The kinematics and chemical stratification of the Type Ia supernova remnant 0519-69.0

We present an analysis of the XMM-Newton and Chandra X-ray data of the young Type Ia supernova remnant 0519-69.0 in the Large Magellanic Cloud. We used data from both the Chandra ACIS and XMM-Newton EPIC-MOS instruments, and high resolution X-ray spectra obtained with the XMM-Newton Reflection Grating Spectrometer. The Chandra data show that there is a radial stratification of oxygen, intermediate mass elements and iron, with the emission from more massive elements more toward the center. Using a deprojection technique we measure a forward shock radius of 4.0(3) pc and a reverse shock radius of 2.7(4) pc. We took the observed stratification of the shocked ejecta into account in the modeling of the X-ray spectra with multi-component NEI models, with the components corresponding to layers dominated by one or two elements. An additional component was added in order to represent the ISM, which mostly contributed to the continuum emission. This model fits the data well, and was also employed to characterize the spectra of distinct regions extracted from the Chandra data. From our spectral analysis we find that the fractional masses of shocked ejecta for the most abundant elements are: M(O)=32%, M(Si/S)=7%/5%, M(Ar+Ca)=1%, and M(Fe) = 55%. From the continuum component we derive a circumstellar density of nH= 2.4(2)/cm^3. This density, together with the measurements of the forward and reverse shock radii suggest an age of 450+/-200 yr,somewhat lower than, but consistent with the estimate based on the optical light echo (600+/-200 yr). From the RGS spectra we measured a Doppler broadening of sigma=1873+/-50 km/s, from implying a forward shock velocity of vS = 2770+/-500 km/s. We discuss the results in the context of single degenerate explosion models, using semi-analytical and numerical modeling, and compare the characteristics of 0519-69.0 with those of other Type Ia supernova remnants.Comment: Astronomy and Astrophysics in press. This version is the A&A accepted version, which contains improved figures and an extended discussion sectio

CRC COVID: Colorectal cancer services during COVID-19 pandemic. Study protocol for service evaluation

COVID-19 has had an impact on the provision of colorectal cancer care. The aim of the CRC COVID study is to describe the changes in colorectal cancer services in the UK and USA in response to the pandemic and to understand the long-term impact

SIT for African malaria vectors: Epilogue

As a result of increased support and the diligent application of new and conventional anti-malaria tools, significant reductions in malaria transmission are being accomplished. Historical and current evolutionary responses of vectors and parasites to malaria interventions demonstrate that it is unwise to assume that a limited suite of tools will remain effective indefinitely, thus efforts to develop new interventions should continue. This collection of manuscripts surveys the prospects and technical challenges for applying a novel tool, the sterile insect technique (SIT), against mosquitoes that transmit malaria. The method has been very successful against many agricultural pest insects in area-wide programs, but demonstrations against malaria vectors have not been sufficient to determine its potential relative to current alternatives, much of which will hinge ultimately upon cost. These manuscripts provide an overview of current efforts to develop SIT and identify key research issues that remain

Systems Analysis of miRNA Biomarkers to Inform Drug Safety

microRNAs (miRNAs or miRs) are short non-coding RNA molecules which have been shown to be dysregulated and released into the extracellular milieu as a result of many drug and non-drug-induced pathologies in different organ systems. Consequently, circulating miRs have been proposed as useful biomarkers of many disease states, including drug-induced tissue injury. miRs have shown potential to support or even replace the existing traditional biomarkers of drug-induced toxicity in terms of sensitivity and specificity, and there is some evidence for their improved diagnostic and prognostic value. However, several pre-analytical and analytical challenges, mainly associated with assay standardization, require solutions before circulating miRs can be successfully translated into the clinic. This review will consider the value and potential for the use of circulating miRs in drug-safety assessment and describe a systems approach to the analysis of the miRNAome in the discovery setting, as well as highlighting standardization issues that at this stage prevent their clinical use as biomarkers. Highlighting these challenges will hopefully drive future research into finding appropriate solutions, and eventually circulating miRs may be translated to the clinic where their undoubted biomarker potential can be used to benefit patients in rapid, easy to use, point-of-care test systems

A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

<p>Abstract</p> <p>Background</p> <p>The tissue factor (TF)-dependent extrinsic pathway has been suggested to be a central mechanism by which the coagulation cascade is locally activated in the lungs of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) and thus represents an attractive target for therapeutic intervention. This study was designed to determine the pharmacokinetic and safety profiles of ALT-836, an anti-TF antibody, in patients with ALI/ARDS.</p> <p>Methods</p> <p>This was a prospective, randomized, placebo-controlled, dose-escalation Phase I clinical trial in adult patients who had suspected or proven infection, were receiving mechanical ventilation and had ALI/ARDS (PaO₂/FiO₂≤ 300 mm). Eighteen patients (6 per cohort) were randomized in a 5:1 ratio to receive ALT-836 or placebo, and were treated within 48 hours after meeting screening criteria. Cohorts of patients were administered a single intravenously dose of 0.06, 0.08 or 0.1 mg/kg ALT-836 or placebo. Blood samples were taken for pharmacokinetic and immunogenicity measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory, coagulation and pulmonary function parameters.</p> <p>Results</p> <p>Pharmacokinetic analysis showed a dose dependent exposure to ALT-836 across the infusion range of 0.06 to 0.1 mg/kg. No anti-ALT-836 antibody response was observed in the study population during the trial. No major bleeding episodes were reported in the ALT-836 treated patients. The most frequent adverse events were anemia, observed in both placebo and ALT-836 treated patients, and ALT-836 dose dependent, self-resolved hematuria, which suggested 0.08 mg/kg as an acceptable dose level of ALT-836 in this patient population.</p> <p>Conclusions</p> <p>Overall, this study showed that ALT-836 could be safely administered to patients with sepsis-induced ALI/ARDS.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01438853">NCT01438853</a></p