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SharecloseShare pageCopy linkAbout sharingimage copyrightPA MediaAll over-50s and those in high-risk groups in the UK have now been offered a first dose of a coronavirus vaccine, the government has announced. It means ministers have met their target of offering a first dose to the top nine priority groups by 15 April. The government said it was on track to offer a first dose to all adults by the end of July, with those in their late 40s expected to be next in England. More than 32 million people in the UK have had their first dose. And on Saturday a record 475,230 second doses were given out, with more than 7.6 million people now fully vaccinated.Under-50s in Northern Ireland have already been asked to book appointments, and more people in the age group in other parts of the UK are now set to get their invitations.When will over-40s get the jab?How many people have been vaccinated so far?UK sets new record for Covid jab second dosesPrime Minister Boris Johnson described the news the vaccination target had been reached as “another hugely significant milestone in our vaccine programme”. “We will now move forward with completing essential second doses and making progress towards our target of offering all adults a vaccine by the end of July.”Health Secretary Matt Hancock said: “I’m delighted the team have done such an amazing job to hit yet another target early.”The tide of this pandemic is turning in every part of the UK, as every day more and more people are being given the safety of a Covid-19 vaccine.” ‘Supply is a key variable for what happens next’Given how quickly the vaccination programme has been rolled out in the UK, hitting the target of all priority groups by mid-April is not unexpected. And remember, there is no published data on the number of people offered jabs, as opposed to those who have actually been vaccinated. However, NHS England has made clear that across the nine groups, 95% have actually had their first doses – that is an average, with take-up rates varying in different groups.The key question is: where next? Pending the advice of the Joint Committee on Vaccination and Immunisation, ministers seem set to give the all-clear for invitations to go out to people in their late 40s. But what’s not known is to what extent supplies of Pfizer and Moderna vaccines will fill the gap caused this month by supply problems with the AstraZeneca doses. The government is sticking to the line that the programme is on track to offer every adult a first dose by late July. But officials qualify it by saying this is “subject to supply” – and that is a key variable.Urging those who are eligible to come forward for the jab, he added: “Vaccines are safe and effective and have already saved more than 10,000 lives. “The vaccine programme has had a significant impact on reducing the pressure on hospitals, helping us to gradually ease restrictions.”Sir Simon Stevens, chief executive of NHS England, said it was an “incredible achievement” to have vaccinated 19 out of 20 people aged over-50 with a first dose.He said the vaccination programme was “without a doubt the most successful in our history”, adding: “It’s one of our tickets out of this pandemic and offers real hope for the future.”The announcement came on the day lockdown restrictions were further eased across the UK.Chris Hopson, chief executive of NHS Providers, representing NHS Trusts, urged people offered a vaccine to take it up, saying: “As we return to pub gardens and sports activities and make our way back to non-essential shops, we must continue do all that we can to prevent the spread of infection and ensure this lockdown will be the last.”The top nine priority groups include all over-50s, over-16s with underlying health conditions, unpaid carers for the elderly and disabled and health and social care workers. It covers 99% of those at high risk of dying with Covid-19.The vaccination roll-out will move on to focus on those aged 40-49.The Joint Committee on Vaccination and Immunisation (JCVI), which advises UK health departments, is expected to publish its final advice on how the government should vaccinate under-50s, and the next phase of the programme is expected to begin this week.NHS organisations in the four nations, in collaboration with devolved administrations, will decide how to carry out the JCVI advice. Last week the Moderna vaccine became the third vaccine to be administered in the UK, alongside the Pfizer-BioNTech and the Oxford-AstraZeneca jabs. The roll-out began in Wales, followed by Scotland, and is expected to be delivered in England next.All under-30s in the UK are to be offered an alternative Covid vaccine to the AstraZeneca jab due to the evidence linking it to rare blood clots.On Monday, the UK recorded 3,568 new coronavirus cases and 13 deaths within 28 days of a positive test. It comes after pub gardens, non-essential shops and hairdressers reopened in England. Northern Ireland’s “stay at home” order also ended on Monday, while in Wales non-essential shops and close-contact services reopened. In Scotland, non-essential shops and hospitality are not due to open until 26 April. Meanwhile, surge testing has been implemented in the Wandsworth and Lambeth areas of south London after a cluster of the South African Covid-19 variant was found. The Department of Health and Social Care called it the “largest surge testing operation to date” following the identification of 44 confirmed and 30 probable cases.LOOK-UP TOOL: How many cases in your area?LOCKDOWN RULES: What are they and when will they end?SOCIAL DISTANCING: How can I meet my friend safely? OXFORD JAB: What is the Oxford-AstraZeneca vaccine?A LIFE CHANGED IN SECONDS: “I’d been living my perfect life”EXTRA-TERRESTRIAL LIFE: Is suggesting evidence of aliens worth jeopardising a career?

