Publisher Health

New research has identified potential treatment that could improve the human immune system’s ability to search out and destroy cancer cells within the body. Scientists have identified a way to restrict the activity of a group of cells which regulate the immune system, which in turn can unleash other immune cells to attack tumours in cancer patients.
“A patient’s immune system is more than able to detect and remove cancer cells and immunotherapy has recently emerged as a novel therapy for many different types of cancers.” Explained Nullin Divecha, Professor of Cell Signalling at the University of Southampton who led the study. “However, cancer cells can generate a microenvironment within the tumour that stops the immune system from working thereby limiting the general use and success of immunotherapy,” he continued.
Detection and removal of cancer cells by the immune system is carried out in part by a group of cells called Teffector cells (Teffs). How well Teff cells work in detecting and removing cancer cells is in part dictated by other T cells called T-regulatory cells, or Tregs for short. Tregs physically interact with the Teff cells and produce molecules which reduce the ability of the Teff cells to work properly.
Prof Divecha added, “Tregs carry out an important function in the human body because without them, the immune system can run out of control and attack normal cells of the body. However, in cancer patients we need to give the Teff cells more freedom to carry out their job.”
Molecules released by tumour cells compound the problem by attracting and accumulating Tregs, further reducing the activity and function of Teff cells. Mechanisms do exist to inhibit Treg cells, however as Treg and Teff cells are very similar, these generally also lead to inhibition of Teff cells.
In this new study, published in the journal Proceedings of the National Academy of Sciences, scientists from the University of Southampton and the National Institute of Molecular Genetics in Milan showed that inhibition of a family of enzymes in cells called PIP4K could be the answer to how to restrict Tregs without affecting Teffs.
The research team isolated Tregs from healthy donors and used genetic technology to suppress the production of the PIP4K proteins. They observed that loss of PIP4Ks from Treg cells stopped them growing and responding to immune signals which would therefore stop them from blocking the growth and function of Teff cells.
Importantly, the loss of the same enzymes in Teff cells did not limit their activity.
“This was surprising because PIP4Ks are in both types of T cells in similar concentrations but our study shows that they seem to have a more important function for Tregs than Teffectors,” said Dr. Alessandro Poli who carried out the experimental research.
Inhibition of PIP4K as a potential therapeutic for patients requires the development of inhibitory molecules. “Towards this end we show that treatment with a drug like inhibitor of PIP4K could enable the immune system to function more strongly and be better equipped to destroy tumour cells.”
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Materials provided by University of Southampton. Note: Content may be edited for style and length.

Government officials and policymakers have tried to use numbers to grasp COVID-19’s impact. Figures like the number of hospitalizations or deaths reflect part of this burden. Each datapoint tells only part of the story. But no one figure describes the true pervasiveness of the novel coronavirus by revealing the number of people actually infected at a given time — an important figure to help scientists understand if herd immunity can be reached, even with vaccinations.
Now, two University of Washington scientists have developed a statistical framework that incorporates key COVID-19 data — such as case counts and deaths due to COVID-19 — to model the true prevalence of this disease in the United States and individual states. Their approach, published the week of July 26 in the Proceedings of the National Academy of Sciences, projects that in the U.S. as many as 60% of COVID-19 cases went undetected as of March 7, 2021, the last date for which the dataset they employed is available.
This framework could help officials determine the true burden of disease in their region — both diagnosed and undiagnosed — and direct resources accordingly, said the researchers.
“There are all sorts of different data sources we can draw on to understand the COVID-19 pandemic — the number of hospitalizations in a state, or the number of tests that come back positive. But each source of data has its own flaws that would give a biased picture of what’s really going on,” said senior author Adrian Raftery, a UW professor of sociology and of statistics. “What we wanted to do is to develop a framework that corrects the flaws in multiple data sources and draws on their strengths to give us an idea of COVID-19’s prevalence in a region, a state or the country as a whole.”
Data sources can be biased in different ways. For example, one widely cited COVID-19 statistic is the proportion of test results in a region or state that come back positive. But since access to tests, and a willingness to be tested, vary by location, that figure alone cannot provide a clear picture of COVID-19’s prevalence, said Raftery.
