A within farm clinical trial to compare two treatments (parenteral antibacterials and hoof trimming) for sheep lame with footrot

From observational studies, farmers who use parenteral antibacterials to promptly treat all sheep with footrot (FR) or interdigital dermatitis (ID) have a prevalence of lameness of <2% compared with a prevalence of 9% lameness reported by farmers who treat lame sheep by trimming affected feet. We tested the hypothesis that prompt treatment of sheep lame with naturally developing FR or ID with parenteral and topical antibacterials reduces the prevalence and incidence of lameness with these conditions compared with less frequent treatment with trimming of hoof horn and applying topical antibacterials. A further hypothesis was that reduction of ID and FR would improve productivity. A lowland sheep flock with 700 ewes was used to test these hypotheses in an 18-month within farm clinical trial with four groups of ewes: two intervention and two control. The duration and severity of lameness was used to categorise sheep into three weighted scores of lameness (WLS): never lame (WLS0), mildly lame/lame for <6 days (WLS1) and severely or chronically lame (WLS2). The intervention reduced the prevalence of lameness due to FR and ID in ewes and lambs and the incidence of lameness in ewes. The WLS was also significantly lower in sheep in the intervention groups. Ewes with a higher WLS were subsequently significantly more likely to have a body condition score <2.5 and to have lame lambs. Significantly more ewes lambed and successfully reared more lambs that were ready for slaughter at a younger age in the intervention versus control groups. There was an increase in the gross margin of £630/100 ewes mated in the intervention group, including the cost of treatment of £150/100 ewes mated. We conclude that prompt parenteral and topical antibacterial treatment of sheep lame with ID and FR reduced the prevalence and incidence of these infectious conditions and led to improved health, welfare and productivity

Safety and protective effects of maternal influenza vaccination on pregnancy and birth outcomes: A prospective cohort study

Background Our study aimed to assess the safety and protective effect of maternal influenza vaccination on pregnancy and birth outcomes. Methods The study population comprised 1253 healthy nulliparous pregnant women in South Australia between 2015 and 2018. Participants were followed prospectively, with vaccination status (confirmed by medical records), pregnancy, and birth outcome data collected by midwives. Adjusted relative risks (aRRs) and adjusted hazard ratios (aHRs) were estimated accounting for time-varying vaccine exposure and temporal nature of each outcome. Findings Maternal influenza vaccination (48%, 603 of 1253) reduced the risk for pre-delivery hospitalisation with influenza like illness (aHR 0•61; 95% CI 0•39, 0•97). Maternal influenza vaccination was not associated with spontaneous abortion (aHR 0•42, 95% CI 0•12, 1•45), chorioamnionitis (aRR 0•78, 95% CI, 0•32, 1•88), gestational hypertension (aHR 0•78, 95% CI 0•47, 1•29), pre-eclampsia (aHR 0.84, 95% CI 0•54, 1•27), gestational diabetes (aHR 1•16, 95% CI 0•82, 1•66) nor preterm birth (aHR 0•94, 95% CI 0•59, 1•49). No associations between antenatal influenza vaccination and congenital anomalies, admission to the neonatal care unit, low Apgar scores, and mechanical ventilation were observed. Results were not materially changed after adjustment for pertussis vaccination. We observed a protective effect of maternal influenza vaccination on low birth weight (aHR 0•46, 95% CI 0•23, 0•94) and a marginal protective effect on small for gestational age births (aHR 0•65, 95% CI 0•40, 1•04) during periods of high influenza activity. Interpretation These results support the safety of maternal influenza vaccination and suggest a protective effect in reducing the rates of low birthweight and small for gestational age births. Funding There was no funding for this study.Hassen Mohammed, Claire T.Roberts, Luke E. Grzeskowiak, Lynne C. Giles, Gustaaf A. Dekker ... et al

Automated quantification of the landing error scoring system with a markerless motion-Capture system

Context: The Landing Error Scoring System (LESS) can be used to identify individuals with an elevated risk of lower extremity injury. The limitation of the LESS is that raters identify movement errors from video replay, which is time-consuming and, therefore, may limit its use by clinicians. A markerless motion-capture system may be capable of automating LESS scoring, thereby removing this obstacle. Objective: To determine the reliability of an automated markerless motion-capture system for scoring the LESS. Design: Cross-sectional study. Setting: United States Military Academy. Patients or Other Participants: A total of 57 healthy, physically active individuals (47 men, 10 women; age ¼ 18.6 6 0.6 years, height ¼ 174.5 6 6.7 cm, mass ¼ 75.9 6 9.2 kg). Main Outcome Measure(s): Participants completed 3 jump-landing trials that were recorded by standard video cameras and a depth camera. Their movement quality was evaluated by expert LESS raters (standard video recording) using the LESS rubric and by software that automates LESS scoring (depth-camera data). We recorded an error for a LESS item if it was present on at least 2 of 3 jump-landing trials. We calculated j statistics, prevalence- and bias-adjusted j (PABAK) statistics, and percentage agreement for each LESS item. Interrater reliability was evaluated between the 2 expert rater scores and between a consensus expert score and the markerless motion-capture system score. Results: We observed reliability between the 2 expert LESS raters (average j ¼ 0.45 6 0.35, average PABAK ¼ 0.67 6 0.34; percentage agreement ¼ 0.83 6 0.17). The markerless motion-capture system had similar reliability with consensus expert scores (average j ¼ 0.48 6 0.40, average PABAK ¼ 0.71 6 0.27; percentage agreement ¼ 0.85 6 0.14). However, reliability was poor for 5 LESS items in both LESS score comparisons. Conclusions: A markerless motion-capture system had the same level of reliability as expert LESS raters, suggesting that an automated system can accurately assess movement. Therefore, clinicians can use the markerless motion-capture system to reliably score the LESS without being limited by the time requirements of manual LESS scoring

Peak knee biomechanics and limb symmetry following unilateral anterior cruciate ligament reconstruction: Associations of walking gait and jump-landing outcomes

Background: Aberrant walking-gait and jump-landing biomechanics may influence the development of post-traumatic osteoarthritis and increase the risk of a second anterior cruciate ligament injury, respectively. It remains unknown if individuals who demonstrate altered walking-gait biomechanics demonstrate similar altered biomechanics during jump-landing. Our aim was to determine associations in peak knee biomechanics and limb-symmetry indices between walking-gait and jump-landing tasks in individuals with a unilateral anterior cruciate ligament reconstruction. Methods: Thirty-five individuals (74% women, 22.1 [3.4] years old, 25 [3.89] kg/m 2 ) with an anterior cruciate ligament reconstruction performed 5-trials of self-selected walking-gait and jump-landing. Peak kinetics and kinematics were extracted from the first 50% of stance phase during walking-gait and first 100 ms following ground contact for jump-landing. Pearson product-moment (r) and Spearman's Rho (ρ) analyses were used to evaluate relationships between outcome measures. Significance was set a priori (P ≤ 0.05). Findings: All associations between walking-gait and jump-landing for the involved limb, along with the majority of associations for limb-symmetry indices and the uninvolved limb, were negligible and non-statistically significant. There were weak significant associations for instantaneous loading rate (ρ = 0.39, P = 0.02) and peak knee abduction angle (ρ = 0.36, p = 0.03) uninvolved limb, as well as peak abduction displacement limb-symmetry indices (ρ= − 0.39, p = 0.02) between walking-gait and jump-landing. Interpretation: No systematic associations were found between walking-gait and jump-landing biomechanics for either limb or limb-symmetry indices in people with unilateral anterior cruciate ligament reconstruction. Individuals with an anterior cruciate ligament reconstruction who demonstrate high-involved limb loading or asymmetries during jump-landing may not demonstrate similar biomechanics during walking-gait

Associations Between Slower Walking Speed and T1ρ Magnetic Resonance Imaging of Femoral Cartilage Following Anterior Cruciate Ligament Reconstruction

Objective: To determine whether walking speed, collected at 6 and 12 months following anterior cruciate ligament reconstruction (ACLR), is associated with inter-extremity differences in proteoglycan density, measured via T1ρ magnetic resonance imaging, in tibiofemoral articular cartilage 12 months following ACLR. Methods: Twenty-one individuals with a unilateral patellar-tendon autograft ACLR (10 women and 11 men, mean ± SD age 23.9 ± 2.7 years, mean ± SD body mass index 23.9 ± 2.7 kg/m2) were recruited for participation in this study. Walking speed was collected using 3-dimensional motion capture at 6 and 12 months following ACLR. The articular cartilage of the medial femoral condyle (MFC) and lateral femoral condyle and medial and lateral tibial condyles was manually segmented and subsectioned into 3 regions of interest (anterior, central, and posterior) based on the location of the meniscus in the sagittal plane. Inter-extremity mean T1ρ relaxation time ratios (T1ρ ACLR extremity / T1ρ contralateral extremity) were calculated and used for analysis. Pearson product-moment correlations were used to determine associations between walking speed and inter-extremity differences in T1ρ relaxation time ratios. Results: Slower walking speed 6 months post-ACLR was significantly associated with higher T1ρ relaxation time ratios in the MFC of the ACLR extremity 12 months following ACLR (posterior MFC, r = −0.51, P = 0.02; central MFC, r = −0.47, P = 0.04). Similarly, slower walking speed at 12 months post-ACLR was significantly associated with higher T1ρ relaxation time ratios in the posterior MFC ACLR extremity (r = −0.47, P = 0.04) 12 months following ACLR. Conclusion: Slower walking speed at 6 and 12 months following ACLR may be associated with early proteoglycan density changes in medial femoral compartment cartilage health in the first 12 months following ACLR

Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major

Background The macrophage infectivity potentiator (Mip) protein, which belongs to the immunophilin superfamily, is a peptidyl-prolyl cis/trans isomerase (PPIase) enzyme. Mip has been shown to be important for virulence in a wide range of pathogenic microorganisms. It has previously been demonstrated that small-molecule compounds designed to target Mip from the Gram-negative bacterium Burkholderia pseudomallei bind at the site of enzymatic activity of the protein, inhibiting the in vitro activity of Mip. Objectives In this study, co-crystallography experiments with recombinant B. pseudomallei Mip (BpMip) protein and Mip inhibitors, biochemical analysis and computational modelling were used to predict the efficacy of lead compounds for broad-spectrum activity against other pathogens. Methods Binding activity of three lead compounds targeting BpMip was verified using surface plasmon resonance spectroscopy. The determination of crystal structures of BpMip in complex with these compounds, together with molecular modelling and in vitro assays, was used to determine whether the compounds have broad-spectrum antimicrobial activity against pathogens. Results Of the three lead small-molecule compounds, two were effective in inhibiting the PPIase activity of Mip proteins from Neisseria meningitidis, Klebsiella pneumoniae and Leishmania major. The compounds also reduced the intracellular burden of these pathogens using in vitro cell infection assays. Conclusions These results indicate that Mip is a novel antivirulence target that can be inhibited using small-molecule compounds that prove to be promising broad-spectrum drug candidates in vitro. Further optimization of compounds is required for in vivo evaluation and future clinical applications

Towards Machine Wald

The past century has seen a steady increase in the need of estimating and predicting complex systems and making (possibly critical) decisions with limited information. Although computers have made possible the numerical evaluation of sophisticated statistical models, these models are still designed \emph{by humans} because there is currently no known recipe or algorithm for dividing the design of a statistical model into a sequence of arithmetic operations. Indeed enabling computers to \emph{think} as \emph{humans} have the ability to do when faced with uncertainty is challenging in several major ways: (1) Finding optimal statistical models remains to be formulated as a well posed problem when information on the system of interest is incomplete and comes in the form of a complex combination of sample data, partial knowledge of constitutive relations and a limited description of the distribution of input random variables. (2) The space of admissible scenarios along with the space of relevant information, assumptions, and/or beliefs, tend to be infinite dimensional, whereas calculus on a computer is necessarily discrete and finite. With this purpose, this paper explores the foundations of a rigorous framework for the scientific computation of optimal statistical estimators/models and reviews their connections with Decision Theory, Machine Learning, Bayesian Inference, Stochastic Optimization, Robust Optimization, Optimal Uncertainty Quantification and Information Based Complexity.Comment: 37 page

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio