Culture

A team of scientists used a telescope on the International Space Station to measure the size of PSR J0740+6620 (J0740, for short), the most massive known neutron star. NASA’s Neutron star Interior Composition Explorer (NICER) has captured unprecedented detail from this stellar remnant to learn more about matter in its core, which is on the threshold of collapsing into a black hole.

The NICER team will introduce their groundbreaking findings at a press conference during the 2021 APS April Meeting. NASA astronaut Christina Koch will join them to talk about how researchers use the space station as a science platform.

From pencils to pulsars

“Matter makes up everything we can see in the universe, from pencils to people to planets. In the heart of a neutron star, it’s on the verge of collapsing into a black hole,” said Cole Miller, an astronomy professor at the University of Maryland, College Park and a member of the NICER team.

“We can’t recreate those conditions on Earth, but scientists can study them from a distance by measuring the masses and sizes of neutron stars and calculating how dense they are.”

Miller will share the results from one of two groups that independently calculated the size of J0740.

Neutron star squeezability

“Our measurements of J0740 help constrain the squeezability of matter in neutron star cores, or at what density neutrons, one of the atomic building blocks, break down into smaller particles,” said Anna Watts, a professor of astrophysics at the University of Amsterdam.

Watts will share the results from the other independent team that calculated J0740’s size.

Combined with data from other neutron stars and multimessenger observations, the J0740 results herald a new age of neutron star science.

FEATURED TALKS

NICER Constraints on the Neutron Star Equation of State (E03.3, E03.4)

4:39 p.m. - 5:06 p.m. CDT, Saturday, April 17, 2021
Thomas Riley
Livestream: Access here
Abstract: http://meetings.aps.org/Meeting/APR21/Session/E03.3

5:06 p.m. - 5:33 p.m. CDT, Saturday, April 17, 2021
Cole Miller
Livestream: Access here
Abstract: http://meetings.aps.org/Meeting/APR21/Session/E03.4

PRESS CONFERENCE

Register for the press conference to be held on Zoom at 10:00 a.m. CDT, Saturday, April 17, 2021.

Speakers:

Zaven Arzoumanian (NICER Science Lead, NASA’s Goddard Space Flight Center)

Cole Miller (Professor of Astronomy, University of Maryland)

Anna Watts (Professor of Astrophysics, University of Amsterdam)

Sanjay Reddy (Professor of Physics, University of Washington)

Christina Koch (NASA Astronaut)

Media Contacts:

Claire Andreoli
Public Affairs Officer
NASA’s Goddard Space Flight Center, Greenbelt, Md.
claire.andreoli@nasa.gov
(301) 286-1940

Jeanette Kazmierczak
Science Writer
NASA’s Goddard Space Flight Center
jeanette.a.kazmierczak@nasa.gov

Researchers from Skoltech and a major European bank have developed a neural network that outperforms existing state-of-the art solutions in using transactional banking data for customer credit scoring. The research was published in the proceedings of the 2020 IEEE International Conference on Data Mining (ICDM).

Machine learning algorithms are already extensively used in risk management, helping banks assess clients and their finances. "A modern human, in particular a bank client, continually leaves traces in the digital world. For instance, the client may add information about transferring money to another person in a payment system. Therefore, every person obtains a large number of connections that can be represented as a directed graph. Such a graph gives an additional information for client's assessment. Efficient processing and usage of the rich heterogeneous information about the connections between clients is the main idea behind our study," the authors write.

Maxim Panov, who heads the Statistical Machine Learning group, and Kirill Fedyanin from Skoltech and their colleagues were able to show that using the data about money transfers between clients improves the quality of credit scoring quite significantly compared to algorithms that only use the target client's data. That would help to make better offers for trustworthy clients while lowering the negative effect of fraudulent activity.

"One of the defining properties of a particular bank client is his or her social and financial interactions with other people. It motivated us to look at bank clients as a network of interconnected agents. Thus, the goal of the study was to find out whether the famous proverb "Tell me who your friends are and I will tell you who you are" applies to financial agents," Panov says.

Their edge weight-shared graph convolutional network (EWS-GCN) uses graphs, where nodes correspond to anonymized identifiers of bank clients and edges are interactions between them, to aggregate information from them and predict the credit rating of a target client. The main feature of the new approach is the ability to process large-scale temporal graphs appearing in banking data as is, i.e. without any preprocessing which is usually complex and leads to partial loss of the information contained in the data.

The researchers ran an extensive experimental comparison of six models and the EWS-GCN model outperformed all its competitors. "The success of the model can be explained by the combination of three factors. First, the model processes rich transactional data directly and thus minimizes the loss of information contained in it. Second, the structure of the model is carefully designed to make the model expressive and efficiently parametrized, and finally, we have proposed a special training procedure for the whole pipeline," Panov notes.

He also says that for the model to be used in banking practice, it has to be very reliable. "Complex neural network models are under the threat of adversarial attacks and due to the lack of knowledge of this phenomenon in relation to our model, we cannot use it in the production process at the moment, leaving it for further research," Panov concludes.