Other statistical methods often try to correct the bias in one data source to model the true prevalence of disease in a region. For their approach, Raftery and lead author Nicholas Irons, a UW doctoral student in statistics, incorporated three factors: the number of confirmed COVID-19 cases, the number of deaths due to COVID-19 and the number of COVID-19 tests administered each day as reported by the COVID Tracking Project. In addition, they incorporated results from random COVID-19 testing of Indiana and Ohio residents as an “anchor” for their method.

What to Know: Breakthrough InfectionsApoorva MandavilliReporting on the coronavirusBreakthrough infections may be more common with the highly contagious Delta variant than with other versions of the virus. But the data are still unclear.There is some evidence that people infected with the variant carry about 1,000-fold more virus in their bodies than those infected with previous variants, and may remain contagious for longer. If that’s true even of vaccinated people, then some of them may be able to spread the virus to others.

A group of nearly 60 major medical organizations, including the American Medical Association and the American Nurses Association, called on Monday for mandatory vaccination of health care workers. As the highly contagious Delta variant drives a new surge of coronavirus cases, vaccination is an ethical obligation for health care workers, the groups said in a joint statement.“Due to the recent Covid-19 surge and the availability of safe and effective vaccines, our health care organizations and societies advocate that all health care and long-term care employers require their workers to receive the Covid-19 vaccine,” the statement said. “This is the logical fulfillment of the ethical commitment of all health care workers to put patients as well as residents of long-term care facilities first and take all steps necessary to ensure their health and well-being.”The statement was signed by a wide array of professional associations, including those representing doctors, nurses, pharmacists and infectious disease experts.In recent weeks, more hospitals and health care systems have announced that they would begin requiring all employees to be vaccinated against the coronavirus. The U.S. Equal Employment Opportunity Commission has said that the mandates are legal, and many hospitals already require employees to get flu shots.“Health care organizations rarely agree on anything, but this is one thing where they are speaking with one voice and unanimity,” said Dr. Ezekiel Emanuel, an oncologist and bioethicist at the University of Pennsylvania, who organized the joint statement. “I think that attests to the wide recognition that this is the right thing to do for this country.”Although many health care workers have been eligible for vaccination since December, when the first shots were authorized, a significant number remain unvaccinated. In New York, for instance, roughly 1 in 4 hospital workers have not yet been vaccinated, according to state data. Nationwide, just 58.7 percent of nursing home employees have been fully vaccinated, according to the Centers for Disease Control and Prevention.Some health care workers have pushed back against vaccine requirements. A small group of employees sued Houston Methodist Hospital over its mandate. The suit was dismissed last month, and more than 150 workers at the hospital were fired or resigned over their refusal to be vaccinated.Some employers have been reluctant to require the vaccines, which currently have an emergency use authorization, until they receive full approval from the Food and Drug Administration. That approval is expected, but could be months away.Dr. Emanuel said that some hospitals and health care organizations were using the lack of full approval as an excuse to push off vaccine mandates. The joint statement noted that the Covid-19 vaccines have proven to be both safe and effective.“With more than 300 million doses administered in the United States and nearly 4 billion doses administered worldwide, we know the vaccines are safe and highly effective at preventing severe illness and death from Covid-19,” Dr. Susan R. Bailey, the immediate past president of the A.M.A., said in a statement.The joint statement said that exceptions could be made for the small subset of employees who are unable to be vaccinated for medical reasons.

In a multi-hospital analysis of individuals who experienced an allergic reaction to their first mRNA COVID-19 vaccine dose, all patients who went on to receive a second dose tolerated it without complications. The research, which was led by allergists at Massachusetts General Hospital (MGH) and is published in JAMA Internal Medicine, indicates that a first dose reaction to COVID-19 vaccination should not keep people from getting a second dose.
