Culture

MADISON - Along with flying and invisibility, high on the list of every child's aspirational superpowers is the ability to see through or around walls or other visual obstacles.
That capability is now a big step closer to reality as scientists from the University of Wisconsin-Madison and the Universidad de Zaragoza in Spain, drawing on the lessons of classical optics, have shown that it is possible to image complex hidden scenes using a projected "virtual camera" to see around barriers.

The technology is described in a report today (Aug. 5, 2019) in the journal Nature. Once perfected, it could be used in a wide range of applications, from defense and disaster relief to manufacturing and medical imaging. The work has been funded largely by the military through the U.S. Defense Department's Advanced Research Projects Agency (DARPA) and by NASA, which envisions the technology as a potential way to peer inside hidden caves on the moon and Mars.

Technologies to achieve what scientists call "non-line-of-sight imaging" have been in development for years, but technical challenges have limited them to fuzzy pictures of simple scenes. Challenges that could be overcome by the new approach include imaging far more complex hidden scenes, seeing around multiple corners and taking video.

"This non-line-of sight imaging has been around for a while," says Andreas Velten, a professor of biostatistics and medical informatics in the UW School of Medicine and Public Health and the senior author of the new Nature study. "There have been a lot of different approaches to it."

The basic idea of non-line of-sight imaging, Velten says, revolves around the use of indirect, reflected light, a light echo of sorts, to capture images of a hidden scene. Photons from thousands of pulses of laser light are reflected off a wall or another surface to an obscured scene and the reflected, diffused light bounces back to sensors connected to a camera. The recaptured light particles or photons are then used to digitally reconstruct the hidden scene in three dimensions.

"We send light pulses to a surface and see the light coming back, and from that we can see what's in the hidden scene," Velten explains.

Recent work by other research groups has focused on improving the quality of scene regeneration under controlled conditions using small scenes with single objects. The work presented in the new Nature report goes beyond simple scenes and addresses the primary limitations to existing non-line-of-sight imaging technology, including varying material qualities of the walls and surfaces of the hidden objects, large variations in brightness of different hidden objects, complex inter-reflection of light between objects in a hidden scene, and the massive amounts of noisy data used to reconstruct larger scenes.

Together, those challenges have stymied practical applications of emerging non-line-of-sight imaging systems.

Velten and his colleagues, including Diego Gutierrez of the Universidad de Zaragoza, turned the problem around, looking at it through a more conventional prism by applying the same math used to interpret images taken with conventional line-of-sight imaging systems. The new method surmounts the use of a single reconstruction algorithm and describes a new class of imaging algorithms that share unique advantages.

Conventional systems, notes Gutierrez, interpret diffracted light as waves, which can be shaped into images by applying well known mathematical transformations to the light waves propagating through the imaging system.

In the case of non-line-of-sight imaging, the challenge of imaging a hidden scene, says Velten, is resolved by reformulating the non-line-of-sight imaging problem as a wave diffraction problem and then using well-known mathematical transforms from other imaging systems to interpret the waves and reconstruct an image of a hidden scene. By doing this, the new method turns any diffuse wall into a virtual camera.

"What we did was express the problem using waves," says Velten, who also holds faculty appointments in UW-Madison's Department of Electrical and Computer Engineering and the Department of Biostatistics and Medical Informatics, and is affiliated with the Morgridge Institute for Research and the UW-Madison Laboratory for Optical and Computational Instrumentation. "The systems have the same underlying math, but we found that our reconstruction is surprisingly robust, even using really bad data. You can do it with fewer photons."

Using the new approach, Velten's team showed that hidden scenes can be imaged despite the challenges of scene complexity, differences in reflector materials, scattered ambient light and varying depths of field for the objects that make up a scene.

The ability to essentially project a camera from one surface to another suggests that the technology can be developed to a point where it is possible to see around multiple corners: "This should allow us to image around an arbitrary number of corners," says Velten. "To do so, light has to undergo multiple reflections and the problem is how do you separate the light coming from different surfaces? This 'virtual camera' can do that. That's the reason for the complex scene: there are multiple bounces going on and the complexity of the scene we image is greater than what's been done before."

According to Velten, the technique can be applied to create virtual projected versions of any imaging system, even video cameras that capture the propagation of light through the hidden scene. Velten's team, in fact, used the technique to create a video of light transport in the hidden scene, enabling visualization of light bouncing up to four or five times, which, according to the Wisconsin scientist, can be the basis for cameras to see around more than one corner.

The technology could be further and more dramatically improved if arrays of sensors can be devised to capture the light reflected from a hidden scene. The experiments described in the new Nature paper depended on just a single detector.

In medicine, the technology holds promise for things like robotic surgery. Now, the surgeon's field of view is restricted when doing sensitive procedures on the eye, for example, and the technique developed by Velten's team could provide a more complete picture of what's going on around a procedure.

In addition to helping resolve many of the technical challenges of non-line-of-sight imaging, the technology, Velten notes, can be made to be both inexpensive and compact, meaning real-world applications are just a matter of time.

Bottom Line: Incorporation of pan-cancer microsatellite instability (MSI) detection into the 74-gene panel Guardant360 liquid biopsy assay showed high concordance with matched tissue samples in nearly 1,000 patients.

Journal in Which the Study was Published: Clinical Cancer Research, a journal of the American Association for Cancer Research

Authors: Martina Lefterova, MD, PhD, laboratory director and medical director at Guardant Health in Redwood City, California; and Scott Kopetz, MD, PhD, associate professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center

Background: "Following the tissue-agnostic approval of pembrolizumab for patients with MSI-high tumors, a barrier to improved outcomes for many patients is the awareness and testing of MSI status," said Kopetz.

Evaluation of MSI status, which is typically performed via tumor biopsy, is underutilized for several reasons, noted Kopetz. Reasons include the inherent invasive nature of traditional biopsies, which may not be feasible in some patients; a lack of viable tissue, which may be required for other analyses; and a lack of routine testing, as MSI-high tumors are relatively rare, he noted. "The addition of MSI detection into a routine, noninvasive sequencing panel following the diagnosis of metastatic cancer could direct clinicians to prescribe immunotherapy and provide patients with better outcomes," Kopetz said.

How the Study Was Conducted and Results: To develop a pan-cancer MSI detection panel, the researchers identified 90 relevant microsatellite loci to include in the Guardant360 panel. The assay was validated by comparing the MSI status as determined via the liquid biopsy test with the MSI status previously determined via standard-of-care tissue testing on 1,145 patients spanning 40 distinct cancer types.

In 949 evaluable patients, the liquid biopsy test identified 87 percent of patients previously reported as MSI-high and 99.5 percent of patients previously reported as MSI-low or microsatellite-stable, representing an overall accuracy of 98.4 percent.

