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Autism, Neuroscience, Pediatrics, Research, Stanford News

Finding of reduced brain flexibility adds to Stanford research on how the autistic brain is organized

Finding of reduced brain flexibility adds to Stanford research on how the autistic brain is organized

A Stanford brain-imaging study has just shown that the brains of children with autism are less able to switch from rest to taking on a new task than the brains of typically developing children.

According to the study, which appears this week in the scientific journal Cerebral Cortex, instead of changing to accommodate a job, connectivity in key brain networks of autistic children looks similar to connectivity in the resting brain. The degree of inflexibility was linked to the intensity of children’s autism symptoms: those with less flexibility had more severe restrictive and repetitive behaviors, one of the hallmarks of the developmental disorder.

From our press release on the research:

“We wanted to test the idea that a flexible brain is necessary for flexible behaviors,” said Lucina Uddin, PhD, a lead author of the study. “What we found was that across a set of brain connections known to be important for switching between different tasks, children with autism showed reduced ‘brain flexibility’ compared with typically developing peers.” Uddin, who is now an assistant professor of psychology at the University of Miami, was a postdoctoral scholar at Stanford when the research was conducted.

“The fact that we can tie this neurophysiological brain-state inflexibility to behavioral inflexibility is an important finding because it gives us clues about what kinds of processes go awry in autism,” said Vinod Menon, PhD, the Rachel L. and Walter F. Nichols, MD, professor of psychiatry and behavioral sciences at Stanford and the senior author of the study.

The study is the first to examine unusual patterns of connectivity in the brains of children with autism while they are performing tasks; Menon’s team has previously published research on connectivity between different regions of the autistic brain at rest. Some regions of the autistic brain are over-connected to each other, that work has shown, and the degree of over-connection is linked to children’s social deficits, perhaps in part because it interferes with their ability to derive pleasure from human voices. Menon’s lab has also explored how differences in the organization of the autistic brain may contribute to better math performance in some people with autism.

“We’re making progress in identifying a brain basis of autism, and we’re starting to get traction in pinpointing systems and signaling mechanisms that are not functioning properly,” Menon told me. “This is giving us a better handle both in thinking about treatment and in looking at change or plasticity in the brain.”

Previously: Greater hyperconnectivity in the autistic brain contributes to greater social deficits, Unusual brain organization found in autistic kids who best peers at math and Stanford study reveals why human voices are less rewarding for kids with autism

Medicine and Literature, Patient Care, Stanford News, Surgery

Surgery: Up close and personal

Surgery: Up close and personal

gholami - smallTens of millions of patients undergo surgery every year in the United States, yet very few have the opportunity to be on the other side and observe a surgical procedure in action.

I had that rare privilege recently in the course of writing a story for Stanford Medicine magazine about surgery and how far the field has come in recent decades. The operating room, I discovered, is a world unto itself. It’s governed by a strict set of rules to help safeguard patients, but within those strictures, there is an elaborate kind of dance and much artistry in the way clinicians work together and finesse the tools to help heal their patients.

Sepideh Gholami, MD, a six-year surgery resident at Stanford who is featured in the story, said it was in part this sense of artistry – the movement, rhythm and pacing – that attracted her to the profession. And like many surgeons, she found it gratifying to be able to use her hands to fix a problem to quickly restore a patient’s well-being. She describes one of her early experiences, assisting in a procedure to remove a life-threatening tumor from a young man’s colon.

“I remember going to the family afterward, saying that we were able to get it all out, and seeing the glow in their faces,” she told me. She said it was reminiscent of the experience of her own mother, who had a tumor extracted from her breast: “This is how it happened for my mom, who is now disease-free,” she said.

In the story, Gholami talks about her rather unusual path from an early childhood in revolutionary Iran to becoming a surgeon in the United States, as well as the changes in the profession that have opened the way  to young women like her. The story also explores the remarkable innovations in technology that have made the patient experience today far less invasive and less painful. Those innovations, as well as new workplace rules that limit trainees’ hours, have dramatically changed the way young surgeons like Gholami are being trained to become the independent, skilled practitioners of the future.

