Stem cell ‘therapy’ blindsthree patients 16 in hemorrhage. They are now blind. plications, includingvisionloss,detachedretinas and treatment, thepatientsexperiencedavariety ofcom- 2015 ataclinicinFlorida. Within aweek following the the paper. thalmology at the School of and co-author of frey Goldberg, MD, PhD, professor andchairofoph- minimally regulated, patient-fundedresearch,” saidJef- agencies of the risks of this kind of cians and regulatory the total hospital costs incurred by gun $6.6 billionfigure isonly afractionof riod, the researchers reported that the related injuries during the nine-year pe patients whowere admittedforfirearm- School of Medicine. cording toastudyby researchers atthe an average of$734.6millionperyear, ac- nationwide from 2006through 2014— talization costs of more than $6.6 billion Volume 9, No.6 Volume 9, By DevikaG.Bansal wounds just ‘tip oftheiceberg’ Initial hospitalcostsforgunshot T By BeckyBach Jeffrey Goldberg andhiscolleaguesexamined thecasesofthree women whowere blindedafterundergoing anunproven stemcelltreatment. A paperdocumentingthecaseswaspublishedMarch The article isa“callThe article toawareness forpatients, physi- In an analysis of data from 267,265 Gun violenceresulted ininitialhospi- treatment thatwastoutedasaclinicaltrialin blinded afterundergoinganunproven stemcell hree peoplewithmaculardegenerationwere The New England Journal of Medicine. INSIDE STANFORD MEDICINE VAL LAWLESS /SHUTTERSTOCK.COM LAWLESS VAL March 27, March 2017 - - to assault. were self-inflicted, unintentional or due talization costsofshootinginjuriesthat Spitzer said. The study included hospi- especially becausetheyare preventable,” professor of surgery. author is Thomas Weiser, MD,associate cal student Sarabeth Spitzer. The senior Public Health. The lead author is medi - March 21intheAmerican Journal of admission — or hospital readmissions. or thosewhoare treated butdiebefore for patientswhoare treated andreleased emergency room visits—medicalcosts shot wounds:It doesnotincludecostsof exists surprisingly said. ofthepatientpopulation, portion Weiser pro- wounds —asmallbutimportant tients are admitted with gunshot or knife Little research ongunviolence “There is a high cost for these injuries, isahighcostfortheseinjuries, “There The studywaspublishedonline Despite the scaleof theproblem, there At Stanford, 10percent oftraumapa- PublishedbytheOfficeofCommunication&PublicAffairs it was called “Study to assess the safety and effects of by theU.S.Nationalrun ofMedicine, Library where trial onClinicalTrials.gov, andresults aregistry database Appealing topatients‘desperateforcare’ extremely unlikely they would regain vision.” cell treatments. “Although Ican’t sayit’s impossible,it’s subsequently treated for complicationsfrom the stem the University ofMiami, where twoofthepatientswere MD, anassociateprofessor ofclinicalophthalmologyat likely toremain blind,saidco-author Thomas Albini, ranged from 20/30 to 20/200. Now, the patients are loss of vision. Before the surgery, the vision in their eyes common, progressive diseaseoftheretina thatleadsto from 72to88—suffered from maculardegeneration,a Two ofthepatientslearnedso-calledclinical The three patients—allwomen,ranginginage See GUN, page6 By ErinDigitale Hu hasvolunteered insuicide-preven wanting todo goodandnotdoharm.” sincereduction team seemed very about pro- and behavioralsciences.“The atry Hu, clinicalassociateprofessor ofpsychi- handled responsibly inthemedia,” said sure thatsomething aboutsuicidewas them. suicide contagion.Hu agreed toadvise cancontributetosince suchportrayals basic plot without romanticizing suicide, lenge: They wantedtoretain thebook’s being bullied by her classmates. school studentwhodiesby suicideafter a bestselling 2007 novel about a high- which premieres March 31,isbasedon agers about mental health issues. tocommunicatewithteen- opportunity itwouldbe an unusuallygood she knew of aNetflix seriesaboutteenagesuicide, MD, wasinvitedtohelpshapethescript on upcomingteen-suicidedrama Psychiatrist advisedproducers “It tomake was a good opportunity The show’s producers facedachal- Reasons Why , series,13 The new When Stanford psychiatrist Rona Hu, NORBERT VON DER GROEBEN degeneration andare the photoreceptor cells,whichplayacriticalrole inmacular ating, ormaturing,intoretinal pigment epitheliumor that theclinicclaimedtouse,are capableofdifferenti- dence thatadipose-derived stemcells,thetypeofcells Goldberg and Albini said. In fact, there is sparse evi suggesting thattheprocedure couldhelprestore vision, No evidenceofvisionrestoration myofibroblasts, a type of cell associated with scarring. the eye, thestemcellsalsocouldhave changedinto solution intotheeye, Albinisaid. When injectedinto caused by injectionofacontaminant orthecellwash of thepatients’ complications,whichcouldhave been attempting the other eye. one eye responds toanexperimentaltreatment before how approach toobserve would optforaconservative flag, AlbiniandGoldberg said,becausemostdoctors patients hadbotheyes treated atonce—anotherred entire process took less than an hour, Albini said. The and injectedintotheireyes. Patients reported thatthe cells were then mixed with the platelet-dense plasma Platelet-dense plasmawas isolatedfrom theblood. The with enzymes,thegoalofobtainingstemcells. and astandard blooddraw. The fattissuewasprocessed patients hadfatcellsremoved from theirabdomens ophthalmology, that is patient-funded,” Albini said. authors said. clinical trialthathasafee should raiseared flag,the dangerous,”that was off-the-charts Albini said. inaclinicalenterprisecase thesewomenparticipated that stemcellsare goingtobetheanswer, butinthis of clinicsappealtopatientsdesperateforcare whohope Albini said. materials given to the patients did not mention a trial, in atrial,althoughtheconsentformandotherwritten Some ofthepatientsbelieved theywere participating macular degeneration.”cells injectedintravitreal indry But even ifexecuted correctly, there is noevidence Shoddy stemcellpreparation mayhave ledtosome At theclinic,whichisnotnamedinpaper, the “I’m notaware ofanylegitimateresearch, atleastin Each patientpaid$5,000fortheprocedure. Any “There’s alotofhopeforstemcells,andthesetypes - do topeople how much collateral damage they can get backatbullies, theymaynotrealize If teens are contemplating suicide to the book;parents are barely mentioned. to thenovel. are “There onlyteenagersin things,” Hu said,describingherreactions ‘Concerned byanumberofthings’ ‘Concerned to her desire to die. explains how eachofthemcontributed they receive thetapes,onwhichHannah bullied her. Two weeks afterherdeath, she arrangestohave senttopeoplewho cassette tapesthat Hannah, records main character, Why ReasonsTh1rt3en ing the subject. tomed todiscuss- already accus- agers, soshewas Palo Alto teen- fortion efforts “I wasconcernedby anumber of In the novel, , the book’s See See Page 4 residencies. going for their would be where they out March 17 students found Medical BLINDED Rona Hu DRAMA, page7 , page6 - Studies of scientific bias targeting the right problems By Jennie Dusheck The team also found that small and highly cited studies because interventions might need to be tailored to the In all fields of science, small studies, early studies and those in peer-reviewed journals seemed more likely needs and problems of individual disciplines of fields. and highly cited studies consistently overestimate ef- to overestimate effects; U.S. studies and early studies One-size-fits all solutions are unlikely to work.” fect size, according to a study led by researchers at the seemed to report more-extreme effects; early-career Solutions and interventions School of Medicine. researchers and researchers working in small or long- A scientist’s early career status, isolation from other distance collaborations were more likely to overestimate Ioannidis likewise cautioned that the data are purely