A new study by Texas A&M University researchers published in PLOS ONE details a new model for making short-term projections of daily COVID-19 cases that is accurate, reliable and easily used by public health officials and other organizations.

Led by Hongwei Zhao, professor of biostatistics at the Texas A&M School of Public Health, researchers used a method based on the SEIR (susceptible, exposed, infected and recovered states) framework to project COVID-19 incidence in the upcoming two to three weeks based on observed incidence cases only. This model assumes a constant or small change in the transmission rate of the virus that causes COVID-19 over a short period.

The model uses publicly available data on new reported cases of COVID-19 in Texas from the COVID-19 Data Repository by the Center for Systems Science and Engineering at Johns Hopkins University. Texas A&M researchers used this data on disease incidence for Texas and a selection of counties that included the Texas A&M campus to estimate the COVID-19 transmission rate.

"The results indicate that this model can be used to reasonably predict COVID-19 cases two to three weeks in advance using only current incidence numbers," Zhao said. "The simplicity of this model is one of its greatest strengths as it can be easily implemented by organizations with few resources. Forecasts from this model can help health care organizations prepare for surges and help public health officials determine whether mask mandates or other policies will be needed."

They forecasted future infections under three possible scenarios: a sustained, constant rate of transmission; one where the transmission rate is five percent higher than current levels, reflecting a decrease in practices to prevent transmission or an increase in conditions that promote transmission; and one where transmission is five percent lower.

Estimating the current effective transmission rate can be tricky, since day-to-day variations in both infections and reporting can dramatically influence this estimate. Thus, the researchers smoothed daily reporting variations using a three-day weighted average and performed additional smoothing to account for data anomalies such as counties reporting several months of cases all at once.

The researchers compared their projections with reported incidence in Texas through four periods in 2020: April 15, June 15, August 15 and October 15. The number of new daily COVID-19 cases reported were relatively low in mid-April, when many businesses were shut down, and then started to increase in early May after phased re-openings began in Texas. The numbers increased sharply after Memorial Day, and then trended downward after a statewide mask mandate was enacted during the summer. Infections increased again after Labor Day, but then seemed to plateau until the middle of October, when the transmission rate was observed again to increase dramatically.

The statewide application of the model showed that it performed reasonably well, with only the second period forecast deviating from the actual recorded incidence, perhaps due to the dramatically changing numbers at the time when a great wave of COVID-19 occurred around the Memorial Day holiday. The model performed similarly well at the county level, though the smaller population and changes in population, such as students moving in and out of the area during the school year, influenced reporting of new cases.

However, the model is limited by the data it uses. Local testing and reporting policies and resources can affect data accuracy, and assumptions about transmission rate based on current incidence are less likely to be accurate further into the future. And as more people contract COVID-19 and recover, or are vaccinated, the susceptible population will change, possibly affecting transmission.

Despite these limitations, the researchers said the model can be a valuable tool for health care facilities and public health officials, especially when combined with other sources of information. The COVID-19 pandemic is not yet over, so having a tool that can determine when and where another surge might occur is important. Similarly, researchers hope to use these new tools at their disposal for future infectious disease needs.

Additionally, the model has been used to create a dashboard that provides real-time data on the spread of COVID-19 state-wide. It has been used locally by university administrators and public health officials.

BOSTON - Approximately one in four patients hospitalized for the acute respiratory distress syndrome (ARDS) associated with severe COVID-19 infections may have a distinct phenotype (disease presentation) or biochemical profile associated with organ dysfunction, blood-clotting abnormalities and greater risk of death than patients with other, seemingly similar forms of the disease, researchers at Massachusetts General Hospital (MGH) have found.

Among 263 patients admitted to intensive care units (ICUs) at MGH for respiratory failure due to severe COVID-19 infection, 70 (26.6%) had increased levels of biomarkers in the bloodstream indicating disordered blood clotting, higher inflammation, and organ dysfunction compared with the other patients, report Sylvia Ranjeva MD, PhD, and Lorenzo Berra, MD, investigators in the Department of Anesthesia, Critical Care and Pain Medicine, and their colleagues in that department and Pulmonary and Critical Care Medicine and Respiratory Care at MGH.

Patients with this more severe phenotype had twice the risk of death, despite minimal differences in respiratory mechanics or in the severity of ARDS between the two phenotypes.

Their findings are published in EClinicalMedicine, an open-access journal of The Lancet group.

ARDS is a catch-all term for lung injury that can arise from many different conditions such as pneumonia, severe influenza, trauma, blood infections or inflammation of the pancreas.

The syndrome can be life-threatening and may require patients to be put on mechanical ventilation, but it has been difficult for clinicians to develop effective therapies because of the wide spectrum of causes associated with it.

Pulmonary care experts typically base treatment decisions for patients with ARDS on how their bodies and immune systems respond to disease. Prior studies have suggested that some patients have what is called a "hyperinflammatory" phenotype, because their bodies respond to disease or injury by unleashing a flood of cytokines (proteins released in response to inflammation) and other substances to fight the disease. Several studies have shown that patients with the hyperinflammatory phenotype have about a 20% greater risk for death compared with other patients.