Many patients with cancer receive immune checkpoint inhibitors that strengthen their immune response against tumor cells. While the medications can be life-saving, they can also cause potentially life-threatening side effects in internal organs. This double-edged sword makes it challenging for clinicians to decide who should be considered candidates for treatment. A new analysis led by researchers at Massachusetts General Hospital (MGH) indicates which patients are at elevated risk of side effects severe enough to require hospitalization. The findings are published in the Journal for ImmunoTherapy of Cancer.
“Understanding the risk factors for predicting high-grade toxicities will help in appropriately selecting patients most likely to tolerate immune checkpoint inhibitor therapy,” says co-senior author Yevgeniy R. Semenov, MD, an investigator in the Department of Dermatology at MGH. “It will also help to identify higher risk patients who should be carefully monitored if they initiate this therapy.”
To this end, Semenov and his colleagues analyzed information from a national health insurance claims database, identifying 14,378 patients with cancer who received immune checkpoint inhibitors in the United States between 2011 and 2019. The team found that 3.5% of patients who received immune checkpoint inhibitors experienced side effects that required patients to be hospitalized and to receive immunosuppression treatments (to counteract the effects of the immune checkpoint inhibitors).
“We found that younger age, melanoma, and kidney cancer were each predictive of the development of severe immunotherapy toxicities,” says Semenov. Patients also faced a higher risk if they received multiple immune checkpoint inhibitors, rather than just one type.
“This study provides the foundation for studying severe immunotherapy toxicities using a Big Data analytic framework, which will be necessary when understanding the impact of these life-saving medications across diverse populations,” says Semenov. “Also, it is the first step in developing robust clinical risk prediction models to identify patients at highest risk for the development of life-threatening treatment complications.”
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Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

Immune checkpoint inhibitors, which boost the immune system’s response against tumor cells, have transformed treatment for many advanced cancers, but short-term clinical trials and small observational studies have linked the medications with various side effects, most commonly involving the skin. A more comprehensive, population-level analysis now provides a thorough look at the extent of these side effects and provides insights on which patients may be more likely to experience them. The research was led by investigators at Massachusetts General Hospital (MGH) and is published in the Journal of the American Academy of Dermatology.
“Immunotherapies, which include immune checkpoint inhibitors, are an increasingly common treatment modality for advanced cancers, with more than 200,000 patients being started on these therapies annually,” says co-senior author Yevgeniy R. Semenov, MD, an investigator in the Department of Dermatology at MGH. “As the use of immune checkpoint inhibitors increases, so will the incidence of adverse events, underscoring the importance of research into their incidence, type and severity.”
Semenov and his colleagues used a “Big Data” approach to study the U.S. prevalence of skin-related side effects, as well as when they arise and how they’re treated, in a large population of patients who received immune checkpoint inhibitors.
The study involved analyzing information from a national health insurance claims database pertaining to 8,637 patients who were treated with immune checkpoint inhibitors as well as an equal number of patients with cancer who did not receive these medications. The overall incidence of skin-related side effects was 25.1%, with a median time of onset of 113 days. “We found that only 10 of more than 40 skin conditions previously reported to be linked to immune checkpoint inhibitors are actually seen at a higher incidence among patients on these medications compared with other patients who were matched by demographics, cancer type and comorbidities,” says Semenov.
These conditions manifested with symptoms of itching, inflammation, rash, skin color loss, swelling or blisters. Patients with melanoma or kidney cancer and those receiving multiple types of immune checkpoint inhibitors were at an especially high risk of developing these skin problems.
