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

Eliciting Dirichlet and Gaussian copula prior distributions for multinomial models

In this paper, we propose novel methods of quantifying expert opinion about prior distributions for multinomial models. Two different multivariate priors are elicited using median and quartile assessments of the multinomial probabilities. First, we start by eliciting a univariate beta distribution for the probability of each category. Then we elicit the hyperparameters of the Dirichlet distribution, as a tractable conjugate prior, from those of the univariate betas through various forms of reconciliation using least-squares techniques. However, a multivariate copula function will give a more flexible correlation structure between multinomial parameters if it is used as their multivariate prior distribution. So, second, we use beta marginal distributions to construct a Gaussian copula as a multivariate normal distribution function that binds these marginals and expresses the dependence structure between them. The proposed method elicits a positive-definite correlation matrix of this Gaussian copula. The two proposed methods are designed to be used through interactive graphical software written in Java

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)

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

Nitric Oxide Signalling Augments Neuronal Voltage-Gated L-Type (CaV1) and P/Q-Type (CaV2.1) Channels in the Mouse Medial Nucleus of the Trapezoid Body

Nitric Oxide (NO) is a diffusible second messenger that modulates ion channels, intrinsic excitability and mediates synaptic plasticity. In light of its activity-dependent generation in the principal neurons of the medial nucleus of the trapezoid body (MNTB), we have investigated its potential modulatory effects on native voltage-gated calcium channels (CaV) within this nucleus. Whole-cell patch recordings were made from brain slices from P13–15 CBA mice. Slices were incubated with the inhibitor of neuronal nitric oxide synthase (nNOS) 7-nitroindazole (10 µM) and pharmacological blockers used to isolate Ca2+ current subtypes. Unpaired observations in the presence and absence of the NO-donors sodium nitroprusside (SNP, 100 µM) or Diethyl-ammonium-nonoate (DEA, 100 µM) were made to elucidate NO-dependent modulation of the expressed CaV subtypes. A differential effect of NO on the calcium channel subtypes was observed: CaV1 and CaV2.1 (L+R- and P/Q+R-type) conductances were potentiated, whereas N+R-type (CaV2.2) and R-type (CaV2.3) current amplitudes were unaffected. L+R-type currents increased from 0.36±0.04 nA to 0.64±0.11 nA and P/Q+R-type from 0.55±0.09 nA to 0.94±0.05 nA, thereby changing the balance and relative contribution of each subtype to the whole cell calcium current. In addition, N+R-type half-activation voltage was left shifted following NO exposure. NO-dependent modulation of P/Q+R and N+R-type, but not L+R-type, channels was removed by inhibition of soluble guanylyl cyclase (sGC) activity. This data demonstrates a differential effect of NO signalling on voltage-gated calcium entry, by distinct NO-dependent pathways

The acute effects of cocoa flavanols on temporal and spatial attention

In this study, we investigated how the acute physiological effects of cocoa flavanols might result in specific cognitive changes, in particular in temporal and spatial attention. To this end, we pre-registered and implemented a randomized, double-blind, placebo- and baseline-controlled crossover design. A sample of 48 university students participated in the study and each of them completed the experimental tasks in four conditions (baseline, placebo, low dose, and high-dose flavanol), administered in separate sessions with a 1-week washout interval. A rapid serial visual presentation task was used to test flavanol effects on temporal attention and integration, and a visual search task was similarly employed to investigate spatial attention. Results indicated that cocoa flavanols improved visual search efficiency, reflected by reduced reaction time. However, cocoa flavanols did not facilitate temporal attention nor integration, suggesting Potential underlying mechanisms are discussed

Comparison of Statistical Algorithms for the Detection of Infectious Disease Outbreaks in Large Multiple Surveillance Systems

A large-scale multiple surveillance system for infectious disease outbreaks has been in operation in England and Wales since the early 1990s. Changes to the statistical algorithm at the heart of the system were proposed and the purpose of this paper is to compare two new algorithms with the original algorithm. Test data to evaluate performance are created from weekly counts of the number of cases of each of more than 2000 diseases over a twenty-year period. The time series of each disease is separated into one series giving the baseline (background) disease incidence and a second series giving disease outbreaks. One series is shifted forward by twelve months and the two are then recombined, giving a realistic series in which it is known where outbreaks have been added. The metrics used to evaluate performance include a scoring rule that appropriately balances sensitivity against specificity and is sensitive to variation in probabilities near 1. In the context of disease surveillance, a scoring rule can be adapted to reflect the size of outbreaks and this was done. Results indicate that the two new algorithms are comparable to each other and better than the algorithm they were designed to replace

Beneficial effect of Sparassis crispa on stroke through activation of Akt/eNOS pathway in brain of SHRSP

Sparassis crispa (S. crispa) is a mushroom used as a natural medicine that recently became cultivatable in Japan. In this study, we investigated not only the preventive effects of S. crispa against stroke and hypertension in stroke-prone spontaneously hypertensive rats (SHRSP) but also the mechanism involved by using studies of the cerebral cortex at a young age. Six-week-old male SHRSP were divided into 2 groups, a control group and an S. crispa group administered 1.5% S. crispa in feed, and we then observed their survival. In addition, rats of the same age were treated with 1.5% S. crispa for 4 weeks and we measured body weight, blood pressure, blood flow from the tail, NOx production, and the levels of expression of several proteins in the cerebral cortex by western blot analysis. Our results showed that the S. crispa group had a delayed incidence of stroke and death and significantly decreased blood pressure and increased blood flow after the administration. Moreover, the quantity of urinary excretion and the nitrate/nitrite concentration in cerebral tissue were higher than those of control SHRSP rats. In the cerebral cortex, phosphor-eNOS (Ser1177) and phosphor-Akt (Ser473) in S. crispa-treated SHRSP were increased compared with those of control SHRSP rats. In conclusion, S. crispa could ameliorate cerebrovascular endothelial dysfunction by promoting recovery of Akt-dependent eNOS phosphorylation and increasing NO production in the cerebral cortex. S. crispa may be useful for preventing stroke and hypertension