human, chimpfacial differences Scientists homeinonoriginof chioed actor, doesn’t but to teach the students aim to entertain vered star of south Indian cinema. eyes riveted onananimatedvideofeaturingNagarjuna, are- uniforms sitcross-legged onthestonefloor, facesgleaming and lis of Hyderabad, more than 100 students in blue and white authorship of the study. entist Tomasz Swigut, PhD, share senior author. Wysocka andseniorresearch sci- uate studentSara Prescott isthelead published onlineSept. 10inCell . Grad- past. shed lightonourrecent evolutionary study gene-expression changesthatcan be mimickedinadish,andthususedto steps ofearlyprimatedevelopment can lular anthropology” toexplainhow some for complex speech.”even use our larynx to houselargerbrains,walkuprightand ment andfacialstructure thatallow us of adaptationsinheadshape,eye place- tures, whichhave undergoneanumber we are interested- incraniofacialstruc cal andsystemsbiology. “In particular, of developmental biology and of chemi anna Wysocka, PhD, associateprofessor us different from thegreat apes, curred duringrecent evolution andmake regulatory changes in our DNA that oc and skin pigmentation. some involved in jaw and nose length to control facialdevelopment, including express different levels ofproteins known searchers foundthatchimpsandhumans genes themselves. In particular, there- rather thandissimilaritiesamongthe and where thegenesare expressed— versity are regulated —how much,when facial development andhumanfacialdi- identical genetic backgrounds. could ariseintwospecieswithnearly pinpoint how differences those structural at theSchoolofMedicine have begunto tive in the primate tree. Now researchers the factthatapesare ournearest rela- different from thatofahuman,despite Volume 7, No.16 By RuthannRichter Indian kidsaboutHIV/AIDS Using starpower toteach By KristaConger The video,featuringanavatar ofthehandsome,musta- At Zilla Parishad High SchoolinthesouthIndian metropo- A studydescribingtheresearch was The researchers coined the term “cel- “We tounderstandthe are trying The keyliesinhow genesinvolved in The faceofachimpanzee isdecidedly inside Stanford test.” riage andhave mygroom getan HIV I wanttogothehospitalbefore mar- learned a lot. Now I have an awareness. the 22-minute video.after viewing “I 13-year-old student,Dharana, said sibly save their lives. could help protect their health and pos some basics about HIV/AIDS that September 14, 2015 September Though “I neverHIVexisted,” knew one ” said Jo- - - her colleagueswondered whetherdiffer- nearby genes are expressed. Prescott and DNA thatcontrol when,where andhow chemical tagsandproteins boundtothe panzee genomes. These regions contain enhancer regions inhumanandchim- ers focusedonareas ofDNAknown as The role ofenhancerregions proteins known tocontrolfacialdevelopment, includingsomeinvolvedinjawandnoselength. Although chimps and humans have almost identical genomes, their genesmake different amounts of For their comparison, the research- See aids, page6 PublishedbytheOfficeofCommunication&PublicAffairs - tern, whichrepeats abnormallyinsome peoplewith DNA sequence ismadeupofasix-nucleotide pat- called frontotemporal dementia. In thisregion, the ALS andanotherrelated neurodegenerative disorder has been associated with the development of both genetic stutterinaregion ofDNAcalledC9orf72 unknown whatcausesmanycasesofthedisease, a progressive neuromuscular disorder. Althoughit’s of the deadly condition. the firsttoopenawindow intothemolecularcauses a cell’s commandcenter. The findingsare among ability tomove proteins into andoutofthenucleus, associated withthediseasewere hampered intheir Medicine. cording toastudyby researchers attheSchoolof symptoms ofamyotrophic lateralsclerosis, ac- responsiblecells maybeatleastpartially forsome By KristaConger T rail getshotterinhuntforcauseof Also known asLouGehrig’s disease,ALSisa The researchers foundthatcellswithamutation A defectinhow proteins are inside transported quences of enhancers quences ofenhancers shown that changes in the DNA se- Wysocka. “Many recent studieshave changed during recent evolution,” said ity of these enhancer regions may have between humans and chimpanzees. could explainmorphologicaldifferences enhancer regions duringdevelopment ences inthewayproteins bindtothese “We wantedtolookathow theactiv- © 2015 Mes © 2015 See face, page6 a Sc of copies. This muta- this region is expandedintohundreds orthousands sociate professor ofgenetics. “But insome people, six-nucleotide pattern,” saidAaron Gitler, PhD, as- ALS or FTD. with thetransport ofproteinsinandoutacell’s nucleus. A mutationlinked toamyotrophiclateral sclerosisinterferes hu “Healthy people have two to five repeats of this mac her who gettutoring relieved inchildren Study: Mathanxiety no attentionhasbeenpaidtohow mathematical expertise. Yet almost classes aswell ascareers thatrely on suing advanced mathandscience life, discouragingthemfrom pur- the anxietypersiststhroughout doing mathproblems. For some, many children feelanxiousabout get remediation of math anxiety.” surprising thatwe could,infact, andbehavioralsciences.“Ittry was Menon, PhD, professor ofpsychia - the study’s seniorauthor, Vinod but isalsoanxiety-reducing,” said not onlyimproves performance, findings is thatcognitive tutoring ment for math anxiety in children. first todocumentaneffective treat- The Journal ofNeuroscience, isthe in the brain’s fear circuits. tutoring fixed abnormal responses from theSchool of Medicine. The gram, according study toanew one-on-one mathtutoringpro- problems canberelieved witha By ErinDigitale Even if they are good at math, mostexciting aspectofour “The The study, publishedSept. 9in Anxiety aboutdoingmath w a vebre See a k medi k Page 4 orientation. month for arrived last students medical First-year o Math, page7 y See a a 979 /shutterst 979 / shutterst ALS ALS, page7 oc oc k

k Girls and boys with autism differ in behavior, brain structure By Erin Digitale with high-functioning forms of autism in the United had less-severe repetitive and restricted behaviors. “This States, he said. replication provides the strongest evidence to date for Girls with autism display less repetitive and restricted Repetitive and restricted behavior is perhaps the gender differences in a core phenotypic feature of au- behavior than boys do, according to a study by research- most widely recognized of the three core features of au- tism,” Menon said. ers at the School of Medicine. tism. It can show up as a child’s preoccupation with a Brain-structure differences The study also found that brain differences between narrow interest, inflexibility about routines or repetitive boys and girls with autism help explain this discrepancy. motions such as hand-flapping. The other core features The brain-scan analysis revealed several gender dif- The study, which was published online Sept. 3 in of autism are social and communication deficits. ferences in brain structure between typically develop- Molecular Autism, gives the best evidence to date that More boys with high-functioning autism ing boys and girls, consistent with the findings of earlier boys and girls exhibit the developmental disorder studies. differently. Among children diagnosed with the high-function- Children with autism, however, had a dissimilar “We wanted to know which specific clinical mani- ing form of autism, boys outnumber girls by four to set of gender differences in their brains — specifi- festations of autism show significant gender differences, one. Scientists were interested in comparing the expres- cally, in the motor cortex, supplementary motor area and whether patterns in the brain’s gray matter could sion of core features of the disorder between sexes be- and a portion of the cerebellum. These regions affect explain behavioral differences,” said the study’s senior cause they have long suspected girls with autism may motor function and planning of motor activity. The author, Vinod Menon, PhD, professor of psychiatry display symptoms differently, causing them to be un- researchers noted that many repetitive behaviors, such and behavioral sciences. Knowledge of the difference derdiagnosed or making it harder for them to get the as hand-flapping, have a motor component. The study could help clinicians better recognize and treat autism most appropriate treatment. demonstrated that patterns of gray matter in these mo- in both sexes, he added. “Understanding this is really “Autism has primarily been studied from the view- tor regions could accurately distinguish girls from boys quite crucial clinically.” point of boys with the disorder,” said Menon, who with autism, Supekar said. The researchers found that “We found strong evidence for gender differences in holds the Rachael L. and Walter F. Nichols, MD, Pro- parts of the motor system that contributed to individual autism,” said postdoctoral scholar Kaustubh Supekar, fessorship. “Understanding gender differences can help scores for repetitive and restricted behaviors were differ- PhD, the study’s lead author. The researchers used two in identifying the behavioral skills that are most impor- ent in boys and girls. large, public databases to examine nearly 800 children tant to remediate in girls vis-a-vis boys.” “Girls and boys with autism differ in their clinical The study examined the severity of autism symptoms and neurobiological characteristics, and their brains are Altanaka / Shutterstock in 128 girls and 614 boys registered with the National patterned in ways that contribute differently to behav- Database for Autism Research. The children ranged in ioral impairments,” Menon said. age from 7 to 13, had IQ scores above 70, and had been “The discovery of gender differences in both behav- evaluated with standard tests for autistic behavior. The ioral and brain measures suggests that clinicians may boys and girls were matched for age, and had the same want to focus diagnosis and treatments for autistic girls average IQ. Girls and boys had similar scores for so- differently than boys,” Supekar added. cial behavior and communication. But girls had lower This research was supported by a NARSAD Young scores on a standard measurement of repetitive and re- Investigator Award, an Atherton Investigator Award, stricted behaviors. the National Institutes of Health and the Simons The researchers then examined data from the Au- Foundation. tism Brain Imaging Data Exchange that included Creation of the ABIDE data set was supported by structural MRI brain scans of 25 boys with autism, 25 the National Institute of Mental Health, the Leon Levy girls with autism, 19 typically developing boys and 19 Foundation, Joseph P. Healy, and the Stavros Niarchos typically developing girls. The individuals among the Foundation. Menon is a member of the Stanford Child groups were matched for age and IQ. The researchers Health Research Institute. A new study shows that there are gender-based differences in the again found that girls and boys did not differ on so- Stanford’s Department of Psychiatry and Behavioral behaviors displayed by children with autism. cial behavior and communication skills, but that girls Sciences also supported the research. ISM

