Body

A new study has highlighted that while much is known about the ever increasing uptake of antidepressant medications around the world, there is very little evidence on safe and effective approaches to discontinuing treatment.

In 2020 there were 78 million prescriptions for antidepressants in England and about half of patients treated have taken them for at least two years. Guidelines typically recommend that antidepressants be taken for up to 6 to 12 months after improvement, or for up to two years in people at risk of relapse, but many people take antidepressants for much longer. Surveys of antidepressant users suggest that up to a half of people on long-term antidepressant prescriptions have no clear medical reason to keep taking them. Long-term use can put people at risk of adverse events such as sleep disturbance, weight gain, sexual dysfunction, bleeding, and gastrointestinal problems, as well as feeling emotionally numb and unable to deal with problems in life without their medication.

In this new study for Cochrane, an international research team, including Professor Tony Kendrick from the University of Southampton, looked at the findings from 33 randomised control trials that included 4,995 participants who were prescribed antidepressants for 24 weeks or longer. In 13 studies, the antidepressant was stopped abruptly; in 18, it was stopped over a few weeks (known as 'tapering'); in four, psychological therapy support was also offered; and in one study, stopping was prompted by a letter to GPs with guidance on tapering. Most tapering schemes lasted four weeks or less and none of the studies used very slow tapering schemes beyond a few weeks - in contrast to new guidelines from the UK Royal College of Psychiatrists that recommend tapering over months or years to safely stop.

The authors were unable to make any firm conclusions about effects and safety of the approaches studied and did not have confidence in the results due to the low certainty of evidence they provided.

'We know the rise in long-term antidepressant use is a major concern around the world,' says lead author Dr Ellen Van Leeuwen from the University of Ghent, Belgium. 'As a GP myself, I see first-hand the struggles many patients have coming off antidepressants. It's of critical concern that we don't know enough about how to reduce inappropriate long-term use or what the safest and most effective approaches are to help people do this. For example, there are over 1,000 studies looking at starting antidepressants, yet we found only 33 trials around the world that examined stopping them. It's clear that this area needs urgent attention.'

Co-author Tony Kendrick, Professor of Primary Care at the University of Southampton is leading the REDUCE trial, testing online and psychologist telephone support for patients withdrawing from long-term antidepressants. He says "More than one in ten adults in England are now taking antidepressants but surveys of long-term users suggest that between a third and a half of these have no evidence-based reason to continue taking them, and they are associated with increasing side effects in the longer term."

A key issue identified by the research team is that previous studies have not distinguished between symptoms of a return of depression and withdrawal symptoms from the medication.

The difficulty of distinguishing between these symptoms presents a real challenge for patients, doctors and researchers alike - often resulting in inappropriate continuation of antidepressant medication and uncertain evidence on which to base healthcare decisions.

Dr Kendrick continues, "Antidepressants are often difficult to stop due to withdrawal symptoms. More research is needed to establish the incidence of withdrawal symptoms in patients, and large randomised controlled trials are needed to test different tapering strategies.

"Ultimately we really need more deprescribing studies - especially in primary care given that's where most prescribing takes place - before we can make more definitive conclusions. In the meantime, we hope this review provides a starting point to help GPs openly discuss continuing or stopping antidepressants with their patients. We also want to raise awareness that withdrawal symptoms from antidepressants are common and can be mistaken for relapse of the underlying condition. Experiencing withdrawal symptoms isn't a sign that the patient has relapsed - it might be that they need to taper more gradually down to much lower doses instead, before eventually stopping."

The design, interpretation, and enforcement of county and municipal laws significantly affect local public health. But accessing those laws can be difficult.
A study by Indiana University researchers found that unlike Indiana state laws, which are collected, catalogued by topic, and kept regularly updated in centralized, publicly available electronic databases, laws in about half of all Indiana counties were not online, or if they were online, they weren't necessarily up to date. This means that in Indiana, there is no comprehensive, up-to-date central source that can be used to study how different local governments respond to similar health-related concerns.

The study, published in the American Journal of Public Health is part of IU's Responding to the Addictions Crisis Grand Challenge.

"We believe that, for the purposes of both research and access to and accountability of local government, it would be valuable for there to be some place in Indiana that has all of the state's local laws collected together," said study co-author Ross Silverman, professor of health policy and management at the Indiana University Richard M. Fairbanks School of Public Health and professor of public health and law at the Indiana University Robert H. McKinney School of Law. "Through our study, we were able to show what it takes to try to build a nearly comprehensive database of the local laws that have been passed in Indiana over the past 25 years or so."

Researchers examined the health-related laws covering the largest possible share of the state population in the least number of discrete jurisdictions by focusing on gathering all local laws from all of Indiana's counties and 20 largest municipalities (112 jurisdictions in total, with municipalities located across 15 counties).

They found that local laws from 77 (68 percent; 57 counties, 20 cities) of the 112 jurisdictions were available online. Forty-two jurisdictions (37 percent; 27 counties, 15 cities) contracted with a commercial enterprise to index and publish their laws and 37 jurisdictions (33 percent; 32 counties, 5 cities) published local laws on their local government websites, although there was variation in ease of access, organization, and completeness.

Of the 77 jurisdictions with information available online, 65 (84 percent; 45 counties, 20 cities) had their laws codified by topic, and 19 (24 percent; all counties) stored individual ordinances as discrete PDFs.

Researchers also found 35 jurisdictions (29 percent; all counties) did not have their laws available online. Researchers were able to contact county auditors to obtain ordinances for 27 of these counties. In the case of the other 18 counties, researchers acquired data on laws by visiting local county offices and scanning documents.

"Just to get the raw data that would allow us to start conducting research on our hypothesis, we accrued significant costs including hundreds of hours, thousands of miles traveled, and more than 25,000 pages of scanned documents to be sorted and filed," Silverman said. "In 2021, it is hard to believe that laws are this difficult to collect."

Additionally, Silverman said, how Indiana localities choose to store and organize their laws complicates surveillance. Currently, county governments can fulfill their obligation to publish, record, and maintain a permanent public record of local laws through keeping official copies in a book in their offices. Furthermore, unlike state statutes, most counties organize their laws chronologically by passage date as opposed to topically.

The study is important, Silverman said, because to assess the impact of law on public health, researchers must be able to obtain accurate, up-to-date, and comprehensive data on local-level laws. While he was surprised by how difficult it was to collect the information, Silverman said Indiana is not unique in the varied ways local governments publish and store laws.

"For many counties, limited resources keep them from converting their files electronically," Silverman said. "We were able to load our scanned county files onto a flash drive which we provided them in an effort to help facilitate open government initiatives, easing residents' access to the laws that govern them."

The researchers said a concerted effort is needed to ensure that local laws of all kinds are stored online in organized, searchable, and open-access systems. Such an effort, they said, is vital to achieve the aspirational goals of policy surveillance at the intrastate level. They recommend that local laws of all kinds be online; that online systems be standardized across jurisdictions, organized, and searchable; and that online systems be freely and openly accessible.

These recommendations not only would assist researchers in examining the public health impact of laws but would facilitate transparency and accountability, Silverman said.

"A concerted effort to fund and implement such an approach to local legal publication will pay dividends in public health and democratic engagement with local government," he said.

Several weeks following the publication of the large real-world Covid-19 vaccine effectiveness study by the Clalit Research Institute in Collaboration with Harvard University in the New England Journal of Medicine (NEJM), additional results focusing on vaccine effectiveness in specific sub-populations have now been published.

While the original publication demonstrated the effectiveness of the Pfizer-BioNTech mRNA vaccine in the general population, outstanding questions remained regarding vaccine effectiveness in specific sub-populations of interest, including the elderly, multi-morbid individuals, and individuals with specific prevalent chronic conditions.

The new study also took place in Israel and evaluated data on approximately 1,400,000 Clalit members, with extended follow-up time compared to the previous study, and additional subpopulations. The advanced methodologies employed meticulous individual matching techniques to enable an as-clean-as-possible analysis of vaccine effectiveness, comparing vaccinated to unvaccinated (control) individuals. The increased sample size and increased follow up time enabled the assessment of vaccine effectiveness in additional sub-populations, which the original vaccine effectiveness study was unable to assess.

The results of the new study make clear that the vaccine is exceedingly effective, with 96% of symptomatic cases and 95% of severe cases prevented (compared with point estimates of 94% and 92% in the previous study). The results also demonstrate that the vaccine is highly effective across all age ranges, with 92% effectiveness in preventing symptomatic disease in individuals 70 years and older.

It is important to note that vaccine effectiveness in prevention of symptomatic disease is slightly lower amongst the multi-morbid population of all ages (88% effective amongst individuals with three or more chronic illnesses or risk factors). Specifically, the effectiveness in preventing symptomatic illness varied in patients with different chronic illnesses: the vaccine was highly effective (96% and 93%) in overweight and obese patients, but slightly less effective in immunosuppressed individuals (84%), patients with heart disease (80%), chronic kidney disease (80%) and diabetes (86%). Effectiveness against severe disease was generally higher.

According to Professor Ran Balicer, Chief Innovation Officer for Clalit and Director of the Clalit Research Institute, "This publication is a direct continuation of the large study published in the New England Journal of Medicine several weeks ago. The updated results based on a larger population with extended follow-up period show that the vaccine is even more effective than previously estimated, preventing 96% of cases and 95% of severe cases of covid-19 in all age groups - a 20 to 25-fold reduction of risk compared to the unvaccinated. Severe disease is dramatically reduced even among patients with some specific chronic conditions, but as suggested in the original study, this protection is mildly reduced among patients with several co-morbidities. These results are very encouraging, as they suggest that most COVID-19 cases will be prevented by vaccination even in the elderly and chronically ill, though there should be expected a somewhat higher rate of infection and severe illness in vaccinated individuals with several comorbidities or immune suppression, compared to the healthy fully vaccinated population.

The main conclusions as we see them: The study further supports the immediate need to vaccinate at any eligible age and especially among those suffering from chronic conditions that are most vulnerable to covid-19 compilations if not vaccinated. But we also note that these chronically ill vaccinated patients should continue to practice caution in circumstances where a significant risk of infection exists, as they still have somewhat higher residual vulnerability after being vaccinated. We are relieved to note that the risk for such circumstances has been consistently falling in Israel over the last few months, to unprecedented low rates of daily cases - a 50-fold decrease in cases to as low as 10 cases per million per day and less than 1 severe case per million per day - and the numbers are still dropping."

A good night's sleep is essential for a healthy body and mind, for when we sleep is when the body resets, repairs, and refreshes itself. A lot of people, however, have trouble falling or staying asleep, a condition known as insomnia that affects up to 30% of the population. It is usually caused by an underlying psychiatric or clinical condition and is associated with a poorer quality of life. Recent genome wide analyses have revealed that a gene MEIS1 is linked with insomnia. Interestingly, this gene has also been implicated in restless leg syndrome and iron-deficiency anemia (IDA), the latter caused by a decrease in the oxygen transporter in the blood--hemoglobin (Hb). While studies have shown a correlation between anemia and sleep disorders in infants and children, less is known about their association in adults.

Thus, in a collaborative study published in Chinese Medical Journal, researchers from China and the USA have carried out a cross-sectional analysis to understand the association between insomnia and anemia in a cohort of 12,614 Chinese adults.

The study's lead scientist, Professor Xiang Gao, explains what motivated him and his colleagues to pursue this work, "Anemia could be a novel risk factor for insomnia, a common sleep disorder. Previous studies are limited in terms of adjusting for variables such as sleep parameters and inflammation status. In the current study, we wanted to overcome these lacunae and explore the dose-dependent relationship between hemoglobin levels and insomnia," he says.

Participants were asked to fill out a questionnaire on their lifestyle habits, health status, and clinical and laboratory assessments at the time of enrollment. These parameters were re-evaluated every two years. Anemia was assessed by measuring Hb levels. An Hb level below 12.0 g/dL in women and below 13.0 g/dL in men was defined as anemia.

Next, insomnia was assessed using the Chinese version of the Athens Insomnia Scale (AIS) with an eight-point questionnaire. The first five questions were related to the sleep procedure including sleep induction, night awakening, awakening early in the morning, total sleep duration, and sleep quality. The remaining three questions assessed their overall well-being, functioning, and daytime sleepiness. An AIS score of more than 6 was considered as insomnia.

Variables including age, physical activity, smoking and alcohol consumption, history of diabetes, blood pressure and cholesterol were adjusted in the analysis. The researchers also used chronic inflammation (high sensitivity C Reactive Protein ?1 mg/L) as a measure to distinguish iron-deficient and non-iron deficient cases of anemia. Furthermore, as chronic inflammation and poor kidney function (estimated Glomerular Filtration Rate 2) are associated with low hemoglobin and a risk of insomnia, they excluded individuals with the aforementioned conditions.

Their analysis revealed that 4.3% of the participants had anemia while 15.2% reported having insomnia. Notably, the presence of prior anemia increased the risk of developing insomnia 6 years later by 32% compared to those without anemia. In addition, severe anemia significantly increased the odds of insomnia relative to mild and moderate anemia. Interestingly, the risk was found to be higher in men than in women. Age, however, was not a significant risk factor.

Next, in order to validate their findings, the researchers compared their observations with three other studies in a meta-analysis. Their findings were indeed robust and suggest a strong correlation between anemia and insomnia.

Prof. Gao concludes by suggesting the future direction here on, "Our results provide a new insight into insomnia etiology and treatment/prevention strategies. Clinical trials can help ascertain if treating anemia may help improve symptoms of insomnia. Further, additional studies can help understand the molecular mechanisms and physiology behind this relationship along with the potential role of MEIS1" he says.

Overall their findings suggest that anemia is an important risk factor for insomnia and patients with anemia must thus be assessed for symptoms of sleep disorders.

In rare cases, people who have been fully vaccinated against COVID and are immune to the virus can nevertheless develop the disease. New findings from The Rockefeller University now suggest that these so-called breakthrough cases may be driven by rapid evolution of the virus, and that ongoing testing of immunized individuals will be important to help mitigate future outbreaks.

The research, published this week in the New England Journal of Medicine, reports results from ongoing monitoring within the Rockefeller University community where two fully vaccinated individuals tested positive for the coronavirus. Both had received two doses of either the Moderna or the Pfizer vaccine, with the second dose occurring more than two weeks before the positive test. One person was initially asymptomatic and then developed typical COVID-19 symptoms; the other developed symptoms prior to testing. Both individuals recovered at home, an outcome consistent with evidence suggesting vaccination is effective in preventing severe disease.

Genome sequencing revealed multiple mutations in both viral samples, including the E484K variant in one individual, first identified in South Africa and Brazil, and the S477N variant in the other individual, which has been spreading in New York since November.

"These patients got vaccinated, had great immune responses, and nonetheless broke through with a clinical infection," says Robert B. Darnell, The Robert and Harriet Heilbrunn Professor, who led the research with immunologist Michel C. Nussenzweig, virologist Paul Bieniasz, and geneticist Richard P. Lifton. The researchers were able to discern a quantifiable amount of virus in saliva samples from routine testing ongoing at Rockefeller, and sequence the viral RNA using a new coronavirus testing method developed in Darnell's lab by postdoctoral associate Ezgi Hacisuleyman with help from senior research associate Nathalie Blachere. Since January, the university has required all employees working on-site to be tested weekly using this saliva-based PCR assay.

The observations suggest what is likely a small but ongoing risk among vaccinated individuals, and the possibility that they may continue to spread the virus.

"The idea that we could be entirely done with testing in the post-vaccine world is probably not a good one right now; for example, even fully vaccinated people who develop respiratory symptoms should consider getting tested for COVID-19," says Darnell. "Conversely, exposure to individuals with known infection, even if fully vaccinated, should be taken seriously and again individuals should consider getting tested."

"Given the scope of the pandemic, there's a huge amount of virus in the world right now, meaning a huge opportunity for mutations to develop and spread," he adds. "That is going to be a challenge for the developers of vaccines over the next months and years."

BOSTON - For many patients with localized lung cancer (non-small-cell lung carcinoma and small cell lung carcinoma), high-dose radiation with concurrent chemotherapy is a potential cure. Yet this treatment can cause severe, acute inflammation of the esophagus (esophagitis) in about one in five patients, requiring hospitalization and placement of a feeding tube.

A team of radiation oncologists at Mass General Cancer Center demonstrate in an early clinical trial that the radiation beam can be carefully "sculpted" to deliver the majority of a radiation dose directly to the tumor while effectively sparing tissues in the side of the esophagus away from the affected lung (the contralateral esophagus), thereby limiting inflammation and preserving swallowing function.

The researchers describe their contralateral esophagus sparing technique (CEST) in a study published in JAMA Oncology.

"Severe grade 3 esophagitis is a terrible complication of radiation and chemotherapy," says co-senior author Henning Willers, MD, director of the Thoracic Radiation Oncology Program at Mass General Cancer Center. "It happens 5% to 10% of the time in patients with non-small-cell lung cancer, and 15% to 20% of the time in patients with small-cell lung cancer. Even grade 2 esophagitis, one step lower in severity, can be really tough, with patients requiring narcotics for many weeks to cope with the pain," he says.

Starting in 2013, Willers and colleagues carefully observed outcomes with various treatment techniques, including radiation methods used to treat head and neck and prostate cancers, and using a method of radiation delivery called intensity-modulated radiation therapy (IMRT) they devised CEST.

The technique involves imaging the esophagus and then shaping a high-dose radiation beam so that the maximal amount of radiation energy is delivered to the tumor, with a steep dropoff in energy across the esophagus, thereby sparing as much as possible the normal tissues and function in the side of the esophagus farthest away from the treatment site.

In their initial clinical experience, investigators saw that among patients with locally advanced lung cancers who were treated with CEST and chemotherapy, none had grade 3 or greater esophagitis, and only about 20% had grade 2 esophagitis, which was relatively mild, despite the fact that these patients had received high doses of radiation.

"In 2014, when I was a radiation oncology resident, I noticed that patients did really, really well with our use of this sparing technique, and with Christine C. Olsen, MD, co-principal investigator of the trial, we moved to test this concept on a formal clinical study," says lead author Sophia C. Kamran, MD, now a staff radiation oncologist at the Cancer Center.

To better determine the frequency of esophagitis in patients treated with CEST, the investigators designed a phase 1 trial with 27 patients, 25 of whom completed combined chemotherapy and radiation. Of this group, ranging from 51 to 81 years of age, 19 had non-small-cell lung cancer, and 6 had small-cell lung cancer.

None of the 25 patients who completed chemoradiation developed grade 3 esophagitis, while 7 experienced grade 2 esophagitis. Other treatment side effects were within the range of what can be expected for this type of cancer. Two-thirds of patients remained alive at two years after chemoradiation, and none had an isolated local tumor recurrence.

"Our findings support emerging national guidelines, which are increasingly recognizing the importance of sparing the esophagus, although an effective method to do so has neither been formalized nor well defined until now. This is the first prospective trial reporting on the use of a formalized technique," says Kamran.

PHILADELPHIA -- (April 22, 2021) -- A synthetic DNA vaccine candidate for Middle East respiratory syndrome coronavirus (MERS-CoV) developed at The Wistar Institute induced potent immune responses and afforded protective efficacy in non-human primate (NHP) models when given intradermally in abbreviated, low-dose immunization regimen. A similar vaccine candidate was previously shown to be safe and tolerable with a three-dose intramuscular injection regimen in a recently completed human phase 1 study and is currently in expanded studies of phase 1/2a trial.

New results were published today in JCI Insight.

"While several vaccine products are being advanced against MERS and other coronaviruses, low-dose delivery and shortened regimes are crucial to rapidly induce protective immunity, particularly during emerging outbreaks, as the current SARS-CoV-2 pandemic has emphasized," said David B. Weiner, Ph.D., Wistar executive vice president, director of the Vaccine & Immunotherapy Center (VIC) and W.W. Smith Charitable Trust Professor in Cancer Research, who led the study.

Researchers evaluated the immunogenicity and protective efficacy of their MERS synthetic vaccine when delivered intradermally using a shortened two-dose immunization schedule compared with intramuscular delivery of higher doses in NHP.

"Given that human efficacy trials for MERS vaccines may be challenging due to the low number of yearly cases, animal models such as our NHP model are valuable as a bridge with human data coming from early-phase clinical trials," said Weiner.

In this study, Weiner and team report robust antibody neutralizing antibodies and cellular immune responses in all conditions tested. A rigorous virus challenge experiment showed that all vaccination groups were protected against MERS-CoV compared to unvaccinated control animals. However, the low-dose regimen with intradermal delivery was more impactful in controlling disease and symptoms than the higher dose delivered intramuscularly in NHP models.

"To our knowledge, this is the first demonstration of protection with an intradermally delivered coronavirus vaccine," said Ami Patel, Ph.D., Caspar Wistar Fellow at the Vaccine & Immunotherapy Center and one of the lead authors of the paper. "Intradermal delivery of synthetic DNA vaccines has significant advantages for rapid clinical development. It can be dose sparing and has higher tolerability in people compared with intramuscular injection. The positive results of this study are important not only for the advancement of this MERS vaccine but also for development of other vaccines."

"Our team is also advancing a COVID-19 vaccine through clinical trials, and we were able to do so in a very short time thanks to our previous experience developing the MERS vaccine," added Weiner.

Importantly, no evidence of adverse effects on the lungs was observed in any of the dosing groups compared to unimmunized control animals. Through the assessment of a large panel of blood cytokines, researchers showed significant decrease in all mediators of inflammation, which further suggests the vaccine prevents the destructive inflammation induced by coronaviruses.

"In the past twenty years, three new coronaviruses have emerged and caused human outbreaks. The current SARS-CoV-2 pandemic has further emphasized the importance of rapid infection control for coronaviruses and other emerging infectious diseases," said Emma L. Reuschel, Ph.D., a staff scientist in the Weiner lab and co-first author on the study. "Vaccine candidates that are simple to deliver, well tolerated, and can be readily deployed in resource-limited settings will be important to achieve control of infection."

AUSTIN, Texas -- Despite advances in medicine and technology, childbirth isn't likely to get much easier on women from a biological perspective.

Engineers at The University of Texas at Austin and University of Vienna revealed in new research a series of evolutionary trade-offs that have created a near-perfect balance between supporting childbirth and keeping organs intact on a day-to-day basis. Human reproduction is unique because of the comparatively tight fit between the birth canal and baby's head, and it is likely to stay that way because of these competing biological imperatives.

The size of the pelvic floor and canal is key to keeping this balance. These opposing duties have constrained the ability of the pelvic floor to evolve over time to make childbirth easier because doing that would sacrifice the ability to protect organs.

"Although this dimension has made childbirth more difficult, we have evolved to a point where the pelvic floor and canal can balance supporting internal organs while also facilitating childbirth and making it as easy as possible," said Krishna Kumar, an assistant professor in the Cockrell School of Engineering's Department of Civil, Architectural and Environmental Engineering who led the research published this week in the journal Proceedings of the National Academy of Sciences.

The pelvic floor in women is a band of muscles that stretches across the bottom of the abdomen from the tailbone to the pubic bone. It supports pelvic organs, including the uterus, bladder and bowel, and it helps stabilize the spine.

A larger pelvic floor and canal would facilitate easier childbirth. But the larger it becomes without additional bones or tissue to support it, the more likely it is to deform under the weight of organs and cause them to fall downward.

These trade-offs, referred to as the pelvic floor hypothesis, were known in the scientific community. But the theory had been difficult to test until this research team used engineering tools to investigate it.

Kumar first started thinking about the problem by comparing the pelvic floor to a trampoline. A bigger trampoline will drop further as weight is applied, whereas a smaller trampoline will hold its structure better.

In addition to studying the size of the pelvic floor, the researchers also looked at thickness. In theory, a thicker pelvic floor could continue to support organs and an expanded size for childbirth. But it did not turn out that way.

"We found that thicker pelvic floors would require quite a bit higher intra-abdominal pressures than humans are capable of generating to stretch during childbirth," said Nicole Grunstra, an affiliated researcher at the University of Vienna's Unit for Theoretical Biology in the Department of Evolutionary Biology. "Being unable to push the baby through a resistant pelvic floor would equally complicate childbirth, despite the extra space available in the birth canal, and so pelvic floor thickness appears to be another evolutionary 'compromise,' in addition to the size of the birth canal."

The team got to this conclusion by applying principles common in civil engineering. Kumar used a Finite Element analysis, a computerized model often deployed to test the design of structures to see whether they will break or wear down when facing high levels of pressure and stress. In this case, Finite Element analysis allowed the team to model the pelvic floor, change its parameters and see how it responds to the stresses of childbirth and protecting organs, which is otherwise impossible to test using clinical data.

This is the first time Finite Element analysis has been used to explore an evolutionary question. However, it isn't the first time Kumar has applied engineering tools to biology.

While at the University of Cambridge in the U.K., where he met his co-authors who are now at the University of Vienna, Kumar applied a transportation analysis technique to herpes to learn more about how it first spread among humans.

This collaboration shows that engineering approaches and tools are relevant to important problems that, at first glance, may seem well outside the discipline, said Kumar, whose primary research involves numerical models for earthquakes, landslides and other disasters.

"You can abstract all the biology away, and it comes down to what happens if you apply stress, what does it do to bodies and structures with different material properties," Kumar said. "If you squint your eyes, a large landslide can look like a pelvic floor."

In a worldwide study of 2,100 pregnant women, those who contracted COVID-19 during pregnancy were 20 times more likely to die than those who did not contract the virus.

UW Medicine and University of Oxford doctors led this first-of-its-kind study, published today in JAMA Pediatrics. The investigation involved more than 100 researchers and pregnant women from 43 maternity hospitals in 18 low-, middle- and high-income nations; 220 of the women received care in the United States, 40 at UW Medicine. The research was conducted between April and August of 2020.

The study is unique because each woman affected by COVID-19 was compared with two uninfected pregnant women who gave birth during the same span in the same hospital.

Aside from an increased risk of death, women and their newborns were also more likely to experience preterm birth, preeclampsia and admission to the ICU and/or intubation. Of the mothers who tested positive for the disease, 11.5% of their babies also tested positive, the study found.

Although other studies have looked at COVID-19's effects on pregnant women, this is among the first study to have a concurrent control group with which to compare outcomes, said Dr. Michael Gravett, one of the study's lead authors.

"The No. 1 takeaway from the research is that pregnant women are no more likely to get COVID-19, but if they get it, they are more likely to become very ill and more likely to require ICU care, ventilation, or experience preterm birth and preeclampsia," he said. Gravett is a professor of obstetrics and gynecology at the University of Washington School of Medicine. Co-investigator Dr. Lavone Simmons is a UW acting assistant professor of OB-GYN.

One caveat, Gravett noted, was that women whose COVID-19 was asymptomatic or mild were not found to be at increased risk for ICU care, preterm birth or preeclampsia. About 40% of the women in this study were asymptomatic. Pregnant women who were obese or had hypertension or diabetes were at the greatest risk for severe disease, the findings showed.

Babies of the women infected with COVID-19 were more likely to be born preterm; but their infections were usually mild, the study found. Breastfeeding seemed not to be related to transmitting the disease. Delivery by Caesarean section, however, might be associated with an increased risk of having an infected newborn, the study found.

Gravett suggested that these and parallel research findings compelled U.S. states' decisions to open vaccine eligibility to pregnant women - who were initially considered a population at low risk for severe COVID-19.

"I would highly recommend that all pregnant women receive the COVID-19 vaccines," based on this research, he said.

The study demonstrates the importance of collecting large-scale, multinational data quickly during a health crisis, Gravett said. Researchers were able to complete the investigation and report findings in only nine months, using infrastructure already in place from the INTERGROWTH-21st Project, which emerged in 2012 to study fetal growth and neonatal outcomes.

PHILADELPHIA-- Art appreciation is considered essential to human experience. While taste in art varies depending on the individual, cognitive neuroscience can provide clues about how viewing art affects our neural systems, and evaluate how these systems inform our valuation of art. For instance, one study shows that viewing art activates motor areas, both in clear representations of movement, like Adam and Eve in Michelangelo's Expulsion from Paradise, and in implied movement through brush strokes, like in Franz Kline's gestural paintings.

Altered neural functioning, like that experienced in patients with Parkinson's disease, changes the way art is both perceived and valued, according to a study published recently in The Journal of Cognitive Neuroscience by researchers from the Penn Center for Neuroaesthetics at the University Pennsylvania's Perelman School of Medicine. They found that people with neurological motor dysfunction demonstrated decreased experiences of motion in abstract art and enhanced preferences for high-motion art, compared to a healthy control group.

"People can experience movement in abstract art, even without implied movement, like brush strokes," says author Anjan Chatterjee, MD, a professor of Neurology and director of the Penn Center for Neuroaesthetics. "These representations of movement systematically affect people's aesthetic evaluations, whether they are healthy individuals or people with Parkinson's disease."

The study examined the aesthetic experiences of 43 people with Parkinson's disease and 40 controls in the same age group. The subjects made motion and aesthetics judgements about 10 Jackson Pollock and 10 Piet Mondrian paintings. Using seven-point Likert scales, participants rated the paintings along nine categories: Liking, Beauty, Interest, Familiarity, Motion, Complexity, Balance, Color-Hue, and Color-Saturation. The Color dimensions served as relatively objective control ratings.

People with Parkinson's disease demonstrated stable and internally consistent preferences for abstract art, but their perception of movement in the paintings was diminished compared to controls. This finding provides evidence that the brain's motor system is involved in translating nonrepresentational information from static visual cues in the image into representations of movement.

For example, Mondrian paintings receiving the highest motion ratings in this study contained more visual elements, overlapping lines, repetition, and many small areas of contrasting colors. Mondrian's final Boogie-Woogie paintings, inspired by the New York jazz scene, are viewed as dynamic and rhythmic, despite an absence of gestural brushwork. The feeling of movement brought about by works like these likely results from the way these visual elements are interpreted, leading to abstract representations of movement rather than simulations of specific bodily actions. Similarly, Pollock paintings may be felt as dynamic because the increasing number of overlapping colors and the manner of paint application leads to more repetition, curvature, and contrast, which are thought to evoke feelings of movement.

"Our findings are particularly significant because, previously, it was posited that viewing abstract art stimulated the motor system because people could envision the gestures the artist took when painting," says lead author, Stacey Humphries, PhD, a postdoctoral researcher in the department of Neurology. "But our research shows that even without those representations of movement, the motor system can interpret static visual clues as movement and in turn impact the viewer's aesthetic appreciation."

The motion effects cannot be attributed purely to greater complexity in the higher motion paintings. Researchers found no significant differences in the complexity ratings or the relationship between complexity and liking of art given by patients and controls.

The researchers note that the patients participated while on their usual medication. One factor not yet considered is the effect that dopaminergic medication might have on aesthetic experiences. Dopamine plays a significant role in the normal functioning of the brain's reward system, which is consequently disturbed in Parkinson's disease.

The fundamental insight of the study is that the brain's ability to construct abstract representations of movement influences people's aesthetic experiences of art.

Researchers at Carnegie Mellon University and McGill University have adapted an algorithm first developed to spot anomalies in data, like typos in patient information at hospitals or errant figures in accounting, to identify similarities across escort ads.

The algorithm scans and clusters similarities in text and could help law enforcement direct their investigations and better identify human traffickers and their victims, said Christos Faloutsos, the Fredkin Professor in Artificial Intelligence at CMU's School of Computer Science, who led the team.

"Our algorithm can put the millions of advertisements together and highlight the common parts," Faloutsos said. "If they have a lot of things in common, it's not guaranteed, but it's highly likely that it is something suspicious."

The team calls the algorithm InfoShield and presented a paper on their findings at this year's IEEE International Conference on Data Engineering (ICDE).

According to the International Labor Organization, an estimated 24.9 million people are trapped in forced labor. Of those, 55% are women and girls trafficked in the commercial sex industry, where most ads are posted online. The same person may write ads for four to six victims, leading to similar phrasing and duplication among listings.

"Human trafficking is a dangerous societal problem which is difficult to tackle," lead authors Catalina Vajiac and Meng-Chieh Lee wrote. "By looking for small clusters of ads that contain similar phrasing rather than analyzing standalone ads, we're finding the groups of ads that are most likely to be organized activity, which is a strong signal of (human trafficking)."

To test InfoShield, the team ran it on a set of escort listings in which experts had already identified trafficking ads. The team found that InfoShield outperformed other algorithms at identifying the trafficking ads, flagging them with 85% precision. Perhaps more importantly, it did not incorrectly flag any escort listings as human trafficking ads when they were not. False positives can quickly erode trust in an algorithm, Faloutsos said.

Proving this success was tricky. The test data set contained actual ads placed by human traffickers. The information in these ads is sensitive and kept private to protect the victims of human trafficking, so the team could not publish examples of the similarities identified or the data set itself. This meant that other researchers could not verify their work.

"We were basically saying, 'Trust us, our algorithm works,'" Vajiac said.

To remedy this, the team looked for public data sets they could use to test InfoShield that mimicked what the algorithm looked for in human trafficking data: text and the similarities in it. They turned to Twitter, where they found a trove of text and similarities in that text created by bots.

Bots will often tweet the same information in similar ways. Like a human trafficking ad, the format of a bot tweet might be the same with some pieces of information changed. Rabbany said that in both cases -- Twitter bots and human trafficking ads -- the goal is to find organized activity.

Among tweets, InfoShield outperformed other state-of-the-art algorithms at detecting bots. Vajiac said this finding was a surprise, given that other algorithms take into account Twitter-specific metrics such as the number of followers, retweets and likes, and InfoShield did not. The algorithm instead relied solely on the text of the tweets to determine bot or not.

"That speaks a lot to how important text is in finding these types of organizations," Vajiac said.

BOSTON - Exclusively using (or "vaping") e-cigarettes can help people quit smoking, but many people using e-cigarettes to quit smoking continue to smoke cigarettes. New research led by investigators at Massachusetts General Hospital (MGH) reveals that respiratory symptoms--such as cough and wheeze--are more likely to develop when people use both e-cigarettes and tobacco cigarettes together compared with using either one alone. The findings are published in the American Journal of Respiratory and Critical Care Medicine, the flagship journal of the American Thoracic Society.

The investigators analyzed information on 20,882 individuals aged 12 years and older in the Population Assessment of Tobacco and Health (PATH) Study, a U.S. nationally representative longitudinal survey.

The analyzed participants had no respiratory symptoms when surveyed in 2015-2016. When they were surveyed about one year later, respiratory symptoms were reported by 10.7% of those who did not use e-cigarettes or tobacco cigarettes, 11.8% of exclusive e-cigarette users, 17.1% of exclusive tobacco smokers, and 19.7% of dual users (those who both vaped e-cigarettes and smoked tobacco cigarettes). Dual users had a 1.9-times higher odds of developing respiratory symptoms compared with exclusive e-cigarette users and a 1.24-times higher odds compared with exclusive tobacco smokers. The risk of new respiratory symptoms among individuals who vaped but did not smoke was not significantly higher than the risk among individuals who neither vaped nor smoked.

"To help people quit smoking, FDA-approved medications, such as the nicotine patch or the medication varenicline, are preferred," says lead author Krishna Reddy, MD, MS, an investigator in MGH's Division of Pulmonary and Critical Care Medicine and the MGH Tobacco Research and Treatment Center. "People who vape e-cigarettes in an effort to stop smoking tobacco cigarettes should be cautioned against using both and instead should switch over completely from smoking to vaping, with an ultimate goal of stopping vaping as well."

Senior author Nancy Rigotti, MD, director of the Tobacco Research and Treatment Center, adds: "This study helps identify how e-cigarettes can best be used to reduce the harms caused by smoking cigarettes. Exclusive e-cigarette use did not increase the risk of new respiratory symptoms while using both products (e-cigarettes and cigarettes) did."

DALLAS, April 22, 2021 -- People with abdominal obesity and excess fat around the body's mid-section and organs have an increased risk of heart disease even if their body mass index (BMI) measurement is within a healthy weight range, according to a new Scientific Statement from the American Heart Association published today in the Association's flagship journal, Circulation.

"This scientific statement provides the most recent research and information on the relationship between obesity and obesity treatment in coronary heart disease, heart failure and arrhythmias," said Tiffany M. Powell-Wiley, M.D., M.P.H., FAHA, chair of the writing committee and a Stadtman Tenure-Track Investigator and chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory in the Division of Intramural Research at the National Heart, Lung, and Blood Institute at the National Institutes of Health in Bethesda, Maryland. "The timing of this information is important because the obesity epidemic contributes significantly to the global burden of cardiovascular disease and numerous chronic health conditions that also impact heart disease."

A greater understanding of obesity and its impact on cardiovascular health highlights abdominal obesity, sometimes referred to as visceral adipose tissue, or VAT, as a cardiovascular disease risk marker. VAT is commonly determined by waist circumference, the ratio of waist circumference to height (taking body size into account) or waist-to-hip ratio, which has been shown to predict cardiovascular death independent of BMI.

Experts recommend both abdominal measurement and BMI be assessed during regular health care visits because a high waist circumference or low waist-to-hip ratio, even in healthy weight individuals, could mean an increased risk of heart disease. Abdominal obesity is also linked to fat accumulation around the liver that often leads to non-alcoholic fatty liver disease, which adds to cardiovascular disease risk.

"Studies that have examined the relationship between abdominal fat and cardiovascular outcomes confirm that visceral fat is a clear health hazard," said Powell-Wiley.

The risk-inducing power of abdominal obesity is so strong that in people who are overweight or have obesity based on BMI, low levels of fat tissue around their midsection and organs could still indicate lower cardiovascular disease risks. This concept, referred to as "metabolically healthy obesity," seems to differ depending on race/ethnicity and sex.

Worldwide, around 3 billion people are overweight (BMI = 25 to 29.9 kg/m2) or have obesity obese(BMI ?30 kg/m2). Obesity is a complex disease related to many factors, including biologic, psychological, environmental and societal aspects, all of which may contribute to a person's risk for obesity. Obesity is associated with greater risk of coronary artery disease and death due to cardiovascular disease and contributes to many cardiovascular risk factors and other health conditions, including dyslipidemia (high cholesterol), type 2 diabetes, high blood pressure and sleep disorders.

For this statement, experts evaluated research on managing and treating obesity, particularly abdominal obesity. The writing group reports that reducing calories can reduce abdominal fat, and the most beneficial physical activity to reduce abdominal obesity is aerobic exercise. Their analysis found that meeting the current recommendations of 150 min/week of physical activity may be sufficient to reduce abdominal fat, with no additional loss from longer activity times. Exercise or a combination of dietary change and physical activity has been shown in some instances to reduce abdominal obesity even without weight loss.

Lifestyle changes and subsequent weight loss improve blood sugar, blood pressure, triglyceride and cholesterol levels - a cluster of factors referred to as metabolic syndrome - and reduce inflammation, improve blood vessel function and treat non-alcoholic fatty liver disease. However, studies of lifestyle change programs have not shown a reduction in coronary artery disease events (such as heart attack or chest pain).

In contrast, bariatric surgery for weight loss treatment is associated with a reduction in coronary artery disease risk compared to non-surgical weight loss. This difference may be attributed to the larger amount of weight loss and the resultant changes in metabolism that are typical after bariatric surgery.

"Additional work is needed to identify effective interventions for patients with obesity that improve cardiovascular disease outcomes and reduce cardiovascular disease mortality, as is seen with bariatric surgery," said Powell-Wiley.

The statement also addresses the "obesity paradox," which is sometimes observed in research, particularly in populations that have overweight or have Class I obesity (BMI = 30 to 34.9 kg/m2). The paradox suggests that even though overweight and obesity are strong risk factors for the development of cardiovascular disease, they are not always a risk factor for negative cardiovascular outcomes. The writing group notes that people with overweight or obesity are often screened earlier for cardiovascular disease than people with healthy weight, thus resulting in earlier diagnoses and treatment.

"The underlying mechanisms for the obesity paradox remain unclear," said Powell-Wiley. "Despite the existence of the paradox for short-term cardiovascular disease outcomes, the data show that patients with overweight or obesity suffer from cardiovascular disease events at an earlier age, live with cardiovascular disease for more of their lives and have a shorter average lifespan than patients with normal weight."

In reviewing the effects of obesity on a common heart rhythm disorder, the writing group reports there is now "convincing data" that obesity may cause atrial fibrillation, a quivering or irregular heartbeat. Estimates suggest obesity may account for one-fifth of all atrial fibrillation cases and 60% of recently documented increases in people with atrial fibrillation. Research has demonstrated people with atrial fibrillation who had intense weight loss experienced a significant reduction in cumulative time spent in atrial fibrillation.

"The research provides strong evidence that weight management be included as an essential aspect of managing atrial fibrillation, in addition to the standard treatments to control heart rate, rhythm and clotting risk," said Powell-Wiley.

The statement identifies areas of future research, including a call for further study of lifestyle interventions that may be most effective in decreasing visceral adiposity and improving cardiovascular outcomes. Powell-Wiley said, "It's important to understand how nutrition can be personalized based on genetics or other markers for cardiovascular disease risk.

She added, "as overweight and obesity prevalence increases among adolescents worldwide, it is critical to address how best to develop upstream primary prevention interventions and better treatment strategies, particularly for young patients with severe obesity."

BOSTON -- Radiation therapy is used as a treatment for more than half of all cancer patients and can be highly effective at shrinking tumors and killing cancer cells. But radiation treatment can also damage healthy tissue, including tissue in the mouth and gastrointestinal tract. This tissue injury can lead to oral mucositis, esophagitis, and proctitis -- painful and sometimes debilitating tissue damage. It's estimated that these injuries occur in over 200,000 patients in the U.S. each year. In a new paper published in Advanced Science, investigators from Brigham and Women's Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital and MIT describe efforts to develop a new personalized, 3D-printed device intended to shield patients who are undergoing radiation therapy and prevent radiation-induced toxicity. The work to date has been conducted in preclinical models and uses simulations to predict effects in humans, laying groundwork for clinical trials for patients.

"When we treat patients with radiation, we do our best to minimize the area of healthy tissue that receives radiation and break up treatment into small doses, but it's a fine balance. We want to administer the most dose we can to shrink the tumor without causing damage to healthy tissue," said lead author James Byrne, MD, PhD, a postdoctoral researcher in the Traverso lab at the Brigham and MIT and a senior resident physician in Radiation Oncology at Brigham, MGH, and Dana-Farber Cancer Institute. "Our goal through this project was to find an innovative solution that could offer personalized protection for patients."

