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Singapore University of Technology and Design (SUTD) researchers have uncovered how the environment can impact highly sensitive quantum behaviours like localisation. Their findings, published in Chaos, could lead to future innovations in the design of superconducting materials and quantum devices, including super precise sensors.

Quantum technology, in particular quantum sensing, promises to measure and capture our world at levels of precision never before possible. Such precision has diverse applications, from speedier and more sensitive medical imaging to recording time on high-frequency market trades, and even the development of sensors that can determine whether the ground beneath us is solid rock or a natural oil-and-gas reservoir.

Yet for all its theoretical potential, one considerable practical challenge remains when producing quantum measuring devices: controlling how they respond to the environment. Real devices are extremely sensitive to noise, which at best reduces their level of precision and at worst leads to unacceptable levels of error. When it comes to crafting ultra-precise sensors, such noise could overwhelm any useful signals.

Understanding how quantum devices respond to noise would help researchers find new ways to protect them from noise, making novel measurement and sensing technologies more feasible. Beyond increasing their accuracy, researchers may even be able to give quantum devices new properties. "If you could tune the amount of noise that these devices experience, you can make them function very differently and get an even more interesting device," explained Associate Professor Dario Poletti from SUTD, who led the study.

For example, scientists have known for decades that disorder in a system can cause a phenomenon called localisation, where a system gets 'stuck' to its initial state. On the other hand, when the particles in a system interact with each other strongly, there is a possibility that they can become 'unstuck,' that is, delocalised.

To study this tug-of-war between disorder and interaction, Poletti and PhD student Xiansong Xu added a third variable: the environment. Beginning with a theoretical model known as the XXZ spin chain, the researchers showed that the environment can have contrasting effects on localisation, depending on the strength of both the disorder and interaction in the system.

Performing numerical computations on the model, the researchers found that putting the system in contact with a dissipative environment such as a bath of photons pushed it towards delocalisation and made it more mobile, fluid and uniform, like water.

Importantly, they also found that while both weakly and strongly interacting systems still showed signs of localisation, the types of localisation were surprisingly different: one grainier and stuck, like sand, and the other, more uniform while still stuck, like ice.

This theoretical discovery suggests that the properties of certain materials can be tuned through changes in the external environment. For example, researchers might be able to turn a material from an insulator into a conductor by shining light on it -- or turn the material from one kind of insulator into another, with applications that go beyond quantum technologies to materials science and nanoelectronics.

"There are already quantum devices out there, and we will likely see more and more of them," Poletti said. "Devices are never truly isolated from their environments, so we would like to better understand how they can work in conjunction with the environment."

"Now the quest is to dig deeper and look for different systems, or go towards real materials and see what else can happen there," he added. "This kind of research is done over many years. We're trying to build fundamental knowledge and tools so that eventually, industry can take over."

In the Philippines, in the early months of the COVID-19 pandemic, there occurred a supply shortage of hydroxychloroquine and methotrexate. Limited access to medication and the life changes caused from the COVID-19 pandemic may prompt patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) to experience disease flares.

The researchers investigated self-reported symptoms of disease flares among patients with rheumatoid arthritis or systemic lupus erythematosus during the COVID-19 pandemic. They collected information through online surveys from 512 patients with SLE or RA. The data included sociodemographic characteristics, self-reported physical symptoms, health service utilization, and availability of hydroxychloroquine and methotrexate.

From the data, 79% of respondents had lupus, while 21% had RA. One-third of the respondents had contact with their attending physician during the two-month quarantine period before the survey. 82% were prescribed hydroxychloroquine and 23.4% were prescribed methotrexate by the doctors, from which 68.6% and 65%, respectively, had "irregular" intake of these medicines due to lack of availability. 66.2% had good health status, 24% showed no symptoms during the two-week period prior to the survey. The most common symptoms experienced were joint pain, muscle pain, headache, and skin rash. 5% of the respondents had a combination of these four most common symptoms.

Irregular supply of hydroxychloroquine among patients with SLE was associated with more frequent appearance of muscle pain or rash. Irregular supply of methotrexate among RA patients prescribed hydroxychloroquine and methotrexate was linked with more frequent occurrence of joint pains with or without swelling. Irregular supply of hydroxychloroquine was associated with less frequent occurrence of dizziness in RA patients.

There was a significant association between the irregular supply of hydroxychloroquine or methotrexate with the presence of muscle pain, rash, or joint pains during the two weeks prior to the survey.

Read the full-text of the article here: https://benthamopen.com/ABSTRACT/TORJ-15-16

The Montreal Heart Institute (MHI) announces that the COLCORONA study results are published today in The Lancet Respiratory Medicine. The article, which is entitled Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial, concludes that, given the lack of oral therapies available to prevent COVID-19 complications among non-hospitalized patients and the observed benefit of colchicine in patients with a PCR-confirmed diagnosis of COVID-19, this anti-inflammatory drug could be considered as a treatment for those at risk of complications.

"Given the current pandemic, while awaiting collective immunity through vaccination around the world, the need for treatments to prevent COVID-19 complications among patients who contract the disease remains", said Dr. Jean-Claude Tardif, Director of the MHI Research Centre, Professor at the Faculty of Medicine of the Université de Montréal and Principal Investigator of COLCORONA. "Our study showed that colchicine could be used to reduce the risk of complications for some patients with COVID-19."

Colchicine is an inexpensive and readily available anti-inflammatory drug. Orally administered, it is currently prescribed to treat gout, Familial Mediterranean Fever and pericarditis. The COLCORONA study assessed colchicine's potential to reduce the risk of COVID-19-related complications in outpatients over 40 years of age with at least one risk factor for disease progression.

The study's primary efficacy endpoint was the composite of death or hospitalization in patients with COVID-19. Of the 4,488 patients enrolled, including those without a PCR-confirmed diagnosis, the primary endpoint occurred in 4.7% of patients in the colchicine group and 5.8% of those in the placebo group, a non-statistically significant result. For the 4,159 patients with a PCR-based diagnosis of COVID-19, the primary endpoint occurred in 4.6% of patients in the colchicine group and 6.0% of patients in the placebo group, a statistically significant result. Serious adverse events were reported in 4.9% of patients in the colchicine group and 6.3% of those in the placebo group.

Notwithstanding these results, it is recommended that studies such as this one be replicated in non-hospitalized patients with a PCR-confirmed diagnosis of COVID-19. Full study results are available here: http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00222-8/fulltext.

"The COLCORONA study expands on our knowledge of the role of oral, cheap and widely available repurposed drugs such as colchicine to treat people early on to prevent serious complications of COVID-19 and can help practitioners and their patients make informed treatment decisions," said Yves Rosenberg, M.D., M.P.H., chief of the Atherothrombosis and Coronary Artery Disease Branch at the National Heart, Lung, and Blood Institute, part of the United States National Institutes of Health.

COLCORONA (NCT04322682) is a randomized, double-blinded, placebo-controlled, home-based clinical trial. It was conducted in Canada, the United States, Europe, South America, and South Africa. The study included 4,488 non-hospitalized patients over 40 years of age with COVID-19 at the time of inclusion, with at least one identified risk factor for COVID-19 complications (e.g., diabetes, hypertension, known respiratory disease, obesity). Patients were randomized to receive colchicine (0.5 mg twice daily for three days and once daily after) or placebo for 30 days.

Scientists from the Wellcome Sanger Institute and the University of Cambridge found that in children with neuroblastoma - a cancer of immature nerve cells - treatment with platinum chemotherapy caused changes to the genome that could then cause leukaemia in some children later on.

The findings, published 27th May 2021 in Blood could lead to an ability to identify which children are more likely to develop the secondary cancer. This in turn could lead to changes in their treatment plan to either avoid these risks or take measures to prepare.

Secondary blood cancer is a challenging complication of childhood neuroblastoma cancer treatment. Every year around 100 children in the UK are diagnosed with neuroblastoma*, and those who had high-risk treatment are at an increased risk of developing secondary blood cancer - leukaemia - after neuroblastoma treatment.

Neuroblastoma often requires intense treatment including several chemotherapy drugs. These powerful drugs kill cancer cells very effectively but unfortunately also have side effects, including damaging the DNA of healthy cells, including bone marrow cells. In up to 7 per cent of childhood neuroblastoma survivors, damaged bone marrow cells go on to develop into secondary leukaemia.

In this new study, researchers from the Wellcome Sanger Institute and the University of Cambridge sequenced the whole genomes of bone marrow and blood samples of two children who both had developed blood cancer following high-risk neuroblastoma treatment. They discovered that the seeds of secondary leukaemia were sown by neuroblastoma chemotherapy right at the beginning of treatment.

Dr Sam Behjati, co-lead author and group leader at the Wellcome Sanger Institute, said: "We have been able to unravel the root of secondary leukaemia in these children which seems to lie in the early stages of neuroblastoma treatment. We hope to further investigate this to try to identify children at higher risk, and to inform a more tailored treatment plan to reduce the risk of secondary leukaemia."

The team found that in both patients the leukaemia had mutations that were caused by neuroblastoma chemotherapy. A wider analysis of 17 children treated for a variety of cancers then identified another child who had undergone neuroblastoma treatment and had developed pre-leukaemia seeds. In the future, it could be possible to identify the children who have a higher risk of developing secondary leukaemia by sequencing their genome and highlighting any genetic drivers that could be pre-cursors for blood cancer.

Dr Grace Collord, joint first author from the Wellcome Sanger Institute, said: "This research would not have been possible without the contributions of the patients and their families, and we are indebted to them for their participation in this study. Understanding the reason why some childhood cancer survivors go on to develop secondary blood cancer is crucial if we are to find a way to help protect against this devastating complication."

Professor John Anderson of Great Ormond Street Hospital, who contributed to this study, said: "Neuroblastoma can be an aggressive disease that requires intense chemotherapy treatment. Occasionally this chemotherapy can cause serious adverse effects such as leukaemia. So these findings are important to inform possible strategies for monitoring for secondary cancer and tailoring individual treatment plans. However, I should stress that it remains vital that children with high risk neuroblastoma continue to receive intense treatment for their cancer."

A breast cancer therapy that requires just one shot of radiotherapy is as effective as traditional radiotherapy, and avoids potential damage to nearby organs, according to a paper by UCL experts.

The results, published in the British Journal of Cancer, mean that eight out of ten patients who receive the treatment, TARGIT-IORT, will not need a long course of post-operative external beam radiotherapy (EBRT). These results strengthen and expand previously published outcomes.

Patients who received the treatment are less likely to go on to experience fatal cardiovascular disease such as heart attacks, lung problems or other cancers. As well as avoiding scattered radiation from EBRT that can damage nearby vital organs, delivering TARGIT-IORT during the lumpectomy procedure seems to lower the likelihood of death if patients do go on to develop cardiovascular disease, protecting in a drug-like manner. This was the case even when EBRT was also given post-operatively, and is thought to be because the treatment changes the microenvironment in the lumpectomy wound.

The researchers say that delivering radiation immediately to the site where the tumour was can reduce the adverse effects of surgical trauma make the site less conducive for cancer growth and could have an 'abscopal' (distant) effect. This is where a treatment such as radiotherapy has a positive effect on tissue away from the operation site, which is increasingly recognised as a beneficial immunological action.

Previous studies have shown that the treatment has fewer radiation-related side effects compared with conventional whole breast radiotherapy, with less pain, a superior cosmetic outcome with fewer changes to the breast as a whole and a better quality of life.

Lead author Professor Jayant Vaidya (UCL Surgery & Interventional Science) said: "With TARGIT-IORT, women can have their surgery and radiation treatment for breast cancer at the same time. This reduces the amount of time spent in hospital and enables women to recover more quickly, meaning they can get back to their lives more quickly."

TARGIT-IORT is delivered immediately after tumour removal (lumpectomy), and under the same anaesthetic, via a small ball-shaped device placed inside the breast, directly where the cancer had been. The single-dose treatment lasts for around 20-30 minutes and replaces the need for extra hospital visits in eight out of ten cases.

Further tumour subgroup analysis also found that there was a significant overall survival benefit with TARGIT-IORT in patients with grade 1 or 2 cancer.

Professor Vaidya added: "These new results make it clear that the TARGIT-IORT is effective in all tumour subgroups of invasive duct cancer, the most common type of breast cancer. Our new online tool can help clinicians make a decision about additional radiotherapy (recommended in a small proportion of cases) for each individual patient.

"The finding that fewer deaths are from the avoidance of scattered radiation and the possible abscopal effect of TARGI-IORT is important and should fuel further research, opening doors to new treatments."

For the clinical trial, which started in March 2000, 2,298 women aged 45 or over with invasive breast cancer and a tumour up to 3.5cm in diameter were randomly assigned to receive either TARGIT-IORT during lumpectomy or post-operative EBRT.

The trial was designed and run from UCL, involved 32 hospitals and medical centres in ten countries: the UK, France, Germany, Italy, Norway, Poland, Switzerland, the USA, Canada and Australia.

Professor Michael Baum (UCL Surgery & Interventional Science) said: These results are the highest level of evidence proving not only the effectiveness of TARGIT-IORT but confirming that it avoids deaths from other causes.

"The new data is biologically very interesting and the new tools will make its application in routine clinical practice much easier. I am pleased that it will benefit thousands of breast cancer patients around the world."

Professor Jeffrey S Tobias (Professor of Clinical Oncology, UCL and UCLH) said: With "TARGIT-IORT, the majority of patients presenting with early localised breast cancer will never need any further radiotherapy.

"They will avoid all the side effects of whole breast radiotherapy. The chance of remaining free of local recurrence (in the breast itself) is the same as with traditional treatment, but our new analysis shows that even if they do get a local relapse, it will not detract from an excellent prognosis - as good as not having a relapse - a rather different state of affairs from the more serious outlook if this were to happen after EBRT."

To date, 45,000 patients in 260 centres in 38 countries have received TARGIT-IORT). The clinicians hope that following the latest results, more patients can be offered the treatment both in the UK and around the world instead of EBRT.

Eating habits amongst the young changed during the lockdown imposed due to COVID-19 and worsened in the case of those belonging to socioeconomically disadvantaged groups. These are the chief findings of an open access study published in specialist journal Nutrients, headed by researchers Alícia Aguilar Martínez, of the Universitat Oberta de Catalunya, and Marina Bosque Prous, of the UOC and UManresa, as part of the DESKcohort project of the interuniversity Epidemiology and Public Health research group GRESP.

The study, of 303 Catalan young people aged between 12 and 18, sought to establish how this age group's diet had changed from March to May 2020, in terms of both eating behaviours and the products consumed. The goal was to collect data to ascertain whether the changes were different depending upon the quality of their diet prior to the pandemic and their socioeconomic position.

For Aguilar Martínez, expert in adolescent nutritional health, "understanding how lockdown affected the quality of the diet of young people helps us determine which factors impact adolescents' food-related decisions and behaviours".

Differences due to socioeconomic position

The study shows how young people in more socioeconomically disadvantaged positions cut back on their consumption of cereals and vegetables and increased their intake of convenience foods. The figures show that the risk of a worsening in the diet of this group is 21% greater for adolescents from other socioeconomic realities. Bosque Prous notes how the figures point to "an increase in inequalities amongst a group already vulnerable before lockdown".

Given the findings, continues this expert in public health, "the public administrations would do well to foster actions and policies that help prevent situations such as these or be better prepared for any future lockdowns". The data gathered in this study, said the researchers, "can be useful in the design of public health actions, programmes and policies aimed at this group".

With regard to the general changes noted, the study finds that 40% of young people have increased their consumption of fruit and 21.5% say that they have eaten a more varied diet. 39.3% have cut their consumption of sweets and pastries, 49.2% that of convenience foods and 49.8% that of sugary soft drinks. On the other hand, 56% acknowledge having snacked between meals and having eaten those meals on a more irregular basis. Nevertheless, the researchers stress that "there is a need to analyse whether these changes, which have arisen over a short period of time, will remain in place in the long term."

Aguilar issues a warning, noting that adolescence is a critical period in the establishment and consolidation of lifestyles that affect both development and the prevention of diseases in adulthood. This is why, she said, there is a need to "focus on the characteristics of more vulnerable groups when it comes to developing public policies and making recommendations on a healthy diet. They must be adapted to those at most risk and prevent any continued increase in nutritional and health inequalities", she advocated.

Analysis using a national medical database revealed that the cumulative incidence of autism spectrum disorders (ASD) in children born in 2009-2014 was 2.75% by the age of five. A research group led by Associate Professor Daimei Sasayama and Professor Hideo Honda of the Department of Child and Adolescent Development Psychiatry, Shinshu University School of Medicine, used a national medical database to analyze autism spectrum disorders in Japan. It was reported that the cumulative incidence showed an increasing trend for each year of birth, and that there were regional differences.

This cumulative incidence of ASD is the highest in the world based on medical diagnosis, suggesting high diagnostic sensitivity in Japan. The proportion of people diagnosed with autism spectrum disorders has increased globally over the last 20 years, with a 2014 US survey reporting a prevalence of 1.68% in 8-year-olds. In addition, a regional cohort study of children's mental development and psychiatry at Shinshu University School of Medicine reported that 3.1% of children had been diagnosed with autism spectrum disorders by school age. Improving screening accuracy is one of the main reasons why more and more people are being diagnosed with autism spectrum disorders. In order to investigate the actual condition of diagnosis of autism spectrum disorder in Japan, the group investigated the cumulative incidence of autism spectrum disorder nationwide and the cumulative incidence by prefecture using National Database (NDB), which aggregates medical data from all over the country.

For children born in 2009-2016 and diagnosed with autism spectrum disorder in 2009-2019, information on gender, year and age at the time of diagnosis, and the prefecture where the diagnosis was made were extracted from NDB. Cumulative incidence was calculated by dividing the number of diagnoses by the number of births each year.

Of the children born in 2009-2016, 313,353 (236,386 boys, 76,967 girls) were diagnosed with autism spectrum disorder in 2009-2019. The lifetime cumulative incidence of autism spectrum disorders at age 5 in children born between 2009 and 2014 was 2.75%. The cumulative incidence tended to increase with each year of birth. By prefecture, the cumulative lifetime incidence of autism spectrum disorders at age 5 ranged from 0.9-7.9% (median 2.4%).

This study published in the journal JAMA Network Open reported that the cumulative incidence of autism spectrum disorders in Japan is high worldwide. It is thought that the nationwide increasing trend is influenced by the recent increase in awareness of autism spectrum disorders. On the other hand, since there are large regional differences in the incidence rate, it is possible that factors such as differences in access to medical care and support also affect the incidence rate. The results of this study show that there is an increasing need to build a support system for autism spectrum disorders. Accurately capturing changes in the frequency of autism spectrum disorders is important both for the realization of an effective support system and for studying the risk factors and etiology of autism spectrum disorders. The research group will continue to investigate trends in the incidence of autism spectrum disorders in Japan and around the world.

Individuals with genetic high cholesterol, heart disease or both, who were infected with COVID-19 had more heart attacks according to new research by the FH Foundation. While previous studies have speculated about poorer outcomes if a person with genetic high cholesterol - called familial hypercholesterolemia (FH) contracts COVID-19, this study from the FH Foundation's national healthcare database is the first to demonstrate higher heart attack rates in the real world. Published online in the American Journal of Preventive Cardiology, the study also importantly confirms that COVID-19 increases heart attack rates in individuals with established atherosclerotic cardiovascular disease (ASCVD).

The FH Foundation performed an analysis of 55,412,462 individuals, separating groups into six matched cohorts including diagnosed FH, probable FH, and ASCVD, with and without COVID-19 infection (as identified by the U07.1 ICD-10 code). The researchers found that rates of heart attacks were highest in those with a COVID-19 diagnosis and the presence of diagnosed FH or probable FH with known ASCVD.

"These results are significant because these data underscore the importance of understanding if individuals have underlying cardiovascular disease or genetic high cholesterol when treating for COVID-19 infection or considering vaccination," said Kelly Myers, study author and chief technology officer of the FH Foundation.

Familial hypercholesterolemia is a common genetic condition that increases an individual's risk for cardiovascular disease by up to 20-fold due to lifelong elevated low density lipoprotein cholesterol (LDL-C) levels. Today, only 10% of the 1.3 million Americans with FH are diagnosed, due to lack of awareness in the medical community and public. To understand the effect of COVID-19 on these individuals, the researchers applied the FIND FH® machine learning model on the dataset.

The study findings have important implications for individuals with FH who are not diagnosed today, say the researchers. "Probable FH" individuals with pre-existing ASCVD who contracted COVID had heart attacks at a seven-times greater annual rate than their counterparts who did not contract the virus (AIDR 15.4% vs 2.1% p-value

"The highest heart attack rates occurred in individuals infected with COVID-19 who had preexisting cardiovascular disease and were flagged by the FIND FH model as probable FH. We speculate that because these individuals have yet to receive an FH diagnosis, they may not be receiving appropriate lipid lowering treatment placing them at significantly higher risk," added Dr. Mary McGowan, study author and chief medical officer for the FH Foundation. "This study is a call to action to diagnose individuals with this deadly genetic condition who are hiding in plain sight within our healthcare system, and take particular precautions related to COVID-19 infections. FH is an untapped opportunity for heart disease prevention."

The FH Foundation plans to leverage this and other ongoing research to continue to advocate to prioritize FH as a public health concern.

BOSTON - Although everyone can benefit from exercise, the mechanistic links between physical fitness and overall health are not fully understood, nor are the reasons why the same exercise can have different effects in different people. Now a study published in Nature Metabolism led by investigators at Beth Israel Deaconess Medical Center (BIDMC) provides insights related to these unanswered questions. The results could be helpful for determining the specific types of exercise most likely to benefit a particular individual and for identifying new therapeutic targets for diseases related to metabolism.

"While groups as a whole benefit from exercise, the variability in responses between any two individuals undergoing the very same exercise regimen is actually quite striking. For example, some may experience improved endurance while others will see improved blood sugar levels," said senior corresponding author Robert E. Gerszten, MD, Chief of the Division of Cardiovascular Medicine at BIDMC. "To date, no aspects of an individual's baseline clinical profile allow us to predict beforehand who is most likely to derive a significant cardiorespiratory fitness benefit from exercise training."

To uncover the details behind exercise's effects on the body and how these might differ from one person to the next, the team, including first author Jeremy Robbins, MD, of the Division of Cardiovascular Medicine at BIDMC, measured the blood levels of approximately 5,000 proteins in 650 sedentary adults before and after a 20-week endurance exercise program.

"We were particularly interested at looking at proteins in the blood to study the effects of exercise because there is a growing body of evidence showing that exercise stimulates the secretion of chemicals into circulation that can impart their effects on distant organs," Robbins said.

A set of 147 proteins in the blood indicated an individual's cardiorespiratory fitness, or VO2max, at the start of the study. Another set of 102 proteins indicated an individual's change in VO2max following the completion of the exercise program.

"We identified proteins that emanate from bone, muscle, and blood vessels that are strongly related to cardiorespiratory fitness and had never been previously associated with exercise training responses," said Gerszten, who is also the Herman Dana Professor of Medicine at Harvard Medical School and a Senior Associate Member of the Broad Institute of MIT and Harvard.

Robbins added, "Even though prior studies have shown that an individual's baseline fitness level is unrelated to their response to exercise training, it was fascinating to see that there was minimal overlap between the protein profiles of baseline VO2max and its response to the exercise training intervention."

With this information, the research team developed a protein score that improved their ability to predict an individual's trainability, or change in VO2max. For example, the score identified individuals who were unable to significantly improve their cardiorespiratory fitness despite participating in the standardized exercise program. "Baseline levels of several proteins predicted who would respond to the exercise training protocol far better than any of our established patient factors," Gerszten said.

In a separate community-based study, though part of the same paper, the scientists found that some of these proteins were linked to an elevated risk of early death, highlighting the link between cardiorespiratory fitness and long-term health outcomes.

"We now have a detailed list of new blood compounds that further inform our understanding of the biology of fitness and exercise adaptation, and predict individual responses to a given exercise regimen," said Gerszten, who is also the Director of the Program in Personal Genomics and Cardiometabolic Disease at BIDMC. "While no pill is ever likely to recapitulate the diversity of benefits from exercise, our study has helped create a roadmap to further explore potential interventions and provides an important step in individualizing exercise as a therapy." He noted that additional research is needed to expand the study's findings to larger populations and to further refine the precise effects of the different proteins before and after exercise.

Bethesda, MD (May 27, 2021) -- Crohn's disease, a type of inflammatory bowel disease (IBD) that causes inflammation (pain and swelling) in the gastrointestinal tract, can cause daily health problems, frequent hospitalizations and surgery when not adequately controlled. While there is no cure for Crohn's disease, there are treatments that can help patients live a symptom-free life.

After a detailed review of available literature, the American Gastroenterological Association (AGA) has released new clinical guidelines outlining the benefits and risks of each drug currently available to Crohn's patients. Based on this research, AGA recommends the early introduction of biologics for patients experiencing luminal and fistulizing Crohn's disease rather than waiting until other treatments fail. These guidelines are published in Gastroenterology, AGA's official journal.

"With many new drugs entering the market, clinician's ability to treat patients with Crohn's disease has improved greatly over the last 20 years," said lead author Joseph D. Feuerstein, MD, from Beth Israel Deaconess, Boston, Massachusetts. "We hope this new guideline serves as a manual for clinicians in selecting the right therapies for their patients, which should lead to improved patient outcomes and less need for invasive surgery."

Key guideline recommendations:

1. Biologics are the most effective drugs for the management of Crohn's and they should be used early, rather than delaying their use until after failure of mesalamine and/or corticosteroids, in patients with moderate to severe or fistulizing Crohn's disease. These drugs are antibodies and can more precisely target the immune system which is causing the inflammation in Crohn's disease.

a. Anti-tumor necrosis factor (anti-TNF) agents or ustekinumab are recommended and vedolizumab is suggested as a first-line treatment.

b. In patients who have previously not responded to anti-TNF agents, AGA recommends ustekinumab or vedolizumab.

c. The biologic natalizumab is no longer recommended due to potential adverse events and the availability of safer treatment options.

Read the AGA Clinical Practice Guideline on the Medical Management of Moderate to Severe Luminal and Fistulizing Crohn's Disease to review all 25 recommendations.

Higher percentage of patients treated with nivolumab and ipilimumab in clinical trial reach the six-and-a-half-year survival mark than those treated with either drug alone.

BOSTON - In the longest follow-up results from a clinical trial of combination immunotherapy for metastatic melanoma, investigators report that nearly half the patients who received the drugs nivolumab and ipilimumab were alive a median of six and a half years after treatment. The results, stemming from the CheckMate 067 clinical trial, represent a new landmark in survival rates for patients with melanoma treated with immune checkpoint inhibitor drugs.

F. Stephen Hodi, MD, the director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber Cancer Institute is co-senior author of the study. Findings will be presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, being held virtually June 4-8.

The clinical trial compared nivolumab and ipilimumab, alone and in combination, in patients with previously untreated stage III or IV melanoma that could not be removed surgically. Both drugs target proteins on T cells known as immune checkpoints, which some cancer cells exploit to spare themselves from an attack by the T cells. By interfering with these proteins, the drugs essentially release the brakes on such an attack. Nivolumab targets the PD-1 checkpoint protein, ipilimumab targets the CTLA-4 checkpoint protein.

In the trial, patients were randomly assigned to receive nivolumab and ipilimumab in combination, nivolumab plus a placebo, or ipilimumab alone. Six and a half years after treatment, participants who received the nivolumab-ipilimumab combination were more likely to be alive and to have had no advance of their disease than those who received either drug alone.

At the six-and-a-half-year mark, 49% of participants treated with the combination therapy were alive, compared to 42% of those treated with nivolumab alone, and 23% of those treated with ipilimumab alone. Progression-free survival - the percentage of patients alive and whose cancer hadn't worsened - was 34% for the combination therapy group, 29% for the nivolumab-only group, and 7% for the ipilimumab-only group.

Median survival - the length of time that at least half the patients were still alive - followed the same pattern. For patients treated with nivolumab and ipilimumab, median survival was 72.1 months, or just over six years. For those treated with just nivolumab, median survival was 36.9 months, and for those treated with just ipilimumab, it was 19.9 months.

"This is the longest follow up for a phase III advanced melanoma clinical trial including nivolumab plus ipilimumab," said Hodi. "It confirms a continued durable benefit for the combination."

An estimated one in seven Ohio women of adult, reproductive age has visited a crisis pregnancy center, a new study has found.

In a survey of 2,529 women, almost 14% said they'd ever attended a center. The prevalence was more than twice as high among Black women and 1.6 times as high among those in the lowest socioeconomic group, found a research team from The Ohio State University. Their study appears in the journal Contraception.

Crisis pregnancy centers are often supported by religious organizations and are designed to discourage women with unintended pregnancies from choosing abortion, though they don't typically advertise themselves as anti-abortion. In Ohio, where more than 100 centers are spread throughout the state, they are funded by state dollars. In 2019, during the time of the survey, the state committed $7.5 million over two years to support the centers. Centers that focus on adoption may also receive funding from the sale of "Choose Life" license plates.

Marketed to pregnant teens and women who are trying to make a decision about their pregnancies, the centers typically provide pregnancy testing and counseling and often offer items such as diapers, formula and other baby supplies. Some centers also offer ultrasounds. They are not medical providers, and are not regulated by the Ohio Medical Board.

"Crisis pregnancy centers are visited by a large number of women in general, and even more women from populations that already face serious barriers to reproductive health care, raising concerns that this may serve as another obstacle to medical care," said Robin Rice, the study's lead author and a medical student at Ohio State.

"They look like medical clinics, and some women might not know if it's a medical facility or not," she said.

The new study provides a first-of-its-kind population-level snapshot of the prevalence of interactions with the centers, a measurement that could help clinicians, reproductive rights advocates and others seeking to ensure Ohio women are receiving appropriate medical care, including information about all of their legal options, she said.

Maria Gallo, a study co-author and professor of epidemiology at Ohio State, said that previous research has found that the centers sometimes provide misinformation about reproductive health -- something that is particularly concerning in cases where women mistakenly think they are visiting a health care provider.

"The state is spending millions of dollars on these centers each year, making it even more important that pregnant women are aware of their missions and the fact that they are not medical providers, but typically religious-based outfits that oppose abortion," she said.

"If these centers are drawing in people who don't have other pregnancy counseling and care options, or don't know what those options might be, that's a concern. And if they're doing medically adjacent procedures, like pregnancy tests and ultrasounds, it could increase the chances that women think they're getting regulated health care when they're not."

Gallo said delays in getting medical care could result in women not receiving a proper diagnosis of early pregnancy complications such as life-threatening ectopic pregnancy.

Rice said it's important that health care providers understand the reach of these centers, and recognize that their patients' experiences may be colored by information they receive at them. Another potential action item based on the study's results: "We could seek to establish legitimate state-funded prenatal clinics in those areas that may not have them," she said.

"Mitigating financial barriers is also important. Crisis pregnancy centers are free, so we might also want to think about ways to offer alternative free support services that also draw women in for comfort and to get free supplies."

From a policy perspective, Gallo said lawmakers may want to rethink the use of state funds for unregulated organizations that have been shown to provide health misinformation.

DALLAS, May 27, 2021 -- Adults who have obsessive-compulsive disorder (OCD) were more than three times as likely to have an ischemic stroke later in life compared to adults who do not have OCD, according to new research published today in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

"The results of our study should encourage people with OCD to maintain a healthy lifestyle, such as quitting or not smoking, getting regular physical activity and managing a healthy weight to avoid stroke-related risk factors," said study senior author Ya-Mei Bai, M.D., Ph.D., a professor in the department of psychiatry at Taipei Veterans General Hospital and National Yang Ming Chiao Tung University College of Medicine, both in Taiwan.

Worldwide, stroke is the second-leading cause of death after heart disease. Stroke is a medical emergency that occurs when blood and oxygen flow to the brain are interrupted, usually by a blood clot (ischemic stroke). Less common is stroke from a burst blood vessel that causes bleeding in the brain (hemorrhagic stroke). In both types of stroke, immediate treatment is critical to prevent brain damage, disability or death. The abbreviation F.A.S.T. can help people remember the warning signs and what to do: F-face drooping, A-arm weakness, S-speech difficulty, T-time to call 9-1-1.

OCD is a common, sometimes debilitating, mental health condition characterized by intrusive, unwanted thoughts, ideas or sensations (obsessions) that make a person feel driven to do something repetitively (compulsions). The repetitive behaviors characteristic of OCD, such as hand washing, checking on things or continuously cleaning, can significantly interfere with a person's daily activities and social interactions. Previous research found that OCD often occurs after stroke or other brain injury. What remained unclear was whether the reverse is true: can OCD increase stroke risk?

To find out, researchers examined health records from 2001-2010 from the Taiwan National Health Insurance Research Database to compare stroke risk between 28,064 adults with OCD and 28,064 adults who did not have OCD. The average age at diagnosis with OCD was 37 years, and women and men were nearly equally represented in the data. Researchers compared stroke risk between the two groups for up to 11 years.

The analysis found:

Adults with OCD were more than three times as likely to have a stroke from a blood clot compared to adults who did not have OCD; the greatest risk was among adults ages 60 and older.

OCD was an independent risk factor for ischemic stroke even after controlling for other factors known to increase stroke risk, including obesity, heart disease, smoking, high blood pressure, high cholesterol and Type 2 diabetes.

No difference in risk was found for a hemorrhagic stroke (burst blood vessel).

Similarly, medications to treat OCD were not associated with an increased risk of stroke.

"For decades, studies have found a relationship between stroke first and OCD later," Bai said. "Our findings remind clinicians to closely monitor blood pressure and lipid profiles, which are known to be related to stroke in patients with OCD."

Limitations of the study were that only stroke among patients who sought health care were included, so some cases may have been missed; and information on disease severity was not included along with family medical history or environmental influences. The study also was observational, so it could only show an association between OCD and later stroke; it does not prove cause and effect.

"More research is needed to understand how the mental processes connected to OCD may increase the risk of ischemic stroke," Bai said.

Urgent investment in new tools is needed to address major global losses of wheat crops which cost £22 billion per year.

Leading scientific experts are calling for governments around the world to come together and fund a new international research platform, to reduce the impact of major wheat pathogens and improve global food security.

The John Innes Centre is calling for an internationally coordinated approach to deliver a new 'R-Gene Atlas', which would help identify new genetic solutions conferring disease resistance for crops, which could be bred into commercial wheat varieties.

Globally, we lose one fifth of the projected wheat yield annually to pests and pathogens totaling losses of 209 million tonnes, worth £22 billion ($31 billion). The climate emergency has the capacity to bring further disruption to global food supplies, as a changing environment brings new types of pests and diseases and increases their spread.

To minimise these losses, and to reduce reliance on chemical solutions, the team calls for broader use of disease resistance to be found in the genome of wheat and its wild relatives. The aim is to provide long-lasting molecular protection against wheat's major pathogens including wheat rusts, blotch diseases, powdery mildew, and wheat blast.

In 2016 global trade saw the wheat blast fungus, typically isolated to South America, arrive in Bangladesh, where it destroyed 15,000 hectares of wheat, resulting in yield losses of 25-30% and threatening wheat production across South Asia.

Wheat R genes work by recognising corresponding molecules in the pathogen called effectors. By identifying the effectors present in pathogen and pest populations, more durable combinations or "stacks" of R genes could be designed.

The R-gene atlas will be a free online portal containing this genetic information and enabling breeders to design gene stacks using computer modelling before starting their breeding in the field.

It will enable users to design molecular markers that could be used to find out what resistance genes they already have in their breeding programme or wheat populations.

The idea builds upon the recent surge in genomic resources available to researchers in wheat, facilitated by advancements in sequencing technologies and bioinformatics. In the past few years, researchers at the John Innes Centre and The Sainsbury Laboratory have rapidly identified and cloned resistance genes in wheat and its wild relatives using technologies such as AgRenSeq, MutRenSeq and MutChromSeq.

The new proposal details how the molecular components involved in disease resistance - R genes and effectors - could be captured from both the host and pathogen. Whole genome sequencing would be carried out on diversity panels of wheat, its progenitors and domesticated and wild relatives.

Association genetics, a method of seeking useful genetic variation, could then be used to look for correlations between the host genotype and disease resistance or susceptibility and the genes responsible for these traits could be identified. The researchers calculate it would cost around £41 million ($58.6 million) to establish the new platform at the required scale. Costed, detailed proposals for the R-Gene Atlas are set out in a new article in Molecular Plant.

This would include sequencing diversity panels of the pathogens and 10 host species of wheat, as well as funding 75 scientists across the world to carry out the work.

This, they suggest, could be funded by contributions of £2 million ($2.9 million) per G20 country spread over five years - a minor investment considering the current financial losses across the world to wheat diseases. This extensively collaborative funding model would spread the risk on a project which would have global reward.

"Compared to the scale of the problem in yield losses to pests and pathogens, this represents excellent value for money" says first author Amber Hafeez. "It is unsustainable to continue feeding 20 per cent of our wheat production to pathogens. Our enterprise applies cutting edge science to a global challenge that is increasing due to the climate emergency."

The proposal involves bringing together an international consortium to allow the project to draw upon existing expertise and resources.

"A lot of the pieces of the puzzle already exist, the idea is to bring them together to make sure we don't duplicate efforts," says Dr Brande Wulff, corresponding author of the article. "We see it as a centrally coordinated model distributed around different countries, using existing capacity.

"Current projections suggest there will be 2.1 billion more people to feed by 2050 and developing disease-resistant crops will be a key part of sustainably feeding us all. We're determined to develop new ways to increase our genetic understanding and deploy it for the benefit of sustainable agriculture, but we cannot do this without investment."

"We are urging the G20 governments to invest in the consortium, which will bring disease resistance genes from lab to field at a scale and speed needed to deal with the current crisis."

The idea has been trialed earlier this year and has drawn an enthusiastic response from the international wheat research community. Amber Hafeez said : "We have been delighted with the initial enthusiastic response to our proposals - many research groups and collaborators have welcomed the idea and we feel this confirms our belief that the time is right for this proposal."

Scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) have identified the first blood biomarker for myocarditis, a cardiac disease that is often misdiagnosed as myocardial infarction. Nevertheless, the diagnosis of myocarditis continues to be challenging in clinical practice.

The study, led by Dr. Pilar Martín and published today in The New England Journal of Medicine, has detected the presence of the human homolog of micro RNA miR-721 in the blood of myocarditis patients.

CNIC General Director Dr. Valentín Fuster emphasizes that these results of paramount importance because they establish the first validated blood marker with high sensitivity and specifity (>90%) for myocarditis. This will allow clinicians to distinguish between this disease and other cardiomyopathies like acute myocardial infarction, myocardial infarction with nonobstructive coronary arteries (MINOCA), and other inflammatory diseases with an autoimmune origin.

"Our finding has great potential as a valuable clinical tool for the precise and noninvasive diagnosis of myocarditis from small drops of blood," says Dr. Martín, whose project is funded by a Fundación BBVA Beca Leonardo award.

The diagnosis of myocarditis is challenging, and the availability of a sensitive and specific marker of acute myocardial inflammation could have a major clinical impact, improving the diagnosis of myocarditis both generally and particularly in its early phases.

An inflammatory disease of the heart

Myocarditis is an inflammatory disease of the heart caused by infection, toxins, drugs, or autoimmune disorders. If untreated, myocarditis can progress to potentially fatal dilated cardiomyopathy, requiring heart transplant.

The prevalence of myocarditis remains uncertain because it is often difficult to achieve a confirmed diagnosis.

Myocarditis, says study co-first author Rafael Blanco-Domínguez, "is often the final diagnosis in patients with MINOCA, which accounts for 10-20% of patients meeting the criteria for myocardial infarction."

Myocarditis is usually diagnosed after coronary angiography or computed tomography scans have discarded coronary artery disease, followed by confirmation of the diagnosis by magnetic resonance imaging (MRI).

However, not all centers have access to MRI technology, and the current gold standard for myocarditis diagnosis is endomyocardial biopsy, an invasive procedure normally reserved for severe cases. There is thus a pressing clinical need for the development of reliable and accessible tools for the early diagnosis of acute myocarditis.

Moreover, adds Raquel Sánchez-Díaz, "myocarditis is a side effect that, although very rare, is potentially serious in cancer patients who are receiving treatment with immunotherapy drugs called "immune checkpoint inhibitors".

There are currently no specific markers for the diagnosis of patients susceptible to developing myocarditis during cancer immunotherapy.

"We identified miR-721 in the blood plasma of mice with autoimmune or viral myocarditis. This miRNA is produced by autoimmune Th17 cells that recognize cardiac antigens derived from proteins such as alpha-myosin," says Rafael Blanco-Domínguez. Continuing, study co-first author Raquel Sánchez-Díaz explains that "these cells attack the myocardium, and are in large part responsible for the pathophysiology of the disease."

The research team went on to identify, clone, and validate the previously unknown human homolog of miR-721. The study confirmed that this miRNA is synthesized in the Th17 cells of myocarditis patients and its expression is exclusively detected in the plasma of these patients.

The biomarker was validated by cardiologists and researchers at numerous hospitals in Spain and abroad. In Spain, key contributors include Drs. Francisco Sánchez-Madrid, Hortensia de la Fuente, Jesús Jiménez-Borreguero, Fernando Alfonso, Isidoro González, and Esteban Dauden of Hospital de La Princesa/ IIS Princesa; Dr. Valentín Fuster of the CNIC, Dr. Borja Ibáñez of Fundación Jiménez Díaz and the CNIC; Dr. Héctor Bueno of Hospital Universitario Doce de Octubre; Dr. Amaia Martínez of Hospital Central de Asturias; Dr. Leticia Fernández Friera of HM Montepríncipe; Dr. Domingo Pascual-Figal of Hospital Virgen de la Arrixaca, and Dr. Villar Guimerans of Hospital Ramón y Cajal y and Instituto de Investigación IRYCIS. Key international contributors include the University of Padua in Italy, Zürich University Hospital in Switzerland, and Massachusetts General Hospital and the Mayo Clinic in the USA.

The researchers are currently designing studies to evaluate the potential of the biomarker as a predictor of short-term and long-term risk, the persistence of myocardial inflammation, and the risk of relapse, clinical progression, and adverse ventricular remodeling.

The CNIC is the sole owner of a patent related to the biomarker and its use for the diagnosis of miocarditis. The CNIC is now exploring licensing agreements with industrial partners to develop and commercialize this technology in order to make it available for clinical use.

For Dr. Fuster, "this study is a shining example of how the basic research carried out at the CNIC contributes to societal wellbeing through the translation of the knowledge gained in the center's laboratories to clinical practice."