When families of patients prefer Spanish at the hospital

By Erin Digitale for such a different interaction,” said the preter, and 78 of which communicated that serve large numbers of Hispanic study’s senior author, Matias Bruzoni, directly in Spanish with their caregivers. patients, to create similar teams catering Spanish-speaking families are more MD, assistant professor of surgery. Bru- The control group was 56 English-speak- to Spanish speakers. “Not only is the pa- satisfied with and better understand zoni is the surgeon for the center, which ing families of any race or ethnicity who tient population growing, the physician their children’s surgical care when they is part of Stanford Children’s Health. spoke with their caregivers in English. population is growing,” he said, adding communicate with the surgical team Hispanics form a large and growing The verbal interaction between the that he sees a growing number of surgical in their native language, according to a part of the U.S. population, particularly caregivers and families included patient stanford children’s health new study from the School of Medicine in , and 25 percent speak little registration; the intake exam, history and and Lucile Packard Children’s Hospital to no English. Although professional physical; explanation of the patient’s di- Stanford. medical interpreters can help bridge agnosis and management plan; surgical The study, which appears in the Sep- the language gap, there are drawbacks consent; and pre- and post-operative in- tember issue of the Journal of Pediatric to using an interpreter compared with structions for the parents and patient. Surgery, examined outcomes in the His- communicating in the patient’s native All families included in the experi- panic Center for Pediatric Surgery at the language: For instance, less information ment answered a questionnaire to as- children’s hospital. All staff members can be communicated in the same-length sess their general satisfaction with their at the center, including the reception- appointment because everything that is care, their feelings about the importance ists, triage staff, nurse practitioners and said must be interpreted. of speaking the same language as their pediatric general surgeon, interact with The study compared patient satis- child’s caregivers, and their feelings about patients and their family members in flu- faction among three groups of families the quality of information they received ent Spanish. Families thus receive all of whose children received surgical care at from hospital staff. their medical care without the need for the hospital between November 2011 Interacting in Spanish Matias Bruzoni is the senior author of a study an interpreter. and July 2013. The two experimental that found Spanish-speaking families were more “Even though the interpreters are groups were made up of Hispanic, exclu- Spanish-speaking families that dis- comfortable when they were able to communicate great, being able to look someone in the sively Spanish-speaking families, 43 of cussed their children’s care in Spanish with surgical teams in their native language, eye and tell them how we feel, and hear which communicated with their English- reported a higher level of satisfaction and without the need for interpreters. directly how they feel about us, makes speaking caregivers via a medical inter- higher ratings of the quality of informa- tion they received compared with the fellows of Hispanic background receiving Inside Stanford Medicine is families in the control group and those training. “We need bilingual and bicul- published monthly in July and that worked through an interpreter. tural staff to help improve our ability to Stanford December and semi-monthly Spanish-speaking families rated the im- provide patient-centered care.” n sid e

i the rest of the year. portance of discussing care in their native Other Stanford-affiliated authors of medicine language more highly than English- the study are medical students Jonathan is produced by Paul Costello speaking families, the study found. Dunlap and Joshua Jaramillo; Raji Kop- Office of Communication & Public Affairs Chief communications officer Although socioeconomic status was polu, a nurse practitioner in surgery; Susan Ipaktchian not assessed in this study, Bruzoni noted Robert Wright, a social science research School of Medicine Director of print & 3172 Porter Drive Web communications that Hispanic families of low socioeco- assistant in pediatric surgery; and Fer- Palo Alto, CA 94304 John Sanford nomic status may have an even greater nando Mendoza, MD, professor of pedi- Mail code 5471 Editor need than others to receive care in their atrics and a member of Stanford’s Child (650) 723-6911 Robin Weiss native language. “There is a big cultural Health Research Institute. http://med.stanford.edu/news/ Graphic designer barrier,” Bruzoni said. “Because of these The research was funded by the His- patients’ circumstances, it is even more panic Center of Excellence at Stanford Send letters, comments and story ideas to John important to work with them using their and the School of Medicine’s Medical Sanford at 723-8309 or at [email protected]. own language.” Scholars Research Program. Please also contact him to receive an e-mail version of Inside Stanford Medicine. He said he wants to encourage other Stanford’s Department of Surgery also clinics and hospitals, particularly those supported the work. ISM 2 September 14, 2015 Inside Stanford Medicine 5 questions Jim Laflin discusses his role as ombudsperson an occasional feature in which an expert answers five questions on a science or policy topic Jim Laflin, JD, is an attorney specializing Resource Center and Office of the Ombuds, helping to resolve a variety of academic and in mediation and conflict resolution who came to the School of Medicine a year ago as its workplace disputes. He has taught courses on mediation and negotiation, published pa- ombudsperson. He is the founder of Concilium, a San Francisco-based mediation firm pers on the issues and lectured widely. through which he mediated complex civil cases throughout California, the Northwest and In a recent interview with writer Ruthann Richter, he discussed his job at the medical Alaska for 20 years. He also has worked as a consultant for UC-San Francisco’s Worklife school and the services offered through his office.

What is the role of the school’s ombudsperson and that involvement can take the form of mediation, facili- first to establish such an office. 1how does he/she help the medical school commu- tated conversations, dialogue, shuttle diplomacy, coach- nity? ing or some combination thereof. Importantly, the What are the biggest challenges of the job? office does not become involved in formal processes, 4 Laflin: The Office of the Ombudsperson serves as a such as investigations, grievances and appeals. Never- Laflin:Some of the biggest challenges involve trust confidential resource for the entire medical school theless, I can offer explanations of those processes and and default thinking. Trust because it’s the foundation community, including faculty, staff, students, graduate how to engage them. of the relationship between the ombudsperson and the students and post-docs, regarding any School of Medi- individuals who come for help. It’s something I never cine-related problem or issue that arises. Typical exam- Why is it important to have an ombudsperson? take for granted. I have to earn it with every person I ples are workplace conflicts arising between colleagues 2 work with. And that takes time, effort, honesty and and/or supervisors, mistreatment, harassment and bul- Laflin: It’s important to have an ombudsperson so compassion. lying, authorship and scientific misconduct disputes, that problems are addressed in a timely, effective and Default thinking is another big challenge. By the re-appointment and promotion concerns, favoritism fair way for all parties concerned. This simply doesn’t time most people reach out to the ombudsperson, and/or discrimination (based on age, race, gender, reli- happen unless organizations such as the medical school they’ve exhausted pretty much all the options they can gion, national origin, etc.), and unfairness proactively create and support informal see for themselves; they can’t think of anything else to in the application of school policy, among channels, such as the ombudsperson, spe- do. This is a normal result of how our minds work, es- other things. cifically focused on that goal. I’m not ar- pecially in stressful circumstances; we replay the same The ombudsperson acts informally, as guing that formal investigatory, appeal and internal narrative over and over again. I call this default a neutral and independent voice for fair- grievance processes aren’t legitimate or that thinking, and I work to help people get out of this box ness, not as an advocate, but in the inter- they don’t have their place. They are and so that they can take a fresh look at their circumstances ests of all sides. Some refer to this as being they do. However, the informal tools of and consider making some different choices. So this is multipartisan. the ombudsperson are far more appropriate another big part of what I do: supporting best thinking So, what does the ombudsperson do? and effective when it comes to improving and moving beyond default thinking. First and foremost, I listen. My office is a communication, restoring trust, building safe place where visitors can be heard with- Jim Laflin more responsible relationships and cutting I imagine that people might shrink from a phone out worrying about repercussions. Some- through bureaucratic red tape to achieve 5 call or visit from you, as they expect you to be the times that’s all visitors want. Beyond that, good outcomes. Otherwise, individuals bearer of bad news. How do you manage socially? I can provide information concerning school policies and the organization suffer the consequences of fes- and formal processes and explain how those policies tering conflict, such as attrition, lost productivity and Laflin: This is a great job, one that I’m grateful for and processes might apply in a specific situation. I don’t lawsuits. and that I thoroughly enjoy coming to every day. Once advise individuals what to do but help them understand people understand what it is that I do, they’re nearly their options. By helping to identify and clarify options, Do most medical schools have an ombudsperson or always appreciative — not only of me personally but visitors can decide and choose for themselves how best 3 is Stanford unusual in this respect? more importantly of the School of Medicine and what to proceed. So self-determination is a major principle it says about the values of the leadership and institution here. Sometimes that can entail further involvement of Laflin: I believe most medical schools now have an that they care enough about this community to devote the ombudsperson, and sometimes not. Where it does, ombudsperson. To Stanford’s credit, it was among the the resources required to support the office. ISM

Carlos Bustamante named chair of new Sino-U.S. Symposium on Department of Biomedical Data Science Medicine set for Oct. 15–16

By Jennie Dusheck Lavori, PhD, professor of health research By Jennie Dusheck and policy, has also agreed to serve as vice will discuss such challenges as trans- Carlos Bustamante, PhD, professor chair of the new department. Lavori will The Ninth Sino-U.S. Sympo- lating medical research into practi- of genetics and founding director of the step down as chair of the Department of sium on Medicine in the 21st Cen- cal benefits for patients, containing Stanford Center for Computational, Evo- Health Research and Policy to take on this tury will be held Oct. 15-16 at the health-care costs, expanding patient lutionary and Human Genomics, has been new role. Bustamante and Lavori will be- Li Ka Shing Center for Learning & access, providing new care delivery appointed chair of the new Department of gin their terms on Oct. 1. Knowledge on the Stanford campus. models for aging populations and Biomedical Data Science. Bustamante is pre-adapted for devel- Hosted by Stanford Medicine, the the increasing incidence of chronic The department will build on the oping the new department, which was two-day event will include panel conditions. School of Medicine’s strengths in using created in June. “I’ve been interested in discussions on precision health, mo- The theme for this year’s event is information technology to advance pre- large-scale data analysis since I was in bile health, population health and big data in health care and how to cision health and work to find common graduate school ” he said. He is a popu- genomics, with breakout sessions on use large-scale computing and data solutions to the challenges lation geneticist whose work has ethics, cancer, brain mapping, neu- analysis to improve health. The sym- of analyzing biomedical data encompassed analyzing genome- roscience, immunology and infec- posium also aims to foster long-term from varied sources, includ- wide patterns of variation within tious disease. collaborations among researchers ing biosensors, electronic and between species. He has used “Stanford Medicine is honored and clinicians in the medical records and genomic such genomic analysis to answer to welcome our Chinese partners to and China. sequencing. basic questions in biology, an- the Stanford campus this year. To- Other keynote speakers include Bustamante, who was thropology and medicine, and gether we will work to find answers Xu Tianle, PhD, president of the ba- involved in planning the has long worked at the interface to some of health care’s most press- sic medicine faculty at Shanghai Jiao department, said he is en- of genomics, computational biol- ing questions,” said Lloyd Minor, Tong University; Bill Brody, MD, thusiastic about his new ogy and mathematical genetics. MD, dean of the School of Medi- PhD, president of the Salk Institute; position. “It’s really a dream Carlos Bustamante After earning a doctoral de- cine, who will be a keynote speaker and Michael Levitt, PhD, Stanford come true,” he said. “Bringing together gree in biology at Harvard in 2001 and at the symposium. professor of structural biology and our exceptional faculty with expertise in completing a postdoctoral fellowship in Partnering with Ruijing Hos- 2013 Nobel laureate in chemistry. statistics, biomedical informatics and ‘big mathematical genetics at the University pital, the Shanghai Jiao Tong Uni- To learn more or to register for data’ analysis creates amazing opportuni- of Oxford in 2002, Bustamante was on versity School of Medicine and the the conference, visit http://med. ties for advancing precision health. Our Cornell University’s faculty in the depart- Salk Institute of Biological Stud- stanford.edu/sino-us.html. The reg- goal is to marry rigorous methods develop- ments of Statistical Sciences and Biology ies, Stanford Medicine will host istration cost is $195 for university ment, large-scale biological data sets, and Statistics and of Computational Biology. researchers, clinicians, industry ex- faculty, postdoctoral scholars, stu- clinical outcomes to uncover the mecha- He joined Stanford’s faculty in 2010. He perts and policymakers from China dents and trainees, and $295 for the nisms of disease and improve health and has received multiple honors and awards, and the United States. Participants general public. ISM well-being,” he said. including a Marshall-Sherfield Fellowship, Lloyd Minor, MD, dean of the School a Sloan Research Fellowship and a John D. of Medicine, said he is pleased that Busta- and Catherine T. MacArthur Fellowship. Please give blood mante will be heading the department. Bustamante said he plans to begin pop- Blood type needed: “Leadership in this area is fundamental to ulating the new department with a core O-, AB- Stanford Medicine’s vision for making pre- of 15-20 faculty from across the medical cision health a reality,” Minor said. “Car- school and add five to 10 “amazing inves- To request an appointment, call 723-7831 or you can make an appointment online. los has an inspiring vision for the future of tigators,” in the coming five years to build 3373 Hillview Ave., Palo Alto • 445 Burgess Drive, Menlo Park, biomedical data science, one that is enthu- up a premier department that engages 515 South Dr., Mountain View siastically shared by the founding faculty.” Stanford’s strengths in biostatistics, bioin- http://bloodcenter.stanford.edu The dean also announced that Philip formatics and computational science. ISM Inside Stanford Medicine September 14, 2015 3 New medical students ponder life-and-death questions at stethoscope ceremony norbert von der groeben By Tracie White coats and stethoscopes during a ceremony on the last day of orientation. Then they stand together as a group Silence fell in Berg Hall when Alvaro Galdos stood and read the Stanford Affirmation, which is a pledge amid a crowd of new medical students and their family written in the spirit of the Hippocratic Oath — an members and recalled the decision to end life support ancient vow to uphold certain ethical standards of for his youngest son, Luis, who was 8 year old. caregiving. “Eleven years ago we lost a son at a hospital in Texas The new cohort of 90 students was chosen from an due to a congenital heart defect,” Galdos said. His applicant pool of 7,200. Twenty-six were born outside oldest son, Francisco, a first-year medical student at the United States. Nine entered with graduate degrees Stanford who was 11 at the time, hopes to become a — eight with master’s degrees, one with a PhD — and pediatric cardiologist. 40 have published in peer-reviewed journals. “As much as we loved him, we didn’t want him to Most had not yet faced the responsibilities they will suffer anymore,” Galdos said. “We knew the end of his encounter routinely as physicians. It was the ethical life was coming. We made the decision to stop every- and emotional challenges ahead that Minor and Prober thing. Was this euthanization? We still wonder.” hoped to explore during the book discussion. “I think What is and isn’t euthanasia? Is there a line between one of the key lessons from this book: If we’re going to euthanasia and murder? How does a physician always make progress in medicine, we’re going to have to face uphold the Hippocratic Oath, which includes a pledge realistically when we make errors,” Minor said. “Prog- to abstain from doing harm? ress only occurs when we are able to frankly address those situations and acknowledge those errors.” norbert von der groeben The book describes health-care workers treating pa- tients in a way that could arguably violate tenets of the Stanford Affirmation. “You will be reciting this later to- day after you receive your white coats and stethoscopes,” Prober said. “Hopefully, the affirmation will have more meaning to you. It will help you to reflect more deeply on the words as you ponder it into the future.” Written by Pulitzer Prize-winning investigative re- porter and Stanford-trained physician Sheri Fink, Five Days at Memorial is filled with ethical conundrums about what constitutes humane health care. The book describes how medical staff and patients in the flooded hospital had to fend for themselves in the days following Hurricane Katrina. After the waters receded, authorities discovered that 45 patients had Clockwise from above: Xylen Washington, 5, tries out the stethoscope belonging to his father, Gabriel Washington, a first-year medical died at the hospital. Three health-care professionals, student. New medical students read the Stanford Affirmation, the School of Medicine’s version of the Hippocratic Oath, during the including one physician, were arrested for murder. A stethoscope ceremony. First-year medical student Yekaterina Shpanskaya greets medical school Dean Lloyd Minor during the ceremony. New Orleans grand jury ultimately refused to indict A group of new medical students pose for a usie at the stethoscope them on charges of involuntary euthanasia and murder, ceremony Aug. 21 on Alumni Green. but exactly what happened during those five days, when kindness or at the other extreme, murder.” temperatures soared, sleep was rare and proper sanita- According to the book, it is clear that physicians ad- tion was nonexistent, remains unclear. ministered life-ending injections of morphine or the These were the types of questions raised during an What is clear, as Prober described it, is that the lack sedative midazolam, or both, in about half of the pa- hour-and-a-half discussion among this year’s class of of planning, communication and panic worsened an tients. The Louisiana Attorney General maintained that new medical students and their family members; Lloyd already unimaginable situation, one that no physician a number of the dead were victims of homicide. Minor, MD, dean of the School of Medicine; and ever wants to face. “It was definitely hard to know what was right or Charles Prober, MD, senior associate dean for medical “As I read the book, I imagined how horrible it wrong,” Minor said. “They showed a lot of courage . would have been to live through this tragedy,” Prober staying behind and working. Lack of communication Donning the white coats said. “It’s amazing they stayed after abandonment by and leadership was a big problem. If there is a villain in the federal government.” this book, it was the parent hospital chain for Memo- The discussion, inspired by the book Five Days at The book, which Fink herself said she hoped would rial. The crew was told, ‘We can’t do anything. You have Memorial, a grim recounting of the horror at a New inspire discussions, captured the imagination of Prober to wait for the military and the Coast Guard.’” Orleans hospital following Hurricane Katrina 10 years and Minor, who described how they met over dinner to Can euthanasia be justified? ago, was part of a three-day orientation for new stu- discuss it. dents in preparation for the start of classes Aug. 24. The “When we met, it became very clear what we could Prober and Minor posed the question to the audi- book was assigned summer reading. talk about,” Prober said. “Did the care providers do the ence, “Is involuntary euthanasia ever justifiable?” The Each year, new medical students receive their white right thing? ... The question is whether or not it was general consensus was that involuntary euthanasia is

Stanford Health Library, in new digs, marks its 25th anniversary this year

By Ruth Schechter The Stanford Health Library, which former hospital, boasts 14-foot ceilings, had hoped to uncover the plaster mu- When her son was diagnosed with a celebrates its 25th anniversary this year, fluted columns and expansive windows rals and handmade metalwork shown in serious kidney and urinary tract defect, is a free community resource for medi- that had been hidden behind drywall. archival photos and architectural plans. Cathy Draper struggled to find informa- cal and health information. Started in a Its stairway entrance is of high-quality But these features, as well as the original tion about his condition. “At that time small storefront in the Stanford Shop- terrazzo, a polished composite hand- terrazzo floors, had been all but demol- it was very difficult to get the informa- ping Center, the library’s main branch made by mixing stone particles into ished in the 1960s redesign. tion we needed — not only to explain now is housed in the Hoover Pavilion, a concrete. “Our goal was not to re-create the the defect, but to help us in making landmark Art Deco building, at the cor- Originally, the first floor of the build- 1930s but to take elements of that treatment decisions,” she said. “I did not ner of Quarry and Palo roads, that was ing held the emergency room, kitchen, style and develop it for continuity. We have a place to go for scientifically based once Palo Alto Hospital. The building labs, morgue and locker rooms for staff. brought in materials to support the look health information.” currently houses the Stanford Neurosci- Stairs led to a formal front door on the without trying to replicate the origi- That changed just a few years later, ence Center and many of Stanford’s pri- second floor, where visitors could wait nal design,” Tingwald said. “While the when she donated a kidney for her son’s mary care clinics. in a reception area before being allowed outside was meticulously restored, we transplant and helped a family member Renovation challenges in to visit patients. Over time the role approached the lobby with a sense of who had just been diagnosed with ovar- of the building changed, as did pub- adaptive reuse. The Health Library was ian cancer. “Our move here was a confluence of lic taste. Though the exterior did not the perfect fit.” “By that time I had heard about the two major changes,” said library direc- change dramatically, a major renovation The designers eliminated several Stanford Health Library,” said Draper, a tor Nora Cain, who oversees satellite in the early 1960s removed most of the small rooms to open up the space and dental hygienist who has been a volun- branches in the Stanford Cancer Cen- deco elements from the interior. fabricated new columns to match the teer at the library for the past 20 years. ter, Stanford Hospital, East Palo Alto “There was not much to save inside,” ones outside. They reconstructed the “It was an invaluable resource while I and the new Stanford Cancer Center said George Tingwald, MD, AIA, a cre- plaster ceiling to match the few origi- researched both of the medical condi- South Bay. “Our building in the shop- dentialed architect, surgeon and direc- nal ceiling panels that remained and tions I was dealing with. Patients are of- ping center was being torn down, and tor of medical planning for Stanford’s installed new overhead fixtures to ten overwhelmed with difficult choices the Hoover Pavilion was being restored. adult and children’s hospitals. “There complement the 85-year-old building’s or complex diagnoses. I know only too We were the ideal entity to respect that were very few remnants of the original style. They fitted the main room with well the need for trustworthy resources space and to accommodate the public.” design. So much had been taken down comfortable chairs for reading, eight so that people can better understand The 2,244-square-foot library, lo- and destroyed.” computer stations, built-in bookshelves, their condition and treatment.” cated in what was the main lobby of the The team of architects and planners movable furniture and enough floor

4 September 14, 2015 Inside Stanford Medicine New medical students ponder life-and-death questions at stethoscope ceremony norbert von der groeben norbert von der groeben New bioscience graduate students begin classes soon By Tracie White

As 112 new graduate students in the biosciences prepare to begin classes Sept. 21, Will Talbot, PhD, professor and chair of devel- opmental biology, is settling into the position of senior associate dean for graduate education and postdoctoral affairs. norbert von der groeben Talbot was appointed to the post Sept. 1, replacing Daniel Herschlag, PhD, pro- fessor of biochemistry. “I am very excited about Will Talbot my new role,” Talbot said. “We are all inspired by the accomplishments of our graduate students and postdoctoral fellows, at Stan- ford and beyond. It is privilege to have a role in their training.” Lloyd Minor, MD, dean of the School of Medi- cine, said, “Will has shown a strong commitment to graduate education and postdoctoral training. Under his leadership, I am confident that the Office of Graduate Education and Postdoctoral Affairs will enjoy a bright future and will continue guiding and Clockwise from above: Xylen Washington, 5, tries out the stethoscope belonging to his father, Gabriel Washington, a first-year medical empowering the next generation of leaders and in- student. New medical students read the Stanford Affirmation, the School of Medicine’s version of the Hippocratic Oath, during the novators in academia and industry.” stethoscope ceremony. First-year medical student Yekaterina Shpanskaya greets medical school Dean Lloyd Minor during the ceremony. The first-year students were selected from a pool of 1,985 applicants. Seventy of the students are men, and 42 are women. Twenty-four of the 112 stu- never OK, even in dire circumstances. dents were born outside the United States, includ- But questions remained. ing Myanmar, the Ukraine and Ghana, and 31 are “Isn’t it equally morally reprehensi- considered underrepresented minorities in the bio- ble letting someone die without care?” sciences. Eighteen hold advanced degrees, including said incoming medical student Mari- 11 with master’s degrees and two with doctorates in posa Garth-Pelly. some patients would be left behind alone without care veterinary medicine. Another student added, “I feel like in the reality of following a mandatory evacuation. Panic reigned. “The arrival of our new graduate students is a the world, [health-care professionals] are also human “Mistakes were made,” Minor said. “But progress wonderful way to start our academic year,” Talbot beings that have needs.” only occurs when we acknowledge those shortcomings said. “This incoming class represents our most di- “I don’t know that I would have made a different and hopefully grow as a person and as a physician.” verse cohort ever, and we are all excited about the decision,” said another student. At the end of the discussion, the students and their great discoveries they will make as students and in The conversation lingered over the book’s vivid families walked outside to Alumni Green, where they the future.” description of the helicopters landing in a poorly accepted their white coats and stethoscopes during a The Office of Graduate Education, in collabora- lit, precarious spot on an aging landing space where ceremony. Parents clicked photos and shed tears. Then tion with Alumni Affairs, will hold the annual PhD health-care workers struggled to carry patients up stairs the entire class stood together and recited the Stanford lab coat ceremony Sept. 30 at the Li Ka Shing Center and through a tunnel to evacuate them. One health- Affirmation, which begins: “On my admission to the for Learning and Knowledge. At the event, each new care worker was badly injured while transporting a practice of medicine, I pledge to devote my life to the student is introduced by his or her program chair and 300-pound patient to a helicopter. The workers feared service of humanity.” ISM presented with a lab coat. ISM

space to accommodate seating for an “I’m amazed how different it is now,” The new location also allows the li- ment classes that address the needs of Stanford Health Library, in new digs, marks its 25th anniversary this year ongoing series of free community lec- said Laura Markman, who has been a li- brary team to work closely with Stan- these patients,” Cain said. “We hope to tures by Stanford physicians. brary volunteer for 17 years. “I remem- ford’s coordinated care clinic, located expand that model to other specialties. “There are so many people in the ber this spot as the hospital lobby, so on the building’s fourth floor, where A resource like this is especially impor- community who were born in this it’s wonderful to me that it is still being clinicians treat patients with chronic tant at a place like Stanford, where treat- building. They come up to me and used by the public. There are no space conditions. ments may be groundbreaking.” ISM thank me for bringing it back. The li- issues here, and it’s easy to sit right next “It’s a model of integration, with brary brings people back into the build- to a patron to help them learn how to clinical care that lets us develop aspects Ruth Schechter is a freelance writer and ing and makes it a real community use the computer or navigate a website.” of our collection and offer self-manage- editor. resource again,” Tingwald said. Community service lane library norbert von der groeben “We started in a nonclinical setting to provide evidence-based information people could trust,” Cain said. “We have access to libraries and databases not available to the general public and can customize packets to any level of expertise.” The library staff respond to about 600 requests a month, with most in- quiries revolving around cancer, aging, nutrition and chronic conditions like diabetes, arthritis and heart disease. Requests come in by phone, by email and in person, with the library’s resources available to anyone in the community — not just patients and their families, Cain said. Librarians and volunteers also work closely with sev- eral Silicon Valley companies’ wellness The lobby of the Hoover Pavilion — left, as it looked in the 1960s — is now home to the Stanford Health Library, right, a free community resource for programs. medical and health information.

Inside Stanford Medicine September 14, 2015 5 a professor of genetics at the Salk Institute for Biological humans. Humans with less than the normal amount of Face Studies and a co-author of the study. PAX3 have a condition called Waardenburg syndrome, continued from page 1 Prescott and her colleagues coaxed human and chim- which includes craniofacial, auditory and pigmentation may mediate morphological differences among species.” panzee iPS cells to become cranial neural crest cells by defects. Genomewide association studies in humans To conduct the study, however, Prescott and her col- growing them in the laboratory under a specific set have identified PAX3 as a region involved in normal leagues had to obtain a specialized type of cell present of conditions. They then examined enhancer regions facial variation. only in very early primate development. The cells, called throughout the genome, looking for those In contrast, another gene known to be in- cranial neural crest cells, originate in humans within that were not just active and therefore likely volved in determining the shape of the beaks about five to six weeks after conception. Although they to be involved in craniofacial development, of finches and the jaw of a fish called a cich- first appear along what eventually becomes the spinal but also those whose patterns or degrees of lid was expressed at higher levels in humans cord, the neural crest cells then migrate over time to af- activity seemed to vary between human and than in chimpanzees. In mice, overexpres- fect facial morphology and differentiate into bone, carti- chimpanzee cells. sion of this gene, BMP4, in cranial neural lage and connective tissue of the head and face. “Of course, humans and chimps are very crest cells causes a marked change in face “These cells are unique,” said Prescott. “If we want closely related,” said Wysocka. “Most of the shape, including a rounding of the skull and to understand what makes human and chimp faces dif- regulatory elements are the same between eyes that are more near the front of the face. ferent, we have to look to the source — to the cell types the two species. But we did find some dif- “We are now following up on some of responsible for making these early patterning decisions. ferences. In particular, we found about Joanna Wysocka these more interesting species-biased en- If we were to look later in development or in adult tis- 1,000 enhancer regions that are what we hancers to better understand how they im- sues, we would see differences between the species but termed species-biased, meaning they are more active pact morphological differences,” said Wysocka. “It’s they will tell us little about how those differences were in one species or the other. Interestingly, many of the becoming clear that these cellular pathways can be used created during embryogenesis. But accessing early cell genes with species-biased enhancers and expression have in many ways to affect facial shape.” types like neural crest cells can be quite difficult, espe- been previously shown to be important in craniofacial Another Stanford-affiliated author of the study is re- cially when studying primates.” development or associated with normal intrahuman fa- search assistant Rajini Srinivasan. To obtain this elusive cell type, the researchers used cial variation.” The research was supported by the National In- induced pluripotent stem cells, or iPS cells, made from Snout length and shape stitutes of Health, the California Institute for Regen- chimpanzees. IPS cells, which are made from easy-to- erative Medicine, the W.M. Keck Foundation and the obtain skin or blood samples, can be coaxed to become In particular, the researchers found that two genes, Innovation Fund. other tissues. Although iPS cells from humans have PAX3 and PAX7, known to affect snout length and Stanford’s departments of Chemical and Systems been well-studied, they’ve only recently been made shape in laboratory mice, as well as skin pigmentation, Biology and of Developmental Biology also supported from chimpanzees in the laboratory of Fred Gage, PhD, were expressed at higher levels in chimpanzees than in the work. ISM

but they are in countries where talking Akkineni, herself a mother, managed to ment Program. AIDS about these things has been taboo or persuade the parents to back down from Akkineni said she is particularly con- continued from page 1 very, very limited. And she’s done it in their demands by assuring them that the cerned about sex trafficking, in which this very culturally sensitive, appropriate schools would introduce materials to ed- girls as young as 3 are sold into brothels, has the third-highest number of AIDS way. It’s really impressive.” ucate the students about HIV. where they may contract HIV and serve cases in the world, knowledge about Each version is carefully tailored to the Akkineni was at a loss; the govern- as reservoirs for the virus. the disease is very low. Sex, the primary local culture, featuring recognizable local ment had banned previous HIV materi- To promote HIV prevention, mode of HIV transmission, is a taboo celebrities in local dress speaking local als as pornographic, and some had been TeachAIDS has distributed 25,000 cop- subject, and there is no in dialects. The organization, supported by burned in public bonfires. She fretted ies of the videos throughout the state, the schools, so students know precious private philanthropy, donates the materi- about where to find AIDS information and has shown them on private and gov- little about a virus that has infected more als to governments, which then distribute that officials would find acceptable. So ernment TV channels, Sorcar said. They than 2 million people in India, according them free of charge to schools, hospitals Sorcar’s visit could not have been more target schools enrolling preadolescents to the Joint Programme and counseling centers. In 2012, the auspicious: “My husband came home and teenagers, reaching students at a vul- on HIV/AIDS. nonprofit was recognized in The Tech and said, ‘You have to meet this young nerable age (most girls marry between TeachAIDS, a nonprofit organization Awards, a signature program of The Tech lady, Piya Sorcar,’” Akkineni said. “It was the ages of 18 and 20), with messages that began as a graduate student’s thesis Museum of Innovation in San Jose that cosmic.” that are simple and clear. project at Stanford, aims to fill that gap honors large-scale initiatives using tech- Within the year, TeachAIDS had re- “For the children, since it’s in ani- nology for phil- leased its first productions in the south mation format, it’s very attractive,” anthropic goals. It Indian state of , which Basaveswara Rao, joint director of in- also has won the has a population of more than 83 million formation, education and communi- TR35 Award from and one of the highest rates of HIV in cation with the Telangana State AIDS MIT, which recog- the country. Akkineni agreed to serve as Control Society, said during the airing of nizes innovations trustee for the organization. the video at Zilla Parishad High School. that could have a Star power “Added to that are the celebrities, who dramatic impact on deliver the message.” the world. It was not Akkineni’s first foray into TeachAIDS has recruited more than First launched in the epidemic. Once a major two dozen Indian celebrities to partici- the hard-hit coun- actress, she had starred in 54 movies by pate in the project, including Amitabh tries of sub-Saharan the time she was in her mid-20s, but Bachchan. With his signature oversized Africa, TeachAIDS then decided to give up full-time acting glasses and renowned voice, he is one of began moving into to devote her time to social activism. An the most influential actors in the history India in 2009, at animal lover, she founded Blue Cross of of Indian cinema. a time when the Hyderabad, the city’s first and only ani- In the Telugu-language version of the disease was rapidly mal shelter, in 1992. Shortly after, she video, narrated by , the actor spreading there. was approached by Karl Sequeira, an tells the students that AIDS is a condi- Students at Zilla Parishad High School, in the south Indian metropolis of “I was reading AIDS activist, who was looking to estab- tion that does not have a cure, so it’s im- Hyderabad, gather to watch an educational video about HIV/AIDS. reports that India lish the city’s first AIDS hospice. It was portant to know how to prevent it. Based was to be a hot zone a period in which people living with the on rigorous research and testing, the with culturally sensitive animated videos, for HIV,” said Sorcar, an adjunct affiliate disease were literally being wrapped up in video provides the suggestion of human as well as interactive versions for use on at the School of Medicine and lecturer blankets and tossed in the garbage, Ak- intimacy by showing a young couple to- computers, that use the voices and faces in the School of Education, in a recent kineni said. Sequeira, who died in 2004, gether, then an image of birds kissing. of celebrity icons to teach the basics of interview over coffee near her office in was moved by the dire need for humane A woman embracing a baby, her breast HIV biology, how the virus is spread and downtown Palo Alto. “Millions of dol- care. fully covered, conveys the concept of how individuals can protect themselves. lars were poured into this problem, but “I was already known as this noto- breastfeeding, one of the ways in which Videos in 14 languages knowledge levels were very low…. It rious ex-actress who was running this an HIV-positive mother can transmit the was disturbing how much was unknown hospice for animals,” Akkineni said in virus to her child. Founded in 2009 by Stanford School about the basics of transmission.” an interview in her office at the animal One of the students, Shirisha, 16, of Education graduate Piya Sorcar, PhD, On a visit to India that year, she man- shelter. “So he thought I was a kindred said: “I understood and was very happy the nonprofit now distributes its videos aged to secure a five-minute interview soul.” In one evening, they raised 2.5 because it’s about health, and I can learn free of charge in more than 80 countries with Nagarjuna, hoping he would agree million rupees, about $40,000 in today’s how to protect myself and tell my family and in 14 languages. In India, the group to be featured in TeachAIDS produc- currency, to start the project, among the and friends. Most parents are not edu- plans to take the program national by the tions. By sheer coincidence, Nagarjuna’s wide-ranging HIV/AIDS and substance- cated and don’t know things. I want to end of the year, distributing as many as wife, actress and activist Amala Akki- abuse services provided now by Freedom take my groom before marriage for an 30,000 copies in each state where preva- neni, had been embroiled just the week Foundation. HIV test” — a move that could save her lence is high and providing versions in before in a heated public debate over the The state of Andhra Pradesh had a life. seven different languages, Sorcar said. expulsion of HIV-positive students from crying need for such services; it claims “The kids learn so much and you can “I think what Piya has done is amaz- the local schools in Hyderabad, India’s the highest prevalence rate of AIDS in see the joy in their eyes to receive these ing,” said Douglas Owens, MD, profes- fourth-most populous city, with some 7 the country. A high rate of heterosexual messages from their beloved role mod- sor of medicine, director of the Center million people. sex outside of marriage, low condom els,” Sorcar said. “The exciting part for for Primary Care and Outcomes Re- Though the AIDS virus cannot be use, a large migrant community and a our team is the palpable energy from the search/Center for Health Policy and transmitted through casual contact, un- flourishing sex-trafficking industry are young people every time the software is adviser to the project. “She started the educated parents were demanding that among the factors that have contributed shown in schools. It’s inspiring to see that program as a PhD student and not only their children not sit side by side in class to spread of the virus, according to a using a research-based process matters — are the videos available in 81 countries with children infected with the virus. report by the United Nations Develop- and it works.” ISM 6 September 14, 2015 Inside Stanford Medicine However, researchers have speculated the genes identified in the yeast screens, the development of ALS and FTD, the ALS that cells with introns harboring ex- they found several that encoded proteins fact that the researchers were able to continued from page 1 panded repeats (as in the C9orf72 gene) responsible for ferrying molecules in and identify specific types of protein families tion is found in about 40 to 60 percent may mistakenly make protein from the out of the nucleus. In particular, a class common among yeast, rodent and hu- of ALS inherited within families and in repeated section even in the absence of of nuclear import proteins called karyo- man cells represents an important step about 10 percent of all ALS cases. This a traditional “start” command. Although pherins appeared important in modu- forward in the field, they said. Future is by far the most common cause of ALS, it’s not known exactly why this abnormal lating the effect of the toxic protein. work will also focus on disentangling the so everyone has been trying to figure out protein translation may occur, previous One, called KAP122, was one of the relative contributions of the RNAs and how this expansion of the repeat contrib- research has shown it does sometimes strongest suppressors of toxicity when repeat proteins produced by the mutated utes to the disease.” happen in regions of the genome with re- overexpressed. C9orf72 gene. Although the repeat occurs in a re- peated nucleotide sequences. norbert von der groeben gion of the gene called an intron, which Jovičić first constructed a se- does not normally carry protein-making ries of yeast strains, each of which instructions, researchers have speculated expressed one of the proteins that a molecular miscue may cause a cell thought to be made from the to mistakenly make RNAs and proteins expanded repeat. She found that from the expanded repeat. one of the proteins, made up of Gitler is the senior author of the study, the amino acids proline and argi- which was published online Aug. 26 in nine, was particularly toxic to the Nature Neuroscience. Postdoctoral scholar yeast cells. Another, with glycine Ana Jovičić, PhD, is the lead author. The and arginine, was also toxic. The Stanford research is complemented by particular toxicity of the arginine- similar findings from two other groups containing proteins in the yeast that were published in the Aug. 27 issue mirrors what had previously been of Nature. found in mammalian cells and in Toxic proteins fruit flies. Using a technique known as a Previous research has shown that pro- genomewide screen, Jovičić then teins made from the expanded section systematically tested whether of nucleotides are toxic to fruit fly and expressing higher-than-normal mammalian cells and trigger neurode- amounts of any one of the yeast’s generation in animal models. However, proteins could suppress the tox- it’s not been clear why. Gitler and Jovičić icity of the arginine-containing Aaron Gitler is the senior author of a study that found that cells with a mutation associated with ALS were hampered in their ability to move proteins into and out of the nucleus, a cell’s command center. used a yeast-based system to understand proteins and allow the mutated what happens in these cells. Although yeast to grow like its unmutated yeast are a single-celled organism without peers. Conversely, she used another tech- When Jovičić and Gitler sought to “Neurodegenerative diseases are very nerves, Gitler has shown that, because nique to investigate whether the loss of confirm their results in mammalian cells, complicated,” said Jovičić. “They likely they share many molecular pathways any one protein could influence the pro- they found that overexpression in rat occur as a result of a defect or defects in with more-complex organisms, they can tein’s toxicity. neurons of a mammalian gene similar to basic biology, which is conserved among be used to model some aspects of neuro- Potential targets for drugs KAP122 more than doubled the survival many distantly related species. We hope nal disease. of neurons expressing the toxic protein. that our research may one day lead to Cells make proteins by copying a Jovičić found 27 genes that, when The researchers then turned their at- new potential therapies for these devas- nucleotide sequence from DNA. This expressed at high levels, suppressed the tention to human cells. They were able tating, progressive conditions.” copy, called RNA, is then shuttled to toxicity of the proline-arginine protein. to directly convert skin cells from three Other Stanford-affiliated authors of the cell’s protein-making factories. Pro- Mutated yeast strains with higher-than- people without the extended nucleotide the paper are graduate students Noori teins are made, or normal levels of repeat and two with the extended repeat Chai, Shizuka Yamada, Gregor Bieri and translated, from any one of these into neurons that could be studied in Nicholas Kramer, and undergraduate the RNA by as- “We hope that our proteins grew bet- the laboratory. They compared the lo- student Joseph Paul III. sembling build- research may one day ter in the presence cation of a protein called RCC1, which The research was supported by the ing blocks called of the arginine- is normally found in the cell’s nucleus, National Institutes of Health, the Pack- amino acids in a lead to new potential containing pro- between the two groups of cells. RCC1 ard Center for ALS Research at Johns sequence dictated therapies.” teins. She also is the human version of one of the yeast Hopkins, a Target ALS Springboard by the order of nu- identified 35 genes proteins that Jovičić found worsened the Fellowship, the J.P.B. Foundation, the cleotides in the RNA string. Every three- that, when highly expressed, made the toxicity of the proline-arginine proteins Helmsley Foundation, the Mathers nucleotide combination either encodes a arginine-containing proteins even more when overexpressed. Foundation, the University of Leuven, particular amino acid or carries a cellular toxic. Finally, she discovered 16 genes They discovered that although RCC1 the European Research Council, the command such as “start” and “stop” to that, when missing from the yeast, ren- was in the nucleus in nearly all the un- Fund for Scientific Research Flanders, facilitate protein production. dered the arginine-containing protein mutated neurons, it was found primar- the Belgian Science Policy Office, the Often, genes include strings of inter- less toxic. These deleted genes are of par- ily in the cytoplasm in about 70 to 80 Association Belge contre les Maladies vening nucleotides called introns that ticular interest because they could be po- percent of neurons with the expanded Neuro-Musculaires and the ALS League don’t contain instructions to make pro- tential targets for drug interventions or repeat. Belgium. teins. These introns are usually removed therapies. Although much remains to be learned Stanford’s Department of Genetics from the RNA before it is translated. When Jovičić and Gitler examined all about how these genes are involved in also supported the work. ISM

before tutoring, replicating a finding that Menon and between tutors and students in a social context plays Math colleagues published in 2012. a role, or whether computerized tutoring can result in continued from page 1 After the first fMRI scan, children participated in the same benefits and brain circuit changes. an intensive, eight-week tutoring program consisting “The tutoring has a standard protocol, but is also to help alleviate this problem. of 22 lessons involving addition and subtraction prob- personalized,” said Menon, who holds the Rachael L. “Math anxiety has been under the radar,” said the lems. Tutors gave the lessons to each child individually. and Walter F. Nichols, MD, Professorship. “If a child study’s lead author, research associate Kaustubh Supe- After tutoring, the math anxiety test and fMRI scans is stuck at a particular concept, the tutor tries to get kar, PhD. “People think it will just go away, but for were repeated. the child beyond the bottleneck in a non- many children and adults, it doesn’t.” All of the children performed better negative, encouraging way.” Because the Measuring math anxiety on addition and subtraction problems af- tutoring happens one-on-one, children ter tutoring. The children who started the do not have the opportunity to feel fear- The new research was based on the idea that the study with high levels of math anxiety had ful about not performing as well as their principles of exposure-based therapy for treating pho- reduced anxiety after tutoring, while those peers, which may also help. “We need bias might also apply to alleviation of math anxiety. in the low-math-anxiety group had no more research to understand that,” Menon Phobias, such as the fear of spiders, can be relieved in change in their anxiety levels. added. affected individuals by repeatedly exposing them in a Anxiety alleviated The researchers also want to investigate safe environment to the thing they fear. whether the anxiety-reducing effects of tu- The new study included 46 children in third grade. After tutoring, the fear circuits and toring will persist as children move on to Vinod Menon Before receiving tutoring, each child took a test that amygdala were no longer activated in chil- learning more complex problem-solving assessed his or her level of math anxiety. The children dren who had begun the study with high skills. were divided into two groups — one with high math math anxiety, confirming that tutoring Other Stanford-affiliated authors of the anxiety, the other with low math anxiety — based on ameliorated the anxiety itself, rather than providing the study are postdoctoral scholars Teresa Iuculano, PhD, whether their math anxiety scores fell above or below kids with a coping mechanism that relies on other brain and Lang Chen, PhD. Menon is a member of the Stan- the median score for all of the children. They also com- circuits. ford Child Health Research Institute. pleted standard neuropsychological assessments and “It’s reassuring that we could actually help these The research was supported by the National Insti- were tested on simple addition problems while having children reduce anxiety by mere exposure to problems,” tutes of Health, the National Alliance for Research on their brains scanned via functional magnetic resonance Supekar said. Schizophrenia and Depression and by an Atherton In- imaging. The brain scans of the children with high The researchers plan to conduct future studies to fig- vestigator award. levels of math anxiety showed activation in the brain’s ure out what aspects of the one-on-one tutoring were Stanford’s Department of Psychiatry and Behavioral fear circuits and so-called “fear center,” or amygdala, helpful. Menon wants to test whether the interaction Sciences also supported the work. ISM Inside Stanford Medicine September 14, 2015 7 o b it ua ry Thomas Stamey, expert on prostate cancer and PSA test, dies at 87

By Jennie Dusheck sought-after urology residency in the country,” Kathryn the PSA test for prostate cancer, but then, ironically, his Stamey said. “It was a very strong, family-oriented de- was also a voluble voice against the test’s use to justify Thomas A. Stamey, MD, a professor emeritus of partment. We had lots of parties, and everybody came unnecessary prostate surgery. In the late 1980s, he pio- urology at the School of Medicine and a noted leader with their children. It became a strongly knit depart- neered the development of the prostate specific antigen, in the study and treatment of prostate cancer, died of ment and very successful.” or PSA, blood test for prostate, which allowed physi- Alzheimer’s disease Sept. 4 at his home in Portola Val- Stamey authored or co-authored cians to estimate the risk that a male ley, California. He was 87. more than 225 scientific papers, four patient had prostate cancer. At Stanford, Stamey helped lay the groundwork books, 30 textbook chapters and seven PSA levels correspond to the size for the now-controversial PSA blood test for prostate monographs. Among many other of the prostate. As men age, it’s com- cancer and helped transform urology and surgery from awards, he received the Hugh Hamp- mon for the prostate to become larger, purely clinical fields to research fields. He made major ton Young Award (1972) and the Ra- leading to higher levels of PSA in the contributions to four areas of medicine: renal hyperten- mon Guiteras Award (1995) from the blood. When surgeons biopsied the sion, urinary tract , urinary incontinence and American Urological Association and prostates of men with high PSA levels, prostate cancer. In 1989, he became the first urologist the Valentine Award (1991) from the they frequently found cancer. How- ever elected to the Institute of Medicine. He was also New York Academy of Medicine. ever, what was not obvious at the time named an honorary fellow of the Royal College of Sur- “He was a giant in the field. His was that both an enlarged prostate and geons Edinburgh. most spectacular achievement at Stan- small prostate cancers are common “Tom Stamey was the founding father of the Stan- ford was making research for surgeons among all men and usually not lethal. ford Department of Urology and led it for more than an important part of an academic That is, most men with a prostate 25 years. He was truly one of the giants in academic career, which was not true of depart- Thomas Stamey cancer will die of something else, and urology, with his biggest impact in the area of prostate ments in many other parts of the coun- treating the prostate cancer can need- cancer,” said Eila Skinner, MD, chair of urology and try,” said Linda Shortliffe, MD, professor of pediatric lessly lead to a much-reduced quality of life. To Stamey’s the Thomas A. Stamey Research Professor in Urology. urology. credit, he recognized this, and in 2004 published a “His research collaborations with John McNeal formed Shortliffe, who did her 1977-81 residency with study showing that the PSA test predicted the size of the the basis of much of what we know about prostate can- Stamey, said, “People talk about translational medicine patient’s prostate, but not the severity of cancer. cer today. He trained over 100 residents and fellows, now, but he was doing it back then.” That research fo- As Stamey said at the time, “Our job now is to stop many of whom went on to be leaders in urology in their cus was the reason, she said, he was the first urologist removing every man’s prostate who has prostate cancer. own right. His influence on the department will go on and one of the first surgeons to be elected to the Insti- We originally thought we were doing the right thing, for many years to come, and I feel privileged to have tute of Medicine. “Tom instituted one year of a medi- but we are now figuring out how we went wrong. known him.” cal residency to be a laboratory year, where residents Some men need prostate treatment but certainly not all ‘A strongly knit department’ worked on research,” Kathryn Stamey said. of them.” The 2004 paper was one the last papers he Authoritative voice wrote, Kathryn Stamey said. Born in North Carolina in 1928, Stamey gradu- But that kind of strong language was typical of ated from Vanderbilt University and went on to earn Shortliffe has vivid memories of working with Stamey, Shortliffe said. “There was never any question a medical degree in 1952 from Johns Hopkins Univer- Stamey and, in particular, of his authoritative voice. She about where he stood.” sity, where he also did his internship and a residency. said that many of Stamey’s former residents wrote to her “He was a compassionate, kind gentleman,” his wife After serving as a urological consultant for the U.S. in response to news of his death, reporting, “I still hear added. “He thought his patients were his heroes, and he Army in the United Kingdom, he joined the faculty of his voice.” loved medicine. He loved learning, he loved everything Johns Hopkins in 1958. In 1961, he came west to Stan- “He had a distinct North Carolina accent, which was about his work. He said he never worked a day in his ford’s medical school as associate professor of surgery not that common on the West Coast,” she said. “It was life. He was just a very kind and loving man.” and chair of the Division of Urology. In 1990, he was like hearing your father’s voice all the time, even though In addition to his work at Stanford, he loved fly-fish- appointed founding chair of the newly created Depart- we were not that much younger than he was. It was a ing, music and travel, she said. ment of Urology and worked to develop it into one of voice you could hear in your sleep.” Even today, she In addition to his wife, Stamey is survived by his the top programs in the nation. said, many of his former surgical residents say they hear five children — Frederick Stamey, Charline Stamey, Stamey’s wife, Kathryn, noted that her husband his voice while working in the operating room. Alex Stamey, Theron Cooper and Allison Stamey — worked with the late Duncan Govan to create the de- Many of the residents Stamey trained went on to and grandchildren Suzi Quist, George Quist, Heather partment. Govan, MD, PhD, a professor emeritus of become departmental chairs around the country, said Magrin, Robin Magrin and Alexis Stamey. urology, died in 2007. “They built the department Kathryn Stamey. A service for Stamey was held Sept.12 in Menlo from scratch, and it became, at its high point, the most Stamey was also one of the first to show the value of Park. ISM

of note reports on significant honors and awards for faculty, staff and students

Leah Backhus, MD, MPH, was ap- pointed associate professor of cardiotho- racic surgery, effective July 1. Backhus specializes in general thoracic surgery Leah Backhus Suzan Carmichael Stephanie Chao Michael Cleary Terry Desser and thoracic surgical oncology. She will lead health services and surgical out- comes research in the Department of cellular responses associated with the on- Cardiothoracic Surgery. Her research set of acute leukemia. The grants support focuses on lung-cancer survivorship and experienced researchers with new and imaging surveillance following treatment promising projects to identify the causes for early-stage lung cancer. of and cures for childhood cancers. Suzan Carmichael, PhD, was pro- Terry Desser, MD, was promoted moted to professor (research) of pedi- to professor of radiology, effective Aug. atrics, effective Aug. 1. Her research 1. Desser served as residency program focuses on nutritional, environmental director in the Department of Radiol- and genetic risk factors for perinatal ogy for 11 years. Her work focuses on Gregory Enns Eben Rosenthal Ronald Witteles outcomes such as birth defects, preterm identifying the human factors related to delivery and stillbirth, and factors affect- success in academic radiology and what ing the care and outcomes of infants who drives the choice of specialties among pointed professor of otolaryngology- cancer. This grant provides $25,000 for have birth defects. medical students. Her clinical interests head and neck surgery, effective July 1. one year to residents and fellows plan- Stephanie Chao, MD, has been ap- lie in the area of cancer overdiagnosis, Rosenthal focuses on developing real- ning to pursue careers in basic science or pointed assistant professor of surgery, particularly in ultrasound diagnosis of time imaging agents to help surgeons clinical research in radiation oncology. effective July 1. Her research focuses thyroid cancer. and pathologists visualize cancer dur- Ronald Witteles, MD, was promoted on eradicating hepatitis B, which is the Gregory Enns, MB, ChB, was pro- ing surgery. He recently completed the to associate professor of medicine, effec- leading cause of liver cancer and liver dis- moted to professor of pediatrics, ef- first clinical trial in the United States for tive June 1. Witteles is program director ease globally. Chao works with the Asian fective June 1. Enns’ research involves near-infrared optical imaging in cancer of the internal medicine residency train- Liver Center at Stanford and helped developing ways to detect and monitor and is initiating this technique in a range ing program at Stanford, and oversees launch the Jade Ribbon Campaign to mitochondrial dysfunction noninva- of tumor types at Stanford. all fellowship programs within internal improve public and physician awareness sively using highly sensitive biomarkers, Jennifer Shah, MD, a resident in medicine. He is also co-director of the about hepatitis B. tandem mass spectrometry and high- radiation oncology, has received a 2015 Stanford Amyloid Center, the largest Michael Cleary, MD, professor of pa- dimensional flow cytometry. He also American Society for Radiation Oncol- center of its kind in the western United thology and of pediatrics, was awarded a is involved in clinical trials using novel ogy Residents/Fellows in Radiation On- States. His research focuses on emerging 2015 innovation grant from Alex’s Lem- therapeutics to treat inborn errors of cology Research Seed Grant to study the treatments for systemic amyloidosis, car- onade Stand Foundation. This award metabolism, with an emphasis on mito- feasibility of performing a specific type of diac complications of cancer therapy, and will provide $250,000 over two years for chondrial disease. CT scan on patients undergoing stereo- evolving diagnostic/therapeutic strategies his research on the molecular events and Eben Rosenthal, MD, has been ap- tactic ablative radiation therapy for lung for cardiac sarcoidosis. ISM 8 September 14, 2015 Inside Stanford Medicine