Culture

Most distant cosmic jet providing clues about early universe

Astronomers using the National Science Foundation's Karl G. Jansky Very Large Array (VLA) and Very Long Baseline Array (VLBA) have found and studied the most distant cosmic jet discovered so far -- a jet of material propelled to nearly the speed of light by the supermassive black hole in a quasar some 13 billion light-years from Earth. The quasar is seen as it was when the universe was only 780 million years old, and is providing scientists with valuable information about how galaxies evolved and supermassive black holes grew when the universe was that young.

The studies indicate that the quasar -- a galaxy harboring a black hole 300 million times more massive than the Sun -- has a jet of fast-moving particles only about 1,000 years old. While other quasars have been found at its distance and beyond, it is the first found at such a distance with the strong radio emission indicating an active jet. Only a small fraction of quasars have such jets.

"The black holes at the cores of many of these very distant quasars are so massive that they challenge our understanding of how they could have grown in the relatively short time available to them that early in the universe's history. One possibility is that jets provided a mechanism that allowed the black holes to grow more quickly. Finding a jet in a quasar at this epoch is an exciting clue about this question," said Emmanuel Momjian, of the National Radio Astronomy Observatory (NRAO).

"Jets have a role in regulating star formation and the growth of their host galaxies, so this discovery is valuable to understanding these processes in the early universe," said Chris Carilli, also of NRAO. "The jets at that time also propelled atoms and magnetic fields into what had been pristine space between the galaxies," he added.

Finding a quasar with bright radio emission at such a distance also can help astronomers learn more about closer objects.

"Distant radio-emitting quasars at the beginning of the evolution of the cosmos also serve as beacons to study material that lies between Earth and the quasars," said Eduardo Banados of the Max Planck Institute for Astronomy in Germany.

As radio waves pass through gas en route to Earth the gas will absorb specific wavelengths in patterns that reveal its composition.

The object, called P172+18, originally was identified as a quasar candidate in 2015 in data from the Pan-STARRS sky survey using a visible-light telescope in Hawaii. The astronomers then noted that NRAO's FIRST survey, done with the VLA, showed a radio-emitting object at the same position. They later made infrared observations that yielded the distance to the object and the mass of the black hole.

Credit: 
National Radio Astronomy Observatory

Stroke affecting the eye requires immediate treatment, can signal future vascular events

DALLAS, March 8, 2021 - While most people think of strokes affecting the brain, they can also affect the eye. Central retinal artery occlusion (CRAO) is a rare form of acute ischemic stroke that occurs when blood flow is blocked to the main artery of the eye. It typically causes painless, immediate vision loss in the impacted eye, with fewer than 20% of people regaining functional vision in that eye.

Today, the American Heart Association published a new scientific statement, "Management of Central Retinal Artery Occlusion," in Stroke, an American Heart Association journal. The American Association of Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section affirms the educational benefit of the scientific statement, and it has been endorsed by the North American Neuro-Ophthalmology Society, the American Academy of Ophthalmology Quality of Care Secretariat and the American Academy of Optometry.

"Central retinal artery occlusion is a cardiovascular problem disguised as an eye problem. It is less common than stroke affecting the brain but is a critical sign of ill health and requires immediate medical attention," said Chair of the statement writing committee Brian C. Mac Grory, M.B.B.Ch., B.A.O., M.R.C.P., an assistant professor of neurology and staff neurologist at the Duke Comprehensive Stroke Center at Duke University School of Medicine in Durham, North Carolina. "Unfortunately, a CRAO is a warning sign of other vascular issues, so ongoing follow-up is critical to prevent a future stroke or heart attack."

In a comprehensive review of the world literature, committee members from the specialties of neurology, ophthalmology, cardiology, interventional neuroradiology, neurosurgery and vitreoretinal surgery summarized the state of the science in this condition. They found indications that this type of stroke can be caused by problems with carotid arteries, the blood vessels in the neck. However, there is also evidence CRAOs could be caused by problems with the heart, such as atrial fibrillation, which is the most common irregular heart rhythm. The risk of having a CRAO increases with age and in the presence of cardiovascular risk factors such as hypertension, hyperlipidemia, Type 2 diabetes, smoking and obesity.

The new scientific statement notes the lack of large clinical trials on CRAOs leads to uncertainty within the medical community of exactly what causes them or the best way to treat them. As a result, there is wide variability in diagnosis and treatment methods. Most concerning, according to Mac Grory, is that many practitioners may not recognize CRAO as a form of stroke resulting in patients receiving delayed testing and treatment, often in the outpatient clinic instead of the emergency department.

"We know acute CRAO is a medical emergency requiring early recognition and triage to emergency medical treatment," Mac Grory said. "There is a narrow time window for effective treatment of CRAO and a high rate of serious related illness. So, if a person is diagnosed in a doctor's office or other outpatient clinic, they should be immediately sent to a hospital emergency department for further evaluation and treatment."

Current literature suggests that treatment with intravenous tissue plasminogen activator (tPA), a "clot buster" that is also used to treat brain strokes, may be effective. But tPA must be administered within 4.5 hours of the first sign of symptoms to be most effective and safe.

The writing committee also noted that emerging treatments, such as hyperbaric oxygen and intra-arterial alteplase, show promise but require further study. Other potential treatments that require further research and evaluation include novel thrombolytics to break up clots and novel neuroprotectants (substances capable of preserving brain function and structure) for use in tandem with other therapies to restore blood flow in the blocked artery.

Because of the potential for future strokes or even heart attacks, patients should undergo urgent screening and treatment of vascular risk factors. The writing committee notes that the complexities of diagnosing and treating CRAOs require a team of specialists working together. Secondary prevention (including monitoring for complications) must be a collaborative effort between neurologists, ophthalmologists, cardiologists and primary care clinicians. Risk factor modification includes lifestyle and pharmacological interventions.

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American Heart Association

Strict environmental laws 'push' firms to pollute elsewhere

COLUMBUS, Ohio - Multinational companies headquartered in countries with tougher environmental policies tend to locate their polluting factories in countries with more lax regulations, a new study finds.

While countries may hope their regulations will reduce emissions of carbon dioxide and other greenhouse gases, these results show that these policies can lead to "carbon leakage" to other nations, said Itzhak Ben-David, co-author of the study and professor of finance at The Ohio State University's Fisher College of Business.

"Firms decide strategically where to locate their production based on existing environmental policies, with the result being that they pollute more in countries with lenient regulations," Ben David said.

"This highlights the importance of worldwide collective action to combat climate change, given the global scale of firms' operations."

The study was published online recently in the journal Economic Policy.

Researchers used a novel dataset covering 1,970 large public firms headquartered in 48 countries and their carbon dioxide emissions in 218 countries from 2008 to 2015. The database was provided by CDP, a nonprofit formerly known as the Carbon Disclosure Project.

"What makes this dataset unique is that we can observe the carbon dioxide emissions of each multinational firm in each country in which it operates," Ben-David said.

"This provides direct evidence of the effect of environmental policies and each firm's actual carbon dioxide emissions at the country level."

The researchers also used rankings from the World Economic Forum that rated the strength of each country's environmental policies on a scale of 1 (worst) to 7 (best).

The results of the new study don't mean that tougher environmental regulations have no effect at all on global emissions, Ben-David said. Findings suggest that stringent policies are still associated with a partial, but positive, impact on reducing overall global pollution.

For example, an increase in the environmental policy score from China (2.1, suggesting weak regulations) to Germany (5.5, stronger regulations) is associated with 44% lower global emissions.

But it is also associated with a 299% increase in foreign emissions when compared to the companies' home countries.

"If you make it more difficult to pollute in a company's home country, firms will move some of that pollution activity to somewhere else," Ben-David said.

The study examined whether stricter policies "pushed" firms to pollute elsewhere or lax regulations "pulled" firms to countries where it was easier to pollute.

"We found that the results were primarily driven by the environmental policies in the home country, rather than by opportunities to pollute elsewhere," he said. "It was more of a 'push' effect than a 'pull' effect."

Not surprisingly, firms in the most polluting industries were the ones most likely to respond to strict policies in their home countries by locating their pollution activities elsewhere.

Overall, most carbon dioxide is released in an average company's home country, but the share of home emissions declined substantially over time from 72% in 2008 to 57% in 2015, the researchers found.

In addition, the number of countries in which the average firm polluted increased from six to nine during the period of the study.

"Environmental regulations in each country do work to somewhat reduce global emissions of carbon dioxide, but they also have this negative side effect of pushing pollution to other countries," Ben-David said.

"Countries need to collaborate if they really want environmental policies to have the strongest impact."

Credit: 
Ohio State University

Virtual avatar coaching with community context for adult-child dyads

image: Selected scenes of the virtual reality avatar experience seen by participants.

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Journal of Nutrition Education and Behavior

Philadelphia, March 8, 2021 - Virtual reality avatar-based coaching shows promise to increase access to and extend the reach of nutrition education programs to children at risk for obesity, according to a new study in the Journal of Nutrition Education and Behavior, published by Elsevier.

Researchers introduced 15 adult-child dyads to a virtual avatar-based coaching program that incorporated age-specific information on growth; physical, social, and emotional development; healthy lifestyles; common nutrition concerns; and interview questions around eating behaviors and food resources and counseling.

"We developed a virtual reality avatar computer program as a way to get kids engaged in learning about nutrition education. The goal was to make this a program that could work to prevent childhood obesity," said lead investigator Jared T. McGuirt, PhD, MPH, Department of Nutrition, University of North Carolina Greensboro, Greensboro, NC, USA. "We were primarily interested in how kids and parents reacted to this program - particularly lower income kids and parents who may not have been able to access this kind of experience in the past."

A key finding in the study was the avatar's ability to spark dialogue between the children and adults around dietary habits and behavior. All children and adults reported liking the program and planned to use it in the future, as they found it fun, informational, and motivating. The personalized social aspect of the avatar experience was appealing, as participants thought the avatar would reinforce guidance and provide support while acting as a cue to change health behaviors.

Looking to future implementation of this program in the public health field, Dr. McGuirt noted: "We feel we have a good start. The program was designed so others can build on it, and hopefully advance this technique into community nutrition education programs.

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Elsevier

Investigating youth suicides among children involved with the welfare system

Suicide is the second leading cause of death among youth aged 5 to 21 years in the United States. Between 2010 and 2019, suicide rates among this group increased 40%.

Youth involved in the child welfare system experience an even greater risk of suicidal behavior, yet research on this vulnerable population is minimal.

To better understand and prevent suicide in this at-risk group, researchers at Nationwide Children's Hospital conducted the first study to compare characteristics and health service utilization patterns of youth suicide decedents (those who died by suicide) and non-decedents who were involved with the child welfare system.

The study, published in Pediatrics and supported by a grant from the National Institute of Mental Health (NIMH), found that youth with child welfare system involvement who died by suicide were significantly more likely to experience out-of-home placements (with the frequency and length of those placements strongly predicting suicidal behavior), more likely to have been diagnosed with mental health and chronic medical conditions or substance use disorders and more likely to have visited physical and mental health care settings in the months before their deaths than matched controls.

Researchers studied 1,320 young people aged 5 to 21 who had at least one open case in Ohio's Statewide Automated Child Welfare Information System (SACWIS) between 2010 and 2017, matching 120 cases of youth who died by suicide to 10 non-decedent controls each based on sex, race, ethnicity, age and year of open case. The study sample was 66% male, 63% non-Hispanic White, 25% non-Hispanic Black and 4% Hispanic. Nearly half of those studied were 15-19 years old when their SACWIS case was opened (44%), with an average age of 15 years.

Youth who died by suicide were twice as likely to have accessed mental health services in the one month and six months prior to their deaths than controls, regardless of the health care setting. Nearly half of suicide decedents with child welfare system involvement used some type of health care services in the one month prior to their death, and almost 90% did so in the preceding six months, compared to 69% of controls. In fact, the odds of a mental health visit in any period or setting were significantly greater for the youth in the child welfare system who died by suicide. A higher incidence of mental health diagnoses among all youth who died by suicide may account for these findings.

Previous research has found that over 90% of all youth who died by suicide had a mental health condition. In this study, however, 59% of suicide decedents had a diagnosed mental health condition compared to less than a third of the control group (31%).

"These findings raise potential concerns about the quality and consistency of mental health screening and care for youth in the welfare system," said Donna Ruch, PhD, a research scientist in the Center for Suicide Prevention and Research at Nationwide Children's and the study's lead author. "They also validate growing recommendations to screen for suicide risk in health care settings. Given the nature of child welfare system involvement, where children are in contact with varied service providers, integrating suicide prevention strategies as a core component of health care delivery in these settings is important."

Additionally, although the number of open SACWIS cases did not significantly differ between suicide decedents and non-decedent controls, those who died by suicide were significantly more likely to have been removed from their homes and placed in foster care, kinship care or another alternative setting.

"Our research suggests youth with child welfare involvement may benefit from both suicide prevention strategies targeting health care settings, such as the Zero Suicide approach, and those that align with family preservation programs," said Dr. Ruch.

Future research to explore and provide empirical support for these kinds of interventions is critical to reduce suicide deaths in this vulnerable population.

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Nationwide Children's Hospital

Research foresees an end to deregulated competitive public transport

Research from the University of Kent predicts an end to deregulated competitive public transport in the UK as a consequence of Covid-19 social distancing measures leading to drastically reduced ridership, requiring a major rethinking of the provision of public transport.

This paper, published in Transport Policy, argues that the situation will require a fundamental approach to long-term policy for transport as a whole. This is an opportunity to reconstruct the system whilst addressing such problems as the environmental impact of transport, congestion and questions of transport justice such as accessibility to transport for disadvantaged groups in society.

Covid-19 has been a major disruptor on all aspects of the transport system, local, national and international. This has been significant for both the UK's public sector and private sector operators and has thrown most business models into disarray, demonstrating the system's fragility to crisis. Whilst the UK Government provides funding for services to continue amid the pandemic, the length of the emergency and the slow recovery threaten this ability to maintain support until demand returns to pre-pandemic levels.

In the UK central government borrowing in fiscal year 2020/21 is expected to reach almost £400 billion as the economy shrinks by an expected 11.3 per cent and unemployment rises to 7.5 per cent. Continued government funding for the public transport system is not sustainable for current pandemic levels of use, in which ridership is down across the system.

In addition to this, the increasing inequality in accessibility to transport according to income, age, disability and other individual and social characteristics was a pre-pandemic issue of major disparity, whilst the environmental crisis continues with transport accounting for a significant share of global emissions. These older issues continue and require immediate addressing.

The paper argues that returning to the old normal is unlikely and that public transport must adjust to increased home working and a fear of crowded spaces. This potentially spells the end of the prevailing model of a deregulated competitive public transport in the UK.

Roger Vickerman, Emeritus Professor of European Economics at Kent and author of the paper said: 'Public transport's flaws required urgent addressing prior to the pandemic and now much remains to be done in designing an inclusive transport system. In the light of the pandemic, we are presented with this opportunity now and may use it to establish a system that is efficient, environmentally considerate, and to the benefit of its users that currently suffer its disadvantages.'

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University of Kent

Making artificial intelligence understandable -- Constructing explanation processes

Researchers at Paderborn and Bielefeld University are hoping to change this, and are discussing how the explainability of artificial intelligence can be improved and adapted to the needs of human users. Their work has recently been published in the respected journal IEEE Transactions on Cognitive and Developmental Systems. The researchers describe explanation as a social practice, in which both parties co-construct the process of understanding.

Explainability research

"Artificial systems have become complex. This is a serious problem - particularly when humans are held accountable for computer-based decisions," says Professor Philipp Cimiano, a computer scientist at Bielefeld University. Particularly in the area of medical prognosis or legal contexts, we need to understand how machine-driven decisions are made, continues Cimiano. He points out that while there are already some approaches that address the explainability of such systems, they do not go far enough. Professor Katharina Rohlfing at Paderborn University agrees that further action is urgently needed: "Citizens have the right for algorithmic decisions to be made transparent. There are good reasons why this issue is specifically mentioned in the European Union's General Data Protection Regulation." The goal of making algorithms accessible is central to what is known as "eXplainable Artificial Intelligence (XAI)": "In explainability research, the focus is currently on the desired outcomes of transparency and interpretability," says Rohlfing, describing the latest research.

Understanding how decisions are made

The team involved in this research study go one step further and are investigating computer-based explanations from various different perspectives. They start from the assumption that explanations are only understandable to the users if they are not just presented to them, but if the users are involved in formulating them: "As we know from many everyday situations, good explanations are worth nothing if they do not take account of the other person's knowledge and experience. Anyone who wonders why their application was rejected by an algorithm is not generally interested in finding out about the technology of machine learning, but asks instead about how the data was processed with regard to their own qualifications," explains Rohlfing.

"When people interact with one another, the dialogue between them ensures that an explanation is tailored to the understanding of the other person. The dialogue partner asks questions for further explanation or can express incomprehension which is then resolved. In the case of artificial intelligence there are limitations to this because of the limited scope for interaction," continues Rohlfing. To address this, linguists, psychologists, media researchers, sociologists, economists and computer scientists are working closely together in an interdisciplinary team. These experts are investigating computer models and complex AI systems as well as roles in communicative interaction.

Explanation as a social practice

The Paderborn and Bielefeld researchers have developed a conceptual framework for the design of explainable AI systems. Rohlfing says: "Our approach enables AI systems to answer selected questions in such a way that the process can be configured interactively. In this way an explanation can be tailored to the dialogue partner, and social aspects can be included in decision-making." The research team regards explanations as a sequence of actions brought together by both parties in a form of social practice.

The aim is for this to be guided by "scaffolding" and "monitoring". These terms come originally from the field of developmental studies. "To put it simply, scaffolding describes a method in which learning processes are supported by prompts and guidance, and are broken down into partial steps. Monitoring means observing and evaluating the reactions of the other party," explains Rohlfing. The researchers' objective is to apply these principles to AI systems.

New forms of assistance

This approach aims to expand on current research and provide new answers to societal challenges in connection with artificial intelligence. The underlying assumption is that the only successful way to derive understanding and further action from an explanation is to involve the dialogue partner in the process of explanation. At its core, this is about human participation in socio-technical systems. "Our objective is to create new forms of communication with genuinely explainable and understandable AI systems, and in this way to facilitate new forms of assistance," says Rohlfing in summary.

The paper is available here: Explanation as a social practice: https://ieeexplore.ieee.org/document/9292993

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Universität Paderborn

Predicting success in therapy with individualized cancer models

image: Cell Surface Stem Cell Marker (green), dividing cells (red) and DNA (blue).

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Marianna Kruithof-de Julio and Marta De Menna

In the EU alone, 78,800 men died of prostate cancer last year. While tumors discovered at an early stage can often be completely removed by surgery and radiation therapy, the prospects of successful treatment are reduced if the cancer has further metastasized. At present, physicians cannot predict drug response or therapy resistance in patients.

Three-dimensional structures

The team led by PD Dr. Marianna Kruithof-de Julio at the Urology Research Laboratory at the Department for BioMedical Research (DBMR) of the University of Bern and Inselspital Bern, has developed a new strategy for the generation of prostate cancer organoids that can contribute to assess therapy response, their work is published in the latest issue of Nature Communications. Drs Sofia Karkampouna and Federico La Manna, the two lead co-authors of the paper, spent over one and a half year in optimizing and efficient protocol for the generation of the patient derived organoids and their detailed characterization. Moreover, in collaboration with the NEXUS Personalized Health Technologies, they have meticulously developed a medium-throughput screen for drug testing.

The researchers led by PD Dr. Kruithof-de Julio have demonstrated that patient-derived organoids retain relevant characteristics of the prostate carcinoma from which they have been originated: not only are they characterized by the same genetic mutations, but they also exhibit similar gene activity patterns.

Paving the way for personalized medicine

PD Dr. Kruithof-de Julio and her collaborators first generated a novel early stage, patient derived xenograft that is treatment naïve, then tested 74 different drugs on organoids from this and other experimental tumor models - identifying 13 compounds that reduced prostate cancer cell viability.

The researchers then tested the efficacy of these compounds on organoids from five prostate cancer patients - two with early-stage tumors and three with advanced metastatic tumors. Interestingly, among the hits ponatinib, so far approved for the treatment of leukemia, proved to be particularly effective in reduction of organoid viability and tumor growth in vivo.

However, for PD Dr. Kruithof-de Julio, the significance of these results lies not only in the drug repurposing but more importantly in promoting an approach that the medical community can undertake. "Our results pave the way for personalized medicine. In our study we only analyzed data from five patients retrospectively," says Kruithof-de Julio. "But we clearly showed that the method would be in principle feasible. Growing the organoids and drug testing can be accomplished in two weeks, a time frame that is compatible with clinical decision making. In collaboration with the Urology Department of the Inselspital, led by Prof Thalmann, we have now already been able to prove this in several cases."

"In my clinical activity, I am regularly confronted by tumors that do not respond to therapy or for which we do not know which therapy to use", says Thalmann. "This is a further step in the direction of individualized medicine, where we might be able to tailor the treatment to the tumor during the course of the disease and better understand its biology." With this approach, the researchers hope to treat patients more efficiently with less side effects and diminished costs.

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University of Bern

Tocilizumab cuts mortality risk in severely ill COVID-19 patients finds new trial conducted in India

Tocilizumab, an anti-inflammatory drug used to treat rheumatoid arthritis, improves outcomes in severely ill COVID-19 patients, finds the results of a new trial conducted in hospitals across India -- one of the world's most ethnically diverse countries. Researchers from the University of Bristol and Medanta Institute of Education and Research in India who led the study, published in The Lancet Respiratory Medicine, say it adds to existing evidence supporting the drug's use in critically ill patients.

Conducted in 12 public and private hospitals across India, the COVID India Tocilizumab (COVINTOC) phase 3 randomised controlled trial aimed to investigate whether tocilizumab could prevent disease progression and mortality in hospitalised patients with moderate to severe COVID-19.

The study team recruited 180 patients (age 18-years and over) who had been hospitalised with moderate to severe COVID-19. Of these, 89 patients were randomised to receive standard care, and 91 patients were randomised to receive standard care plus tocilizumab.

Patients were followed up over a 28-day period to record any clinical improvement markers and assess disease progression from moderate to severe or from severe to death. The team also recorded whether patients experienced adverse events, serious adverse events, and post-treatment infections, and requirement for renal replacement drugs.

Analysis of the data revealed a subset of patients with severe disease in whom tocilizumab might have a reduced risk for progression to death if treated with tocilizumab in addition to standard care. However, clinical parameters or biomarkers to reliably identify these patients and the optimal timing of treatment during COVID-19 progression remain unknown. The authors conclude that while the study does not support the routine use of tocilizumab in adults with COVID-19 it adds to the growing evidence suggesting it may help some severely ill patients.

The trial's co-author, Professor A. V. Ramanan from the University of Bristol's School of Clinical Sciences, and Consultant Paediatric Rheumatologist at Bristol Royal Hospital for Children, said: "Our study suggests tocilizumab might still be effective in patients with severe COVID-19 and so should be investigated further in future studies. It adds to existing evidence from the RECOVERY and REMAP-CAP studies which demonstrate that tocilizumab does have a significant impact on reducing mortality in those with COVID-19 requiring oxygen or being ventilated.

"After dexamethasone (steroids), this is still the most significant advance in the treatment of COVID that has an impact in reducing deaths."

Lead Dr Arvinder Soin, Chairman of the Medanta Liver Transplantation Institute at Gurugram, India, said: "While there were no differences in mortality and the need for ventilation among the two groups of patients when moderate and severe categories of patients were considered together, a subgroup analysis of the severe patients in the two groups showed a lower mortality at 28 days (8/50; 16 per cent) among those who received tocilizumab compared to those who did not (14/41; 34 per cent). The reported adverse events did not differ between the tocilizumab and standard care arms.

"Given the conflicting results of the previous studies, millions were wasted last year on the indiscriminate use of tocilizumab, as the precise stage of the disease in which to use the drug was not clear. This study plugs an important gap in knowledge on COVID treatment and clarifies that tocilizumab should be administered to patients in the severe category. Incidentally, last month, two major studies from the UK - the RECOVERY Trial and the REMAP-CAP study - have revealed similar findings, that tocilizumab reduces mortality among patients with severe COVID-19."

