PPARα contributes to protection against metabolic and inflammatory derangements associated with acute kidney injury in experimental sepsis

Abstract Sepsis‐associated acute kidney injury (AKI) is a significant problem in critically ill children and adults resulting in increased morbidity and mortality. Fundamental mechanisms contributing to sepsis‐associated AKI are poorly understood. Previous research has demonstrated that peroxisome proliferator‐activated receptor α (PPARα) expression is associated with reduced organ system failure in sepsis. Using an experimental model of polymicrobial sepsis, we demonstrate that mice deficient in PPARα have worse kidney function, which is likely related to reduced fatty acid oxidation and increased inflammation. Ultrastructural evaluation with electron microscopy reveals that the proximal convoluted tubule is specifically injured in septic PPARα deficient mice. In this experimental group, serum metabolomic analysis reveals unanticipated metabolic derangements in tryptophan‐kynurenine‐NAD+ and pantothenate pathways. We also show that a subgroup of children with sepsis whose genome‐wide expression profiles are characterized by repression of the PPARα signaling pathway has increased incidence of severe AKI. These findings point toward interesting associations between sepsis‐associated AKI and PPARα‐driven fatty acid metabolism that merit further investigation

Draft Genome Sequence of the Iridescent Marine Bacterium Tenacibaculum discolor Strain IMLK18

We report here the draft genome sequence of a strain of Tenacibaculum discolor (Bacteroidetes) that was isolated from the river-ocean interface at Trunk River in Falmouth, Massachusetts. The isolation and genomic sequencing were performed during the 2016 and 2018 Microbial Diversity summer programs at the Marine Biological Laboratory in Woods Hole, Massachusetts

Motion robust MR fingerprinting scan to image neonates with prenatal opioid exposure

Background: A noninvasive and sensitive imaging tool is needed to assess the fast-evolving baby brain. However, using MRI to study non-sedated babies faces roadblocks, including high scan failure rates due to subjects motion and the lack of quantitative measures for assessing potential developmental delays. This feasibility study explores whether MR Fingerprinting scans can provide motion-robust and quantitative brain tissue measurements for non-sedated infants with prenatal opioid exposure, presenting a viable alternative to clinical MR scans. Assessment: MRF image quality was compared to pediatric MRI scans using a fully crossed, multiple reader multiple case study. The quantitative T1 and T2 values were used to assess brain tissue changes between babies younger than one month and babies between one and two months. Statistical Tests: Generalized estimating equations (GEE) model was performed to test the significant difference of the T1 and T2 values from eight white matter regions of babies under one month and those are older. MRI and MRF image quality were assessed using Gwets second order auto-correlation coefficient (AC2) with its confidence levels. We used the Cochran-Mantel-Haenszel test to assess the difference in proportions between MRF and MRI for all features and stratified by the type of features. Results: In infants under one month of age, the T1 and T2 values are significantly higher (p<0.005) compared to those between one and two months. A multiple-reader and multiple-case study showed superior image quality ratings in anatomical features from the MRF images than the MRI images. Conclusions: This study suggested that the MR Fingerprinting scans offer a motion-robust and efficient method for non-sedated infants, delivering superior image quality than clinical MRI scans and additionally providing quantitative measures to assess brain development

Draft Genome Sequence of the Iridescent Marine Bacterium Tenacibaculum discolor Strain IMLK18

We report here the draft genome sequence of a strain of Tenacibaculum discolor (Bacteroidetes) that was isolated from the river-ocean interface at Trunk River in Falmouth, Massachusetts. The isolation and genomic sequencing were performed during the 2016 and 2018 Microbial Diversity summer programs at the Marine Biological Laboratory in Woods Hole, Massachusetts

Report of the 13th Genomic Standards Consortium Meeting, Shenzhen, China, March 4–7, 2012

This report details the outcome of the 13th Meeting of the Genomic Standards Consortium. The three-day conference was held at the Kingkey Palace Hotel, Shenzhen, China, on March 5–7, 2012, and was hosted by the Beijing Genomics Institute. The meeting, titled From Genomes to Interactions to Communities to Models, highlighted the role of data standards associated with genomic, metagenomic, and amplicon sequence data and the contextual information associated with the sample. To this end the meeting focused on genomic projects for animals, plants, fungi, and viruses; metagenomic studies in host-microbe interactions; and the dynamics of microbial communities. In addition, the meeting hosted a Genomic Observatories Network session, a Genomic Standards Consortium biodiversity working group session, and a Microbiology of the Built Environment session sponsored by the Alfred P. Sloan Foundatio

Updated standardized definitions for efficacy endpoints in adjuvant breast cancer clinical trials: STEEP Version 2.0

Purpose The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed.Methods We conducted systematic searches of ClinicalTrials.gov for adjuvant systemic and local-regional therapy trials for breast cancer to investigate if the primary end points reported met STEEP criteria. On the basis of common STEEP deviations, we performed a series of simulations to evaluate the effect of excluding non-breast cancer deaths and new nonbreast primary cancers from the invasive disease-free survival end point.Results Among 11 phase III breast cancer trials with primary efficacy end points, three had primary end points that followed STEEP criteria, four used STEEP definitions but not the corresponding end point names, and four used end points that were not included in the original STEEP manuscript. Simulation modeling demonstrated that inclusion of second nonbreast primary cancer can increase the probability of incorrect inferences, can decrease power to detect clinically relevant efficacy effects, and may mask differences in recurrence rates, especially when recurrence rates are low.Conclusion We recommend an additional end point, invasive breast cancer-free survival, which includes all invasive disease-free survival events except second nonbreast primary cancers. This end point should be considered for trials in which the toxicities of agents are well-known and where the risk of second primary cancer is small. Additionally, we provide end point recommendations for local therapy trials, low-risk populations, noninferiority trials, and trials incorporating patient-reported outcomes

Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP.

PURPOSE: The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007 and updated in 2021 (STEEP 2.0), provide standardized definitions of adjuvant breast cancer (BC) end points. STEEP 2.0 identified a need to separately address end points for neoadjuvant clinical trials. The multidisciplinary NeoSTEEP working group of experts was convened to critically evaluate and align neoadjuvant BC trial end points. METHODS: The NeoSTEEP working group concentrated on neoadjuvant systemic therapy end points in clinical trials with efficacy outcomes-both pathologic and time-to-event survival end points-particularly for registrational intent. Special considerations for subtypes and therapeutic approaches, imaging, nodal staging at surgery, bilateral and multifocal diseases, correlative tissue collection, and US Food and Drug Administration regulatory considerations were contemplated. RESULTS: The working group recommends a preferred definition of pathologic complete response (pCR) as the absence of residual invasive cancer in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0 per AJCC staging). Residual cancer burden should be a secondary end point to facilitate future assessment of its utility. Alternative end points are needed for hormone receptor-positive disease. Time-to-event survival end point definitions should pay particular attention to the measurement starting point. Trials should include end points originating at random assignment (event-free survival and overall survival) to capture presurgery progression and deaths as events. Secondary end points adapted from STEEP 2.0, which are defined from starting at curative-intent surgery, may also be appropriate. Specification and standardization of biopsy protocols, imaging, and pathologic nodal evaluation are also crucial. CONCLUSION: End points in addition to pCR should be selected on the basis of clinical and biologic aspects of the tumor and the therapeutic agent investigated. Consistent prespecified definitions and interventions are paramount for clinically meaningful trial results and cross-trial comparison

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson