagean, E.; Todo-Bom, A.; Tomassen, P.; Toskala, E.; van Drunen, C. M.; Bousquet, J.; Zuberbier, T.; Jarvis, D.; Burney, P. 2011. Chronic rhinosinusitis in Europe - An underestimated disease. A GA2LEN study. Allergy, 66(9): 1216–1223.

Hatipoglu, H. G.; Cetin, M. A.; Yuksel, E. 2005. Concha bullosa types: their relationship with sinusitis, ostiomeatal and frontal recess disease. Diagnostic and Interventional Radiolology, 11(3): 145–149.

Havas, T. E.; Motbey, J. A.; Gullane, P. J. 1988. Prevalence of incidental abnormalities on computed tomographic scans of the paranasal sinuses. Archives of Otolaryngology- Head and Neck Surgery, 114(8): 856–859.

Hellings, P. W.; Klimek, L.; Cingi, C.; Agache, I.; Akdis, C.; Bachert, C.; Bousquet, J.; Demoly, P.; Gevaert, P.; Hox, V.; Hupin, C.; Kalogjera, L.; Manole, F.; Mösges, R.; Mullol, J.; Muluk, N. B.; Muraro, A.; Papadopoulos, N.; Pawankar, R.; Rondon, C.; Rundenko, M.; Seys, S. F.; Toskala, E.; Van Gerven, L.; Zhang, L.; Zhang, N.; Fokkens, W. J. 2017. Non-allergic rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Allergy, 72(11): 1657–1665.

Higgins, T. S.; Reh, D. D. 2012. Environmental pollutants and allergic rhinitis. Current Opinion in Otolaryngology & Head and Neck Surgery, 20(3): 209–214.

Higuera, S.; Lee, E. I.; Cole, P.; Hollier, L. H.; Stal, S. 2007. Nasal trauma and the deviated nose. Plastic and Reconstructive Surgery, 120(7 Suppl. 2): S64–S75.

Hincak, Z.; Cavalli, F.; Durman, A. 2013. The cranial analysis of eight skulls from collective grave of the Early Bronze Age Vucedol site (East Slavonia, Croatia). Collegium Antropologicum, 37(1): 229–237.

Holden, W. E.; Wilkins, J. P.; Harris, M.; Milczuk, H. A.; Giraud, G. D. 1999. Temperature conditioning of nasal air: effects of vasoactive agents and involvement of nitric oxide. Journal of Applied Physiology, 87(4): 1260–1265.

Holton, N.; Yokley, T.; Butaric, L. 2013. The morphological interaction between the nasal cavity and maxillary sinuses in living humans. The Anatomical Record, 296(3): 414–426.

Holton, N.; Yokley, T.; Figueroa, A. 2012. Nasal septal and craniofacial form in 165

European- and African-derived populations. Journal of Anatomy, 221(3): 263–274.

Hoppa, R. D. 1996. Representativeness and bias in cemetery samples. Implications for palaeodemoggraphic reconstructions of past populations. Doctoral dissertation. Hamilton, McMaster University.

Hoskison, E.; Daniel, M.; Rowson, J. E.; Jones, N. S. 2012. Evidence of an increase in the incidence of odontogenic sinusitis over the last decade in the UK. The Journal of Laryngology & Otology, 126(1): 43–46.

Howell, D. C. 2014. Fundamental statistics for the behavioural sciences. 8th edition. Wadsworth, Cengage Learning.

Howells, W. W. 1973. Cranial variation in man: a study by multivariate analysis of patterns of difference among recent human populations. Massachusetts, Harvard University.

Hur, M.-S.; Won, H.-S.; Kwak, D.-S.; Chung, I.-H.; Kim, I.-B. 2016. Morphological patterns and variations of the nasal septum components and their clinical implications. Journal of Craniofacial Surgery, 27(8): 2164–2167.

Hussain, K.; Wijetunge, D. B.; Grubnic, S.; Jackson, I. T. 1994. A comprehensive analysis of craniofacial trauma. The Journal of Trauma, 36(1): 34–47.

Hwang, K.; You, S. H.; Kim, S. G.; Lee, S. I. 2006. Analysis of nasal bone fractures; A six-year study of 503 patients. The Journal of Craniofacial Surgery, 17(2): 261–264.

Ihde, L. L.; Forrester, D. M.; Gottsegen, C. J.; Masih, S.; Patel, D. B.; Vachon, L. A.; White, E. A.; Matcuk, G. R. 2011. Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. Radiographics, 31(7): 1865–1882.

IHS - Headache Classification Committee of the International Headache Society 2013. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia, 33(9): 629–808.

Iida, S.; Hassfeld, S.; Reuther, T.; Schweigert, H.-G.; Haag, C.; Klein, J.; Mühling, J. 2003. Maxillofacial fractures resulting from falls. Journal of Cranio-Maxillofacial Surgery, 31(5): 278–283.

166

Isidro, A.; Malgosa, A. 2003. Paleopatología: la enfermedad no escrita. Barcelona, Elsevier-Masson.

Isobe, M.; Murakami, G.; Kataura, A. 1998. Variations of the uncinate process of the lateral nasal wall with clinical implications. Clinical Anatomy, 11(5): 295–303.

Jaakkola, M. S.; Quansah, R.; Hugg, T. T.; Heikkinen, S. A. M.; Jaakkola, J. J. K. 2013. Association of indoor dampness and molds with rhinitis risk: a systematic review and meta-analysis. Journal of Allergy and Clinical Immunology [Online], 132(5): 1099– 1110.e18. DOI: 10.1016/j.jaci.2013.07.028.

Jackes, M. 2011. Representativeness and bias in archaeological skeletal samples. In: Agarwal, S. C.; Glencross, B. A. (eds.) Social bioarchaeology. Oxford, Wiley- Blackwell: 107–146.

Jackman, J. H.; Kennedy, R. J. 2006. Pathophisiology of sinusitis. In: Brook, I. (ed.) Sinusitis: from microbiology to management. Infectious disease and therapy. New York, Taylor & Francis Group: 109–134.

Jankowski, R.; Nguyen, D. T.; Poussel, M.; Chenuel, B.; Gallet, P.; Rumeau, C. 2016. Sinusology. European Annals of Otorhinolaryngology, Head and Neck Diseases, 133(4): 263–268.

Janovic, A.; Antic, S.; Rakocevic, Z.; Djuric, M. 2013. Paranasal sinus osteoma: is there any association with anatomical variations? Rhinology, 51(1): 54–60.

Javadrashid, R.; Naderpour, M.; Asghari, S.; Fouladi, D. F.; Ghojazadeh, M. 2014. Concha bullosa, nasal septal deviation and paranasal sinusitis; a computed tomographic evaluation. B-ENT, 10(4): 291–298.

Jefferson, Y. 2010. Mouth breathing: adverse effects on facial growth, health, academics, and behavior. General Dentistry, 58(1): 18–25.

Jeon, S. P.; Kang, S. J.; Kim, J. W.; Kim, Y. H.; Sun, H. 2013. New nasal fracture classification for patients with silicone implants. Journal of Plastic Surgery and Hand Surgery, 47(5): 363–367.

Jin, H. R.; Lee, J. Y.; Jung, W. J. 2007. New description method and classification

167

system for septal deviation. Journal of Rhinology, 14(1): 27–31.

Jones, N. 2001. The nose and paranasal sinuses physiology and anatomy. Advanced Drug Delivery Reviews, 51(1–3): 5–19.

Jones, N. S. 2002. CT of the paranasal sinuses: a review of the correlation with clinical, surgical and histopathological findings. Clinical Otolaryngology and Allied Sciences, 27(1): 11–17.

Jones, N. S.; Strobl, A.; Holland, I. 1997. A study of the CT findings in 100 patients with rhinosinusitis and 100 controls. Clinical Otolaryngology and Allied Sciences, 22(1): 47–51.

Juarez, C. A.; Hughes, C. E. 2014. Intimate partner violence (IPV): demographics, skeletal injury patterns, and the limitations. In: Wedel, V. L.; Galloway, A. (eds.) Broken bones: anthropological analysis of blunt force trauma. 2nd edition. Springfield, Charles C Thomas: 350–361.

Juliano, M. L.; Machado, M. A. C.; Carvalho, L. B. C.; Prado, L. B. F.; Prado, G. F. 2009. Mouth breathing children have cephalometric patterns similar to those of adult patients with obstructive sleep apnea syndrome. Arquivos de Neuro-Psiquiatria, 67(3B): 860–865.

Jung, H.; Park, S. K.; Kim, J.-R. 2012. Polyps originating from accessory middle turbinate and secondary middle turbinate. The Journal of Laryngology & Otology, 126(7): 729–732.

Junqueira, L. C.; Carneiro, J. 2008. Histologia básica. 11th edition. Rio de Janeiro, Guanabara Koogan.

Kajan, Z. D.; Khademi, J.; Nemati, S.; Niksolat, E. 2016. The effects of septal deviation, concha bullosa, and their combination on the depth of posterior palatal arch in cone-beam computed tomography. Journal of Dentistry, Shiraz University of Medical Sciences, 17(1): 26–31.

Kakizaki, H. 2015. Anatomy, physiology, and immunology of the lacrimal system. In: Ali, M. J. (ed.) Principles and practice of lacrimal surgery. New Delhi, Springer India: 17–33. 168

Kamal, S.; Ali, M. J. 2015. Primary acquired nasolacrimal duct obstruction (PANDO) and secondary acquired lacrimal duct obstructions (SALDO). In: Ali, M. J. (ed.) Principles and practice of lacrimal surgery. New Delhi, Springer India: 133–141.

Kantarci, M.; Karasen, R. M.; Alper, F.; Onbas, O.; Okur, A.; Karaman, A. 2004. Remarkable anatomic variations in paranasal sinus region and their clinical importance. European Journal of Radiology, 50(3): 296–302.

Kaplan, M. J.; Harsh IV, G. R.; Joshua, B.; Chute, D. J.; Berry, G. J. 2012. Pathology of the sinonasal region and anterior and central skull base. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 548–569.

Kapusuz Gencer, Z.; Ozkiris, M.; Okur, A.; Karacavus, S.; Saydam, L. 2013. The effect of nasal septal deviation on maxillary sinus volumes and development of maxillary sinusitis. European Archives of Oto-Rhino-Laryngology, 270(12): 3069–3073.

Kawalski, H.; Spiewak, P. 1998. How septum deformations in newborns occur. International Journal of Pediatric Otorhinolaryngology, 44(1): 23–30.

Kawauchi, H. 2013. Macrophage. In: Önerci, T. M. (ed.) Nasal physiology and pathophysiology of nasal disorders. New York, Springer: 77–88.

Kayalioglu, G.; Oyar, O.; Govsa, F. 2000. Nasal cavity and paranasal sinus bony variations: a computed tomographic study. Rhinology, 38(3): 108–113.

Keast, A.; Sofie, Y.; Dawes, P.; Lyons, B. 2008. Anatomical variations of the paranasal sinuses in Polynesian and New Zealand European computerized tomography scans. Otolaryngology-Head and Neck Surgery, 139(2): 216–221.

Keir, J. 2009. Why do we have paranasal sinuses? The Journal of Laryngology & Otology, 123(1): 4–8.

Kendall, R.; Kendall, E. J.; Macleod, I.; Gowland, R.; Beaumont, J. 2015. An unusual exostotic lesion of the maxillary sinus from Roman Lincoln. International Journal of Paleopathology, 11: 45–50.

Kennedy, D. W.; Senior, B. A.; Gannon, F. H.; Montone, K. T.; Hwang, P.; Lanza, D.

169

C. 1998. Histology and histomorphometry of ethmoid bone in chronic rhinosinusitis. The Laryngoscope, 108(4): 502–507.

Kennedy, D. W.; Zinreich, S. J. 1988. The functional endoscopic approach to inflammatory sinus disease: current perspectives and technique modifications. American Journal of Rhinology, 2(3): 89–96.

Kern, R. C.; Decker, J. R. 2013. Functional defense mechanisms of the nasal respiratory epithelium. In: Önerci, T. M. (ed.) Nasal physiology and pathophysiology of nasal disorders. New York, Springer: 27–46.

Khalid, A. N.; Hunt, J.; Perloff, J. R.; Kennedy, D. W. 2002. The role of bone in chronic rhinosinusitis. The Laryngoscope, 112(11): 1951–1957.

Khanobthamchai, K.; Shankar, L.; Hawke, M.; Bingham, B. 1991. The secondary middle turbinate. The Journal of Otolaryngology, 20(6): 412–413.

Kim, H. J.; Cho, M. J.; Lee, J.-W.; Kim, Y. T.; Kahng, H.; Kim, H. S.; Hahm, K.-H. 2006. The relationship between anatomic variations of paranasal sinuses and chronic sinusitis in children. Acta Oto-Laryngologica, 126(10): 1067–1072.

Kim, H. Y. 2013. Statistical notes for clinical researchers: assessing normal distribution (2) using skewness and kurtosis. Restorative Dentistry & Endodontics [Online], 38(1): 52-54. DOI: 10.5395/rde.2013.38.1.52

Kim, I.-S.; Lee, M.-Y.; Lee, K.-I.; Kim, H.-Y.; Chung, Y.-J. 2008. Analysis of the development of the nasal septum according to age and gender using MRI. Clinical and Experimental Otorhinolaryngology, 1(1): 29–34.

Kinsui, M. M.; Guilherme, A.; Yamashita, H. K. 2002. Variações anatômicas e sinusopatias: estudo por tomografia computadorizada. Revista Brasileira de Otorrinolaringologia, 68(5): 645–652.

Kline, R. B. 2011. Principles and practice of structural equation modeling. 3rd edition. New York, The Guilford Press.

Koo, S. K.; Kim, J. D.; Moon, J. S.; Jung, S. H.; Lee, S. H. 2017. The incidence of concha bullosa, unusual anatomic variation and its relationship to nasal septal deviation:

170

a retrospective radiologic study. Auris Nasus Larynx, 44(5): 561–570.

Koskinen, O. M.; Husman, T. M.; Meklin, T. M.; Nevalainen, A. I. 1999. The relationship between moisture or mould observations in houses and the state of health of their occupants. The European Respiratory Journal, 14(6): 1363–1367.

Krakowka, K. 2017. Violence-related trauma from the Cistercian Abbey of St Mary Graces and a late Black Death cemetery. International Journal of Osteoarchaeology, 27(1): 56–66.

Krenz-Niedbała, M.; Łukasik, S. 2016. Prevalence of chronic maxillary sinusitis in children from rural and urban skeletal populations in Poland. International Journal of Paleopathology, 15: 103–112.

Kridel, R. W. H. 2004. Considerations in the etiology, treatment, and repair of septal perforations. Facial Plastic Surgery Clinics of North America, 12(4): 435–450.

Krouse, J. H.; Stachler, R. J. 2006. Anatomy and physiology of the paranasal sinuses. In: Brook, I. (ed.) Sinusitis: from microbilogy to management. New York, Taylor & Francis Group: 95–108.

Kruse, A.; Pieles, U.; Riener, M. O.; Zunker, C.; Bredell, M. G.; Gratz, K. W. 2009. Craniomaxillofacial fibrous dysplasia: a 10-year database 1996-2006. British Journal of Oral and Maxillofacial Surgery, 47(4): 302–305.

Kucybała, I.; Janik, K. A.; Ciuk, S.; Storman, D.; Urbanik, A. 2017. Nasal septal deviation and concha bullosa – Do they have an impact on maxillary sinus volumes and prevalence of maxillary sinusitis? Polish Journal of Radiology, 82: 126–133.

Kwak, S. G.; Kim, J. H. 2017. Central limit theorem: the cornerstone of modern statistics. Korean Journal of Anesthesiology, 70(2): 144–156.

Kwiatkowska, B.; Gawlikowska-Sroka, A.; Szczurowski, J.; Nowakowski, D.; Dzięciołowska-Baran, E. 2011. A case of concha bullosa mucopyocele in a Medieval human skull. International Journal of Osteoarchaeology, 21(3): 367–370.

Laine, F. J.; Smoker, W. R. 1992. The ostiomeatal unit and endoscopic surgery: anatomy, variations, and imaging findings in inflammatory diseases. American Journal

171

of Roentgenology, 159(4): 849–857.

Lam, W. W. M.; Liang, E. Y.; Woo, J. K. S.; Van Hasselt, A.; Metreweli, C. 1996. The etiological role of concha bullosa in chronic sinusitis. European Radiology, 6(4): 550– 552.

Landis, J. R.; Koch, G. G. 1977. The measurement of observer agreement for categorical data. Biometrics, 33(1): 159–174.

Lane, A. P.; Turner, J. H. 2012. Etiologic factors in chronic rhinosinusitis. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 171–181.

Langley, N. R.; Jantz, L. M.; Ousley, S. D.; Jantz, R. L.; Milner, G. 2016. Data collection procedures for forensic skeletal material 2.0. [Online]. Knoxville, Tennessee. [Accessed June 05, 2017] Available at: https://fac.utk.edu/wp- content/uploads/2016/03/DCP20_webversion.pdf.

Lanza, D. C.; Kennedy, D. W. 1997. Adult rhinosinusitis defined. Otolaryngology-Head and Neck Surgery, 117(3 Suppl.): S1–S7.

Larrea-Oyarbide, N.; Valmaseda-Castellón, E.; Berini-Aytés, L.; Gay-Escoda, C. 2007. Osteomas of the craniofacial region. Review of 106 cases. Journal of Oral Pathology & Medicine, 37(1): 38–42.

Lau, C. L.; Ching, W. M.; Tong, W. L.; Chan, K. L.; Tsui, K. L.; Kam, C. W. 2008. 1700 victims of intimate partner violence: characteristics and clinical outcomes. Hong Kong Medical Journal, 14(6): 451–457.

Laverick, S.; Patel, N.; Jones, D. C. 2008. Maxillofacial trauma and the role of alcohol. British Journal of Oral and Maxillofacial Surgery, 46(7): 542–546.

Lawson, W.; Patel, Z. M.; Lin, F. Y. 2008. The development and pathologic processes that influence maxillary sinus pneumatization. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, 291(11): 1554–1563.

Le, B. T.; Dierks, E. J.; Ueeck, B. A.; Homer, L. D.; Potter, B. F. 2001. Maxillofacial injuries associated with domestic violence. Journal of Oral and Maxillofacial Surgery,

172

59(11): 1277–1283.

Lee, D.-H.; Joo, Y.-E.; Lim, S.-C. 2013. Accessory middle turbinate accompanying a mucocele. Surgical Practice, 17(2): 74–76.

Lee, J. H.; Cho, B. K.; Park, W. J. 2010. A 4-year retrospective study of facial fractures on Jeju, Korea. Journal of Cranio-Maxillofacial Surgery, 38(3): 192–196.

Lee, J. T.; Kennedy, D. W.; Palmer, J. N.; Feldman, M.; Chiu, A. G. 2006. The incidence of concurrent osteitis in patients with chronic rhinosinusitis: a clinicopathological study. American Journal of Rhinology, 20(3): 278–282.

Lee, K. H. 2009. Interpersonal violence and facial fractures. Journal of Oral and Maxillofacial Surgery, 67(9): 1878–1883.

Lee, K. H.; Snape, L.; Steenberg, L. J.; Worthington, J. 2007. Comparison between interpersonal violence and motor vehicle accidents in the aetiology of maxillofacial fractures. ANZ Journal of Surgery, 77(8): 695–698.

Lee-Wing, M. W.; Ashenhurst, M. E. 2001. Clinicopathologic analysis of 166 patients with primary acquired nasolacrimal duct obstruction. Ophthalmology, 108(11): 2038– 2040.

Lessa, F. C. R.; Enoki, C.; Feres, M. F. N.; Valera, F. C. P.; Lima, W. T. A.; Matsumoto, M. A. N. 2005. Influência do padrão respiratório na morfologia craniofacial. Revista Brasileira de Otorrinolaringologia, 71(2): 156–160.

Leung, N.; Mawby, T. A. R.; Turner, H.; Qureishi, A. 2016. Osteitis and chronic rhinosinusitis: a review of the current literature. European Archives of Oto-Rhino- Laryngology, 273(10): 2917–2923.

Lewis, M. E.; Roberts, C. A.; Manchester, K. 1995. Comparative study of the prevalence of maxillary sinusitis in later Medieval urban and rural populations in Northern England. American Journal of Physical Anthropology, 98(4): 497–506.

Liebe-Harkort, C. 2012. Cribra orbitalia, sinusitis and linear enamel hypoplasia in Swedish Roman Iron Age adults and subadults. International Journal of Osteoarchaeology, 22(4): 387–397.

173

Lima, P. 1908. Bibliotheca. Catalogo das dissertações inauguraes apresentadas á Escola Medica desde a sua fundação. In: D’Almeida, T. (ed.) Annuario da Escola Medico- Cirurgica do Porto II. Porto, Typographia Industrial Portugueza (A Vapor): 183–255.

Lin, J. K.; Wheatley, F. C.; Handwerker, J.; Harris, N. J.; Wong, B. J. F. 2014. Analyzing nasal septal deviations to develop a new classification system. JAMA Facial Plastic Surgery, 16(3): 183–187.

Lin, Y.-L.; Lin, Y.-S.; Su, W.-F.; Wang, D. C.-H. 2006. A secondary middle turbinate co-existing with an accessory middle turbinate: an unusual combination of two anatomic variations. Acta Oto-Laryngologica, 126(4): 429–431.

Linnau, K. F.; Stanley, R. B.; Hallam, D. K.; Gross, J. A.; Mann, F. A. 2003. Imaging of high-energy midfacial trauma: what the surgeon needs to know. European Journal of Radiology, 48(1): 17–32.

Lino, R. 2001. Casas portuguesas: alguns apontamentos sobre o arquitectar das casas simples. 10th edition. Lisboa, Cotovia.

Lloyd, G. A. S. 1988. Diagnostic imaging of the nose and paranasal sinuses. London, Springer.

Lloyd, G. A. S. 1990. CT of the paranasal sinuses: study of a control series in relation to endoscopic sinus surgery. The Journal of Laryngology & Otology, 104(6): 477–481.

Lloyd, G. A. S.; Lund, V. J.; Scadding, G. K. 1991. CT of the paranasal sinuses and functional endoscopic surgery: a critical analysis of 100 symptomatic patients. The Journal of Laryngology & Otology, 105(3): 181–185.

Lobato, J. C. 1931. Faculdade de Medicina de Lisboa: Hospital Escolar. Estatística do segundo ano de Clínica da Garganta-Nariz-Ouvidos. Novembro de 1929 a Novembro de 1930. Lisboa Médica, 6(8 Suppl.): S35–S49.

Lopatiene, K.; Babarskas, A. 2002. Malocclusion and upper airway obstruction. Medicina, 38(3): 277–283.

Lopes, C. C. R. 2001. As clarissas de Coimbra dos séculos XIV a XVII : paleobiologia de uma comunidade religiosa de Santa Clara-a-Velha. Master dissertation. Coimbra,

174

University of Coimbra.

Lopes, C. C. R. 2014. As mil caras de uma doença – Sífilis na sociedade Coimbrã no início do século XX. Doctoral dissertation. Coimbra, University of Coimbra.

Lopes, C.; Powell, M. L.; Santos, A. L. 2010. Syphilis and cirrhosis: a lethal combination in a XIX century individual identified from the Medical Schools Collection at the University of Coimbra (Portugal). Memórias do Instituto Oswaldo Cruz, 105(8): 1050–1053.

Lothrop, H. A. 1903. The anatomy of the inferior ethmoidal turbinate bone with particular reference to cell formation; Surgical importance of such ethmoid cells. Annals of Surgery, 38(2): 233–255.

Loureiro, G.; Loureiro, C.; Neves, J. C.; Miguéis, A. C.; Nunes, C. 2004. Rinite alérgica. In: Todo-Bom, A. (ed.) Atlas da imunoalergologia. Algés, Euromédice, Edições Médicas: 95–115.

Lovell, N. C. 1997. Trauma analysis in Palaeopathology. Yearbook of Physical Anthropology, 40: 139–170.

Lund, V. J. 2012. Malignant sinonasal tumors. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 409–424.

Lund, V. J.; Kennedy, D. W. 1995. Quantification for staging sinusitis. The staging and therapy group. The Annals of Otology, Rhinology & Laryngology, 167(Suppl.): S17– S21.

Lund, V. J.; Stammberger, H.; Fokkens, W. J.; Beale, T.; Bernal-Sprekelsen, M.; Eloy, P.; Georgalas, C.; Gerstenberger, C.; Hellings, P.; Herman, P.; Hosemann, W. G.; Jankowski, R.; Jones, N.; Jorissen, M.; Leunig, A.; Onerci, M.; Rimmer, J.; Rombaux, P.; Simmen, D.; Tomazic, P. V.; Tschabitscherr, M.; Welge-Luessen, A. 2014. European position paper on the anatomical terminology of the internal nose and paranasal sinuses. Rhinology, 24(Suppl.): S1–S34.

Lundberg, J. O. 2008. Nitric oxide and the paranasal sinuses. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, 291(11): 1479–1484. 175

Lundberg, J. O.; Nordvall, S. L.; Weitzberg, E.; Kollberg, H.; Alving, K. 1996. Exhaled nitric oxide in paediatric asthma and cystic fibrosis. Archives of Disease in Childhood, 75(4): 323–326.

Lundberg, J. O.; Weitzberg, E.; Nordvall, S. L.; Kuylenstierna, R.; Lundberg, J. M.; Alving, K. 1994. Primarily nasal origin of exhaled nitric oxide and absence in Kartagener’s syndrome. The European Respiratory Journal, 7(8): 1501–1504.

Lundström, A.; McWilliam, J. S. 1987. A comparison of vertical and horizontal cephalometric variables with regard to heritability. European Journal of Orthodontics, 9(2): 104–108.

Lynnerup, N.; Boldsen, J. 2012. Leprosy (Hansen’s disease). In: Grauer, A. L. (ed.) A companion to Paleopathology. Oxford, Wiley-Blackwell: 458–471.

Machado, A.; Hines, D.; Matos, M. 2016. Help-seeking and needs of male victims of intimate partner violence in Portugal. Psychology of Men & Masculinity, 17(3): 255– 264.

Machado, A.; Matos, M. 2014. Homens vítimas na intimidade: análise metodológica dos estudos de prevalência. Psicologia & Sociedade, 26(3): 726–736.

Madani, G.; Beale, T. J. 2009. Sinonasal inflammatory disease. Seminars in Ultrasound, CT and MRI, 30(1): 17–24.

Madani, S. A.; Hashemi, S. A.; Kianejad, A. H.; Heideri, S. 2013. Association between anatomical variations of the sinonasal region and chronic rhino sinusitis: a prospective case series study. Scientific Journal of the Faculty of Medicine in Niš, 30(2): 73–77.

Magalhães, B. M. 2013. Os irreconciliados da fé da Inquisição de Évora: análise paleobiológica de uma amostra osteológica Moderna proveniente do “Quintal da limpeza dos cárceres”. Master dissertation. Coimbra, University of Coimbra.

Magalhães, B. M.; Lopes, C.; Santos, A. L. 2017. Differentiating between rhinosinusitis and mastoiditis surgery from postmortem medical training: a study of two identified skulls and hospital records from early 20th century Coimbra, Portugal. International Journal of Paleopathology, 17: 10–17.

176

Magnano, M.; Boffano, P.; Machetta, G.; Garibaldi, E.; Delmastro, E.; Gabriele, P. 2015. Chondrosarcoma of the nasal septum. European Archives of Otorhinolaryngology, 272(3): 765–772.

Magryś, A.; Paluch-Oleś, J.; Kozioł-Montewka, M. 2011. Microbiology aspects of rhinosinusitis. In: Marseglia, G. L.; Caimmi, D. P. (eds.) Peculiar aspects of rhinosinusitis. Rijeka, InTech: 27–38.

Manchester, K. 1994. Rhinomaxillary lesions in syphilis: differential diagnosis. In: Dutour, O.; Pálfi, G.; Berato, J.; Brun, J.-P. (eds.) L’origine de la syphilis en Europe: avant ou aprés 1493? Paris, Editions Errance: 79–80.

Manfredi, C.; Martina, R.; Grossi, G. B.; Giuliani, M. 1997. Heritability of 39 orthodontic cephalometric parameters on MZ, DZ twins and MN-paired singletons. American Journal of Orthodontics and Dentofacial Orthopedics, 111(1): 44–51.

Mariño-Sánchez, F.; Valls-Mateus, M.; Cardenas-Escalante, P.; Haag, O.; Ruiz- Echevarría, K.; Jiménez-Feijoo, R.; Lozano-Blasco, J.; Giner-Muñoz, M. T.; Plaza- Martin, A. M.; Mullol, J. 2017. Influence of nasal septum deformity on nasal obstruction, disease severity, and medical treatment response among children and adolescents with persistent allergic rhinitis. International Journal of Pediatric Otorhinolaryngology, 95: 145–154.

Marôco, J. 2014. Análise estatística com o SPSS Statistics. 6th edition. Pêro Pinheiro, ReportNumber, Análise e Gestão de Informação, Lda.

Marques, C.; Matos, V.; Costa, T.; Zink, A.; Cunha, E. 2018. Absence of evidence or evidence of absence? A discussion on paleoepidemiology of neoplasms with contributions from two Portuguese human skeletal reference collections (19th–20th century). International Journal of Paleopathology, 21: 83–95.

Marques, C.; Santos, A. L.; Cunha, E. 2013. Better a broader diagnosis than a misdiagnosis: the study of a neoplastic condition in a male individual who died in early 20th century (Coimbra, Portugal). International Journal of Osteoarchaeology, 23(6): 664–675.

Márquez, S. 2008. The paranasal sinuses: the last frontier in craniofacial biology. The

177

Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, 291(11): 1350–1361.

Martin, A. D.; McCulloch, R. G. 1987. Bone dynamics: stress, strain and fracture. Journal of Sports Sciences, 5(2): 155–163.

Marttila, O.; Jaakkola, J. J. K.; Vilkka, V.; Jappinen, P.; Haahtela, T. 1994. The South Karelia air pollution study: the effects of malodorous sulfur compounds from pulp mills on respiratory and other symptoms in children. Environmental Research, 66(2): 152– 159.

Maru, Y. K.; Gupta, Y. 1999. Concha bullosa: frequency and appearances on sinonasal CT. Indian Journal of Otolaryngology and Head and Neck Surgery, 52(1): 40–44.

Matos, V. 1999. Paleobiologia dos restos humanos da necrópole do Prazo. Undergraduate dissertation in Human Sciences. Coimbra, University of Coimbra.

Matos, V. M. J. 2009. O diagnóstico retrospectivo da lepra: complementaridade clínica e paleopatológica no arquivo médico do Hospital-Colónia Rovisco Pais (século XX, Tocha, Portugal) e na colecção de esqueletos da leprosaria Medieval de St. Jorgen’s (Odense, Dinamarca). Doctoral dissertation. Coimbra, University of Coimbra.

Matos, V. M. J.; Santos, A. L. 2013. Leprogenic odontodysplasia: new evidence from the St. Jørgen’s Medieval leprosarium cemetery (Odense, Denmark). Anthropological Science, 121(1): 43–47.

Matos, V.; Magno, G.; Amoroso, A.; Garcia, S. 2017. The case of a Portuguese postman who died from leprosy in 1931 and the paleopathological analysis of his skeleton. Poster presented at the 44th Annual North American Meeting of the Paleopathology Association; New Orlean, USA; 17-19 April 2017.

Mays, S. 2010. Archaeological skeletons support a northwest European origin for Paget’s disease of bone. Journal of Bone and Mineral Research, 25(8): 1839–1841.

Mays, S. 2012. Nasal septal deviation in a Mediaeval population. American Journal of Physical Anthropology, 148(3): 319–326.

Mays, S. 2018. How should we diagnose disease in Palaeopathology? Some

178

epistemological considerations. International Journal of Paleopathology, 20: 12–19.

Mays, S.; Mavrogordato, M.; Lambert, J.; Sofaer, J. 2014. The prevalence and health implications of concha bullosa in a population from Mediaeval England. International Journal of Osteoarchaeology, 24(5): 614–622.

Mays, S.; Vincent, S.; Snow, M.; Robson-Brown, K. 2011. Concha bullosa, a neglected condition in Palaeopathology. International Journal of Paleopathology, 1(3–4): 184– 187.

Mazza, D.; Bontempi, E.; Guerrisi, A.; Del Monte, S.; Cipolla, G.; Perrone, A.; Lo Mele, L.; Marini, M. 2007. Paranasal sinuses anatomic variants: 64-slice CT evaluation. Minerva Stomatologica, 56(6): 311–318.

McNamara, J. A. 1981. Influence of respiratory pattern on craniofacial growth. The Angle Orthodontist, 51(4): 269–300.

Mehle, M. E.; Schreiber, C. P. 2005. Sinus headache, migraine, and the otolaryngologist. Otolaryngology-Head and Neck Surgery, 133(4): 489–496.

Mello, C. 1931. Operações estéticas do nariz, sem cicatriz exterior. Lisboa Médica, 5(8 Suppl.): S5–S7.

Melo, C. 1932. Operações estéticas do nariz. Escolioses. A Medicina Contemporanea, 18(Suppl.): S3–S7.

Meloni, F.; Mini, R.; Rovasio, S.; Stomeo, F.; Teatini, G. P. 1992. Anatomic variations of surgical importance in ethmoid labyrinth and sphenoid sinus. A study of radiological anatomy. Surgical and Radiologic Anatomy, 14(1): 65–70.

Meltzer, E. O.; Hamilos, D. L. 2011. Rhinosinusitis diagnosis and management for the clinician: a synopsis of recent consensus guidelines. Mayo Clinic Proceedings, 86(5): 427–443.

Meltzer, E. O.; Hamilos, D. L.; Hadley, J. A.; Lanza, D. C.; Marple, B. F.; Nicklas, R. A.; Adinoff, A. D.; Bachert, C.; Borish, L.; Chinchilli, V. M.; Danzig, M. R.; Ferguson, B. J.; Fokkens, W. J.; Jenkins, S. G.; Lund, V. J.; Mafee, M. F.; Naclerio, R. M.; Pawankar, R.; Ponikau, J. U.; Schubert, M. S.; Slavin, R. G.; Stewart, M. G.; Togias,

179

A.; Wald, E. R.; Winther, B. 2006. Rhinosinusitis: developing guidance for clinical trials. Journal of Allergy and Clinical Immunology, 118(5 Suppl.): S17–S61.

Meltzer, E. O.; Hamilos, D. L.; Hadley, J. A.; Lanza, D. C.; Marple, B. F.; Nicklas, R. A.; Bachert, C.; Baraniuk, J.; Baroody, F. M.; Benninger, M. S.; Brook, I.; Chowdhury, B. A.; Druce, H. M.; Durham, S.; Ferguson, B.; Gwaltney, J. M.; Kaliner, M.; Kennedy, D. W.; Lund, V.; Naclerio, R.; Pawankar, R.; Piccirillo, J. F.; Rohane, P.; Simon, R.; Slavin, R. G.; Togias, A.; Wald, E. R.; Zinreich, S. J. 2004. Rhinosinusitis: establishing definitions for clinical research and patient care. Journal of Allergy and Clinical Immunology, 114(6): 155–212.

Menger, D.-J.; Fokkens, W. J.; Lohuis, P. J. F. M.; Ingels, K. J.; Nolst Trenité, G. J. 2007. Reconstructive surgery of the leprosy nose: a new approach. Journal of Plastic, Reconstructive & Aesthetic Surgery, 60(2): 152–162.

Merrett, D. C. 2003. Maxillary sinusitis among the Moatfield people. In: Williamson, R. F.; Pfeiffer, S. (eds.) Bones of the ancestors: the archaeology and osteobiography of the Moatfield Ossuary. Quebec, Canadian Museum of Civilization: 241–261.

Merrett, D. C.; Pfeiffer, S. 2000. Maxillary sinusitis as an indicator of respiratory health in past populations. American Journal of Physical Anthropology, 111(3): 301–318.

Milbrath, M. M.; Madiedo, G.; Toohill, R. J. 1994. Histopathological analysis of the middle turbinate after ethmoidectomy. American Journal of Rhinology, 8(1): 37–42.

Milczuk, H. A.; Dalley, R. W.; Wessbacher, F. W.; Richardson, M. A. 1993. Nasal and paranasal sinus anomalies in children with chronic sinusitis. The Laryngoscope, 103(3): 247–252.

Mirra, J. M.; Brien, E. W.; Tehranzadeh, J. 1995. Paget’s disease of bone: review with emphasis on radiologic features, Part II. Skeletal Radiology, 24(3): 173–184.

Mitchell, P. D. 2011. Retrospective diagnosis and the use of historical texts for investigating disease in the past. International Journal of Paleopathology, 1(2): 81–88.

Mitchell, P. D. 2017. Improving the use of historical written sources in paleopathology. International Journal of Paleopathology, 19: 88–95.

180

Mladina, R. 1987. The role of maxillar morphology in the development of pathological septal deformities. Rhinology, 25(3): 199–205.

Mladina, R. 2012. Clinical implications of septal deformities. Romanian Journal of Rhinology, 2(5): 10–13.

Mladina, R.; Cujić, E.; Šubarić, M.; Vuković, K. 2008. Nasal septal deformities in ear, nose, and throat patients. American Journal of Otolaryngology, 29(2): 75–82.

Mladina, R.; Skitarelić, N.; Cingi, C.; Muluk, N. B. 2017. Some forensic aspects of the nasal septal deformities. Romanian Journal of Rhinology, 7(28): 227–234.

Mladina, R.; Skitarelić, N.; Poje, G.; Šubarić, M. 2015. Clinical implications of nasal septal deformities. Balkan Medical Journal, 32(2): 137–146.

Mohammadi, A.; Ghasemi-Rad, M. 2011. Nasal bone fracture – Ultrasonography or computed tomography? Medical Ultrasonography, 13(4): 292–295.

Mohebbi, A.; Ahmadi, A.; Etemadi, M.; Safdarian, M.; Ghourchian, S. 2012. An epidemiologic study of factors associated with nasal septum deviation by computed tomography scan: a cross sectional study. BMC Ear, Nose, and Throat Disorders [Online], 12: 15. DOI: 10.1186/1472-6815-12-15.

Moleson, T. 1995. Rates of ageing in the eighteenth century. In: Saunders, S. R.; Herring, A. (eds.) Grave reflections: portraying the past through cemetery studies. Toronto, Canadian Scholars Press: 199–222.

Møller-Christensen, V. 1967. Evidence of leprosy in earlier peoples. In: Brothwell, D.; Sandison, A. T.; Dawson, W. R. (eds.) Diseases in antiquity. Springfield, Charles C Thomas: 295–306.

Møller-Christensen, V.; Bakke, S. N.; Melson, R. S.; Waaler, E. 1952. Changes in the anterior nasal spine and the alveolar process of the maxillary bone in leprosy. International Journal of Leprosy, 20(3): 335–340.

Møller-Christensen, V.; Weiss, D. L. 1971. One of the oldest datable skeletons with leprous bone-changes from the Naestved Leprosy Hospital churchyard in Denmark. International Journal of Leprosy and Other Mycobacterial Diseases, 39(2): 172–182.

181

Momeni, A. K.; Roberts, C. C.; Chew, F. S. 2007. Imaging of chronic and exotic sinonasal disease: review. American Journal of Roentgenology, 189(6 Suppl.): S35– S45.

Mondin, V.; Rinaldo, A.; Ferlito, A. 2005. Management of nasal bone fractures. American Journal of Otolaryngology, 26(3): 181–185.

Montagu, A. 1951. An introduction to Physical Anthropology. 2nd edition. Springfield, Charles C Thomas.

Morais-Almeida, M.; Santos, N.; Pereira, A. M.; Branco-Ferreira, M.; Nunes, C.; Bousquet, J.; Fonseca, J. A. 2013. Prevalence and classification of rhinitis in preschool children in Portugal: a nationwide study. Allergy, 68(10): 1278–1288.

Muñoz, I. C. L.; Orta, P. B. 2014. Comparison of cephalometric patterns in mouth breathing and nose breathing children. International Journal of Pediatric Otorhinolaryngology, 78(7): 1167–1172.

Murray, J. A.; Maran, A. G.; Busuttil, A.; Vaughan, G. 1986. A pathological classification of nasal fractures. Injury, 17(5): 338–344.

Murteira, B.; Ribeiro, C. S.; Silva, J. A.; Pimenta, C. 2002. Introdução à estatística. Lisboa, McGraw-Hill.

Mushrif-Tripathy, V. 2014. Maxillary sinusitis from India: a bio-cultural approach. Korean Journal of Physical Anthropology, 27(1): 11–28.

Muthiyan, G. G.; Hattangdi, S. S.; Kasat, P. A.; Ambiye, M. V. 2014. A case of accessory middle turbinate. International Journal of Anatomical Variations, 7(1): 118– 119.

Mutijima, E.; Delvenne, P.; El-Shazly, A. E. 2014. Osteitis in chronic rhinosinusitis: a histopathological study of human ethmoid bone remodeling in allergic versus nonallergic chronic rhinosinusitis. Advances in Cellular and Molecular Otolaryngology [Online], 2(1). DOI: 10.3402/acmo.v2.23504.

Mygind, N.; Dahl, R. 1998. Anatomy, physiology and function of the nasal cavities in health and disease. Advanced Drug Delivery Reviews, 29(1–2): 3–12.

182

Nadas, S.; Duvoisin, B.; Landry, M.; Schnyder, P. 1995. Concha bullosa: frequency and appearances on CT and correlations with sinus disease in 308 patients with chronic sinusitis. Neuroradiology, 37(3): 234–237.

Naeimi, M.; Azarnoosh, E.; Gholparvar, M. S. J.; Naeimi, M. R. 2013. Histopathologic relationship between ethmoid sinus and ipsilateral middle turbinate in non-polypose chronic sinusitis by FESS. Indian Journal of Otolaryngology and Head and Neck Surgery, 65(Suppl. 2): S324–S328.

Narendrakumar, V.; Subramanian, V. 2016. Anatomical variations in ostiomeatal complex among patient undergoing functional endoscopic sinus surgery. International Journal of Clinical Rhinology, 9(1): 28–32.

Nawrocki, S. P. 1995. Taphonomic processes in historical cemeteries. In: Grauer, A. L. (ed.) Bodies of evidence: reconstructing history through skeletal analysis. New York, Wiley-Liss: 49–66.

Nazri, M.; Bux, S. I.; Tengku-Kamalden, T. F.; Ng, K.-H.; Sun, Z. 2013. Incidental detection of sinus mucosal abnormalities on CT and MRI imaging of the head. Quantitative Imaging in Medicine and Surgery, 3(2): 82–88.

Neskey, D.; Eloy, J. A.; Casiano, R. R. 2009. Nasal, septal, and turbinate anatomy and embryology. Otolaryngologic Clinics of North America, 42(2): 193–205.

Neto, F. J. S. M. 2005. Estudo paleobiológico da necrópole da Igreja da Misericórdia de Almada (séculos XVI-XVIII). Master dissertation. Coimbra, University of Coimbra.

Neves, J. A. B. 1889. Clinica externa: um caso de ozena curada pelo chloridrato de potassa. Coimbra Médica, 9(6): 88–89.

Nielsen-Marsh, C. M.; Smith, C. I.; Jans, M. M. E.; Nord, A.; Kars, H.; Collins, M. J. 2007. Bone diagenesis in the European Holocene II: taphonomic and environmental considerations. Journal of Archaeological Science, 34(9): 1523–1531.

Norlander, T.; Westrin, K. M.; Stierna, P. 1994. The inflammatory response of the sinus and nasal mucosa during sinusitis: implications for research and therapy. Acta Oto- Laryngologica, 114(515): 38–44.

183

Nouraei, S. A. R.; Elisay, A. R.; Dimarco, A.; Abdi, R.; Majidi, H.; Madani, S. A.; Andrews, P. J. 2009. Variations in paranasal sinus anatomy: implications for the pathophysiology of chronic rhinosinusitis and safety of endoscopic sinus surgery. Journal of Otolaryngology - Head & Neck Surgery, 38(1): 32–37.

Odes, E. J.; Delezene, L. K.; Randolph-Quinney, P. S.; Smilg, J. S.; Augustine, T. N.; Jakata, K.; Berger, L. R. 2018. A case of benign osteogenic tumour in Homo naledi: evidence for peripheral osteoma in the U.W. 101-1142 mandible. International Journal of Paleopathology, 21: 47–55.

Oliveira, E. V.; Galhano, F. 2000. Arquitectura tradicional Portuguesa. 4th edition. Lisboa, Publicações Dom Quixote.

Oneal, R. M.; Beil, R. J. 2010. Surgical anatomy of the nose. Clinics in Plastic Surgery, 37(2): 191–211.

Onwuchekwa, R. C.; Alazigha, N. 2017. Computed tomography anatomy of the paranasal sinuses and anatomical variants of clinical relevants in Nigerian adults. Egyptian Journal of Ear, Nose, Throat and Allied Sciences, 18(1): 31–38.

Orlandi, R. R. 2010. A systematic analysis of septal deviation associated with rhinosinusitis. The Laryngoscope, 120(8): 1687–1695.

Orlandi, R. R.; Kingdom, T. T.; Kennedy, D. W.; Hwang, P. H.; Smith, T. L.; Alt, J. A.; Baroody, F. M.; Batra, P. S.; Bernal-Sprekelsen, M.; Bhattacharyya, N.; Chandra, R. K.; Chiu, A.; Citardi, M. J.; Cohen, N. A.; DelGaudio, J.; Desrosiers, M.; Dhong, H. J.; Douglas, R.; Ferguson, B.; Fokkens, W. J.; Georgalas, C.; Goldberg, A.; Gosepath, J.; Hamilos, D. L.; Han, J. K.; Harvey, R.; Hellings, P.; Hopkins, C.; Jankowski, R.; Javer, A. R.; Kern, R.; Kountakis, S.; Kowalski, M. L.; Lane, A.; Lanza, D. C.; Lebowitz, R.; Lee, H. M.; Lin, S. Y.; Lund, V.; Luong, A.; Mann, W.; Marple, B. F.; McMains, K. C.; Metson, R.; Naclerio, R.; Nayak, J. V.; Otori, N.; Palmer, J. N.; Parikh, S. R.; Passali, D.; Peters, A.; Piccirillo, J.; Poetker, D. M.; Psaltis, A. J.; Ramadan, H. H.; Ramakrishnan, V. R.; Riechelmann, H.; Roh, H. J.; Rudmik, L.; Sacks, R.; Schlosser, R. J.; Senior, B. A.; Sindwani, R.; Stankiewicz, J. A.; Stewart, M.; Tan, B. K.; Toskala, E.; Voegels, R.; Wang, de Y.; Weitzel, E. K.; Wise, S.; Woodworth, B. A.; Wormald, P. J.; Wright, E. D.; Zhou, B.; Kennedy, D. W. 2016. International consensus statement on

184

allergy and rhinology: rhinosinusitis. International Forum of Allergy & Rhinology, 6(Suppl. 1): S22–S209.

Ortner, D. J. 2003. Identification of pathological conditions in human skeletal remains. San Diego, Academic Press.

Ortner, D. J. 2008. Skeletal manifestations of leprosy. In: Magilton, J.; Lee, F.; Boylston, A. (eds.) “Lepers outside the gate”. Excavations at the cemetery of the Hospital of St. James and St. Mary Magdalene, Chichester, 1986-87 and 1993. York, Council of British Archaeology: 198–207.

Oudin, A.; Richter, J. C.; Taj, T.; Al-Nahar, L.; Jakobsson, K. 2016. Poor housing conditions in association with child health in a disadvantaged immigrant population: a cross-sectional study in Rosengård, Malmö, Sweden. BMJ Open [Online], 6(1): e007979. DOI: 10.1136/bmjopen-2015-007979.

Ozcan, K. M.; Selcuk, A.; Özcan, İ.; Akdogan, O.; Dere, H. 2008. Anatomical variations of nasal turbinates. Journal of Craniofacial Surgery, 19(6): 1678–1682.

Özdoğan, F.; Özel, H. E.; Esen, E.; Altıparmak, E.; Genç, S.; Selçuk, A. 2017. An often neglected area in crooked nose: middle turbinate pneumatization. Brazilian Journal of Otorhinolaryngology, 83(5): 563–567.

Palkovich, A. M. 2001. Taking another look: the reanalysis of existing collections. In: Williams, E. (ed.) Human remains: conservation, retrieval, and analysis. Oxford, Archaeopress: 143–149.

Panhuysen, R. G. A. M.; Coened, V.; Bruintjes, T. D. 1997. Chronic maxillary sinusitis in Medieval Maastricht, The Netherlands. International Journal of Osteoarchaeology, 7(6): 610–614.

Papillault, G. 1919. The international agreement for the unification of craniometric and cephalometric measurements: report of the commission appointed by the XIII International Congress of Prehistoric Anthropology and Archaeology at Monaco (1906). American Journal of Physical Anthropology, 2(1): 46–60.

Park, H.-K.; Lee, J.-Y.; Song, J.-M.; Kim, T.-S.; Shin, S.-H. 2014. The retrospective study of closed reduction of nasal bone fracture. Maxillofacial Plastic and 185

Reconstructive Surgery, 36(6): 266–272.

Passalacqua, N. V.; Fenton, T. W. 2012. Developments in skeletal trauma: blunt-force trauma. In: Dirkmaat, D. C. (ed.) A companion to Forensic Anthropology. Chichester, Wiley-Blackwell: 400–411.

Paulsen, F.; Waschke, J. 2012. Sobotta: atlas de anatomia humana. Cabeça, pescoço e neuroanatomia. 23rd edition. Rio de Janeiro, Editora Guanabara Koogan Ltda.

Pérez-Piñas, I.; Sabaté, J.; Carmona, A.; Catalina-Herrera, C. J. J.; Jiménez-Castellanos, J. 2000. Anatomical variations in the human paranasal sinus region studied by CT. Journal of Anatomy, 197(2): 221–227.

Peric, A.; Rasic, D.; Grgurevic, U. 2016. Surgical treatment of rhinogenic contact point headache: an experience from a tertiary care hospital. International Archives of Otorhinolaryngology, 20(2): 166–171.

Perloff, J. R.; Gannon, F. H.; Bolger, W. E.; Montone, K. T.; Orlandi, R.; Kennedy, D. W. 2000. Bone involvement in sinusitis: an apparent pathway for the spread of disease. The Laryngoscope, 110(12): 2095–2099.

Phillips, P. S.; Sacks, R.; Marcells, G. N.; Cohen, N. A.; Harvey, R. J. 2011. Nasal nitric oxide and sinonasal disease. Otolaryngology-Head and Neck Surgery, 144(2): 159–169.

Pina-Cabral, J. 1986. Sons of Adam, daughters of Eve: the peasant worldview of the Alto Minho. Oxford, Clarendon Press.

Pinhasi, R.; Bourbou, C. 2007. How representative are human skeletal assemblages for population analysis? In: Pinhasi, R.; Mays, S. (eds.) Advances in human Palaeopathology. Chichester, John Wiley & Sons, Ltd: 31–44.

Pinto, R. J. S. 2012. Memórias Figueirenses: estudo paleoantropológico de um ossário da igreja matriz de São Julião da Figueira da Foz. Master dissertation. Coimbra, University of Coimbra.

Pittore, B.; Al Safi, W.; Jarvis, S. J. 2011. Concha bullosa of the inferior turbinate: an unusual cause of nasal obstruction. Acta Otorhinolaryngologica Italica, 31(1): 47–49.

Poje, G.; Zinreich, J. S.; Skitarelić, N.; Đurić Vuković, K.; Passàli, G. C.; Passàli, D.; 186

Mladina, R. 2014. Nasal septal deformities in chronic rhinosinusitis patients: clinical and radiological aspects. Acta Otorhinolaryngologica Italica, 34(2): 117–122.

Pollak, S.; Saukko, P. 2017. Blunt injury. In: Houck, M. M. (ed.) Forensic Anthropology. San Diego, Academic Press: 203–213.

Ponikau, J.; Kita, H.; Sherris, D. A. 2013. The role of eosinophils in rhinologic diseases. In: Önerci, T. M. (ed.) Nasal physiology and pathophysiology of nasal disorders. New York, Springer: 95–108.

Powers, N. 2011. Osteological evidence. In: Emery, P. H.; Wooldridge, K. (eds.) St. Pancras burial ground: excavations at St. Pancras International, the London terminus of High Speed 1, 2002–3. London, Gifford: 127–153.

Prasad, S.; Varshney, S.; Bist, S. S.; Mishra, S.; Kabdwal, N. 2013. Correlation study between nasal septal deviation and rhinosinusitis. Indian Journal of Otolaryngology and Head & Neck Surgery, 65(4): 363–366.

Premužić, Z.; Rajić Šikanjić, P.; Mašić, B. 2013. Frontal sinus osteoma in a 16th century skeleton from Zagreb, Croatia. International Journal of Paleopathology, 3(1): 54–58.

Prüss-Üstün, A.; Corvalán, C. 2006. Preventing disease through healthy environments: towards an estimate of the environmental burden of disease. Geneva, World Health Organization.

Rallis, G.; Stathopoulos, P.; Igoumenakis, D.; Krasadakis, C.; Mourouzis, C.; Mezitis, M. 2015. Treating maxillofacial trauma for over half a century: how can we interpret the changing patterns in etiology and management? Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 119(6): 614–618.

Redfern, R. C. 2017. Identifying and interpreting domestic violence in archaeological human remains: a critical review of the evidence. International Journal of Osteoarchaeology, 27(1): 13–34.

Reh, D. D.; Lin, S. Y.; Clipp, S. L.; Irani, L.; Alberg, A. J.; Navas-Acien, A. 2009. Secondhand tobacco smoke exposure and chronic rhinosinusitis: a population-based case-control study. American Journal of Rhinology and Allergy, 23(6): 562–567.

187

Reis, J. 1987. A industrialização num país de desenvolvimento lento e tardio: Portugal, 1870-1913. Análise Social, 23(2): 207–227.

Reitzen, S. D.; Chung, W.; Shah, A. R. 2011. Nasal septal deviation in the pediatric and adult populations. Ear, Nose, & Throat Journal, 90(3): 112–115.

Retzius, A. 1846. Sur les formes du crane des habitants du Nord. Annales des Sciences Naturelles, 3(VI): 133–172.

Revista de jornaes: O tractamento da coryza. 1884. Coimbra Médica, 4(12): 188.

Revista de jornaes: Tratamento da epistaxis. 1885. Coimbra Médica, 5(23): 381.

Revista de jornaes: Tratamento do catarrho naso-pharyngeo. 1882. Coimbra Médica, 2(3): 43–44.

Ribeiro, A. L. R.; Gillet, L. C. S.; Vasconcelos, H. G.; Rodrigues, L. C.; Pinheiro, J. J. V.; Alves-Junior, S. M. 2016. Facial fractures: large epidemiologic survey in northern Brazil reveals some unique characteristics. Journal of Oral and Maxillofacial Surgery

[Online], 74(12): 2480.e1-2480.e12. DOI: 10.1016/j.joms.2016.08.015.

Riccomi, G.; Minozzi, S.; Pantano, W.; Catalano, P.; Aringhieri, G.; Giuffra, V. 2018. Paleopathological evidence of paranasal lesions: two cases of frontal sinus osteomata from Imperial Rome. International Journal of Paleopathology, 20: 60–64.

Riello, A. P. F. L.; Boasquevisque, E. M. 2008. Anatomical variants of the ostiomeatal complex: tomographic findings in 200 patients. Radiologia Brasileira, 39(34): 149–154.

Roberts, C. A. 2002. The antiquity of leprosy in Britain: the skeletal evidence. In: Roberts, C. A.; Lewis, M. E.; Manchester, K. (eds.) The past and present of leprosy: archaeological, historical, palaeopathological and clinical approaches. BAR International Series 1054. Oxford, Archaeopress: 213–222.

Roberts, C. A. 2007. A bioarcheological study of maxillary sinusitis. American Journal of Physical Anthropology, 133(2): 792–807.

Rocha, A. 1897. Conferencia internacional sobre a lepra. Berlin, 1897. Coimbra Médica, 17(33): 515–518.

188

Rocha, M. A. 1995. Les collections ostéologiques humaines identifiées du Musée Anthropologique de l’Université de Coimbra. Antropologia Portuguesa, 13: 7–38.

Rodrigues, J. 1998. Redefinindo a rinite – Diagnóstico diferencial das rinites. Revista Portuguesa de Imunoalergologia, 5(4): 345–347.

Rodrigues, M. H. C. 1906. Indicações das intervenções cirurgicas nas sinusites frontaes: dissertação inaugural. Lisboa, Typographia de J. F. Pinheiro.

Rohrich, R. J.; Adams, W. P. 2000. Nasal fracture management: minimizing secondary nasal deformities. Plastic and Reconstructive Surgery, 106(2): 266–273.

Roman, R. A.; Hedeşiu, M.; Gersak, M.; Fidan, F.; Băciuţ, G.; Băciuţ, M. 2016. Assessing the prevalence of paranasal sinuses anatomical variants in patients with sinusitis using Cone Beam Computer Tomography. Clujul Medical, 89(3): 419–421.

Roozbahany, N. A.; Nasri, S. 2013. Nasal and paranasal sinus anatomical variations in patients with rhinogenic contact point headache. Auris Nasus Larynx, 40(2): 177–183.

Ross, S. M. 2014. Introduction to probability and statistics for engineers and scientists. 5th edition. London, Academic Press.

Saddki, N.; Suhaimi, A. A.; Daud, R. 2010. Maxillofacial injuries associated with intimate partner violence in women. BMC Public Health [Online], 10: 268. DOI: 10.1186/1471-2458-10-268.

Sadr, S. M.; Ahmadinejad, M.; Saedi, B.; Razaghian, F.; Rafiee, M. 2012. Anatomical variations in sinus imaging in sinusitis: a case control study. B-ENT, 8(3): 185–189.

Saedi, B.; Rashan, A. R.; Lipan, M.; Nayak, J. V.; Most, S. P. 2015. Consistent ipsilateral development of the posterior extension of the quadrangular cartilage and bony spur formation in nasal septal deviation. Otolaryngology-Head and Neck Surgery, 152(3): 444–448.

Saito, H. 2013. Mast cells. In: Önerci, T. M. (ed.) Nasal physiology and pathophysiology of nasal disorders. New York, Springer: 69–75.

Sanches, A. R. 1756. Tratado de conservaçaô da saude dos povos: obra util, e igualmente neceffaria a os magiftrados, capitaens generais, capitaens de mar, e guerra, 189

prelados, abbadeffas, medicos, e pays de familias: com hum appendix consideraçoins fobre os terremotos, com a n. Paris, E fe vende em Lisboa, em cafa de Bonardel e Du Beux, Mercadores de Livros.

Santorini, G. D. 1724. Observationes anatomicae. Venice, Battista Recurti.

Santos, C.; Ferreira, M. T. 2004. Relatório antropológico do material exumado do exterior da Ermida do Espírito Santo – Maiorga, Alcobaça. Research report in Human Sciences. Coimbra, University of Coimbra.

Santos, W. M.; Prado, P. S. A. 2017. Frequency of nasal septum deviation and concha bullosa: forensic anthropological implications. Brazilian Journal of Forensic Sciences, Medical Law and Bioethics, 7(1): 92–100.

Sarafoleanu, C.; Negrila-Mezei, A. 2014. Is there any relationship between septal deformities and chronic rhinosinusitis? Romanian Journal of Rhinology, 4(13): 49–54.

Sari, S.; Dalgic, B.; Yilmaz, M.; Poyraz, A. 2007. Nasal septal perforation in an adolescent girl with Crohn’s Disease: a rare extraintestinal manifestation. Digestive Diseases and Sciences, 52(5): 1285–1287.

Sarkar, P. S.; Bhosale, P. R.; Bharthi, A. R.; Ananthasivan, R. 2016. Computed tomography scan correlation between anatomic variations of paranasal sinuses and chronic rhinosinusitis. International Journal of Scientific Study, 4(4): 122–128.

Sarna, A.; Hayman, L. A.; Laine, F. J.; Taber, K. H. 2002. Coronal imaging of the osteomeatal unit: anatomy of 24 variants. Journal of Computer Assisted Tomography, 26(1): 153–157.

Savino, G.; Battendieri, R.; Traina, S.; Corbo, G.; D’Amico, G.; Gari, M.; Scarano, E.; Paludetti, G. 2014. External vs. endonasal dacryocystorhinostomy: has the current view changed? Acta Otorhinolaryngologica Italica, 34(1): 29–35.

Savoye, I.; Loos, R.; Carels, C.; Derom, C.; Vlietinck, R. 1998. A genetic study of anteoposterior and vertical facial proportions using model-fitting. The Angle Orthodontist, 68(5): 467–470.

Sayan, N. B.; Üçok, C.; Karasu, H. A.; Günhan, Ö. 2002. Peripheral osteoma of the oral

190

and maxillofacial region: a study of 35 new cases. Journal of Oral and Maxillofacial Surgery, 60(11): 1299–1301.

Schalek, P. 2011. Rhinosinusitis – Its impact on quality of life. In: Marseglia, G. L.; Caimmi, D. P. (eds.) Peculiar aspects of rhinosinusitis. Ryjeka, InTech: 3–26.

Scheuer, L.; Black, S. M. 2000. Developmental juvenile osteology. San Diego, Elsevier Academic Press.

Schiller, J. S.; Lucas, J. W.; Peregoy, J. A. 2012. Summary health statistics for U.S. adults: national health interview survey, 2011. Vital and Health Statistics, 10(256): 1– 218.

Schmider, E.; Ziegler, M.; Danay, E.; Beyer, L.; Bühner, M. 2010. Is it really robust? Reinvestigating the robustness of ANOVA against violations of the normal distribution assumption. Methodology, 6(4): 147–151.

Schneider, D.; Kämmerer, P. W.; Schön, G.; Dinu, C.; Radloff, S.; Bschorer, R. 2015. Etiology and injury patterns of maxillofacial fractures from the years 2010 to 2013 in Mecklenburg-Western Pomerania, Germany: a retrospective study of 409 patients. Journal of Cranio-Maxillofacial Surgery, 43(10): 1948–1951.

Schultz, M.; Timme, U.; Schmidt-Schultz, T. H. 2007. Infancy and childhood in the pre- Columbian North American Southwest–first results of the palaeopathological investigation of the skeletons from the Grasshopper Pueblo, Arizona. International Journal of Osteoarchaeology, 17(4): 369–379.

Scribano, E.; Ascenti, G.; Loria, G.; Cascio, F.; Gaeta, M. 1997. The role of the ostiomeatal unit anatomic variations in inflammatory disease of the maxillary sinuses. European Journal of Radiology, 24(3): 172–174.

Sedaghat, A. R.; Gray, S. T.; Wilke, C. O.; Caradonna, D. S. 2012. Risk factors for development of chronic rhinosinusitis in patients with allergic rhinitis. International Forum of Allergy & Rhinology, 2(5): 370–375.

Seiberling, K.; Wormald, P.-J. 2012. Benign sinonasal tumor. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 394–408. 191

Serafim, I. J. B. 2017. Análise biocultural de indivíduos exumados do Mosteiro de São Vicente de Fora (Lisboa). Master dissertation. Coimbra, University of Coimbra.

Šešelj, M.; Duren, D. L.; Sherwood, R. J. 2015. Heritability of the human craniofacial complex. The Anatomical Record, 298(9): 1535–1547.

Sethi, N. 2015. The significance of osteitis in rhinosinusitis. European Archives of Oto- Rhino-Laryngology, 272(4): 821–826.

Sevinc, O.; Barut, C.; Kacar, D.; Is, M. 2013. Evaluation of the lateral wall of the nasal cavity in relation to septal deviation. International Journal of Morphology, 31(2): 438– 443.

Shah, R. K.; Dhingra, J. K.; Carter, B. L.; Rebeiz, E. E. 2003. Paranasal sinus development: a radiographic study. The Laryngoscope, 113(2): 205–209.

Shimizu, T. 2013. Mucus, goblet cell, submucosal gland. In: Önerci, T. M. (ed.) Nasal physiology and pathophysiology of nasal disorders. New York, Springer: 1–14.

Shpilberg, K. A.; Daniel, S. C.; Doshi, A. H.; Lawson, W.; Som, P. M. 2015. CT of anatomic variants of the paranasal sinuses and nasal cavity: poor correlation with radiologically significant rhinosinusitis but importance in surgical planning. American Journal of Roentgenology, 204(6): 1255–1260.

Silva, A. M. 1993. Os restos humanos da gruta artificial de São Pedro do Estoril II: estudo antropológico. Research report in Human Sciences. Coimbra, University of Coimbra.

Silva, A. M. 1999. Estudo paleobiológico dos esqueletos exumados do Convento de São Francisco de Santarém na campanha de 1996. 3o relatório. Research report in Human Sciences. Coimbra, University of Coimbra.

Silva, A. M. 2002. Antropologia funerária e paleobiologia das populações portuguesas (litorais) do Neolítico final-Calcolítico. Doctoral dissertation. Coimbra, University of Coimbra.

Silvestre, F. J.; Perez-Herbera, A.; Puente-Sandoval, A.; Bagán, J. V. 2010. Hard palate perforation in cocaine abusers: a systematic review. Clinical Oral Investigations, 14(6):

192

621–628.

Slavin, R. G.; Spector, S. L.; Bernstein, I. L.; Kaliner, M. A.; Kennedy, D. W.; Virant, F. S.; Wald, E. R.; Khan, D. A.; Blessing-Moore, J.; Lang, D. M.; Nicklas, R. A.; Oppenheimer, J. J.; Portnoy, J. M.; Schuller, D. E.; Tilles, S. A.; Borish, L.; Nathan, R. A.; Smart, B. A.; Vandewalker, M. L. 2005. The diagnosis and management of sinusitis: a practice parameter update. The Journal of Allergy and Clinical Immunology, 116(6 Suppl.): S13–S47.

Smith, K. D.; Edwards, P. C.; Saini, T. S.; Norton, N. S. 2010. The prevalence of concha bullosa and nasal septal deviation and their relationship to maxillary sinusitis by volumetric tomography. International Journal of Dentistry [Online], Article ID 404982. DOI: 10.1155/2010/404982.

Smith, O. C.; Pope, E. J.; Symes, S. A. 2016. Look until you see: identification of trauma in skeletal material. In: Steadman, D. W. (ed.) Hard evidence: case studies in Forensic Anthropology. New York, Routledge: 190–204.

Smith, S. K. 2010. Differential diagnosis and discussion of a large nasal neoplasm from a late Bronze Age Athenian male. International Journal of Osteoarchaeology, 20(6): 731–736.

Sousa, P. N. 1888. Reseção do maxillar superior: dissertação inaugural apresentada á Escola Medico-Cirurgica do Porto. Porto, Typ. da Empreza Litteraria e Typographica.

Spector, S. 2001. The linkage between rhinitis, sinusitis, and asthma. Clinical and Applied Immunology Reviews, 1(3–4): 229–234.

Stallman, J. S.; Lobo, J. N.; Som, P. M. 2004. The incidence of concha bullosa and its relationship to nasal septal deviation and paranasal sinus disease. American Journal of Neuroradiology, 25(9): 1613–1618.

Stammberger, H. 1986. Endoscopic endonasal surgery-concepts in treatment of recurring rhinosinusitis. Part I. Anatomic and pathophysiologic considerations. Otolaryngology-Head and Neck Surgery, 94(2): 143–147.

Stammberger, H.; Kennedy, D. W.; Boger, M. W. E.; Clement, P. A. R.; Hosemann, W.; Kuhn, F. A.; Lanza, D. C.; Leopold, D. A.; Ohnishi, T.; Passàli, D.; Schaefer, S. D.; 193

Wayoff, M. R.; Zinreich, S. J. 1995. Paranasal sinuses: anatomic terminology and nomenclature. The Annals of Otology, Rhinology & Laryngology, 167(Suppl.): S7–S16.

Stammberger, H.; Posawetz, W. 1990. Functional endoscopic sinus surgery. Concept, indications and results of the Messerklinger technique. European Archives of Otorhinolaryngologyryngology, 247(2): 63–76.

Standring, S.; Borley, N. R.; Collins, P.; Crossman, A. L.; Gatzoulis, M. A.; Healy, J. C.; Johnson, D.; Mahadevan, V.; Newell, R. L. M.; Wigley, C. 2008. Gray's anatomy: the anatomical basis of clinical practice. 40th edition. London, Churchill Livingstone.

Steele, J. P.; Gregg, J. B.; Clifford, S.; Holzhueter, A. M. 1965. Paleopathology in the Dakotas. South Dakota Journal of Medicine, 18(10): 17–29.

Stranc, M. F.; Robertson, G. A. 1979. A classification of injuries of the nasal skeleton. Annals of Plastic Surgery, 2(6): 468–474.

Subarić, M.; Mladina, R. 2002. Nasal septum deformities in children and adolescents: a cross sectional study of children from Zagreb, Croatia. International Journal of Pediatric Otorhinolaryngology, 63(1): 41–48.

Subramanian, S.; Lekhraj Rampal, G. R.; Wong, E. F. M.; Mastura, S.; Razi, A. 2005. Concha bullosa in chronic sinusitis. The Medical Journal of Malaysia, 60(5): 535–539.

Sundar, G. 2015. Lacrimal trauma and its management. In: Ali, M. J. (ed.) Principles and practice of lacrimal surgery. New Delhi, Springer India: 159–170.

Sundman, E. A.; Kjellström, A. 2013a. Chronic maxillary sinusitis in Medieval Sigtuna, Sweden: a study of sinus health and effects on bone preservation. International Journal of Osteoarchaeology, 23(4): 447–458.

Sundman, E. A.; Kjellström, A. 2013b. Signs of sinusitis in times of urbanization in viking age-early Medieval Sweden. Journal of Archaeological Science, 40(12): 4457– 4465.

Swain, S. K.; Behera, I. C.; Mohanty, S.; Sahu, M. C. 2016. Rhinogenic contact point headache – Frequently missed clinical entity. Apollo Medicine, 13(3): 169–173.

SWGANTH. 2011. Trauma analysis. [Online]. [Accessed October 10, 2016]. Available 194

at: https://www.nist.gov/sites/default/files/documents/2018/03/13/swganth_trauma.pdf.

Tabachnick, B. G.; Fidell, L. S. 2007. Using multivariate statistics. 5th edition. Boston, Pearson Education, Inc.

Tammemagi, C. M.; Davis, R. M.; Benninger, S. M.; Holm, A. L.; Krajenta, R. 2010. Secondhand smoke as a potential cause of chronic rhinosinusitis: a case-control study. Archives of Otolaryngology - Head & Neck Surgery, 136(4): 327–334.

Teixeira, J.; Certal, V.; Chang, E. T.; Camacho, M. 2016. Nasal septal deviations: a systematic review of classification systems. Plastic Surgery International [Online], Article ID 7089123. DOI: 10.1155/2016/7089123.

Teul, I.; Lorkowski, J.; Lorkiewicz, W.; Nowakowski, D. 2013. Sinusitis in people living in the Medieval ages. In: Cohen, I. R.; Lajtha, A.; Lambris, J. D.; Paoletti, R.; Rezaei, N. (eds.) Advances in experimental medicine and biology. Volume 788. Dordrecht, Springer: 133–138.

Tezer, M. S.; Tahamiler, R.; Canakçioğlu, S. 2006. Computed tomography findings in chronic rhinosinusitis patients with and without allergy. Asian Pacific Journal of Allergy and Immunology, 24(2–3): 123–127.

Therapeutica: Formulario. Contra a constipação. 1892a. Coimbra Médica, 12(3): 45.

Therapeutica: Formulario. Contra a constipação chronica. 1889a. Coimbra Médica, 9(6): 92–95.