Allergic reactions after mRNA COVID-19 vaccinations have been reported to be as high as 2%, with anaphylaxis — a life-threatening whole-body allergic reaction — occurring in up to 2.5 per 10,000 people. To examine whether it’s safe to proceed with a second mRNA COVID-19 vaccine dose after a dose one reaction, investigators from MGH, Vanderbilt University Medical Center, University of Texas Southwestern Medical Center and Yale School of Medicine combined data from patients who sought allergy specialist care at their hospitals after a reaction to their first mRNA COVID-19 vaccine dose. “These reactions could include symptoms such as itching or hives or flushing. The patients included were all advised by allergy specialists after their dose one reaction,” explains co-lead author Matthew S. Krantz, MD, of Vanderbilt University Medical Center.
Among 189 patients, 32 (17%) experienced anaphylaxis after their first dose of mRNA COVID-19 vaccine. A total of 159 patients (84%) went on to receive a second dose. All 159 patients, including 19 individuals who had experienced anaphylaxis following the first dose, tolerated the second dose. Thirty-two patients (20%) reported immediate and potentially allergic symptoms associated with the second dose that were self-limited, mild, and/or resolved with antihistamines alone.
“One important point from this study is that these immediate onset mRNA vaccine reactions may not be mechanistically caused by classic allergy, called immediate hypersensitivity or Ig-E-mediated hypersensitivity. For classic allergy, re-exposure to the allergen causes the same or even worse symptoms,” says co-senior author Kimberly G. Blumenthal, MD, MSc, co-director of the Clinical Epidemiology Program within MGH’s Division of Rheumatology, Allergy and Immunology.
The study’s findings suggest that it’s safe for most individuals to receive a second dose of the mRNA COVID-19 vaccine, notes co-senior author Aleena Banerji, MD, clinical director of the Allergy and Clinical Immunology Unit at MGH. “After first dose reactions, allergy specialists may be useful to help guide risk/benefit assessments and assist with completion of safe vaccination,” she says.
This study was funded by the National Institutes of Health and MGH.
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Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

Even in the absence of bark beetle outbreaks and wildfire, trees in Colorado subalpine forests are dying at increasing rates from warmer and drier summer conditions, found recent University of Colorado Boulder research.
The study, published in the May print issue of the Journal of Ecology, also found that this trend is increasing. In fact, tree mortality in subalpine Colorado forests not affected by fire or bark beetle outbreaks in the last decade has more than tripled since the 1980s.
“We have bark beetle outbreaks and wildfires that cause very obvious mortality of trees in Colorado. But we’re showing that even in the areas that people go hiking in and where the forest looks healthy, mortality is increasing due to heat and dry conditions alone,” said Robert Andrus, lead author of the study and postdoctoral researcher at Washington State University. “It’s an early warning sign of climate change.”
These deaths are not only affecting larger trees, thus reducing forests’ carbon storage, but hotter and drier conditions are making it difficult for new trees to take root across the southern Rockies in Colorado, southern Wyoming and northern parts of New Mexico.
It’s well known that rising temperatures and increasing drought are causing tree deaths in forests around the globe. But here in Colorado, researchers found that heat and drought alone are responsible for over 70% of tree deaths in the 13 areas of subalpine forest they measured over the past 37 years. That’s compared with about 23% of tree deaths due to bark beetles and about 5% due to wind damage.
“It was really surprising to see how strong the relationship is between climate and tree mortality, to see that there was a very obvious effect of recent warmer and drier conditions on our subalpine forests,” said Andrus, who conducted this research while completing his graduate degree in physical geography at CU Boulder. “The rate of increasing mortality is alarming.”
With temperatures in Colorado having risen by about 2 degrees Fahrenheit since the 1980s and increasing more quickly at higher elevations, estimates of another possible 2.5 or more degrees of warming in the next few decades due to climate change indicate that the rate of tree deaths will only increase.

People who are just beginning treatment for high blood pressure can benefit equally from two different classes of medicine — angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) — yet ARBs may be less likely to cause medication side effects, according to an analysis of real-world data published today in Hypertension, an American Heart Association journal.
While the class of blood pressure-lowering medicines called angiotensin-converting enzyme (ACE) inhibitors may be prescribed more commonly, angiotensin receptor blockers (ARBs) work just as well and may cause fewer side effects. Currently, ACE inhibitors are prescribed more commonly than ARBs as a first-time blood pressure control medicine.
The findings are based on an analysis of eight electronic health record and insurance claim databases in the United States, Germany and South Korea that include almost 3 million patients taking a high blood pressure medication for the first time with no history of heart disease or stroke.
Both types of medicines work on the renin-angiotensin-aldosterone system, a group of related hormones that act together to regulate blood pressure. ACE inhibitors lower blood pressure by blocking an enzyme early in the system so that less angiotensin, a chemical that narrows blood vessels, is produced, and blood vessels can remain wider and more relaxed. ARBs block receptors in the blood vessels that angiotensin attaches to, diminishing its vessel-constricting effect.
“In professional guidelines, several classes of medications are equally recommended as first-line therapies. With so many medicines to choose from, we felt we could help provide some clarity and guidance to patients and health care professionals,” said RuiJun Chen, M.D., M.A., lead author of the study, assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pennsylvania, and NLM postdoctoral fellow at Columbia University at the time of the study.
The AHA/ACC 2017 Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults says the primary medications for treating high blood pressure are thiazide diuretics, ACE inhibitors, ARBs, and calcium channel blockers as they have been shown to reduce cardiovascular events. Physical activity and other lifestyle changes are recommended for managing all levels of high blood pressure, even if medication is required.

Charts and maps tracking the progress of Covid vaccination programmes.

About three million adults in the U.S. have been diagnosed with A-fib, a heart-rhythm abnormality that’s on the rise. Here’s how to recognize the signs and treat it.Ned Hallick, a lighting specialist accustomed to hauling heavy equipment, was 63 when he first noticed occasional spells of lightheadedness. Then one day, Mr. Hallick, who lives in Brooklyn, told me, “I became so exhausted that walking up the subway stairs felt like I was climbing a mountain.”His primary care doctor, suspecting a heart problem, did several tests, including an EKG, and based on the results, referred him to a cardiologist. Diagnosis: atrial fibrillation, or A-fib, the most commonly occurring heart-rhythm abnormality.In A-fib, the atria, the two upper chambers of the heart, beat rapidly and chaotically out of sync with the ventricles, the heart’s lower pumping chambers that are responsible for circulating blood throughout the body. The ventricles may then be unable to pump enough blood to meet the body’s needs, resulting in sluggish circulation, fatigue and breathlessness.A-fib affects some three million adults in the United States, a number that is expected to quadruple in the coming decade as the population ages and risk factors like obesity, diabetes and high blood pressure become even more common. The lifetime risk of developing A-fib is greater than 20 percent, yet many people don’t even know they have it.Proper diagnosis and prompt treatment, however, can be lifesaving. In a report published in The New England Journal of Medicine in January, Dr. William G. Stevenson and Dr. Gregory F. Michaud, cardiologists at Vanderbilt University Medical Center, wrote that untreated A-fib can raise the risk of stroke by fourfold in men and about 6-fold in women, and can raise the risk of heart failure by three times and 11 times, respectively. A-fib is also associated with dementia, likely the result of strokes and impaired circulation to the brain caused by the abnormal heart rhythm. The condition is directly or indirectly responsible for more than 158,000 deaths a year.How do I know if I have A-fib?Those affected may feel their heart race, pound or flutter periodically for minutes at a time, or they may notice occasional episodes of shortness of breath, dizziness or undue fatigue upon exertion. The symptoms can be triggered by excessive consumption of alcohol or caffeine. In some people with A-fib, the abnormal rhythms come and go, while in others, they persist and the heart is unable to restore a normal rhythm without treatment.Unfortunately, many people with A-fib, including Mr. Hallick, dismiss such symptoms as nothing unusual, especially when they go away on their own.Your doctor can do an EKG or a treadmill heart test, or you may wear a portable monitor for several weeks to look for abnormal heart rhythms, to confirm a diagnosis of A-fib. Such tests can help distinguish A-fib from less serious conditions that may cause the heart to flutter, like anxiety and stress.How is A-fib treated?If A-fib is confirmed, your doctor may try to shock the heart back into a normal rhythm using a procedure called electrical cardioversion, in which an electrical current is applied to the chest using paddles. You will be sedated for the brief procedure and not feel the shocks.Longer term, most patients with A-fib can be effectively and safely treated with medication, usually drugs called beta blockers and calcium blockers that help the heart sustain a normal rhythm. Patients are also given an anticoagulant to prevent blood clots.Several currently popular anticoagulants, including Xarelto (rivaroxaban), which Mr. Hallick takes, have persistent anti-clotting effects even if patients miss a dose or two, which may help to avert a stroke. These anticoagulants also do not require close repeated monitoring of their effects on clotting, unlike their predecessor Coumadin (warfarin), which was for many years the leading anticoagulant to treat A-fib. Coumadin has one important advantage over the newer medications of an almost immediate reversal of its anti-clotting effect when patients must stop taking it to prevent excessive bleeding, say, before surgery or following an injury.Can drugs for A-fib stop working?Yes, that’s what happened with Mr. Hallick. He was doing well on medication for seven years until May, when a routine checkup revealed that, unbeknown to him, his A-fib had recurred and his heart was beating 165 times a minute, about double the normal rate.“I had been getting a little out of breath and finding it harder to walk uphill, but I wrote it off,” he recalled. “I thought I’m now 70 and maybe really out of shape thanks to the pandemic.”A medication change and two shocks to try to restore a normal heart rhythm helped only briefly, and Mr. Hallick has just undergone a procedure that promises a more lasting benefit: destruction of the cells along the back wall of his heart’s left atrium that are transmitting erratic signals to the ventricles. The procedure, called ablation, involves snaking a catheter through a vein into the atrium and usually either burning or freezing the cells that misfire.How effective is ablation at treating A-fib?Controlled trials have shown that over time, ablation is significantly more effective in correcting A-fib than drug therapy. In one recent study of 203 patients, ablation successfully prevented A-fib a year later in about 75 percent of patients in one group, whereas drug therapy helped only 45 percent of the patients in the other. In otherwise healthy people like Mr. Hallick, ablation often can be done as an outpatient procedure, followed by a few days of limited activity while the heart heals from resulting inflammation.Dr. Stevenson of Vanderbilt said some patients with persistent A-fib prefer to undergo ablation rather than continually taking medications, which can cause bleeding problems or other side effects. On the other hand, the benefit of ablation is sometimes delayed. In the first few months after ablation, he said, about half of patients experience abnormal heart rhythms and may require a cardiac shock or drug treatment until the heart fully recovers from the procedure.Are there new treatments for A-fib on the horizon?Mr. Hallick is participating in an ongoing clinical trial of a new and presumably safer procedure called pulsed field ablation that destroys the errant cells by making holes in them with electrical shocks. The procedure is said to be faster than other ablation techniques like cautery or freezing, and less likely to damage the esophagus, which lies next to the atrium.The new technique, known commercially as Farapulse, was approved for use in Europe in January but is not yet licensed by the Food and Drug Administration in the United States. It is being tested in a controlled clinical trial involving at least 350 patients at more than 30 American medical centers, including the Mount Sinai Health System in New York.“If we’re going to switch, we need to prove that pulsed field ablation is clearly better and safer than what we do now,” Dr. Stevenson said.You can learn more about this study and others at clinicaltrials.gov.