Previously: Stanford Medicine magazine opens up the world of surgery
Photo of Gholami by Max Aguilera-Hellweg

Cancer, Health Costs, In the News, Stanford News, Videos

TV spot features a more humane approach to late-stage cancer care

Is it possible to cut the costs of late-stage cancer care by 30 percent and provide a much better experience for patients?

That’s the question that recently brought an Al Jazzera America TV news crew out to the VA Palo Alto Health Care System, to interview patients enrolled in a new Stanford-designed pilot study on cancer care. You can watch their 9-minute video on this topic here.

The guiding principle behind this cancer-care program is this: Make sure that patients are fully informed about survival odds and treatment side effects well before they’re on the brink of death, when emotions overwhelm the decision-making skills of patients, their families and clinicians.

“Eighty percent of all cancer patients express a desire to die at home, yet only 10 percent do,” says Manali Patel, MD, the VA hospital oncologist running this study. “These end-of-life conversations, which typically take two hours in the beginning and require many follow-on conversations, are too hard, time-consuming and draining for a busy oncologist to do well.”

For these life-and-death discussions, patients are assigned personal care coaches who help them understand the big picture — treatment side effects, survival odds and pain-relief options. They also have access to a 24-hour symptom-management hotline and an option for in-home chemotherapy.

Architects of this new cancer care model, working with Arnold Milstein, MD, at Stanford’s Clinical Excellence Research Center, estimate that this program will lead to fewer unwanted treatments and expensive emergency room visits, saving the overall heath-care system money, while at the same time improving patient quality of life.

Previously: Communicating with terminally ill patients: A physician’s perspective, Identifying disparities in palliative care among cancer and non-cancer patients, Uncommon hero: A young oncologist fights for more humane cancer care, The money crunch: Stanford Medicine magazine’s new special report and New Stanford center to address inefficient health care

Research, Science, Stanford News

They said “Yes”: The attitude that defines Stanford Bio-X

They said "Yes": The attitude that defines Stanford Bio-X

bio-X peopleI write a lot about interdisciplinary research (it’s my job), but it was just recently that I heard the best description of what it is that makes interdisciplinary collaborations possible. It came from Carla Shatz, PhD, who directs Stanford Bio-X — an interdisciplinary institute founded in 1998 that brings together faculty from the schools of medicine, humanities & sciences and engineering. She told me:

You have to be able to walk into someone’s lab and say, “You know, I have this problem in my lab. Would you like to have a cup of coffee and talk about it?” And then that person needs to say, “Yes.”

We were talking about a recent report by the National Research Council of the National Academies. They had put together a workshop and then published a report giving advice and best practices for supporting interdisciplinary research. The report used Bio-X as a success story for the type of innovation that can come out of programs that cross disciplines.

Nowhere in the report is there a subhead reading, “Faculty have to say yes,” but a lot of the other advice is straight out of the Bio-X playbook. The institute needs to be located at the cross section of several schools or departments (check). The institute needs a building that brings people together (check). The institute needs to support students (check). The institute needs to be a financial value add rather than taxing participating departments (check).

This isn’t specifically called out in the report, but Shatz added that a good interdisciplinary institute also needs good food. She pointed out that people come from all over campus to eat at Nexus, located in the middle of the Clark Center that houses Bio-X and serves as a focus for its activities. It turns out scientists are just like the rest of us: offer good food and they will come. And then they will chat, and the next thing you know they’ll be collaborating.

I wrote a Q&A with Shatz based on our conversation. From now on, when I hear the phrase “She said yes” I’ll think of her, and her great description of the attitude that underlies collaboration.

Previously: Bio-X Kids Science Day inspires young scientists, Dinners spark neuroscience conversation, collaboration, Stanford’s Clark Center, home to Bio-X, turns 10 and Pioneers in science
Photo from Bio-X

Research, Science, Stanford News, Stem Cells

Induced pluripotent stem cell mysteries explored by Stanford researchers

Induced pluripotent stem cell mysteries explored by Stanford researchers

Induced pluripotent stem cells, also called iPS cells, made from easily accessible skin or other adult cells, are ideal for disease modeling, drug discovery and, possibly, cell therapy. That’s because they can be generated in large numbers and grown indefinitely in the laboratory. They also reflect the genetic background of the person from whom they were generated. However, some fundamental questions still remain before they’re ready for the full glare of the clinical limelight. Does it matter what type of starting cells scientists use to create the pluripotent stem cells? And what’s the best control to use when studying the effect of a particular, patient-specific mutation?

Now Stanford cardiologist Joseph Wu, MD, PhD, and his colleagues have addressed and answered these questions. Their work was published yesterday in two back-to-back papers in the Journal of the American College of Cardiology. (Each paper is also accompanied by an editorial.) As Wu explained in an e-mail to me:

If your goal is to generate healthy iPS cell derivatives for regenerative therapy, it’s important to know whether the starting material makes a difference. For example, if I’m treating Alzheimer’s disease, is there a benefit to using iPS cell-derived brain cells made from brain cells? Likewise, if I’m treating a skin disorder, is there a benefit to using iPS cell-derived skin cells made from skin cells? As cardiologists, we are asked this quite often and each time, I had to say “I don’t know.” So we decided to do a study comparing the differentiation and functional ability of iPS cell-derived cardiomyocytes generated from two different sources: skin and heart. We also wanted to devise more efficient ways for researchers to quickly and easily create their own “designer” iPS cell lines to study particular mutations.

To answer the first question, the researchers created iPS cells from two types of starter cells: human fetal skin cells and cardiac progenitor cells. Not surprisingly, only the cardiac progenitor cells expressed genes known to be expressed in heart tissue. Wu and his colleagues then exposed the newly created pluripotent stem cells to growing conditions that favor the development of heart muscle cells called cardiomyocytes. They found that, although iPS cells derived from cardiac progenitor cells were more efficient at becoming cardiomyocytes, both types of starting material produced heart muscle cells that functioned similarly after a period of growth in the laboratory. As Wu explained:

These two populations of cells are essentially no different from one another over time. It appears that they lost the memory of their starting material (this memory is stored in the form of chemical tags on the cells’ DNA in a phenomena known as epigenetic marking). This suggests that I could take my own skin cells, make iPS cells and then create specialized brain, heart, liver or kidney cells for cell therapy. This is much easier than biopsying each tissue, and could be a good way to create universal iPS cell lines for research or cell therapy.

In the second paper, Wu and his colleagues devised a way to introduce specific mutations into iPS cells before transforming them into particular tissues. The approach relies on the use of what’s known as “dominant negative” mutations that exert their disruptive effect even when the unmutated gene is still present. This is important because it’s much easier and quicker than previous similar efforts, which required a complicated, time-consuming procedure to snip out and then replace individual genes. The technique also allows researchers to generate two cell lines that are identical except for the mutation under study. That way researchers can be confident that differences between the cell lines are due only to that mutation, which is particularly important when the lines are used to test the effect of therapeutic drugs. Again, from Wu:

Investigators can make their own designer iPS cell lines to study particular mutations with genetically identical controls to use in their experiments. We won’t have to make new iPS cells from each patient, which is laborious and time consuming. Instead we can create standardized lines to study many different mutations alone and in combination. This has the potential to revolutionize the field of disease modeling and drug discovery.

The two papers describe ongoing research in the Wu lab designed to optimize iPS cells for a variety of applications. The group, including graduate student Arun Sharma, recently published research using human iPS cell-derived cardiomyocytes to investigate the effect of various antiviral drugs againse coxsackievirus, a leading cause of an infection of the middle layer of the heart wall in children and the elderly. The research is the first time that iPS cell-derived heart muscle has been used to investigate the mechanisms behind an acquired viral disease.

Previously: A new era for stem cells in cardiac medicine? A simple, effective way to generate patient-specific heart muscle cells, “Clinical trail in a dish” may make common medicines safer, say Stanford scientists and Lab-made heart cells mimic common cardiac disease in Stanford study

Events, Medicine X, Mental Health, Stanford News, Technology

Medicine X spotlights mental health, medical team of the future and the “no-smartphone” patient

Medicine X spotlights mental health, medical team of the future and the “no-smartphone” patient

Larry_ChuInnovative thinkers and thought leaders engaged in using emerging technologies to enhance health-care delivery and advance the practice of medicine will gather here in early September for Stanford Medicine X.

As Lloyd Minor, MD, dean of the School of Medicine, comments in a release today, Larry Chu, MD, associate professor of anesthesia at Stanford and executive director of the conference, “has made this the go-to event for e-patients, physicians and innovators who want to get together to map out the future of health care.” Chu also notes that the conference  “has distinguished itself through a singular commitment to inclusivity and by finding new ways to bring every voice and perspective into important conversations about health care.”

Now in its third year, Medicine X is building on this inclusive spirit by exploring a variety of new themes during its 2014 program. More from our release:

This year’s program will spotlight the relationship between physical and mental well-being with three breakout panels. Psychologist Ann Becker-Shutte, PhD, will moderate a session on how mental health affects overall health. A conversation about emerging technologies in mental health will be led by Malay Gandhi, managing director of Rock Health, a business accelerator for health-care technology startup companies. Additionally, patient advocate Sarah Kucharski will direct a discussion about depression caused by chronic disease and about coping through online communities.

“Mental health is imperative to address in the overall conversation about the future of health care,” said Chu. “We need to be thinking about the health of the whole person, not just a patient’s individual symptoms or disease.”

The three-day event will also feature panels on what the medical team of the future may look like; how patients with chronic diseases can use self-tracking tools to improve their health and support one another; ways for the pharmaceutical industry to partner with patients in the drug discovery and clinical trial process; and opportunities to connect with “no-smartphone” patients — those who don’t have the access or resources to fully engage with health-enhancing technologies.

Keynote speakers for this year’s conference, being held Sept. 5-7, include Daniel Siegel, MD, clinical professor of psychiatry at the University of California-Los Angeles; Barron Lerner, MD, PhD, professor of medicine and population health at New York University School of Medicine; and Charles Ornstein, a Pulitzer Prize-winning journalist and senior reporter at ProPublica.

For information about the program or to  register the Medicine X website. Last year’s conference sold out, and space is limited for this year’s event.

Previously: Medicine X Live! to host Hangout on design thinking for patient engagement, Quite the reach: Stanford Medicine X set record for most number of tweets at a health-care conference, Videos from Medicine X now available and “You belong here”: A recap of Stanford Medicine X
Photo of Larry Chu by StanfordMedicineX

More news about Stanford Medicine X is available in the Medicine X category.

Cancer, Dermatology, In the News, Public Safety, Research, Stanford News

A closer look at new research showing disproportionate rates of melanoma in Marin County

Last week, Cancer Prevention Institute of California/Stanford Cancer Institute researcher Christine Clarke, PhD, shared results of a new report (.pdf) showing that a county in California has higher numbers of melanoma skin cancer than the rest of the state. On this morning’s Forum Clarke joined two other guests, including Stanford dermatologist Susan Swetter, MD, director of the Pigmented Lesion and Melanoma Program at the Stanford Cancer Institute, to discuss the research and to offer skin safety and screening tips for the summer.

It’s worth a listen – especially if you live in the county just north of San Francisco.

Previously: Melanoma rates exceed rates of lung cancer in some areasWorking to protect athletes from sun dangers, As summer heats up take steps to protect your skin, Stanford study: Young men more likely to succumb to melanoma, New research shows aspirin may cut melanoma risk and Working to prevent melanoma

Medicine and Literature, Stanford News, Surgery

Stanford Medicine magazine opens up the world of surgery

Stanford Medicine magazine opens up the world of surgery

surgeon hands - 560

It used to be “big hole, big surgeon” — but no more, according to Stanford’s chair of surgery, Tom Krummel, MD, who’s one of the surgeons featured in Stanford Medicine magazine’s report on surgery and life in the operating room, “Inside job: Surgeons at work.”

During his career of more than 30 years, Krummel has seen a massive shift from open surgeries to minimally invasive procedures — major surgeries conducted with tools that work through small openings.

“We do the same big operation. We just don’t make a big hole,” he said in the article leading off the report.

In the same issue, CNN’s chief medical correspondent, neurosurgeon Sanjay Gupta, MD, talks about why he’s “doubling down” on his support for medical marijuana.

As the editor, I’m biased — but I think it’s worth a read, along with the rest of the issue, which includes:

The issue also includes a report on research on Alzheimer’s disease, and an excerpt from Surgeon General’s Warning, a new book by Associated Press medical reporter Mike Stobbe on the fall from power of the U.S. surgeon general. The digital edition offers audio interviews with Gupta, Stobbe, Stanford surgeon and humanitarian-aid volunteer Sherry Wren, MD, and photographer Max Aguilera-Hellweg, MD.

Previously: The vanishing U.S. surgeon general: A conversation with AP reporter Mike Stobbe, Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questions, From womb to world: Stanford Medicine Magazine explores new work on having a baby and Factoring in the environment: A report from Stanford Medicine magazine
Photo by Max Aguilera-Hellweg

Medical Education, Rural Health, Stanford News

Stanford internships provide Bay Area students with work experience, opportunity to discover passions

Stanford internships provide Bay Area students with work experience, opportunity to discover passions

14093-internyu_newsThis summer high school students from around the Bay Area are interning at labs and departments across Stanford. A recent Stanford Report story highlights the type of projects students are working on and how the internships provide them with valuable work experience and the opportunity to discover their passion. From the article:

Palo Alto High School student Catherine Yu [pictured to the right], for example, is interning at the Stanford Blood Center in the immunology and pathology lab. She described her task as gathering data to help her supervisor’s research project.

“Every intern is assigned to a supervisor who is working on an experiment, which will hopefully be turned into a paper submitted for a journal,” said Yu, who will be a senior in September. “My work consists of separating blood into T cells, monocytes, dendritic cells, and then culturing them together; it’s very neat.”

Yu said being the only high school student in her lab presents her with a series of challenges.

“It’s definitely a different dynamic where they expect you to learn a lot of information at a very fast pace,” Yu said. “I have to stay on my toes so I don’t fall behind.”

Previously: Internships expose local high-schoolers to STEM careers and academic life, Residential learning program offers undergrads a new approach to scientific inquiry, The “transformative experience” of working in a Stanford stem-cell lab and Stanford’s RISE program gives high-schoolers a scientific boost
Photo by L.A. Cicero

Cancer, Genetics, Research, Stanford News

Stanford partnering with Google [x] and Duke to better understand the human body

Stanford partnering with Google [x] and Duke to better understand the human body

Most biomedical research is focused on disease and specific treatments for illness, rather than on understanding what it means to be healthy. Now researchers at Stanford, in collaboration with Duke University and Google [x], are planning a comprehensive initiative to understand the molecular markers that are key to health and the changes in those biomarkers that may lead to disease. The project was featured in a Wall Street Journal article today.

The study is at the very early stages, with researchers planning to enroll 175 healthy participants in a pilot trial later this year. The participants will undergo a physical exam and provide samples of blood, saliva and other body fluids that can be examined using new molecular testing tools, such as genome sequencing.  The pilot study will help the researchers design and conduct a much larger trial in the future.

“We continue as a global community to think about health primarily only after becoming ill,” Sanjiv Sam Gambhir, MD, PhD, professor and chair of radiology, told me. “To understand health and illness effectively, we have to have a better understanding of what ‘normal’ or ‘healthy’ really means at the biochemical level.”

“The study being planned will allow us to better understand the variation of many biomarkers in the normal population and what parameters are predictive of illness and may eventually change as a given individual transitions from a healthy to a diseased state. This will be a critical study that will likely help the field of health care for decades to come,” said Gambhir, who also directs the Canary Center at Stanford for Cancer Early Detection.

The researchers hope the work will provide insights on a variety of medical conditions, such as cancer and heart disease, and point to new methods for early detection of illness. Their studies will focus on the genetic basis of disease, as well as the complex interplay between genes and environment.

These kinds of studies haven’t been done before because of the cost and complexity of molecular measurement tools, the scientists say. However, the cost of some technologies, such as DNA sequencing, has been steadily declining, while some new tools and new ways of analyzing large quantities of data have just recently become available. So a first step in the study is to determine how best to use these technologies and determine what questions need to explored on a larger scale.

The work is sponsored by Google [x] and will be led by Andrew Conrad, PhD, a cell biologist and project manager at the company.

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