The researchers also evaluated MSI status using the liquid biopsy test in 28,459 consecutive samples from patients with advanced cancer. Among this cohort, 278 samples representing 16 unique tumor types were identified as MSI-high; MSI prevalence was high in endometrial, colorectal, and gastric cancers, while MSI prevalence was low in lung, bladder, and head and neck cancers, which is consistent with previous reports using tissue samples, noted Lefterova.

Additionally, the researchers evaluated the clinical outcomes of 16 patients with metastatic gastric cancer that had previously progressed following standard-of-care chemotherapy; these patients had MSI-high tumors detected using the liquid biopsy test and were treated with either pembrolizumab (15 patients) or nivolumab (one patient). Among these patients, the objective response rate and disease control rate were 63 percent and 81 percent, respectively, which are comparable to the responses for patients identified as MSI-high through tissue testing, explained Kopetz.

Authors' Comments: "The results from our study show that Guardant360, a liquid biopsy test, can deliver valid MSI-high results that can be used to guide treatment planning for patients with advanced cancer," said Lefterova. "The addition of MSI detection increases the utility of the assay to direct clinicians beyond targeted therapies to include immunotherapies," she said.

"By adding MSI testing into a non-invasive screening panel, clinicians can routinely scan for this prognostic factor without ordering a separate test," added Kopetz.

"Our results show that MSI detection in blood samples is not only possible, but valid and informative for immunotherapy selection in patients with a wide range of advanced solid tumors," said Lefterova.

Study Limitations: As a limitation to the study, of the more than 28,000 plasma samples evaluated for MSI status, only a subset of them were matched to tissue samples, noted Kopetz. Another limitation of the study is that only one liquid biopsy test was studied, and the results cannot be applied more broadly to other tests, noted Lefterova.

Funding & Disclosures: This study was sponsored by Guardant Health. Lefterova is a current employee of Guardant Health. Kopetz declares no conflict of interest.

PITTSBURGH, Aug. 5, 2019 - Scientists at Magee-Womens Research Institute (MWRI), collaborating with clinicians at UPMC Magee-Womens Hospital and UPMC Children's Hospital of Pittsburgh report two cases in which young transgender women attempted to recover their fertility after starting and stopping gender-affirming medications.

The study, published today in Pediatrics, found that one transgender woman was able to produce viable sperm after a few months of discontinuing her puberty-halting medication, whereas a different patient on hormone therapy could not produce sperm during the time she could psychologically tolerate being off her medication.

"We were interested in examining the timeline for getting viable sperm after stopping masculinity-suppressing medication," said lead author Hanna Valli-Pulaski, Ph.D., a research assistant professor at MWRI. "Going on and off gender-affirming medications can cause psychological distress in this population and it's important patients have a discussion with their health care provider before starting or stopping any treatment."

The research team examined medical records of two transgender women who tried to preserve their sperm after stopping hormone therapy and compared their semen quality against eight other transgender women who elected to preserve their sperm before beginning therapy. All of the study participants came through the Fertility Preservation Program in Pittsburgh between 2015 and 2018 as young adults.

One of the patients who elected to preserve their sperm after beginning therapy had been taking the drug Lupron--a sex hormone blocker that halts puberty when taken in adolescence--for six months. She elected to stop taking Lupron to attempt sperm cryopreservation.

Five months later, she was able to produce a sperm sample comparable to those collected from the eight transgender women who saved their sperm prior to undergoing treatment.

Although this one case shows that it's possible to recover sperm after starting gender-affirming therapy, stopping medication for even just a few months can be psychologically distressing, Valli-Pulaski said. For male-to-female transgender individuals, facial hair can start to sprout and the voice begin to deepen after just a few months of stopping medication. It's possible to reverse these effects, but it would take time.

What's more, a second case included in this study showed that fertility doesn't always return quickly after going off gender-affirming drugs.

This patient had been taking estradiol and spironolactone for more than two years. Four months after stopping treatment, she was still unable to produce viable sperm, and at that point, she decided to stop trying for fertility preservation and proceeded with gender reassignment surgery.

The sperm production results of the two study participants provide valuable information that clinicians can share with future patients wishing to have biological children after beginning gender-affirming therapy, notes Valli-Pilaski.

"Right now, there's not much information available about fertility preservation for transgender patients," Valli-Pulaski said. "If you have any data, it's important to share so that patients, researchers and clinicians can learn from it."

A genetic mutation that slowed down the development of the prefrontal cortex (PFC) in two or more children may have triggered a cascade of events leading to acquisition of recursive language and modern imagination 70,000 years ago.

This new hypothesis, called Romulus and Remus and coined by Dr. Vyshedskiy, a neuroscientist from Boston University, might be able to solve the long-standing mystery of language evolution. It is published in the open-science journal Research Ideas and Outcomes (RIO).

Numerous archeological and genetic evidence have already convinced most paleoanthropologists that the speech apparatus has reached essentially modern configurations before the human line split from the Neanderthal line 600,000 years ago. Considering that the chimpanzee communication system already has 20 to 100 different vocalizations, it is likely that the modern-like remodeling of the vocal apparatus extended our ancestors' range of vocalizations by orders of magnitude. In other words, by 600,000 years ago, the number of distinct verbalizations used for communication must have been on par with the number of words in modern languages.

On the other hand, artifacts signifying modern imagination, such as composite figurative arts, elaborate burials, bone needles with an eye, and construction of dwellings arose not earlier than 70,000 years ago. The half million-year-gap between the acquisition of the modern speech apparatus and modern imagination has baffled scientists for decades.

While studying acquisition of imagination in children, Dr. Vyshedskiy and his colleagues discovered a temporal limit for the development of a particular component of imagination. It became apparent that modern children who have not been exposed to full language in early childhood never acquire the type of active constructive imagination essential for juxtaposition of mental objects, known as Prefrontal Synthesis (PFS).

Dr. Vyshedskiy explains:

"To understand the importance of PFS, consider these two sentences: "A dog bit my friend" and "My friend bit a dog." It is impossible to distinguish the difference in meaning using words or grammar alone, since both words and grammatical structure are identical in these two sentences. Understanding the difference in meaning and appreciating the misfortune of the 1st sentence and the humor of the 2nd sentence depends on the listener's ability to juxtapose the two mental objects: the friend and the dog. Only after the PFC forms the two different images in front of the mind's eye, are we able to understand the difference between the two sentences. Similarly, nested explanations, such as "a snake on the boulder to the left of the tall tree that is behind the hill," force listeners to use PFS to combine objects (a snake, the boulder, the tree, and the hill) into a novel scene. Flexible object combination and nesting (otherwise known as recursion) are characteristic features of all human languages. For this reason, linguists refer to modern languages as recursive languages."

Unlike vocabulary and grammar acquisition, which can be learned throughout one's lifetime, there is a strong critical period for the development of PFS and individuals not exposed to conversations with recursive language in early childhood can never acquire PFS as adults. Their language is always lacking understanding of spatial prepositions and recursion that depend on the PFS ability. In a similar manner, pre-modern humans would not have been able to learn recursive language as adults and, therefore, would not be able to teach recursive language to their own children, who, as a result, would not acquire PFS. Thus, the existence of a strong critical period for PFS acquisition creates a cultural evolutionary barrier for acquisition of recursive language.

The second predicted evolutionary barrier was a faster PFC maturation rate and, consequently, a shorter critical period. In modern children the critical period for PFS acquisition closes around the age of five. If the critical period in pre-modern children was over by the age of two, they would have no chance of acquiring PFS. A longer critical period was imperative to provide enough time to train PFS via recursive conversations.

An evolutionary mathematical model, developed by Dr. Vyshedskiy, predicts that humans had to jump both evolutionary barriers within several generations since the "PFC delay" mutation that is found in all modern humans, but not in Neanderthals, is deleterious and is expected to be lost in a population without an associated acquisition of PFS and recursive language. Thus, the model suggests that the "PFC delay" mutation triggered simultaneous synergistic acquisition of PFS and recursive language.

This model calls for:

two or more children with extended critical period due to "PFC delay" mutation;

these children spending a lot of time talking to each other;

inventing the recursive elements of language, such as spatial prepositions;

acquiring recursive-conversations-dependent PFS;

teaching recursive language to their offsprings.

The hypothesis is named after the celebrated twin founders of Rome, Romulus and Remus. Similar to legendary Romulus and Remus, whose caregiver was a wolf, the real children's caregivers had an animal-like communication system with many words, but no recursion. Their parents could not have taught them spatial prepositions or recursion; children had to invent recursive elements of language themselves. Such an invention of a new recursive language has been observed in contemporary children, for example among deaf children in Nicaragua.

"The acquisition of PFS and recursive language 70,000 years ago resulted in what was in essence a behaviorally new species: the first behaviorally modern Homo sapiens," concludes Dr. Vyshedskiy. "This newly acquired power for fast juxtaposition of mental objects in the process of PFS dramatically facilitated mental prototyping and led to fast acceleration of technological progress. Armed with the unprecedented ability to mentally simulate any plan and equally unprecedented ability to communicate it to their companions, humans were poised to quickly become the dominant species."

Humans acquired an ability to trap large animals and therefore gained a major nutritional advantage. As the population grew exponentially, humans diffused out of Africa and quickly settled in the most habitable areas of the planet, arriving in Australia around 50,000 years ago. These humans were very much like modern humans since they possessed both components of full language: the culturally transmitted recursive language along with the innate predisposition towards PFS, enabled by the "PFC delay" mutation.

Adults are really good at paying attention only to what you tell them to - but children don't ignore anything.

That difference can actually help children do better than adults in some learning situations, a new study suggests.

Researchers surprised adults and 4- and 5-year-old children participating in the study by making information that was irrelevant at the beginning of the experiment suddenly important for a task they had to complete.

"Adults had a hard time readjusting because they didn't learn the information they thought wouldn't be important," said Vladimir Sloutsky, co-author of the study and professor of psychology at The Ohio State University.

"Children, on the other hand, recovered quickly to the new circumstances because they weren't ignoring anything. I'm sure a lot of parents will recognize that tendency of children to notice everything, even when you wish they wouldn't."

Sloutsky conducted the study with Nathaniel Blanco, a postdoctoral researcher in psychology at Ohio State. Their research was published online in the journal Developmental Psychology and will appear in a future print edition.

The results show that children tend to distribute their attention broadly, while adults use selective attention to focus on information they believe is most important, Sloutsky said.

"Distributing attention may be adaptive for young children. By being attentive to everything, they gather more information which helps them learn more," Blanco said.

In one study, the researchers had 34 adults and 36 4-year-old children take part in a learning task.

They were presented with colorful images of "alien" creatures on a computer that had seven identifiable features, including antennae, head and tail.

Participants were told there were two types of creatures, called Flurps and Jalets, and that they had to figure out which ones were which.

One feature was always different on Flurps and Jalets - for example, the Jalets may have a blue tail and the Flurps an orange tail. In addition, the children and adults were told that most (but not all) of the Flurps had a certain type of feature, such as pink antennae.

One of the features was never mentioned in the instructions and it did not differ between the types of creatures. This was what the researchers called the "irrelevant feature."

After training, participants were shown a series of images of the creatures on the computer screen and indicated whether each one was a Flurp or a Jalet.

But halfway through the experiment, the researchers made an unannounced switch: The irrelevant feature became the feature that would determine whether the creature was a Flurp or a Jalet. This feature, which had been the same for both creatures before the switch, was now different.

After the shift, the adults were more confused than the children were - they were less likely to learn the importance of the new feature.

In contrast, children were quick to realize that the formerly irrelevant feature was now the feature that would always reveal the difference between Flurps and Jalets.

Adults tried to use the probabilistic rules (such as "most of the Flurps have pink antennae") to guide their choices after the shift.

In this study, adults suffered from "learned inattention," Blanco said. They didn't pay attention to the formerly irrelevant feature because they believed it wouldn't be important.

Children as young as those in this study often have difficulty focusing attention in the way that the adults did, Sloutsky said.

"The immediate reason is the immaturity of their pre-frontal cortex," he said. "But we believe that distributing attention broadly also helps them learn more."

Sloutsky emphasized that adults have no problem distributing attention broadly if necessary. But in many tasks that adults do every day, selective attention is helpful.

"It is clear that for optimal performance at most jobs, selective attention is necessary. But distributed attention might be useful when you're learning something new and need to see everything that is going on."

A new analysis of data on more than 900 Baltimore adults by Johns Hopkins Medicine researchers has linked stressful life experiences among middle-aged women -- but not men -- to greater memory decline in later life.

The researchers say their findings add to evidence that stress hormones play an uneven gender role in brain health, and align with well-documented higher rates of Alzheimer's disease in women than men.

Although the researchers caution their study was designed to show associations among phenomena, and not determine cause and effect, they say that if future studies demonstrate that stress response does factor into the cause of dementia, then strategies designed to combat or moderate the body's chemical reactions to stress may prevent or delay onset of cognitive decline.

The findings are published in the July issue of the International Journal of Geriatric Psychiatry.

According to the Alzheimer's Association, 1 in 6 women over age 60 will get Alzheimer's disease, compared with 1 in 11 men. There currently are no proven treatments that prevent or halt progression of the disease.

"We can't get rid of stressors, but we might adjust the way we respond to stress, and have a real effect on brain function as we age," says Cynthia Munro, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "And although our study did not show the same association for men, it sheds further light on the effects of stress response on the brain with potential application to both men and women," she adds.

Munro says prior research by other investigators shows that the effect of age on the stress response is three times greater in women than in men. Separately, other research has shown that stressful life experiences can result in temporary memory and cognitive problems.

To further explore whether stressful life experiences can be linked to developing long-term memory problems in women especially, Munro and her team used data collected on 909 Baltimore residents for the National Institute of Mental Health Epidemiologic Catchment Area study. That study recruited participants from 1981 to 1983 from five cities in the U.S. to determine the prevalence of psychiatric disorders.

