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The first case of the novel coronavirus, COVID-19, in the United States was in late January. By mid-March, "social distancing" had entered the public lexicon. People altered their routines and local jurisdictions suggested, urged, or required changes meant to slow the disease's spread.

By the end of June, however, public health officials and news outlets were talking about a second wave. In July, many states were pausing or reversing their plans to reopen while, for the second time, hospital systems worried about running out of room.

What could we have done better?

In an "editor's pick" paper published today in the journal Chaos of the American Institute of Physics, Washington University in St. Louis researchers in the lab of Rajan Chakrabarty, associate professor in the department of Energy, Environmental and Chemical Engineering at the McKelvey School of Engineering, modeled the interplay between the duration and intensity of social distancing. They found a law of diminishing returns, showing that longer periods of social distancing are not always more successful when it comes to slowing the spread, and that any strategy that involves social distancing requires other steps be taken in tandem.

"Conventional wisdom was, the more intense and long-term the social distancing, the more you will curb the disease spread," Chakrabarty said

"But that is true if you have social distancing implemented with contact tracing, isolation and testing. Without those, you will give rise to a second wave."

Added Payton Beeler, a second year doctoral student in Chakrabarty's lab, who also worked with Pai Liu, a postdoctoral fellow: "What we have found is that if social distancing is the only measure taken, it must be implemented extremely carefully in order for its benefits to be fully realized."

Their susceptible, exposed, infected, and recovered (SEIR) dynamics model used data gathered by Johns Hopkins University between March 18 and March 29, a period marked by a rapid surge in COVID-19 cases and the onset of social distancing in most US states. Calibrating their model using these datasets allowed the authors to analyze unbiased results that had not yet been affected by large-scale distancing in place.

Unique to this project was the use of age stratification; the model included details on how much people of different age groups interact, and how that affects the spread of transmission.

No matter what strategy they looked at, one thing was clear, Chakrabarty said: "Had social distancing been implemented earlier, we probably would've done a better job."

Researchers found that, over the short-term, more distancing and less hospital demand go hand in hand -- but only up to two weeks. After that, time spent distancing does not benefit hospital demand as much; society would have to increase social distancing time exponentially in order to see a linear decrease in hospital demand.

Thus the diminishing return: Society would see smaller and smaller benefits to hospital demand the longer it spent social distancing.

If social distancing "alone" is to be implemented longer than two weeks, a moderate shut down, say between 50-70%, could be more effective for the society than a stricter complete shut-down in yielding the largest reduction in medical demands.

Another strategy for flattening the curve involves acting intermittently, alternating between strict social distancing and no distancing to alleviate the strain on hospitals -- as well as some of the other strains on the economy and well-being imposed by longer-term distancing.

According to the model, the most efficient distancing- to- no-distancing ratio is 5 to 1; one day of no distancing for every five days at home. Had society acted in this way, hospital burden could have been reduced by 80%, Chakrabarty said. Exceeding this ratio, the model showed a diminishing return.

Critically, the researchers note that social distancing policy as a whole-of-government approach could not be successful without the implementation of wide-spread testing, contact tracing, and isolation of those found to be infected.

"And you have to do it aggressively," Chakrabarty said. "If you do not, what you're going to do, the moment you lift social distancing, is give rise to a second wave."

That's because the people who are leaving their homes after distancing themselves are, ostensibly, all susceptible to COVID-19.

"Bending the curve using social distancing alone is analogous to slowing down the front of a raging wildfire without extinguishing the glowing embers," said Chakrabarty, whose other line of research focuses on the impacts of wildfires on climate and health.

"They are waiting to start their own fires once the wind carries them away."

The model cannot inform strategies going forward because it used data collected in March, before any large-scale social distancing was implemented. But Chakrabarty said it may be able to inform our actions if we find ourselves in a similar situation in the future.

"Next time, we must act faster, and be more aggressive when it comes to contact tracing and testing and isolation," Chakrabarty said. "Or else this work was for nothing."

July 15, 2020 -The first consensus-based nomenclature for arterial and venous waveforms has been published online first today in Vascular Medicine (VMJ) and the Journal for Vascular Ultrasound (JVU). This publication reflects a multispecialty collaboration in partnership with the Society for Vascular Medicine (SVM) and the Society for Vascular Ultrasound (SVU), with Writing Committee members nominated by both organizations. This document addresses a significant area of confusion in vascular testing.

According to Dr. Esther Kim, Chair of the Writing Committee and member of the SVM Board of Trustees: "Over a decade ago, the lack of a standardized nomenclature to describe spectral Doppler waveforms was demonstrated to result in confusion amongst ultrasound professionals. Not surprisingly, this can lead to negative clinical outcomes, and the primary intent of this consensus statement is to improve communication amongst all practitioners who care for vascular patients. The Writing Committee was commissioned by the SVM and SVU, representing a logical collaboration between sonographers and interpreting physicians, both critical providers of vascular care."

In addition to proposed standardized nomenclature, the comprehensive document is rich with examples of waveforms to illustrate use of the standardized terminology and to help implement the findings in clinical practice. The document covers arteries and veins in vascular territories throughout the body including the carotid, peripheral arterial, peripheral venous, renal, and mesenteric circulation.

"The hope of the Writing Committee is that this document will help us all to 'speak the same language,' and thereby advance the field of vascular ultrasound and improve patient care," says Dr. Kim.

The document has been endorsed by both SVM and SVU, and both organizations are committed to disseminate its findings. Comments from both societies are below.

Kelly Byrnes, President of SVU: "Sonographers have long been proponents for standardizing Doppler waveform nomenclature, with Bob Scissons being among the earliest and most vocal standard-bearers. The characterization of waveforms is basic to the diagnosis of vascular disease, and there have been more than a few spirited debates on the topic! It is extremely gratifying to see the fruits of this years-long collaboration between SVU and SVM result in this much-needed Consensus Statement. We owe a great deal of thanks to the Writing Committee for this substantial contribution to the profession."

Dr. Raghu Kolluri, President of SVM: "This Consensus Statement helps vascular specialists better communicate and seeks to mitigate discordance in the terminology of the Doppler waveform...a combined effort of the sonographers performing the tests and interpreting vascular physicians is the best approach to improve communication amongst caregivers. So, SVM-SVU collaboration makes perfect sense. We hope that this new Doppler waveform nomenclature will eliminate confusion and lead to appropriate diagnosis and better patient care."

The document is designed for immediate implementation in vascular labs and for educational purposes. The article is free to download for a limited time.

Researchers at the University of Illinois at Chicago have developed a new drug that prevents blood clots without causing an increased risk of bleeding, a common side effect of all antiplatelet medications currently available.

A new study published in the journal Science Translational Medicine describes the drug and its delivery mechanisms and shows that the drug is also an effective treatment for heart attack in animal models.

Xiaoping Du, UIC professor of pharmacology and regenerative medicine at the College of Medicine, led the research.

"Unfortunately, current antiplatelet medications prevent the blood clotting that cause heart attack and stroke but also disrupt platelets' ability to stop bleeding if a blood vessel is torn," Du said. "In some cases, severe bleeding can be life-threatening. The magic of this new drug is it prevents clots but does not make people prone to bleeding, which other drugs have failed to do."

In a previous study, Du and his colleagues identified a signaling mechanism that is important in the blood clotting process but not required for platelets' ability to adhere to a wound and prevent bleeding. Based on this finding, the researchers derived a peptide to target the signaling mechanism and designed a nanoparticle that successfully delivered the peptide into platelets.

The peptide-derived nanoparticle drug -- called M3mP6 high-loading peptide nanoparticle, of HLPN -- was then tested in mice as a possible treatment for heart attacks.

Du said a heart attack can cause heart failure and death in two different ways. One, from the initial damage caused by the clot, which blocks blood flow and reduces oxygen supply. This typically is treated by a procedure called angioplasty and a stent to open the artery, combined with antiplatelet drugs to prevent it from clotting again. However, fresh blood flowing into the damaged heart tissue following the reopening of the artery can trigger inflammation, causing leaks and clots in small blood vessels and further damage to the heart, Du said.

"This is called reperfusion injury and this is the second way a heart attack can lead to heart failure or death," Du said. "We were hopeful that this new drug, which does not cause blood vessel leaks, would help limit reperfusion injury and reduce the chance of heart failure and death, and our hypothesis was proved correct -- we saw very promising results from our study."

In the study, among mice that received the treatment, administered as an injection, there was reduced damage to the heart, reduced clotting and reduced inflammation. There also was improved heart function and improved survival.

"It is very exciting to see such promising results in the lab and we hope to one day test this in humans," Du said.

In a new study published in Science Translational Medicine, Robert Levy, Ph.D., along with graduate student and first author Cameron Bader and colleagues, have shown that inhibiting the STING protein pathway could protect certain patients from graft versus host disease, the most serious complication from bone marrow (stem cell) transplants.

"This pathway is very important in allogeneic (donor) stem cell transplants," said Dr. Levy, professor of microbiology and immunology at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. "We found that, in preclinical models of transplants which mimic those performed between HLA (human leukocyte antigen) matched patients, we would want to interfere with the STING pathway to minimize graft versus host disease and the complications associated with this disorder."

Allogeneic bone marrow transplants, in which patients receive new blood-producing cells from a donor, are often a major component in leukemia and lymphoma treatments, as aggressive chemotherapy is used to destroy the patient's own marrow cells. However, the donated cells can also generate their own immune response, pitting the grafted cells against their new host. Graft versus host disease (GVHD) can cause skin rashes, nausea, diarrhea, and liver damage, and is the major non-relapse cause of mortality in these patients.

In the paper, Dr. Levy's team tested whether STING could be modulated to control GVHD. In one instance, they created an animal model that replicates an allogeneic transplant from a sibling match and found that when STING was absent, the symptoms of GVHD were reduced. However, when investigating STING in an unmatched transplant model, in which donor and recipient were not closely related, the absence of the pathway made GVHD worse.

Further investigation showed this surprising difference was caused by distinct immune system T cells. When transplanting only CD8 T cells, excluding the CD4 variety, the lab replicated the positive results in the unmatched model, reducing GVHD.

"That told us the cell populations that mediate GVHD really affect the role STING plays in these transplants," said Dr. Levy. "STING can worsen GVHD or it can provide a protective effect. We figured out that, when the CD8 T cells are present in the transplant, they get rid of the antigen-presenting cells that drive CD4 T cells. So, if you get rid of those antigen-presenting cells, and you don't drive CD4 T cells, you can also mitigate GVHD."

Dr. Levy believes inhibiting STING in matched patients could potentially reduce their risks of developing GVHD. However, there may be an added benefit: STING could also be boosted to activate T cells and promote a stronger immune response against cancer cells. In this scenario, clinicians might want to selectively inhibit and boost STING - at different times - when treating cancer patients.

"With matched siblings, like our preclinical model, we would want to block STING during the early part of the transplant to prevent serious graft versus host disease," said Dr. Levy. "Then later, we might want to go in and activate STING to help generate tumor immunity against the remaining leukemia or lymphoma cells."

A joint report published by researchers at the Irish Longitudinal Study on Ageing (TILDA) and ALONE examines issues of loneliness and social isolation in older adults. The report offers fresh insight into the experiences of those over 70 who were advised to 'cocoon' as part of public health measures to curtail the spread of the COVID-19 virus. New data from ALONE which documents increased feelings of loneliness, anxiety and isolation in older adults throughout the pandemic, is compared with experiences of loneliness and isolation in older adults before the COVID-19 outbreak.

Previous research into this area has shown that strong social ties may protect people from emotional distress, cognitive decline, and physical disability, while loneliness and social isolation can cause harm to physical and psychological wellbeing. Both loneliness and social isolation have been strongly associated with poorer quality of life and other measures of well-being.

The TILDA study offers unique insights into the health, habits and experiences of older adults living in Ireland through its longitudinal research, examining a variety of key areas that affect older adults such as physical and mental health as well as economic and social factors. Research from TILDA highlights the prevalence of loneliness and social isolation in its nationally representative survey of participants which gives clear insight into the experiences of older people.

What does TILDA's research show prior to the pandemic?

Over 70% of TILDA participants reported that they never or rarely feel lonely; less than 25% feel lonely some of the time while just 5% reported feeling lonely often.

Of those living alone, 31% are rarely lonely, 32% sometimes lonely and 37% often lonely.

Of those living with others, 49% are least lonely, 30% sometimes and 21% often lonely.

Researchers point out that most older adults are not often lonely and appear quite resilient, while data from ALONE's helpline suggest that the COVID-19 pandemic has taken a toll on older people.

The rise of loneliness in a pandemic

Measures introduced to curb the spread of the COVID-19 virus, including physical distancing, and self-isolation particularly affected those over 70 who were 'cocooning'; disrupting daily routines and social interactions with friends and family. Following the outbreak of the virus, ALONE's Support and Telephone Befriending service continued remotely with volunteers calling and sending regular texts to older people with health and well-being tips and practical supports. Almost 500 smartphones were distributed to older adults with limited means of social interaction. Following an increase in calls for support, ALONE established a dedicated phoneline to provide help and services to vulnerable older adults who may have needed them. Report data from ALONE highlights increased feelings of loneliness and isolation amongst older people during the COVID-19 pandemic.

What does ALONE's research show?

The ALONE national support line has received 26,174 calls during the period: March 9th to July 5th, 2020.

55% of callers were from the over 70s, the cohort advised to 'cocoon'.

75% of callers to the helpline were living alone.

There has been an increase in callers who are putting off medical treatment or examination, including after falls.

ALONE has seen a rise in callers reporting negative emotions, including suicidal ideation during the pandemic.

Callers have most often requested support for their physical health, befriending, and emotional and mental health needs.

The data highlights that public health measures such as social distancing and cocooning to curb the spread of the virus has increased levels of loneliness and social isolation in older people. This may have a negative effect on the well-being of older adults and suggests that public policies should be developed to ensure that these issues are addressed. Researchers suspect that current physical distancing and social isolation measures will be most keenly felt by those who rely on community or church-based social participation and engagement.

A future research project led by TILDA in collaboration with ALONE will investigate and document the impact of the COVID-19 pandemic on the health and general well-being of older adults.

Professor Rose Anne Kenny, Principal Investigator of TILDA said:

''This collaborative report between ALONE and TILDA offers a unique perspective into how older adults have been affected by the COVID-19 pandemic. TILDA research shows that most older adults are not often lonely and highlights the resilience of older adults as they adapt to an ever-changing world. The world has witnessed how older adults have been disproportionately affected by the pandemic. ALONE's research provides front- line evidence that shows the true toll public health measures have had on older people with increased feelings of loneliness, anxiety and isolation. The impact of the pandemic is now being studied in the TILDA cohort and will be reported later this year. This will more precisely inform the impact of COVID-19 on loneliness and social isolation, and areas for policy intervention.''

Sean Moynihan, Chief Executive Officer of ALONE said:

''ALONE's coordinated National Response to the COVID-19 pandemic allowed us to respond with immediacy to the concerns newly emerging, and existing issues being elevated from older people. We worked to keep all our services operative through adaptation of their structures. The presence of this virus in society has further solidified existing issues while further alienating some older people, as we have seen extensive increases in loneliness through the isolation experienced from cocooning. We established a loneliness taskforce to ensure we were putting provisions in place to safeguard older people, presently, and into the future. Society needs to understand that loneliness can happen to anyone and can damage both your physical and mental health. It is distressing and we want to work towards breaking down this stigma. As Ireland's ageing population continues to develop, we must remember that there are several thousands of older people behind every percentage."

Creutzfeldt-Jakob disease (CJD) is a serious minority neurodegenerative disease, with an annual rate of 1.5 cases per million inhabitants, which represents approximately 11 cases each year in Catalonia. CJD is a very rapid and fatal disease, in fact, the mean life expectancy is six months after diagnosis. The characteristic symptoms are dementia and the rapid and progressive loss of motor and mental abilities. A team from the Bellvitge Biomedical Research Institute (IDIBELL) and CIBERNED, together with two German research groups from the University of Göttingen and the University of Münster (WWU), have just designed a very user-friendly model that will allow determining the life expectancy of CJD patients at the diagnosis moment.

The model, presented in an article in the Alzheimer's and Dementia journal, has been created based on four basic parameters that all doctors have at the time of CJD diagnosis: age, sex, variant of the prion protein gene (PRNP) and the concentration of the tau protein in the cerebrospinal fluid. In CJD patients, the PRNP gene is frequently sequenced to determine if the origin of the disease is genetic or sporadic, so it is easy to know which of the three possible variants of this gene is present. On the other hand, the concentration of tau in the cerebrospinal fluid is an indicator of neuronal damage, frequently measured in the diagnosis of neurodegenerative diseases.

The team, in which Dr. Franc Llorens, principal investigator of the IDIBELL Neuropathology group and CIBERNED has participated, has designed six tables that combine the four basic parameters and allows the extrapolation of patients' life expectancy. "This is the first model for the prognosis of patients with CJD," says Dr. Llorens, and adds, "it is a user-friendly tool that does not require prior knowledge of statistics, epidemiology or the disease itself." The researchers are satisfied with the forecast accuracy of this new model, they consider it "a good starting point to optimizing with new factors that may be interesting in the future," says Dr. Nicole Rübsamen of the University of Münster.

Why knowing life expectancy is so important?

For family conciliation, knowing the life expectancy of a patient helps the family and the patient himself to prepare for the final moment, also allows palliative care and therapeutic support to be adapted, and thus improve the quality of life. But also, knowing this information is useful for the efficacy studies of new treatments for the disease. If we do not know what the initial life expectancy was, we cannot determine if a specific treatment has brought him a benefit, and therefore, the lengthening of life expectancy.

In neurodegenerative diseases, especially those with rapid progression, one of the best ways to know if a treatment works is to determine if it lengthens life expectancy. This can only be determined if we can predict the initial life expectancy, before treatment, and compare it with that obtained after treatment. These are much more reliable and objective data than neuropsychological analyzes, where there are always subjective components, and in many cases, they cannot be performed in these patients.

The largest cohort in the world

This study shows results from the world's largest cohort of CJD patients, over 1,200 cases. This is a rare disease, with a very low prevalence, that is why it took to the National Reference Center in Germany 25 years, from 1993 to 2017, to gather enough data to do a study.

Philadelphia, July 15, 2020 - As the COVID-19 pandemic spread across the United States, governments at the state and local levels issued emergency declarations and shut down schools. With no treatment and no vaccine, this was seen as the best way to stop the spread of the SARS-CoV-2 virus. Researchers from Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania's Perelman School of Medicine have conducted one of the first studies to measure the efficacy of social distancing in the early days of the COVID-19 pandemic. They found that states that were slow to implement such orders saw higher COVID-19 death rates.

The findings were published this month in Clinical Infectious Diseases.

Researchers analyzed more than 55,000 COVID-19 deaths across 37 states between January 21, 2020 and April 29, 2020. They tested the association between the timing of emergency declarations and school closings with 28-day mortality. The findings showed that each day of delayed intervention lead to a 5 to 6% increase in mortality risk. Even when excluding New York and New Jersey to account for the impact of excess deaths from the New York City area, the models still showed similar results.

"Before this study, we assumed social distancing worked based on modeling and studies of prior pandemics, but we didn't have substantial quantitative data to show its effectiveness for COVID-19," said Nadir Yehya, MD, lead author and Assistant Professor in the Division of Critical Care Medicine at CHOP and the Hospital of the University of Pennsylvania. "Our analyses demonstrate that states that issued emergency declarations earlier helped curb the spread of the disease. These results confirm how important it is to implement social distancing measures early to reduce Covid-19 deaths."

The researchers were able to adjust for multiple confounders, including population density, age, and demographics, but were unable to adjust for potentially important confounders, such as outbreaks in long-term care facilities. Nor did their data explore individual behavior or the association between the duration of social distancing orders and outcomes.

"The implementation of social distancing measures is fundamentally political, as the process is decided upon by elected officials," Dr. Yehya said. "Real-time, scientific evidence of the efficacy of these measures will be helpful for informing future policy decisions."

Heart Failure impacts between three to four per cent of the general population. While commonly related to heart attacks it can also be due to a condition called dilated cardiomyopathy (DCM), a disease characterized by an enlarged and weak heart muscle that can't efficiently pump blood.

An international, multi-centre study led by Dr. James White, MD, a clinician and researcher at the University of Calgary's Cumming School of Medicine (CSM), has revealed magnetic resonance imaging (MRI) can be used to predict major cardiac events for people diagnosed DCM.

White's study, published in Circulation Cardiovascular Imaging, confirms about 40 per cent of patients with DCM have scarring patterns on their heart muscle which can be seen with MRI. These patterns are associated with higher risk of future heart failure admissions, life-threatening heart rhythms and death.

The study, which was the largest ever-conducted using MRI in patients with DCM, also shows that cardiac MRI can play an important role in guiding the care of individual patients with heart failure. White says that treating patients with DCM is challenging because there is a lack of understanding into what causes the disease, and why patients respond differently to the available treatments.

"We have tended to think of dilated cardiomyopathy as one type of heart disease and that all patients should respond the same way, but we are learning that it is a collection of disease states that affect each patient differently," says White, explaining those that don't respond well to treatments are more prone to cardiac arrest, which kills about 35,000 Canadians annually. "The purpose of our study was to see if we could find individual patient features that can help us prescribe life-saving therapies, such as the implantable cardioverter defibrillator."

White and his team assembled the MINICOR (Multimodal International Cardiovascular Outcomes Registry) group, which involves 12 centres from Canada, the United States, Spain and Italy, to provide researchers access to highly standardized data collected from patients around the world with the goal of promoting personalized care for patients with cardiovascular disease.

"We can have a much greater impact on patient care and on clinical practice in general when we work together," says White "The true benefit of initiatives like this is our ability to test innovative ideas quickly and show they can work in different health-care systems and patient populations. This is the unique power of multi-national collaborations."

Given the disproportionate impact that COVID-19 has on older adults in terms of death and lasting disability, and the impact of common aging-related comorbidities like diabetes and cardiovascular disease, Buck Institute professor and practicing geriatrician John Newman, MD, PhD, can make a compelling argument that those infected with the SARS-CoV2 virus are suffering from an aging-related disease, no matter how old they are when they get infected. In a review published in Med, a Cell Press journal, Newman and a consortium of colleagues encourage researchers studying aging, metabolism, and immunity to turn their attention to ketone bodies, which are being widely studied for their roles in aging and aging-related diseases. The research team views ketone bodies as a possible therapeutic against COVID-19, seasonal flu and other respiratory infections.

Ketone bodies are compounds naturally produced during fat metabolism. They provide energy to cells and can also reprogram cellular functions. Eating a ketogenic diet - which is high fat, low protein, and low carbohydrates - ramps up the production of the primary ketone beta-hydroxybutyrate acid (BHB).

