He pushed back against doctors who recommended surgery on infants born with ambiguous genitalia, arguing for acceptance of diversity.Academic conferences are usually staid affairs, but the 1973 International Symposium on Gender Identity, held in Dubrovnik, Yugoslavia, was an exception. Everything was peaceful until a psychologist named John Money stood and yelled, “Mickey Diamond, I hate your guts!”Milton Diamond, a sexologist who had gone by Mickey since childhood, was sitting on the other side of the room. Dr. Money and Dr. Diamond were bitter rivals: Dr. Money, a nationally recognized researcher at Johns Hopkins University, had long argued that sexual and gender identity are neutral at birth and shaped primarily by an infant’s surroundings.Dr. Diamond, who was just beginning his career at the University of Hawaii, strongly disagreed, and had said so repeatedly — including in a widely read 1965 critique of Dr. Money’s work. He took particular issue with Dr. Money’s recommendation that intersex infants have surgery to “correct” their genitals.Dr. Money rushed over to Dr. Diamond, getting in his face, furiously insisting he was right.Dr. Diamond only replied, “The data is not there.”At one point, eyewitnesses reported that Dr. Money slugged Dr. Diamond, though Dr. Diamond later said he didn’t remember it.The incident, reported by the journalist John Colapinto in Rolling Stone magazine and in a subsequent book, “As Nature Made Him: The Boy Who Was Raised as a Girl” (2000), was especially heated because of a recent announcement by Dr. Money.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

A group of researchers at the University of California San Diego School of Medicine led an investigation that offers new insight into the causes of spina bifida, the most common structural disorder of the human nervous system.
Work of the group, led by Keng Ioi Vong, Ph.D., and Sangmoon Lee, M.D. Ph.D., both from the laboratory of Joseph G. Gleeson, M.D., at the UC San Diego School of Medicine Department of Neurosciences and the Rady Children’s Institute for Genomic Medicine, reveals the first link between spina bifida and a common chromosomal microdeletion in humans. The study demonstrates that individuals carrying this chromosomal deletion — present in one of 2,500 live births — demonstrate a risk of spina bifida more than 10 times greater than the general public.
The study also underscores the potential role of a common food supplement in reducing the risk of spina bifida. The findings were recently published in the journal Science.
Gleeson, Rady Professor in the Department of Neuroscience and director of neuroscience at Rady Children’s Institute for Genomic Medicine, is the senior author of the study. He explained that spina bifida, also known as meningomyelocele, affects one in every 3,000 newborns. Unfortunately, the causes are mostly unknown. A few mutations were reported but could only explain a tiny fraction of risk, Gleeson added.
To uncover the genetic causes of the disease, Gleeson’s UC San Diego lab joined with colleagues from across the globe to establish the Spina Bifida Sequencing Consortium in 2015. The consortium began focusing on a tiny deletion in chromosome 22. Chromosome microdeletions refer to a condition in which several genes in a chromosome are missing. The group’s target condition, known as 22q11.2del, has been implicated in a number of other disorders. They began looking for 22q11.2del in spinal bifida patients.
“All patients we recruited have the most severe form of spina bifida, and all underwent best-practice comprehensive genomic sequencing,” Gleeson said. “We identified 22q11.2del in 6 out of 715 patients. This may not seem a high percentage, but this is by far the most common single genetic variation that could contribute to spina bifida.”
He went on to say the group identified eight additional spina bifida patients who carried the deletion from a cohort of approximately 1,500 individuals recruited because of the presence of the common 22q11.2 deletion, Gleeson said.

The researchers then narrowed the cause among the many genes in the 22q11.2 deletion to a single gene known as CRKL. Gleeson explained that there are nine other genes in this chromosomal region that could have been the cause. He said the team began a process of elimination, “knocking out” each of the mouse genes one-by-one, when they received a fortuitous email from Dolores Lamb from Weil Cornell College of Medicine. Lamb had noted some of the mice in their vivarium that were missing Crkl and showed spina bifida. (Vong explained that researchers use all capital letters to describe the gene in humans, and lower-case for mice. )Lamb’s group heard about the Gleeson lab project throughs the Spina Bifida Association.
“This finding really got us excited because it meant that CRKL disruption might be sufficient for spina bifida,” said Vong, co-first author of the study. “We removed the mouse Crkl gene ourselves and confirmed that some of the mice developed neural tube defects, including spina bifida.” Most of the other genes in 22q11.2 deletion were subsequently excluded, he added.
They next turned their attention to how folic acid may modulate CRKL-mediated spina bifida. Vong noted that prior studies in humans demonstrated that folic acid (also known as vitamin B-9) supplementation prior to conception reduces the incidence of spina bifida and other neural tube defects by up to 30-50 percent, but the mechanisms are still a mystery.
“When we deprived the Crkl mutant female mice of folic acid in their chow, many more of their offspring had neural tube defects, and the severity increased dramatically,” Vong explained. “This suggests that folic acid taken by pregnant women may not only reduce the risk, but also the severity of neural tube defects in their offspring.”
“We hope our findings can help the research community to better understand causes of neural tube defects, especially the causes attributable to common genetic findings like 22q11.2 deletion,” Gleeson said. “We also hope our findings can contribute to healthy pregnancies, improved women’s health, and improved outcomes for children.”
Co-authors associated with the University of San Diego School of Medicine Department of Neurosciences, as well as with Rady Children’s Institute for Genomic Medicine, (in addition to Joseph G. Gleeson Sangmoon Lee and Keng Ioi Vong) are: Renee George, Bryn Gerding, Kiely N. James, Valentina Stanley, Nan Jiang, Kameron Alu, Naomi Meave, Fiza Jiwani, Isaac Tang, Ashna Nisal, Ishani Jhamb, Arzoo Patel, Aakash Patel, Jennifer McEvoy-Venneri, Chelsea Barrows, Celina Shen, Yoo-Jin Ha and Robyn Howarth. Other co-authors include Hal S. Meltzer, of the University of California San Diego Rady Children’s Hospital Department of Neurosurgery; Anna S. Nidhiry, of Rady Children’s Institute for Genomic Medicine; and the Spina Bifida Sequencing Consortium.
This work was supported by the Center for Inherited Disease Research grant HHSN268201700006I, the Yale Center for Genomic Analysis, the Broad Institute, the UC Irvine Genomics Core, the UCSD Institute for Genomic Medicine, the UCSD Transgenic Core, UCSD Microscopy Core grant P30 NS047101, and Columbia Microscopy Core grant S10 OD032447- 01. Other support came from the National Institutes of Health, including National Institute of Diabetes and Digestive and Kidney Diseases, and by support from the Howard Hughes Medical Institute and Rady’s Children Institute for Genomic Medicine to Joseph G. Gleeson.

A tiny, flexible electronic device that wraps around the spinal cord could represent a new approach to the treatment of spinal injuries, which can cause profound disability and paralysis.
A team of engineers, neuroscientists and surgeons from the University of Cambridge developed the devices and used them to record the nerve signals going back and forth between the brain and the spinal cord. Unlike current approaches, the Cambridge devices can record 360-degree information, giving a complete picture of spinal cord activity.
Tests in live animal and human cadaver models showed the devices could also stimulate limb movement and bypass complete spinal cord injuries where communication between the brain and spinal cord had been completely interrupted.
Most current approaches to treating spinal injuries involve both piercing the spinal cord with electrodes and placing implants in the brain, which are both high-risk surgeries. The Cambridge-developed devices could lead to treatments for spinal injuries without the need for brain surgery, which would be far safer for patients.
While such treatments are still at least several years away, the researchers say the devices could be useful in the near-term for monitoring spinal cord activity during surgery. Better understanding of the spinal cord, which is difficult to study, could lead to improved treatments for a range of conditions, including chronic pain, inflammation and hypertension. The results are reported in the journal Science Advances.
“The spinal cord is like a highway, carrying information in the form of nerve impulses to and from the brain,” said Professor George Malliaras from the Department of Engineering, who co-led the research. “Damage to the spinal cord causes that traffic to be interrupted, resulting in profound disability, including irreversible loss of sensory and motor functions.”
The ability to monitor signals going to and from the spinal cord could dramatically aid in the development of treatments for spinal injuries, and could also be useful in the nearer term for better monitoring of the spinal cord during surgery.

“Most technologies for monitoring or stimulating the spinal cord only interact with motor neurons along the back, or dorsal, part of the spinal cord,” said Dr Damiano Barone from the Department of Clinical Neurosciences, who co-led the research. “These approaches can only reach between 20 and 30 percent of the spine, so you’re getting an incomplete picture.”
By taking their inspiration from microelectronics, the researchers developed a way to gain information from the whole spine, by wrapping very thin, high-resolution implants around the spinal cord’s circumference. This is the first time that safe 360-degree recording of the spinal cord has been possible — earlier approaches for 360-degree monitoring use electrodes that pierce the spine, which can cause spinal injury.
The Cambridge-developed biocompatible devices — just a few millionths of a metre thick — are made using advanced photolithography and thin film deposition techniques, and require minimal power to function.
The devices intercept the signals travelling on the axons, or nerve fibres, of the spinal cord, allowing the signals to be recorded. The thinness of the devices means they can record the signals without causing any damage to the nerves, since they do not penetrate the spinal cord itself.
“It was a difficult process, because we haven’t made spinal implants in this way before, and it wasn’t clear that we could safely and successfully place them around the spine,” said Malliaras. “But because of recent advances in both engineering and neurosurgery, the planets have aligned and we’ve made major progress in this important area.”
The devices were implanted using an adaptation to routine surgical procedure so they could be slid under the spinal cord without damaging it. In tests using rat models, the researchers successfully used the devices to stimulate limb movement. The devices showed very low latency — that is, their reaction time was close to human reflexive movement. Further tests in human cadaver models showed that the devices can be successfully placed in humans.

