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

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Ultrafast transient generation of spin-densitywave order in the normal state of BaFe2As2 driven by coherent lattice vibrations

The interplay among charge, spin and lattice degrees of freedom in solids gives rise to intriguing macroscopic quantum phenomena such as colossal magnetoresistance, multiferroicity and high-temperature superconductivity. Strong coupling or competition between various orders in these systems presents the key to manipulate their functional properties by means of external perturbations such as electric and magnetic fields or pressure. Ultrashort and intense optical pulses have emerged as an interesting tool to investigate elementary dynamics and control material properties by melting an existing order. Here, we employ few-cycle multi-terahertz pulses to resonantly probe the evolution of the spin-density-wave (SDW) gap of the pnictide compound BaFe2As2 following excitation with a femtosecond optical pulse. When starting in the low-temperature ground state, optical excitation results in a melting of the SDW order, followed by ultrafast recovery. In contrast, the SDW gap is induced when we excite the normal state above the transition temperature. Very surprisingly, the transient ordering quasi-adiabatically follows a coherent lattice oscillation at a frequency as high as 5.5 THz. Our results attest to a pronounced spin-phonon coupling in pnictides that supports rapid development of a macroscopic order on small vibrational displacement even without breaking the symmetry of the crystal

Interactional justice at work is related to sickness absence: a study using repeated measures in the Swedish working population

Background: Research has shown that perceived unfairness contributes to higher rates of sickness absence. While shorter, but more frequent periods of sickness absence might be a possibility for the individual to get relief from high strain, long-term sickness absence might be a sign of more serious health problems. The Uncertainty Management Model suggests that justice is particularly important in times of uncertainty, e.g. perceived job insecurity. The present study investigated the association between interpersonal and informational justice at work with long and frequent sickness absence respectively, under conditions of job insecurity. Methods: Data were derived from the 2010, 2012, and 2014 biennial waves of the Swedish Longitudinal Occupational Survey of Health (SLOSH). The final analytic sample consisted of 19,493 individuals. We applied repeated measures regression analyses through generalized estimating equations (GEE), a method for longitudinal data that simultaneously analyses variables at different time points. We calculated risk of long and frequent sickness absence, respectively in relation to interpersonal and informational justice taking perceptions of job insecurity into account. Results: We found informational and interpersonal justice to be associated with risk of long and frequent sickness absence independently of job insecurity and demographic variables. Results from autoregressive GEE provided some support for a causal relationship between justice perceptions and sickness absence. Contrary to expectations, we found no interaction between justice and job insecurity. Conclusions: Our results underline the need for fair and just treatment of employees irrespective of perceived job insecurity in order to keep the workforce healthy and to minimize lost work days due to sickness absence

Oxygen Sensing in Drosophila: Multiple Isoforms of the Prolyl Hydroxylase Fatiga Have Different Capacity to Regulate HIFα/Sima

Background: The Hypoxia Inducible Factor (HIF) mediates cellular adaptations to low oxygen. Prolyl-4-hydroxylases are oxygen sensors that hydroxylate the HIF alpha-subunit, promoting its proteasomal degradation in normoxia. Three HIFprolyl hydroxylases, encoded by independent genes, PHD1, PHD2, and PHD3, occur in mammals. PHD2, the longest PHD isoform includes a MYND domain, whose biochemical function is unclear. PHD2 and PHD3 genes are induced in hypoxia to shut down HIF dependent transcription upon reoxygenation, while expression of PHD1 is oxygen-independent. The physiologic significance of the diversity of the PHD oxygen sensors is intriguing. Methodology and Principal Findings: We have analyzed the Drosophila PHD locus, fatiga, which encodes 3 isoforms, FgaA, FgaB and FgaC that are originated through a combination of alternative initiation of transcription and alternative splicing. FgaA includes a MYND domain and is homologous to PHD2, while FgaB and FgaC are shorter isoforms most similar to PHD3. Through a combination of genetic experiments in vivo and molecular analyses in cell culture, we show that fgaB but not fgaA is induced in hypoxia, in a Sima-dependent manner, through a HIF-Responsive Element localized in the first intron of fgaA. The regulatory capacity of FgaB is stronger than that of FgaA, as complete reversion of fga loss-of-function phenotypes is observed upon transgenic expression of the former, and only partial rescue occurs after expression of the latter. Conclusions and Significance: Diversity of PHD isoforms is a conserved feature in evolution. As in mammals, there are hypoxia-inducible and non-inducible Drosophila PHDs, and a fly isoform including a MYND domain co-exists with isoforms lacking this domain. Our results suggest that the isoform devoid of a MYND domain has stronger regulatory capacity than that including this domain.Fil:Acevedo, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Centanin, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Dekanty, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Wappner, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation

<p>Abstract</p> <p>Background</p> <p>Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed <it>EFS </it>(<it>embryonal Fyn-associated substrate</it>) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated <it>EFS </it>promoter region CpG island in tumor classification and metastatic progression.</p> <p>Methods</p> <p><it>EFS </it>methylation was determined by direct sequencing of PCR products from bisulfite-treated DNA or by sequence analysis of individual cloned PCR products. The results were associated with clinical features of tumors and tumor-related death of patients.</p> <p>Results</p> <p>Analysis of 16 UM showed full methylation of the <it>EFS </it>CpG island in 8 (50%), no methylation in 5 (31%) and partial methylation in 3 (19%) tumors. Kaplan-Meier analysis revealed a higher risk of metastatic progression for tumors with <it>EFS </it>methylation (p = 0.02). This correlation was confirmed in an independent set of 24 randomly chosen tumors. Notably, only UM with <it>EFS </it>methylation gave rise to metastases. Real-time quantitative RT-PCR expression analysis revealed a significant inverse correlation of <it>EFS </it>mRNA expression with <it>EFS </it>methylation in UM. We further found that <it>EFS </it>methylation is tissue-specific with full methylation in peripheral blood cells, and no methylation in sperm, cultured primary fibroblasts and fetal muscle, kidney and brain. Adult brain samples, cultured melanocytes from the uveal tract, fetal liver and 3 of 4 buccal swab samples showed partial methylation. <it>EFS </it>methylation always affects both alleles in normal and tumor samples.</p> <p>Conclusions</p> <p>Biallelic <it>EFS </it>methylation is likely to be the result of a site-directed methylation mechanism. Based on partial methylation as observed in cultured melanocytes we hypothesize that there might be methylated and unmethylated precursor cells located in the uveal tract. The <it>EFS </it>methylation of a UM may depend on which type of precursor cell the tumor originated from.</p

The influence of re-employment on quality of life and self-rated health, a longitudinal study among unemployed persons in the Netherlands

__Abstract__ Background: Unemployed persons have a poorer health compared with employed persons and unemployment may cause ill health. The aim of this study was to investigate the effect of re-employment on quality of life and health among unemployed persons on social benefits. Methods. A prospective study with 18 months follow-up was conducted among unemployed persons (n=4,308) in the Netherlands, receiving either unemployment benefits or social security benefits. Quality of life, self-rated health, and employment status were measured at baseline and every 6 months of follow up with questionnaires. Generalized estimating equations (GEE) modeling was performed to study the influence of re-employment on change in self-rated health and quality of life over time. Results: In the study population 29% had a less than good quality of life and 17% had a poor self-rated health. Persons who started with paid employment during the follow-up period were more likely to improve towards a good quality of life (OR 1.76) and a good self-rated health (OR 2.88) compared with those persons who remained unemployed. Up to 6 months after re-employment, every month with paid employment, the likelihood of a good quality of life increased (OR 1.12). Conclusions: Starting with paid employment improves quality of life and self-rated health. This suggests that labour force participation should be considered as an important measure to improve health of unemployed persons. Improving possibilities for unemployed persons to find paid employment will reduce socioeconomic inequalities in health

Synthetic Heparan Sulfate Oligosaccharides Inhibit Endothelial Cell Functions Essential for Angiogenesis

Heparan sulfate (HS) is an important regulator of the assembly and activity of various angiogenic signalling complexes. However, the significance of precisely defined HS structures in regulating cytokine-dependent angiogenic cellular functions and signalling through receptors regulating angiogenic responses remains unclear. Understanding such structure-activity relationships is important for the rational design of HS fragments that inhibit HS-dependent angiogenic signalling complexes.We synthesized a series of HS oligosaccharides ranging from 7 to 12 saccharide residues that contained a repeating disaccharide unit consisting of iduronate 2-O-sulfate linked to glucosamine with or without N-sulfate. The ability of oligosaccharides to compete with HS for FGF2 and VEGF165 binding significantly increased with oligosaccharide length and sulfation. Correspondingly, the inhibitory potential of oligosaccharides against FGF2- and VEGF165-induced endothelial cell responses was greater in longer oligosaccharide species that were comprised of disaccharides bearing both 2-O- and N-sulfation (2SNS). FGF2- and VEGF165-induced endothelial cell migration were inhibited by longer 2SNS oligosaccharide species with 2SNS dodecasaccharide activity being comparable to that of receptor tyrosine kinase inhibitors targeting FGFR or VEGFR-2. Moreover, the 2SNS dodecasaccharide ablated FGF2- or VEGF165-induced phosphorylation of FAK and assembly of F-actin in peripheral lamellipodia-like structures. In contrast, FGF2-induced endothelial cell proliferation was only moderately inhibited by longer 2SNS oligosaccharides. Inhibition of FGF2- and VEGF165-dependent endothelial tube formation strongly correlated with oligosaccharide length and sulfation with 10-mer and 12-mer 2SNS oligosaccharides being the most potent species. FGF2- and VEGF165-induced activation of MAPK pathway was inhibited by biologically active oligosaccharides correlating with the specific phosphorylation events in FRS2 and VEGFR-2, respectively.These results demonstrate structure-function relationships for synthetic HS saccharides that suppress endothelial cell migration, tube formation and signalling induced by key angiogenic cytokines