The investigators’ real-world data also found that skin-related symptoms tended to arise later than those noted in clinical trials. In addition, they found that clinicians often prescribed systemic corticosteroids to treat them even though these drugs should generally be avoided due to concerns that they may blunt the anti-tumor effects of immunotherapy.
“These findings are of particular clinical relevance to both dermatologists and oncologists caring for patients receiving immune checkpoint inhibitors,” says Semenov. For example, clinicians should be on the lookout for the 10 conditions identified in this analysis as patients continue taking these medications. “The real-world delays in the time to presentation of many of these conditions should also revise clinicians’ understanding of when to expect patients to present with these toxicities and not to rule out a delayed onset of symptoms as being unrelated to immunotherapy,” adds Semenov.
The findings also suggest an opportunity for improving care for patients, he says: “Dermatologists can work with oncologists to facilitate evaluations of these vulnerable patients so that they can take steps to prevent progression to more severe toxicities.”
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Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

When winter storms threaten to make travel dangerous, people often turn to salt, spreading it liberally over highways, streets and sidewalks to melt snow and ice. Road salt is an important tool for safety, because many thousands of people die or are injured every year due to weather related accidents. But a new study led by Sujay Kaushal of the University of Maryland warns that introducing salt into the environment — whether it’s for de-icing roads, fertilizing farmland or other purposes — releases toxic chemical cocktails that create a serious and growing global threat to our freshwater supply and human health.
Previous studies by Kaushal and his team showed that added salts in the environment can interact with soils and infrastructure to release a cocktail of metals, dissolved solids and radioactive particles. Kaushal and his team named these cascading effects of introduced salts Freshwater Salinization Syndrome, and it can poison drinking water and cause negative effects on human health, agriculture, infrastructure, wildlife and the stability of ecosystems.
Kaushal’s new study is the first comprehensive analysis of the complicated and interconnected effects caused by Freshwater Salinization Syndrome and their impact on human health. This work suggests that the world’s freshwater supplies could face serious threats at local, regional and global levels if a coordinated management and regulation approach is not applied to human sources of salt. The study, which calls on regulators to approach salts with the same level of concern as acid rain, loss of biodiversity and other high-profile environmental problems, was published April 12, 2021, in the journal Biogeochemistry.
“We used to think about adding salts as not much of a problem,” said Kaushal, a professor in UMD’s Department of Geology and Earth System Science Interdisciplinary Center. “We thought we put it on the roads in winter and it gets washed away, but we realized that it stuck around and accumulated. Now we’re looking into both the acute exposure risks and the long-term health, environmental, and infrastructure risks of all these chemical cocktails that result from adding salts to the environment, and we’re saying, ‘This is becoming one of the most serious threats to our freshwater supply.’ And it’s happening in many places we look in the United States and around the world.”
When Kaushal and his team compared data and reviewed studies from freshwater monitoring stations throughout the world, they found a general increase in chloride concentrations on a global scale. Chloride is the common element in many different types of salts like sodium chloride (table salt) and calcium chloride (commonly used for road salt). Drilling down into data from targeted regions, they also uncovered a 30-year trend of increasing salinity in places like the Passaic River in northern New Jersey and a 100-mile-plus stretch of the Potomac River that supplies drinking water to Washington, D.C.
The major human-related salt source in areas such the Northeastern U.S. is road salts, but other sources include sewage leaks and discharges, water softeners, agricultural fertilizers and fracking brines enriched with salts. In addition, indirect sources of salts in freshwater include weathering roads, bridges and buildings, which often contain limestone, concrete or gypsum, all of which release salt as they break down. Ammonium-based fertilizers can also lead to the release of salts in urban lawns and agricultural fields. In some coastal environments, sea-level rise can be another source of saltwater intrusion.

Spanking may affect a child’s brain development in similar ways to more severe forms of violence, according to a new study led by Harvard researchers.
The research, published recently in the journal Child Development, builds on existing studies that show heightened activity in certain regions of the brains of children who experience abuse in response to threat cues.
The group found that children who had been spanked had a greater neural response in multiple regions of the prefrontal cortex (PFC), including in regions that are part of the salience network. These areas of the brain respond to cues in the environment that tend to be consequential, such as a threat, and may affect decision-making and processing of situations.
“We know that children whose families use corporal punishment are more likely to develop anxiety, depression, behavior problems, and other mental health problems, but many people don’t think about spanking as a form of violence,” said Katie A. McLaughlin, John L. Loeb Associate Professor of the Social Sciences, director of the Stress & Development Lab in the Department of Psychology, and the senior researcher on the study. “In this study, we wanted to examine whether there was an impact of spanking at a neurobiological level, in terms of how the brain is developing.”
According to the study’s authors, corporal punishment has been linked to the development of mental health issues, anxiety, depression, behavioral problems, and substance use disorders. And recent studies show that approximately half of parents in U.S. studies reported spanking their children in the past year and one-third in the past week. However, the relationship between spanking and brain activity has not previously been studied.
McLaughlin and her colleagues — including Jorge Cuartas, first author of the study and a doctoral candidate in the Harvard Graduate School of Education, and David Weissman, a post-doctoral fellow in the Department of Psychology’s Stress & Development Lab — analyzed data from a large study of children between the ages of three and 11. They focused on 147 children around ages 10 and 11 who had been spanked, excluding children who had also experienced more severe forms of violence.

The state of Pennsylvania and the city of Los Angeles are accelerating plans for wider Covid-19 vaccine eligibility this week, as the United States approaches universal eligibility for adults.Most states and U.S. territories have already expanded access to include anyone over 16. Others, including Massachusetts, New Jersey, Oregon and Washington state, have plans in place for universal adult access to start in the next few days. All states are expected to get there by Monday, a deadline set by President Biden.Some states have local variations in eligibility, including Illinois, where Chicago did not join a statewide expansion that began Monday.California as a whole has set Thursday as its date, but Mayor Eric Garcetti of Los Angeles said on Sunday that all residents age 16 or older in his city, the nation’s second largest, would become eligible two days earlier. In Pennsylvania, Gov. Tom Wolf said on Monday that all adults there would be eligible on Tuesday, six days earlier than previously planned.“We need to maintain acceleration of the vaccine rollout, especially as case counts and hospitalization rates have increased,” Mr. Wolf said in a statement.Expanded eligibility has not always brought immediate access. Demand for vaccination continues to outstrip supply in much of the nation, with people scrambling to book scarce appointments as they become available. And supplies of Johnson & Johnson’s one-dose vaccine will be extremely limited until federal regulators approve production at a Baltimore manufacturing plant with a pattern of quality-control lapses, the White House’s pandemic response coordinator said on Friday.“We urge patience as we continue to ramp up our operations, obtain more doses, and enter this new phase of our campaign to end the pandemic,” Mr. Garcetti said.More than 119 million people — or more than one-third of the U.S. population — have now received at least one dose of a Covid-19 vaccine, according to the Centers for Disease Control and Prevention. The nation is administering about 3 million doses a day on average.Two of the three vaccines authorized for use in the U.S. — those made by Moderna and Johnson & Johnson — are authorized for use in adults. The third, from Pfizer-BioNTech, is authorized for anyone 16 or older, and the company is seeking to expand that range to include youths 12 to 15. No vaccine has yet been authorized for use in younger children.When All Adults Are Eligible for the Vaccine in Each StateSee more detail on eligibility in your state as of April 9 »

A new algorithm can predict which genes cause cancer, even if their DNA sequence is not changed. A team of researchers in Berlin combined a wide variety of data, analyzed it with “Artificial Intelligence” and identified numerous cancer genes. This opens up new perspectives for targeted cancer therapy in personalized medicine and for the development of biomarkers.
In cancer, cells get out of control. They proliferate and push their way into tissues, destroying organs and thereby impairing essential vital functions. This unrestricted growth is usually induced by an accumulation of DNA changes in cancer genes — i.e. mutations in these genes that govern the development of the cell. But some cancers have only very few mutated genes, which means that other causes lead to the disease in these cases.
A team of researchers at the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin and at the Institute of Computational Biology of Helmholtz Zentrum München developed a new algorithm using machine learning technology to identify 165 previously unknown cancer genes. The sequences of these genes are not necessarily altered — apparently, already a dysregulation of these genes can lead to cancer. All of the newly identified genes interact closely with well-known cancer genes and have been shown to be essential for the survival of tumor cells in cell culture experiments.
Additional targets for personalized medicine
The algorithm, dubbed “EMOGI” for Explainable Multi-Omics Graph Integration, can also explain the relationships in the cell’s machinery that make a gene a cancer gene. As the team of researchers headed by Annalisa Marsico describe in the journal Nature Machine Intelligence, the software integrates tens of thousands of data sets generated from patient samples. These contain information about DNA methylations, the activity of individual genes and the interactions of proteins within cellular pathways in addition to sequence data with mutations. In these data, a deep-learning algorithm detects the patterns and molecular principles that lead to the development of cancer.
“Ideally, we obtain a complete picture of all cancer genes at some point, which can have a different impact on cancer progression for different patients,” says Marsico, head of a research group at the MPIMG until recently and now at Helmholtz Zentrum München. “This is the foundation for personalized cancer therapy.”
Unlike with conventional cancer treatments such as chemotherapy, personalized therapy approaches tailor medication precisely to the type of tumor. “The goal is to select the best therapy for each patient — that is, the most effective treatment with the fewest side effects. Additionally, we would be able to identify cancers already at early stages, based on their molecular characteristics.”

What exactly happens when the corona virus SARS-CoV-2 infects a cell? In an article published in Nature, a team from the Technical University of Munich (TUM) and the Max Planck Institute of Biochemistry paints a comprehensive picture of the viral infection process. For the first time, the interaction between the coronavirus and a cell is documented at five distinct proteomics levels during viral infection. This knowledge will help to gain a better understanding of the virus and find potential starting points for therapies.
When a virus enters a cell, viral and cellular protein molecules begin to interact. Both the replication of the virus and the reaction of the cells are the result of complex protein signaling cascades. A team led by Andreas Pichlmair, Professor of Immunopathology of Viral Infections at the Institute of Virology at TUM, and Matthias Mann, Head of the Department of Proteomics and Signal Transduction at the Max Planck Institute of Biochemistry, has systematically recorded how human lung cells react to individual proteins of the covid-19 pathogen SARS-CoV-2 and the SARS coronavirus, the latter of which has been known for some time.
A detailed interaction map
To this end, more than 1200 samples were analyzed using the state-of-the-art mass spectrometry techniques and advanced bioinformatic methods. The result is a freely accessible dataset that provides information on which cellular proteins the viral proteins bind to and the effects of these interactions on the cell. In total, 1484 interactions between viral proteins and human cellular proteins were discovered. “Had we only looked at proteins, however, we would have missed out on important information,” says Andreas Pichlmair. “A database that only includes the proteome would be like a map containing just the place names but no roads or rivers. If you knew about the connections between the points on that map, you could gain much more useful information.”
According to Pichlmair, important counterparts to the network of traffic routes on a map are protein modifications called phosphorylation and ubiquitination. Both are processes in which other molecules are attached to proteins, thereby altering their functions. In a listing of proteins, these changes are not measured, so that there is no way of knowing whether proteins are active or inactive, for example. “Through our investigations, we systematically assign functions to the individual components of the pathogen, in addition to the cellular molecules that are switched off by the virus,” explains Pichlmair. “There has been no comparable mapping for SARS-CoV-2 so far,” adds Matthias Mann. “In a sense, we have taken a close look at five dimensions of the virus during an infection: its own active proteins and its effects on the host proteome, ubiquitinome, phosphoproteome and transcriptome.”
Insights into how the virus works
Among other things, the database can also serve as a tool to find new drugs. By analyzing protein interactions and modifications, vulnerability hotspots of SARS-CoV-2 can be identified. These proteins bind to particularly important partners in cells and could serve as potential starting points for therapies. For example, the scientists concluded that certain compounds would inhibit the growth of SARS-CoV-2. Among them were some whose antiviral function is known, but also some compounds which have not yet been studied for efficacy against SARS-CoV-2. Further studies are needed to determine whether they show efficacy in clinical use against Covid-19.
“Currently, we are working on new anti Covid-19 drug candidates, that we have been able to identify through our analyses,” says Andreas Pichlmair. “We are also developing a scoring system for automated identification of hotspots. I am convinced that detailed data sets and advanced analysis methods will enable us to develop effective drugs in a more targeted manner in the future and limit side effects in advance.”
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Materials provided by Technical University of Munich (TUM). Note: Content may be edited for style and length.

When the COVID-19 pandemic hit in early 2020, many families found themselves suddenly isolated together at home. A year later, new research has linked this period with a variety of large, detrimental effects on individuals’ and families’ well-being and functioning.
The study — led by Penn State researchers — found that in the first months of the pandemic, parents reported that their children were experiencing much higher levels of “internalizing” problems like depression and anxiety, and “externalizing” problems such as disruptive and aggressive behavior, than before the pandemic. Parents also reported that they themselves were experiencing much higher levels of depression and lower levels of coparenting quality with their partners.
Mark Feinberg, research professor of health and human development at Penn State, said the results — recently published in the journal Family Process — give insight into just how devastating periods of family and social stress can be for parents and children, and how important a good coparenting relationship can be for family well-being.
“Stress in general — whether daily hassles or acute, crisis-driven stress — typically leads to greater conflict and hostility in family relationships,” Feinberg said. “If parents can support each other in these situations, the evidence from past research indicates that they will be able to be more patient and more supportive with their children, rather than becoming more harsh and angry.”
Feinberg added that understanding what can help parents maintain positive parenting practices, such as a positive coparenting relationship, is key for helping protect children during future crises — whether those crises are pandemics, economic shocks or natural disasters.
While cross-sectional studies have suggested there has been a negative impact of the pandemic on families, the researchers said this study is one of the first to measure just how much these factors have changed within families before and after the pandemic hit.

New research from McMaster University suggests the pandemic has created a paradox where mental health has become both a motivator for and a barrier to physical activity.
People want to be active to improve their mental health but find it difficult to exercise due to stress and anxiety, say the researchers who surveyed more than 1,600 subjects in an effort to understand how and why mental health, physical activity and sedentary behavior have changed throughout the course of the pandemic.
The results are outlined in the journal PLOS ONE.
“Maintaining a regular exercise program is difficult at the best of times and the conditions surrounding the COVID-19 pandemic may be making it even more difficult,” says Jennifer Heisz, lead author of the study and an associate professor in the Department of Kinesiology at McMaster.
“Even though exercise comes with the promise of reducing anxiety, many respondents felt too anxious to exercise. Likewise, although exercise reduces depression, respondents who were more depressed were less motivated to get active, and lack of motivation is a symptom of depression,” she says.
Respondents reported higher psychological stress and moderate levels of anxiety and depression triggered by the pandemic. At the same time, aerobic activity was down about 20 minutes per week, strength training down roughly 30 minutes per week, and sedentary time was up about 30 minutes per day compared to six months prior to the pandemic.
Those who reported the greatest declines in physical activity also experienced the worst mental health outcomes, the researchers reported, while respondents who maintained their physical activity levels fared much better mentally.
Researchers also found economic disparities played a role, particularly among younger adults.
“Just like other aspects of the pandemic, some demographics are hit harder than others and here it is people with lower income who are struggling to meet their physical activity goals,” says Maryam Marashi, a graduate student in the Department of Kinesiology and co-lead author of the study. “It is plausible that younger adults who typically work longer hours and earn less are lacking both time and space which is taking a toll.”
After analysing the data, the researchers designed an evidence-based toolkit which includes the following advice to get active: Adopt a mindset: Some exercise is better than none. Lower exercise intensity if feeling anxious. Move a little every day. Break up sedentary time with standing or movement breaks. Plan your workouts like appointments by blocking off the time in your calendar.”Our results point to the need for additional psychological supports to help people maintain their physical activity levels during stressful times in order to minimize the burden of the pandemic and prevent the development of a mental health crisis,” says Heisz.
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Materials provided by McMaster University. Note: Content may be edited for style and length.