Bayes linear kinematics in the analysis of failure rates and failure time distributions

Collections of related Poisson or binomial counts arise, for example, from a number of different failures in similar machines or neighbouring time periods. A conventional Bayesian analysis requires a rather indirect prior specification and intensive numerical methods for posterior evaluations. An alternative approach using Bayes linear kinematics in which simple conjugate specifications for individual counts are linked through a Bayes linear belief structure is presented. Intensive numerical methods are not required. The use of transformations of the binomial and Poisson parameters is proposed. The approach is illustrated in two examples, one involving a Poisson count of failures, the other involving a binomial count in an analysis of failure times

Evaluation of elicitation methods to quantify Bayes linear models

The Bayes linear methodology allows decision makers to express their subjective beliefs and adjust these beliefs as observations are made. It is similar in spirit to probabilistic Bayesian approaches, but differs as it uses expectation as its primitive. While substantial work has been carried out in Bayes linear analysis, both in terms of theory development and application, there is little published material on the elicitation of structured expert judgement to quantify models. This paper investigates different methods that could be used by analysts when creating an elicitation process. The theoretical underpinnings of the elicitation methods developed are explored and an evaluation of their use is presented. This work was motivated by, and is a precursor to, an industrial application of Bayes linear modelling of the reliability of defence systems. An illustrative example demonstrates how the methods can be used in practice

Extent of Methionine Limitation in Peak-, Early-, and Mid-Lactation Dairy Cows

Five multiparous, ruminally and duodenally cannulated Holstein cows were assigned to 5 × 5 Latin squares at wk 2 (experiment 1), wk 11 to 13 (experiment 2), and wk 17 to 19 postpartum (experiment 3) to determine extent of Met limitation. Treatments were duodenally infused and consisted of 10 g/d of l-Lys plus 0, 3.5, 7.0, 10.5, or 16.0 g/d of dl-Met in experiments 1 and 2 and 8 g/d of l-Lys plus 0, 5, 10, 15, or 20 g/d of dl-Met in experiment 3. Calculated Lys contributions to total AA (TAA) in duodenal digesta for control treatments were 8.6, 7.5, and 9.0% for experiments 1, 2, and 3, respectively. Methionine contributions to TAA for the 5 infusion treatments were 1.9, 2.1, 2.2, 2.4, and 2.7% for experiment 1; 2.1, 2.3, 2.4, 2.5, and 2.7% for experiment 2; and 1.8, 2.0, 2.2, 2.4, and 2.5% for experiment 3, respectively. Milk protein yield increased linearly in experiments 1 and 2, indicating that Met contribution to TAA in duodenal digesta for maximal milk protein synthesis exceeded 2.7 for early-lactation cows. In experiment 2, a quadratic relationship was found between level of infused Met and milk protein content, with the response reaching a plateau when 12.2 g of Met was infused, corresponding with a Met contribution to TAA in duodenal digesta of 2.4%. In experiment 3, milk protein content increased quadratically, but milk yield declined linearly with increasing levels of infused Met; hence, milk protein yield was unaffected by treatment. The calculated plateau point of the milk protein content response curve was determined to be 12.4 g of infused Met, which corresponds to a Met contribution to TAA in duodenal digesta of 2.3%. Experiment 3 results indicate that the required level of Met in duodenal digesta for maximizing milk protein yield is lower than that required for maximizing milk protein content

A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis

Who knows best? A Q methodology study to explore perspectives of professional stakeholders and community participants on health in low-income communities

Abstract Background Health inequalities in the UK have proved to be stubborn, and health gaps between best and worst-off are widening. While there is growing understanding of how the main causes of poor health are perceived among different stakeholders, similar insight is lacking regarding what solutions should be prioritised. Furthermore, we do not know the relationship between perceived causes and solutions to health inequalities, whether there is agreement between professional stakeholders and people living in low-income communities or agreement within these groups. Methods Q methodology was used to identify and describe the shared perspectives (‘subjectivities’) that exist on i) why health is worse in low-income communities (‘Causes’) and ii) the ways that health could be improved in these same communities (‘Solutions’). Purposively selected individuals (n = 53) from low-income communities (n = 25) and professional stakeholder groups (n = 28) ranked ordered sets of statements – 34 ‘Causes’ and 39 ‘Solutions’ – onto quasi-normal shaped grids according to their point of view. Factor analysis was used to identify shared points of view. ‘Causes’ and ‘Solutions’ were analysed independently, before examining correlations between perspectives on causes and perspectives on solutions. Results Analysis produced three factor solutions for both the ‘Causes’ and ‘Solutions’. Broadly summarised these accounts for ‘Causes’ are: i) ‘Unfair Society’, ii) ‘Dependent, workless and lazy’, iii) ‘Intergenerational hardships’ and for ‘Solutions’: i) ‘Empower communities’, ii) ‘Paternalism’, iii) ‘Redistribution’. No professionals defined (i.e. had a significant association with one factor only) the ‘Causes’ factor ‘Dependent, workless and lazy’ and the ‘Solutions’ factor ‘Paternalism’. No community participants defined the ‘Solutions’ factor ‘Redistribution’. The direction of correlations between the two sets of factor solutions – ‘Causes’ and ‘Solutions’ – appear to be intuitive, given the accounts identified. Conclusions Despite the plurality of views there was broad agreement across accounts about issues relating to money. This is important as it points a way forward for tackling health inequalities, highlighting areas for policy and future research to focus on