researchers and involvement in misconduct also ap- effect sizes; and, not surprisingly, researchers with a his- observational, not experimental, and the question of pear to be risk factors for unreliable results, the research tory of misconduct tended to overestimate effect sizes. how to reduce bias is far from clear. For example, he team reported. On the other hand, studies by highly cited authors said, just because small studies tend to give exaggerated A paper describing the work was published online who published frequently were not more affected by results doesn’t mean we should stop doing them. “One March 20 in the Proceedings of the National Academy bias than average. Research by men was no more likely might say immediately, well, we need to do large stud- of Sciences. The lead author is Stanford senior research to show bias than that of women. And scientists in ies,” he said. “That would be an intervention. But you scientist Daniele Fanelli, PhD, and the senior author is countries with very strong incentives to publish, such as can’t necessarily translate an association directly into an MD, DSc, professor of medicine and of the United States, didn’t seem to have effective intervention.” NORBERT VON DER GROEBEN health research and policy. more bias than studies from countries “I think that one can take Virtually all scientific work may be afflicted by some where the pressure was less. These re- each one of these biases and say, kind of bias, Ioannidis said. But how common different sults confirm, with much greater ac- ‘Well, let’s try to reduce it or kinds of bias are, what factors cause bias, which kinds curacy, previous studies on retractions eliminate it,’” he added. “Some of bias are most common in different disciplines and and corrections and studies using of them are easier to reduce or how bias can be reduced are all questions being exam- more indirect proxies of bias. eliminate, but then we have to ined by researchers who study how science is done. “A country that has incentives to see what that does to the wider “I think that this is a mapping exercise,” said Ioan- publish more may also have other scientific literature.” nidis. “It maps all the main biases that have been pro- features that make its science better,” That said, Ioannidis said he posed across all 22 scientific disciplines. Now we have a Ioannidis said. believes that many fields would map for each scientific discipline, which biases are im- Each kind of bias may result from benefit from having both larger portant and which have a bigger impact, and therefore a variety of mechanisms. For example, studies and the involvement of scientists can think about where do they want to go in small studies, it’s easier to get “sta- numerous authors who are close next with their field.” tistical significance” if the effect size enough to monitor one anoth- To show which sources of scientific bias were most is large. Since studies with statistically er’s work. “But that’s something common, the researchers reviewed more than 3,000 significant results are more likely to be that is an extrapolation,” he said. meta analyses that included nearly 50,000 individual published, it follows that small studies Making science better is John Ioannidis is the senior author of a study research studies across 22 scientific fields. with large effects are also more likely that found the biggest single source of bias quite possible, he said. “Phys- “Our study tested with much greater accuracy than to be published. Even independent of across all fields of science comes from small- ics, for example, at some point before several hypotheses about the prevalence and statistical significance, larger effects study effects. decided that they’ve had enough causes of bias,” said Fanelli. “Our results send a reassur- are more likely to be published than of these tiny studies done by ing message, but only in part.” smaller effects. small teams, and they went Types of bias Ioannidis said that in the data they examined, the for a multi-team collaborative model,” he said. “That influence of different kinds of bias changed over time changed the entire paradigm of how they do research. The researchers examined seven hypothesized kinds and seemed to depend on the individual scientist. “We It probably largely removed the problem of small-study of scientific bias: show that some of the patterns and risk factors seem to bias.” • Small-study effect: when studies with small sam- be getting worse in intensity over time,” he said. “This When physicists work together on huge projects, ple sizes report large effect sizes. is particularly driven by the social sciences, so if you said Ioannidis, “you don’t have the problem of these • Gray literature bias: the tendency of smaller or broke scientific fields into big bins of biology, medi- thousands and tens of thousands of physicists, each one statistically insignificant effects to be reported in PhD cine, physical sciences and social sciences, it seems that of them running their tiny experiment, and then just theses, conference proceedings or personal communi- the social sciences are seeing the more prominent wors- waiting to collate the results after the fact and trying to cations rather than in peer-reviewed literature. ening of these biases over time.” make sense of them.” • Early-extremes effect: when extreme or contro- One of the most unexpected findings of the study, Since each field of science has a slightly different versial findings are published early just because they Fanelli said, was that the kinds and amounts of bias profile of biases, it makes sense, he said, for each one are astonishing. were very irregularly distributed across the literature. to choose the best ways to reduce the biases afflicting • Decline effect: when reports of extreme effects “Although bias may be worryingly high in specific re- their field. are followed by subsequent reports of reduced effects. search areas, it is nonexistent in many others,” he said. “This has to be a grass-roots movement,” Ioannidis • Citation bias: the larger the effect size, the more “So bias does not undermine the scientific enterprise as said. “It has to be something that scientists believe is likely the study will be cited. a whole.” good for their science to do. Top-down approaches, • United States-effect: when U.S. researchers over- Another finding of the study is that the relative mag- such as institutions and funding agencies trying to pro- estimate effect sizes. nitude of biases closely reflects the level of attention mote best practices, could also help, but it has to be • Industry bias: when industry sponsorship and that they receive in the literature. That is, the kinds of an agreement, and an agreement among all these stake- affiliation affect the direction and size of reported ef- biases researchers are most concerned about are in fact holders. And obviously, scientists need to believe that fects. the ones they should be concerned by. “Our under- this is something that will help the results and their sci- The Stanford team also looked at factors that have standing of bias is improving, and our priorities are set ence to be more reliable.” been hypothesized to increase the risk of bias, such as on the right targets,” said Fanelli. A researcher at Leiden University also co-authored size and types of collaborations, the gender of the re- But that’s no cause for complacency, he said. “We the paper. This research was entirely supported by the searchers or pressure to publish. perhaps understand bias better, but we are far from U.S. Office of Research Integrity. By far, the greatest bias came from small studies, having rid science of it. Indeed, our results suggest Stanford’s departments of Medicine and of Health while other sources of bias had relatively small effects. that the challenge might be greater than many think and Research Policy also supported the work. ISM

Researchers create three-dimensional bladder reconstruction

By Jackie Flynn the contours of a cave with a flashlight. that it’s sometimes difficult to orient the postdoctoral scholar at Stanford who is The way doctors examine the blad- Using cameras attached to long, flexible location of masses within the bladder’s now a software engineer at Google der for tumors or stones is like exploring instruments called endoscopes, they find blood-vessel-lined walls. Bladder cancer has among the highest This could change with a new com- recurrence rates of any cancer. Fifty to 70 Inside Stanford Medicine is puter-vision technique developed by percent of tumors return after removal, published monthly in July and Stanford researchers that creates three- according to Liao. Being able to see each STANFORD December and semi-monthly dimensional bladder reconstructions out patient’s bladder as a digital 3-D model

INSIDE the rest of the year. of the endoscope’s otherwise fleeting im- could improve surgical planning and MEDICINE ages. With this fusion of medicine and help doctors monitor cancer recurrence. is produced by Paul Costello engineering, doctors could develop or- “Endoscopy of the bladder, called Office of Communication & Public Affairs Chief communications officer gan maps, better prepare for operations cystoscopy, is an integral part of cancer Susan Ipaktchian and detect early cancer recurrences. management. Anything you can do to School of Medicine Director of print & 3172 Porter Drive Web communications “The beauty of this project is that we improve endoscopy is helpful,” Liao said. Palo Alto, CA 94304 John Sanford can take data that doctors are already “Surgeons are always looking for better Mail code 5471 Editor collecting,” said Audrey Bowden, PhD, ways to see cancer in order to remove it (650) 723-6911 Robin Weiss assistant professor of electrical engineer- more effectively.” http://med.stanford.edu/news/ Graphic designer ing. A paper describing the work was Broadly applicable technique published online March 8 in Biomedi- Send letters, comments and story ideas to John cal Optics Express. Bowden shares senior One of the technique’s advantages is Sanford at 723-8309 or at [email protected]. authorship with Joseph Liao, MD, an that doctors don’t have to buy new hard- Please also contact him to receive an e-mail version of Inside Stanford Medicine. associate professor of urology. The lead ware or modify their techniques signifi- author is Kristen Lurie, PhD, a former cantly. Through See BLADDER, page 3 2 MARCH 27, 2017 INSIDE STANFORD MEDICINE Antibody fights pediatric brain tumors in preclinical testing By Erin Digitale healthy and malignant cells. When CD47 is blocked by cious and less toxic?” Five types of pediatric brain cancer were safely and antibodies, immune cells called macrophages can detect Anti-CD47 antibodies also may have an advantage effectively treated in mice by an antibody that causes the cancer cells’ “eat me” signals. Macrophages then se- over other immunotherapies in that they activate mac- immune cells to engulf and eat tumors without hurt- lectively target, engulf and destroy the cancer cells with- rophages, which completely engulf and eat cancer cells, ing healthy brain cells, according to a new study by re- out harming healthy cells, because normal cells lack the Cheshier noted. “In many forms of immunotherapy, searchers at the School of Medicine. “eat me” signals. the cells you target die and spill their contents, which The immune therapy studied consists of antibod- Study highlights can cause dysregulated immune responses,” he said. ies against a cellular “don’t eat me” signal called CD47. Anti-CD47 antibodies may produce fewer such side ef- Developed at Stanford, the anti-CD47 antibodies are The Stanford team conducted a long series of experi- fects, though the idea remains to be tested. already being tested in early clinical trials in ments using different combinations of tu- Other Stanford co-authors of the paper are medical adults who have tumors outside the central mor cells and healthy cells in culture, as well students Abdullah Feroze, Rogelio Esparza and Mi- nervous system. But they have never been as in various mouse models in which hu- chael Zhang; postdoctoral scholars Suzana Kahn, PhD, tried against pediatric brain tumors until man brain cancer cells had been implanted Anne Volkmer, MD and Stephen Willingham, PhD; now. in mice. Highlights of their experiments in- research assistants Anitha Ponnuswami, Theresa Storm, The new study pitted anti-CD47 an- cluded the following: Cyndhavi Narayanan and Pauline Chu; senior research tibodies against human cancer cells that • The team confirmed that all the vari- associate Jie Liu, MD, PhD; undergraduate research as- had been grown in a dish and implanted ous cancers tested express the CD47 “don’t sociate Chase Richard; Aaron McCarthy, a former life in mice. The tests targeted five aggressive eat me” signal, as well as an “eat me” signal sciences research professional and animal colony man- pediatric brain tumors: Group 3 medullo- called CRT. ager; Patricia Lovelace, research and development engi- blastoma, atypical teratoid rhabdoid tumor, Samuel Cheshier • In a dish, Group 3 medulloblastoma neer; Simone Schubert, life science researcher; visiting primitive neuroectodermal tumor, pediatric cells treated with anti-CD47 antibod- scholar Gregor Hutter, MD, PhD; Griffith Harsh, MD, glioblastoma and diffuse intrinsic pontine glioma. ies were engulfed and eaten by macrophages, while professor of neurosurgery; Michelle Monje, MD, PhD, “For many of these tumors, there’s just no treat- healthy brain cells were not harmed. assistant professor of neurology; Yoon-Jae Cho, MD, a ment,” said Samuel Cheshier, MD, PhD, assistant pro- • In mice with a partially functioning immune sys- former assistant professor of neurology and neurologi- fessor of neurosurgery. “Diagnosis is synonymous with tem that had been transplanted with any of the five cal sciences; Ravi Majeti, MD, PhD, associate professor a death sentence.” types of pediatric brain tumors, treating the mice with of medicine; senior scientist Jens Volkmer, MD; Paul The study was published March 15 in Science Trans- anti-CD47 antibodies significantly reduced the pres- Fisher, MD, professor of pediatrics; Gerald Grant, MD, lational Medicine. Cheshier shares senior authorship ence of those tumors. associate professor of neurosurgery; Gary Steinberg, of the paper with Irving Weissman, MD, the Virginia • In mice, the antibody crossed the blood-brain MD, PhD, professor of neurosurgery; Hannes Vogel, and D.K. Ludwig Professor for Clinical Investigation in barrier in significant amounts after being injected into MD, professor of pathology and of pediatrics; and Mi- Cancer Research and professor of pathology and of de- the peritoneal space. This was an important finding chael Edwards, MD, professor of neurosurgery. velopmental biology. The lead authors are postdoctoral because some other forms of immunotherapy are un- Cheshier, Monje, Majeti, Fisher, Grant and Edwards scholar Sharareh Gholamin, MD, and senior research able to cross this barrier. In mice transplanted with are members of Stanford’s Child Health Research In- scientist Siddhartha Mitra, PhD. Group 3 medulloblastoma, anti-CD47 antibodies stitute. Cheshier, Weissman, Harsh, Monje, Majeti, ‘Very, very active tumor-killing’ were more effective at treating the primary tumor if Fisher, Grant, Vogel and Edwards are members of the given in the peritoneal space, but better at treating me- Stanford Cancer Institute. Many childhood brain tumors are inoperable. Some tastases if given directly into the cerebrospinal fluid. Scientists from SickKids, the Hospital for Sick Chil- also lack effective chemotherapy drugs, or require ra- • Mixing healthy human neural progenitor cells dren in Toronto; University Hospital, Dusseldorf; and diation and chemotherapy so toxic to the developing with anti-CD47 antibodies did not cause any damage Johns Hopkins University also contributed to the study. brain that they cause devastating long-term side effects. to the neural progenitor cells, either in their viability The study was funded by National Institute of In contrast with the toxic profile of existing treatments, or ability to proliferate, suggesting that the antibodies Neurological Disorders and Stroke; the National Can- the preclinical trials conducted by Cheshier’s team indi- would not interfere with brain development. cer Institute; the California Institute for Regenerative cate that anti-CD47 antibodies specifically target can- • In mice with a fully functioning immune system Medicine; the Price Family Charitable Fund; the Center cer cells while leaving healthy brain cells alone. that had been implanted with cells from a high-grade for Children’s Brain Tumors at Stanford; St. Baldrick’s “The most exciting aspect of our findings is that no glioma cell line, anti-CD47 antibodies significantly Foundation; the American Brain Tumor Foundation; matter what kind of brain tumor we tested it against, prolonged survival of the animals, from an average of the Seibel Stem Cell Institute; the Pew Charitable this treatment worked really well in the animal models,” 21 days for those in the untreated group to 32 and 38 Trusts; the Dr. Mildred-Scheel Foundation/German said Cheshier, who is also a pediatric neurosurgeon at days for those receiving low and high doses of antibod- Cancer Aid; the German Research Foundation; the Lucile Packard Children’s Hospital Stanford. In mice ies, respectively. McKenna Claire Foundation; the Matthew Larson that had been implanted with both normal human • In mice treated with anti-CD47 antibodies, their Foundation; Alex’s Lemonade Stand Foundation; The brain cells and human brain cancer cells, “there was brains, examined after treatment, showed that macro- Cure Starts Now; the Lyla Nsouli Foundation; the no toxicity to normal human cells but very, very active phages concentrated at the sites of the tumors. Further Dylan Jewett, Connor Johnson, Zoey Ganesh, Dylan tumor-killing in vivo,” he said. tests showed that macrophages got inside the tumors. Frick, Abigail Jensen, Wayland Villars and Jennifer Given the encouraging results of the new study The anti-CD47 antibodies did not completely elimi- Kranz memorial funds; the Virginia and D. K. Ludwig and the ongoing research on anti-CD47 antibodies in nate all tumors, suggesting that the antibodies may not Fund for Cancer Research; the Lucile Packard Foun- adults, the antibodies are expected to reach clinical tri- be able to completely penetrate large tumors, the re- dation for Children’s Health; the National Institutes of als in children with brain cancer in one to two years, he searchers noted. Health; the Tashia and John Morgridge Endowed Pedi- added. To maximize their effects, the antibodies will likely atric Faculty Scholar and Fellowships Awards; and the The anti-CD47 antibodies help the immune system need to be combined with other forms of cancer treat- Anne T. and Robert M. Bass Endowed Faculty Scholar- to detect an important difference between cancerous ment, a concept the researchers plan to investigate fur- ship in Pediatric Cancer and Blood Diseases. The study and healthy cells: Cancer cells make “eat me” signals ther, Cheshier said. In the future, patients may receive was also funded by gifts from George Landegger; Rider that are displayed on their cell surfaces, while healthy combinations of immune therapies and lower doses of and Victoria McDowell; Charles Comey and Judith cells do not. However, cancer cells hide these “eat me” standard cancer treatments, he said, adding, “The ques- Huang; and Colin and Jenna Fisher. signals by producing large quantities of CD47, a “don’t tion is: Can we wisely combine immune therapies and Stanford’s Department of Neurology & Neurological eat me” protein that is found on the surface of both other approaches to make cancer treatment more effica- Sciences also supported the work. ISM

Bladder for surgery. Lesions, tumors and scars in ing matched the able to navigate continued from page 2 the bladder are hard to find, both ini- tissue phantom around a virtual tially and during surgery. with few errors. organ,” Liao the use of advanced computer-vision “Sometimes you don’t have a sense — This tech- said. algorithms, the team reconstructed the where was I in the bladder?” Liao said. nique is the first The other shape and internal appearance of a blad- Seeing a three-dimensional rendering of of its kind and Stanford co- der using the video footage from a rou- an organ before operating, like having a still has room for author of the tine cystoscopy, which would ordinarily map before embarking on a trip, could improvement, paper is Dimitar have been discarded or not recorded in make the procedure easier for doctors. the researchers Zlatev, MD, a the first place. Other potential applications include us- said. Primarily, Audrey Bowden Joseph Liao resident in urol- “In endoscopy, we generate a lot of ing the digital 3-D reconstruction as a the 3-D models ogy. A researcher data, but currently they’re just tossed visual medical record. tend to flatten out bumps on the bladder at Max Planck Institute in Germany was away,” said Liao. Accurate rendering wall, including tumors. With the model also a co-author. Although the team developed the alone, this may make tumors harder to Bowden is a member of Stanford technique for the bladder, it could be To test the accuracy of their bladder spot. The team is now working to ad- Bio-X and of the Stanford Child Health applied to other hollow organs where reconstruction, the team first created a vance the realism, in shape and detail, of Research Institute. Liao is a member of doctors routinely perform endoscopy, in- model based on endoscopy images taken the models. Stanford Bio-X and of the Stanford Can- cluding the stomach or colon. “We were in a three-dimensional-printed bladder, Future directions, according to the cer Institute. the first group to achieve complete 3-D known as a tissue phantom. Because the researchers, include using the algorithm This research was supported by the bladder models using standard clinical details of the tissue phantom are known, for disease and cancer monitoring within National Science Foundation and the equipment, which makes this research the researchers could directly compare it the bladder over time to detect subtle Max Planck Center for Visual Comput- ripe for rapid translation to clinical prac- to their rendering. According to Bowden, changes, as well as combining it with ing and Communication. tice,” Lurie said. tissue phantoms provide a standard for other imaging technologies. Stanford’s departments of Urology According to Liao, these three-dimen- biological modeling analysis. The team “The technology has immense poten- and of Electrical Engineering also sup- sional images could help doctors prepare found that its three-dimensional render- tial, not to mention the fun factor to be ported the work. ISM INSIDE STANFORD MEDICINE MARCH 27, 2017 3 After years of preparation, students ‘match’ to residencies PHOTOS BY JOHN GREEN By Tracie White plishments of the students, and congratulating them: “You’re embark- At 8:55 a.m., as Nuriel Moghavem ing upon a tremendously exciting got up from his table to accept the period in your career and your life of sealed, red envelope with his future medicine,” he said. “Congratulations hidden inside, his two younger broth- to all of you.” ers punched him in the shoulder — Next, Charles Prober, MD, se- for luck. nior associate dean for medical edu- The neurologist-in-training, who is cation, took the podium to start the also passionate about health care pol- countdown. icy and took a year off from medical “The envelopes cannot be opened, school to work as a legislative assistant anywhere in the country, until 9 a.m. in Sacramento, was, for the moment, Pacific time,” Prober told the crowd of at loose ends. students, families, friends and advis- “Oh yeah, now I’m nervous,” said ers seated at tables in Berg Hall. With Moghavem, taking deep breaths and several minutes left to wait, Prober staring at his shoes while his brothers described for the crowd some of the grinned at him from behind. history of Match Day. He was one of 70 soon-to-be gradu- The matching process is a tradi- ating Stanford medical students who tion that dates back to 1952, with took part in Match Day on March 17 assignments ultimately de- at the Li Ka Shing Center for Learning termined by a nonprofit organization, and Knowledge. Thousands of other the National Resident Matching Pro- medical students across the United gram. The organization uses a com- States were, at the same moment, also puter algorithm to align the choices of waiting to find out where they would the applicants with those of the resi- Graduating medical students Grace Laidlaw, Tom Roberts and Grace Hunter compare results on Match Day after they and their peers were handed envelopes revealing where they would be be spending the next three or more dency programs. It’s a roughly year- spending their residencies. years of their lives as residents. The long process for medical students who, scene was nerve-wracking. in their final year of medical school, “You kind of put all your eggs in fill out applications in the summer, plastic surgery and ophthalmology. Hirotsu, who matched in dermatology, one basket, and today you’re going to then travel across the country to inter- “Sixty-six percent are going to hugging her classmate and friend Mon- see if they hatch,” said Kelsey Hirotsu, views in the fall. This year’s students two states: California and Harvard,” ica Coughlan, both in tears. “I’m going who dressed up in heels and curls to logged maybe a million frequent flier Prober said — Harvard traditionally to Stanford.” Hirotsu’s boyfriend grinned find out where she would be match- miles, traveling to a thousand or so in- is a popular matching spot for Stan- and said how hard she had worked to ing in dermatology. Her parents’ flight terviews, Prober said. ford students — to laughter from the get to this day, adding that her parents from Ohio was delayed due to bad Then with just one minute left crowd. “Twenty-nine percent are stay- should be arriving any moment. weather, and her mom was “freak- before the big moment, Prober gave ing at Stanford.” Coughlan matched in orthopedic sur- ing out,” Hirotsu said, laughing as the crowd a few clues as to what was ‘Ten, nine, eight …’ gery at the University of California-San she repeated her mom’s frenzied cry, waiting inside the soon-to-be opened Francisco. “We’re not going to be there for the envelopes. The 70 students would be Finally, Prober started counting “I’m so incredibly happy,” said envelopes!” matching into 20 different disciplines. down the seconds: “Ten, nine, eight Coughlan, adding that while opening ‘Congratulations to all of you’ About 47 percent were matching ….” At exactly 9 a.m., the students be- her letter, “I literally almost collapsed.” into general disciplines, such as fam- gan ripping open their envelopes, and Across the room, Moghavem took his Lloyd Minor, MD, dean of the ily medicine and pediatrics, while the the screams erupted, followed by hugs, time. School of Medicine, opened the cer- remaining 53 percent were matching tears and dozens of photos. He watched as emotion erupted emonies, applauding the accom- into sub-specialties, such as neurology, “I’m so happy, so happy!” yelled around the room, then with his parents and brothers gathered close around, he carefully opened his envelope with shak- ing hands, read the letter, nodded his head and hugged his mom. He matched at Stanford, his first choice. “We have big shoes to fill,” said his brother, Eli Moghavem, nodding to the youngest brother, a senior in high school, who was busy uploading the news to his friends on Snapchat. His mom beamed with pride at her oldest son, the one who said in kinder- garten that he wanted to be a patholo- gist, who was always kind and caring and “always has to do the right thing.” Moghevam said that making a differ- ence in people’s lives is what motivates him. American-born but of Iranian de- scent, he worried about other Iranian- born medical students matching this day whose plans may have been disrupted by the Trump administration’s proposed travel ban. “I’m fortunate. I was born in this country so I didn’t have to worry about that, although my family all comes from Iran,” he said, adding that he’s the first doctor in his large, extended family. “I expect a lifetime of family mem- bers sending me weird pictures of their rashes,” he said. His shoulders sagged a bit with relief and joy, and he smiled. ISM

(Clockwise from top left) Nuriel Moghavem learned that he was accepted to the residency program in neurology at Stanford. Monica Coughlan, left, and Arhana Chattopadhyay talk during Match Day at the Li Ka Shing Center for Learning and Knowledge. Coughlan matched to UCSF in orthopedic surgery, and Chattopadhyay matched to plastic surgery at Stanford. Mark Gaertner poses for a photo with his girlfriend, Lyly Truong, after learning he was accepted to the residency program in neurology at UCLA.

4 MARCH 27, 2017 INSIDE STANFORD MEDICINE Researchers look to Lego for automation of biology experiments

By Andrew Myers INGMAR RIEDEL-KRUSE storms was the inspiration for the Lego Elementary and secondary school Mindstorms sets. students who later want to become sci- “I saw how students and teachers were entists and engineers often get hands-on already using Lego robotics in and out- inspiration by using off-the-shelf kits to side school, usually to build and program build and program robots. But so far it’s moving car-type robots, and I was ex- been difficult to create robotic projects cited by that,” he said. “But I saw a vac- to foster interest in the “wet” sciences — uum for bioengineers like me. I wanted biology, chemistry and medicine — so to bring this kind of constructionist, called because experiments in these fields hands-on learning with robots to the life often involve fluids. sciences.” Now, Stanford bioengineers and their Do it yourself collaborators have shown how an off- the-shelf kit can be modified to create In their PLoS Biology paper, the team robotic systems capable of transferring members offer step-by-step building precise amounts of fluids between flasks, plans and several fundamental experi- test tubes and experimental dishes. ments targeted to elementary, middle By combining the Lego Mindstorms and high school students. They also offer robotics kit with a cheap and easy-to- experiments that students can conduct find plastic syringe, the researchers cre- Building a liquid-handling robot: Start with a Lego Mindstorms system (left); add a motorized pipette for using common household consumables ated a set of liquid-handling robots that dropping fluids (center); and then perform simple experiments, such as showing how liquids of different like food coloring, yeast or sugar. In one approach the performance of the far salt densities can be layered. experiment, colored liquids with distinct more costly automation systems found at salt concentrations are layered atop one universities and biotech labs. another to teach about liquid density. “We really want kids to learn by do- The robots are designed to pipette flu- mechanical engineering and computer Other tests measure whether liquids are ing,” said Ingmar Riedel-Kruse, PhD, as- ids from and into cuvettes and multiple- programming. They could also gain a acids, like vinegar, or bases, like baking sistant professor of bioengineering. well plates — types of plastic containers deeper appreciation of the value of ro- soda, or which sugar concentration is “We show that with a few relatively commonly used in laboratories. Depend- bots in life sciences experiments. best for yeast. Yet another experiment inexpensive parts, a little training and ing on the specific design, the robots can Riedel-Kruse uses color-sensing some imagination, students can create handle liquid volumes far smaller than 1 said he drew in- light meters to their own liquid-handling robots and microliter, a droplet about the size of a spiration from “We really want kids to align color-coded then run experiments on them — so the single coarse grain of salt. Riedel-Kruse constructionism, cuvettes. students learn about engineering, coding believes that these Lego designs might a learning theory learn by doing.” The coding as- and the wet sciences at the same time,” even be useful for specific professional or that advocates pect of the robot is he added. academic liquid-handling tasks that nor- project-based elementary, Riedel- Robots meet biology mally require robots costing many thou- learning in which students make tangible Kruse said. A simple programming lan- sands of dollars. objects and connect different ideas and guage allows students to place symbols A paper describing the work was His overarching idea is to enable stu- areas of knowledge and thereby con- telling the robot what to do: Start. Turn published March 21 in PLoS Biology. dents to learn the basics of robotics and struct mental models to understand the motor on. Do a loop. And so forth. The Riedel-Kruse is the senior author. The the wet sciences in an integrated way. world around them. One of the leading robots can be programmed and operated lead author is postdoctoral scholar Lukas Students could learn to collaborate while theorists in the field was Seymour Pap- in different ways. In some experiments, Gerber. also developing STEM skills, such as ert, whose seminal 1980 book Mind- students push but- See LEGO, page 8

As Moore’s law hits limits, new generation of brainlike computers emerges

By Nathan Collins neers could fit more components on a chip, those chips the point: most personal computers operate nowhere would become more and more unreliable. near the limits on conventional chips. Neuromorphic For five decades, Moore’s law held up pretty well: At around the same time, Boahen and others came computers would be most useful in embedded systems Roughly every two years, the number of transistors that to understand that the brain had enormous computing that have extremely tight energy requirements, such as could fit on a chip doubled, all while costs steadily de- power — orders of magnitude more than what people very low-power neural implants or on-board computers clined. Today, however, transistors and other electronic have built, even today — even though it used vastly in autonomous drones. components are so small they’re beginning to bump up less energy and remarkably unreliable components: L.A. CICERO / STANFORD NEWS SERVICE against fundamental physical size limits. neurons. Moore’s law has reached its end, and it’s going to take How does the brain do it? something different to meet the need for computing that is ever faster, cheaper and more efficient. While others have built brain-inspired computers, As it happens, Kwabena Boahen, PhD, a Stanford Boahen said, he and his collaborators have developed professor of bioengineering and of electrical engineer- a five-point prospectus — manifesto might be the bet- ing, has a pretty good idea what that something more is: ter word — for how to build neuromorphic computers brainlike, or neuromorphic, computers that are vastly that directly mimic in silicon what the brain does in more efficient than the conventional digital computers flesh and blood. we’ve grown accustomed to. The first two points of the prospectus concern neu- This is not a vision of the future, Boahen said. As he rons themselves, which unlike computers operate in a lays out in the March/April issue of Computing in Sci- mix of digital and analog mode. In their digital mode, ence and Engineering, the future is now. neurons send discrete, all-or-nothing signals in the “We’ve gotten to the point where we need to do form of electrical spikes, akin to the ones and zeros of something different,” said Boahen, who is also a mem- digital computers. But they process incoming signals by ber of Stanford Bio-X and the Stanford adding them all up and firing only once a threshold is Institute. “Our lab’s three decades of experience has put reached — more akin to a dial than a switch. Kwabena Boahen has written “A Neuromorph’s Prospectus,” us in a position where we can do something different, That observation led Boahen to try using transistors outlining how to build computers that directly mimic in silicon what something competitive.” in a mixed digital-analog mode. Doing so, it turns out, the brain does in flesh and blood. 30 years in the making makes chips both more energy efficient and more ro- bust when the components do fail, as about 4 percent “It’s complementary,” Boahen said. “It’s not going to It’s a moment Boahen has been working toward his of the smallest transistors are expected to do. replace current computers.” entire adult life, and then some. He first got interested From there, Boahen builds on neurons’ hierarchical The other challenge: getting others, especially chip in computers as a teenager growing up in Ghana. But organization, distributed computation and feedback manufacturers, on board. Boahen is not the only one the more he learned, the more traditional computers loops to create a vision of an even more energy efficient, thinking about what to do about the end of Moore’s law looked like a giant, inelegant mess of memory chips and powerful and robust neuromorphic computer. or looking to the brain for ideas. IBM’s TrueNorth, for processors connected by weirdly complicated wiring. The future of the future example, takes cues from neural networks to produce a Both the need for something new and the first ideas radically more efficient computer architecture. On the for what that would look like crystalized in the mid- But it’s not just a vision. Over the last 30 years, Boa- other hand, it remains fully digital, and, Boahen said, 1980s. Even then, Boahen said, some researchers could hen’s lab has actually implemented most of its ideas in 20 times less efficient than Neurogrid would be had it see the end of Moore’s law on the horizon. As transis- physical devices, including Neurogrid, one of the first been built with TrueNorth’s 28-nanometer transistors. tors continued to shrink, they would bump up against truly neuromorphic computers. In another two or three Boahen is also a member of Stanford SystemX and fundamental physical limits on their size. Eventually, years, Boahen said, he expects they will have designed the Stanford Computer Forum. His work was sup- they’d get so small that only a single lane of electron and built computers implementing all of the prospec- ported by a Director’s Pioneer Award and a Transfor- traffic could get through under the best circumstances. tus’s five points. mative Research Award from the National Institutes What had once been electron superfreeways would soon Don’t expect those computers to show up in your of Health and a grant from the U.S. Office of Naval be tiny mountain roads, and while that meant engi- laptop anytime soon, however. Indeed, that’s not really Research. ISM INSIDE STANFORD MEDICINE MARCH 27, 2017 5 Listings on ClinicalTrials.gov are not types of procedures. to check if a trial is affiliated with an aca- Blinded fully scrutinized for scientific soundness, “We expect health care providers to demic medical center, Goldberg said. continued from page 1 Goldberg said. Although still visible on take every precaution to ensure patient The lead author is Ajay Kuriyan, MD, cells some researchers are targeting to de- the website, the listing now states: “This safety, but this definitely shows that the assistant professor of ophthalmology velop therapies. study has been withdrawn prior to en- lack of oversight can lead to bad players at the University of Rochester Medical “There is a lot of very well-founded rollment.” The clinic is also no longer and bad outcomes. It’s alarming,” Albini Center. Researchers from the University evidence for the positive potential of performing these eye injections, although said. of Miami, Univer- stem therapy for many human diseases, it is still seeing patients, Albini said. The au- sity of Rochester, but there’s no excuse for not designing a ‘It’s alarming’ thors acknowl- University of Okla- trial properly and basing it on preclinical edged that it is “There’s no excuse for homa and the Cen- research,” Goldberg said. The procedures were arguably not difficult for pa- not designing a trial ter for Sight also The “trial” lacked nearly all of the subject to Food and Drug Administra- tients to know co-authored the components of a properly designed clini- tion approval because the cells were not whether a clini- properly and basing it on study. cal trial, including a hypothesis based on transferred between patients and were cal trial, or a stem preclinical research.” The report was laboratory experiments, assignment of a considered “minimally processed,” ac- cell therapy, is le- funded by the Na- control group and treatment group, col- cording to Title 21, Part 1271.10, of the gitimate. Goldberg tional Institutes of lection of data, masking of clinical and Code of Federal Regulations. The FDA recommended that patients considering Health, Research to Prevent Blindness, patient groups, and plans for follow-up, released more specific guidelines in Oc- a stem cell treatment consult a website, the Department of Defense and the Goldberg and Albini said. “There was tober 2015, after these procedures were A Closer Look at Stem Cells, main- Klorfine Foundation. a whole list of egregious things,” Albini performed, establishing the requirement tained by the International Society for Stanford’s Department of Ophthal- said. for FDA oversight and approval for these Stem Cell Research. It is also advisable mology also supported the work. ISM

Gun ful when making health policy costs through Medicare, Medicaid, private insurance continued from page 1 decisions.” or out of their pockets. Patients were overwhelmingly The Stanford team set out male, and there was a correlation between their insur- to estimate the national medi- ance status and how they sustained their injuries. For little research on gun violence cal costs of firearm injuries over example, shootings of young and poor individuals in- from a public health perspec- a nine-year period by using sured by Medicaid comprised two-thirds of firearm tive. This is, in part, due to publicly available data in the injuries, and they were most often victims of assault. a measure Congress passed Nationwide Inpatient Sample, In contrast, older Medicare-insured patients were more in 1996 that restricts federal the largest database in the likely to suffer from self-inflicted gunshot wounds. funding for firearms research, Thomas Weiser Sarabeth Spitzer United States, which houses The study captures costs for a very limited experi- Spitzer said. information from about 8 mil- ence because the costs of firearm injuries continue in Past studies have looked lion hospital discharges each many different ways, Spitzer said. “There’s a cost if into the total costs of firearm injuries — medical as year. The researchers picked patients who were admit- you’re readmitted, there’s long-term rehab, and a lot of well as social — but most have focused either on par- ted for firearm-related injuries and analyzed the severity these patients end up needing long-term health care,” ticular states or within narrow time ranges. Analyzing of their wounds, the cost of their care, where they were she said, adding that she and her colleagues will next data from 2012, a Mother Jones investigation estimated hospitalized and how they paid for the hospitalizations. systematically analyze costs of hospital readmissions. that the annual cost of gun violence in America exceeds Government bears large share of cost “It’s amazing that we don’t know as much about the $229 billion, as much as $3.4 billion of which includes medical costs of firearm injuries,” said David Hemen- emergency services, police investigations and long-term Spitzer and her colleagues interrogated the data to way, director of the Harvard Injury Control Center, medical- and mental-health care costs. The actual costs address two primary questions: What were the total who was not involved in the study. “[This study] high- of hospital visits are difficult to tease out from these fig- medical costs when gunshot victims were first hospital- lights that this is just the tip of the iceberg.” ures, and it is unclear who actually ends up paying for ized, and where did the financial burden of medical care Other Stanford co-authors of the study are Kristan them. fall? Staudenmayer, MD, associate professor of surgery; Da- “Firearm injuries are tied to one of the most con- The team found that the government bears about 40 vid Spain, MD, professor of surgery; and research scien- troversial political issues in the country, so it is impor- percent of the total costs. “It’s a very high financial bur- tist Lakshika Tennakoon. tant for all sides to have access to fact-based research,” den,” Spitzer said. The research was supported by the Stanford Medical Spitzer said. “Cost information can be especially help- The researchers found that victims paid for hospital Scholars Fellowship Program. ISM

Fathers, in addition to mothers, now sought for Stanford eating-disorder study

VGSTOCKSTUDIO / SHUTTERSTOCK.COM

By Erin Digitale of the timing and content of a meal, and children decide whether to eat and Mothers who have previously had an how much. The researchers will also eating disorder often struggle to teach help each family identify specific, indi- their children healthy eating habits, vidualized ways that the parent’s eating- research has shown. Now, a School of disorder history might affect them and Medicine study of how to help them is develop techniques to counteract pos- being expanded to include fathers, mak- sible problems. ing it the first study in the world to of- “We want to help educate parents fer this type of targeted intervention for and also help them work through their dads. anxieties that if they open the gate, the “We have really sparse information on child will have no limit,” Sharvit said. fathers with eating disorders,” said Shiri “We want to help parents feel that they Sadeh-Sharvit, PhD, a visiting scholar can manage their own concerns and al- at Stanford who is helping to lead the low their child to regulate his or her own new study. “Although eating disorders hunger and satiety.” are very stigmatized in women, there is The researchers hypothesize that the even more stigma in men. And men may study will help parents avoid pressuring not understand the potential impact of children to eat too little or too much, their eating disorder on their children, that children will take more responsibil- since feeding is, in many families, still ity for regulating their own hunger and perceived as an issue that mothers worry cluded only two-parent families; single- healthy development. Or, the parents fullness, and that parents will communi- more about.” parent families are now also being asked may closely monitor how much a child cate better about eating patterns. In 2014, Sharvit and her collaborators to join. For the 16-week study period, eats and tell him or her when to stop The study’s principal investigator is began testing a method aimed at helping the researchers will work with the par- eating. James Lock, MD, PhD, professor of psy- mothers with a history of eating disor- ent to build healthy family interactions Such well-intentioned efforts can chiatry and behavioral sciences at Stan- ders nurture good eating habits in their around food. backfire, Sharvit said. “There is a lot of ford and a clinician who treats eating young children. The researchers began Unhealthy control evidence that the more you control or disorders at Lucile Packard Children’s their study in women who were living restrict a child’s eating, the more likely Hospital Stanford. with their partners and small children. Prior research has shown that parents they are to eat more when the parent is Families who are interested in partici- The eligibility criteria for the study have with a history of disordered eating may not around and become overweight.” pating in the research can contact Sadeh- been extended, and the researchers are try to exercise an unhealthy degree of In the newly expanded study, the Sharvit at 497-4949 or shiris@stanford. now recruiting families with a child be- control over their children’s food intake. Stanford researchers will meet with edu for more information. tween the ages of 1 and 5 whose mother For instance, parents who fear their chil- families 12 times during the 16-week Information about all of Stanford’s or father has had anorexia nervosa, buli- dren becoming overweight may prevent period. Parents will learn about the eating-disorder studies that are seeking mia nervosa or binge-eating disorder in their kids from eating high-fat or high- “Division of Responsibility” model of participants is available online at http:// the past. The study had previously in- carbohydrate foods that are needed for feeding, in which parents are in charge edresearch.stanford.edu/studies.html. ISM 6 MARCH 27, 2017 INSIDE STANFORD MEDICINE 5 questions Adelsheim on Santa Clara County suicide report an occasional feature in which an expert answers five questions on a science or policy topic Earlier this month, the federal government chiatry and behavioral sciences at the School of Medicine and a child and adoles- released a report on risk factors for suicide cent psychiatrist at Lucile Packard Children’s Hospital Stanford, has been involved in among youth in Santa Clara County. The report, which was requested by members of several efforts to improve mental health care for young people in the community. He the Palo Alto community in response to youth suicides in 2009 and 2014, reviewed spoke with science writer Erin Digitale about the new report, which was produced by the of suicidal behaviors in young people living in the county, as well as the Centers for Disease Control and the Substance Abuse and Mental Health Services aspects of the community response. Steven Adelsheim, MD, clinical professor of psy- Administration.

