A comprehensive study of GRB 070125, a most energetic gamma ray burst

We present a comprehensive multiwavelength analysis of the bright, long duration gamma-ray burst GRB 070125, comprised of observations in $\gamma$-ray, X-ray, optical, millimeter and centimeter wavebands. Simultaneous fits to the optical and X-ray light curves favor a break on day 3.78, which we interpret as the jet break from a collimated outflow. Independent fits to optical and X-ray bands give similar results in the optical bands but shift the jet break to around day 10 in the X-ray light curve. We show that for the physical parameters derived for GRB 070125, inverse Compton scattering effects are important throughout the afterglow evolution. While inverse Compton scattering does not affect radio and optical bands, it may be a promising candidate to delay the jet break in the X-ray band. Radio light curves show rapid flux variations, which are interpreted as due to interstellar scintillation, and are used to derive an upper limit of $2.4 \times 10^{17}$ cm on the radius of the fireball in the lateral expansion phase of the jet. Radio light curves and spectra suggest a high synchrotron self absorption frequency indicative of the afterglow shock wave moving in a dense medium. Our broadband modeling favors a constant density profile for the circumburst medium over a wind-like profile ($R^{-2}$). However, keeping in mind the uncertainty of the parameters, it is difficult to unambiguously distinguish between the two density profiles. Our broadband fits suggest that \event is a burst with high radiative efficiency ($> 60$).Comment: 50 pages, 33 figures, sty file included, Appeared in 20 Aug 2008 edition of Astrophysical Journa

Immunogenicity of a DNA vaccine candidate for COVID-19

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study

Whole-genome sequencing of 490,640 UK Biobank participants

Whole-genome sequencing provides an unbiased and complete view of the human genome and enables the discovery of genetic variation without the technical limitations of other genotyping technologies. Here we report on whole-genome sequencing of 490,640 UK Biobank participants, building on previous genotyping effort1. This advance deepens our understanding of how genetics associates with disease biology and further enhances the value of this open resource for the study of human biology and health. Coupling this dataset with rich phenotypic data, we surveyed within- and cross-ancestry genomic associations and identified novel genetic and clinical insights. Although most associations with disease traits were primarily observed in individuals of European ancestries, strong or novel signals were also identified in individuals of African and Asian ancestries. With the improved ability to accurately genotype structural variants and exonic variation in both coding and UTR sequences, we strengthened and revealed novel insights relative to whole-exome sequencing2,3 analyses. This dataset, representing a large collection of whole-genome sequencing data that is available to the UK Biobank research community, will enable advances of our understanding of the human genome, facilitate the discovery of diagnostics and therapeutics with higher efficacy and improved safety profile, and enable precision medicine strategies with the potential to improve global health

Development of a Skin-Directed Scoring System for Stevens-Johnson Syndrome and Epidermal Necrolysis

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent. Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN. Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement. Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated. Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology

Axillary Ultrasound Evaluation in Breast Cancer Patients: A Multidisciplinary Viewpoint and Middle Ground

Abstract Over the past decade, there has been a trend toward de-escalation of axillary surgery. Certain patients may now forego axillary lymph node dissection even in the setting of a positive sentinel lymph node biopsy (SLNB), and some patients may not even undergo a SLNB. However, there is wide variability in the imaging approach to assessing axillary lymph nodes in patients with breast cancer. Approaches range from performing axillary US in all patients with newly diagnosed breast cancer to omitting axillary imaging evaluation in all patients. This article provides a multidisciplinary middle ground approach for axillary nodal evaluation. The clinical impact and rationale for appropriate axillary nodal imaging are discussed and an imaging algorithm is proposed.</jats:p

Risk prediction for sudden cardiac death from image derived cardiac motion and structure features

Systems and methods for personalized sudden cardiac death risk prediction that generates fingerprints of imaging features of cardiac structure and function. One or more fingerprints and clinical data may be used to generate a risk score. The output risk score may be used to predict the time of death in order to select high-risk patients for implantable cardioverter-defibrillator treatment

Effectiveness of Pediatric Asthma Pathways in Community Hospitals: A Multisite Quality Improvement Study.

Pathways guide clinicians through evidence-based care of specific conditions. Pathways have been demonstrated to improve pediatric asthma care, but mainly in studies at tertiary children's hospitals. Our global aim was to enhance the quality of asthma care across multiple measures by implementing pathways in community hospitals.MethodsThis quality improvement study included children ages 2-17 years with a primary diagnosis of asthma. Data were collected before and after pathway implementation (total 28 mo). Pathway implementation involved local champions, educational meetings, audit/feedback, and electronic health record integration. Emergency department (ED) measures included severity assessment at triage, timely systemic corticosteroid administration (within 60 mins), chest radiograph (CXR) utilization, hospital admission, and length of stay (LOS). Inpatient measures included screening for secondhand tobacco and referral to cessation resources, early administration of bronchodilator via metered-dose inhaler, antibiotic prescription, LOS, and 7-day readmission/ED revisit. Analyses were done using statistical process control.ResultsWe analyzed 881 ED visits and 138 hospitalizations from 2 community hospitals. Pathways were associated with increases in the proportion of children with timely systemic corticosteroid administration (Site 1: 32%-57%, Site 2: 62%-75%) and screening for secondhand tobacco (Site 1: 82%-100%, Site 2: 54%-89%); and decreases in CXR utilization (Site 1: 44%-29%), ED LOS (Site 1: 230-197 mins), and antibiotic prescription (Site 2: 23%-3%). There were no significant changes in other outcomes.ConclusionsPathways improved pediatric asthma care quality in the ED and inpatient settings of community hospitals

Real-World Effectiveness of a Third Dose of mRNA-1273 Versus BNT162b2 on Inpatient and Medically Attended COVID-19 Among Immunocompromised US Adults

Abstract Introduction Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US). Methods This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method. Results In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506–0.887), 29.3% (0.707; 0.573–0.858), and 23.4% (0.766; 0.626–0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860–0.976), 6.4% (0.936; 0.895–0.978), and 2.4% (0.976; 0.935–1.017), respectively. Conclusions Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US