Patient reported outcomes (PROs) in clinical trials: is 'in-trial' guidance lacking? a systematic review.

BACKGROUND: Patient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on 'in-trial' activity (recruitment, data collection and data inputting) and the management of 'concerning' PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this review was to determine the extent and nature of published guidelines addressing these areas. METHODS AND FINDINGS: Systematic review of 1,362 articles identified 18 eligible papers containing 'in-trial' guidelines. Two independent authors undertook a qualitative content analysis of the selected papers. Guidelines presented in each of the articles were coded according to an a priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86-0.97), and validity (<2% residual category coding). The majority of guidelines present were concerned with 'pre-trial' activities (72%), for example, outcome measure selection and study design issues, or 'post-trial' activities (16%) such as data analysis, reporting and interpretation. 'In-trial' guidelines represented 9.2% of all guidance across the papers reviewed, with content primarily focused on compliance, quality control, proxy assessment and reporting of data collection. There were no guidelines surrounding the management of concerning PRO data. CONCLUSIONS: The findings highlight there are minimal in-trial guidelines in publication regarding PRO data collection and management in clinical trials. No guidance appears to exist for researchers involved with the handling of concerning PRO data. Guidelines are needed, which support researchers to manage all PRO data appropriately and which facilitate unbiased data collection

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

Characterization, Comparative Genomics and Genome Mining for Antibiotics and Secondary Metabolite of two Actinomycetales isolates

Actinomycetes are ubiquitous Gram (+) bacteria commonly found to have high G+C content and best known for their metabolic by-products and novel enzymes [1]. Isolates CCMMD2014 & MRMD2014 were co-cultured from soil impacted by a rusty fire hydrant in Woods Hole, MA. The Streptomyces sp. and Curtobacterium sp. isolates were identified by marker genes for 16S rRNA, rpoB, xylose isomerase, tryptophan synthase beta chain and Cytochrome P450 monooxygenase. Both isolates showed lactic acid fermentation and urease activity. The co-isolates were separated by selective culturing with antibiotics. In addition, whole genome sequencing revealed distinct inherent metabolic pathways in each culture that allowed for mutually exclusive selective culture conditions. Assembly was done using HGAP3 with Celera8 assembler using SMRT portal [2,3]. Annotation was done using the RAST server [4], with 7540 and 3969 CDS for Streptomyces sp. and Curtobacterium sp. respectively being revealed by AMIGene and BASys [5,6]. Subsequently, antiSMASH [7], was used to predict 52 and 26 secondary metabolite biosynthetic clusters that included genes for lantipeptides, terpenes, siderophores, polyketide synthases type I and II, bacteriocin and nonribosomal peptide synthase genes for Streptomyces sp. and Curtobacterium sp. respectively. The isolates have genes of potentially beneficial traits that could help study, among others, the role of fimbrial adhesins and iron in biofilm formation and investigation on natural products

MEDLI2 Flight Heat Flux Sensor Environment and Planetary Protection Testing

Mars 2020 will fly the Mars Entry, Descent, and Landing Instrumentation II (MEDLI2) sensor suite consisting of a total of seventeen instrumented thermocouple sensor plugs, eight pressure transducers, two total heat flux sensors, and one radiometer embedded in the thermal protection system (TPS). Of the MEDLI2 instrumentation, eleven instrumented thermocouple plugs and seven pressure transducers will be installed on the heatshield of the Mars 2020 vehicle while the rest will be installed on the backshell. The goal of the MEDLI2 instrumentation is to directly inform the large performance uncertainties that contribute to the design and validation of a Mars entry system. A better understanding of the entry environment and TPS performance could lead to reduced design margins enabling greater payload mass-fraction and smaller landing ellipses. The MEDLI2 total heat flux sensors and radiometer are new instruments that were not flown on the Mars Science Laboratory mission. These sensors directly measure the surface heat flux and radiation at specific backshell locations. The total heat flux sensors use a Schmidt-Boelter sensing element. The radiometer version uses a sapphire window placed over the Schmidt-Boelter sensing element to separate the radiative component of the total heat flux. MEDLI2 recently planned and executed protoflight environmental testing as well planetary protection measures on the flight and flight-spare total heat flux sensors and radiometers. This testing is required to provide confidence in the performance of the flight-lot sensors when exposed to flight-like environments, and to reduce the risk of biological contamination on the planet of Mars with microbes from Earth

Radiation damage in the LHCb vertex locator

The LHCb Vertex Locator (VELO) is a silicon strip detector designed to reconstruct charged particle trajectories and vertices produced at the LHCb interaction region. During the first two years of data collection, the 84 VELO sensors have been exposed to a range of fluences up to a maximum value of approximately 45 × 1012 1 MeV neutron equivalent (1 MeV neq). At the operational sensor temperature of approximately −7 °C, the average rate of sensor current increase is 18 μA per fb−1, in excellent agreement with predictions. The silicon effective bandgap has been determined using current versus temperature scan data after irradiation, with an average value of Eg = 1.16±0.03±0.04 eV obtained. The first observation of n+-on-n sensor type inversion at the LHC has been made, occurring at a fluence of around 15 × 1012 of 1 MeV neq. The only n+-on-p sensors in use at the LHC have also been studied. With an initial fluence of approximately 3 × 1012 1 MeV neq, a decrease in the Effective Depletion Voltage (EDV) of around 25 V is observed. Following this initial decrease, the EDV increases at a comparable rate to the type inverted n+-on-n type sensors, with rates of (1.43±0.16) × 10−12 V/ 1 MeV neq and (1.35±0.25) × 10−12 V/ 1 MeV neq measured for n+-on-p and n+-on-n type sensors, respectively. A reduction in the charge collection efficiency due to an unexpected effect involving the second metal layer readout lines is observed

Complete Genome Sequence of Curtobacterium sp. Strain MR_MD2014, Isolated from Topsoil in Woods Hole, Massachusetts

Here, we present the 3,443,800-bp complete genome sequence of Curtobacterium sp. strain MR_MD2014 (phylum Actinobacteria). This strain was isolated from soil in Woods Hole, MA, as part of the 2014 Microbial Diversity Summer Program at the Marine Biological Laboratory in Woods Hole, MA