Some 63% of the participants were women and 60% were white. Participants were an average age of 47 during their mid-life check-in in the 90s.

After enrollment, participants returned to trial sites for interviews and checkups three additional times: once in 1982, once between 1993 and 1996, and once between 2003 and 2004.

During the third visit, participants were asked if they experienced a traumatic event in the past year such as combat, rape, a mugging, some other physical attack, watching someone else attacked or killed, receiving a threat, or living through a natural disaster. Some 22% of men and 23% of women reported at least one traumatic event within the past year before their visit.

They also were asked about stressful life experiences such as a marriage, divorce, death of a loved one, job loss, severe injury or sickness, a child moving out, retirement, or birth of a child. About 47% of men and 50% of women reported having at least one stressful life experience in the year before their visit.

At the third and fourth visits, the researchers tested the participants using a standardized learning and memory test developed by Iowa researchers. The test included having participants recall 20 words spoken aloud by the testers immediately after they heard them, and again 20 minutes later.

At the third visit, participants could recall on average eight words immediately and six words later. Participants also had to identify the words spoken to them among a written list of 40 words. During the third visit, participants correctly identified on average 15 words. By the fourth visit, participants recalled an average of seven words immediately, six words after a delay, and correctly recognized almost 14 words.

The researchers measured any decreases in performance on the tests between the third and fourth visits, and then compared those decreases with participants' reports of stressful life experiences or traumatic events to see if there was an association.

Munro's team found that having a greater number of stressful life experiences over the last year in midlife in women was linked to a greater decline in recalling words later and recognizing those words. Women who experienced no stressful life experiences within the past year at the third visit were able to remember on average 0.5 fewer words when given the same memory test at the fourth visit. Women with one or more stressful life experiences, however, recalled on average one fewer word at the fourth visit than they had at the third visit. The ability to recognize words declined by an average of 1.7 words for women with at least one stressor at the third visit compared with a 1.2-word decline for women without stressors at midlife.

They didn't see the same trend in women who had traumatic events. Munro says that this finding suggests that ongoing stress, such as that experienced during a divorce, may have more of a negative impact on brain functioning than distinct traumatic events. This makes sense, Munro believes, because what we call "chronic stress" can impair the body's ability to respond to stress in a healthy manner.

The researchers did not see an association in men between a drop in word recall or recognition and experiencing either stressful life experiences or traumatic events in midlife.

Stress much earlier in life also wasn't predictive of cognitive decline later in either men or women.

"A normal stress response causes a temporary increase in stress hormones like cortisol, and when it's over, levels return to baseline and you recover. But with repeated stress, or with enhanced sensitivity to stress, your body mounts an increased and sustained hormone response that takes longer to recover," says Munro. "We know if stress hormone levels increase and remain high, this isn't good for the brain's hippocampus -- the seat of memory."

The researchers say that stress reduction hasn't gotten a whole lot of attention compared with other factors that may contribute to dementia or Alzheimer's, and that it might be worth exploring stress management techniques as a way to delay or prevent disease.

Munro adds that there are medications being developed to combat how our brains handle stress, and that these may be used in conjunction with other behavioral stress coping techniques to reduce the impact of stress on aging minds.

Alzheimer's Disease International reports that 44 million people worldwide live with Alzheimer's disease.

Expectant parents' emotional struggles predict emotional and behavioural problems in 2-year-olds, new research shows. The same study reveals, for the first time, that couple conflict helps explain emotional problems in very young children.

The team of researchers - from the Universities of Cambridge, Birmingham, New York and Leiden - say their findings highlight a pressing need for greater support for couples before, during and after pregnancy to improve outcomes for children. The study is the first to examine the influence of both mothers' and fathers' wellbeing before and after birth on children's adjustment at 14 and 24 months of age.

Lead author, Professor Claire Hughes from Cambridge's Centre for Family Research, said: "For too long, the experiences of first-time dads has either been side-lined or treated in isolation from that of mums. This needs to change because difficulties in children's early relationships with both mothers and fathers can have long-term effects.

"We have already shared our findings with the NCT (National Childbirth Trust) and we encourage the NHS and other organisations to reconsider the support they offer."

The study, published today in Development & Psychopathology, drew on the experiences of 438 first-time expectant mothers and fathers who were followed up at 4, 14 and 24 months after birth. These parents were recruited in the East of England, New York State and the Netherlands.

The researchers found that the prenatal wellbeing of first-time mothers had a direct impact on the behaviour of their children by the time they were two years old. Mothers who suffered from stress and anxiety in the prenatal period were more likely to see their child display behavioural problems such as temper tantrums, restlessness and spitefulness.

The researchers also found that two-year-olds were more likely to exhibit emotional problems - including being worried, unhappy and tearful; scaring easily; or being clingy in new situations - if their parents had been having early postnatal relationship problems. These ranged from a general lack of happiness in the relationship to rows and other kinds of conflict.

Hughes says: "Our findings highlight the need for earlier and more effective support for couples to prepare them better for the transition to parenthood."

Links between child outcomes and parental wellbeing have been shown in other studies, but this is the first to involve couples, track parental wellbeing in both parents over an extended period of time, and focus on child behaviour in the first two years of life. While there is growing evidence for the importance of mental health support for expectant and new mothers, this study highlights the need to extend this support to expectant fathers and to go beyond individual well-being to consider the quality of new mothers' and fathers' couple relationships.

The researchers acknowledge that genetic factors are likely to play a role but they accounted for parents' mental health difficulties prior to their first pregnancy and after their child's birth. Co-author Dr Rory Devine, a developmental psychologist at the University of Birmingham, says "Our data demonstrate that mental health problems during pregnancy have a unique impact on children's behaviour problems."

Using standardized questionnaires and in-person interviews, participating mothers and fathers reported on their symptoms of anxiety and depression in the third trimester of pregnancy and when their child was 4, 14 and 24 months old. At each of these visits, parents also completed standardized questionnaire measures of couple relationship quality and children's emotions and behaviour.

Hughes says: "There has been an assumption that it's really difficult to get dads involved in research like this. But our study draws on a relatively large sample and is unique because both parents answered the same questions at every stage, which enabled us to make direct comparisons."

The research is part of an ongoing project examining the wellbeing and influence of new mothers and fathers. In a closely linked study, published in Archives of Women's Mental Health in July 2019, the team found that fathers share in traumatic memories of birth with their partners far more than has previously been recognised. This study compared the wellbeing of parents in the third trimester of pregnancy with that when their child was four months old.

Co-author, Dr Sarah Foley, also from Cambridge's Centre for Family Research said: "If mum has a difficult birth, that can be a potentially traumatic experience for dads".

"What both studies show is that we need to make antenatal support much more inclusive and give first-time mums and dads the tools they need to communicate with each other and better prepare them for this major transition. With resources stretched, parents are missing out on the support they need."

Getting patients to wear an obesity simulation suit, popularly known as a 'fat suit', may prove a useful teaching aid and help to uncover medical student prejudice against obesity, suggests a proof of concept study published in the online journal BMJ Open.

Destigmatising obesity is important for the future healthcare of obese or overweight patients, who may have a range of health issues linked to their weight, and whose numbers have been rising steadily, say the researchers.

Stigma around obesity not only makes it harder for people who are obese to seek help for health issues, but also means health professionals may blame them for putting on too much weight and treat them less respectfully than other patients.

The researchers wanted to find out if an 'obesity simulation suit' worn by a patient might provide a realistic way of teaching tomorrow's doctors about obesity and help to uncover their associated prejudices.

They set up a role play in groups of 10 of a routine encounter between a 'family doctor' and a 'patient with diabetes' wearing an obesity simulation suit designed to simulate the appearance of grade 2 obesity (30-39 kg/m2).

In all, 207 second year medical students from one medical school in Germany, 13 patients involved in the university's communication course, and 22 teachers took part in the study.

Participants were asked to fill in one of three different questionnaires variously assessing how realistic the role play had been, whether the 'suit' was an effective teaching aid, and how difficult it was to wear. Attitudes to obesity were assessed, using the weight control/blame section of the validated Anti-Fat Attitudes Test (AFAT).

AFAT scores responses on a five point scale, where 1 equals strong disagreement and 5 equals strong agreement to statements such as: 'if fat people really wanted to lose weight, they could'; 'fat people have no will power'; and 'most fat people are lazy.'

The students were also asked about the degree to which they felt they could engage in empathic conversation with the patient.

The responses showed that all participants felt the suit was realistic, with nearly two thirds of students (65%) and more than four out of 10 teachers (43.5%) saying that it made the role play more convincing, with some students reporting that it prompted obesity stereotyping.

And both students and teachers correctly assessed the level of obesity.

Teachers rated the suit's value as a teaching aid quite highly, with around three out of four (74%) respondents saying they felt it facilitated empathy in the role play. The students also tended to agree that it helped them empathise with the patient.

But more than half the patients (54%) mentioned that the suit was very hot to wear and around one in four (23%) said it was cumbersome to put on and take off.

The AFAT responses showed that students harboured more negative attitudes towards obesity than either the teachers or the patients.

Students were more likely to agree more strongly with the statements 'fat people could lose weight if they really wanted to,' 'most fat people are lazy', and 'there is no excuse for being fat'.

The researchers acknowledge that they only used female patients for the study so were unable to take account of any gender specific factors, nor were they able to assess the extent to which the exercise may have reduced any bias towards obese people.

But they conclude: "Despite these limitations, we strongly believe that integrating an obesity simulation suit into the routine undergraduate medical teaching context is a valuable tool. It can raise medical students' awareness for communication encounters with patients with obesity."

Roadside verges provide a vital refuge for pollinators - but they must be managed better, new research shows.

With many pollinator species in decline, the University of Exeter study shows verges can provide food and a home for pollinators such as bees, butterflies and hoverflies.

But the study emphasises that not all verges are equal. It found pollinators prefer less busy roads and areas deeper into verges.

It also found that cutting verges in summer, which removes wildflowers, makes them useless for pollinators for weeks or even months.

"Road verges can provide a fantastic home for wildflowers and pollinators, which is often lacking in our vast agricultural landscapes," said lead author Ben Phillips, of the Environment and Sustainability Institute on Exeter's Penryn Campus in Cornwall.

"But management is key - some road verges need to be cut for safety, but at the moment we cut far more than we need to.

"Most verges are cut in summer - the peak of flowering - but where possible they should be left until autumn, when pollinators are less active.

"Our results show that the part of the verge within two metres of the road contains the fewest pollinators.

"This is often the most important part to cut for road safety and visibility, so where possible only this part should be cut in summer."

A campaign by conservation charity Plantlife to save wildlife on road verges includes a petition signed by more than 70,000 people.

Plantlife's key message, strongly supported by the new study, is to "cut less, cut later".

With 97% of wildflower meadows lost since the 1930s, the new study emphasises the vital role that road verges could play in conserving pollinators and other wildlife.

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information.

1. Electric fans not safe for relieving the heat when temperatures are high and humidity is low

Abstract: http://annals.org/aim/article/doi/10.7326/M19-0512

URLs go live when the embargo lifts

In hot, arid conditions with a relatively low heat index, electric fans may be detrimental to health and are not advisable. However, in hot, but very humid weather conditions with a much higher heat index, fans lowered core temperature and cardiovascular strain and improved comfort. Findings from a brief research report are published in Annals of Internal Medicine.

Researchers from the University of Sydney recruited volunteers on campus to examine the effect of electric fan use on thermal strain (rectal temperature), cardiovascular strain (heart rate and blood pressure), risk for dehydration (whole-body sweat rate), and thermal comfort (assessed using 120-mm visual analogue scale). Volunteers were monitored during a 2-hour exposure to simulated peak conditions of two types of heat waves: One that was very hot and dry (mimicking the peak conditions of the California heatwave in July 2018, and the Ahmedabad heatwave in May 2018) and one that was cooler but more humid and with a higher heat index (representing the peak conditions reported during the Chicago heatwave in July 1995, and the Shanghai heatwave in July 2017). The researchers found that in a hot, humid condition with a heat index of 56 °C, fans lowered core temperature and cardiovascular strain, and improved thermal comfort. However, fans were detrimental for all measures in the very hot, dry condition, despite a lower heat index of 46 °C.

According to the researchers, these findings highlight the issues that may arise when heat index values are used to recommend fan use during heat waves - as presently done by the US Environmental Protection Agency (EPA). The effectiveness of fans depends on the climate, but climate dependency is not adequately captured by heat index values. Fans may be a cheaper and more accessible alternative to air conditioning for some people, such as those living in parts of the United States that have higher humidity, or Southeast Asia, South America, and Europe, where temperatures rarely exceed 40 °C but are also accompanied by moderately high humidity.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the senior author, Ollie Jay, PhD, please contact Michelle Blowers at michelle.blowes@sydney.edu.au.

2. Adults with cerebral palsy at increased risk for mental health disorders

Abstract: http://annals.org/aim/article/doi/10.7326/M18-3420

Editorial: http://annals.org/aim/article/doi/10.7326/M19-1951

Patient Summary: http://annals.org/aim/article/doi/10.7326/P19-0010

URLs go live when the embargo lifts

Compared with adults without cerebral palsy (CP), adults with CP have an elevated prevalence of mental health disorders, some of which may be more pronounced in patients with comorbid neurodevelopmental disorders, such as intellectual disabilities, autism spectrum disorders, or epilepsy. Findings from a cross-sectional analysis are published in Annals of Internal Medicine.

Persons with CP have an increased risk for secondary chronic conditions during childhood, including mental health disorders. However, little is known about how these disorders affect adults with CP.

Researchers from the University of Michigan studied a patient database to determine the prevalence of mental health disorders among adults with CP compared with those without CP. They found that men and women with CP alone had higher age-standardized prevalence than men and women without CP for schizophrenic disorders, mood affective disorders, anxiety disorders, and disorders of adult personality and behavior. Men with CP also had higher rates of alcohol- and/or opioid-related disorders, whereas women with CP did not. According to the researchers, these findings suggest that increasing clinical awareness of the mental health disorders and risks among adults with CP, improving clinical screening strategies, and developing efficient referral resources for mental health care services may help reduce the burden of mental health disorders in this population.

According to the authors of an accompanying editorial from Oregon State University, this research is important because it shines a light on an important issue facing a vulnerable population. The editorialists suggest that physicians may require additional training to care for adults with developmental disabilities so that these patients can get the care they need. It is also important to recognize the stressors faced by this population that can contribute to their mental health, such as trauma from abuse, neglect, intrusive therapeutic procedures, poverty, and social isolation.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Daniel G. Whitney, PhD, please contact Kylie Uban at kylieo@med.umich.edu. To reach the editorialist, Gloria Krahn, PhD, PMH, please contact her directly at Gloria.Krahn@oregonstate.edu or 503-423-7186 (cell).

3. Focused cardiac ultrasonography limited by low specificity

Abstract: http://annals.org/aim/article/doi/10.7326/M19-1337

Editorial: http://annals.org/aim/article/doi/10.7326/M19-1918

URLs go live when the embargo lifts

Focused cardiac ultrasonography (FoCUS) may be more useful for ruling out significant cardiovascular pathology in patients at low suspicion of disease, than for confirming cardiovascular disease strongly suspected on clinical examination. Clinicians should understand the inherent limitations of FoCUS to best utilize it in clinical practice. Findings from a systematic review and meta-analysis are published in Annals of Internal Medicine.

The inaccuracy of physical examination is a long-recognized issue in the clinical setting. Incorporating ultrasonography units, such as FoCUS, could improve the diagnostic yield of bedside patient evaluation for cardiovascular disease.

Researchers from the University of Ottaway Heart Institute reviewed 9 published studies to compare the accuracy of FoCUS-assisted clinical assessment versus clinical assessment alone for diagnosing left ventricular dysfunction or valvular disease in adults having cardiovascular evaluation. They found that FoCUS enabled significantly greater sensitivity, but not greater specificity, than clinical assessment alone. As such, they concluded that FoCUS may be better for ruling out clinically significant cardiovascular pathology in patients at low suspicion of disease rather than for confirming suspected cardiovascular disease. Based on these findings, the researchers suggest that clinicians must understand the situations where formal echocardiography should be pursued and the inherent limitations of FoCUS in terms of both image acquisition and interpretation, before adopting its use in practice.

The authors of an accompanying editorial from Cedars-Sinai Medical Center say that hand-held ultrasonography could be the fifth pillar of the physical examination and improve the accuracy of bedside diagnosis, but caution that its effectiveness is limited by the skills and expertise of the clinician. They suggest that incorporating hand-held ultrasonography in the primary care setting, where the majority of echocardiograms are ordered, could greatly improve downstream work-up and cost-effectiveness.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Benjamin Hibbert, MD, PhD, please contact the Ottawa Heart communications office at communications@ottawaheart.ca. To reach the editorialist Robert J. Siegel, MD, please contact Sally Stewart at Sally.Stewart@cshs.org.

4. Hepatologists debate screening and management of nonalcoholic fatty liver disease

Annals 'Beyond the Guidelines' discussions are based on real Beth Israel Deaconess Medical Center Grand Rounds

Abstract: http://annals.org/aim/article/doi/10.7326/M19-1125

URLs go live when the embargo lifts

Current guidelines from the American Association for the Study of Liver Disease make specific recommendations for the screening and management of patients with nonalcoholic fatty liver disease (NAFLD). However, not all patients fit neatly within the parameters of expert recommendations, making it necessary for clinicians to make decisions based on individual patient characteristics. Hepatologists from Beth Israel Deaconess Medical Center (BIDMC) and University of Michigan Medical Center debate care for a patient with suspected NAFLD in a multicomponent educational article being published in Annals of Internal Medicine.

NAFLD is defined by hepatic fat accumulation that is not attributable to other causes, such as excessive alcohol use. About one-third of the U.S. adult population has nonalcoholic fatty liver disease, and the obesity epidemic is the suspected culprit. The condition has no symptoms, but if left untreated, it may lead to cirrhosis or hepatocellular carcinoma. NAFLD is reversible with lifestyle changes, such as weight loss and improved diet.

Two hepatologists offer differing opinions on how to manage an at-risk patient. Z. Gordon Jiang, MD, PhD recommends that high-risk patients, including those with type 2 diabetes, morbid obesity, or a family history of cryptogenic cirrhosis, be screened for fibrosis in the primary care setting with a non-invasive modality. In addition to recommending lifestyle changes, he would monitor the patient for fibrosis regularly. Elliot Tapper, MD recommends screening only patients with type 2 diabetes who are at the highest risk for advanced fibrosis from NAFLD. He advises a one-time assessment for patients with NAFLD to determine whether advanced fibrosis is present and hepatology consultation is needed. He also recommends lifestyle changes for the patient.

All 'Beyond the Guidelines' papers are based on the Department of Medicine Grand Rounds at BIDMC in Boston and include print, video, and educational components. A list of topics is available at http://www.annals.org/grandrounds.

The safety and effectiveness of electric fans in heatwaves depend on the climate and basing public health advice on common weather metrics could be misleading, according to a new study from the University of Sydney.

The research calls into question current guidelines from most public health authorities, including the World Health Organization, that suggest fans may not be beneficial when the temperature rises above 35 degrees Celsius (95°F), as well as recommendations based on heat index caps.

Researchers from the University's Thermal Ergonomics Laboratory simulated heatwave conditions to examine the effect of electric fan use on an individual's core temperature, cardiovascular strain, risk of dehydration and comfort levels.

The results, published today in Annals of Internal Medicine, show that in a hot, humid condition with a heat index of 56 °C (133°F) fans lowered core temperature and cardiovascular strain, and improved thermal comfort.

However, fans were detrimental for all measures in very hot, dry conditions despite a lower heat index of 46 °C (115°F).

Heat index is a commonly used weather metric that expresses both air temperature and relative humidity. It was designed to help convey how hot weather conditions feel to the average person.

The United States Environmental Protection Agency (USEPA) states that fan use above a heat index of 37.2°C (99°F) "actually increases the heat stress the body must respond to."

Senior author Associate Professor Ollie Jay of the Faculty of Health Sciences and Charles Perkins Centre said recent conditions in Europe and the United States reinforce the urgent need for evidence-based health advice to help protect people against heat-related illness.

