1154 Diabetes Care Volume 40, September 2017

George Alberti: A Myriad Philip Home of Contributions to Diabetes and Beyond Diabetes Care 2017;40:1154–1158 | https://doi.org/10.2337/dci17-0006 PROFILES IN PROGRESS

before marriage. Mayer-Alberti-Strasse irreverent” in an interview for The BMJ can still in found in Koblenz, but the young in 2016 (2). More Cambridge than Oxford George Alberti settled with his family in in fact. Gateshead, U.K.; U.K. citizenship was Medical students at Oxford usually granted to all in November 1946. studied Animal Physiology as an interca- The northeast of England was clearly a lated Bachelor of Arts degree, and it was hit with the young Albertidhe returned not unusual for those with academic pre- later in life from the south of England tensions to go on to do a DPhil (Oxford’s to be professor of Clinical Biochemistry PhD). George chose to do his in the Bio- and subsequently professor of Medicine chemistry Department, at an exciting and in Newcastle (see below). But as a lad he expanding time for the discipline in the crossed the River Tyne to Newcastle’s early 1960s. The department and the lab- Royal Grammar School, an institution oratory in which he worked were those of with a strong record for forwarding its Hans Krebs (one of the greatest of Hitler’s pupils to England’s top universities; gifts) (1), but George was glad not to be George went on to Balliol College Oxford. supervised by such a taskmaster. His Balliol is perhaps better known as a cradle thesis topic was “Amino Acid Metabo- of high-flying politicians and civil servants, lism in Mitochondria” (3), so already we and this may have confirmed George see the biochemical interest deviating Alberti’s (partly correct) view of his own from the then increasingly fashion- personality as “laid back, iconoclastic, able topic of gene expression and protein K. George M.M. Alberti

Medawar and Pyke, in Hitler’s Gift (1), re- cord the movement out of Germany in the 1930s of world-class academic talent from within the Jewish diaspora. But among the Jewish migrants was one too young yet to show such talent, indeed a mere toddler, escaping with mother and brother as the door closed in 1939. Kurt George Matthew Mayer Alberti was born in September of 1937. His father William Peter(afterthefamily’s names were duly Young George. Left: George and older brother (Peter) with grandparents (Willi and Hedwig Lachmann) in anglicized) was a printer, and his mother Koblenz, Germany, prior to the family’s move to England. Middle: George as a schoolboy, circa 1947. Edith Elizabeth was a research physicist Right: George and his mother, Edith, circa 1962

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, U.K. Corresponding author: Philip Home, [email protected]. © 2017 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license. care.diabetesjournals.org Home 1155

synthesis into intermediary metabolism, methods, pH by direct measurement, and though at that time at a cellular organelle potassium by flame photometry, to which level. George added insulin by radioimmunoas- Serendipity broke the leg of George’s say. Together these set the scene for a supervisor at that time, and George had series of investigations into the biochem- to take over tutorials of undergraduates. ical disturbance and management of ke- Oxford tutorials were intensive for both toacidosis. But perhaps it was Turner’s parties, and in this case the tutor (George) recent observation that insulin had a had to learn rapidly about insulindand half-life in plasma of 4–5 min that led to was duly hooked for life to insulin and the realization that the then current ap- George at the IDF Western Pacific Region meeting diabetes. When later asked why he chose proach to treatment of ketoacidosis (of- in Asia, circa 1980s the field of diabetes, George responded, ten 100 units as an intravenous bolus and “I chose diabetes because of my training 100 units subcutaneously) made no phar- in biochemistry and the fact that I sud- macological sense. A published letter denly found myself teaching endocrinol- from George Alberti makes it clear that Association for the Study of Diabetes ogy as a graduate student . . . and was maintaining intravenous lines as an alter- (EASD) (and thus editorship of Diabetolo- fascinated by the then dispute about native approach was not found reliable in gia), and the International Diabetes whether insulin acted on the cell surface routine clinical practice at the time, lead- Federation (IDF) (see below). Further Ger- or within the cell.” After this laboratory ing to the famous and career-establishing man connections were made, notably fi experience he returned to being a clinical article in The Lancet on low-dose hourly with the nascent arti cial pancreas com- medical student, with one chosen