Disease associated with equine coronavirus infection and high case fatality rate.

BackgroundEquine coronavirus (ECoV) is associated with clinical disease in adult horses. Outbreaks are associated with a low case fatality rate and a small number of animals with signs of encephalopathic disease are described.ObjectivesThe aim of this study is to describe the epidemiological and clinical features of two outbreaks of ECoV infection that were associated with an high case fatality rate.Animals14 miniature horses and 1 miniature donkey testing fecal positive for ECoV from two related disease outbreaks.MethodsRetrospective study describing the epidemiological findings, clinicopathological findings, and fecal viral load from affected horses.ResultsIn EcoV positive horses, 27% (4/15) of the animals died or were euthanized. Severe hyperammonemia (677 μmol/L, reference range ≤ 60 μmol/L) was identified in one animal with signs of encephalopathic disease that subsequently died. Fecal viral load (ECoV genome equivalents per gram of feces) was significantly higher in the nonsurvivors compared to animals that survived (P = .02).Conclusions and clinical importanceEquine coronavirus had a higher case fatality rate in this group of miniature horses than previously reported in other outbreaks of varying breeds. Hyperammonemia could contribute to signs of encephalopathic disease, and the fecal viral load might be of prognostic value in affected horses

Placental Pathology in Relation to Uterine Artery Doppler Findings in Pregnancies with Severe Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler Changes

OBJECTIVES: Current guidelines for diagnosis and management of early-onset intrauterine growth restriction (IUGR) rely on umbilical artery Doppler (UAD), without including uterine artery Doppler (UtAD). We hypothesized that IUGR cases with abnormal UAD but normal UtAD has a different spectrum of placental pathology compared with those with abnormal UtAD. STUDY DESIGN: Retrospective review of pregnancies with sonographic evidence of IUGR and abnormal UAD prior to delivery. Cases with ≥ 1 UtAD record(s) after 18(+0) weeks' gestation and placental pathology were included. Cases were stratified according to initial UtAD pulsatility index (PI) values (n = 196): normal (n = 19; PI < 95th centile for gestational age/no notching), intermediate (n = 69; PI ≥ 95th centile/no/unilateral notching) and abnormal (n = 108; PI ≥ 95th centile/bilateral notching). Pregnancy outcomes and placental pathology were compared between groups. RESULTS: Women in the normal group delivered later than those in the abnormal group (30.1 ± 3.5 vs. 28.0 ± 3.5 weeks; mean ± standard deviation; p = 0.03). Their placentas exhibited higher rates of chronic intervillositis (15.8 vs. 0.9%; p = 0.01), chorangiosis (15.8 vs. 0.9%; p < 0.0001), and massive perivillous fibrin deposition (21.1 vs. 7.4%; p = 0.05), but had lower rates of uteroplacental vascular insufficiency (26.3 vs. 79.6%; p < 0.0001). CONCLUSION: Approximately 10% of pregnancies with early-onset IUGR and abnormal UAD exhibited normal UtAD waveforms. They delivered later, and their placentas exhibited unusual placental pathologies

Evaluation of the immunomodulatory effects of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in C57BL/6 mice.

2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate was designed to replace perfluorooctanoic acid (PFOA), which has been mostly phased out of U.S. production due to environmental persistence, detectable human and wildlife serum concentrations, and reports of systemic toxicity. In rodent models, PFOA exposure suppresses T cell-dependent antibody responses (TDAR) and vaccine responses in exposed humans. To determine replacement compound effects on TDAR and related parameters, male and female C57BL/6 mice were gavaged with 0, 1, 10, or 100 mg/kg/day for 28 days. Mice immunized with antigen on day 24 were evaluated for TDAR and splenic lymphocyte subpopulations five days later. Serum and urine were collected for test compound concentrations and liver peroxisome proliferation was measured. Relative liver weight at 10 and 100 mg/kg and peroxisome proliferation at 100 mg/kg were increased in both sexes. TDAR was suppressed in females at 100 mg/kg. T lymphocyte numbers were increased in males at 100 mg/kg; B lymphocyte numbers were unchanged in both sexes. Females had less serum accumulation and higher clearance than males, and males had higher urine concentrations than females at all times and doses. While this PFOA-replacement compound appears less potent at suppressing TDAR relative to PFOA, it produces detectable changes in parameters affected by PFOA; further studies are necessary to determine its full immunomodulatory profile and potential synergism with other per- and polyfluoroalkyl substances of environmental concern

Economic evidence for nonpharmacological asthma management interventions: A systematic review

Asthma management, education and environmental interventions have been reported as cost‐effective in a previous review (Pharm Pract (Granada), 2014;12:493), but methods used to estimate costs and outcomes were not discussed in detail. This review updates the previous review by providing economic evidence on the cost‐effectiveness of studies identified after 2012, and a detailed assessment of the methods used in all identified studies. Twelve databases were searched from 1990 to January 2016, and studies included economic evaluations, asthma subjects and nonpharmacological interventions written in English. Sixty‐four studies were included. Of these, 15 were found in addition to the earlier review; 53% were rated fair in quality and 47% high. Education and self‐management interventions were the most cost‐effective, in line with the earlier review. Self‐reporting was the most common method used to gather resource‐use data, accompanied by bottom‐up approaches to estimate costs. Main outcome measures were asthma‐related hospitalizations (69%), quality of life (41%) and utility (38%), with AQLQ and the EQ‐5D being the most common questionnaires measured prospectively at fixed time points. More rigorous costing methods are needed with a more common quality of life tool to aid greater replicability and comparability amongst asthma studies

Tree migration-rates : narrowing the gap between inferred post-glacial rates and projected rates

Faster-than-expected post-glacial migration rates of trees have puzzled ecologists for a long time. In Europe, post-glacial migration is assumed to have started from the three southern European peninsulas (southern refugia), where large areas remained free of permafrost and ice at the peak of the last glaciation. However, increasing palaeobotanical evidence for the presence of isolated tree populations in more northerly microrefugia has started to change this perception. Here we use the Northern Eurasian Plant Macrofossil Database and palaeoecological literature to show that post-glacial migration rates for trees may have been substantially lower (60–260 m yr–1) than those estimated by assuming migration from southern refugia only (115–550 m yr–1), and that early-successional trees migrated faster than mid- and late-successional trees. Post-glacial migration rates are in good agreement with those recently projected for the future with a population dynamical forest succession and dispersal model, mainly for early-successional trees and under optimal conditions. Although migration estimates presented here may be conservative because of our assumption of uniform dispersal, tree migration-rates clearly need reconsideration. We suggest that small outlier populations may be a key factor in understanding past migration rates and in predicting potential future range-shifts. The importance of outlier populations in the past may have an analogy in the future, as many tree species have been planted beyond their natural ranges, with a more beneficial microclimate than their regional surroundings. Therefore, climate-change-induced range-shifts in the future might well be influenced by such microrefugia

Direct Observation of Electrostatically Driven Band Gap Renormalization in a Degenerate Perovskite Transparent Conducting Oxide

We have directly measured the band gap renormalization associated with the Moss-Burstein shift in the perovskite transparent conducting oxide (TCO), La-doped BaSnO_{3}, using hard x-ray photoelectron spectroscopy. We determine that the band gap renormalization is almost entirely associated with the evolution of the conduction band. Our experimental results are supported by hybrid density functional theory supercell calculations. We determine that unlike conventional TCOs where interactions with the dopant orbitals are important, the band gap renormalization in La-BaSnO_{3} is driven purely by electrostatic interactions

The experience of long-term opiate maintenance treatment and reported barriers to recovery: A qualitative systematic review

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery

Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials : a consensus study

Background: Current methodological guidelines provide advice about the assessment of sub-group analysis within RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of criteria that will facilitate the grading of evidence for moderators, in systematic reviews. Method: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique, and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising authors who have published methodological papers in this area, and researchers who have been active in the study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers’ Handbook, and the process was repeated. Results: The recommendations are that meta-analysts report both confirmatory and exploratory findings for subgroups analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based apriori statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study: Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions must be presented. Conclusions: There is consensus from a group of 21 international experts that methodological criteria to assess moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research. These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies