Background. Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case ...definitions, standardized diagnostic approaches, and priorities for research. Methods. In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. Results. We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. Conclusions. We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.
Dusty star-forming galaxies at high redshift (1 < z < 3) represent the most intense star-forming regions in the universe. Key aspects to these processes are the gas heating and cooling mechanisms, ...and although it is well known that these galaxies are gas-rich, little is known about the gas excitation conditions. Only a few detailed radiative transfer studies have been carried out owing to a lack of multiple line detections per galaxy. Here we examine these processes in a sample of 24 strongly lensed star-forming galaxies identified by the Planck satellite (LPs) at z ∼ 1.1-3.5. We analyze 162 CO rotational transitions (ranging from Jup = 1 to 12) and 37 atomic carbon fine-structure lines (C i) in order to characterize the physical conditions of the gas in the sample of LPs. We simultaneously fit the CO and C i lines and the dust continuum emission, using two different non-LTE, radiative transfer models. The first model represents a two-component gas density, while the second assumes a turbulence-driven lognormal gas density distribution. These LPs are among the most gas-rich, IR-luminous galaxies ever observed ( L L IR ( 8 − 1000 m ) ∼ 10 13 − 14.6 L ; 〈 LMISM 〉 = (2.7 1.2) × 1012 M , with L ∼ 10-30 the average lens magnification factor). Our results suggest that the turbulent interstellar medium present in the LPs can be well characterized by a high turbulent velocity dispersion ( 〈 ΔVturb 〉 ∼ 100 km s−1) and ratios of gas kinetic temperature to dust temperature 〈 Tkin/Td 〉 ∼ 2.5, sustained on scales larger than a few kiloparsecs. We speculate that the average surface density of the molecular gas mass and IR luminosity, M ISM ∼ 103-4 M pc−2 and L IR ∼ 1011-12 L kpc−2, arise from both stellar mechanical feedback and a steady momentum injection from the accretion of intergalactic gas.
We estimate total mass (M500), intracluster medium (ICM) mass (MICM), and stellar mass (M*) in a Sunyaev–Zel’dovich effect (SZE) selected sample of 91 galaxy clusters with masses M500 ≳ 2.5 × 1014 M⊙ ...and redshift 0.2 < z < 1.25 from the 2500 deg^2 South Pole Telescope SPT-SZ survey. The total masses M500 are estimatedfrom the SZE observable, the ICM masses MICM are obtained from the analysis of Chandra X-ray observations, and the stellar masses M* are derived by fitting spectral energy distribution templates to Dark Energy Survey griz optical photometry and WISE or Spitzer near-infrared photometry. We study trends in the stellar mass, the ICM mass, the total baryonic mass, and the cold baryonic fraction with cluster halo mass and redshift. We find significant departures from self-similarity in the mass scaling for all quantities, while the redshift trends are all statistically consistent with zero, indicating that the baryon content of clusters at fixed mass has changed remarkably little over the past ≈9 Gyr. We compare our results to the mean baryon fraction (and the stellar mass fraction) in the field, finding that these values lie above (below) those in cluster virial regions in all but the most massive clusters at low redshift. Using a simple model of the matter assembly of clusters from infalling groups with lower masses and from infalling material from the low-density environment or field surrounding the parent haloes, we show that the measured mass trends without strong redshift trends in the stellar mass scaling relation could be explained by a mass and redshift dependent fractional contribution from field material. Similar analyses of the ICM and baryon mass scaling relations provide evidence for the so-called ‘missing baryons’ outside cluster virial regions.
Selenium nanoparticles (SeNPs) are well reported to exhibit pharmacological activities both in vitro and in vivo. However, literature is devoid of studies on the impact of SeNPs and/or metformin (M) ...against streptozotocin (STZ)-mediated oxidative brain injury and behavioral impairment. Consequently, to fill this gap, diabetes was induced in male Wistar rats by feeding with 10% fructose solution for 2 weeks, followed by a single dose intraperitoneal injection of STZ (40 mg/kg body weight bwt). After rats were confirmed diabetic, they were treated orally with 0.1 mg/kg bwt of SeNPs ± M (50 mg/kg bwt), and normal control (NC) received citrate buffer (2 mg/mL) for 5 weeks. In comparison with the diabetic control (DC), SeNPs, and/or M significantly (
p
< 0.05) lowered blood glucose levels, but increased insulin secretion and pancreatic β-cell function. An increase in locomotor and motor activities evidenced by improved spontaneous alternation, locomotor frequency, hinding, and increased mobility time were observed in treated groups. In addition, there was enhanced brain antioxidant status with a lower acetylcholinesterase (AChE) activity and oxidative-inflammatory stress biomarkers. A significant downregulation of caspase 3 and upregulation of parvalbumin and Nrf2 protein expressions was observed in treated groups. In some of the studied parameters, treated groups were statistically (
p
< 0.05) insignificant compared with the normal control (NC) group. Overall, co-treatment elicited more efficacy than that of the individual regimen.
To compare the effectiveness of different technique modifications in laparoscopic donor nephrectomy.
Systematic review and meta-analyses.
Searches of PubMed, EMBASE, Web of Science and Central from ...January 1st 1997 until April 1st 2014.
All cohort studies and randomized clinical trials comparing fully laparoscopic donor nephrectomy with modifications of the standard technique including hand-assisted, retroperitoneoscopic and single port techniques, were included.
The primary outcome measure was the number of complications. Secondary outcome measures included: conversion to open surgery, first warm ischemia time, estimated blood loss, graft function, operation time and length of hospital stay. Each technique modification was compared with standard laparoscopic donor nephrectomy. Data was pooled with a random effects meta-analysis using odds ratios, weighted mean differences and their corresponding 95% confidence intervals. To assess heterogeneity, the I2 statistic was used. First, randomized clinical trials and cohort studies were analyzed separately, when data was comparable, pooled analysis were performed.
31 studies comparing laparoscopic donor nephrectomy with other technique modifications were identified, including 5 randomized clinical trials and 26 cohort studies. Since data of randomized clinical trials and cohort studies were comparable, these data were pooled. There were significantly less complications in the retroperitoneoscopic group as compared to transperitoneal group (OR 0.52, 95%CI 0.33-0.83, I2 = 0%). Hand-assisted techniques showed shorter first warm ischemia and operation times.
Hand-assistance reduces the operation and first warm ischemia times and may improve safety for surgeons with less experience in laparoscopic donor nephrectomy. The retroperitoneoscopic approach was significantly associated with less complications. However, given the, in general, poor to intermediate quality and considerable heterogeneity in the included studies, further high-quality studies are required.
The review protocol was registered in the PROSPERO database before the start of the review process (CRD number 42013006565).
Abstract
The high-frequency radio sky has historically remained largely unexplored due to the typical faintness of sources in this regime, and the modest survey speed compared to observations at ...lower frequencies. However, high-frequency radio surveys offer an invaluable tracer of high-redshift star formation, as they directly target the faint radio free–free emission. We present deep continuum observations at 34 GHz in the COSMOS and GOODS-North fields from the Karl G. Jansky Very Large Array (VLA), as part of the COLD
z
survey. The deep COSMOS mosaic spans
down to
σ
= 1.3
μ
Jy beam
−1
, while the wider GOODS-N observations cover
to
σ
= 5.3
μ
Jy beam
−1
. We detect a total of 18 galaxies at 34 GHz, of which nine show radio emission consistent with being powered by star formation; although for two sources, this is likely due to thermal emission from dust. Utilizing deep ancillary radio data at 1.4, 3, 5, and 10 GHz, we decompose the spectra of the remaining seven star-forming galaxies into their synchrotron and thermal free–free components, and find typical thermal fractions and synchrotron spectral indices comparable to those observed in local star-forming galaxies. We further determine free–free star formation rates (SFRs), and show that these are in agreement with SFRs from spectral energy distribution-fitting and the far-infrared/radio correlation. Our observations place strong constraints on the high-frequency radio emission in typical galaxies at high redshift, and provide some of the first insights into what is set to become a key area of study with future radio facilities, such as the Square Kilometer Array Phase 1 and next-generation VLA.
The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This ...includes a longitudinal observational cohort study, a pilot and ancillary study program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy for detailed clinical, histopathological, and molecular phenotyping at the time of clinically indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and biannually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histological data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for nephrotic syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.
Mutations that alter signaling of RAS/MAPK-family proteins give rise to a group of Mendelian diseases known as RASopathies. However, among RASopathies, the matrix of genotype-phenotype relationships ...is still incomplete, in part because there are many RAS-related proteins and in part because the phenotypic consequences may be variable and/or pleiotropic. Here, we describe a cohort of ten cases, drawn from six clinical sites and over 16,000 sequenced probands, with de novo protein-altering variation in RALA, a RAS-like small GTPase. All probands present with speech and motor delays, and most have intellectual disability, low weight, short stature, and facial dysmorphism. The observed rate of de novo RALA variants in affected probands is significantly higher (p = 4.93 x 10(-11)) than expected from the estimated random mutation rate. Further, all de novo variants described here affect residues within the GTP/GDP-binding region of RALA; in fact, six alleles arose at only two codons, Val25 and Lys128. The affected residues are highly conserved across both RAL- and RAS-family genes, are devoid of variation in large human population datasets, and several are homologous to positions at which disease-associated variants have been observed in other GTPase genes. We directly assayed GTP hydrolysis and RALA effector-protein binding of the observed variants, and found that all but one tested variant significantly reduced both activities compared to wild-type. The one exception, S157A, reduced GTP hydrolysis but significantly increased RALA-effector binding, an observation similar to that seen for oncogenic RAS variants. These results show the power of data sharing for the interpretation and analysis of rare variation, expand the spectrum of molecular causes of developmental disability to include RALA, and provide additional insight into the pathogenesis of human disease caused by mutations in small GTPases.
ABSTRACT
Recent studies have suggested that red quasars are a phase in quasar evolution when feedback from black hole accretion evacuates obscuring gas from the nucleus of the host galaxy. Here, we ...report a direct link between dust-reddening and molecular outflows in quasars at z ∼ 2.5. By examining the dynamics of warm molecular gas in the inner region of galaxies, we find evidence for outflows with velocities 500–1000 km s−1 and time-scales of ≈0.1 Myr that are due to ongoing quasar energy output. We infer outflows only in systems where quasar radiation pressure on dust in the vicinity of the black hole is sufficiently large to expel their obscuring gas column densities. This result is in agreement with theoretical models that predict radiative feedback regulates gas in the nuclear regions of galaxies and is a major driving mechanism of galactic-scale outflows of cold gas. Our findings suggest that radiative quasar feedback ejects star-forming gas from within nascent stellar bulges at velocities comparable to those seen on larger scales, and that molecules survive in outflows even from the most luminous quasars.
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