The researchers say their approach could change how spinal injuries are treated in future. Current attempts to treat spinal injuries involve both brain and spinal implants, but the Cambridge researchers say the brain implants may not be necessary.
“If someone has a spinal injury, their brain is fine, but it’s the connection that’s been interrupted,” said Barone. “As a surgeon, you want to go where the problem is, so adding brain surgery on top of spinal surgery just increases the risk to the patient. We can collect all the information we need from the spinal cord in a far less invasive way, so this would be a much safer approach for treating spinal injuries.”
While a treatment for spinal injuries is still years away, in the nearer term, the devices could be useful for researchers and surgeons to learn more about this vital, but understudied, part of human anatomy in a non-invasive way. The Cambridge researchers are currently planning to use the devices to monitor nerve activity in the spinal cord during surgery.
“It’s been almost impossible to study the whole of the spinal cord directly in a human, because it’s so delicate and complex,” said Barone. “Monitoring during surgery will help us to understand the spinal cord better without damaging it, which in turn will help us develop better therapies for conditions like chronic pain, hypertension or inflammation. This approach shows enormous potential for helping patients.”
The research was supported in part by the Royal College of Surgeons, the Academy of Medical Sciences, Health Education England, the National Institute for Health Research, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI).

Researchers at the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center (MECCC) have shown that a breakthrough therapy for treating blood cancers can be adapted to treat solid tumors — an advance that could transform cancer treatment. The promising findings, reported today in Science Advances, involve CAR-T cell therapy, which supercharges the immune system to identify and attack cancer cells.
“CAR-T cell therapy has revolutionized the treatment of blood cancers such as leukemia and lymphoma but hasn’t worked well against solid tumors,” said Xingxing Zang, Ph.D., the paper’s senior author. “We found that our changes to standard CAR-T cell therapy can significantly boost its effectiveness against solid tumors, including often-fatal pancreatic cancer and glioblastomas.” Dr. Zang is a member of MECCC Cancer Therapeutics Research Program and professor of microbiology & immunology, of oncology, of medicine, and of urology, the Louis Goldstein Swan Chair in Cancer Research and the founding director of MECCC’s Institute for Immunotherapy of Cancer at Albert Einstein College of Medicine. The first author of the paper is Christopher Nishimura, an M.D./Ph.D. student in Dr. Zang’s lab.
Developing Personalized Cancer Killers
Dr. Zang and his colleagues created five CAR-T therapies that they tested on mice implanted with several types of solid human tumors. One of the therapies — which used two novel components — proved superior in safely and effectively shrinking not only glioblastoma and pancreatic tumors but lung cancer tumors as well.
CAR-T cell therapy, short for chimeric antigen receptor (CAR)-T cell therapy, is a marvel of genetic engineering that transforms T cells (a type of immune cell) into cancer-seeking missiles programmed to attack on contact. The therapy involves extracting the patient’s own T cells and equipping them with a single gene that codes for several different proteins. (“Chimeric” comes from the Chimera of Greek mythology with its lion’s head, goat’s body, and serpent’s tail.) The genetically modified T cells are allowed to multiply and are then infused back into the patient.
Their specially designed gene enables the infused T cells to express synthetic CAR receptors on their surface. The CARs can recognize specific proteins, known as antigens, that protrude from cancer cells. Thanks to their new CARs, the T cells are able to home in on cancer cells and then switch to attack mode.
CARs contain four key proteins, and Dr. Zang and his colleagues achieved success against solid tumors by altering two of them.

Five CAR-Ts Confront Three Types of Cancer
All five CAR-T therapies developed by the Zang team used the same novel targeting protein: a monoclonal antibody that binds to B7-H3, a cancer-cell antigen widely expressed on most solid tumors and their blood vessels. Dr. Zang had previously helped to discover that B7-H3 allows tumors to evade immune attack by interfering with T cells.
“We wanted our CARs to not only attach T cells to solid tumors but also — by binding specifically to B7-H3 — to prevent B7-H3 from interfering with the T cells’ ability to attack and destroy cancer cells and their blood vessels,” said Dr. Zang.
Simply attaching CAR-T cells to tumor cells isn’t enough to kill them. CARs must also include a costimulatory protein to help activate T cells once they’ve made contact with cancer cells. Four of the five CAR-T cell therapies developed by Dr. Zang’s lab used previously deployed costimulatory proteins. But their fifth therapy used a protein never before tried in CAR-T cell therapy. In 2015, Dr. Zang discovered that T cells possess a receptor he called TMIGD2 that activates T cells when stimulated. He later realized that incorporating TMIGD2 into CAR-T cells might enable them to overcome the challenges posed by solid tumors.
“Factors such as low-oxygen levels and immune checkpoints inside solid tumors make for a hostile microenvironment that can strongly suppress immune attack by T cells — which also have trouble penetrating solid tumors’ dense connective tissue network,” Dr. Zang said. “It seemed possible that using TMIGD2 as a costimulatory protein could give CAR-T cells the activation boost they need to reach cancer cells and persist within solid tumors.”
These novel CAR-T therapies were tested on mice bearing three solid human tumors: pancreatic, lung, and glioblastoma. All were equally likely to bind their T cells to cancer cells, since their CARs all possessed the same novel antibody aimed at the B7-H3 antigen. The most effective one possessed both the novel antibody and the TMIGD2 protein — a CAR that Dr. Zang calls a TMIGD2 Optimized Potent/Persistent (TOP) CAR.

The TOP Choice
The CAR-T therapy with TOP CAR proved best at keeping mice with pancreatic, lung, and glioblastoma tumors alive. For example, TOP CAR treatment enabled 7 out of 9 mice with glioblastoma tumors to survive, compared with a maximum survival of 3 out of 9 mice achieved by any of the other CAR-T therapies. It was also superior with respect to key effectiveness and safety parameters.
Dr. Zang plans to further develop TOP CAR into an “off-the shelf” platform that can simultaneously target B7-H3 as well as other tumor antigens and can readily be tailored for treating many different types of solid tumors. Einstein has intellectual property protection for a portfolio of Dr. Zang’s research and is interested in securing commercial partners to help to move his novel TOP CAR therapy into clinical trials in the near future, including for cancer of the brain, liver, pancreas, ovary, prostate, lung, bladder, colon, and others. Over the past several years, Dr. Zang has developed two other anti-cancer drugs that are being evaluated in phase 1 and phase 2 clinical trials in the United States and other countries.
The paper is titled “TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors.” Other Einstein authors are Devin Corrigan, M.S., Xiang Yu Zheng, B.S., Phillip M. Galbo Jr., Ph.D., Shan Wang, M.D., Yao Liu, Ph.D., Yau Wei, M.D., Linna Suo, M.D.,Wei Cui, Ph.D. and Deyou Zheng, Ph.D. Other authors are Nadia Mercado, Sc.M., of Brown University School of Public Health and Cheng Cheng Zhang, Ph.D., of the University of Texas Southwestern Medical Center.
Dr. Zang and Mr. Nishimura are inventors of two pending patents: Chimeric antigen receptors comprising a TMIGD2 costimulatory domain and associated methods of using the same; and Chimeric antigen receptors targeting B7-H3 (CD276) and associated methods. Dr. Zang is an inventor of a pending patent: Monoclonal antibodies against IgV domain of B7-H3 and uses thereof. Other authors declare no conflicts of interest.

The American College of Cardiology (ACC) and the American Heart Association (AHA) today released a new clinical guideline for effectively managing individuals diagnosed with hypertrophic cardiomyopathy (HCM). The guideline reiterates the importance of collaborative decision-making with patients who have HCM and provides updated recommendations for the most effective treatment pathways for adult and pediatric patients.
HCM is an inherited cardiac condition most often caused by a gene mutation that makes the heart muscle too thick (hypertrophy), which impairs its ability to adequately pump blood throughout the body. HCM affects approximately 1 in every 500 individuals; however, a significant portion of cases remain undiagnosed because many people do not exhibit symptoms. Occasionally, the first time HCM is diagnosed is after a sudden death. People who do have symptoms may experience episodes of fainting, chest pain, shortness of breath or irregular heartbeats.
“Incorporating the most recent data, this new guideline equips clinicians with the latest recommendations for the treatment of HCM,” said Steve R. Ommen, MD, FACC, medical director of the Mayo Hypertrophic Cardiomyopathy Clinic and chair of the guideline writing committee. “We’re seeing more evidence that patients with HCM can return to their normal daily lives with proper care and management.”
Updated recommendations in the guideline reflect recent evidence about HCM treatment and management including new forms of pharmacologic management; participation in vigorous recreational activities and competitive sports; and risk stratification for sudden cardiac death (SCD) with an emphasis on pediatric patients.
The guideline includes recommendations for adding cardiac myosin inhibitors, a new class of medication for patients with symptomatic obstructive HCM who do not get adequate symptom relief from first-line drug therapy. Symptomatic obstructive HCM is a type of HCM where the heart muscle is restricted. Cardiac myosin inhibitors are the first FDA-approved class of medication to specifically target the thickening of the heart muscle instead of treating the symptoms, however they are monitored under the FDA’s Risk Evaluation and Mitigation Strategies (REMS) program, which may create additional steps and time for both the clinician and the patient. Clinicians require special training to prescribe the medication, and patients require regular screenings.
“These new drugs offer an alternative for patients who have failed first-line therapy and either want to delay or possibly avoid more aggressive options,” Ommen said. “With this guideline, we’re providing clinicians with point-of-care guidance about effectively using this first-in-class, evidence-based treatment option and improving their patients’ quality of life.”
In addition to medication treatment, growing evidence is showing that the benefits of exercise outweigh the potential risks for patients with HCM. Low to moderate intensity recreational exercise should be part of how HCM patients manage their overall health. For some HCM patients, competitive sports may be considered in consultation with HCM clinical specialists.
“Recommendations for physical activity continue to evolve with research,” Ommen said. “As part of a healthy lifestyle, patients with HCM are now encouraged to engage in low-to-moderate intensity physical activities. We’re seeing how vigorous physical activities can be reasonable for some individuals. With shared decision-making between the clinician and the patient, some patients may even be able to return to competitive sports.”
Poorly managed HCM may lead to many complications including SCD. The new guideline includes recommendations for assessing and managing the risk of SCD by establishing clear risk markers. Guidance for integrating risk markers with tools to estimate an individual patient’s SCD risk score is recommended to aid in the patient/clinician shared decision-making regarding implantable cardioverter defibrillator placement, incorporating a patient’s personal level of risk tolerance and specific treatment goals including quality of life.
Several recommendations in the new guideline extend to pediatric patients. A specific pediatric risk stratification for SCD is emphasized, with risk calculators specific to children and adolescents and stressing the importance of HCM centers with expertise in pediatrics. The new guideline extends exercise stress testing recommendations to include children diagnosed with HCM to help determine functional capacity and provide prognostic feedback.

Many parents ponder why one of their children seems more emotionally troubled than the others. A new study in the United Kingdom reveals a possible basis for those differences.
Adolescents who view their households as more unstructured, disorganized, or hectic than their siblings develop more mental health and behavioral problems in early adulthood, according to the study. The findings are published in Psychological Science, a journal of the Association for Psychological Science.
In research tracking thousands of twins born in the mid-1990s, Sophie von Stumm, a psychology professor at the University of York, found that teenagers who perceived their homes as more disorganized, unstructured, or fast-paced than their siblings suffered more anxiety and depression and engaged in more substance use and problem behavior. If future research confirms those findings, she said, psychologists could develop interventions that modify adolescents’ perceptions of their home environments.
von Stumm said she’s long been curious about why people who share an experience come away with vastly different perceptions and interpretations of what happened. For her study, she used data from 4,732 same-sex twin pairs from the Twins Early Development Study (TEDS), an ongoing examination of twins born in the mid-1990s in England and Wales. She excluded data from opposite-sex twin pairs to rule out potential gender-based differences in perceptions.
At ages 9, 12, 14, and 16, the twins and their parents rated the level of routine, noise, and general confusion in the home.
“Some households are more chaotic than others: There’s always a TV or radio playing, different people come and go every day, and there are no routines, like regular bedtimes or mealtimes,” von Stumm explained.
In reviewing responses from the twins at age 16, she observed that siblings could have significantly different views about the atmosphere in their home. One sibling might view the household as far more noisy and fast-paced than the other.

“You’d think the siblings grew up in different families,” von Stumm said. “That’s how subjective their perceptions are.”
At age 23, the twins completed a questionnaire designed to measure their educational attainment, employment status, income, substance use, sexual risk-taking, conflicts with the law, mental health, and behavioral tendencies. Those who had, at age 16, reported experiencing greater household chaos than their twin siblings scored higher on depression, anxiety, antisocial behavior, and other mental health problems. The results were consistent across both identical and fraternal twin pairs.
“Siblings who perceived the household as more chaotic than their brothers or sisters reported poorer mental health outcomes in young adulthood,” von Stumm said. “This association was evident from adolescence onwards, confirming theories that the onset of mental health issues likely is during teenage years.”
von Stumm said she next plans to explore the precise age and reasons that siblings start to differ in their perceptions of household chaos.
“It is possible that children who experience more adverse events in early life than their siblings, like suffering an injury or being excluded from school, develop a heightened sensitivity to household chaos that then has long-term effects on their mental health,” she said. “Because many common adverse early-life events, such as parental conflict or separation, affect all children of a family, we don’t know yet if there are specific ones that can cause poor long-term mental health.”

