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

Characterization of TEM1/endosialin in human and murine brain tumors

<p>Abstract</p> <p>Background</p> <p><it>TEM1/endosialin </it>is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern of <it>TEM1/endosialin </it>in astrocytic and metastatic brain tumors and investigated its role as a therapeutic target in human endothelial cells and mouse xenograft models.</p> <p>Methods</p> <p><it>In situ </it>hybridization (ISH), immunohistochemistry (IH) and immunofluorescence (IF) were used to localize <it>TEM1/endosialin </it>expression in grade II-IV astrocytomas and metastatic brain tumors on tissue microarrays. Changes in <it>TEM1/endosialin </it>expression in response to pro-angiogenic conditions were assessed in human endothelial cells grown <it>in vitro</it>. Intracranial U87MG glioblastoma (GBM) xenografts were analyzed in nude <it>TEM1/endosialin </it>knockout (KO) and wildtype (WT) mice.</p> <p>Results</p> <p><it>TEM1/endosialin </it>was upregulated in primary and metastatic human brain tumors, where it localized primarily to the tumor vasculature and a subset of tumor stromal cells. Analysis of 275 arrayed grade II-IV astrocytomas demonstrated <it>TEM1/endosialin </it>expression in 79% of tumors. Robust <it>TEM1/endosialin </it>expression occurred in 31% of glioblastomas (grade IV astroctyomas). <it>TEM1/endosialin </it>expression was inversely correlated with patient age. TEM1/endosialin showed limited co-localization with CD31, αSMA and fibronectin in clinical specimens. <it>In vitro</it>, <it>TEM1/endosialin </it>was upregulated in human endothelial cells cultured in matrigel. Vascular <it>Tem1/endosialin </it>was induced in intracranial U87MG GBM xenografts grown in mice. <it>Tem1/endosialin </it>KO vs WT mice demonstrated equivalent survival and tumor growth when implanted with intracranial GBM xenografts, although <it>Tem1/endosialin </it>KO tumors were significantly more vascular than the WT counterparts.</p> <p>Conclusion</p> <p><it>TEM1/endosialin </it>was induced in the vasculature of high-grade brain tumors where its expression was inversely correlated with patient age. Although lack of <it>TEM1/endosialin </it>did not suppress growth of intracranial GBM xenografts, it did increase tumor vascularity. The cellular localization of <it>TEM1/endosialin </it>and its expression profile in primary and metastatic brain tumors support efforts to therapeutically target this protein, potentially via antibody mediated drug delivery strategies.</p

Thermodynamic Behavior of a Model Covalent Material Described by the Environment-Dependent Interatomic Potential

Using molecular dynamics simulations we study the thermodynamic behavior of a single-component covalent material described by the recently proposed Environment-Dependent Interatomic Potential (EDIP). The parameterization of EDIP for silicon exhibits a range of unusual properties typically found in more complex materials, such as the existence of two structurally distinct disordered phases, a density decrease upon melting of the low-temperature amorphous phase, and negative thermal expansion coefficients for both the crystal (at high temperatures) and the amorphous phase (at all temperatures). Structural differences between the two disordered phases also lead to a first-order transition between them, which suggests the existence of a second critical point, as is believed to exist for amorphous forms of frozen water. For EDIP-Si, however, the unusual behavior is associated not only with the open nature of tetrahedral bonding but also with a competition between four-fold (covalent) and five-fold (metallic) coordination. The unusual behavior of the model and its unique ability to simulation the liquid/amorphous transition on molecular-dynamics time scales make it a suitable prototype for fundamental studies of anomalous thermodynamics in disordeered systems.Comment: 48 pages (double-spaced), 13 figure

Music Attenuates Excessive Visual Guidance of Skilled Reaching in Advanced but Not Mild Parkinson's Disease

Parkinson's disease (PD) results in movement and sensory impairments that can be reduced by familiar music. At present, it is unclear whether the beneficial effects of music are limited to lessening the bradykinesia of whole body movement or whether beneficial effects also extend to skilled movements of PD subjects. This question was addressed in the present study in which control and PD subjects were given a skilled reaching task that was performed with and without accompanying preferred musical pieces. Eye movements and limb use were monitored with biomechanical measures and limb movements were additionally assessed using a previously described movement element scoring system. Preferred musical pieces did not lessen limb and hand movement impairments as assessed with either the biomechanical measures or movement element scoring. Nevertheless, the PD patients with more severe motor symptoms as assessed by Hoehn and Yahr (HY) scores displayed enhanced visual engagement of the target and this impairment was reduced during trials performed in association with accompanying preferred musical pieces. The results are discussed in relation to the idea that preferred musical pieces, although not generally beneficial in lessening skilled reaching impairments, may normalize the balance between visual and proprioceptive guidance of skilled reaching

Anti-angiogenic effect of high doses of ascorbic acid

Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of tumor cells. However, therapeutic effects have been reported at concentrations insufficient to induce direct tumor cell death. We hypothesized that AA may exert anti-angiogenic effects. To test this, we expanded endothelial progenitor cells (EPCs) from peripheral blood and assessed, whether or not high dose AA would inhibit EPC ability to migrate, change energy metabolism, and tube formation ability. We also evaluated the effects of high dose AA on angiogenic activities of HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical arterial endothelial cells). According to our data, concentrations of AA higher than 100 mg/dl suppressed capillary-like tube formation on Matrigel for all cells tested and the effect was more pronounced for progenitor cells in comparison with mature cells. Co-culture of differentiated endothelial cells with progenitor cells showed that there was incorporation of EPCs in vessels formed by HUVECs and HUAECs. Cell migration was assessed using an in vitro wound healing model. The results of these experiments showed an inverse correlation between AA concentrations relative to both cell migration and gap filling capacity. Suppression of NO (nitric oxide) generation appeared to be one of the mechanisms by which AA mediated angiostatic effects. This study supports further investigation into non-cytotoxic antitumor activities of AA