But until now, it has been unclear whether patient responses to ARDS from other causes are the same as responses to ARDS associated with COVID-19, Ranjeva explains.

"The motivation for our work is that if we can identify subsets of patients with different biochemical characteristics, and then those patients respond differently to treatment or have different clinical outcomes, we would be one step closer to a more mechanism-based understanding of ARDS," she says.

The researchers identified two distinct phenotypes of COVID-19-associated ARDS that had substantial differences in their responses to disease and in risk for death, despite having minimal differences in respiratory function and oxygenation levels.

Patients with the less common but more serious phenotype could be identified by increases in markers of organ dysfunction (for example, kidney function and cardiac biomarkers) and by increased evidence of blood-clotting dysfunction (coagulopathy).

Their results suggest that disruption of the normal regulation of blood vessels and circulation could be a key feature of critical illness, severe symptoms, and death related to COVID-19 infections, the researchers write.

Researchers at the University of Zurich show that increased sensitivity in a specific region of the brain contributes to the development of anxiety and depression in response to real-life stress. Their study establishes an objective neurobiological measure for stress resilience in humans.

Some people don't seem to be too bothered when it comes to handling stress. For others, however, prolonged exposure to stress can lead to symptoms of anxiety and depression. While stress resilience is a widely discussed concept, it is still very challenging to predict people's individual response to increased levels of stress. Lab experiments can only go so far in replicating the chronic stress many people experience in their day-to-day lives, as stress simulated in the lab is always limited in exposure time and intensity.

It is possible, however, to observe a group of medical students who are all about to face real-life stress for an extended period - during their six-month internship in the emergency room. This is precisely the real-life situation on which a team of researchers involving Marcus Grueschow and Christian Ruff from the UZH Zurich Center for Neuroeconomics and Birgit Kleim from the Department of Psychology and the University Hospital of Psychiatry Zurich based their study.

Stress as a response to cognitive conflict and loss of control

Before starting their internship, the subjects were given a task that required them to process conflicting information. This conflict task activates the locus coeruleus-norepinephrine (LC-NE) system, a region of the brain associated with regulating our response to stress and resolving conflict. However, the intensity of LC-NE activation - often referred to as the "firing rate" - varies from one person to the next.

Subjects with a higher LC-NE responsivity showed more symptoms of anxiety and depression following their emergency room internships. "The more responsive the LC-NE system, the more likely a person will develop symptoms of anxiety and depression when they're exposed to prolonged stress," Marcus Grueschow summarizes their findings.

Objective measure predicting stress resilience

With their study, the scientists have identified an objective neurobiological measure that can predict a person's stress response. This is the first demonstration that in humans, differences in LC-NE responsivity can be used as an indicator for stress resilience. "Having an objective measure of a person's ability to cope with stress can be very helpful, for example when it comes to choosing a profession. Or it could be applied in stress resilience training with neuro-feedback," Marcus Grueschow explains.

This does not mean that aspiring doctors or future police officers will all have to have their brain scanned. "There might be an even more accessible indicator for stress resilience," Christian Ruff says. Research with animals suggests that stimulation of the LC-NE system correlates with pupil dilation. "If we could establish the same causal link between pupil dilation and the LC-NE system in humans, it would open up another avenue," he adds.

The COVID-19 disease due to infection by the SARS-CoV2 virus has changed the behavior patterns of humanity by becoming a pandemic of international scope. To date, more than 136 million people have suffered from the disease and more than 2.9 million of them have lost their lives. It is important to remember that the symptoms of the infection vary widely in the population, from individuals who do not present any symptoms to those who need admission to intensive care units with emergency assisted ventilation. It is largely unknown what factors are responsible for this range of very different clinical pictures. Today, an article published in the journal EBiomedicine, The Lancet's sister journal for laboratory findings, by the group of professor Manel Esteller at the University of Barcelo and ICREA Research Professor and Dr. Aurora Pujol, also ICREA Professor and head of the Neurometabolic Diseases Group of the Bellvitge biomedical campus, shows that the epigenetic endowment of each person influences the severity of the COVID-19 disease.

"Given the high number of people infected by the virus that have saturated all health systems in the world, it would be nice to have ways to predict in advance whether the virus infection in a given individual will require hospitalization or can simply be controlled on an outpatient basis. It is known that advanced age and the co-existence of other pathologies (cardiovascular, obesity, diabetes, immune defects) are associated with a greater severity of the infection, but what happens to the rest of the population?" -Dr. Esteller wondered in the article in the EBiomedicine journal and adds - "We decided to study more than 400 people who had tested positive for COVID-19 who did not belong to any of these risk groups and study their genetic material depending on whether they had not had symptoms, or they were very mild, or instead they had been admitted to the hospital requiring respiratory assistance" adds Esteller.

"We found that there were epigenetic variations, the chemical switches that regulate DNA activity, in the individuals positive for the virus who developed a severe COVID-19. These modifications occurred mainly in genes associated with an excessive inflammatory response and in genes that reflect an overall worse state of health. Interestingly, 13% of the world population presents this epigenetic signature (EPICOVID), thus, this is the group at maximum risk that we must take special care of. " - concludes the researcher.

Key takeaways

Pancreatic, liver, bile duct, and stomach cancer operations are inherently complex and initially often take place at large cancer centers where surgical teams perform a large volume of procedures.
Readmission to a different hospital from where patients had these operations initially performed markedly increases death risk.
There are ways to address care fragmentation with newly identified risk factors for readmission; cancer hospitals should seek to determine safe sites of care for readmissions after these types of operations.

CHICAGO: New research reveals that 28 percent of patients who are readmitted to the hospital with complications after surgical removal of pancreatic, liver, or stomach cancer go to a different hospital for follow-up care. This fragmentation of health care is associated with a 50 percent increased odds of dying, according to a study published online by the Journal of the American College of Surgeons ahead of print.

The researchers from Washington University School of Medicine, St. Louis, sought to identify patient and hospital characteristics that raise the death risk during readmission to an outside hospital--one other than the original hospital where the operation was performed, referred to as the index hospital. Using the state inpatient databases from the federal Healthcare Cost and Utilization Project, the investigators evaluated data from adults undergoing surgical removal of liver, pancreatic, bile duct, and gastric cancers beginning in 2006. Patients lived in California, Florida, or New York.

A total of 31,256 patients were discharged from the hospital postoperatively, and 7,536, or 24 percent, were readmitted to any hospital in the first three months after discharge. Among readmitted patients, 28 percent, or 2,123, went to an outside hospital. As in prior research,1 the study findings showed a higher death rate for those patients versus patients returning to the index hospital: 8 percent versus 5.4 percent.

Centralized cancer care not always aligned with readmissions

Most operations to remove liver, pancreatic, bile duct or stomach cancers take place at regional medical centers where surgical teams perform a large volume of these complex procedures.2 These operations have high rates of complications and readmissions, and large surgical volume is associated with improved outcomes.

"This centralization of cancer surgical care means many patients travel great distances to undergo their operations and therefore may need to present instead to a hospital closer to home if they experience complications. That hospital may not have access to the patient's surgical records or even the specialists to care for patients with such complex medical problems," said the study's lead investigator, David G. Brauer, MD, MPHS. "Patients who experience this type of care fragmentation die more often than patients who don't experience care fragmentation. Convenience of care should not come at the expense of getting the appropriate care."

Readmission risk factors

The researchers identified the following risk factors for readmission to an outside hospital:

Longer time since the first discharge: a median, or middle value, of 25 days versus 12 days for patients readmitted to the index hospital
Living much farther from the index hospital than other readmitted patients: 24 miles versus 10 miles
Living in a rural area, older age, and white race*

(*The reason for a racial disparity will be the subject of future study but could be because white patients make up a larger proportion of rural populations compared with more metropolitan populations in the states studied.)

Ways to address fragmented care

Based on identified risk factors from this study, Dr. Brauer recommended the following ways to reduce care fragmentation for these patients:

Index hospitals should identify patients who have the "clear" risk factors found in this study, such as living far away and older age, and should determine safe sites of care for hospital readmission.
Surgeons might consider more frequent follow-up and telehealth visits with at-risk patients.
At-risk patients should ask their surgeons where they should go if they have a complication.
When patients choose an outside hospital for readmission, they should ask the treating physicians to communicate with their surgeons.
If there is any concern regarding the patient, the readmission hospital should divert care back to the surgeon or another higher-acuity hospital.

Care fragmentation is complex

The investigators noted finding characteristics of readmission hospitals that resulted in fewer in-hospital deaths, even at outside hospitals. These factors included teaching hospitals and hospitals that performed at least 100 of these cancer operations annually. However, Dr. Brauer said multivariable statistical analyses found no significant mortality association with these hospital characteristics, indicating the reasons for care fragmentation are complex.

In addition, Dr. Brauer noted geographical distance was a barrier to care access. However, neither greater distance from the index hospital nor longer time between discharge and readmission had an association with more deaths, suggesting other factors contributed to the mortality difference at outside hospitals. "Our analysis shows that returning to the original surgeon and hospital to manage complications, while preferable, may not always be an absolute necessity," Dr. Brauer said.

He concluded: "There is a suggestion that certain hospital-level characteristics, such as high surgical volume, may make an outside facility safer for postoperative readmission care. It also depends on the specifics of the patient and severity of postoperative complication, barriers to access care, and the treating physicians, including their familiarity with the patient's cancer operation."

Dr. Brauer led the research team while a surgical resident at Washington University School of Medicine, St. Louis. He is now a clinical fellow in surgical oncology at Memorial Sloan-Kettering Cancer Center, New York City. Other study authors are Ningying Wu, PhD; Matthew R. Keller, MS; Sarah A. Humble, MS; Ryan C. Fields, MD, FACS; Chet W. Hammill, MD, MCR, FACS; William G. Hawkins, MD, FACS; Graham A. Colditz, MD, DrPH; and Dominic E. Sanford, MD, MPHS, all from Washington University School of Medicine, St. Louis.

Hamilton, ON (April 14, 2021) - Modified immune cells that ruthlessly kill cancerous tumours may prove a game-changer for people living with late-stage cancer.

McMaster University researchers Ali Ashkar and Sophie Poznanski have uncovered that changing the metabolism of natural killer (NK) immune cells allows these cells to overcome the hostile conditions found inside tumours and destroy advanced ovarian and lung cancer.

In the past decade cancer immunotherapy has achieved tremendous therapeutic effects in patient with blood cancers. However, the immunosuppressive conditions found inside solid tumours, whose aggressive growth starves surrounding healthy tissues of energy, have until now remained a formidable barrier for immune cell therapies.

"In this study, we discovered that the metabolism, or energy "hub", of NK cells is paralyzed by tumours, causing the NK cells to undergo an energy crisis and lose their tumour killing functions," said Poznanski, a McMaster PhD student.

"With that understanding, we were able to reverse the dysfunction of NK cells by repurposing a pre-existing metabolism drug that restored their energy production," she added.

Poznanski is lead author of the paper published this week in the journal Cell Metabolism and a Vanier Scholar.

While these findings answered the decades-old question of how it is that NK cells are suppressed by tumours, the study has another major discovery.

"Drawing on the old adage 'To defeat your enemy, you have to think like your enemy', we additionally discovered that NK cells can be modified to mimic the metabolism of tumours," Poznanski said.

She added that the modified NK cells proved to be far better adapted for the hostile tumour environment.

"We were just hoping that the modified NK cells would better resist suppression in tumours. We were astounded to see that not only did they show no suppression, but they paradoxically functioned better inside of the tumour than outside of it."

"This is the first report of an anti-tumour immune cell that exploits the hostility of tumours for their own advantage" said senior author Ashkar, professor of medicine and the Canada Research Chair in Natural Immunity and NK Cell Function.

"Generating cytotoxic immune cells to have tumour-like metabolism is key for their anti-tumour functions in a very hostile environment of a solid tumour. This could be a paradigm shift for immune cell-based cancer immunotherapy."

So far, NK cells have only proven effective against blood cancers, he said. "The re-programmed and trained NK cells could mean patients with otherwise terminal cancers may have a safe and an effective treatment option. Lung and ovarian cancer are two examples of cancers whose survival rates have remained low over the last 30 or so years."

He added that immunotherapy with NK cells has already proven safe with few, if any, side effects.

Hal Hirte agrees. He is an associate professor of oncology at McMaster, an author of the study and a medical oncologist for Hamilton Health Sciences.

"This could have real potential for the treatment of ovarian cancer, lung cancer, and other poor prognosis tumours.

"Ovarian cancer, in particular, is one of the most immunosuppressive tumour types which is a major reason survival rates have not improved. The therapeutic effects observed in preclinical models in this study presents a major breakthrough for the field.

"Certainly, the next step is to move this promising therapy to clinical trials in patients, and we plan to have the trials underway soon to test this approach in patients with recurrent ovarian cancer."

The DNA molecule is not naked in the nucleus. Instead, it is folded in a very organized way by the help of different proteins to establish a unique spatial organization of the genetic information. This 3D spatial genome organization is fundamental for the regulation of our genes and has to be established de novo by each individual during early embryogenesis. Researchers at the MPI of Immunobiology and Epigenetics in Freiburg in collaboration with colleagues from the Friedrich Mischer Institute in Basel now reveal a yet unknown and critical role of the protein HP1a in the 3D genome re-organization after fertilisation. The study published in the scientific journal Nature identifies HP1a as an epigenetic regulator that is involved in establishing the global structure of the genome in the early Drosophila embryo.

The information of the human genome is encoded by approximately 3 billion DNA base pairs and packaged into 23 pairs of chromosomes. If all chromosomes could be disentangled and linearly aligned, they would be a thin thread of about 2 meters. The DNA molecule must be extensively packaged to fit inside the nucleus, the size of which is in the micrometer range. "The DNA thread is not simply stuffed into the cell nucleus. Instead, it is folded in a very organized way to ensure that different parts of the genome, sometimes several thousand base pairs away from each other, can intercommunicate for appropriate gene functions," says Nicola Iovino, group leader at the MPI of Immunobiology and Epigenetics in Freiburg.

Part of this packaging are histone proteins acting as spools around which DNA is winded and thereby compacted. This complex of DNA and proteins is called chromatin. As such, chromatin is the fundament for further packaging of the genetic material into chromosomes whose structure is mostly known for its characteristic cross shape. The chromosomes themself occupy distinct positions within the nucleus, known as chromosome territories, that also enable efficient packaging and organization of the genome.

The full machinery contributing to this 3D chromatin organization remains unexplored. Now the lab of Nicola Iovino at the MPI in Freiburg, in collaboration with Luca Giorgetti from the Friedrich Miescher Institute in Basel (Switzerland), was able to show the fundamental role of the heterochromatin protein 1a (HP1a) in the reorganization of the 3D chromatin structure after fertilization. By combining powerful Drosophila genetics with 3D genome modeling, they discovered that HP1a is required to establish a proper chromatin 3D structure at multiple hierarchical levels during early embryonic development.

Early embryos as a model to study chromatin reprogramming

The degree of packaging as well as the corresponding gene activity is influenced by epigenetic modifications. These are small chemical groups that are installed on the histones. "Proteins that carry out these epigenetic modifications can be thought of as being either writers, erasers or reader of the given epigenetic modification. We discovered that the reader protein HP1a is required to establish chromatin structure during early embryonic development in Drosophila", says Fides Zenk, first-author of the study.

Early embryonic development is a particularly interesting time window to study the processes governing the organization of chromatin. At fertilization, two highly specialized cells - sperm and egg - fuse. The resulting totipotent zygote will ultimately give rise to all the different cells of the body. Interestingly most of the epigenetic modifications that shape chromatin are erased and have to be established de novo. In Drosophila, the lab of Nicola Iovino had previously shown that after fertilization chromatin undergoes major restructuring events. Thus, it is the ideal model system to study the processes underlying the establishment of chromatin structure.

De novo establishment of 3D genome architecture

When the genome of the zygote is activated for the first time after fertilization, it triggers global de novo 3D chromatin reorganization including a clustering of highly compacted regions around the centromere (pericentromeric), the folding of chromosome arms and the segregation of chromosomes into active and inactive compartments. "We identified HP1a as an important epigenetic regulator necessary to maintain individual chromosome integrity but also central for establishing the global structure of the genome in the early embryo," says Nicola Iovino.

3D genome simulation

These findings and data collected in Drosophila embryos have then been used by collaborators from the Friedrich Miescher Institute (FMI) lead by Luca Giorgetti to build realistic three-dimensional models of chromosomes. This is possible because chromosomes inside the cell nucleus are polymers, very large molecules composed of chains of smaller components (monomers) - in this case consecutive DNA base pairs and the DNA-binding proteins that together constitute the chromatin fiber. Like all other polymers, be it silk, polyethylene or polyester, chromatin obeys a general set of physical laws described by a branch of physics known as 'polymer physics'. These laws can be encoded into computer programs and used to simulate the three-dimensional shape of chromosomes in the nucleus.

"The advantage of this approach is that it allows simulating the effects of very large numbers of mutations. This enables researchers to explore scenarios that are beyond experimental reach, such as the simultaneous depletion of many different proteins that would require years of lab work. By comparing simulations with the outcome of experiments, this approach also allows to test alternative hypotheses concerning the mechanisms that lay at the basis of experimental observations," says Luca Giorgetti, group leader at the Friedrich Miescher Institute in Basel.

In this case, FMI researchers used polymer models of the entire Drosophila genome to ask the question: based on the basic laws of polymer physics, is it possible that the depletion of a single protein - HP1 - leads to a massive change in the associations and shape of chromosomes in the nucleus? Or are additional mechanisms needed to explain the experimental observations? "We found that removal of the protein to its binding sites in the simulations accounted for the full set of experimental results, thus providing further confirmation that HP1 plays a key role in establishing the three-dimensional structure of the genome" says Yinxiu Zhan, co-first-author of the study.

Leesburg, VA, April 15, 2021--A Scientific E-Poster to be presented at the 2021 ARRS Virtual Annual Meeting found that as the United States Medical Licensing Examination (USMLE) Step 1 transitions from a numerical score to pass or fail--as early as January 2022--radiology residency program directors will likely rely on USMLE Step 2 Clinical Knowledge (CK) scores as an objective and standardized metric to screen applicants.

"However," wrote lead investigator Rebecca Zhang of the University of Maryland School of Medicine in Baltimore, "program directors remain unsure whether they will require Step 2 CK scores at the time of application or before interviewing applicants."

To evaluate the anticipated importance of various application metrics when Step 1 becomes pass or fail, Zhang's team distributed an anonymous and voluntary 14-item electronic survey to 308 active members of the Association of Program Directors in Radiology, performing secondary analyses to compare responses based on the current use of a Step 1 scoring screen.

With 29% of respondents completing the online survey, a majority (64%) of program directors noted that an applicant's Step 2 CK score will likely be one of the top three most important factors in assessing applicants, followed by class ranking (51%) and the Medical Student Performance Evaluation or Dean's Letter (37%). Most (90%) of respondents predicted their programs may or definitively will require Step 2 CK scores before reviewing an application, and 50% of respondents anticipated extending interview invitations at a later date to receive Step 2 CK scores.

Acknowledging that additional research may identify other objective metrics for holistic evaluations, "these results did not significantly differ between programs who currently use a Step 1 scoring screen and those who do not," the authors of this ARRS Annual Meeting E-Poster concluded.

Leesburg, VA, April 15, 2021--A Scientific E-Poster to be presented at the 2021 ARRS Virtual Annual Meeting found that in the setting of a high pretest probability of COVID-19 infection or with a quick turnaround of the rapid real-time reverse transcriptase-polymerase chain reaction (RT-PCR) COVID-19 test, a chest x-ray (CXR) scoring system may be used prospectively to predict patient outcomes.

"We developed an accurate and reliable tool for classifying COVID-19 severity, which can be used both at the attending chest radiologist and junior resident level. This study identifies the laboratory, clinical and radiographic data that predict important patient outcomes such as death, intubation, and the need for chronic renal replacement therapy (CRRT)," wrote first author Russell Reeves of Thomas Jefferson University in Philadelphia, PA.

Reeves and colleagues identified patients with nucleic acid-confirmed COVID-19 admitted to an urban multicenter health system from March 16 to April 13, 2020. Three cardiothoracic radiologists and three diagnostic radiology residents then independently scored their admission CXRs, based on extent and severity of COVID-19 pneumonia. Demographic variables, clinical characteristics, and admission laboratory values were collected, while interrater reliability among attending, resident, and the combined group of graders was assessed.

Of the 240 patients (142 males, 98 females; median age, 65 years) who met the inclusion criteria, interrater reliability for CXR scoring was high (mean, 0.686) among the attending, residents, and combination of graders. Furthermore, there was no difference in outcomes across gender, race, ethnicity, or those with either a history of lung cancer or chronic obstructive pulmonary disease. Although CXR severity proved an independent predictor of death (p

"These findings are supported by prior work, validating the utility of CXR for patient prognostication, while adding new insight into COVID-19 infection during the initial presentation," the authors of this ARRS Annual Meeting E-Poster concluded.

A study published this week in The Lancet Public Health examines how we can use our income assistance systems to address drug use and drug-related harm.

The study, led by University of British Columbia (UBC) medical sociologist Dr. Lindsey Richardson and conducted at the British Columbia Centre on Substance Use (BCCSU), tests whether varying the timing and frequency of income assistance payments can mitigate drug-related harms linked to the existing once-monthly payment schedule that is common across North America and Europe. Monthly synchronized income assistance payments have long been linked to considerable and costly increases in drug use and resulting harm, including overdose, hospital admission, treatment interruption and emergency service calls.

The study finds that varying when people who use drugs receive their income assistance payments reduces escalations in drug use around government payment days as well as individual payment days outside the week of the standard government schedule. However, changes also have unintended consequences that may increase individual drug-related harm, specifically exposure to violence. The study confirms preliminary results reported at multiple scientific meetings.

"As drug use and drug-related harm continue to be a defining public health challenge that has only been exacerbated by the COVID-19 pandemic, innovative thinking about how social and preventive approaches can help mitigate these harms is critical," says Dr. Richardson, research scientist at BCCSU, associate professor at UBC and principal investigator of the study. "These complex findings signal the potential for the income assistance system to address both the consequences of poverty as well as the severe drug-related harm seen each month around payments."

Researchers at the BCCSU followed 194 participants in Vancouver, British Columbia for six-month periods between 2015 and 2019 to evaluate the impact of alternative payment schedules. In British Columbia, income assistance is distributed on the last Wednesday of each month.

Two interventions were evaluated in comparison with the standard monthly cheque distribution: a staggered schedule where participants receive payments monthly on a day that does not fall during the week of synchronized government disbursement; and a split and staggered schedule, where participants receive semi-monthly payments two weeks apart on days that do not fall during the week of synchronized government disbursement.

The study found:

Intervention participants were about one-third as likely to increase their drug use on government payment days when they received their payments either desynchronized from government payments or desynchronized and in smaller increments, particularly in terms of the frequency of use and quantity of substances used.

Intervention participants were about one-half as likely to increase their drug use on their individual payment days when they received their payments.

Study analyses also identified that participants in the staggered study group may be more likely to be exposed to violence.

While conducted locally, the study's findings have important applications for contexts that see drug-related harm concentrate around income support payments. The study illustrates the importance of experimental research in anticipating the intended and unintended effects of social and other policy reforms. It also points to the importance of preventive, in addition to reactive responses such as naloxone administration to the ongoing crisis of drug use, drug toxicity and overdose.

There have been longstanding calls for upstream interventions to address the inequitable distribution of drug-related harm among disadvantaged populations. This study responds with an innovative experimental study specifically focusing on a known social determinant of health, applying sociological knowledge about the social drivers of drug use to a long-identified challenge for individuals, service providers and first responders.

Importantly, the findings of the study do not justify the drug testing of benefit recipients nor the retrenchment or withdrawal of benefits for people who use drugs, practices that are largely deemed unfair, immoral and objectionable.

The study authors urged that any changes to income assistance schedules must accommodate the complexity of people's lives and avoids a one-size-fits-all approach by allowing for choice in preferred schedule, providing flexibility to change as life circumstances change and focusing on the autonomy and dignity of recipients.

Tokyo, Japan - A team of scientists led by the Institute of Biomaterials and Bioengineering at Tokyo Medical and Dental University (TMDU) have created novel molecules that prevent human immunodeficiency virus (HIV) particles from attacking immune cells. This is accomplished by injecting compounds mimicking the protein the virus usually uses to enter the cells. This work may lead to new treatments for HIV that may be more effective at stopping the proliferation of the virus with fewer side effects.

HIV is a very dangerous pathogen because it attacks the very immune cells, including T helper cells, that are needed for the body to fight back. An HIV particle first gains entrance to a T helper cell by attaching to a CD4 protein on its surface. Once inside, the reproduction machinery of the T helper cell is hijacked to make copies of HIV, ultimately killing the host cell. Many treatments, such as antiretroviral drugs, attempt to block this reproduction process, but finding a way to prevent the HIV from attaching in the first place would be a better approach.

