Whole-heart ventricular modeling has come a long way in recent years and is currently witnessing the evolution of a variety of computational approaches, especially within the realm of personalized technologies for patient-specific clinical applications.
Ventricular arrhythmias, which are abnormal heartbeats, are one of the leading causes of mortality worldwide. To pursue a better mechanistic understanding of ventricular arrhythmias, Johns Hopkins University researchers are turning to whole-heart computational models.
In Biophysics Reviews, from AIP Publishing, the researchers describe the progress using various computational approaches to address the mechanisms of cardiac dysfunction and issues related to the clinical application of computation-driven diagnostic and therapeutic approaches for cardiac disease and arrhythmias.
The heart’s electrical properties can be modeled via fundamental biophysical principles determined through basic science experiments.
Whole-heart computational models are multiscale, which means they factor in both cellular- and organ-level properties. These models include most of the biophysical complexity of an individual patient’s cardiac pathology.
This complex biophysical system “can be represented using a set of mathematical equations,” said Natalia A. Trayanova, a co-author and professor of biomedical engineering and medicine at Johns Hopkins University. “Solving these equations using computer software allows us to run detailed simulations to mimic the heart’s electrical activity.”
Computational models of the heart linking cellular electrophysiology to whole-organ behavior are emerging as promising platforms for in-silico evaluation of novel diagnostic and therapeutic strategies.
“Personalized computational modeling of patient hearts is making strides developing models that incorporate the individual geometry and structure of the heart, as well as other patient-specific information,” Trayanova said.
These patient-specific models can help predict risk of sudden cardiac death or the outcome of a cardiac procedure.
“Patient-specific models are also used for determining the optimal treatment for arrhythmia, both atrial and ventricular, with the latter often based on different biophysical underpinnings,” said Trayanova. “These types of models can enable fast evaluation of medical device settings and patient-​selection criteria, as well as the development of novel therapeutic agents.
“Computational modeling can also be combined synergistically with machine learning approaches to better account for the information available within patient health records.”
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With fewer people on the road during the early days of the pandemic, more drivers were speeding and driving recklessly, resulting in more crashes being deadly, a new study found.
Researchers at The Ohio State University conducted a detailed analysis of traffic in Franklin County, Ohio, which includes Columbus, from Feb. 1 to May 8, 2020 — the period right before and after COVID-19 stay-at-home orders were instituted by the state governor.
While the total number of collisions declined after the lockdown, the proportion of those crashes that were incapacitating or fatal more than doubled, results showed.
“More of the crashes that did occur were severe, not just because of less congestion, but also because of drivers who were speeding, and driving under the influence of alcohol or drugs,” said Jonathan Stiles, lead author of the study and a postdoctoral researcher in geography at Ohio State.
Pandemic driving also led to far fewer rear-end collisions and more single-vehicle crashes, findings revealed.
The study was published this week in the journal Transportation Research Record and will appear in a special issue on COVID-19.

Classic antidepressants could help improve modern cancer treatments. They slowed the growth of pancreatic and colon cancers in mice, and when combined with immunotherapy, they even stopped the cancer growth long-term. In some cases the tumors disappeared completely, researchers at UZH and USZ have found. Their findings will now be tested in human clinical trials.
Serotonin is a neurotransmitter that is also known as the happiness hormone because of its beneficial effects on mood. In depressed people, the concentration of serotonin in the brain is reduced. The hormone also influences many other functions throughout the body. The majority of the serotonin is not located in the brain, but is stored in the blood platelets. Serotonin reuptake inhibitors (SSRIs), which are used to treat depression, increase serotonin levels in the brain but decrease peripheral serotonin in platelets.
SSRIs slow tumor growth
The involvement of serotonin in carcinogenesis was already known. Until now, however, the underlying mechanisms had remained obscure. Now, researchers at the University of Zurich (UZH) and University Hospital Zurich (USZ) have shown that SSRIs or other drugs that lower peripheral serotonin levels can also slow cancer growth in mice. “Drugs that are already approved for clinical use as antidepressants could help improve treatment of hitherto incurable pancreatic and colorectal cancers,” says Pierre-Alain Clavien, director of the Department of Surgery and Transplantation.