attach- intramuscular insulin injection (6). Even munity, as German science reestablished ment being to the diabetes medical unit now that is worth rereadingdthe em- itself. Industrial contacts were also devel- in Oxford. Here we get a first public phasis is as much on fluid replacement oped, two of the most fruitful being with glimpse of an interest in diabetes and clin- and careful monitoring of plasma potas- Boehringer Mannheim and with Novo In- ical biochemistry, with an article in The sium as on the insulin delivery. And in his dustri, both having strong clinical bio- Lancet on the accuracy and precision bibliography it was already number 31 of chemistry interests, the latter through ’ of the new-fangled near-patient technol- what is now over 1,100 original contributions. Lisa Heding s research and development ogy of glucose measurement, the Ames A notable temporary influence in laboratory in Bagsvaerd. Dextrostix (4). Oxford was a visiting professor, Knud This then set the scene for a diversity Clearly George’s clinical talents were Lundbaek, with whom George talked end- of activity in diabetes research and care appreciated, for his obligatory supervised lessly about diabetes and philosophy. and later beyond. An interesting com- postqualification year was on the house Later George did spend a little time with mentary from 2002 looks back on the ’ (intern) in Oxford at the Radcliffe In- him in Arhus,˚ where he established valu- impact of George s work and output in firmary teaching hospital, a post for the able and lasting collaborations on metab- the 1970s and 1980s and includes a list of selected few. But the restless scientist olites and hormones in particular with those publications he thought most im- then moved for further clinical-academic Hans Ørskov. portant (7). Also at that time, George Al- training to Boston, at Harvard in the But a career needs academic space, berti became a target for those seeking Endocrine-Metabolic Unit at Peter Bent and a base, and Oxford could not then training in diabetes clinical research from Brigham Hospital and then the Biochem- offer those in either clinical biochemistry around the world, and the Newcastle unit ical Pharmacology Unit at Massachusetts or medicine. Nick Hales, who had recently attracted an extraordinary diversity of General Hospital. His work there focused taken up the clinical biochemistry chair young fellows from Italy, the Netherlands, on mineralocorticoid activity, but he re- in Cambridge, drew George’s attention Tanzania, Cameroon, Australia, Singa- ally wanted to be with diabetes at the to the vacancy in Southampton (1973). pore, Paraguay, and elsewhere. These Joslin and indeed spent much “spare” While George rapidly established his unit people returned home and established time there, notably picking up Stu Soeldner’s in Southampton, using the automated in- internationally recognized careers, as of insulin assay (5). George (with the assay) termediary metabolite assays and adopt- course did a bunch of more homegrown subsequently returned to the Radcliffe ing the Biostator artificial pancreas, he fellows. as a clinical fellow in the Nuffield Depart- began to nurture some notable future ment of Clinical Medicine, with associ- contributors to academic diabetes. A few Insulin Therapy ated lecturer status at Oriel College. His years later a new opportunity arose with The role of insulin science and insu- sole clinical commitment was to the di- the vacancy in a similar post in Newcastle lin measurement in stimulating George abetes services. (1978), which was doubly attractive, being Alberti’s career and the translation of From that appointment we see the in- home territory and having a strong biochemical and pharmacological under- terest in diabetes flowering, notably in endocrinology unit under Reg Hall. But standings into a revolution in the man- work with Derek Hockaday, a talented George’s networking had already begun agement of diabetic ketoacidosis is if idiosyncratic diabetologist. At the time to foster other collaborations, notably discussed above. But George in later life clinical biochemistry had advanced to with Harry Keen and thus pumped in- highlighted other areas of diabetes man- allow glucose-specific assay in blood/ sulin therapy, glucose control and comp- agement with insulin as being of his great- plasma by glucose oxidase, intermediary lications, and the trio of the World est contributions (7), and it is difficult to metabolites by enzymatic dehydrogenase Health Organization (WHO), European disagree. 1156 Profiles in Progress Diabetes Care Volume 40, September 2017

Quite how the concept of continuous George immediately saw the potential Roy Taylor (insulin insensitivity), Loranne subcutaneous insulin infusion (CSII) was for “reversing” the glucose clamp in Agius (hepatocyte biochemistry), Sally generated between John Parsons, Harry order to compare animal and human in- Marshall (nephropathy), and Mark Walker Keen, and George Alberti, apparently in sulins in terms of potency and clearance (genetics). Others made their mark out- the back of a London taxi, may never be kinetics when given intravenously side Newcastle, notably Murray Stewart, known. But its potential appeal as a tool (10,11), using the Biostator. Newcastle the current chief medical officer for phar- in studying insulin pharmacokinetics and then led the first multicenter randomized maceuticals at GlaxoSmithKline. in improving blood glucose control to clinical trial of the new Novo human insu- address the issue of control and compli- lins in the early 1980s, although by to- International Initiatives cations was immediately compelling to day’s standards it looks like a limited It is quite difficult to give an overview of George and Harry. The initial work began and weak effort. George Alberti’s international activities in at Guy’s Hospital, London, in March 1976, Further work, which George later said diabetes and indeed in noncommunica- as Harry Keen had medical beds there. he felt was a particularly important con- ble diseases more widely. As a flavor his The early articles followed later after a tribution, concerned management of di- curriculum vitae lists 16 WHO-related po- research fellow was recruited (8); the ar- abetes in surgery (12), work begun in sitions over 30 years (1979–2009). And ticles rapidly received global attention, Southampton. At that time surgical care then there are the EASD activities, numer- uptake and diversification, and challenge. had a poor record for acute hyper- and ous roles in the IDF, and work on major Indeed multiple daily insulin injections hypoglycemic complications. The essence projects in Tanzania and in Cameroon. A (MDI, mealtime and basal insulin) grew was glucose-insulin-potassium infusion number of the WHO and IDF activities as a general paradigm from that chal- together with bedside monitoring and were in close collaboration with his close lenge, and the need for measures of con- specialist service training and supervision. friend Paul Zimmet (Melbourne; .100 trol ensured the success of Boehringer’s This further expanded the role of the di- joint articles), and this includes the exten- 20-800 test strip and the glycated hemo- abetes specialist nurse, and, with the sive health surveys and population pre- globin assay, both the subject of studies in need for their skills in patient education, ventive activity in Mauritius over several Newcastle. The Newcastle laboratory un- insulin dose adjustment through self- decades (15), after the regional WHO der Jackie Burrin also tried very hard to monitoring, and use of pen-injectors, office became concerned at the high di- develop and automate chemical methods made for a major expansion in the make- abetes prevalence on that sugarcane- for measurement of the latter, trumped up of George’s clinical team at Freeman growing island. eventually by high-performance liquid Hospital. But the surgical collaboration George is listed not as a member but chromatography. also extended to open heart surgery rather the rapporteur of the 1980 report Not all ventures were a success then, (13) and intensive care management, from the WHO Expert Committee on clas- and the Newcastle/Guy’scollaboration along with a series of impactful articles sification and diagnosis of diabetes, and plunged into the deployment of insulin in that area, notably with Martin Elliott his hand (or brain) can be strongly de- pumps and, by diverse routes, into brittle and Geoff Gill. tected in the writings (16). This was car- diabetes. George’s prize lecture to the The article that has perhaps touched ried through to the 1997, 2005, and EASD in 1980 addressed the topic and the largest number of people with diabe- 2009 Expert Committees, two of which echoed around the world, but it would tes, but is now largely forgotten, also he co-chaired. These take us through now be seen as missing the essence of dates from the 1980s and also derived changes in diagnostic levels, changes in the problem. from an understanding of insulin absorp- terminology (to “type 1” and “type 2” di- As noted above, one interest in CSII tion profiles, this time of extended-acting abetes), alignment with U.S. national was its possible use to test the diabetes insulins. A long-running controversy had recommendations, and the like. Beyond control and complications hypothesis. been as to whether prebreakfast hyper- diagnosis and classification are docu- Another key article from his own bibliog- glycemia was reactive to night hypoglyce- ments on diabetes complications, preven- raphy that George highlights is that of the mia or to insulin deficiency due to the tion of diabetes, and later the metabolic Kroc study, for which Newcastle was the limited duration of action of NPH and syndrome. Aligned with this activity were central laboratory, the feasibility study for zinc-complexed insulins. The article, in important contributions to the IDF, begin- the Diabetes Control and Complications The BMJ in 1983, established the advan- ning with the WHO/IDF (joint) Execu- Trial (DCCT) (9). An intercontinental tage of giving the extended-acting insulin tive Committee in the 1980s, which he study, it taught us many lessons and en- late in the evening (14); it is now difficult chaired for 3 years. In IDF he rose to pres- abled funding for the DCCT; however, the to understand how radical not giving an ident in 2000–2003, but he has continued international courier system for biochem- insulin before a meal seemed at the time, to contribute since to expert groups no- ical samples was proved unreliable in the but of course the new timing rapidly be- tably in collaboration with Paul Zimmet 1980s, and the DCCT was therefore per- came standard, even for the new long- on such topics as the metabolic syndrome formed in North America alone. acting insulin analogs 20 years later. (17), sleep apnea, and, as late as 2016, Three other areas are worth noting. The Newcastle unit retained an interest bariatric surgery. Human insulin for clinical trials became in continuous glucose sensing in the Initiation into the realities of interna- available from Eli Lilly (again via Harry Keen) 1980s, but other activities under the lead- tional life began early. The 1982 IDF in 1980 and from Novo through George’s ership of Alberti appointees from that World Diabetes Congress was in Nairobi. Copenhagen and U.K. connections. With decade blossomed and continue to this George was the chair of the scientificpro- his insulin pharmacology background day, including international names like gram and arrived early to find a congress care.diabetesjournals.org Home 1157

center designed for political perfor- EASD meeting) and president for the actually do medical ward rounds for un- mances, not a scientific meeting. Slide 1992–1995 triennium. Along the way he selected admissions in Newcastle for a projectors were acquired, white bed- took on the editorship of Diabetologia, while, but his junior staffs’ views on his sheets hung as display screens, and vari- reading and editing every published arti- abilities are not recorded. He then be- ous materials taped over windows for cle personally in detail and leaving his as- came dean of the Medical Faculty. blackout. The congress was a success. sistant editor (your current author) to Alongside these activities George Al- Meanwhile George led a party to a local pick up the myriad changes implemented berti remained active in U.K. diabetes, in diabetes education program at Kisumu on or not by anxious authors in successful particular through roles in the British Di- Lake Victoriadan 8-h, 225-mile (360-km) revisions. A Diabetes Care editorial cele- abetic Association (now Diabetes UK), no- drive. He opened the meeting in a sub- brated George’s approach (18). He also tably in its Medical and ScientificSection terranean lecture theater that promptly founded, as secretary, the EASD Study (indeed from 1974), then Research Com- lost all lighting, but he continued in pitch Group on Artificial Insulin Delivery Sys- mittee, then Council, then as chair of the blackness for a further 8 min (no mobile tems, Pancreas and Islet Transplantation, organization in 2009. While it hardly phones then). His voice then suggested giving it (in a typically irreverent touch) seems possible, given the wealth of other we move upstairs, and the meeting con- the acronym AIDSPIT. He never attended activities, he at the same time was active tinued successfully without electric one of its annual meetings, but they con- in the Royal College of Physicians (of Lon- teaching aids for the rest of the day. tinue to this day. don), being a member and then chair of His two biggest international projects Of even more impact, certainly in the their Diabetes and Endocrinology Com- were (and continue) in Tanzania and last 10 years, was the first of the Euro- mittee before being elected president of Cameroon. All such projects depend on pean diabetes guidelines. The first docu- the College, the highest position for any engaging the right people on the ground, ment, correctly entitled “a consensus physician in the U.K., in 1997. This drove and here Kaushik Ramaiya and Jean- view,” grew from a meeting organized interests more broadly than diabetes, Claude Mbanya, having spent time in by George Alberti and Arnold Gries in though the Africa projects remained im- Newcastle, have been key collaborators, Berlin in 1987, with the “blessing” of portant to him; notably while at the Col- not just in the projects but in senior posi- IDF Europe. This evolved into a more com- lege he pushed forward policies over tions in IDF regionally and globally. Many prehensive Desktop Guide for the Manage- specialty training for medical graduates, other researchers have been involved of ment of Non-insulin-dependent gaining friends and enemies. Other con- course, familiar names now in the diabe- Diabetes Mellitus in 1989. A number of fea- tributions were to the U.K. Medical Re- tes epidemiology and care field, with tures are notable: no systematic literature search Council and the U.K. General perhaps one of the more important and review was used, and both were highly Medical Council, the latter responsible least recognized being Donald McLarty. influenced by the authors’ views and no- for standards of medical practice. George possibly took his cues from Harry tably those of a small executive group. He retired from Newcastle University Keen’s Whitehall and Bedford studies and One company (Boehringer Mannheim) in 2002. But “retirement” has not been Paul Zimmet’s work in Mauritius, and a provided the funding. But the reception quiet. As noted above contributions to key component was always to base policy was good, just at a time when the IDF/ international activities continued. A on measured disease impact and hence WHO (Europe) St. Vincent Declaration national role in the reconfiguration of on high-quality epidemiological findings. was having significant international im- emergency medical services saw George George already knew the importance of pact, and so a further iteration followed giving continued advice to U.K. ministers science to the development of diabetes in 1993 under its auspices and with a of health (he was on government com- care from his biochemical/insulin work wider consultative group (19). Though mittees from 1976), and his charisma discussed abovedtheattitudeof“get sometimes a poor finisher, George Alberti and communication skills enabled him to the data and then apply it” was imple- did not rest there, however, and moved on explain the modern medical advantages of mented in rural Africa. to a more evidence-based approach (though fewer, more distant but more highly George once professed that there was not systematic) for the Desktop Guide to skilledservicestogatherings of concerned nothing he liked better than lecturing Type 2 Diabetes Mellitus (with a sister for local people. A notable national contribu- about diabetes. He certainly did his com- type 1 diabetes) in 1998–1999 (20). These tion was the chairing of a U.K. national plement internationally, talking on a wide guidelines can be seen as setting the working party on the health care response series of topics. Of course he was also in- scene for the guidelines, position state- to violence against women and children, a volved in organizing meetings globally ments, and consensus views developed document which has raised and directed other than for IDF/EASD, and a notable and still evolving in the decades since, attention in the area ever since (21). The series was held under the auspices of some of which are now truly evidence- Imperial College London provided an Nobuo Sakamoto’s unit in Nagoya, work- based and free of commercial funding. academic anchor for a while, while the hos- ing with Nigishi Hotta. pital local to his London residence (King’s And Back in the U.K. College Hospital) found itself with a new Meanwhile, Back in Europe, and Back in Newcastle, George moved from and active chairman, returning the com- Diabetes Guidelines Clinical Biochemisty to the chair of pliment more recently by rescuing George’s In 1977 George joined the Executive Medicine in 1985, with a brief sojourn in health from a serious illness. Council of the EASD, becoming its secre- Nashville with Alan Cherrington where he Inevitably the London-based activities tary in the early 1980s (and therefore was studied biochemical effects of catechol- drew George away from Newcastle. Addi- responsible for the content of the annual amines on Alan’s dog model. George did tional enticements were his love of the 1158 Profiles in Progress Diabetes Care Volume 40, September 2017

