Necroptosis Is an Important Severity Determinant and Potential Therapeutic Target in Experimental Severe Pancreatitis

Peer reviewe

User-centered development of a Virtual Research Environment to support collaborative research events

This paper discusses the user-centred development process within the Collaborative Research Events on the Web (CREW) project, funded under the JISC Virtual Research Environments (VRE) programme. After presenting the project, its aims and the functionality of the CREW VRE, we focus on the user engagement approach, grounded in the method of co-realisation. We describe the different research settings and requirements of our three embedded user groups and the respective activities conducted so far. Finally we elaborate on the main challenges of our user engagement approach and end with the project’s next steps

Disk and Envelope Structure in Class 0 Protostars: I. The Resolved Massive Disk in Serpens FIRS 1

We present the first results of a program to characterize the disk and envelope structure of typical Class 0 protostars in nearby low-mass star forming regions. We use Spitzer IRS mid-infrared spectra, high resolution CARMA 230 GHz continuum imaging, and 2-D radiative transfer models to constrain the envelope structure, as well as the size and mass of the circum-protostellar disk in Serpens FIRS 1. The primary envelope parameters (centrifugal radius, outer radius, outflow opening angle, and inclination) are well constrained by the spectral energy distribution (SED), including Spitzer IRAC and MIPS photometry, IRS spectra, and 1.1 mm Bolocam photometry. These together with the excellent uv-coverage (4.5-500 klam) of multiple antenna configurations with CARMA allow for a robust separation of the envelope and a resolved disk. The SED of Serpens FIRS 1 is best fit by an envelope with the density profile of a rotating, collapsing spheroid with an inner (centrifugal) radius of approximately 600 AU, and the millimeter data by a large resolved disk with Mdisk~1.0 Msun and Rdisk~300 AU. These results suggest that large, massive disks can be present early in the main accretion phase. Results for the larger, unbiased sample of Class~0 sources in the Perseus, Serpens, and Ophiuchus molecular clouds are needed to determine if relatively massive disks are typical in the Class 0 stage.Comment: Comments: 13 pages, 8 figures, 3 tables; accepted for publication in the Ap

High-Resolution, Wide-Field Imaging of the Galactic Center Region at 330 MHz

We present a wide field, sub-arcminute resolution VLA image of the Galactic Center region at 330 MHz. With a resolution of ~ 7" X 12" and an RMS noise of 1.6 mJy/beam, this image represents a significant increase in resolution and sensitivity over the previously published VLA image at this frequency. The improved sensitivity has more than tripled the census of small diameter sources in the region, has resulted in the detection of two new Non Thermal Filaments (NTFs), 18 NTF candidates, 30 pulsar candidates, reveals previously known extended sources in greater detail, and has resulted in the first detection of Sagittarius A* in this frequency range. A version of this paper containing full resolution images may be found at http://lwa.nrl.navy.mil/nord/AAAB.pdf.Comment: Astronomical Journal, Accepted 62 Pages, 21 Figure

A multi-center, open-labeled, cluster-randomized study of the safety of double and triple drug community mass drug administration for lymphatic filariasis

BackgroundThe Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings.Methods and findingsLarge community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 μg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P ConclusionsIn this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA.Trial registrationClinicaltrials.gov registration number: NCT02899936

High Burden of Impetigo and Scabies in a Tropical Country

Scabies and impetigo are often thought of as nuisance diseases, but have the potential to cause a great deal of morbidity and even mortality if infection becomes complicated. Accurate assessments of these diseases are lacking, particularly in tropical developing countries. We performed a series of studies in infants and primary school children in Fiji, a tropical developing country in the South Pacific. Impetigo was very common: more than a quarter of school-aged children and 12% of infants had active impetigo. Scabies was also very common affecting 18% of school children and 14% of infants. The group A streptococcus was the most common infective organism followed by Staphylococcus aureus. The size of the problem has been underestimated, particularly in the Pacific. It is time for more concerted public health efforts in controlling impetigo and scabies

Protocol for a cluster-randomised non-inferiority trial of one versus two doses of ivermectin for the control of scabies using a mass drug administration strategy (the RISE study).

INTRODUCTION: Scabies is a significant contributor to global morbidity, affecting approximately 200 million people at any time. Scabies is endemic in many resource-limited tropical settings. Bacterial skin infection (impetigo) frequently complicates scabies infestation in these settings. Community-wide ivermectin-based mass drug administration (MDA) is an effective control strategy for scabies in island settings, with a single round of MDA reducing population prevalence by around 90%. However, current two-dose regimens present a number of barriers to programmatic MDA implementation. We designed the Regimens of Ivermectin for Scabies Elimination (RISE) trial to investigate whether one-dose MDA may be as effective as two-dose MDA in controlling scabies in high-prevalence settings. METHODS AND ANALYSIS: RISE is a cluster-randomised non-inferiority trial. The study will be conducted in 20 isolated villages in Western Province of Solomon Islands where population prevalence of scabies is approximately 20%. Villages will be randomly allocated to receive either one dose or two doses of ivermectin-based MDA in a 1:1 ratio. The primary objective of the study is to determine if ivermectin-based MDA with one dose is as effective as MDA with two doses in reducing the prevalence of scabies after 12 months. Secondary objectives include the effect of ivermectin-based MDA on impetigo prevalence after 12 and 24 months, the prevalence of scabies at 24 months after the intervention, the impact on presentation to health facilities with scabies and impetigo, and the safety of one-dose and two-dose MDA. ETHICS AND DISSEMINATION: This trial has been approved by the ethics review committees of the Solomon Islands and the Royal Children's Hospital, Australia. Results will be disseminated in peer-reviewed publications and in meetings with the Solomon Islands Ministry of Health and Medical Services and participating communities. TRIAL REGISTRATION DETAILS: Australian New Zealand Clinical Trials Registry: ACTRN12618001086257. Date registered: 28 June 2018

Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility

Rheumatoid arthritis (RA) is an archetypal, common, complex autoimmune disease with both genetic and environmental contributions to disease aetiology. Two novel RA susceptibility loci have been reported from recent genome-wide and candidate gene association studies. We, therefore, investigated the evidence for association of the STAT4 and TRAF1/C5 loci with RA using imputed data from the Wellcome Trust Case Control Consortium (WTCCC). No evidence for association of variants mapping to the TRAF1/C5 gene was detected in the 1860 RA cases and 2930 control samples tested in that study. Variants mapping to the STAT4 gene did show evidence for association (rs7574865, P = 0.04). Given the association of the TRAF1/C5 locus in two previous large case–control series from populations of European descent and the evidence for association of the STAT4 locus in the WTCCC study, single nucleotide polymorphisms mapping to these loci were tested for association with RA in an independent UK series comprising DNA from >3000 cases with disease and >3000 controls and a combined analysis including the WTCCC data was undertaken. We confirm association of the STAT4 and the TRAF1/C5 loci with RA bringing to 5 the number of confirmed susceptibility loci. The effect sizes are less than those reported previously but are likely to be a more accurate reflection of the true effect size given the larger size of the cohort investigated in the current study

The BIMA Survey of Nearby Galaxies (BIMA SONG). II. The CO Data

The BIMA Survey of Nearby Galaxies is a systematic imaging study of the 3 mm CO J = 1--0 molecular emission within the centers and disks of 44 nearby spiral galaxies. The typical spatial resolution of the survey is 6", or 360 pc at the average distance (12 Mpc) of the sample, over a field of view of 10kpc. The velocity resolution of the CO observations is 4 km/s. The sample was not chosen based on CO or infrared brightness; instead, all spirals were included that met the selection criteria of vsun = -20deg, inc <= 70deg, D25 < 70', and BT < 11.0. The detection rate was 41/44 sources or 93%. Fully-sampled single-dish CO data were incorporated into the maps for 24 galaxies; these single-dish data comprise the most extensive collection of fully-sampled, two-dimensional single-dish CO maps of external galaxies to date. We also tabulate direct measurements of the global CO flux densities for these 24 sources. We demonstrate that the measured ratios of flux density recovered are a function of the signal-to-noise of the interferometric data. We examine the degree of central peakedness of the molecular surface density distributions and show that the distributions exhibit their brightest CO emission within the central 6" in only 20/44 or 45% of the sample. We show that all three Local Group spiral galaxies have CO morphologies that are represented in SONG, though the Milky Way CO luminosity is somewhat below the SONG average, and M31 and M33 are well below average. This survey provides a unique public database of integrated intensity maps, channel maps, spectra, and velocity fields of molecular emission in nearby galaxies.Comment: Full-color reprints available from the authors; full resolution figures also available in electronic version of published article or at http://astro.berkeley.edu/~thelfer/bimasong_supplement.pd