"Our results suggest that under environmental conditions that represent the vast majority of peak heatwaves in the United States and Europe fans should be recommended and the guidelines issued by most public health authorities are unnecessarily conservative," said Associate Professor Jay.

"It is only when the air temperature is very high and humidity is very low that fans are detrimental, which can be seen in arid conditions such as Phoenix or Las Vegas in the US, or Adelaide in South Australia."

Methods

Twelve healthy male volunteers were monitored for thermal strain (rectal temperature), cardiovascular strain (heart rate and blood pressure), risk for dehydration (whole body sweat rate), and thermal comfort (assessed using 120-mm visual analogue scale) over a two-hour exposure to simulated peak conditions of two types of heat waves.

One was very hot and dry replicating the peak conditions of the California heatwave in July 2018, and the other was cooler but more humid with a higher heat index representing the peak conditions during the Chicago heatwave in July 1995, and Shanghai heatwave in July 2017.

Next steps

Associate Professor Jay said while larger studies are needed, the current research and earlier work published in the Journal of the American Medical Association suggests that neither temperature or heat index caps are the best basis for public health advice on the use of fans.

His team is currently examining the effectiveness of a range of different low-resource cooling strategies that can be easily implemented in different heatwave conditions by the elderly and people with medical conditions like coronary artery disease. They are also assessing the impact of different prescription medications on the type of advice that should be issued to the general public in advance of extreme heat events.

Police violence is a leading cause of death of young men in the United States with black men 2.5 times more likely to be killed by law enforcement over their lifetime than white men, according to a Rutgers study.

The study, published in PNAS, examined fatality risks during police encounters - some 11,456 between 2013-2017 - and found that African-American men and women, American Indian/Alaska Native men and women and Latino men face a higher lifetime risk of being killed by police than do their white peers.

"The inequality is not surprising," said lead author Frank Edwards, assistant professor in the School of Criminal Justice at Rutgers University-Newark, noting the police killings of black men like Michael Brown and Eric Garner and boys like Tamir Rice and the protests that followed bringing national attention to the racialized character of police violence against civilians.

"All you have to do is turn on the news to see that people of color are at a much greater risk of police-related harm. What we lack in this country are the solid estimates of police related deaths because there is no official database where this information is stored."

The Rutgers study used data compiled by the National Vital Statistic System's mortality files and Fatal Encounters (FE), a journalist-led database that documents deaths involving police where cases are identified through public records and news coverage. Edwards said the unofficial media-based methods provide more comprehensive information on police violence than the limited official data collected.

The aim of the research, Edwards said, is to highlight the need to create a database that would accurately reflect the police violence that occurs.

"We haven't really known for sure how often these killings have been happening because the data hasn't been good enough," said Edwards. "But if we are going to try and change police practices that aren't working, we need to track this information better."

While statistics show that police in the United States kill more people than police in other advanced industrial democracies, researchers say real estimates of how often this occurs are not available. Official data is needed because these violent encounters, they insist, have profound effects on health, neighborhoods, life chances and politics, and have resulted in structural inequalities in the United States between people of color and white people.

The study found that the risk of death for each group peaks between the ages of 20 and 35 and declines with age. The highest mortality rate for men is between the ages of 25-29 when police use-of-force is deemed to be one of the leading causes of death, behind accidents - including drug overdoses, motor vehicle traffic death and other accidental fatalities - suicide, other homicides, heart disease and cancer.

Black men face a 1 in 1,000 chance of being killed by police over their lifetime compared to about 1 in 2,000 for men in general and about 1 in 33,000 for women - about 20 times lower than men.

This new research found that American Indian men were 1.5 times more likely to be killed by police than white men and American Indian women were about 1.5 times more likely to be killed by police than white women. While Latino men were 1.4 times more likely to be killed than their white counterparts, Latina women were about 1.2 times less likely to be killed than white women. Black women, however, were 1.4 times more likely to be killed by police than white women.

Edwards says the study reinforces calls to treat police violence - which has increased by as much as 50 percent since 2008 - as a public health issue. While black people are disproportionately more likely than white people to be killed by police, the rate of white deaths by police have also been increasing in recent years, according to the research.

"The Bureau of Justice Statistics needs to develop a comprehensive system that would track police-related deaths," said Edwards. ''We need to increase transparency of police use-of-force if we are going to decrease the number of civilian deaths in this country as a result of these encounters."

The study stops short in evaluating current policy but says reforms are needed, including the creation of more social welfare and public health programs, adequate funding of community-based services and restricting the use of armed officers as first responders to mental health and other crisis situations where police killings have taken place.

"Our work should examine how race, gender, age, social class, disability and where someone lives exposes them to this type of violence and death," Edwards said.

ITHACA, N.Y. - Foreign-born Ph.D. graduates with science and engineering degrees from American universities apply to and receive offers for technology startup jobs at the same rate as U.S. citizens, but are only half as likely to actually work at fledgling companies, a Cornell University study has found.

Instead, they choose to work at large technology companies with the resources and experience to sponsor foreign workers for highly coveted H-1B or permanent residency visas.

The findings suggest visa policies are an obstacle for small companies seeking to hire foreign-born workers with specialized, in-demand skills. Because so many Ph.D. graduates in STEM fields are international - more than half in some disciplines - this creates an uneven playing field for startups competing with established companies to attract top talent.

"Startups are an important engine for innovation and economic growth," said Michael Roach, assistant professor Charles H. Dyson School of Applied Economics and Management at Cornell. "A key insight from this research is that rather than fostering entrepreneurial activity, U.S. visa policies may disadvantage young technology startups - and this applies to startups founded by immigrants and U.S. citizens alike.

"But hiring is one of the key challenges for early-stage technology startups, and current U.S. visa policies make it even harder."

Roach is a co-author of "Why Foreign STEM Ph.D.s are Unlikely to Work for U.S. Technology Startups," which published Aug. 5 in Proceedings of the National Academy of Sciences. The research was based on a nine-year survey of more than 2,300 Ph.D.s, beginning in graduate school and following them into their careers.

Tech skills such as machine learning and data science are in extremely high demand by companies, and unemployment among Ph.D. graduates in STEM fields is less than 2%. According to the National Science Foundation's Science and Engineering Indicators 2018, half of the people who receive doctorates from U.S. universities in computer science were born in other countries, so access to this pool of workers is key for small and large companies alike.

"Over the past few decades, the American economy has become more dependent on science and technology innovation for growth, and at the same time, our science and technology Ph.D. programs have become more dependent on foreign talent," said co-author John Skrentny, director of the Yankelovich Center for Social Science Research at the University of California, San Diego.

"We often see great innovations coming from Google and Apple, but a lot of their innovation is actually from buying startups," Skrentny said. "These startups have trouble accessing the foreign talent our best universities are graduating."

Ph.D.s with U.S. citizenship whose first jobs are in industrial research and development are nearly twice as likely to work at startups as foreign-born Ph.D.s, even though both groups applied for and were offered startup jobs at the same rate. Nearly 16% of Ph.D.s who are U.S. citizens worked at startups after graduation, compared with nearly 7% of foreign Ph.D.s who required a work visa.