Evolution of 18F-FDG-PET/CT findings in patients following COVID-19 pneumonia: An Initial Investigation

Background: The evolution of pulmonary 18F-FDG uptake is unknown in patients with pneumonia due to SARS-CoV-2 (COVID-19 pneumonia) and in those with persistent respiratory symptoms post-COVID-19 termed Post-COVID-19 Lung-Disease (PCLD). The aim of this study was to assess the temporal evolution of pulmonary 18F-FDG uptake and identify a potential role for the use of 18F-FDG-PET/CT imaging in the management of these patients. Methods: Clinical data and CT imaging of all patients that underwent 18F-FDG-PET/CT imaging at UCLH, Lon-don during the UK pandemic were reviewed to find evidence of active or recovered SARS-CoV-2 infection. Results of PCR tests were used where available. Patients were divided in to acute (early and late) COVID-19 pneumonia, PCLD and asymptomatic recovery. 18F-FDG uptake in the lungs was measured as a target-to-background ratio (SUVmax/SUVmin) TBRlung which was compared to temporal-stage and plasma CRP. Results: There were 50 patients in total (median 61y, range 18-87y, 32-male): 23 incidental acute COVID-19 pneumonia cases identified retrospectively (8 Early, 15 Late), 9 asymptomatic recovered patients, and 18 cases performed for PCLD. In acute COVID-19 patients <3 weeks since disease onset TBRlung was strongly correlated with time since disease onset (rs=0.81, p<0.001)

A frequentist framework of inductive reasoning

Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

A Soluble Guanylate Cyclase–Dependent Mechanism Is Involved in the Regulation of Net Hepatic Glucose Uptake by Nitric Oxide in Vivo

OBJECTIVE We previously showed that elevating hepatic nitric oxide (NO) levels reduced net hepatic glucose uptake (NHGU) in the presence of portal glucose delivery, hyperglycemia, and hyperinsulinemia. The aim of the present study was to determine the role of a downstream signal, soluble guanylate cyclase (sGC), in the regulation of NHGU by NO. RESEARCH DESIGN AND METHODS Studies were performed on 42-h–fasted conscious dogs fitted with vascular catheters. At 0 min, somatostatin was given peripherally along with 4× basal insulin and basal glucagon intraportally. Glucose was delivered at a variable rate via a leg vein to double the blood glucose level and hepatic glucose load throughout the study. From 90 to 270 min, an intraportal infusion of the sGC inhibitor 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) was given in −sGC (n = 10) and −sGC/+NO (n = 6), whereas saline was given in saline infusion (SAL) (n = 10). The −sGC/+NO group also received intraportal SIN-1 (NO donor) to elevate hepatic NO from 180 to 270 min. RESULTS In the presence of 4× basal insulin, basal glucagon, and hyperglycemia (2× basal ), inhibition of sGC in the liver enhanced NHGU (mg/kg/min; 210–270 min) by ∼55% (2.9 ± 0.2 in SAL vs. 4.6 ± 0.5 in −sGC). Further elevating hepatic NO failed to reduce NHGU (4.5 ± 0.7 in −sGC/+NO). Net hepatic carbon retention (i.e., glycogen synthesis; mg glucose equivalents/kg/min) increased to 3.8 ± 0.2 in −sGC and 3.8 ± 0.4 in −sGC/+NO vs. 2.4 ± 0.2 in SAL (P < 0.05). CONCLUSIONS NO regulates liver glucose uptake through a sGC-dependent pathway. The latter could be a target for pharmacologic intervention to increase meal-associated hepatic glucose uptake in individuals with type 2 diabetes