The trial was conducted against incredible odds across multiple sites under difficult conditions in a country that has the second highest COVID-19 caseload in the world.

Professor Ramanan added: "Challenges to conducting randomised controlled trials during the COVID-19 pandemic are exacerbated in low-and middle-income countries, and several hurdles were encountered during this trial in India. Patients treated with drugs not licenced for the condition they have or compassionate use of treatments in patients with COVID-19 is common and can impede enrolment into clinical trials. Ensuring follow-up is challenging for patients who are likely to be discharged early because of the high demand on hospital resources and for patients who might have logistical difficulty travelling for return visits. We believe it is important that all potential therapies be trialled across diverse settings, not only in North America and Europe."

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University of Bristol

BU researchers identify basic mechanisms that regulate HIV expression

(Boston)--Despite the positive advances that anti-human immunodeficiency virus (HIV) therapy, commonly called anti-retroviral therapy (ART) or highly active antiretroviral therapy (HAART), has had on the life expectancy of HIV-positive people, finding a cure for HIV or acquired immunodeficiency syndrome (AIDS) has remained elusive.

"One of the major challenges in curing HIV is that there is a persistent latent reservoir of virus that is not targeted by current antiretroviral treatments and is hidden from immune cells. When treatment is interrupted, this reservoir of the virus allows the HIV to rapidly rebound," explained corresponding author Andrew J. Henderson, PhD, professor of medicine and microbiology at Boston University School of Medicine.

In an effort to identify cellular pathways that influence the establishment, maintenance and reversal of HIV persistence, the researchers conducted studies with yeast to screen a large library of human factors for binding to HIV deoxyribonucleic acid (DNA) sequences responsible for virus' expression. As a result, they identified several factors as potential regulators and confirmed that a subset of factors did control HIV in infected cells by increasing and decreasing levels of HIV expression.

"Our study identified novel transcription factors that influence HIV and provide an appreciation into cellular networks that influence activation and repression of different HIV strains," said Henderson.

According to the researchers, understanding the mechanisms that control HIV expression will provide insight into HIV replication, latency and pathogenesis. "By gaining an understanding of the cellular pathways that control HIV, we might be able to target them and alter the behavior of this latent reservoir," Henderson added.

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Boston University School of Medicine

COVID-19: Biomarkers linked to severe forms of the disease

A team of researchers from the CHUM Research Centre has identified new biomarkers associated with the severity of COVID-19 in infected patients.

Recent scientific literature has shown that the immune response plays a central part in the severity of COVID-19 disease. Understanding the immune responses generated during the course of the disease is therefore essential to determine which patients are at highest risk for serious complications and death from the disease.

In a new study published in the Journal of Clinical Investigation, scientists and clinicians led by Dr.?Catherine Larochelle, researcher at the CHUM Research Centre, have shown that a set of immune alterations are specifically linked to infection with the SARS-CoV-2 virus, as well as to the severity of COVID-19 disease, its 30-day evolution, and its 60-day mortality. These biomarkers could represent potential therapeutic targets.

We have discussed this with Dr. Larochelle, Professor at the Université de Montréal (Department of Neuroscience) and principal author of the study.

Q. Your experimental approach is rather unique. Based on the immune profiling you conducted, how were you able to identify the patients most at risk for a poor prognosis?

Above all, this is the result of a tremendous collective effort by several dozen people involved in research and clinical work at the CHUM, who participated in this study and in the Quebec?COVID-19 (BQC19) Biobank.

Based on a blood test, we were able to inventory the immune cell populations present in 50 patients with SARS-CoV-2 and compare them to those of 22 patients (of similar gender and age) hospitalized for other acute illnesses, and those of 49 healthy controls.

This immune profiling allowed us to identify subsets of "dysregulated" immune cells specific to patients affected by SARS-CoV-2. Most notably, some of these immune alterations were associated with ventilation needs and mortality in these same patients.

These markers specific to SARS-CoV-2 could then help us to identify the patients at greatest risk, and suggest new avenues for developing therapeutic targets.

In addition, we confirm what has been observed in other studies: disturbances in the immune system such as neutrophilia or lymphopenia, for example, are related to the severity of the disease in hospitalized patients, but are not specific to SARS-CoV-2.

From a clinical perspective, this could explain why general anti-inflammatory treatments such as steroids seem to work in COVID-19 and other acute diseases.

Q. How do you see your results being used directly in a clinical setting? Is it technically feasible?

These assays could be easily transferred to clinical settings, because we worked with very small amounts of blood--less than one millilitre--to develop these immune profiles.

In our experimental approach, we used techniques commonly employed in hospital laboratories: use of surface antibodies to "stain" the cells that express certain markers, flow cytometry (cell characterization and counts), etc. In a clinical setting, this could help track the progress of patients over time and ultimately identify those at high risk who would require closer monitoring.

Q. What therapeutic horizons do you envision for your research work?

I hope that our study will lead to the development of biomarkers that will help us stratify patients based on their risk of developing a severe form of the disease. This should also allow us to identify new therapeutic targets, and to better select those patients who might benefit from certain available therapeutic approaches.

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University of Montreal Hospital Research Centre (CRCHUM)

Hybrid microbes: Genome transfer between different bacteria strains explored

Bacteria integrate genetic material from other bacterial strains more easily than previously thought, which can lead to improved fitness and accelerated evolution. This is shown in a recent study by biophysicists at the University of Cologne. The team analysed genome transfer between bacteria of different lineages. The study was published in the journal PNAS.

In the experiment, the team brought one strain of bacteria into contact with DNA fragments from another strain. The uptake of foreign genetic material is known as horizontal gene transfer -- in contrast to vertical gene transfer, by which genes are inherited from a parent cell of the same lineage. The results show that laboratory evolution through horizontal gene transfer can rapidly produce hybrid organisms of different lineages with extensive genomic and functional changes. "It is a bit like interbreeding modern humans and Neandertals'", says Dr. Fernanda Pinheiro of the Institute of Biological Physics at the University of Cologne and author of the study. The bacteria readily integrated foreign DNA at many sites in the genome. Within 200 generations, the research team observed the exchange of up to 14 percent of the bacterium's core genes.

Horizontal gene transfer is an important factor in bacterial evolution that can operate across species boundaries. "Yet we know little about the rate and genomic targets of cross-strain gene transfer. Also, little is known so far about the effects on the physiology and fitness of the recipient organism", says Pinheiro. From a scientific perspective, hybrid creatures whose parents belong to different species raise fundamental evolutionary biology questions: What combinations of traits yield viable organisms? What are the limits of evolutionary processes when more than one species is involved in reproduction? "Our study makes an important contribution here," Pinheiro adds.

Is the uptake of genes random or does it follow a definite pattern? As the researchers observed, some functional units of the foreign genome were repeatedly imported and the resulting hybrid bacteria had higher growth rates. "This implies that cross-lineage gene exchange drives evolution very efficiently," Pinheiro says. Integrating foreign genes through horizontal gene transfer produces new combinations of genes yet preserves essential structures that make a cell viable. Thus, the study opens new perspectives for future work: to combine transfer evolution experiments and synthetic biology methods to engineer functional innovations.

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University of Cologne

Hospital-based violence intervention program engages vulnerable populations

image: A retrospective cohort study of violent penetrating injury in Boston 2013-2018.

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KIRSTY CHALLEN, B.SC., MBCHB, MRES, PH.D., LANCASHIRE TEACHING HOSPITALS, UNITED KINGDOM.

DES PLAINES, IL - A Boston violence intervention advocacy program is effectively engaging the client population that hospital-based violence intervention programs (HVIPs) have been designed to support. This is the conclusion of a study titled Boston Violence Intervention Advocacy Program: Challenges and Opportunities for Client Engagement and Goal Achievement, to be published in the March 2021 issue of Academic Emergency Medicine (AEM), a journal of the Society for Academic Emergency Medicine (SAEM).

According to the study, HVIPs should consider which types of client needs prove most challenging to address and which novel strategies will engage vulnerable populations not typically targeted by intervention programs. These results speak to the difficulties of program attrition and the complexities of altering the life course for victims of violence.

The lead author of the study is Elizabeth C. Pino, PhD, from the Department of Emergency Medicine and the Boston Violence Intervention Program at Boston Medical Center.

Commenting on the study is Tolulope Sonuyi, MD, an emergency medicine physician and assistant professor for the Detroit Medical Center and Wayne State University, respectively, who specializes in health-centered intervention and prevention strategies around community violence.

"With the increased cognizance of the impact that social determinants of health (SDOH) have on the health of emergency department patients, this is a timely study that nicely demonstrates the influence that critical SDOH domains play in the role of the chronic recurrent disease process of community violence. Furthermore, this study provides a framework to understand the impact that patient characteristics have on the uptake of therapeutic intervention and highlights the challenges that come with addressing the upstream factors of complex biopsychosocial disease processes such as community violence. This is important in informing efforts on a systemic and structural level so that more targeted, efficient, and customized strategies may be considered."

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Society for Academic Emergency Medicine

No more sitting in the dark?

(COLUMBUS, Ohio) - Concussion, a form of traumatic brain injury, is a common injury among children and teens. Concussions can have adverse effects on physical, cognitive, emotional and sleep health. Clinical guidelines for managing concussion in children and teens traditionally recommend complete physical and cognitive rest until symptom resolution, followed by a gradual return to activities like school and sports. These guidelines are often disputed and based on expert consensus as opposed to strong evidence. The challenge has been how to quantify the amount of physical and cognitive activity that children and teens should engage in during recovery. A new study by researchers at the Center for Injury Research and Policy, Sports Medicine, and Emergency Medicine at Nationwide Children's Hospital investigated objectively measured, self-paced physical and cognitive activity across the first week post-concussion.

The study, published today in the Journal of Head Trauma Rehabilitation, found that self-paced physical and cognitive activity during the first week after sustaining a concussion alone neither hastened nor prolonged concussion recovery in children and teens. These findings indicate that children and teens with concussion may have some flexibility to determine their own activity levels during recovery. Physicians may encourage safe, non-contact, light physical activity if it does not make youths' concussion symptoms worse, while also continuing to emphasize appropriate amounts of necessary rest.

Study participants were 11 to 17 years old, seen within 72 hours of injury in the emergency department or a concussion clinic through Nationwide Children's Hospital and received a physician-confirmed diagnosis of concussion. They wore two devices - one to measure their physical activity and sleep around the clock, and one to measure their cognitive activity outside of school. Participants rated their daily concussion symptoms by completing the Postconcussion Symptom Scale during the first week post-injury.

Researchers found that while daily physical and cognitive activity increased across the first week post-injury, daily post-concussion symptoms decreased. Increased daily step count was associated with an increased likelihood of early symptom resolution. However, this association was not statistically significant after adjusting for acute post-concussion symptoms and other covariates.

"This study is the first to objectively measure self-paced cognitive activity during the first week post-injury," said Ginger Yang, PhD, MPH, lead author of the study and principal investigator in the Center for Injury Research and Policy at Nationwide Children's. "While increased physical and cognitive activity may help reduce post-concussion symptoms, reduced symptoms may also lead to increased physical and cognitive activity levels, highlighting the need for further research to better understand this bi-directional relationship." Such research will provide evidence of when an individual is ready for physical and cognitive activity after concussion and what level of activity is most appropriate. This information could be used by clinicians to inform treatment decisions, including individualized physical and cognitive activity recommendations post-concussion.

"Concussions behave somewhat like snowflakes in that they are not all the same, and the specific effects of concussion on our young patients varies greatly - one size or treatment does not, necessarily, fit all," said Thomas Pommering, DO, co-author of the study and division chief of sports medicine at Nationwide Children's. "The strength of this study is that it appears that children and adolescents with concussions are generally pretty good at self-pacing their physical and cognitive activity so as to not prolong their recovery. With the guidance of physicians, there may be room for personalized treatment plans based on the symptom burden, while still following important guidelines protecting the patient from repeat head injury during the recovery time."

Data for this study came from youth-parent dyads referred to the study team by their school athletic trainer or recruited at the Nationwide Children's Hospital emergency department or concussion clinics. Following a physician-confirmed diagnosis of concussion, youth-parent dyads were contacted by research staff and enrolled within 72 hours post-injury after providing written assent and consent. Enrolled dyads were then followed until symptom resolution (defined as being symptom-free or symptoms returned to pre-injury level), or 45 days post-injury, whichever occurred first.

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Nationwide Children's Hospital

Latest research delineates the effectiveness of "quitlines" for smoking cessation

While cigarette smoking continues to be the leading cause of preventable disease, disability and death in the U.S., the evidence base for cessation support has revealed that telephone call centers, or "quitlines," have been a particularly successful intervention, according to the Centers for Disease Control and Prevention (CDC), which recently published a compilation of scientific research in the American Journal of Preventive Medicine.

Titled "The Role of Quitlines in Tobacco Cessation," the supplement is composed of nine peer-reviewed articles and three commentaries presenting the latest science on quitlines' effectiveness for smoking termination. The compilation demonstrates the relevance and importance of call centers as an essential population-level tool designed to increase successful smoking suspension outcomes, and their role as part of a comprehensive approach to tobacco control. Furthermore, it points to shifts in the commercial tobacco product landscape that will require the ongoing improvement and innovation in quitlines' technology to continue to effectively support smokers who want to quit to successfully cease.

According to the CDC, nearly 500,000 U.S. adults die prematurely of smoking tobacco or exposure to second-hand smoke, while over 16 million live with a serious illness caused by smoking each year. Additionally, smoking-related disease among adults costs the U.S. over $300 billion annually, including $170 billion in direct medical care and $150 billion in lost productivity due to premature death.

While cigarette smoking has significantly decreased among U.S. adults since the 1960s, 14 percent were still smokers in 2019, and its prevalence remains high among individuals who are less educated, low-income, LGBT, of a certain race and ethnicity, and people with behavioral health concerns.

"The supplement presents the latest evidence on quitlines from leading tobacco control and prevention researchers and practitioners," said Guest Co-editor Emily F. Gates, an assistant professor of Measurement, Evaluation, Statistics & Assessment at Boston College's Lynch School of Education and Human Development. "It showcases the efforts to customize services to reduce health disparities, recognizes the diverse tobacco product environment, and outlines ways to expand quitlines' reach through technological innovation, such as mobile apps and text messaging. Although compiled prior to the COVID-19 pandemic, it nonetheless reinforces the urgency and value of quitting tobacco, and the benefits of quitlines in facilitating the achievement of that critically important goal."

CDC Researcher Rebecca Glover-Kudon served as co-editor in coordination with a CDC working group and lead editors of the American Journal of Preventive Medicine.

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Boston College