Now, a team of researchers led by Tokyo Medical and Dental University (TMDU) created a new family of molecules that act as decoy CD4 proteins. The HIV particles preferentially attach with the fake molecules, instead of those at the surface of a cell. The scientists found that adding a polyethylene glycol (PEG) improved the pharmacokinetics. "Hybrid molecules that mimic CD4 and also have a PEG unit attached with an uncleavable linker showed better anti-HIV activity with lower cytotoxicity," first author Takuya Kobayakawa says.

Computer simulations run by the team supported the hypothesis that the hybrid molecule works better because it can interact electrostatically with a carboxylate group on the virus. In tests with a rhesus macaque, the hybrid molecule remained in the system longer compared with the parent compound. "These CD4 mimics have strong synergistic interactions with neutralizing antibodies for fighting HIV," senior author Hirokazu Tamamura says. New combined treatment protocols may be developed to help take advantage of the new molecules. The work is published in the Journal of Medicinal Chemistry as "Hybrids of Small-Molecule CD4 Mimics with Polyethylene Glycol Units as HIV Entry Inhibitors." (DOI:10.1021/acs.jmedchem.0c01153).

It is often said that before air travel our skies were bluer yet how, in the 21st century, could we ever know what light and colors were like one hundred years ago? Recently, a group of researchers from EPFL's Audiovisual Communications Laboratory, in the School of Computer and Communication Sciences (IC), had a unique opportunity to try to find out.

Normally hidden treasures locked away in the vaults of a handful of museums, the researchers were offered access to some of the original photographic plates and images of the scientist and inventor Gabriel Lippmann, who won the 1908 Nobel Prize in physics for his method of reproducing colors in photography.

In a paper just published in the Proceedings of the National Academy of Sciences (PNAS) the authors explain that most photographic techniques take just three measurements, for red, green and blue, however they discovered that Lippmann's historical approach typically captured 26 to 64 spectral samples of information in the visible region. His technique, based on the same interference principles that recently enabled gravitational waves to be detected and which is the foundation of holography and much of modern interferometric imaging, has been almost completely forgotten today.

"These are the earliest multi-spectral light measurements on record so we wondered whether it would be possible to accurately recreate the original light of these historical scenes," said Gilles Baechler, one of the paper's authors, "but the way the photographs were constructed was very particular so we were also really interested in whether we could create digital copies and understand how the technique worked."

The researchers found that the multi-spectral images reflected from a Lippmann plate contained distortions, although the reproduced colors looked accurate to the eye. When they examined the full spectrum reflected from a Lippmann plate, and compared it to the original, they measured a number of inconsistencies, many of which have never been documented, even in modern studies.

"We ended up modeling the full process from the multi-spectral image that you capture, all the way to recording it into the photograph. We were able to capture the light reflected back from it and measure how it differed from the original," explained Baechler. So, could the team replicate century old light?

"With the historic plates there are factors in the process that we just cannot know but because we understood how the light differed, we could create an algorithm to get back the original light that was captured. We were able to study invertibility, that is, given a spectrum produced by a Lippmann photograph we know it is possible to undo the distortions and reconstruct the original input spectrum. When we got our hands dirty and made our own plates using the historical process, we were able to verify that the modeling was correct," he continued.

While fully modeling a Nobel-prize-winning imaging technique is of significant interest in its own right, the researchers believe that revisiting Lippmann's photographic technique can inspire new technological developments this century.

The team has already built a prototype of a digital Lippmann camera and is particularly intrigued by the possibilities of multi-spectral image synthesis as well as new multi-spectral camera, printing and display designs.

"This enables us to contrast the subjective perception of stress with an objective measurement method and compare the two," explains Nina Minkley. Contrary to expectations, it turned out that the effort invested in the task does not increase with its difficulty, nor does the stress level. The study was featured in the journal Frontiers in Education on 12. April 2021.

Simple questionnaire surveys criticised

To date, the stress experience of students has mostly been surveyed with questionnaires. But this approach has been criticised, because many factors have an effect on one's own perception that have nothing to do with the task. "For example, women often report higher stress levels than men," points out Nina Minkley. The researchers can only speculate why this is the case. In the current study, they used an objective method of measuring stress levels.

They equipped 209 secondary school students who were working on biology tasks with chest straps that monitor the heart rate. They also had the participants fill out several questionnaires on their self-concept, their interest in biology and their perception of the tasks. "When we are relaxed, the individual heartbeats differ slightly, whereas when we are stressed, they are less variable," explains Nina Minkley. Thus, the change in heart rate variability is an objective measurement of the stress level.

Mental effort causes stress

Comparing the questionnaire answers with the measured heart rates revealed that it was mainly mental engagement, i.e. the effort the students invested in solving the tasks, that correlated with the objective stress level. Contrary to expectations, however, more difficult tasks did not increase stress. "Perhaps some tasks can be so difficult that students don't even try to work on them," concludes Nina Minkley. "Such objective measures could be used in future studies primarily to survey subjective cognitive stress dimension."