A Bayesian elicitation of veterinary beliefs regarding systemic dry cow therapy: variation and importance for clinical trial design

The two key aims of this research were: (i) to conduct a probabilistic elicitation to quantify the variation in veterinarians’ beliefs regarding the efficacy of systemic antibiotics when used as an adjunct to intra-mammary dry cow therapy and (ii) to investigate (in a Bayesian statistical framework) the strength of future research evidence required (in theory) to change the beliefs of practising veterinary surgeons regarding the efficacy of systemic antibiotics, given their current clinical beliefs. The beliefs of 24 veterinarians in 5 practices in England were quantified as probability density functions. Classic multidimensional scaling revealed major variations in beliefs both within and between veterinary practices which included: confident optimism, confident pessimism and considerable uncertainty. Of the 9 veterinarians interviewed holding further cattle qualifications, 6 shared a confidently pessimistic belief in the efficacy of systemic therapy and whilst 2 were more optimistic, they were also more uncertain. A Bayesian model based on a synthetic dataset from a randomised clinical trial (showing no benefit with systemic therapy) predicted how each of the 24 veterinarians’ prior beliefs would alter as the size of the clinical trial increased, assuming that practitioners would update their beliefs rationally in accordance with Bayes’ theorem. The study demonstrated the usefulness of probabilistic elicitation for evaluating the diversity and strength of practitioners’ beliefs. The major variation in beliefs observed raises interest in the veterinary profession's approach to prescribing essential medicines. Results illustrate the importance of eliciting prior beliefs when designing clinical trials in order to increase the chance that trial data are of sufficient strength to alter the clinical beliefs of practitioners and do not merely serve to satisfy researchers

Functional Uniform Priors for Nonlinear Modelling

This paper considers the topic of finding prior distributions when a major component of the statistical model depends on a nonlinear function. Using results on how to construct uniform distributions in general metric spaces, we propose a prior distribution that is uniform in the space of functional shapes of the underlying nonlinear function and then back-transform to obtain a prior distribution for the original model parameters. The primary application considered in this article is nonlinear regression, but the idea might be of interest beyond this case. For nonlinear regression the so constructed priors have the advantage that they are parametrization invariant and do not violate the likelihood principle, as opposed to uniform distributions on the parameters or the Jeffrey's prior, respectively. The utility of the proposed priors is demonstrated in the context of nonlinear regression modelling in clinical dose-finding trials, through a real data example and simulation. In addition the proposed priors are used for calculation of an optimal Bayesian design.Comment: submitted for publicatio

Effect of Short Term Exercise and High Fat Diet on Skeletal Muscle miR133a

Micro RNAs (miR) are small non-coding RNA that regulate gene expression at the post-transcriptional level. miR133a is abundant in cardiac and skeletal muscle. In skeletal muscle, miR133a is best known for its regulatory role in myogenesis and differentiation. Nie (2016) found that muscle miR133a expression increased after acute exercise and with 12w of treadmill exercise training in mice. Knockdown of miR133a in transgenic mice resulted in blunted skeletal muscle mitochondrial biogenesis and function in response to exercise training (Nie, 2016) suggesting a role for miR133a in regulating the normal skeletal muscle metabolic adaptive response to exercise. Among other miR, skeletal muscle miR133a is reported as downregulated in insulin-resistant muscle. Insulin resistance in mice fed a high-fat diet is detectable after 3 days on diet (Lee, 2011). In this study, voluntary, rather than forced, exercise was employed to test whether miR133a expression is regulated early in the adoption of increased daily physical activity

High-Precision Measurement of the 19Ne Half-Life and Implications for Right-Handed Weak Currents

We report a precise determination of the 19Ne half-life to be $T_{1/2} = 17.262 \pm 0.007$ s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current Standard Model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.Comment: 5 pages and 5 figures. Paper accepted for publication in Phys. Rev. Let

Reference priors for high energy physics

Bayesian inferences in high energy physics often use uniform prior distributions for parameters about which little or no information is available before data are collected. The resulting posterior distributions are therefore sensitive to the choice of parametrization for the problem and may even be improper if this choice is not carefully considered. Here we describe an extensively tested methodology, known as reference analysis, which allows one to construct parametrization-invariant priors that embody the notion of minimal informativeness in a mathematically well-defined sense. We apply this methodology to general cross section measurements and show that it yields sensible results. A recent measurement of the single top quark cross section illustrates the relevant techniques in a realistic situation

Bringing positional processes back in: occupational gender segregation in ‘non-academic’ work

This article highlights that organisations mask a 'gendered substructure' and a 'positional substructure', and reinforces the importance of (re)incorporating the effects of positional processes as an analytical concern in current analysis of occupational segregation. Drawing on the concept of 'inequality regimes', we use the case of 'non-academic' workers in Scottish higher education institutions as the context in which to explore how gendered and positional processes may be perpetuating occupational gender segregation ─ focusing on finance, registry, security and cleaning staff. Our findings show how embedded gendered and positional processes are reinforcing occupational gender segregation in many areas of non-academic work. We reveal that some gendered processes are position-sensitive and that stereotyped language use and related biases impact the progression and treatment of workers at the 'bottom' ─ and the compounding effects on women. We show that positions within organisational opportunity structures cannot merely be read off grading hierarchies and argue that any analysis of positional substructures necessitates uncovering the potential existence of multiple organisational hierarchies and other forms of positional advantage/disadvantage, whilst recognising that positional substructures are not static

Mismatch Repair Proteins Initiate Epigenetic Alterations during Inflammation-Driven Tumorigenesis

Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model of inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment of epigenetic proteins to chromatin, initiating methylation and gene silencing in tumors. Compared with normal epithelium and noninflammation-induced tumors, inflammation-induced tumors gained DNA methylation at CpG islands, some of which are associated with putative tumor suppressor genes. Hypermethylated genes exhibited enrichment of repressive chromatin marks and reduced expression prior to tumorigenesis, at a time point coinciding with peak levels of inflammation-associated DNA damage. Loss of MutS homolog 2 (MSH2), a mismatch repair (MMR) protein, abrogated early inflammation-induced epigenetic alterations and DNA hypermethylation alterations observed in inflammation-induced tumors. These results indicate that early epigenetic alterations initiated by inflammation and MMR proteins lead to gene silencing during tumorigenesis, revealing a novel mechanism of epigenetic alterations in inflammation-driven cancer. Understanding such mechanisms will inform development of pharmacotherapies to reduce carcinogenesis

Participatory budgeting, community engagement and impact on public services in Scotland

The institutional engagement and analysis needed to effectively integrate the requirements of equality legislation into participatory budgeting (PB) processes requires a transformational approach. Equality processes appear to exist in parallel with PB activity, rather than being operationalized as integral to the objectives and character of PB activity at local level. This paper proposes that PB and the Public Sector Equality Duty (PSED) in the Equality Act 2010 share a transformative intent and potential, but that this is undermined by siloed thinking on equalities and enduring discriminatory behaviour and practices. The paper concludes with propositions for aligning the conceptual links between equality and community empowerment and, thereby, participation in local financial decision-making in practice

Uses of strength-based interventions for people with serious mental illness: a critical review

Background: For the past 3 decades, mental health practitioners have increasingly adopted aspects and tools of strength-based approaches. Providing strength-based intervention and amplifying strengths relies heavily on effective interpersonal processes. Aim: This article is a critical review of research regarding the use of strength-based approaches in mental health service settings. The aim is to discuss strength-based interventions within broader research on recovery, focussing on effectiveness and advances in practice where applicable. Method: A systematic search for peer-reviewed intervention studies published between 2001 and December 2014 yielded 55 articles of potential relevance to the review. Results: Seven studies met the inclusion criteria and were included in the analysis. The Quality Assessment Tool for Quantitative Studies was used to appraise the quality of the studies. Our review found emerging evidence that the utilisation of a strength-based approach improves outcomes including hospitalisation rates, employment/educational attainment, and intrapersonal outcomes such as self-efficacy and sense of hope. Conclusion: Recent studies confirm the feasibility of implementing a high-fidelity strength-based approach in clinical settings and its relevance for practitioners in health care. More high-quality studies are needed to further examine the effectiveness of strength-based approaches