While the purported and reported benefits of eating the strictly controlled diet have made ketogenic-related food products and supplements wildly popular, Newman, senior author of the review, is quick to point out that there is much unknown about the biology of BHB and the physiology of how it impacts various systems in the body. "I want to be clear that there is no evidence that a ketogenic diet is protective in any way against COVID-19," he said. "In fact there may be instances where BHB could promote viral replication of SARS-CoV2, the specific virus that causes the disease. But given the promise that BHB shows against many of the age-related risk factors for COVID-19 such as heart disease and diabetes we want to take advantage of this unique opportunity to bring geroscience to the fight against COVID-19. "

Small clinical trials in humans have shown proof-of-concept that BHB can improve cardiac function in those with heart failure and improve key aspects of cognitive health. In the laboratory setting BHB shows promise against type 2 diabetes and dampens harmful inflammation. Elevation of blood ketones has been shown to be broadly protective against hypoxia-related tissue damage, which occurs in severe respiratory infections. Doctors at Johns Hopkins University plan on testing a ketogenic diet on a small group of intubated patients suffering from COVID-19. The hope is that the diet will improve oxygen exchange, reduce the duration of time on ventilators and perhaps most importantly, reduce the systemic inflammation that leads to the cytokine storm that often proceeds the development of acute respiratory distress syndrome.

"Basic research shows that BHB directly inhibits the activation of the pro-inflammatory pathway NLRP3, which is central to the disease pathogenesis of COVID-19 and is a likely contributor to the cytokine storm," said Brianna Stubbs, PhD, a Buck researcher with expertise in ketone biology and lead author of the review. "Understanding how BHB impacts innate immunity following infection is one of the key preclinical questions we hope researchers will be eager to tackle."

"Dying is not the only bad outcome from COVID-19," says Newman. "Some survivors are presenting with long-term severe memory impairments, extreme exhaustion and weakness from muscle wasting following an extended time in the hospital." Pointing out the fact that BHB and other ketones act on multiple systems in the body, the authors are hoping for clinical studies that test ketone supplementation as a way to bolster muscle function and attenuate or avoid delirium among those who have been infected. Key preclinical and clinical questions are included in the review and are detailed at http://www.impactmetabolism.org.

"Age-related risk factors are putting older adults at particular peril for COVID-19. Those that survive it, no matter what their age, can emerge with symptoms that are associated with aging," said Newman. "Studying ketone bodies in this current environment not only holds promise in the fight against COVID-19, but the research is also likely to yield results that could help all of us live better longer in the absence of a pandemic."

July 15, 2020 - Since the start of the COVID-19 pandemic, thousands of Americans have had to delay recommended but elective orthopedic surgical procedures, such as joint replacement surgery or knee arthroscopy. Now an expert panel has issued recommendations to guide safe resumption of elective orthopedic surgery. The guidelines appear in the July 15, 2020 issue of The Journal of Bone & Joint Surgery, published in the Lippincott portfolio in partnership with Wolters Kluwer.

"As we resume elective surgical procedures, it is important to understand what practices and protocols should be altered or implemented in order to minimize the risk of pathogen transfer during the severe acute respiratory syndrome (SARS)-CoV-2 pandemic," according to the guideline statement by the International Consensus Group and Research Committee of the American Association of Hip and Knee Surgeons. The lead author is Javad Parvizi, MD, FRCS, of the Rothman Institute, Philadelphia.

The recommendations were developed using the Delphi method, including two rounds of voting on the gleaned recommendations from the literature, explains Prof. Bill Walter of Royal North Shore Hospital, Sydney, another senior author on the study. Following this method, the consensus guidelines were approved by an international panel of 77 expert physicians and scientists in orthopedic surgery, infectious disease, microbiology and virology, and anesthesia.

Coronavirus Spurs Changes in Managing Elective Orthopedic Surgery
The guidelines "are based on the available scientific evidence, albeit scant," and will likely change with the rapidly evolving understanding of COVID-19. The guideline statement presents a set of 30 recommendations in four categories:

General. The guidelines include criteria for when hospitals and surgical centers can resume elective procedures, based on factors such as local trends in COVID-19 cases and availability of personal protective equipment and testing supplies. "The prevalence of COVID-19 in the local community will have a big impact on how these recommendations are implemented," said Prof. Walter.

"Patients who are currently infected with COVID-19 should not undergo elective surgery," the expert panel writes. They also state that surgery should be "possibly deferred in the early phases" in elderly patients (75 years or older) and those with health problems that put them at a high risk for COVID-19.

Preoperative. Several added steps in the preadmission process are recommended, including screening for symptoms of COVID-19, wearing masks, practicing social distancing, and limiting family members and visitors in the hospital. In areas with a high prevalence of SARS-CoV-2, mandatory diagnostic testing is recommended before elective surgery. Currently, there is no evidence to recommend SARS-CoV-2 antibody testing before surgery.

"It is critical for patients undergoing elective surgery to be educated on the protocols that are in place to minimize SARS-CoV-2 transmission to themselves, family members, other patients, and hospital personnel," the expert panel writes.

Intraoperative. The intraoperative section includes recommendations for carrying out surgery-addressing factors like operating room ventilation systems, necessary personal protective equipment, cleaning of the operating room between procedures, and more. The guidelines suggest considering regional anesthesia, when possible, to avoid aerosolizations and the increased risk of virus transmission that may occur with intubation during general anesthesia. Other recommendations include the use of absorbable sutures or skin glue, occlusive dressing and so on, all aimed at reducing the need for patients' return to the office in the early postoperative period.

Postoperative. Postoperative recommendations include safeguards in the post-anesthesia care unit, such as wearing masks and putting distance between patients. Length of hospital stay should be minimized, and follow-up visits should be carried out via telemedicine, when possible.

The expert panel hopes their recommendations will be helpful in resuming recommended elective surgical procedures in patients with painful, potentially disabling orthopedic conditions. The task force emphasizes: "Each hospital and health system should consider their unique situation in terms of SARS-CoV-2 prevalence, staffing capabilities, personal protection equipment supply, and so on when determining how and when to implement these recommendations."

LOS ANGELES - Researchers from USC and UCLA have found that exposure to flaring -- the burning off of excess natural gas -- at oil and gas production sites is associated with 50% higher odds of preterm birth, compared with no exposure.

"Our study finds that living near flaring is harmful to pregnant women and babies," said Jill Johnston, an environmental health scientist at the Keck School of Medicine of USC. "We have seen a sharp increase in flaring in Texas' Eagle Ford Shale, and this is the first study to explore the potential health impacts."