Although new, effective treatments — such as targeted antibodies or immunotherapies — have been available for several years, most patients with advanced-stage abdominal tumors such as colon or pancreatic cancer die within a few years of diagnosis. One problem is that the tumor cells become resistant to the drugs over time and are no longer recognized by the immune system. Now, the research group led by Pierre-Alain Clavien and Anurag Gupta has discovered the role serotonin plays in this tumor cell resistance mechanism.
Without serotonin, the immune system recognizes the cancer cells again
Cancer cells use serotonin to boost the production of a molecule that is immunoinhibitory, known as PD-L1. This molecule binds to killer T cells, a specific type of immune cell that recognizes and eliminates tumor cells, and renders them dysfunctional. The cancer cells thus avoid being destroyed by the immune system. In experiments with mice, the researchers were able to show that SSRIs or peripheral serotonin synthesis inhibitors prevent this mechanism. “This class of antidepressants and other serotonin blockers cause immune cells to recognize and efficiently eliminate tumor cells again. This slowed the growth of colon and pancreatic cancers in the mice,” Clavien says.
Hope for novel combination therapies
PD-L1, via which serotonin exerts its effect, is also the target of modern immunotherapies, also called immune checkpoint inhibitors. In a next step, the researchers tested a dual treatment approach in mice: They combined immunotherapy, which increases the activity of killer T cells, with drugs that reduce peripheral serotonin. The results were impressive: Cancer growth was suppressed in the animal models in the long term, and in some mice the tumors disappeared completely.
“Our results provide hope for cancer patients, as the drugs used are already approved for clinical use. Testing such drug combinations on cancer patients in clinical trials can be fast-forwarded due to the known safety and efficacy of the drugs,” says Pierre-Alain Clavien.
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The measures adopted in mid-March 2020 to contain the COVID-19 pandemic both greatly reduced people’s mobility and effectively prevented the spread of COVID-19 in the following three weeks. That is the result of a recent study by an international team of economists led by Junior Professor Dr Emanuel Hansen at the University of Cologne’s Faculty of Management, Economics, and Social Sciences and Professor Dr Ulrich Glogowsky at Johannes Kepler University in Linz (Austria). The results demonstrate how important the early policy measures were for the further course of the coronavirus pandemic in Germany. The study has appeared in the interdisciplinary open-access journal PLoS ONE.
In the spring of 2020, the COVID-19 pandemic was spreading rapidly across Europe. After initial hesitation, in mid-March the German government and the Conference of Federal State Prime Ministers (Ministerpräsidentenkonferenz) decided in quick succession on a series of measures to restrict social contacts, including the closing of schools, childcare facilities, and shops. Even private meetings of people from different households were limited. German policy-makers thus implemented rapid and far-reaching contact restrictions. In the early stages of the first wave of the virus, masks were not yet mandatory. Neither vaccinations nor rapid tests were available. Within a few weeks, COVID-19 infections in the country declined sharply, causing contact restrictions to be gradually relaxed again beginning on 20 April 2020.
Despite the rapid decline in infections in Germany, the effectiveness of the contact restrictions has been disputed repeatedly, both by the public and by experts. In particular, it was argued that even without the enacted measures, the spread of the virus would have been curbed by automatic changes in people’s behaviour.
To answer this controversial question, the team of authors led by Junior Professor Dr Emanuel Hansen estimated the causal effect of the policy measures using detailed figures from the Robert Koch Institute as well as anonymized movement data from private mobile phone providers from the more than 400 German districts in a quasi-experimental analysis. The analysis exploits that the first COVID-19 infections occurred in some districts before the contact restrictions began, while in other districts they occurred much later. By comparing districts with early and late outbreaks, the researchers estimated how citizens’ behaviour and the infection rate would have evolved in Germany without social distancing measures. The causal effect of all measures thus corresponds to the difference between the inferred hypothetical development without social distancing and the actual development with contact restrictions in place.
Based on this analysis, the authors derived the following results: In a first step, based on the mobile phone data they found that the policies in fact reduced people’s spatial movements by an average of 30 per cent, as they were intended to do. In a second step, they found evidence of the effective containment of the pandemic: already within the first three weeks, contact restrictions in Germany prevented more than 80 per cent of COVID infections and more than 60 per cent of the deaths that would have followed. Put differently, the researchers estimate that there would have been about 500,000 additional infections and about 5,400 additional deaths without the German measures by early April alone. Further analysis shows that the contact restrictions have greatly slowed the rate of infections in all population groups. However, in the age group of over 60-year-olds, the containment rate was somewhat weaker than in younger people. The researchers see one plausible explanation for this in that the closing of schools and childcare facilities had a more direct and pronounced effect on children and their parents than on the generation of grandparents.
“The results of our study show that the early measures to contain the COVID-19 pandemic in Germany were successful — contrary to repeated claims in parts of the public,” Emanuel Hansen remarked. “Without these contact restrictions, Germany would probably have experienced an overload of the healthcare system, like some other European countries did.” With no other tools available in the early stages of the pandemic like vaccination or rapid testing, there was no viable alternative, Hansen added, despite the economic and social costs of closing schools and businesses. The study focused exclusively on the first COVID-19 wave in Germany and does not allow conclusions on the effects of policies in later waves of the pandemic.
Junior Professor Dr Emanuel Hansen is a member of the UoC’s Faculty of Management, Economics, and Social Sciences, the Center for Macroeconomic Research (CMR) und the Center for Social and Economic Behavior (C-SEB).
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The largest randomised placebo-controlled trial of the antibiotic amoxicillin for treating chest infections in children — one of the most common acute illnesses treated in primary care in developed countries, has found it is little more effective at relieving symptoms than the use of no medication. The study, published in The Lancet and funded by the National Institute for Health Research (NIHR), wasled by researchers from the University of Southampton and supported by centres at the Universities of Bristol, Oxford and Cardiff.
Although viruses are believed to cause many of these infections in children, whether or not antibiotics are beneficial in treatment of chest infections in children is still debated. While research so far in adults has shown that antibiotics are not effective for uncomplicated chest infections until now, there has not been the same level of research in children.
Researchers sought to test whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) lower respiratory tract chest infections in primary care. The trial recruited 432 children aged six months to twelve years-old with acute uncomplicated chest infections from primary care practices in England and Wales who were then randomly assigned to receive either amoxicillin or a placebo three times a day for seven days. Doctors or nurse-prescribers assessed symptoms at the start of the study and parents, with help from their children where possible, completed a daily symptom diary.
Only a small, non-significant, difference in the duration of symptoms were reported between the two groups: children given the placebo had symptoms which were rated moderately bad or worse for around 6 days on average after seeing the doctor, and those given antibiotics got better only 13 per cent quicker.
Furthermore, this was true even for the groups of children where the doctor heard sounds in the chest, the child had a fever, where the doctor rated the child as more unwell, the child coughed up phlegm or had a rattly chest, or the child was short of breath.
Just four children in the placebo group and five in the antibiotic group required further assessment at hospital. The costs to parents, such as the time needed to be off work or the cost of over-the-counter remedies, was very similar in both groups.
Paul Little, Professor of Primary Care Research at the University of Southampton and the study’s lead author, said: “Children given amoxycillin for chest infections where the doctor does not think the child has pneumonia do not recover much more quickly.
“Indeed, using amoxicillin to treat chest infections in children not suspected of having pneumonia is not likely to help and could be harmful. Overuse of antibiotics, which is dominated by prescribing of antibiotics in primary care, particularly when they are ineffective, can lead to side effects and the development of antibiotic resistance. Antibiotic resistance is one of the biggest threats to the health of the public, and in future could make much of what is currently routine medical practice very difficult or impossible — such having surgical operations or supporting people who are being treated for cancer.”
Alastair Hay, a GP and Professor of Primary Care at the University of Bristol’s Centre for Academic Primary Care, and one of the study’s co-authors, added: “The ARTIC PC trial is one of the very few studies to report on the effectiveness of prescribing antibiotics among younger children presenting with chest infections in primary care. It was designed to be able to detect a clinically important 3-day improvement in symptom duration.
“Our results suggest that unless pneumonia is suspected, clinicians should provide ‘safety-netting’ advice such as explaining what illness course to expect and when it would be necessary to re-attend but not prescribe antibiotics for most children presenting with chest infections.”
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Adults who needed to track their blood pressure regularly to confirm or refute a hypertension diagnosis preferred monitoring blood pressure at home versus at a clinic, kiosk or with a 24-hour wearable device, according to preliminary research presented today at the American Heart Association’s Hypertension Scientific Sessions 2021. The meeting is the premier scientific exchange focused on recent advances in basic and clinical research on high blood pressure and its relationship to cardiac and kidney disease, stroke, obesity and genetics, and is being held virtually Sept. 27-29, 2021.
According to the American Heart Association, about 1 of every 2 of U.S. adults has high blood pressure, or hypertension. More than one in three adults with high blood pressure might not know they have it. High blood pressure is defined as having a systolic pressure (the top number in a reading) of 130 mm Hg or higher, or a diastolic pressure (the bottom number) of 80 mm Hg or higher.
“Most hypertension is diagnosed and treated based on blood pressure measurements taken in a doctor’s office, even though the U.S. Preventive Services Task Force and the American Heart Association recommend that blood pressure measurements be taken outside of the clinical setting to confirm the diagnosis before starting treatment,” said lead study author Beverly Green, M.D., M.P.H., senior investigator and family physician at Kaiser Permanente Washington Health Research Institute and Kaiser Permanente Washington in Seattle. “It is the standard that blood pressure monitoring should be done either using home blood pressure monitoring or 24-hour ambulatory blood pressure monitoring prior to diagnosing hypertension.”
24-hour ambulatory blood pressure monitoring devices, worn day and night to take continuous blood pressure readings, are generally considered the “gold standard” for out-of-office measurement to determine a diagnosis of high blood pressure. However, blood pressure measured on a home device, with a traditional blood pressure arm cuff, can be a more practical and convenient approach.
Green and colleagues studied adherence and acceptability of different blood pressure measuring methods among 510 adults who had elevated blood pressure yet had not been diagnosed with high blood pressure. They were participants in the Blood Pressure Checks for Diagnosing Hypertension (BP-CHECK) trial. Participants in the study were an average age of 59 years old; 75% were non-Hispanic white, 7% African American, 6% Asian, 5% Hispanic white and 7% other; half were male; and the average blood pressure was 150/88 mm Hg. None of the participants were taking blood pressure-lowering medications.
Participants were randomly assigned to one of three groups for determining a new diagnosis of hypertension: clinic measurements, home monitoring or kiosk blood pressure monitoring.
Those in the group for clinic measurements were asked to return to the clinic for at least one additional blood pressure check, as is routine in diagnosing hypertension in clinical practice. The home group received home blood pressure machines, were trained to use them and were asked to take their blood pressure twice a day with two measurements each time, for five days, for a total of 20 measurements. The kiosk group was asked to take their blood pressure at a kiosk in their clinic or at a nearby pharmacy on three separate days, with three measurements each time, for a total of nine measurements. All participants were asked to complete their group-assigned diagnostic regimens within 3 weeks, and then to complete 24-hour ambulatory blood pressure monitoring. Researchers compared adherence to and the acceptability among each diagnostic method.
They measured adherence to monitoring by noting the percent of individuals in each group who completed their assigned measurement method as instructed. They measured acceptability with questionnaires.
Researchers found: Overall acceptability was highest for the at-home group, followed by the clinic and kiosk groups. 24-hour ambulatory blood pressure monitoring was the least acceptable option. Participants were least likely to adhere to the monitoring regimen in the kiosk group. Adherence was more than 90% among those in the home testing group; more than 87% in the clinic group; nearly 68% in the kiosk group; and 91% for 24-hour ambulatory monitoring among all participants.”Home blood pressure monitoring was the most preferred option because it was convenient, easy to do, did not disturb their daily personal or work routine as much, and was perceived as accurate,” Green said. “Participants reported that ambulatory blood pressure monitoring disturbed daily and work activities, disrupted sleep and was uncomfortable.”
When asked which diagnostic testing regimen they would prefer, more than half chose home blood pressure monitoring, especially if they were assigned to the home group, where almost 80% preferred home monitoring.