SharecloseShare pageCopy linkAbout sharingimage copyrightPA MediaThe number of people testing positive for Covid-19 has continued to fall in the UK, the latest daily figures show.The UK recorded 29,173 new cases on Sunday – down from 48,161 logged a week earlier on 18 July.The number of new infections by date reported has fallen for five days in a row for the first time since February.It is also the first time since the start of the pandemic that a sustained drop in cases has not coincided with a national lockdown.”The data at present is looking good for at least the summer,” said Prof Paul Hunter from the University of East Anglia.”Today’s figures do not of course include any impact of last Monday’s end of restrictions. It will not be until about next Friday before the data includes the impact of this change.”What could be causing the fall in cases?Public Health England tweeted the daily figures for Sunday, saying there had been a delay in updating the government’s coronavirus dashboard.It said 46,563,452 people had now had a first dose of a Covid vaccine, while 37,160,659 had received a second dose.The dashboard later updated to show there have been a further 28 deaths within 28 days of a positive test.The seven-day average of cases, which smooths out daily fluctuations, is showing a 15.4% decline compared with the week before.In Scotland, case numbers started falling earlier than in England – with some evidence the decline may have been triggered by the football team’s exit from the Euro 2020 tournament, although the downward trend has continued since then.”There has been a lot of conversation about a football-related bounce in infections and whether we were seeing a wave-within-a-wave,” said Mark Woolhouse, professor of infectious disease epidemiology at the University of Edinburgh.”In Scotland though it’s now starting to look like it’s a longer-term trend. We haven’t seen any sign of cases picking up [since the football finished]”.The figures show the number of people taking Covid tests has fallen over the past fortnight, which scientists say could explain some of the drop in reported case numbers but is very unlikely to be the only factor.Better weather over the past fortnight across much of the country may also have helped as more socialising took place outside.The latest figures from the Office for National Statistics suggest 92% of adults in the UK now have antibodies to the virus in their blood, either through a previous infection or at least one vaccination dose.Real world data shows one dose of the AstraZeneca and Pfizer vaccines is between 30% and 36% effective at preventing a symptomatic Covid infection with the dominant Delta variant. After two doses that rises to 67% for the AstraZeneca jab and 88% for the Pfizer jab. Both jabs are even more effective against hospitalisation and death.The vaccines can never offer 100% protection but as more of the population is jabbed so there is less opportunity for the virus to infect and spread.What impact could the 19 July unlocking have?Covid rules in England were relaxed on 19 July, removing social distancing restrictions in bars and restaurants and allowing nightclubs to reopen.Any rise in infections linked to that unlocking is unlikely to show up in the daily case numbers for some days to come.In other countries, such as the Netherlands and Spain, the reopening of nightclubs has been followed by a sharp rise in infections, and in some areas the policy was quickly reversed.Some scientists say the impact of unlocking in England is extremely hard to predict but could be offset by a reduction in younger children mixing as schools close for the summer holidays.”If I was a betting man, I would now say that the impact of 19 July will not be sufficient to start case numbers increasing again, but I cannot be certain,” said Paul Hunter, professor of medicine at the University of East Anglia.Others are more cautious. Prof Woolhouse from Edinburgh University said there “may well” be another rise in cases this summer.”There are at least eight million adults who have had no vaccination at all, plus most children under 18. That is still a lot of material for the virus to work with… and if the change in behaviour is dramatic enough [after 19 July], then we could see cases increase again.”What about the impact on hospitals?Since the start of the pandemic a rise in infections has always led, some weeks later, to a corresponding increase in hospitalisations and deaths.The vaccine rollout has significantly weakened that relationship but has not broken it completely.As of 22 July there were 5,001 Covid patients in hospital across the UK, up from a low of 871 on 27 May but still well below the 39,254 in hospital at the height of the winter wave in January.The time lag between infections and hospital admissions means that number is likely to continue to rise over at least the next week, even if infections continue to fall.Trying to predict what will happen in the longer term is a much more difficult task for data scientists and epidemiologists.THE R NUMBER: What it means and why it mattersTEST AND TRACE: How does it work?VACCINE: When will I get the jab?GLOBAL SPREAD: How many worldwide cases are there?Most agree that there is unlikely to be a defined end-point to this pandemic. Instead the disease may become endemic – meaning it continues to circulate at a lower level in pockets of the population with smaller spikes driven by changes to behaviour and seasonal effects.Earlier this month, the NHS was given the green light to start planning a Covid vaccine booster programme to try to minimise another wave of infections this winter.Scientists serving on the Joint Committee on Vaccination and Immunisation recommended 30 million of the most vulnerable should receive a third dose. They will include all adults aged 50 and over and anyone over 16 who qualifies for a flu jab.”This is a very difficult phase of epidemic to predict and very careful surveillance and monitoring will remain important for weeks and months to come,” said Prof Woolhouse. “There is nothing yet that undermines the government’s decision to unlock on 19 July but [we will] have to continue to watch.”THE SEARCH FOR A NEW RAP STAR BEGINS: Six artists compete for the chance to win a £20k music prizeNO BALLS: Tune into our new cricket podcast to hear all things The Hundred and more!