New research from a multi-disciplinary team at Trinity College Dublin suggests a “tailored vaccine” might hold the key to treating bacteria-driven flares of eczema in children.
The team has taken several leaps forward in understanding how the immune response works in cases of eczema driven by the common, troublesome Staphylococcus aureus bacterium, and in doing so they have identified new cellular targets for a vaccine.
Eczema, also known as atopic dermatitis, affects up to one in four children in Ireland. Common symptoms include itchy, dry skin, and — when bacteria are involved — weeping wounds that can progress to more severe infections and have a detrimental effect on the quality of life of patients and their families. Although very rare, life-threatening systemic infections such as septicaemia may arise.
“There is a real need for new options to treat and prevent infected flares of eczema in children. Current strategies are limited in their success and — even when they do provide relief — the effects may be short-term as symptoms often return. Although antibiotics are needed in some cases, scientists are trying hard to deliver alternative options due to the growing problems posed by antimicrobial resistance,” said Dr Julianne Clowry, Consultant Dermatologist, Visiting Research Fellow at Trinity, and lead author of the study.
“In combination, these factors make a tailored vaccine a very attractive target as it could limit the severity of eczema, lead to better longer-lasting outcomes, and reduce the need for antibiotics — all while also reducing the risk of complications and potentially the development of other atopic diseases, such as hayfever and asthma.”
The researchers, from Trinity’s Schools of Medicine, Computer Science and Statistics, as well as from Biochemistry and Immunology, uncovered important “immune signatures” in children with infected flares of eczema. Pinpointing these signatures provides them with specific new targets, which is helpful from a theoretical vaccine design perspective.
Working with 93 children between 0 and 16, the researchers compared immune responses between 3 groups of patients: eczema and a confirmed S. aureus skin infection, eczema but no S. aureus skin infection, and a healthy group of volunteers.

The key discovery was that the proportions of certain immune cells known as “T cells,” as well as other biomarkers, varied considerably in the different groups. There are many different types of T cells in our bodies but they all play unique roles in our immune response, helping to regulate the way we respond to infections.
This main result highlights that the immune response was impacted in those with infected flares of eczema — with the suppression of some of the important T cells that drive an effective immune response. These findings provide an early blueprint in developing future therapies which could provide targeted effective relief from recurrent flares of eczema.
Alan Irvine, Professor of Dermatology at Trinity, said: “While an interaction between the Staphylococcus aureus bug and eczema has been known for many decades, novel scientific approaches are continuing to make key discoveries about the complex relationship between these bacteria and human responses to it. Our work outlines new discoveries about how children with eczema respond immunologically to infection with this common bacterium.”
Rachel McLoughlin, Professor in Immunology at Trinity and senior author on the study, added: “This work has identified an overall pattern of immune suppression associated with infected flares of eczema, which results in the suppression of specific T cells that are vital to help initiate an effective immune response. Further work is now required to broaden the scope of these results, by expanding to a larger number of people. This will help confirm if the patterns identified are consistent among different age groups, and in sub-groups with greater ethnic diversity.
“We believe that a more comprehensive understanding of the immune response to this bacteria S. aureus in eczema, has significant potential to revolutionise treatment approaches and make a major translational impact in the management of eczema.”

