How does reviewing the evidence change veterinary surgeons' beliefs regarding the treatment of ovine footrot? A quantitative and qualitative study

Footrot is a widespread, infectious cause of lameness in sheep, with major economic and welfare costs. The aims of this research were: (i) to quantify how veterinary surgeons’ beliefs regarding the efficacy of two treatments for footrot changed following a review of the evidence (ii) to obtain a consensus opinion following group discussions (iii) to capture complementary qualitative data to place their beliefs within a broader clinical context. Grounded in a Bayesian statistical framework, probabilistic elicitation (roulette method) was used to quantify the beliefs of eleven veterinary surgeons during two one-day workshops. There was considerable heterogeneity in veterinary surgeons’ beliefs before they listened to a review of the evidence. After hearing the evidence, seven participants quantifiably changed their beliefs. In particular, two participants who initially believed that foot trimming with topical oxytetracycline was the better treatment, changed to entirely favour systemic and topical oxytetracycline instead. The results suggest that a substantial amount of the variation in beliefs related to differences in veterinary surgeons’ knowledge of the evidence. Although considerable differences in opinion still remained after the evidence review, with several participants having non-overlapping 95% credible intervals, both groups did achieve a consensus opinion. Two key findings from the qualitative data were: (i) veterinary surgeons believed that farmers are unlikely to actively seek advice on lameness, suggesting a proactive veterinary approach is required (ii) more attention could be given to improving the way in which veterinary advice is delivered to farmers. In summary this study has: (i) demonstrated a practical method for probabilistically quantifying how veterinary surgeons’ beliefs change (ii) revealed that the evidence that currently exists is capable of changing veterinary opinion (iii) suggested that improved transfer of research knowledge into veterinary practice is needed (iv) identified some potential obstacles to the implementation of veterinary advice by farmers

Disaggregation of SMOS soil moisture over West Africa using the Temperature and Vegetation Dryness Index based on SEVIRI land surface parameters

The overarching objective of this study was to produce a disaggregated SMOS Soil Moisture (SM) product using land surface parameters from a geostationary satellite in a region covering a diverse range of ecosystem types. SEVIRI data at 15 minute temporal resolution were used to derive the Temperature and Vegetation Dryness Index (TVDI) that served as SM proxy within the disaggregation process. West Africa (3 N, 26 W; 28 N, 26 E) was selected as a case study as it presents both an important North-South climate gradient and a diverse range of ecosystem types. The main challenge was to set up a methodology applicable over a large area that overcomes the constraints of SMOS (low spatial resolution) and TVDI (requires similar atmospheric forcing and triangular shape formed when plotting morning rise temperature versus fraction of vegetation cover) in order to produce a 0.05 degree resolution disaggregated SMOS SM product at sub-continental scale. Consistent cloud cover appeared as one of the main constraints for deriving TVDI, especially during the rainy season and in the southern parts of the region and a large adjustment window (105x105 SEVIRI pixels) was therefore deemed necessary. Both the original and the disaggregated SMOS SM products described well the seasonal dynamics observed at six locations of in situ observations. However, there was an overestimation in both products for sites in the humid southern regions; most likely caused by the presence of forest. Both TVDI and the associated disaggregated SM product was found to be highly sensitive to algorithm input parameters; especially of conditions of high fraction of vegetation cover. Additionally, seasonal dynamics in TVDI did not follow the seasonal patters of SM. Still, its spatial heterogeneity was found to be a good proxy for disaggregating SMOS SM data; main river networks and spatial patterns of SM extremes (i.e. droughts and floods) not seen in the original SMOS SM product were revealed in the disaggregated SM product for a test case of July-September 2012. The disaggregation methodology thereby successfully increased the spatial resolution of SMOS SM, with potential application for local drought/flood monitoring of importance for the livelihood of the population of West Africa

Glycaemia as a sign of the viability of the foetuses in the last days of gestation in dairy goats with pregnancy toxaemia