The research appears July 15 in the journal Environmental Health Perspectives.

The study examined 23,487 live births to women living within the Eagle Ford region between 2012 to 2015. The Eagle Ford Shale geological formation, measuring 50 miles wide and 400 miles long, is one of the most productive oil and gas regions in the country due to hydraulic fracturing or "fracking." In a previous study, the research team estimated the area was subject to more than 43,000 flaring events between 2012 and 2016.

Flares, which can burn for weeks at a time, have been shown to release chemicals such as benzene as well as fine particle pollution, carbon monoxide, nitrogen oxides, heavy metals and black carbon. Several of these combustion-related pollutants have been associated with a higher risk of preterm birth and reduced birthweight in other contexts.

Of the births analyzed by researchers, 10.6% were preterm, occurring before the 37th completed week of pregnancy. Preterm birth is associated with complications such as immature lungs, difficulty regulating body temperature, poor feeding and slow weight gain.

The researchers used satellite observations to measure flaring activity because systemic reporting of flaring is lacking. They adjusted for other known risk factors for preterm birth in their analysis, including age, smoking, insurance status and access to prenatal care, and concluded that exposure to a high amount of flaring was associated with 50% higher odds of preterm birth compared with no exposure. A high amount of flaring was defined as 10 or more nightly flare events within three miles of the pregnant woman's home.

"Women who identified as Latina or Hispanic in our study were exposed to more flaring and more likely to see an increased risk of preterm birth, raising environmental justice concerns about the oil and gas boom in south Texas," said Lara Cushing, an environmental health scientist with the UCLA Fielding School of Public Health who co-led the study with Johnston. "Our study adds to the evidence that oil and gas development is negatively impacting birth outcomes and suggests stricter regulation of the industry is needed."

Women who lived within three miles of a high number of oil and gas wells also had higher odds of a preterm birth than mothers who did not live near wells. Their babies were also born weighing 19.4 grams, or seven ounces, lighter on average. This suggests that, in addition to flaring, other exposures related to oil and gas wells may also be adversely impacting pregnancy, the researchers said.

The majority (55%) of the women in the study population identified as Latina or Hispanic, and the odds of preterm birth among Hispanic women exposed to high levels of flaring was greater than the corresponding odds among non-Hispanic White women, who made up 37% of the study population. Nearly 60% of women in the study were on public health insurance (Medicaid) and 17% were foreign born.

In recent years, the U.S. has been responsible for the highest number of flares of any country, flaring an estimated 14.1 billion square meters of natural gas in 2018. Eighty percent of flaring is occurring in Texas and in North Dakota shale plays, where much of the U.S. fracking occurs. That said, according to researchers, flaring largely remains underreported and unregulated.

The COVID-19 pandemic is having a disproportionate, negative impact on the careers of scientists with young children at home, a new survey finds.

Researchers at Northwestern University's Kellogg School of Management led the study, finding broad discrepancies in the pandemic's impact on scientists. Most notably, researchers with young children have been forced to drastically reduce the amount of time they spend on their research, which could have long-term effects on their careers and could exacerbate existing inequalities.

While the majority of survey respondents reported reduced work hours after the start of the pandemic, those with at least one child under the age of five reported a 17% greater reduction compared to peers without young dependents. Such a reduction could lead to fewer publications for those scientists, potentially affecting tenure decisions and driving other long-lasting career impacts.

"We're truly in the biggest crisis of our generation, yet we know so little about how the COVID-19 pandemic is impacting our professional career paths," said corresponding author Dashun Wang, associate professor and director of Northwestern's Center for the Science of Science and Innovation. "The need to care for dependents is clearly not unique to the scientific workforce, so these results may also be relevant for broader labor categories and may have broad relevance for shaping a more effective response to the pandemic's impact in science and beyond."

The research was published today (July 15) in Nature Human Behaviour. Kyle Myers of Harvard University is lead author. Co-authors include researchers from Harvard and Yale University.

Research findings are based on more than 4,000 responses to a survey sent to scientists in Europe and the United States in mid-April. The survey solicited information about how scientists' work changed from the onset of the pandemic and how their research output might be affected in the near future.

It also included questions about a wide range of individual characteristics, including field of study, career stage (e.g. tenure status), demographics (e.g. age, gender, number and age of dependents in the household) and other relevant factors such as institutional closures and personal exemptions from said closures.

The researchers also found broad differences in work impact based on gender and field of study. For example, women reported a larger reduction in work hours compared to men, and scientists who study the laboratory sciences, such as chemistry and biology, reported a larger reduction compared to scientists in fields such as statistics or economics.

"Institutions that don't take into account this varied impact likely will fare worse than those that do," Wang said, noting that policies such as extending the tenure clock for all faculty, while well-meaning, could exacerbate existing inequalities. "The main challenge is that in science, the production cycle drastically outlasts the time window required for an effective response, so by the time the impact becomes apparent, it is often too late to respond."

The researchers suggest that policymakers, at both the government and institutional levels, should work to better understand how pandemic response policies impact various groups so they can better design policy responses that help those who need it most.

"The pandemic has caused us to look at the issue of childcare in a new way," Wang said. "We have so far overlooked the stark difference between work-from-home and shelter-at-home, with the latter implying that dependents are also at home and need care."

Researchers at the University of East Anglia and University of Manchester have made an important breakthrough that could lead to 'kinder' treatments for children with bone cancer, and save lives.

Current treatment is gruelling, with outdated chemotherapy cocktails and limb amputation. But despite all of this, the five-year survival rate is poor at just 42 per cent - largely because of how rapidly bone cancer spreads to the lungs.

New research published today identifies a set of key genes that drive bone cancer spread to the lungs in patients. In further experiments in mice with engineered human bone cancer cells that lack these key genes, the cancer cannot spread to the lungs.

The research was led by Dr Darrell Green, from UEA's Norwich Medical School and Dr Katie Finegan from the University of Manchester.

Darrell was inspired to study childhood bone cancer after his best friend died from the disease as a teenager. Now, the team has made what could be the most important discovery in the field for more than 40 years.

Dr Green said: "Primary bone cancer is a type of cancer that begins in the bones. It's the third most common solid childhood cancer, after brain and kidney, with around 52,000 new cases every year worldwide.

"It can rapidly spread to other parts of the body, and this is the most problematic aspect of this type of cancer. Once the cancer has spread it is very difficult to treat.

"Around a quarter of patients have cancer that has already spread by the time they are diagnosed. Around half of patients with apparent localised disease relapse, with cancer spread detected later on. These figures have remained stagnant, with no significant breakthroughs in treatment, for more than four decades.

"In high school, my best friend Ben Morley became ill with primary bone cancer. His illness inspired me to do something about it myself because during my studies I realised that this cancer has been all but left behind others in terms of research and treatment progress. So I studied and went through university and obtained my PhD to eventually work in primary bone cancer.

"I want to understand the underlying biology of cancer spread so that we can intervene at the clinical level and develop new treatments so that patients won't have to go through the things my friend Ben went through. Ultimately we want to save lives and reduce the amount of disability caused by surgery."

The research team investigated the most common type of primary bone cancer called osteosarcoma.

The genetic drivers that cause osteosarcoma are well known (TP53 and RB1 structural variants) but much less is known about what drives its spread to other parts of the body.

Dr Green said: "Because primary bone cancer spreads so fast to other parts of the body, it's very important to solve exactly why this happens.

"We developed new technology to isolate circulating tumour cells in the blood of patients. These cells are critical for scientific study because they effectively carry out the metastatic process. This was extremely challenging because there is only one such cell per billion normal blood cells - it took over a year to develop but we cracked it.

"It was also challenging because most studies investigating circulating tumour cells are performed in common adult cancers where the methods significantly differ because the cancer biology is so different.

"Osteosarcoma is a less common sarcoma cancer so we had to start from scratch to not only find these cells in the first place, but to keep them alive so we could profile their gene expression."

After profiling tumours, circulating tumour cells (CTCs) and metastatic tumours from patient donors, they were able to identify a potential driver for metastasis - known as MMP9.

Dr Green said: "This driver that we identified is well known in cancer, but it is also considered 'un-druggable' because the cancer quickly becomes resistant to treatment, or it finds a way to escape being targeted.

"So we thought we would try something a bit clever and find the 'master regulator' of MMP9 so that we could 'action' the 'un-actionable'."

The team began collaborating with researchers at the University of Manchester who were working on the proposed master regulator of MMP9 - MAPK7 - in several cancers using mouse models including osteosarcoma.

Together, they engineered human osteosarcoma cells to contain a silenced version of MAPK7. They found that when these cells were put into mice, the primary tumour grew much more slowly. Importantly, it didn't spread to the lungs - even when the tumours were left to grow for a long time.

"Getting even deeper, our study shows that silencing MAPK7 stopped metastasis because that gene pathway was hijacking a particular part of the immune system that caused the spread," said Dr Green.

"This is really important because not only do we now have a gene pathway associated with metastasis, we know that removing this gene pathway actually stops cancer spread in a live animal. And we also know how and why this is happening - through hijacking the immune system.

"The next step already gearing up to take place is to silence this pathway in treatment form, now that we have shown how critical this pathway is.

"If these findings are effective in clinical trials, it would no doubt save lives and improve quality of life because the treatment should be much kinder, compared to the gruelling chemotherapy and life changing limb amputation that patients receive today."

Senior author Dr Katherine Finegan from the University of Manchester said: "It has been great to work together with Darrell and the team at UEA. This is the first output from a new co-operative we have set up to tackle the significant unmet need that is finding an effective treatment once osteosarcoma has spread. This co-operative called OMeNet brings together researchers from across the UK to cohesively study the spread of osteosarcoma and expedite the discovery of new treatments.

"Using Darrell's genetic insights from patient material, we were able to validate their work in models of primary bone cancer. As a result, we have highlighted a potential new way to treat metastatic bone cancer by targeting a key protein that promotes metastases: MAPK7.

This work has uncovered a novel treatment option for osteosarcoma, something we have not had for the last 40 years.

"In the Finegan lab we are already in the process of developing new drugs against MAPK7, which we hope to implement for the benefit of primary bone cancer patients in the future.

"We would also like to thank the charity Friends of Rosie who funded the work in the Manchester lab and support childhood cancer research here in the North West."

Super Strong Sophie

One of the patients who donated tissue to the study was five-year-old 'Super Strong' Sophie Taylor from Norwich. She was first diagnosed with osteosarcoma in January 2018, and underwent surgery to amputate part of her leg, as well as chemotherapy.

Sadly Sophie was taken to hospital with breathing difficulties a year after diagnosis at the beginning of January 2019, where her family were told there was extensive cancer in her lungs. She passed away on January 18, 2019.

Sophie's dad Alex Taylor said: "Sophie was diagnosed with Osteosarcoma in January 2018. Unfortunately it was in her lungs at the time it was found.

"When we were informed necrosis from chemotherapy was low we embarked on finding additional options and were fortunate to come into contact with Dr Darrell Green.

"We did not hesitate in offering Sophie's tumour for research and to also have her DNA and RNA analysed to link it to additional drugs to pursue. It gave us hope and it was amazing to have Darrell fighting in our corner.

"Unfortunately the way Sophie's journey panned out we didn't get to try the options we put on the table but we are extremely pleased that Sophie has been able to help in the way she did.

"We will continue to support Darrell and the work he does and Sophie's future charity will aim to support the continuation of bone cancer research so future Sophies get a better outcome.

"We are delighted Darrell's work is being recognised, he is a remarkable man and we are really grateful for his support during treatment, after treatment and since Sophie's passing. He truly deserves the credit and recognition he receives.

"Sophie was simply a child from out of this world, she demonstrated strength and courage beyond comprehension and deserved a much better outcome. She had her leg amputated, months of hard chemotherapy, nursed an awful wound from surgery and just got on with it, fulfilling a range of achievements including going to the top of Snowdon, playing football with and becoming close friends Leicester City's James Maddison, and she inspired many people around the world. We are so proud of how she fought and even more so that she has contributed to research which will be lifesaving for future children.

"We will add this to her legacy and share it with pride and will continue to 'takeasophie' and stick our tongue out at cancer just like Sophie did. Thank you Darrell and well done that your immense hard work is paying off, we are very proud of you."

CLEVELAND, Ohio (July 15, 2020)--Abdominal weight gain, which is common during the postmenopause period, is associated with an array of health problems, including diabetes and heart disease. A new study suggests that the use of antidepressants, beta-blockers, and insulin during the menopause transition is partially to blame for such unhealthy weight gain. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Many medications prescribed for hypertension, diabetes, depression, and/or other mental health problems are associated with unintentional weight gain. Unfortunately, postmenopausal women, who already have a high prevalence of being overweight or obese, are more likely to be treated with weight-promoting medications for these various health problems at the time of the menopause transition. In this new study based on data collected from women who participated in the Women's Health Initiative, researchers sought to quantify the magnitude of the association between weight-promoting medications and a 3-year weight change in postmenopausal women.

The study measured body mass index (BMI) and waist circumference at baseline and at 3 years and cross-checked the results with an inventory of prescribed medicines, including antidepressants, beta-blockers, insulin, and/or glucocorticosteroids. On the basis of these results, the researchers concluded that taking at least one weight-promoting medication was associated with a greater increase in BMI and waist circumference compared with women not on these medications. Both of these measurements increased with the number of weight-promoting drugs prescribed. Those who took either antidepressants or insulin, or a combination of antidepressants and beta-blockers, were most likely to have a significant increase in BMI compared with nonusers. Racial and ethnic minority women--groups with a higher weight at baseline--also were more susceptible to weight gain associated with the use of prescription medications.

In response to the study's results, the researchers suggest a need for healthcare providers to be more vigilant when prescribing various medications to postmenopausal women. Specifically, healthcare providers need to determine whether various medications are absolutely necessary, whether alternative options are available, and whether the lowest dose is being prescribed to provide the desired results.

Study results appear in the article "The association between weight-promoting medication use and weight gain in postmenopausal women: findings from the Women's Health Initiative."

"This study highlights the significant adverse health effects of obesity and the association between use of weight-promoting medications such as antidepressants, antihypertensives, and insulin and weight gain in midlife women. In addition to ensuring that these weight-promoting medications are used judiciously and in the lowest doses needed to achieve the desired outcomes, lifestyle strategies to mitigate these adverse effects, such as diet quality, physical activity level, and sleep quality and duration, should be emphasized," says Dr. Stephanie Faubion, NAMS medical director.

OAK BROOK, Ill. - Cardiac CT exams performed to assess heart health also provide an effective way to screen for osteoporosis, potentially speeding treatment to the previously undiagnosed, according to a study published in Radiology.

Osteoporosis is a disease that causes the bones to weaken and become vulnerable to fracture. It affects an estimated 200 million people worldwide. Early detection and treatment are important, as several classes of drugs are effective at reducing the risk of fractures that exact a devasting toll on victims. A National Osteoporosis Foundation report last year found that nearly 20 percent of Medicare fee-for-service beneficiaries died within 12 months of a new osteoporotic fracture.

Bone mineral density (BMD) tests can diagnose osteoporosis, but the number of people who get these tests is suboptimal.

"Osteoporosis is a prevalent, under-diagnosed and treatable disease associated with increased morbidity and mortality," said study lead author Josephine Therkildsen, M.D., from Herning Hospital, Hospital Unit West, in Herning, Denmark. "Effective anti-osteoporotic treatment exists and so, identifying individuals with greater fracture rate who may benefit from such treatment is imperative."

Dr. Therkildsen and colleagues recently looked at cardiac CT, a test done to assess heart health, as an opportunistic way to screen for osteoporosis. Because the cardiac CT scan also visualizes the thoracic vertebrae, the bones that form the vertebral spine in the upper trunk, it is relatively easy to add a BMD test to the procedure.

The study involved 1,487 participants who underwent cardiac CT for evaluation of heart disease. Participants also had BMD testing of three thoracic vertebrae using quantitative CT software.

Of the 1,487 people in the study, 179, or 12%, had very low BMD. During follow-up of just over three years on average, 80 of the participants, or 5.3%, were diagnosed with a fracture. The fracture was osteoporosis-related in 31 of the 80 people.

The association between a very low BMD and a higher rate of fracture strongly suggests that thoracic spine BMD may be used to guide osteoporosis preventive measures and treatment decisions, the study authors said.

Adding BMD testing to cardiac CT is feasible and applicable in a clinical setting, according to Dr. Therkildsen. It does not add time to the exam and doesn't expose the patient to any additional radiation. In fact, Dr. Therkildsen said, technological advances over time have reduced the radiation dose given at cardiac CT. BMD measurements can be made using existing non-enhanced CT images as long as a suitable calibration system is ensured, scanner stability is continuously monitored and systematic imaging acquisition techniques are implemented.

"We believe that opportunistic BMD testing using routine CT scans can be done with little change to normal clinical practice and with the benefit of identifying individuals with a greater fracture rate," Dr. Therkildsen said.

Although the researchers used cardiac CT images in the study, in theory any CT images that include a view of relevant bone structures could be used for measuring BMD. The development of fully automated software for BMD measurements further enhances the adaptability and convenience of this approach.

Additional research will help pin down the optimal BMD cut-off values for treatment while providing more data on fracture risk based on gender and areas of the body. The impact of clinical risk factors in combination with BMD measured from CT scans for the assessment of fracture risk would also benefit further study.

"Our research group is dedicated to extend the research in this field, as we believe it should be added to clinical practice," Dr. Therkildsen said.