Therapeutica: Formulario. Contra a corysa. 1892b. Coimbra Médica, 12(8): 126.

Therapeutica: Formulario. Contra a corysa. 1893a. Coimbra Médica, 13(1): 14.

Therapeutica: Formulario. Contra a corysa aguda. 1892c. Coimbra Médica, 12(5): 78.

Therapeutica: Formulario. Contra a coryza. 1890. Coimbra Médica, 10(1): 13.

Therapeutica: Formulario. Contra a coryza. 1892d. Coimbra Médica, 12(16): 253–254.

Therapeutica: Formulario. Contra a coryza. 1895a. Coimbra Médica, 15(1): 15.

Therapeutica: Formulario. Contra a coryza aguda. 1893b. Coimbra Médica, 13(17):

195

271.

Therapeutica: Formulario. Contra a coryza aguda. 1895b. Coimbra Médica, 15(32): 522–523.

Therapeutica: Formulario. Contra a coryza rebelde. 1891. Coimbra Médica, 11(19): 297.

Therapeutica: Formulario. Contra a ozena. 1889b. Coimbra Médica, 9(6): 92–95.

Therapeutica: Formulario. Contra a rinhite chronica. 1900a. Coimbra Médica, 20(27): 430–431.

Therapeutica: Formulario. Contra as infecções bacterianas das fossas nasaes. Contra as suppurações do nariz e ouvido medio e externo. 1896. Coimbra Médica, 16(2): 31.

Therapeutica: Formulario. Contra as rhinites. 1889c. Coimbra Médica, 9(13): 206–207.

Therapeutica: Medicações, medicamentos e formulario. Contra a ozena. 1900b. Coimbra Médica, 20(26): 416.

Timperley, D.; Schlosser, R. J.; Harvey, R. J. 2010. Chronic rhinosinusitis: an education and treatment model. Otolaryngology-Head and Neck Surgery, 143(5 Suppl. 3): S3–S8.

Titche, L. L. 1977. Nasal septal deflection in prehistoric Arizona indians. Arizona Medicine, 34(3): 158–159.

Tjaden, P.; Thoennes, N. 2000. Prevalence and consequences of male-to-female and female-to-male intimate partner violence as measured by the National Violence Against Women Survey. Violence Against Women, 6(2): 142–161.

Todo-Bom, A.; Loureiro, C.; Almeida, M. M.; Nunes, C.; Delgado, L.; Castel-Branco, G.; Bousquet, J. 2007. Epidemiology of rhinitis in Portugal: evaluation of the intermittent and the persistent types. Allergy, 62(9): 1038–1043.

Todo-Bom, A.; Loureiro, C.; Rodrigues, V.; Burney, P.; Mota-Pinto, A. 2012. Epidemiologia da asma e rinossinusite no Centro de Portugal. Contributo da alergia. Revista Portuguesa de Imunoalergologia, 20(3): 193–200.

Tonai, A.; Baba, S. 1996. Anatomic variations of the bone in sinonasal CT. Acta 196

Otolaryngologica, 525(Suppl.): S9–S13.

Topinard, P. 1876. L’Anthropologie. Paris, C. Reinwald et Cie, Libraires Éditeurs.

Torres, P.; Costa, S.; Ferreira, J.; Silveira, C.; Miranda, A. I.; Teixeira, J. P.; Pereira, M. C.; Mendes, A. 2017. Poluição atmosférica: breve revisão da situação em Portugal e os impactos na saúde pública. Boletim Epidemiológico Observações, 6(19): 20–25.

Toskala, E. 2012. Unified airway disease. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 104–109.

Tosun, F.; Gerek, M.; Ozkaptan, Y. 2000. Nasal surgery for contact point headaches. Headache, 40(3): 237–240.

Tovi, F.; Benharroch, D.; Gatot, A.; Hertzanu, Y. 1992. Osteoblastic osteitis of the maxillary sinus. The Laryngoscope, 102(4): 426–430.

Tran, N. P.; Vickery, J.; Blaiss, M. S. 2011. Management of rhinitis: allergic and nonallergic. Allergy, Asthma & Immunology Research, 3(3): 148–156.

Tuli, I. P.; Sengupta, S.; Munjal, S.; Kesari, S. P.; Chakraborty, S. 2013. Anatomical variations of uncinate process observed in chronic sinusitis. Indian Journal of Otolaryngology and Head and Neck Surgery, 65(2): 157–161.

Tunçyürek, Ö.; Eyigör, H.; Songu, M. 2013. The relationship among concha bullosa, septal deviation and chronic rhinosinusitis. Journal of Medical Updates [Online], 3(1). DOI: 10.2399/jmu.2013001002.

Umbelino, C.; Santos, A. L.; Assis, S. 2012. Beyond the cause of death: other pathological conditions in a female individual from the Coimbra Identified Skeletal Collection (Portugal). Anthropological Science, 120(1): 73–79.

Uygur, K.; Tüz, M.; Doğru, H. 2003. The correlation between septal deviation and concha bullosa. Otolaryngology-Head and Neck Surgery, 129(1): 33–36.

Uzun, L.; Aslan, G.; Mahmutyazicioglu, K.; Yazgan, H.; Savranlar, A. 2012. Is pneumatization of middle turbinates compensatory or congenital? Dento Maxillo Facial Radiology, 41(7): 564–570. 197

Valencia, M. P.; Castillo, M. 2008. Congenital and acquired lesions of the nasal septum: a practical guide for differential diagnosis. Radiographics, 28(1): 205–223.

Vallois, H. V. 1965. Anthropometric techniques. Current Anthropology, 6(2): 127–143.

Van Crombruggen, K.; Van Bruaene, N.; Holtappels, G.; Bachert, C. 2010. Chronic sinusitis and rhinitis: clinical terminology chronic rhinosinusitis further supported. Rhinology Journal, 48(1): 54–58.

Van Crombruggen, K.; Zhang, N.; Gevaert, P.; Tomassen, P.; Bachert, C. 2011. Pathogenesis of chronic rhinosinusitis: inflammation. Journal of Allergy and Clinical Immunology, 128(4): 728–732.

Van Spronsen, P. H. 2010. Long-face craniofacial morphology: cause or effect of weak masticatory musculature? Seminars in Orthodontics, 16(2): 99–117.

Vaquinhas, I. 1992. Notas para a história da violência rural, em Portugal, na segunda metade do século XIX. Separata da Revista Portuguesa de História, 27: 145–163.

Vaquinhas, I.; Guimarães, M. A. P. 2011. Economia doméstica e governo do lar. Os saberes domésticos e as funções da dona de casa. In: Mattoso, J. (ed.) História da vida privada em Portugal. A época Contemporânea. Lisboa, Círculo de Leitores e Temas e Debates: 194–221.

Vaz, M. J. 2014. O crime em Lisboa. 1850-1910. Lisboa, Tinta da China.

Videler, W. J. M.; Georgalas, C.; Menger, D. J.; Freling, N. J. M.; van Drunen, C. M.; Fokkens, W. J. 2011. Osteitic bone in recalcitrant chronic rhinosinusitis. Rhinology, 49(2): 139–147.

Vieira, L. 1890. Pathologia cirurgica: anestesia local pela cocaina. Coimbra Médica, 10(6): 87–90.

Vieira, L. 1893. Clinica medica: tratamento da coryza chronica. Coimbra Médica, 13(23): 356–357.

Vieira, L. 1895. As constipações, sua pathogenia e prophylaxia. Coimbra Médica, 15(1): 2–5.

198

Vig, K. W. L. 1998. Nasal obstruction and facial growth: the strength of evidence for clinical assumptions. American Journal of Orthodontics and Dentofacial Orthopedics, 113(6): 603–611.

Vincent, T. E. S.; Gendeh, B. S. 2010. The association of concha bullosa and deviated nasal septum with chronic rhinosinusitis in functional endoscopic sinus surgery patients. The Medical Journal of Malaysia, 65(2): 108–111.

Walden, M. J.; Zinreich, S. J.; Aygun, N. 2015. Radiology of the nasal cavity and paranasal sinuses. In: Flint, P. W.; Haughey, B. H.; Lund, V.; Niparko, J. K.; Robbins, K. T.; Thomas, J. R.; Lesperance, M. M. (eds.) Cummings otolaryngology. Philadelphia, Elsevier: 658–677.e2.

Waldron, T. 1994. Counting the dead: the epidemiology of skeletal populations. Chichester, John Wiley & Sons.

Waldron, T. 2007. Palaeoepidemiology: the measure of disease in the human past. Walnut Creek, Left Coast Press Inc.

Waldron, T. 2009. Palaeopathology. Cambridge, Cambridge University Press.

Walker, P. L. 1989. Cranial injuries as evidence of violence in prehistoric southern California. American Journal of Physical Anthropology, 80(3): 313–323.

Walker, P. L. 1997. Wife beating, boxing, and broken noses: skeletal evidence for the cultural patterning of violence. In: Martin, D. L.; Frayer, D. W. (eds.) Troubled times: violence and warfare in the past. Boca Raton, Taylor & Francis Group: 145–179.

Walker, P. L. 2001. A bioarchaeological perspective on the history of violence. Annual Review of Anthropology, 30(1): 573–596.

Wani, A. A.; Kanotra, S.; Lateef, M.; Ahmad, R.; Qazi, S. M.; Ahmad, S. 2009. CT scan evaluation of the anatomical variations of the ostiomeatal complex. Indian Journal of Otolaryngology and Head & Neck Surgery, 61(3): 163–168.

Wasterlain, R. S. C. N. 2006. “Males” da boca: estudo da patologia oral numa amostra das colecções osteológicas identificadas do Museu Antropológico da Universidade de Coimbra: finais do séc. XIX inícios do séc. XX. Doctoral dissertation. Coimbra,

199

University of Coimbra.

Wee, J. H.; Kim, D. W.; Lee, J.-E.; Rhee, C.-S.; Lee, C. H.; Min, Y.-G.; Kim, D.-Y. 2012. Classification and prevalence of nasal septal deformity in Koreans according to two classification systems. Acta Oto-Laryngologica, 132(Suppl. 1): S52–S57.

Wells, C. 1964. Chronic sinusitis with alveolar fistulae of Mediæval date. The Journal of Laryngology & Otology, 78(3): 320–322.

Wells, C. 1977. Disease of the maxillary sinus in antiquity. Medical and Biological Illustration, 27: 173–178.

Wescott, D. J. 2017. Biomechanics of bone trauma. In: Houck, M. M. (ed.) Forensic Anthropology. San Diego, Academic Press: 185–191.

Westrin, K. M.; Norlander, T.; Stierna, P.; Carlsöö, B.; Nord, C. E. 1992. Experimental maxillary sinusitis induced by Bacteroides fragilis. A bacteriological and histological study in rabbits. Acta Otolaryngologica, 112(1): 107–114.

White, T. D.; Folkens, P. A. 2005. The human bone manual. San Diego, Elsevier.

Willner, A.; Choi, S. S.; Vezina, L. G.; Lazar, R. H. 1997. Intranasal anatomic variations in pediatric sinusitis. American Journal of Rhinology, 11(5): 355–360.

Wise, S. K.; Orlandi, R. R.; DelGaudio, J. M. 2012. Sinonasal development and anatomy. In: Kennedy, D. W.; Hwang, P. H.; Stammberger, H. R.; Gralapp, C. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Thieme Medical Publishers: 1–20.

Witterick, I. J.; Vescan, A. D. 2012. Complications of rhinosinusitis. In: Kennedy, D. W.; Hwang, P. H. (eds.) Rhinology: diseases of the nose, sinuses, and skull base. New York, Taylor & Francis: 261–270.

Wolf, G.; Anderhuber, W.; Kuhn, F. 1993. Development of the paranasal sinuses in children: implications for paranasal sinus surgery. Annals of Otology, Rhinology & Laryngology, 102(9): 705–711.

Wolf, J. S.; Biedlingmaier, J. F. 2001. The middle turbinate in endoscopic sinus surgery. Current Opinion in Otolaryngology & Head and Neck Surgery, 9(1): 23–26. 200

Wood, J. W.; Milner, G. R.; Harpending, H. C.; Weiss, K. M. 1992. The osteological paradox: problems of inferring prehistoric health from skeletal samples. Current Anthropology, 33(4): 343–370.

Woog, J. J. 2007. The incidence of symptomatic acquired lacrimal outflow obstruction among residents of Olmsted County, Minnesota, 1976-2000 (an American Ophthalmological Society thesis). Transactions of the American Ophthalmological Society, 105: 649–666.

Wu, V.; Huff, H.; Bhandari, M. 2010. Pattern of physical injury associated with intimate partner violence in women presenting to the emergency department: a systematic review and meta-analysis. Trauma, Violence, & Abuse, 11(2): 71–82.

Yakopson, V. S.; Flanagan, J. C.; Ahn, D.; Luo, B. P. 2011. Dacryocystorhinostomy: history, evolution and future directions. Saudi Journal of Ophthalmology, 25(1): 37–49.

Yamamoto, K.; Kuraki, M.; Kurihara, M.; Matsusue, Y.; Murakami, K.; Horita, S.; Sugiura, T.; Kirita, T. 2010. Maxillofacial fractures resulting from falls. Journal of Oral and Maxillofacial Surgery, 68(7): 1602–1607.

Yasan, H.; Doĝru, H.; Baykal, B.; Döner, F.; Tüz, M. 2005. What is the relationship between chronic sinus disease and isolated nasal septal deviation? Otolaryngology- Head and Neck Surgery, 133(2): 190–193.

Yigit, O.; Acioglu, E.; Cakir, Z. A.; Sisman, A. S.; Barut, A. Y. 2010. Concha bullosa and septal deviation. European Archives of Oto-Rhino-Laryngology, 267(9): 1397– 1401.

Yildirim, I.; Okur, E. 2003. The prevalence of nasal septal deviation in children from Kahramanmaras, Turkey. International Journal of Pediatric Otorhinolaryngology, 67(11): 1203–1206.

Zandi, M.; Saleh, M.; Seyed Hoseini, S. R. 2011. Are facial injuries caused by stumbling different from other kinds of fall accidents? Journal of Craniofacial Surgery, 22(6): 2388–2392.

Zephro, L.; Galloway, A. 2014. The biomechanics of fracture production. In: Wedel, V.; Galloway, A. (eds.) Broken bones: anthropological analysis of blunt force trauma. 2nd 201

edition. Springfield, Charles C Thomas: 33–45.

Ziari, M.; Shen, S.; Amato, R. J.; Teh, B. S. 2006. Metastatic renal cell carcinoma to the nose and ethmoid sinus. Urology [Online], 67(1): 199.e21-199.e23. DOI: 10.1016/j.urology.2005.07.052.