Green suggests health care professionals routinely offer home blood pressure monitoring to their patients with elevated blood pressure. This might involve providing home blood pressure monitors, training patients and collecting and averaging several days of blood pressure readings.
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Children who eat a better diet, packed with fruit and vegetables, have better mental wellbeing — according to new research from the University of East Anglia.
A new study published today is the first to investigate the association between fruit and vegetable intakes, breakfast and lunch choices, and mental wellbeing in UK school children.
It shows how eating more fruit and veg is linked with better wellbeing among secondary school pupils in particular. And children who consumed five or more portions of fruit and veg a day had the highest scores for mental wellbeing.
The study was led by UEA Health and Social Care Partners in collaboration with Norfolk County Council.
The research team say that public health strategies and school policies should be developed to ensure that good quality nutrition is available to all children before and during school to optimise mental wellbeing and empower children to fulfil their full potential.
Lead researcher Prof Ailsa Welch, from UEA’s Norwich Medical School, said: “We know that poor mental wellbeing is a major issue for young people and is likely to have long-term negative consequences.

The microbiota in the nose and upper throat likely contains biomarkers for assessing how sick an individual infected with SARS-CoV-2 may get and for developing new treatment strategies to improve their outcome, researchers say.
This nasopharyngeal microbiota is generally considered a frontline protection against viruses, bacteria and other pathogens that enter these natural passageways, says Dr. Sadanand Fulzele, geriatric researcher in the Department of Medicine at the Medical College of Georgia at Augusta University.
Distinct patterns emerged when the researchers examined the microbiota of 27 individuals age 49 to 78 who were negative for the virus, 30 who were positive but had no symptoms, and 27 who were positive with moderate symptoms that did not require hospitalization, they report in the journal Diagnostics.
“Millions of people get infected and relatively few of them become symptomatic. This might be one of the reasons,” says Dr. Ravindra Kolhe, director of MCG’s Georgia Esoteric and Molecular Laboratory, or GEM Lab. which has performed more than 100,000 COVID tests.
The most significant changes were in those who were symptomatic, including about half those patients not having a sufficient amount of microbiota to even sequence, says corresponding author Fulzele.
They were surprised to find these “low reads” of bacteria in the nasopharyngeal cavity of symptomatic individuals versus only two and four individuals in the negative and positive with no symptoms groups, respectively. The vast majority of the positive individuals with no symptoms still had sufficient microbiota, notes first author Kolhe.

When people think of DNA, they visualize a string-like double helix structure. In reality, the DNA double helix in cells is supercoiled and constrained into loops. This supercoiling and looping are known to influence every aspect of DNA activity, but how this happens has not been clear.
Published in the journal Nature Communications, a study by researchers at Baylor College of Medicine shows that supercoiling and looping can transmit mechanical stress along the DNA backbone. The stress can promote the separation of the strands of the double helix at specific distant sites, exposing the DNA bases, which may facilitate repair, replication, transcription or other aspects of DNA function.
“DNA stores a cell’s genetic information in a stable and protected form that is readily accessible for the cell to carry on its activities,” said corresponding author Dr. Lynn Zechiedrich, Kyle and Josephine Morrow Chair in molecular virology and microbiology at Baylor. “Organisms achieve this seemingly paradoxical goal by storing DNA in supercoiled loops. In the current study, we investigated how supercoiling and looping modulate DNA activity.”
Zechiedrich and her collaborators began by making small pieces of supercoiled DNA, like those present in living cells. They took a short, linear DNA double helix and twisted it once, twice, three times or more, either in the direction of the turn of the double helix (positive supercoiling) or against it (negative supercoiling). Then they connected the ends together forming a loop.
“In a previous study, we had looked at the 3-D structures of the supercoiled minicircles with electron cryotomography (cryo-ET), an imaging technique that produces high-resolution 3-D views of large molecules,” said Zechiedrich, a member of Baylor’s Dan L Duncan Comprehensive Cancer Center. “We observed a surprisingly wide variety of minicircle shapes depending on the specific supercoiling level. Many of the shapes we observed contained sharply bent DNA. This observation was unexpected.”
It was unexpected because the models indicate that supercoiled DNA circles would behave more like a twisted rubber band.