The Kilo-Degree Survey is an optical wide-field survey designed to map the matter distribution in the Universe using weak gravitational lensing. In this paper, we use these data to measure the ...density profiles and masses of a sample of ∼1400 spectroscopically identified galaxy groups and clusters from the Galaxy And Mass Assembly survey. We detect a highly significant signal (signal-to-noise-ratio ∼120), allowing us to study the properties of dark matter haloes over one and a half order of magnitude in mass, from M ∼ 1013–1014.5 h
−1 M⊙. We interpret the results for various subsamples of groups using a halo model framework which accounts for the mis-centring of the brightest cluster galaxy (used as the tracer of the group centre) with respect to the centre of the group's dark matter halo. We find that the density profiles of the haloes are well described by an NFW profile with concentrations that agree with predictions from numerical simulations. In addition, we constrain scaling relations between the mass and a number of observable group properties. We find that the mass scales with the total r-band luminosity as a power law with slope 1.16 ± 0.13 (1σ) and with the group velocity dispersion as a power law with slope 1.89 ± 0.27 (1σ). Finally, we demonstrate the potential of weak lensing studies of groups to discriminate between models of baryonic feedback at group scales by comparing our results with the predictions from the Cosmo-OverWhelmingly Large Simulations project, ruling out models without AGN feedback.
OPTN/SRTR 2017 Annual Data Report: Liver Kim, W. R.; Lake, J. R.; Smith, J. M. ...
American journal of transplantation,
February 2019, Letnik:
19, Številka:
S2
Journal Article
Recenzirano
Odprti dostop
Data on adult liver transplants performed in the US in 2017 are notable for (1) continued growth in numbers of new waitlist registrants (11,514) and of transplants performed (8,082); (2) continued ...increase in the transplant rate (51.5 per 100 waitlist‐years); (3) a precipitous decrease in waitlist registrations and transplants for hepatitis C‐related indications; (4) reciprocal increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non‐alcoholic fatty liver disease; and (5) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity. Variability in transplant rates remained by candidate race, presence of hepatocellular carcinoma, urgency status (status 1A versus model for end‐stage liver disease (MELD) score >35), and geography. More than half of all children listed for liver transplant in 2017 were aged younger than 5 years in 2017, and the highest rate of pretransplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than the past, as evidenced by higher MELD/pediatric end‐stage liver disease scores and listings at status 1A and 1B. Higher acuity at transplant is likely due to lack of access to suitable donor organs, which has been compensated for by persistent trends toward use of partial or split liver grafts and ABO‐incompatible grafts. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time.
Following destabilization of the medial meniscus (DMM), mice develop experimental osteoarthritis (OA) and associated pain behaviors that are dependent on the stage of disease. We aimed to describe ...changes in gene expression in knee-innervating dorsal root ganglia (DRG) after surgery, in order to identify molecular pathways associated with three pre-defined pain phenotypes: “post-surgical pain”, “early-stage OA pain”, and “persistent OA pain”.
We performed DMM or sham surgery in 10-week old male C57BL/6 mice and harvested L3-L5 DRG 4, 8, and 16 weeks after surgery or from age-matched naïve mice (n = 3/group). RNA was extracted and an Affymetrix Mouse Transcriptome Array 1.0 was performed. Three pain phenotypes were defined: “post-surgical pain” (sham and DMM 4-week vs 14-week old naïve), “early OA pain” (DMM 4-week vs sham 4-week), and “persistent OA pain” (DMM 8- and 16-week vs naïve and sham 8- and 16-week). ‘Top hit’ genes were defined as P < 0.001. Pathway analysis (Ingenuity Pathway Analysis) was conducted using differentially expressed genes defined as P < 0.05. In addition, we performed qPCR for Ngf and immunohistochemistry for F4/80+ macrophages in the DRG.
For each phenotype, top hit genes identified a small number of differentially expressed genes, some of which have been previously associated with pain (7/67 for “post-surgical pain”; 2/14 for “early OA pain”; 8/37 for “persistent OA pain”). Overlap between groups was limited, with 8 genes differentially regulated (P < 0.05) in all three phenotypes. Pathway analysis showed that in the persistent OA pain phase many of the functions of differentially regulated genes are related to immune cell recruitment and activation. Genes previously linked to OA pain (CX3CL1, CCL2, TLR1, and NGF) were upregulated in this phenotype and contributed to activation of the neuroinflammation canonical pathway. In separate sets of mice, we confirmed that Ngf was elevated in the DRG 8 weeks after DMM (P = 0.03), and numbers of F4/80+ macrophages were increased 16 weeks after DMM (P = 0.002 vs Sham).
These transcriptomics findings support the idea that distinct molecular pathways discriminate early from persistent OA pain. Pathway analysis suggests neuroimmune interactions in the DRG contribute to initiation and maintenance of pain in OA.
Review of Particle Physics Workman, R L; Klempt, E; Agashe, K ...
Progress of theoretical and experimental physics,
08/2022, Letnik:
2022, Številka:
8
Journal Article
Recenzirano
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Abstract
The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 2,143 new measurements from 709 papers, we list, evaluate, and average measured ...properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. Particle properties and search limits are listed in Summary Tables. We give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 120 reviews are many that are new or heavily revised, including a new review on Machine Learning, and one on Spectroscopy of Light Meson Resonances.
The Review is divided into two volumes. Volume 1 includes the Summary Tables and 97 review articles. Volume 2 consists of the Particle Listings and contains also 23 reviews that address specific aspects of the data presented in the Listings.
The complete Review (both volumes) is published online on the website of the Particle Data Group (pdg.lbl.gov) and in a journal. Volume 1 is available in print as the PDG Book. A Particle Physics Booklet with the Summary Tables and essential tables, figures, and equations from selected review articles is available in print, as a web version optimized for use on phones, and as an Android app.
We demonstrate a compact, open-path, quantum cascade-laser-based atmospheric ammonia sensor operating at 9.06 mu m for high-sensitivity, high temporal resolution, ground-based measurements. ...Atmospheric ammonia (NH3) is a gas-phase precursor to fine particulate matter, with implications for air quality and climate change. Currently, NH3 sensing challenges have led to a lack of widespread in situ measurements. Our open-path sensor configuration minimizes sampling artifacts associated with NH3 surface adsorption onto inlet tubing and reduced pressure sampling cells, as well as condensed-phase partitioning ambiguities. Multi-harmonic wavelength modulation spectroscopy allows for selective and sensitive detection of atmospheric pressure-broadened absorption features. An in-line ethylene reference cell provides real-time calibration ( plus or minus 20% accuracy) and normalization for instrument drift under rapidly changing field conditions. The sensor has a sensitivity and noise-equivalent limit (1 sigma ) of 0.15 ppbv NH3 at 10 Hz, a mass of ~ 5 kg and consumes ~ 50 W of electrical power. The total uncertainty in NH3 measurements is 0.20 ppbv NH3 plus or minus 10%, based on a spectroscopic calibration method. Field performance of this open-path NH3 sensor is demonstrated, with 10 Hz time resolution and a large dynamic response for in situ NH3 measurements. This sensor provides the capabilities for improved in situ gas-phase NH3 sensing relevant for emission source characterization and flux measurements.
Please cite this paper as: von Dadelszen P, Dwinnell S, Magee LA, Carleton BC, Gruslin A, Lee B, Lim KI, Liston RM, Miller SP, Rurak D, Sherlock RL, Skoll MA, Wareing MM, Baker PN, for the Research ...into Advanced Fetal Diagnosis and Therapy (RAFT) Group. Sildenafil citrate therapy for severe early‐onset intrauterine growth restriction. BJOG 2011;118:624–628.
Currently, there is no effective therapy for severe early‐onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR‐complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early‐onset IUGR abdominal circumference (AC) < 5th percentile and either the gestational age was <25+0 weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil‐naive early‐onset IUGR controls. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early‐onset IUGR‐complicated pregnancies.
Recurrent epidemics of influenza are observed seasonally around the world with considerable health and economic consequences. A key quantity for the control of infectious diseases is the reproduction ...number, which measures the transmissibility of a pathogen and determines the magnitude of public health interventions necessary to control epidemics. Here we applied a simple epidemic model to weekly indicators of influenza mortality to estimate the reproduction numbers of seasonal influenza epidemics spanning three decades in the United States, France, and Australia. We found similar distributions of reproduction number estimates in the three countries, with mean value 1-3 and important year-to-year variability (range 0·9-2·1). Estimates derived from two different mortality indicators (pneumonia and influenza excess deaths and influenza-specific deaths) were in close agreement for the United States (correlation= 0·61, P<0·001) and France (correlation = 0·79, P<0·001), but not Australia. Interestingly, high prevalence of A/H3N2 influenza viruses was associated with high transmission seasons (P = 0·006), while B viruses were more prevalent in low transmission seasons (P = 0·004). The current vaccination strategy targeted at people at highest risk of severe disease outcome is suboptimal because current vaccines are poorly immunogenic in these population groups. Our results suggest that interrupting transmission of seasonal influenza would require a relatively high vaccination coverage (>60%) in healthy individuals who respond well to vaccine, in addition to periodic re-vaccination due to evolving viral antigens and waning population immunity.
Summary Objective/Method Aggrecanase activity, most notably ADAMTS-5, is implicated in pathogenic cartilage degradation. Selective monoclonal antibodies (mAbs) to both ADAMTS-5 and ADAMTS-4 were ...generated and in vitro , ex vivo and in vivo systems were utilized to assess target engagement, aggrecanase inhibition and modulation of disease-related endpoints with the intent of selecting a candidate for clinical development in osteoarthritis (OA). Results Structural mapping predicts the most potent mAbs employ a unique mode of inhibition by cross-linking the catalytic and disintegrin domains. In a surgical mouse model of OA, both ADAMTS-5 and ADAMTS-4-specific mAbs penetrate cartilage following systemic administration, demonstrating access to the anticipated site of action. Structural disease modification and associated alleviation of pain-related behavior were observed with ADAMTS-5 mAb treatment. Treatment of human OA cartilage demonstrated a preferential role for ADAMTS-5 inhibition over ADAMTS-4, as measured by ARGS neoepitope release in explant cultures. ADAMTS-5 mAb activity was most evident in a subset of patient-derived tissues and suppression of ARGS neoepitope release was sustained for weeks after a single treatment in human explants and in cynomolgus monkeys, consistent with high affinity target engagement and slow ADAMTS-5 turnover. Conclusion This data supports a hypothesis set forth from knockout mouse studies that ADAMTS-5 is the major aggrecanase involved in cartilage degradation and provides a link between a biological pathway and pharmacology which translates to human tissues, non-human primate models and points to a target OA patient population. Therefore, a humanized ADAMTS-5-selective monoclonal antibody (GSK2394002) was progressed as a potential OA disease modifying therapeutic.
Summary
Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious ...pathogens) are thought to play a major role in the development of autoimmune diseases. In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity.
Foods that have similar carbohydrate content can differ in the amount they raise blood glucose. The effects of this property, called the glycemic index, on risk factors for cardiovascular disease and ...diabetes are not well understood.
To determine the effect of glycemic index and amount of total dietary carbohydrate on risk factors for cardiovascular disease and diabetes.
Randomized crossover-controlled feeding trial conducted in research units in academic medical centers, in which 163 overweight adults (systolic blood pressure, 120-159 mm Hg) were given 4 complete diets that contained all of their meals, snacks, and calorie-containing beverages, each for 5 weeks, and completed at least 2 study diets. The first participant was enrolled April 1, 2008; the last participant finished December 22, 2010. For any pair of the 4 diets, there were 135 to 150 participants contributing at least 1 primary outcome measure.
(1) A high-glycemic index (65% on the glucose scale), high-carbohydrate diet (58% energy); (2) a low-glycemic index (40%), high-carbohydrate diet; (3) a high-glycemic index, low-carbohydrate diet (40% energy); and (4) a low-glycemic index, low-carbohydrate diet. Each diet was based on a healthful DASH-type diet.
The 5 primary outcomes were insulin sensitivity, determined from the areas under the curves of glucose and insulin levels during an oral glucose tolerance test; levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides; and systolic blood pressure.
At high dietary carbohydrate content, the low- compared with high-glycemic index level decreased insulin sensitivity from 8.9 to 7.1 units (-20%, P = .002); increased LDL cholesterol from 139 to 147 mg/dL (6%, P ≤ .001); and did not affect levels of HDL cholesterol, triglycerides, or blood pressure. At low carbohydrate content, the low- compared with high-glycemic index level did not affect the outcomes except for decreasing triglycerides from 91 to 86 mg/dL (-5%, P = .02). In the primary diet contrast, the low-glycemic index, low-carbohydrate diet, compared with the high-glycemic index, high-carbohydrate diet, did not affect insulin sensitivity, systolic blood pressure, LDL cholesterol, or HDL cholesterol but did lower triglycerides from 111 to 86 mg/dL (-23%, P ≤ .001).
In this 5-week controlled feeding study, diets with low glycemic index of dietary carbohydrate, compared with high glycemic index of dietary carbohydrate, did not result in improvements in insulin sensitivity, lipid levels, or systolic blood pressure. In the context of an overall DASH-type diet, using glycemic index to select specific foods may not improve cardiovascular risk factors or insulin resistance.
clinicaltrials.gov Identifier: NCT00608049.
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