Zielnik-Jurkiewicz, B.; Olszewska-Sosińska, O. 2006. The nasal septum deformities in children and adolescents from Warsaw, Poland. International Journal of Pediatric Otorhinolaryngology, 70(4): 731–736.

Zinreich, S. J.; Kennedy, D. W.; Rosenbaum, A. E.; Gayler, B. W.; Kumar, A. J.; Stammberger, H. 1987. Paranasal sinuses: CT imaging requirements for endoscopic surgery. Radiology, 163(3): 769–775.

Zuckerkandl, E. 1893. Anatomie normale et pathologique des fosses nasales et de leur annexes pneumatiques. Paris, G. Masson.

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Appendices

A1. Nasal trauma by side and sex. Side (right/left) Collection Sex N n/n -/n n/- nt/nt -/nt nt/- n/nt nt/n n % n % n % n % n % n % n % n %

Male 322 241 74.8 10 3.1 23 7.1 32 9.9 2 0.6 1 0.3 5 1.6 8 2.5

MSSC Female 187 147 78.6 11 5.9 13 7 10 5.3 - - - - 2 1.1 4 2.1 Total 509 388 76.2 21 4.1 36 7.1 42 8.3 2 0.4 1 0.2 7 1.4 12 2.4

Male 510 455 89.2 14 2.7 6 1.2 19 3.7 - - 1 0.2 4 0.8 11 2.2

IESC Female 476 412 86.6 23 4.8 23 4.8 12 2.5 ------6 1.3

Total 986 867 87.9 37 3.8 29 2.9 31 3.1 - - 1 0.1 4 0.4 17 1.7

Male 138 119 86.2 1 0.7 - - 10 7.2 - - 1 0.7 2 1.4 5 3.6

HISC Female 137 118 86.1 6 4.4 - - 6 4.4 - - - - 4 2.9 3 2.2 Total 275 237 86.2 7 2.5 - - 16 5.8 - - 1 0.4 6 2.2 8 2.9 Male 970 815 84 25 2.6 29 3 61 6.3 2 0.2 3 0.3 11 1.1 24 2.5 Total Female 800 677 84.6 40 5 36 4.5 28 3.5 - - - - 6 0.8 13 1.6 Total 1770 1492 84.3 65 3.7 65 3.7 89 5 2 0.1 3 0.2 17 1 37 2.1 n = normal; nt = nasal bone trauma; - = nasal bone missing or damaged;

A2. Middle turbinate hypertrophy by side and sex. Side (right/left) Collection Sex N n/n -/n n/- h/h -/h h/- n/h h/n n % n % n % n % n % n % n % n % Male 303 155 51.2 12 4 11 3.6 44 14.5 5 1.7 7 2.3 34 11.2 35 11.6 MSSC Female 179 98 54.7 10 5.6 6 3.4 30 16.8 2 1.1 2 1.1 14 7.8 17 9.5 Total 482 253 52.5 22 4.6 17 3.5 74 15.4 7 1.5 9 1.9 48 10 52 10.8 Male 433 224 51.7 27 6.2 29 6.7 65 15 4 0.9 6 1.4 37 8.5 41 9.5 IESC Female 467 239 51.2 23 4.9 29 6.2 69 14.8 6 1.3 8 1.7 49 10.5 44 9.4 Total 900 463 51.4 50 5.6 58 6.4 134 14.9 10 1.1 14 1.6 86 9.6 85 9.4 Male 145 76 52.4 7 4.8 3 2.1 23 15.9 3 2.1 - - 17 11.7 16 11 HISC Female 157 78 49.7 5 3.2 4 2.5 28 17.8 1 0.6 3 1.9 15 9.6 23 14.6 Total 302 154 51 12 4 7 2.3 51 16.9 4 1.3 3 1 32 10.6 39 12.9 Male 881 455 51.6 46 5.2 43 4.9 132 15 12 1.4 13 1.5 88 10 92 10.4 Total Female 803 415 51.7 38 4.7 39 4.9 127 15.8 9 1.1 13 1.6 78 9.7 84 10.5 Total 1684 870 51.7 84 5 82 4.9 259 15.4 21 1.2 26 1.5 166 9.9 176 10.5 n = normal turbinate; h = hypertrophied turbinate; - = turbinate missing or damaged;

A3. Type of paradoxical curvature by side and sex. Type by side (right/left) Collection Sex N 0/0 -/0 0/- 1/0 0/1 1/1 -/1 1/- 2/0 0/2 2/1 1/2 2/2 -/2 2/- n % n % n % n % n % n % n % n % n % n % n % n % n % n % n % Male 303 109 36 9 3 11 3.6 28 9.2 33 10.9 53 17.5 6 2 3 1 2 0.7 7 2.3 7 2.3 17 5.6 12 4 2 0.7 4 1.3 MSSC Female 179 80 44.7 8 4.5 5 2.8 14 7.8 17 9.5 26 14.5 2 1.1 2 1.1 4 2.2 4 2.2 6 3.4 5 2.8 3 1.7 2 1.1 1 0.6 Total 482 189 39.2 17 3.5 16 3.3 42 8.7 50 10.4 79 16.4 8 1.7 5 1 6 1.2 11 2.3 13 2.7 22 4.6 15 3.1 4 0.8 5 1 Male 433 172 39.7 24 5.5 26 6 36 8.3 30 6.9 77 17.8 5 1.2 9 2.1 5 1.2 10 2.3 11 2.5 15 3.5 11 2.5 2 0.5 - - IESC Female 467 200 42.8 19 4.1 26 5.6 35 7.5 33 7.1 84 18 7 1.5 9 1.9 1 0.2 8 1.7 14 3 19 4.1 7 1.5 3 0.6 2 0.4 Total 900 372 41.3 43 4.8 52 5.8 71 7.9 63 7 161 17.9 12 1.3 18 2 6 0.7 18 2 25 2.8 34 3.8 18 2 5 0.6 2 0.2 Male 145 63 43.4 8 5.5 2 1.4 7 4.8 10 6.9 40 27.6 2 1.4 - - 1 0.7 - - 2 1.4 8 5.5 1 0.7 - - 1 0.7 HISC Female 157 63 40.1 4 2.5 4 2.5 15 9.6 12 7.6 35 22.3 2 1.3 3 1.9 4 2.5 3 1.9 3 1.9 5 3.2 4 2.5 - - - - Total 302 126 41.7 12 4 6 2 22 7.3 22 7.3 75 24.8 4 1.3 3 1 5 1.7 3 1 5 1.7 13 4.3 5 1.7 - - 1 0.3 Male 881 344 39 41 4.7 39 4.4 71 8.1 73 8.3 170 19.3 13 1.5 12 1.4 8 0.9 17 1.9 20 2.3 40 4.5 24 2.7 4 0.5 5 0.6 Total Female 803 343 42.7 31 3.9 35 4.4 64 8 62 7.7 145 18.1 11 1.4 14 1.7 9 1.1 15 1.9 23 2.9 29 3.6 14 1.7 5 0.6 3 0.4 Total 1684 687 40.8 72 4.3 74 4.4 135 8 135 8 315 18.7 24 1.4 26 1.5 17 1 32 1.9 43 2.6 69 4.1 38 2.3 9 0.5 8 0.5 0 = Absent; 1 = Small paradoxical curvature; 2 = Large paradoxical turbinate; - = turbinate missing or damaged.

A4. Accessory turbinate by side and sex.

Side (right/left) Collection Sex N n/n -/n n/- at/at -/at at/- n/at at/n n % n % n % n % n % n % n % n % Male 263 159 60.5 26 9.9 28 10.6 20 7.6 1 0.4 3 1.1 11 4.2 15 5.7 MSSC Female 165 102 61.8 11 6.7 14 8.5 12 7.3 6 3.6 7 4.2 9 5.5 4 2.4 Total 428 261 70 37 8.6 42 9.8 32 7.5 7 1.6 10 2.3 20 4.7 19 4.4 Male 339 234 69 22 6.5 26 7.7 23 6.8 8 2.4 5 1.5 7 2.1 14 4.1 IESC Female 377 251 66.6 27 7.2 29 7.7 19 5 6 1.6 9 2.4 21 5.6 15 4 Total 716 485 67.7 49 6.8 55 7.7 42 5.9 14 2 14 2 28 3.9 29 4.1 Male 119 81 68.1 7 5.9 9 7.6 7 5.9 2 1.7 2 1.7 3 2.5 8 6.7 HISC Female 137 100 73 10 7.3 13 9.5 5 3.6 2 1.5 1 0.7 2 1.5 4 2.9 Total 256 181 70.7 17 6.6 22 8.6 12 4.7 4 1.6 3 1.2 5 2 12 4.7 Male 721 474 65.7 55 7.6 63 8.7 50 6.9 11 1.5 10 1.4 21 2.9 37 5.1 Total Female 679 453 66.7 48 7.1 56 8.2 36 5.3 14 2.1 17 2.5 32 4.7 23 3.4 Total 1400 927 66.2 103 7.4 119 8.5 86 6.1 25 1.8 27 1.9 53 3.8 60 4.3 n = normal uncinate process; at = accessory turbinate; - = uncinate process missing or damaged;

A5. Middle turbinate spicules by side and sex. Side (right/left) Collection Sex N n/n -/n n/- sp/sp -/sp sp/- n/sp sp/n n % n % n % n % n % n % n % n % Male 303 150 49.5 12 4 11 3.6 83 27.4 5 1.7 7 2.3 16 5.3 19 6.3 MSSC Female 179 61 34.1 8 4.5 4 2.2 66 36.9 4 2.2 4 2.2 13 7.3 19 10.6 Total 482 211 43.8 20 4.1 15 3.1 149 30.9 9 1.9 11 2.3 29 6 38 7.9 Male 433 162 37.4 22 5.1 24 5.5 139 32.1 9 2.1 11 2.5 29 6.7 37 8.5 IESC Female 467 90 19.3 13 2.8 17 3.6 242 51.8 16 3.4 20 4.3 28 6 41 8.8 Total 900 252 28 35 3.9 41 4.6 381 42.3 25 2.8 31 3.4 57 6.3 78 8.7 Male 145 62 42.8 6 4.1 1 0.7 44 30.3 4 2.8 2 1.4 15 10.3 11 7.6 HISC Female 157 34 21.7 3 1.9 5 3.2 84 53.5 3 1.9 2 1.3 14 8.9 12 7.6 Total 302 96 31.8 9 3 6 2 128 42.4 7 2.3 4 1.3 29 9.6 23 7.6

Male 881 374 42.5 40 4.5 36 4.1 266 30.2 18 2 20 2.3 60 6.8 67 7.6

Total Female 803 185 23 24 3 26 3.2 392 48.8 23 2.9 26 3.2 55 6.8 72 9

Total 1684 559 33.2 64 3.8 62 3.7 658 39.1 41 2.4 46 2.7 115 6.8 139 8.3

n = normal turbinate; sp = presence of spicules; - = turbinate missing or damaged;

A6. Bone formations within the maxillary sinuses by side and sex. Side (right/left) Collection Sex N n/n -/n n/- rs/rs -/rs rs/- n/rs rs/n n % n % n % n % n % n % n % n % Male 109 34 31.2 14 12.8 16 14.7 15 13.8 8 7.3 12 11 6 5.5 4 3.7 MSSC Female 89 7 7.9 14 15.7 8 9 28 31.5 10 11.2 13 14.6 5 5.6 4 4.5 Total 198 41 20.7 28 14.1 24 12.1 43 21.7 18 9.1 25 12.6 11 5.6 8 4 Male 250 83 33.2 31 12.4 24 9.6 49 19.6 13 5.2 24 9.6 11 4.4 15 6 IESC Female 263 70 26.6 28 10.6 29 11 59 22.4 23 8.7 29 11 10 3.8 15 5.7 Total 513 153 29.8 59 11.5 53 10.3 108 21.1 36 7 53 10.3 21 4.1 30 5.8 Male 85 23 27.1 8 9.4 11 12.9 14 16.5 10 11.8 4 4.7 7 8.2 8 9.4 HISC Female 77 13 16.9 9 11.7 16 20.8 16 20.8 10 13 3 3.9 5 6.5 5 6.5 Total 162 36 22.2 17 10.5 27 16.7 30 18.5 20 12.3 7 4.3 12 7.4 13 8 Male 444 140 31.5 53 11.9 51 11.5 78 17.6 31 7 40 9 24 5.4 27 6.1 Total Female 429 90 21 51 11.9 53 12.4 103 24 43 10 45 10.5 20 4.7 24 5.6 Total 873 230 26.3 104 11.9 104 11.9 181 20.7 74 8.5 85 9.7 44 5 51 5.8 n = normal sinus; bf = presence of bone formations; - = not available for examination.

A7. Degree of bone changes in the individuals presenting at least one maxillary sinus available for examination. Side (right/left) Collection Sex N 0/- -/0 0/0 0/1 0/2 0/3 1/- -/1 1/0 1/1 1/2 1/3 n % n % n % n % n % n % n % n % n % n % n % n % Male 109 16 14.7 14 12.8 34 31.2 6 5.5 - - - - 7 6.4 - - - - 2 1.8 1 0.9 - - MSSC Female 89 8 9 14 15.7 7 7.9 3 3.4 2 2.2 - - 3 3.4 4 4.5 4 4.5 4 4.5 2 2.2 1 1.1 Total 198 24 12.1 28 14.1 41 20.7 9 4.5 2 1 - - 10 5.1 4 2 4 2 6 3 3 1.5 1 0.5 Male 250 24 9.6 31 12.4 83 33.2 6 2.4 5 2 - - 11 4.4 6 2.4 7 2.8 11 4.4 5 2 1 0.4 IESC Female 263 29 11 28 10.6 70 26.6 6 2.3 4 1.5 - - 12 4.6 10 3.8 6 2.3 6 2.3 6 2.3 1 0.4 Total 513 53 10.3 59 11.5 153 29.8 12 2.3 9 1.8 - - 23 4.5 16 3.1 13 2.5 17 3.3 11 2.1 2 0.4 Male 85 11 12.9 8 9.4 23 27.1 2 2.4 5 5.9 - - 1 1.2 5 1 5 5.9 3 3.5 1 1.2 - - HISC Female 77 16 20.8 9 11.7 13 16.9 2 2.6 3 3.9 - - 1 1.3 - - 2 2.6 3 3.9 1 1.3 - - Total 162 27 16.7 17 10.5 36 22.2 4 2.5 8 4.9 - - 2 1.2 5 3.1 7 4.3 6 3.7 2 1.2 - - Male 444 51 11.5 53 11.9 140 31.7 14 3.1 10 2.2 - - 19 4.3 11 2.5 12 2.7 16 3.6 7 1.6 1 0.2 Total Female 429 53 12.4 51 11.9 90 21 11 2.6 9 2.1 - - 16 3.7 14 3.3 12 2.8 13 3 9 2.1 2 0.5 Total 873 104 11.9 104 11.9 230 26.4 25 2.9 19 2.2 - - 35 4 25 2.9 24 2.7 29 3.3 16 1.8 3 0.3

Side (right/left) Collection Sex N 2/- -/2 2/0 2/1 2/2 2/3 3/- -/3 3/0 3/1 3/2 3/3 n % n % n % n % n % n % n % n % n % n % n % n % Male 109 3 2.8 7 6.4 2 1.8 1 0.9 8 7.3 - - 2 1.8 1 0.9 2 1.8 1 0.9 2 1.8 - - MSSC Female 89 7 7.9 4 4.5 - - 6 6.7 9 10.1 - - 3 3.4 2 2.2 - - - - 3 3.4 3 3.4 Total 198 10 5.1 11 5.6 2 1 7 3.5 17 8.6 - - 5 2.5 3 1.5 2 1 1 0.5 5 2.5 3 1.5 Male 250 11 4.4 7 2.8 7 2.8 6 2.4 17 6.8 2 0.8 2 0.8 - - 1 0.4 - - 2 0.8 5 2 IESC Female 263 12 4.6 9 3.4 8 3 8 3 21 8 3 1.1 5 1.9 4 1.5 1 0.4 1 0.4 3 1.1 10 3.8 Total 513 23 4.5 16 3.1 15 2.9 14 2.7 38 7.4 5 1 7 1.4 4 0.8 2 0.4 1 0.2 5 1 15 2.9 Male 85 3 3.5 3 3.5 2 2.4 2 2.4 5 5.9 2 2.4 - - 2 2.4 1 1.2 - - - - 1 1.2 HISC Female 77 2 2.6 8 10.4 3 3.9 3 3.9 7 9.1 - - - - 2 2.6 ------2 2.6 Total 162 5 3.1 11 6.8 5 3.1 5 3.1 12 7.4 2 1.2 - - 4 2.5 1 0.6 - - - - 3 1.9 Male 444 17 3.8 17 3.8 11 2.5 9 2 30 6.8 4 0.9 4 0.9 3 0.7 4 0.9 1 0.2 4 0.9 6 1.4 Total Female 429 21 4.9 21 4.9 11 2.6 17 4 37 8.6 3 0.7 8 1.9 8 1.9 1 0.2 1 0.2 6 1.4 15 3.5 Total 873 38 4.4 38 4.3 22 2.5 26 3 67 7.7 7 0.8 12 1.4 11 1.3 5 0.6 2 0.2 10 1.1 21 2.4

0 = no alterations; 1 = isolated alterations; 2 = isolated alterations to half of the sinus; 3 = more than half of the sinus has alterations; - = not available for examination.

A8. Descriptive statistics for the three groups studied (‘concha bullosa’, ‘maxillary rhinosinusitis’, and ‘control’). Measurement Group Males Females Total n Mean s.d. Range n Mean s.d. Range n Mean s.d. Range

1 25 133.06 5.81 123.0-144.0 28 127.75 4.71 119.0-138.5 53 130.26 5.85 119.0-144.0 Basion-bregma height 2 28 132.34 5.49 121.0-143.5 28 127.18 4.85 118.0-134.0 56 129.76 5.75 118.0-143.5 (BBH) 3 30 131.38 4.77 122.0-141.0 26 128.21 3.67 122.0-135.0 56 129.91 4.55 122.0-141.0

1 21 96.52 5.80 86.0-107.0 18 93.67 5.85 86.0-103.0 39 95.21 5.92 86.0-107.0 Basion-prosthion length 2 20 94.40 6.60 82.5-109.0 18 91.78 5.36 83.5-100.5 38 93.16 6.11 82.5-109.0 (BPL) 3 24 94.77 5.31 86.0-106.0 16 92.19 5.80 84.0-102.5 40 93.74 5.59 84.0-106.0

1 21 71.57 4.84 62.5-81.0 19 68.21 3.84 61.0-75.5 40 69.98 4.65 61.0-81.0 Nasion-prosthion height 2 20 69.85 3.87 61.0-75.0 18 65.56 3.46 59.5-71.5 38 67.82 4.23 59.5-75.0 (NPH) 3 24 70.44 3.56 64.0-78.0 17 65.41 3.35 58.0-71.0 41 68.35 4.25 58.0-78.0

Nasal height 1 25 52.96 3.72 47.5-62.5 28 48.70 2.95 42.5-55.0 53 50.71 3.94 42.5-62.5 (NLH) 2 26 51.90 3.86 45.0-61.5 28 48.64 2.81 44.0-54.0 54 50.21 3.71 44.0-61.5 3 30 52.07 3.33 44.0-60.0 28 47.95 2.62 43.5-54.0 58 50.08 3.64 43.5-60.0

1 27 33.91 2.19 29.5-39.0 29 33.26 1.83 29.0-36.5 56 33.57 2.02 29.0-39.0 Orbital height 2 29 33.90 2.15 28.5-37.0 29 33.22 1.67 30.5-37.0 58 33.56 1.94 28.5-37.0 (OBH) 3 30 33.55 1.30 31.5-36.5 30 32.90 1.98 30.0-37.0 60 33.23 1.70 30.0-37.0

1 27 103.28 3.83 94.0-111.0 29 99.26 3.78 92.5-107.0 56 101.20 4.28 92.5-111.0 Bifrontal breadth 2 29 101.17 4.85 91.5-112.0 28 98.77 3.28 92.0-105.0 57 99.99 4.29 91.5-112.0 (FMB) 3 30 100.58 3.88 94.5-109.0 30 97.70 2.84 92.5-102.5 60 99.14 3.67 92.5-109.0

1 26 112.98 4.71 103.0-125.0 27 108.41 4.90 100.0-117.0 53 110.65 5.29 100.0-125.0 Nasion-bregma chord 2 28 111.09 4.92 102.0-120.0 28 107.23 4.65 97.0-116.0 56 109.16 5.12 97.0-120.0 (FRC) 3 30 110.28 4.72 100.0-121.0 28 108.38 4.35 99.0-117.0 58 109.36 4.61 99.0-121.0

1 23 52.59 5.02 41.5-60.5 27 52.63 5.33 44.5-65.0 50 52.61 5.14 41.5-65.0 Zygoorbitale breadth 2 24 53.27 6.16 40.0-65.0 26 52.77 6.50 40.0-68.0 50 53.01 6.28 40.0-68.0 ZOB) 3 27 49.98 4.58 42.5-59.0 28 49.95 4.28 39.0-58.5 55 49.96 4.39 39.0-59.0

1 23 117.20 6.57 106.0-133.5 14 109.61 5.23 101.0-121.0 37 114.32 7.08 101.0-133.5 Intercondilar width 2 21 113.88 6.55 103.0-125.0 20 111.98 7.32 98.0-125.0 41 112.95 6.92 98.0-125.0 (W 1) 3 17 115.03 5.79 106.5-125.5 20 111.23 5.00 101.0-118.0 37 112.97 4.64 101.0-125.5

1 21 30.76 3.18 22.0-35.0 21 29.48 3.18 25.0-35.0 42 30.12 3.20 22.0-35.0 Symphysial height 2 20 31.30 2.62 25.5-36.0 17 28.41 3.46 24.0-36.5 37 29.97 3.33 24.0-36.5 (H 1) 3 23 30.48 2.80 25.0-36.5 16 28.00 2.15 24.0-32.0 39 29.46 2.81 22.0-36.5

1 25 71.05 3.43 64.6-77.2 27 70.92 2.63 67.0-77.2 52 70.98 3.01 64.6-77.2 Cranial length-height index 2 28 71.54 3.40 64.5-80.8 28 71.17 2.81 66.8-75.6 56 71.36 3.10 64.5-80.8 (CLHI) 3 30 71.22 3.24 64.6-77.9 26 71.16 2.96 65.2-77.2 56 71.19 3.09 64.6-77.9

1 23 96.61 4.32 89.4-105.9 26 96.93 4.76 86.2-105.4 49 96.78 4.52 86.2-105.9 Cranial breadth-height index 2 28 96.45 3.85 89.1-102.7 27 94.77 4.37 87.5-102.4 55 95.63 4.16 87.5-102.7 (CBHI) 3 30 96.60 4.74 87.9-104.9 23 94.45 2.72 90.4-100.0 53 95.67 4.10 87.9-104.9

1 20 92.39 7.68 81.9-110.1 17 81.90 6.18 72.0-91.4 37 87.57 8.73 72.0-110.1 Upper facial index 2 19 87.73 7.42 70.8-99.8 18 79.69 5.50 72.0-88.4 37 83.82 7.64 70.8-99.8 (UFI) 3 24 88.70 6.80 75.5-101.6 15 79.88 5.41 70.2-88.8 39 85.31 7.59 70.2-101.6

1 27 83.32 6.33 71.4-94.0 29 85.55 5.32 77.1-98.6 56 84.47 5.88 71.4-98.6 Orbital index 2 29 83.89 5.68 73.8-94.7 28 82.27 4.76 71.9-91.3 57 83.10 5.27 71.9-94.7 (OI) 3 30 84.83 4.85 73.6-97.1 30 85.78 4.85 77.2-96.1 60 85.31 4.83 73.6-97.1

1 27 187.41 7.79 168.5-201.0 27 180.11 5.72 168.0-192.0 54 183.76 7.71 168.0-201.0 Glabello-occipital length 2 29 184.86 7.11 174.0-203.0 29 178.81 6.10 169.5-193.0 58 181.84 7.24 169.5-203.0 (GOL) 3 30 184.67 6.95 174.0-204.0 29 179.83 7.18 166.5-200.0 59 182.29 7.42 166.5-204.0

1 27 101.72 5.12 88.0-110.0 29 97.24 4.73 88.0-108.0 56 99.40 5.38 88.0-110.0 Basion-nasion length 2 29 100.52 4.87 92.0-111.5 29 96.17 4.03 85.0-103.0 58 98.35 4.94 85.0-111.5 (BNL) 3 30 99.60 3.79 91.0-107.0 29 95.21 4.40 87.0-103.0 59 97.44 4.63 87.0-107.0

1 25 137.94 5.76 127.0-151.0 26 131.73 3.58 126.0-139.0 51 134.77 5.67 126.0-151.0 Maximum cranial breadth 2 29 137.31 4.77 129.0-147.0 28 133.91 3.47 126.0-140.0 57 135.64 4.49 126.0-147.0 (MCB) 3 30 136.20 5.94 122.0-153.0 27 135.15 4.28 125.0-143.0 57 135.70 5.20 122.0-153.0

1 24 128.79 5.47 121.0-143.0 26 120.62 4.43 111.0-129.0 50 124.54 6.41 111.0-143.0 Bizygomatic breadth 2 27 126.69 6.21 111.0-118.5 29 122.00 4.54 110.0-134-0 56 124.26 5.85 110.0-138.5 (ZYB) 3 30 126.32 4.76 115.0-135.0 24 121.46 3.63 115.0-129.0 54 124.16 4.90 115.0-135.0

1 27 40.76 1.60 37.0-44.0 29 38.93 1.76 35.0-43.0 56 39.81 1.90 35.0-44.0 Orbital breadth 2 29 40.47 2.10 37.5-45.5 28 40.43 1.31 38.5-44.5 57 40.45 1.74 37.5-45.5 (OBB) 3 30 39.63 2.00 34.0-43.5 30 38.37 1.25 35.0-40.0 60 39.00 1.77 34.0-43.5

1 20 23.73 1.85 18.5-27.0 22 23.91 1.52 21.5-27.0 42 23.82 1.67 18.5-27.0 Nasal breadth 2 25 23.70 2.17 19.0-27.0 19 23.29 1.90 20.0-27.0 44 23.52 2.04 19.0-27.0 (NLB) 3 28 22.66 1.64 19.5-25-5 24 22.83 1.32 20.5-25-5 52 22.74 1.49 19.5-25.5

1 26 90.92 4.73 82.0-103.0 29 87.22 3.98 79.5-96.0 55 88.97 4.69 79.5-103.0 Bimaxillary breadth 2 27 90.37 4.49 81.5-100.0 28 88.29 6.22 70.0-97.0 55 89.31 5.49 70.0-100.0 (ZMB) 3 30 88.03 4.38 78.5-97.0 29 86.05 4.52 75.0-94.0 59 87.06 4.52 75.0-97.0

1 27 20.74 3.04 15.0-26.0 29 20.60 1.95 17.5-25.5 56 20.67 2.51 15.0-26.0 Interorbital breadth 2 29 20.26 2.34 15.0-25.0 28 18.64 1.77 16.0-22.5 57 19.47 2.22 15.0-25.0 (DKB) 3 30 20.15 2.78 15.5-30.5 30 19.22 1.77 15.0-23.0 60 19.68 2.36 15.0-30.5

1 25 9.64 1.48 5.5-14.0 28 9.41 1.74 5.5-13.0 53 9.52 1.61 5.5-14.0 Simotic chord 2 29 8.48 1.92 6.0-14.5 29 9.36 1.77 6.0-14.0 58 8.92 1.88 6.0-14.5 (WNB) 3 30 9.00 1.93 5.5-14.0 30 9.10 1.59 6.5-12.0 60 9.05 1.76 5.5-14.0

1 25 73.40 3.57 68.7-82.5 26 73.17 2.60 68.3-79.1 51 73.29 3.08 68.3-82.5 Cranial index 2 29 74.33 2.59 69.9-80.8 28 74.89 2.99 68.1-80.2 57 74.60 2.78 68.1-80.8 (CI) 3 30 73.79 2.92 69.0-84.5 26 75.43 2.84 70.5-82.0 56 74.55 2.97 69.0-84.5

1 20 12.57 1.46 10.3-16.6 22 11.76 1.02 9.6-13.8 42 12.14 1.30 9.6-16.6 Nasal index 2 23 12.19 1.36 9.9-14.3 19 11.36 1.24 9.9-13.8 42 11.81 1.36 9.9-14.3 (NI) 3 28 11.82 1.10 9.7-13.4 23 10.96 0.89 9.6-13.8 51 11.44 1.09 9.6-13.4 Group: 1=Concha bullosa; 2=Maxillary rhinosinusitis; 3=Control.