Byrne collaborated with a multi-disciplinary team on the work, including experts in radiation oncology, physicists, mechanical engineers, and gastroenterologists.

"It's not uncommon for gastroenterologists to be called in to consult on a case to support a patient who is experiencing side effects of radiation in the esophagus, small intestine or anywhere else in the gastrointestinal tract," said corresponding author C. Giovanni Traverso, MB, BChir, PhD, a gastroenterologist and biomedical engineer in the Division of Gastroenterology at the Brigham and MIT. "A couple of years ago, James and I began brainstorming -- what if we could develop a shield that could help protect a significant portion of normal tissue in the radiation field?"

Byrne and colleagues tested a broad range of materials -- both solid and liquid -- from which to construct the radioprotective shields. The team focused on high atomic number (Z) materials, which can prevent gamma and X-rays from passing through, and other materials to reduce radiation backscatter. Using CT scans from patients, the team created designs unique to individual patients and used 3D-printing to generate them. They tested their shields in rats and pigs. They found that the shields could protect healthy tissue in the mouth and rectum in rats with good feasibility and reproducibility of placement in pigs. In simulations of human patients, the team estimated that the device could reduce radiation to areas in the mouth by 30 percent for head and neck cancer patients, and in the gastrointestinal tract by 15 percent in prostate cancer patients, without reducing radiation dose to the tumor.

The authors note that this work is an initial proof-of-concept study and additional investigations will be needed to translate the devices for use in the clinic. However, their results so far suggest that personalized shields could someday help reduce the risk of radiation toxicity.

"Our results support the feasibility of personalized devices for reducing the side effects of radiation therapy," said Byrne. "This personalized approach could be applicable to a variety of cancers and holds the potential to reduce the burden of radiation injury and toxicity for our patients."

Bottom Line: When given a choice, most individuals with an average risk of colorectal cancer said they would prefer a stool-based screening test for colorectal cancer over colonoscopy, the method most often recommended by health care providers.

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

Author: Xuan Zhu, PhD, senior health services analyst at the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery

Background: Although colorectal cancer is the second most frequent cause of cancer-related death in the United States, about one-third of eligible American adults have never completed a colorectal cancer screening test, explained lead author Zhu. Zhu added that colorectal cancer screening is particularly underutilized by individuals experiencing socioeconomic disadvantages, racial and ethnic minorities, and certain age groups.

The U.S. Preventive Services Task Force (USPSTF) recommends several colorectal cancer screening methods for adults ages 50 to 75 with an average risk for this disease, and the USPSTF draft guideline update released in October 2020 recommends lowering the age of screening initiation to 45. The three most common tests are an annual fecal immunochemical test or fecal occult blood test (FIT/FOBT) that detects blood in the stool; the multitarget stool DNA (mt-sDNA) test (Cologuard), completed every three years, which detects altered DNA from cancer cells, precancerous polyps, or blood in the stool; and a colonoscopy every 10 years, which involves a gastroenterologist examining the colon with a camera and removing any precancerous polyps while a patient is under sedation.

"Previous research has shown that fewer patients complete colorectal cancer screening when only colonoscopy is recommended compared to when stool-based options are also recommended," said Zhu.

How the Study was Conducted: In this study, Zhu and colleagues evaluated patient preferences for colorectal cancer screening through a survey conducted in collaboration with the National Opinion Research Center at the University of Chicago. The survey included short descriptions of FIT/FOBT, mt-sDNA, and colonoscopy, and asked a nationally representative sample of adults ages 40 to 75 to choose between two options presented at a time. A total of 1,595 respondents completed the survey. The researchers focused their analysis on a subgroup of 1,062 respondents aged 45 to 75 with an average risk of colorectal cancer.

Results: When presented with a choice, 66 percent of respondents said they preferred mt-sDNA over colonoscopy, and 61 percent said they preferred FIT/FOBT over colonoscopy. When asked to choose between the two stool-based options, 67 percent indicated a preference for mt-sDNA over FIT/FOBT.

The investigators also examined differences in patient preferences across sociodemographic characteristics, access to health care, awareness of colorectal cancer screening, and prior experience completing a test. While mt-sDNA was preferred over colonoscopy for all age groups examined, a larger proportion of older adults (ages 65 to 75 years) said they preferred colonoscopy compared to those in younger age groups (ages 45 to 54 years).

Similarly, the preference for mt-sDNA over colonoscopy was higher among non-Hispanic white individuals compared with non-Hispanic Black and Hispanic individuals. Half of Hispanic and non-Hispanic Black respondents preferred stool-based tests over colonoscopy, with a preference for mt-sDNA over FIT/FOBT. Zhu said the observed differences among age and racial/ethnic groups might have reflected variations in preferences or disparities in access to information about newer testing methods.

Respondents without insurance were 2.5 times more likely to prefer less expensive stool-based tests over colonoscopy. The overall awareness of stool-based tests was about 60 percent, compared to 90 percent for colonoscopy, indicating that there is an opportunity to improve patient education about stool-based options, Zhu noted. Study participants who were aware of stool-based tests were two times more likely to prefer mt-sDNA over FIT/FOBT, and those who had previously had a stool-based test were 2.8 times more likely to choose FIT/FOBT over colonoscopy. By contrast, those who had previously had a colonoscopy were less than half as likely to prefer a stool-based test over colonoscopy and those who had a provider recommend colonoscopy in the past 12 months were 40 percent less likely to prefer mt-sDNA over colonoscopy.

Author's Comments: "The best colorectal cancer screening test is the one that patients are most likely to complete," Zhu said.

The findings highlight the importance of patient education about available screening options and taking patients' needs, preferences, and values into account in shared decision-making discussions to increase colorectal cancer screening rates, Zhu added. "Providing patients with as-needed navigation support, from initiation of screening to completion of a colonoscopy after stool-based tests show abnormal results may increase screening completion and adherence."

Study Limitations: Limitations of this study include the observational design, meaning that causal relationships cannot be inferred, the reliance on self-reported data rather than objective measures, and limiting the scope of the study to the three colorectal cancer screening tests most commonly recommended by health care providers.