The researchers used the results of the survey, which began in 2010 and focused on Ph.D. students in STEM fields at 39 leading U.S. research universities, to rule out several possible explanations for this disparity. They asked questions gauging participants' interest in working at startups; more foreign-born students said they were interested than students who are citizens.

They considered whether international graduates were more risk-averse than U.S. citizens, indicating that, despite their interest, they'd ultimately be more inclined to work for larger, more stable companies, but the survey also showed foreign-born Ph.D.s had a greater tolerance for risk.

Studies have shown that startups pay lower salaries to their employees than established companies in exchange for equity, but the researchers also found in the survey that foreign-born Ph.D.s rated high pay as less important to their ideal job than their U.S. citizen counterparts.

Though the study did not provide a direct link between visa policies and the hiring of foreign-born workers, the body of evidence indicates visa requirements play a role, the researchers said. Revisiting visa policy as it relates to startups might help them thrive and stimulate the economy, Roach said.

"The findings of this study suggest the need to consider immigration policies that make it easier for technology startups to hire highly skilled foreign workers with Ph.D.s from U.S. research universities," he said. "We may want to consider ways to make it easier for high-growth startups to hire the workers they need."

Many studies have documented disparities in cardiovascular care for minorities, specifically African Americans compared to white patients. Coronary artery bypass grafting (CABG) is a common procedure in the United States, and the outcomes and post-surgical care for African Americans tend to be worse. Investigators from Brigham and Women's Hospital examined whether patients insured through TRICARE -- a universal insurance and equal-access system that covers more than 9 million active-duty members, veterans and their families -- experienced these disparities. The team found no racial disparities in quality-of-care outcomes, providing insights about the potential impacts of universal insurance and an equal-access health care system. The findings are published in Health Affairs.

"In our study, we found a complete absence of racial disparities," said first author Muhammad Ali Chaudhary, MD, a research fellow at the Center for Surgery and Public Health in the Department of Surgery at the Brigham. "In the military, the color of your uniform matters more than the color of your skin. Here, we have an opportunity to look beyond just the impact of universal insurance. This is a system that may be eliminating other factors that contribute to racial disparities in care such as implicit provider bias, health care segregation, differential access to care, and mistrust in the system."

The study included 8,183 TRICARE patients, aged 18-64, who had undergone CABG. The study took its data from TRICARE health care claims from the Military Health System Data Repository for the years of 2006 to 2014.

The primary outcomes for the study were prescription of beta blockers, prescription of statins, and readmission rates within a 30-day period following surgery. All three outcomes are quality-of-care metrics endorsed by the National Quality Forum (NQF) for CABG. African Americans were found to have 10 percent greater odds of beta-blocker prescription than whites and 10 percent lower odds of 30-day readmission, but neither of these findings reached statistical significance. The team found no difference in statin prescription by race. Overall, the study showed no significant difference in quality-of-care metrics for African American and white patients following CABG.

Since the data from the study were taken from a database, researchers could not account for a doctor's reasoning in choosing to prescribe, or not to prescribe, medication. Since TRICARE is a military insurance, its patients might not accurately model the United States population. However, the TRICARE population is socially, geographically and ethnically diverse, and only 20 percent of those covered by TRICARE are actively serving. The rest are veterans and family members of veterans or active-duty members. Unlike Medicare, which provides data for a limited age range, TRICARE covers people of all ages, which may serve as a better model of the American working population.

"It's one of the hypotheses that we've been building for years: Universal health care access and equal access can eradicate racial disparities," said Chaudhary. "With TRICARE, we have a model that provides a window into the potential impacts of universal insurance and an equal-access health care system."

DURHAM, N.C. -- A team of Duke researchers has discovered that cells lining the gut of zebrafish -- and probably humans too -- have a remarkable defense mechanism when faced with certain kinds of toxins: they hit the eject button.

"The gut has the challenging job of handling all the chemicals that we consume or produce, and some of those chemicals can be damaging. So the gut has evolved many interesting ways to defend against damage," said Ted Espenschied, a Duke graduate student who led the effort as part of his dissertation research.

The Duke team was testing more than 20 non-steroidal anti-inflammatory drugs (NSAID) in an attempt to make the zebrafish a new model for studying chemical injury in the gut. The fish are cheap to maintain, easy to breed, and most importantly, translucent for the early part of their lives, Rawls said. It's also easy to administer chemical exposures and measure their environmental conditions via the tank water.

The researchers found something unexpected.
"It's often the case that drugs have multiple off-target effects," said John Rawls, an associate professor of molecular genetics and microbiology and director of the Duke Microbiome Center.

But only one of the drugs they tested seemed to create any measurable differences in the fish, an old NSAID called Glafenine. It had been an over-the-counter oral painkiller used in Europe and the Middle East for three decades, but was taken off the market after being linked to kidney and liver damage.

Glafenine was making the fish shed up to a quarter of the cells lining their intestines overnight by a process called delamination. What hadn't been recognized before is that delamination, which seems catastrophic, is actually a highly effective defense strategy.

The lining of the gut is a single layer of finger-like epithelial cells packed closely together. When a gut epithelial cell is distressed, it somehow becomes marked for destruction. During delamination, neighboring epithelial cells push against the doomed cell to loosen its anchor to the basement membrane they all stand on. The neighbors squeeze in on it and crowd it out until it pops up and is carried away to die in the gut.

"We weren't expecting delamination to be protective," Espenschied said.

Espenschied pivoted on the unexpected finding. "Only one NSAID had this remarkable effect of causing delamination of the gut epithelium and we were wracking our brains trying to figure it out," Espenschied said.

"So we chased it," Rawls added.

After many experiments and a detailed analysis of Glafenine's chemical properties, Espenscheid determined that it wasn't the drug's NSAID qualities that harmed the gut, but rather its ability, apparently unique among NSAIDs, to inhibit a cellular structure known as the multidrug-resistant, or MDR, efflux pump.

These pumps exist to help purge unwelcome chemicals from the interior of the cell. Cancer researchers have been very interested in finding ways to block MDR efflux pumps because tumors ramp them up dramatically to push chemotherapies out of cancer cells, foiling cancer therapy.

Much less is known about what the pumps do in normal cells. "We do know that if you block these pumps, cells are unable to clear toxic chemicals and problems ensue," Rawls said. When Glafenine blocks the MDR efflux pumps in zebrafish, the gut responds with delamination, by means the researchers haven't yet identified.

"We don't know yet which cells leave and why," Espenschied said. "What separates that cell from its neighbors is a really fascinating question that we don't know the answer to yet."

"Delamination is a common solution to a lot of different insults," Rawls said. "But it's been challenging to understand if that is contributing to damage and disease, or a beneficial adaptation to the insult. Our work shows that it's actually beneficial."