has greatly benefited the many millions of comparison of the activity and disposal of semi- those with diabetes. synthetic human insulin and porcine insulin in normal man by the glucose clamp technique. Dia- betologia 1982;22:41–45 12. Alberti KGMM, Thomas DJB. The manage- Acknowledgments. It would not be possible for ment of diabetes during surgery. Br J Anaesth the author to fully acknowledge George Alberti’s 1979;51:693–710 contributions to his own career, without which he 13. Elliott MJ, Gill GV, Home PD, Noy GA, Holden could not have written this article. Thanks are due MP, Alberti KGMM. A comparison of two regimens for use of his curriculum vitae and the answering for the management of diabetes during open-heart of queries on his early career. Nor is it possible to surgery. Anesthesiology 1984;60:364–368 d mention more than a fraction of his collaborators 14. Francis AJ, Home PD, Hanning I, Alberti to the rest, apologies. KGMM, Tunbridge WMG. Intermediate acting No potential conflicts of in- Duality of Interest. insulin given at bedtime: effect on blood glucose terest relevant to this article were reported. concentrations before and after breakfast. Br Med J (Clin Res Ed) 1983;286:1173–1176 George and Stephanie hiking in the English Lake References District 15. Magliano DJ, Soderberg¨ S, Zimmet PZ, et al. 1. Medawar J, Pyke D. Hitler’s gift. Chatham, Mortality, all-cause and cardiovascular disease, Mackays of Chatham, and New York, Academic, over 15 years in multiethnic mauritius: impact of hills of the Lake District of northwest Eng- 2001 diabetes and intermediate forms of glucose toler- 2. Anonymous. George Alberti: laid back, icono- land, where he has a country retreat, and ance. Diabetes Care 2010;33:1983–1989 clastic, irreverent. BMJ 2016;353:i2331 16. World Health Organization. WHO Expert of Stephanie Amiel, whom he married in 3. Alberti KGMM. Amino acid metabolism in mi- Committee on Diabetes Mellitus. Second Report 1998. Their joint enjoyment of opera as tochondria. DPhil thesis, Oxford, Oxford Univer- [Internet]. Geneva, World Health Organization, well as that of diabetes helped. He also sity, 1964 1980. Available from http://apps.who.int/iris/ admits to spending a certain amount of 4. Alberti KGMM, Middleton GG, Caird FI. The bitstream/10665/41399/1/WHO_TRS_646.pdf. accuracy of Dextrostix in the estimation of blood Accessed 20 January 2017 time gardening and chopping wood, be- – sugar. Lancet 1965;2:319 321 17. Alberti KGMM, Zimmet P, Shaw J; IDF Epide- ing an avid reader of classical crime fic- 5. Soeldner JS, Slone D. Critical variables in the miology Task Force Consensus Group. The meta- radioimmunoassay of serum insulin using the tion, and having an addiction to peanut bolic syndrome–anewworldwidedefinition. double antibody technic. Diabetes 1965;14: brittle. His three sons (from his first mar- Lancet 2005;366:1059–1062 771–779 riage) also dispersed geographically and 18. Skyler JS. The shoulder bag. Diabetes Care 6. Alberti KGMM, Hockaday TDR, Turner RC. 1981;4:331–331 academically, now being an academic Small doses of intramuscular insulin in the treat- 19. Alberti KGMM, Gries FA, Jervell J, Krans HM; GP (family doctor) in Middlesbrough, ment of diabetic “coma.” Lancet 1973;2:515–522 European NIDDM Policy Group. A desktop guide professor of Cultural Anthropology at 7. Hanney SR, Home PD, Frame I, Grant J, Green for the management of non-insulin-dependent di- Framingham (MA), and keeper of Science P, Buxton MJ. Identifying the impact of diabetes research. Diabet Med 2006;23:176–184 abetes mellitus (NIDDM): an update. Diabet Med and Technology at the National Museum – 8. Pickup JC, Keen H, Parsons JA, Alberti KGMM. 1994;11:899 909 of Scotland, Edinburgh. George also has Continuous subcutaneous insulin infusion: an ap- 20. European Diabetes Policy Group. A desktop 10 grandchildren, though none live nearby. proach to achieving normoglycaemia. BMJ 1978; guide to type 2 diabetes mellitus [Internet]. Euro- George was knighted in the year 1:204–207 pean Diabetes Policy Group 1999. Diabet Med 1999;16:716–730. Available from www.staff.ncl 2000 for his dedication to the field of di- 9. Kroc Collaborative Study Group. Blood glucose control and the evolution of diabetic retinopathy .ac.uk/philip.home/t2dg1999.pdf. Accessed abetes. Sir K. George M.M. Alberti may and albuminuria. A preliminary multicenter trial. 20 January 2017 refer to himself as laid back and irrever- N Engl J Med 1984;311:365–372 21. Taskforce on the Health Aspects of Violence ent, but there is nothing irreverent about 10. Massi-Benedetti M, Burrin JM, Capaldo B, Against Women and Children. Responding to vio- the footprint he has made in the field Alberti KGMM. A comparative study of the activity lence against women and children – theroleof of diabetes. His campaign for change in of biosynthetic human insulin and pork insulin the NHS [Internet]. London, Department of using the glucose clamp technique in normal sub- Health, 2010. Available from www.health.org.uk/ management and urgent care, his bio- jects. Diabetes Care 1981;4:163–167 sites/health/files/RespondingtoViolenceAgainst chemical/insulin work, and his research 11. Home PD, Massi-Benedetti M, Shepherd WomenAndChildrenTheRoleofTheNHS_guide in the treatment of diabetic ketoacidosis GAA, Hanning I, Alberti KGMM, Owens DR. A .pdf. Accessed 20 January 2017