Psychiatrists and mental health professionals have a new standard for managing major depression, thanks to refreshed clinical guidelines published today by the Canadian Network for Mood and Anxiety Treatments (CANMAT).
The CANMAT guidelines are the most widely used clinical guidelines for depression in the world. The new version integrates the latest scientific evidence and advances in depression care since the previous guidelines were published in 2016. The update was led by researchers at the University of B.C. and the University of Toronto, alongside a national working group of more than 40 academic clinical experts and patient partners.
“These recommendations not only represent the evidence and broad consensus of leading experts in depression research and care, but, importantly, they also reflect the perspectives of patients with lived experience,” says co-lead author Dr. Raymond Lam, professor of psychiatry at UBC and co-director of the Mood Disorders Centre at the Djavad Mowafaghian Centre for Brain Health. “Our hope is that this update will empower clinicians with the latest recommendations that can help achieve better outcomes and improved quality of life for the millions of people affected by depression.”
More than one in 10 Canadians will experience depression at some point in their lives, making it one of the largest public health burdens in Canada. However, it is estimated that only 20 per cent of people receive adequate treatment.
The updated guidelines cover eight primary topic areas that map the patient care journey, from assessment and diagnosis through to the selection of treatments and strategies to prevent recurrence. The question-and-answer format is designed to be practical, accessible and easy for clinicians to use.
To develop the refreshed guidelines, the working group conducted a comprehensive literature review of new scientific evidence published since the previous 2016 guidelines. Drafts were revised based on review by patient partners, expert peer review and a defined expert consensus process.
The resulting recommendations are organized by lines of treatment based on the level of evidence supporting each therapy and factors such as safety, tolerability and feasibility. Guidance is provided to aid healthcare professionals in choosing the right treatment option with an emphasis on collaborative decision-making.

“Depression is a complex and highly individualized condition,” says Dr. Lam. “The guidelines highlight the importance of collaborating with patients in care decisions and providing a personalized treatment approach that carefully considers a person’s needs, preferences and treatment history.”
The guidelines underline the strong evidence base for well-established first-line treatments, including a number of medications, as well as psychological treatments such as cognitive behavioural therapy, interpersonal therapy and behavioural activation. Based on recent evidence, a number of new psychological and pharmacological treatments were added to the list of treatment options.
“Notable additions to the new guidelines are a strong emphasis on patient participation in choosing treatment, applying outcome measures throughout care, and an overview of digital mental health tools in the management of depression,” says co-lead author Dr. Sidney Kennedy, professor of psychiatry at the University of Toronto and director of the Centre for Depression and Suicide Studies at Unity Health Toronto.
The guidelines include further direction on how healthcare professionals can incorporate lifestyle interventions, such as exercise, nutrition and sleep hygiene. They also explore when neuromodulation treatments should be considered and what should be done when a patient doesn’t respond to initial treatments or develops treatment-resistant depression.
“Many well-established psychological and behavioural interventions have accumulated more support for their efficacy across different delivery formats,” says co-author Dr. Lena Quilty, associate professor of psychiatry at the University of Toronto and senior scientist at the Centre for Addiction and Mental Health. “We are especially pleased to report on evidence for new interventions that target depression as well as commonly co-occurring challenges such as anxiety or disrupted cognitive processes. We hope that these additional alternatives provide more opportunities for integrated attention to these multi-faceted issues.”
CANMAT is a network of academic and clinical experts dedicated to improving clinical care for people with mood and anxiety disorders. The new depression guidelines were published today in The Canadian Journal of Psychiatry. The researchers will be releasing updated versions of the CANMAT Pocket Guide to Depression for clinicians and the CHOICE-D Patient and Family Guide to Depression Treatment.

Children who experience chronic lack of sleep from infancy may be at increased risk of developing psychosis in early adulthood, new research shows.
Researchers at the University of Birmingham examined information on nighttime sleep duration from a large cohort study of children aged between 6 months and 7 years old. They found that children who persistently slept fewer hours, throughout this time period, were more than twice as likely to develop a psychotic disorder in early adulthood, and nearly four times as likely to have a psychotic episode.
While previous research has highlighted links between sleep problems and psychosis at specific time points, this is the first study to show that persistent lack of sleep is a strong predictor of psychosis.
Lead author, Dr Isabel Morales-Muñoz, said: “It’s entirely normal for children to suffer from sleep problems at different points in their childhood, but it’s also important to know when it might be time to seek help. Sometimes sleep can become a persistent and chronic problem, and this is where we see links with psychiatric illness in adulthood.
“The good news is that we know that it is possible to improve our sleep patterns and behaviours. While persistent lack of sleep may not be the only cause of psychosis in early adulthood, our research suggests that it is a contributing factor, and it is something that parents can address.”
The results, published in JAMA Psychiatry, were based on data taken from the Avon Longitudinal Study of Parents and Children (ALSPAC), which includes records of 12,394 children from 6 months to 7 years, and 3,889 at 24 years old.
While the association between lack of sleep in childhood and psychosis in early adulthood was robust in the study, the team have not proven a causal link and other factors associated with both childhood sleep and psychosis need to be explored.
The team looked, for example, at overall immune system health in the children to see whether impairments in the immune system could also account for some of the associations between lack of sleep and psychosis. This was tested at nine-years-old by measuring levels of inflammation in blood samples. Results showed that a weakened immune system could partially explain the links between lack of sleep and psychosis, but other unknown factors are also likely to be important.
Dr Morales- Muñoz’ research is part of the Mental Health Mission Midlands Translational Centre, led by the University of Birmingham and funded by the National Institute for Health and Care Research. Its aim is to test and validate treatments in early psychosis and depression among children and young people.
“We know that early intervention is really important in helping young people with mental illness. One of the priorities of the Midlands Mental Health Mission Translational Research Centre of Excellence is to develop and test targeted interventions that could have a real impact on young people who have an illness or who are at risk of developing one. Understanding the role that good sleep hygiene plays in positive mental health could be a really important part of this process.”

Despite the high prevalence of substance abuse and its often devastating outcomes, especially among disadvantaged populations, few Americans receive treatment for substance use disorders. However, the rise of mobile health technologies can make treatments more accessible.
Researchers at the University of Oklahoma are creating and studying health interventions delivered via smartphones to make effective, evidence-based treatments available to those who cannot or don’t want to enter traditional in-person treatment. Michael Businelle, Ph.D., co-director of the TSET Health Promotion Center, a program of OU Health Stephenson Cancer Center, recently published a paper in the Annual Review of Clinical Psychology that details the current landscape of mobile health technology for substance use disorders and suggests a roadmap for the future.
The Health Promotion Research Center (HPRC) is at the forefront of mobile health technologies worldwide, having attracted $65 million in grants and supporting nearly 100 mobile health studies. Within HPRC, Businelle leads the mHealth Shared Resource, which launched the Insight™ mHealth Platform in 2015 to create and test technology-based interventions. A multitude of health apps are available commercially, but few have undergone the research necessary to determine if they are effective. Businelle sees the promise of rigorously tested smartphone apps to fill gaps in substance abuse treatment.
“According to the Substance Abuse and Mental Health Services Administration, only 6% of people with substance use disorders receive any form of treatment,” Businelle said. “There are many reasons — we have a shortage of care providers, people may not have reliable transportation, may not be able to get away from work, or they may not be able to afford treatment. However, 90% of all U.S. adults own smartphones, and technology now allows us to create highly tailored interventions delivered at the time that people need them.”
Businelle and his team have many mobile health studies underway for substance abuse, and the Insight™ mHealth Platform is used by other research institutions across the United States. The mobile health field is large and growing, not only for substance abuse but for mental health disorders like depression and anxiety. In his publication, Businelle makes several recommendations for research going forward.
Re-randomize clinical trial participants
Thus far, most clinical trials for mobile health interventions have mirrored traditional clinical trials studying new drugs, in which participants are randomly assigned to receive a new drug or a placebo and stay in those groups for the duration of the trial. But that approach doesn’t work well for substance abuse trials, Businelle said. For example, if people don’t quit smoking on their targeted quit date, they are unlikely to quit during the trial. Unlike traditional trials, mobile health apps can be programmed to re-randomize participants, or move them to a different intervention that might work better for them, he said.

“Instead of being stuck receiving a treatment that we know isn’t likely to be effective for an individual, the app can easily re-randomize participants to different treatments,” he said. “Just because they weren’t successful with one type of intervention doesn’t mean that another one won’t work.”
Objectively verify self-reports
Most substance abuse interventions have historically relied on people to report their own relapses. Unfortunately, because of stigma, people don’t always report their usage truthfully, Businelle said. However, technology can now be used to biochemically verify self-reported substance use. In six of his smoking cessation trials, Businelle verifies whether participants have smoked by asking them to blow into a small device connected to a smartphone that detects the presence of carbon monoxide. Facial recognition software confirms the participant is the one testing.
“It is really important for the accuracy of our studies to objectively verify what people report,” he said. “We are also developing similar noninvasive technologies that can detect the use of other types of substances without collecting urine or blood samples.”
What is a successful outcome?
In mobile health substance abuse trials, success is often measured by whether a person is still using a substance at the end of the trial. But reality isn’t usually so straightforward. Businelle said people may stop and start using a substance several times during a six-month trial. Instead of emphasizing the end result, he recommends using technology to assess the effectiveness of an intervention at daily, weekly and monthly intervals. By understanding the number of days of abstinence or number of days until a relapse, for example, the intervention can be more accurately assessed and improved.
Mobile health technology has disadvantages, such as the potential lack of a therapeutic relationship that can develop between patient and therapist, and because some people may need more intensive treatments than mobile health can provide. However, mobile health is still in its infancy.
“Mobile health interventions may reduce stigma because people do not have to attend treatment in person,” Businelle said. “Because there is a severe shortage of qualified therapists, always-available behavior change apps could become a first line of treatment for substance abuse, with traditional counseling being reserved for those who do not respond to mobile health interventions.”