Pregnancy toxaemia is one of the most common diseases affecting small ruminants in the last month of gestation. Nearly 80% of the foetal growth occurs in the last 6 weeks of gestation. Fat goats and goats carrying twins and triplets are at greater risk. Pregnancy toxaemia is characterized by metabolic acidosis, hypoglycaemia and ketonaemia and a very high mortality rate. In our study five does with pregnancy toxaemia showed a marked hyperglycaemia (12.4 ± 5.4 mmol/L). Although our findings are based on a small population sample (10 goats), we nonetheless postulate that hyperglycaemia could be explained by the death of the foetuses. Caesarian surgery was performed on four of the five does with hyperglycaemia (HG does). In the fifth, kidding was induced. In this group, two does had two dead foetuses, two had three dead foetuses and one does had four foetuses, only one of which was alive. Caesarian surgery was performed on all five does with hypoglycaemia (LG does). Four does of the LG group had three foetuses and one had two foetuses, all alive. The HG doe had lower rectal temperatures, lower sodium and higher urea nitrogen (BUN) in the blood when compared with the LG does. As the condition of affected does may deteriorate quickly, the results of the present study suggest that in the last days of pregnancy goats with pregnancy toxaemia and concurrent hypoglycaemia should be considered for caesarian surgery

Emergency Ultra-Deep Hypothermia in Cardiac Arrest Induced by Blood Loss (Experimental Study on Nonhuman Primates)

The survival rate of critically injured individuals with severe blood loss and cardiac arrest is close to zero.Aim. To evaluate the feasibility of using emergency ultra-deep hypothermia (EUDH) in an experimental model of cardiac arrest induced by blood loss in nonhuman primates.Materials and Methods. Five male olive baboons (Papio anubis), weighing 19.8 (18.8–23.8) kg, were subjected to severe blood loss leading to cardiac arrest. After 1 minute of observation and 3 minutes of cardiopulmonary resuscitation (CPR), aortic arch cooling was initiated using extracorporeal membrane oxygenation (ECMO) with a 4°C solution to achieve a nasopharyngeal temperature of 10°C. Whole-body cooling followed until a rectal temperature of 16°C was reached. Balloon catheters were used to disconnect the upper and lower halves of the body. Once the target temperatures were reached, the ECMO circuit was turned off and an open laparotomy was performed to simulate damage control strategies. One hour after cardiac arrest, slow rewarming began at a rate of 1°C per 10 minutes to 1°C per hour, accompanied by reinfusion of previously collected blood. After return of spontaneous circulation (ROSC), sustained breathing, and tracheal extubation, the animals were transferred to a vivarium.Results. During deep hypothermia, cerebral oximetry values remained within normal limits in all animals. Sustained ROSC was recorded in 4 of 5 animals at temperatures between 22–25°C. Two animals survived to the end of the experiment but died after extubation, 44 and 19 hours after the start of the experiment. Cooling rates for survivors were 7–11 minutes compared to 23–37 minutes for non-survivors. Causes of death included systemic hypoperfusion with subsequent reperfusion syndrome as evidenced by progressive lactate elevation, elevated creatine phosphokinase levels, cerebral edema, myocardial ischemia, and transient coagulopathy.Conclusion. EUDH supports adequate cerebral perfusion during temporary circulatory arrest. Recovery of cardiac activity and, in some cases, awakening are achievable during the rewarming phase. Causes of death and possible corrective measures require further investigation

BID-F1 and BID-F2 Domains of Bartonella henselae Effector Protein BepF Trigger Together with BepC the Formation of Invasome Structures

The gram-negative, zoonotic pathogen Bartonella henselae (Bhe) translocates seven distinct Bartonella effector proteins (Beps) via the VirB/VirD4 type IV secretion system (T4SS) into human cells, thereby interfering with host cell signaling [1], [2]. In particular, the effector protein BepG alone or the combination of effector proteins BepC and BepF trigger massive F-actin rearrangements that lead to the establishment of invasome structures eventually resulting in the internalization of entire Bhe aggregates [2], [3]. In this report, we investigate the molecular function of the effector protein BepF in the eukaryotic host cell. We show that the N-terminal [E/T]PLYAT tyrosine phosphorylation motifs of BepF get phosphorylated upon translocation but do not contribute to invasome-mediated Bhe uptake. In contrast, we found that two of the three BID domains of BepF are capable to trigger invasome formation together with BepC, while a mutation of the WxxxE motif of the BID-F1 domain inhibited its ability to contribute to the formation of invasome structures. Next, we show that BepF function during invasome formation can be replaced by the over-expression of constitutive-active Rho GTPases Rac1 or Cdc42. Finally we demonstrate that BID-F1 and BID-F2 domains promote the formation of filopodia-like extensions in NIH 3T3 and HeLa cells as well as membrane protrusions in HeLa cells, suggesting a role for BepF in Rac1 and Cdc42 activation during the process of invasome formation

Citrobacter rodentium is an unstable pathogen showing evidence of significant genomic flux.

Citrobacter rodentium is a natural mouse pathogen that causes attaching and effacing (A/E) lesions. It shares a common virulence strategy with the clinically significant human A/E pathogens enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC) and is widely used to model this route of pathogenesis. We previously reported the complete genome sequence of C. rodentium ICC168, where we found that the genome displayed many characteristics of a newly evolved pathogen. In this study, through PFGE, sequencing of isolates showing variation, whole genome transcriptome analysis and examination of the mobile genetic elements, we found that, consistent with our previous hypothesis, the genome of C. rodentium is unstable as a result of repeat-mediated, large-scale genome recombination and because of active transposition of mobile genetic elements such as the prophages. We sequenced an additional C. rodentium strain, EX-33, to reveal that the reference strain ICC168 is representative of the species and that most of the inactivating mutations were common to both isolates and likely to have occurred early on in the evolution of this pathogen. We draw parallels with the evolution of other bacterial pathogens and conclude that C. rodentium is a recently evolved pathogen that may have emerged alongside the development of inbred mice as a model for human disease

A Unified Framework for Trend Uncertainty Assessment in Climate Data Record: Application to the Analysis of the Global Mean Sea Level Measured by Satellite Altimetry

Estimating trends from Climate Data Records (CDRs) of Essential Climate Variables (ECVs) is necessary to detect persistent changes in Earth’s climate and geophysical processes and states. Accurately describing trend uncertainty is also essential to determining the significance of observed changes and attributing drivers. However, despite the importance of uncertainty, no established trend assessment approach properly accounts for all known sources of trend uncertainty. Most approaches either neglect part of known measurement uncertainty, such as measurement system instability, or ignore the influence of natural climate variability on trend estimation. Such neglect can result in over-confidence in trend estimates. With the intent of providing the most realistic uncertainty intervals for climate data record time series data, this study discusses problems and limitations of current approaches. It emphasizes the need to account for the combined influence of measurement uncertainties (i.e., stability of the observational system) and natural climate variability on trend uncertainty. This study proposes a novel trend-uncertainty assessment approach unifying available measurement uncertainty information with empirical modelling of natural climate variability within the same trend-estimation framework. As a proof of concept, the proposed approach is applied to the analysis of trends in a Global Mean Sea Level (GMSL) time-series. This GMSL application demonstrates that combining available measurement uncertainty assessment with variance modelling is expected to lead to more realistic uncertainty evaluations in sea-level trends. This unified approach is potentially applicable to virtually any CDR and could enhance the reliability of climate change analysis through an improved trend uncertainty assessment in climate studies

Current and Historical Drivers of Landscape Genetic Structure Differ in Core and Peripheral Salamander Populations

With predicted decreases in genetic diversity and greater genetic differentiation at range peripheries relative to their cores, it can be difficult to distinguish between the roles of current disturbance versus historic processes in shaping contemporary genetic patterns. To address this problem, we test for differences in historic demography and landscape genetic structure of coastal giant salamanders (Dicamptodon tenebrosus) in two core regions (Washington State, United States) versus the species' northern peripheral region (British Columbia, Canada) where the species is listed as threatened. Coalescent-based demographic simulations were consistent with a pattern of post-glacial range expansion, with both ancestral and current estimates of effective population size being much larger within the core region relative to the periphery. However, contrary to predictions of recent human-induced population decline in the less genetically diverse peripheral region, there was no genetic signature of population size change. Effects of current demographic processes on genetic structure were evident using a resistance-based landscape genetics approach. Among core populations, genetic structure was best explained by length of the growing season and isolation by resistance (i.e. a ‘flat’ landscape), but at the periphery, topography (slope and elevation) had the greatest influence on genetic structure. Although reduced genetic variation at the range periphery of D. tenebrosus appears to be largely the result of biogeographical history rather than recent impacts, our analyses suggest that inherent landscape features act to alter dispersal pathways uniquely in different parts of the species' geographic range, with implications for habitat management

Expression of the Salmonella Spp. Virulence Factor SifA in Yeast Alters Rho1 Activity on Peroxisomes

SifA is a virulence protein required for assembly and tubulation of a modified phagosome that promotes Salmonella replication. We show that SifA expressed in yeast induces membrane invagination during peroxisome proliferation and requires functional Rho1p. This is consistent with SifA ability to interact with RhoA and the fact that it is a GEF structural homologue