What did the report say about suicide rates and pre- What else did the report reveal? How have Stanford Children’s Health and Lucile 1cipitating circumstances behind youth suicides in 3 5 Packard Children’s Hospital Stanford responded to Santa Clara County? ADELSHEIM: When you look broadly at the entire the need for better mental health services for our com- county and note the rate of suicides in males aged 20 to munity’s youth? ADELSHEIM: The report found that youth suicide rates 24, it raises important questions about how young peo- for residents of Santa Clara County have remained re- ple who are no longer high school age can access mental ADELSHEIM: We have formed many productive ally stable, with no significant difference over time since health services. I think we need to recognize their cri- partnerships. We’re doing a lot of work with schools 2003. When you look across the board at the county’s ses and build better access to early mental health care in Santa Clara and San Mateo counties, where we’ve 10- to 24-year-olds, the annual suicide rate is 5.4 per across the board. We also need to start asking why these been providing direct care, prevention efforts, early 100,000 people, which is very similar to the Califor- young men are less likely to access mental health care intervention, and training and support for school staff nia rate of 5.3 per 100,000. The national suicide rate and build programs for them to easily get it. around suicide prevention. We’re working with groups among this age group is higher than rates for our county The contrast between youth suicide rates in rural and like Project Safety Net in Palo Alto and the HEARD and state, at about 8 per 100,000. urban areas of Northern California is also noteworthy. Alliance to increase the range of support available for Looking at the county’s youth suicides in detail, two- According to the data the CDC examined, Bay Area young people, as well as providing community educa- thirds occurred among young people aged 20 to 24, and counties have rates that are very similar to the state rate tion. We’re also working to launch a program for youth three-fourths of young people who died by suicide were of around 5 to 6 suicide deaths per 100,000 young peo- with early signs of psychosis to help decrease suicide risk male. Their ethnicity distribution was close to that of ple, while rural counties have much higher rates. The among those in the early stages of serious psychiatric the county as a whole. When the researchers looked at top three were Mendocino (16.2 per 100,000), Lake conditions. youth who died by suicide, the cities of Palo Alto and (15.2 per 100,000) and Humboldt (12.5 per 100,000) In addition, we’ve partnered with Mills Peninsula Morgan Hill did have higher rates than the county as counties. Hospital to have Stanford child and adolescent psy- a whole: 14.1 suicide deaths per 100,000 among Palo One difficulty is that many rural counties generally chiatrist staff several pediatric inpatient mental health Alto residents and 12.7 per 100,000 among Morgan lack the financial support to provide the same access beds. Having hospital beds available for youth in cri- Hill residents. to evidence-based interventions across large rural ar- sis is important, but only one piece of the puzzle. We A key finding of the report was that many people eas. A possible solution is building out telehealth and also want to be able to help young people much earlier. who died by suicide had faced a recent crisis or mental telepsychiatry capacity, which we at Stanford have done To that end, we’ve been developing a local version of health issue. About a third were currently being treated in a small way by providing this kind of support to a the headspace program, based on a successful Austra- for mental illness, and 48 percent had pediatric practice in Monterey. There may be lian program of the same name, for providing outpa- current mental health problems, includ- value in expanding these types of support to tient counseling and other early-intervention services ing depression, substance abuse and more rural counties to expand access to mental to youth. Santa Clara County has allocated funding for alcohol dependence. Fifty-two percent health care. two staff positions, a youth development specialist and had had a recent life crisis, such as a a school employment specialist, and we’re partnering breakup with a boyfriend or girlfriend, One area of focus for the CDC report was with the county to potentially access additional innova- problems at school or a significant 4 the quality of news reporting about Santa tion grant funding to support the development of two argument. Clara County’s youth suicides. What does the county headspace sites. media need to improve? The headspace model is designed to help youth aged To what extent do you think the find- ADELSHEIM: Responsible news reporting 12 to 25, so it’s a potential access point for young peo- ings support or refute assumptions 2 Steven Adelsheim is an important element of reducing suicide ple aged 20 to 24 who might not otherwise get mental people may have made about youth sui- contagion among youth, but the CDC report health care. Our marketing for headspace will include cides in Santa Clara County? shows that local and national coverage of youth suicides messages saying that this is a place to go for help re- ADELSHEIM: Locally, before the report came out, was fairly uneven in quality. Problems the CDC docu- covering from breakups and other difficult life events, there was a sense that losses of young people in the Palo mented in media reports included use of sensationalis- rather than overtly branding it as a mental health clinic. Alto area were much larger compared to the county as tic terms and headlines, as well as photos or language We hope this approach will help us draw in a larger a whole. It’s true that the rate of youth suicides within depicting the means by which people had died. Those swath of young people. Palo Alto was found to be higher than for young people should be avoided in news coverage of suicides. Overall, we are supporting a broad range of com- elsewhere in the county, and there may be some ongo- Also, there are several things media stories can in- munity-based services. We want to have capacity that ing stressors among Palo Alto youth, such as academic clude to make coverage more responsible, which the stretches from prevention to early intervention to acute- stress, that the community is working hard to address. report found were sometimes missing. For instance, it care services, and we’re really proud to partner with so But the findings also make clear that no single factor helps to talk about suicide as a public health issue that many community groups to work toward this worthy explains suicide-related deaths. is multifactorial and can have important mental health goal. The report reflects well on efforts the Palo Alto com- aspects. It’s useful to talk about hope and tell stories of munity has been making to improve all aspects of men- people who were struggling but then did better. And it’s Individuals in crisis can receive help from the Santa Clara tal health among young people. Strong partnerships very important to say that treatment for mental health County Suicide & Crisis Hotline at (855) 278-4204. have been formed between the school district, the city, problems works, to say there are treatment options, and Help is also available from anywhere in the United States parents, teens, mental health care providers — includ- to provide contact information for crisis services and via Crisis Text Line (text HOME to 741741) or the Na- ing our team at Stanford — and many others. All these say, “If you’re concerned that you may harm yourself, tional Suicide Prevention Lifeline at (800) 273-8255. All partners deserve credit because their efforts are making here is the place to go.” Overall, avoiding sensationalism three services are free, confidential and available 24 hours a difference. and showing that help is available are really important. a day, seven days a week. ISM

Drama important,” Hu said. “I’d like to use the scene to BETH DUBBER / NETFLIX continued from page 1 help teach medical students and residents.” Depicting the bullies they love. The people they want to punish are of- ten those who are least likely to learn something, Hu also advised the producers on portraying and those who are most likely to be hurt are not the the bullies, as well as the scene in which Han- ones they wanted to hurt in the first place.” nah dies. “I wanted to make sure the bullies are In the Netflix series, Hannah’s mother is a much depicted as people, and show that people can more prominent character than in the novel, and contribute to bullying in ways that are maybe the series shows her pain and sadness, Hu said. thoughtless but not malicious,” she said. If the Another problem with the book: The school bullies were too one-dimensional, it would be easy counselor Hannah approaches for help comes across for viewers to dismiss them as simply mean; show- as inept. ing them as real people is more likely to prompt “We didn’t want teens to feel like if they went to viewers to think through how they treat their own adults for help, the adults would be uncaring,” Hu peers. said. The dialogue for Hannah’s interaction with The scene in which Hannah dies, Hu said, the counselor remained the same as in the novel, “had to be sad, lonely and not inspire copycats.” but at Hu’s advice, the counselor was given a back Instead of the Romeo-and-Juliet glamour used in story, and script writers added several nonverbal de- many fictionalized depictions of suicide, the pro- tails to his conversation with Hannah. For instance, ducers showed Hannah in a baggy sweatshirt, in the phone rings repeatedly while they talk, and the pain, crying. counselor closes his eyes or shakes his head at diffi- “We wanted to convey that suicide isn’t a good cult parts of the conversation, indicating to Hannah option; instead it is the end of all options and in- that he may be too busy to help her, or not willing flicts pain on people you love,” Hu said. “And we to hear what she is saying. wanted to show that you can get help, that Han- “The producers did a nice job of depicting little nah misses opportunities for help and that teens things that add up to someone missing something around her have opportunities to help her.” ISM 13 Reasons Why, a drama about teen suicide, debuts March 31 on Netflix. INSIDE STANFORD MEDICINE MARCH 27, 2017 7 p eo p le Conference on future of medical education set for April 22-23 COURTESY OF STANFORD MEDICINE X By Tracie White we use data and analytics to bet- ter understand the entire person Stanford Medicine X|ED, an academic conference on in order to tailor the best therapy the future of medical education, will be held April 22-23 and treatments for an individual at the Li Ka Shing Center for Learning and Knowledge person — precision health,” Chu at the School of Medicine. said. “This new concept, preci- In its inaugural year as a stand-alone conference, the sion education, applies a similar event will focus on how to increase diversity within the notion to framing an educational health care workforce and among medical educators, experience, looking at a learner’s and the application of “precision education” — meet- entire learning footprint — how ing the needs of future learners through new technology many times a learner interacts and tools, and personalized education. with an online learning manage- The Medicine X|ED conference began two years ago ment system, opens an email or as a part of the academic health-innovation conference webpage, quiz question, app, Medicine X, but it has been spun off as a separate event flash card.” this year. Keynote speakers at the con- “Medicine X aims to transform health care by elevat- ference will be: ing under-heard voices from its front-line stakeholders, • Clay Johnson, MD, the including patients, caregivers, providers –– people with inaugural dean of the new Dell expertise to transform academic medicine from the bot- Medical School at the University tom up,” said Lawrence Chu, MD, professor of anes- of Texas-Austin. thesiology, perioperative and pain medicine at Stanford • Dan Schwartz, PhD, dean Charles Prober, senior associate dean for medical education, speaks last year at Stanford and founder and director of Medicine X. “We realized of the Stanford Graduate School Medicine X | ED, an event that focuses on the future of medical education. that in order to make real impactful change in health of Education and the author of a care, we needed to dedicate resources to reach the future new book, The ABC’s of How We Learn. parative Effectiveness Research — a main stage break- leaders of tomorrow early enough to make a difference. • Neha Sangwan, MD, developer of a program for out session. Medicine X|ED is our answer to that unmet need.” health care workers’ own care, a program she calls “self- • A main stage panel on the role of games in medi- Examining ways to improve medical education care in health care.” cal education, moderated by Parvati Dev, PhD, former • Erik Brodt, MD, a physician who works to im- director of Stanford University Medical Media and In- The conference will bring together a broad range of prove Native American health and medical training, formation Technology. stakeholders in health care education — from patients, who will speak about using digital media storytelling to Among the many workshops and learning labs, to providers, researchers, industry leaders, designers, inspire American Indian youth. scheduled topics include design thinking for future doc- technologists and medical educators. The goal is to ex- Key events over the two-day event include: tors, integrating the expanding health care system, de- amine new methods of improving medical education, • Diversity 2.0 — a main stage breakout panel ses- veloping leadership and self-empowerment and games organizers said. sion focused on advancing the conversation on diversity as a solution for medical training. “We challenge educators to examine medical educa- and inclusion within medical education. For more information or to register for the confer- tion in the ways we look at medical treatment, where • Patient-Centered Outcomes Research and Com- ence, visit: https://medicinex.stanford.edu/ed. ISM

Team led by Sanjay Basu wins third place in data analysis contest

A team led by Sanjay Basu, MD, PhD, assistant treatment. The work could Lego professor of medicine, has been awarded third place potentially reduce the chance continued from page 5 in contest designed to promote the sharing of clinical of life-threatening side ef- trial data. fects, such as kidney failure. tons to actuate individual motors. In other exper- Contestants used a data set to identify a new sci- A first-, second- and third- iments, students preprogram all motor actions to entific or clinical finding. The data set was developed place winner were selected watch their experiments executed automatically. during the Systolic Blood Pressure Intervention Trial, from 143 entries based on “It’s kind of easy. Just define a few parameters, known as SPRINT, which compared intensive man- which entry provided the and the system works,” he said, adding, “These agement to standard management of blood pressure. most clinically useful infor- robots can support a range of educational experi- The Massachusetts Medical Society sponsored the mation. Judging was done by Sanjay Basu ments, and they provide a bridge between me- contest, called the SPRINT Data Analysis Challenge, a panel of experts and crowd- chanical engineering, programming, life sciences which was held to promote the sharing and reuse of voting by the public. and chemistry. They would be great as part of in- data. The three winners will present their findings at a school and after-school STEM programs.” Basu’s team used the data to develop and validate meeting in April. STEM-ready a clinical decision score that identifies patients who Basu’s team included Joseph Rigdon, PhD, a Stan- are likely to experience benefits and unlikely to experi- ford engineering research associate, and researchers Riedel-Kruse said these activities meet sev- ence harms when undergoing intensive blood pressure from the University of Michigan. ISM eral important goals for promoting multidisci- plinary STEM learning as outlined by the Next Generation Science Standards and other national initiatives. He stressed the cross-disciplinary in- ology, has received the 2017 Genetics Society of America struction value that integrates robotics, biology, of note Medal. The award honors outstanding contributions to chemistry, programming and hands-on learning reports on significant honors and awards the field of genetics in the past 15 years. Kingsley was in a single project. for faculty, staff and students recognized for his experimental work, beginning with The team has co-developed these activities different species of three-spine stickleback fish, which with students and a science teacher, and then RENUMATHY DHANASEKARAN, MD, instructor of medi- provided insights into how vertebrates evolve in natu- tested them with elementary and middle school cine, has received one of three 2017 Junior Faculty ral environments. He has now expanded his inquiry into students over the course of several weeks of in- Development Awards from the American College of understanding human traits, including aspects of skin, struction. Instructions for developing the ro- Gastroenterology. The award, which provides $100,000 skeletal and brain evolution. bots are now ready for wider dissemination to an a year for three years, supports junior investigators work- KARIM SALLAM, MD, clinical instructor of medicine, open-access community that can expand upon ing toward independent careers in clinical research in has received the American College of Cardiology’s Wil- the plans, capabilities and experiments for this gastroenterology or hepatology. Dhanasekaran’s proj- liam W. Parmley Young Author Achievement Award. new breed of fluid-handling robots, and they ect is “Plasma glycoproteomic biomarkers for invasive The award recognizes two papers published in the Jour- might even be suitable to support certain research human hepatocellular carcinoma,” and her mentor is nal of the American College of Cardiology by authors applications. Dean Felsher, MD, PhD, professor of medicine and of early in their careers. Sallam’s paper, published Nov. 8, “We would love it if more students, do-it- pathology. 2016, was “Patient-specific and genome-edited induced yourself learners, STEM teachers and researchers ALFREDO DUBRA, PhD, was appointed associate profes- pluripotent stem cell-derived cardiomyocytes elucidate would embrace this type of work, get excited and sor of ophthalmology, effective Oct. 1, 2016. His focus is single-cell phenotype of Brugada syndrome.” His men- then develop additional open-source instructions on using ophthalmologic imaging technologies to reveal tor is Joseph Wu, MD, PhD, professor of medicine and and lesson plans for others to use,” Riedel-Kruse ocular, vascular, neurodegenerative and systemic diseases. of radiology and director of the Stanford Cardiovascular said. DAVID KINGSLEY, PhD, professor of developmental bi- Institute. ISM For more information, see the PLoS Biol- ogy paper and Riedel-Kruse’s lab website. Other co-authors of the paper are a science teacher at Isaac Newton Graham Middle School in Mountain View and one current and two for- mer high school students. Funding was provided by grants from the Na- tional Science Foundation. Stanford’s Department of Bioengineering, which is jointly operated by the School of Medi- cine and the School of Engineering, also sup- Renumathy Dhanasekaran Alfredo Dubra David Kingsley Karim Sallam ported the work. ISM 8 MARCH 27, 2017 INSIDE STANFORD MEDICINE