A Dimension-Adaptive Multi-Index Monte Carlo Method Applied to a Model of a Heat Exchanger

We present an adaptive version of the Multi-Index Monte Carlo method, introduced by Haji-Ali, Nobile and Tempone (2016), for simulating PDEs with coefficients that are random fields. A classical technique for sampling from these random fields is the Karhunen-Lo\`eve expansion. Our adaptive algorithm is based on the adaptive algorithm used in sparse grid cubature as introduced by Gerstner and Griebel (2003), and automatically chooses the number of terms needed in this expansion, as well as the required spatial discretizations of the PDE model. We apply the method to a simplified model of a heat exchanger with random insulator material, where the stochastic characteristics are modeled as a lognormal random field, and we show consistent computational savings

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration

Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABA(A) α2-subunit are associated with ethanol dependence. Variations in this gene also convey sensitivity to the subjective effects of ethanol, indicating a role in mediating ethanol-related behaviours. We therefore investigated the consequences of deleting the α2-subunit on the ataxic and rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol were explored in GABA(A) α2-subunit wildtype (WT) and knockout (KO) mice using a Rotarod apparatus, wire hang and the duration of loss of righting reflex. Following training, KO mice showed shorter latencies to fall than WT littermates under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the righting reflex than WT mice. To ensure the acute effects are not due to the gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did not differ between genotypes. To investigate ethanol's rewarding properties, WT and KO mice were trained to lever press to receive increasing concentrations of ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self-administered ethanol at similar rates, with no differences in the numbers of reinforcers earned. These data indicate a protective role for α2-subunits, against the acute sedative and ataxic effects of ethanol. However, no change was observed in ethanol self administration, suggesting the rewarding effects of ethanol remain unchange

High cable forces deteriorate pinch force control in voluntary-closing body-powered prostheses

It is generally asserted that reliable and intuitive control of upper-limb prostheses requires adequate feedback of prosthetic finger positions and pinch forces applied to objects. Body-powered prostheses (BPPs) provide the user with direct proprioceptive feedback. Currently available BPPs often require high cable operation forces, which complicates control of the forces at the terminal device. The aim of this study is to quantify the influence of high cable forces on object manipulation with voluntary-closing prostheses. Able-bodied male subjects were fitted with a bypass-prosthesis with low and high cable force settings for the prehensor. Subjects were requested to grasp and transfer a collapsible object as fast as they could without dropping or breaking it. The object had a low and a high breaking force setting. Subjects conducted significantly more successful manipulations with the low cable force setting, both for the low (33 % more) and high (50 %) object’s breaking force. The time to complete the task was not different between settings during successful manipulation trials. In conclusion: high cable forces lead to reduced pinch force control during object manipulation. This implies that low cable operation forces should be a key design requirement for voluntary-closing BPPs

Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review.

Background: Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications. Methods: We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age. Results: 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation. Conclusion: There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

Preliminary effects and acceptability of a co-produced physical activity referral intervention

Objectives: To explore the preliminary effects and acceptability of a co-produced physical activity referral intervention. Study Design: Longitudinal design with data collected at baseline and post a 12-week physical activity referral intervention. Setting. Community leisure centre. Methods: 32 adults with controlled lifestyle-related health conditions took part in a physical activity referral intervention (co-produced by a multidisciplinary stakeholder group) comprising 12 weeks’ subsidised fitness centre access plus four behaviour change consultations. A complete case analysis (t-tests and magnitude-based inferences) was conducted to assess baseline-to-12-week change in physical activity, cardiometabolic, and psychological measures. Semi-structured interviews were conducted (n=12) to explore experiences of the intervention. Results: Mean improvements were observed in cardiorespiratory fitness-2 (3.6 ml.kg.-1min-1 (95% confidence interval 1.9 to 5.4) P<0.001) and moderate-to-vigorous physical activity (12.6 min.day (95% CI 4.3 to 29.6) P=0.013). Participants were positive about the support from exercise referral practitioners, but experienced some challenges in a busy and under staffed gym environment. Conclusions: A co-produced physical activity referral intervention elicited short-term improvements in physical activity and cardiometabolic health. Further refinements may be required, via ongoing feedback between stakeholders, researchers and service users, to achieve the intended holistic physical activity focus of the intervention, prior to a definitive trial

On the context-dependent scaling of consumer feeding rates

This is the final version. Available from Wiley via the DOI in this record.The stability of consumer–resource systems can depend on the form of feeding interactions (i.e.functional responses). Size-based models predict interactions–and thus stability–based on con-sumer–resource size ratios. However, little is known about how interaction contexts (e.g. simpleor complex habitats) might alter scaling relationships. Addressing this, we experimentally mea-sured interactions between a large size range of aquatic predators (4–6400 mg over 1347 feedingtrials) and an invasive prey that transitions among habitats: from the water column (3D interac-tions) to simple and complex benthic substrates (2D interactions). Simple and complex substratesmediated successive reductions in capture rates–particularly around the unimodal optimum–and promoted prey population stability in model simulations. Many real consumer–resource sys-tems transition between 2D and 3D interactions, and along complexity gradients. Thus, Context-Dependent Scaling (CDS) of feeding interactions could represent an unrecognised aspect of foodwebs, and quantifying the extent of CDS might enhance predictive ecology

The relationship between job satisfaction, burnout, and turnover intention among physicians from urban state-owned medical institutions in Hubei, China: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Throughout China, a growing number of physicians are leaving or intending to depart from their organizations owing to job dissatisfaction. Little information is available about the role of occupational burnout in this association. We set out to analyze the relationship between job satisfaction, burnout, and turnover intention, and further to determine whether occupational burnout can serve as a mediator among Chinese physicians from urban state-owned medical institutions.</p> <p>Methods</p> <p>A cross-sectional survey was carried out in March 2010 in Hubei Province, central China. The questionnaires assessed sociodemographic characteristics, job satisfaction, burnout, and turnover intention. The job satisfaction and occupational burnout instruments were obtained by modifying the Chinese Physicians' Job Satisfaction Questionnaire (CPJSQ) and the Chinese Maslach Burnout Inventory (CMBI), respectively. Such statistical methods as one-way ANOVA, Pearson correlation, GLM-univariate and structural equation modeling were used.</p> <p>Results</p> <p>Of the 1600 physicians surveyed, 1451 provided valid responses. The respondents had medium scores (3.18 +/-0.73) on turnover intention, in which there was significant difference among the groups from three urban areas with different development levels. Turnover intention, which significantly and negatively related to all job-satisfaction subscales, positively related to each subscale of burnout syndrome. Work environment satisfaction (<it>b </it>= -0.074, <it>p < 0.01</it>), job rewards satisfaction (<it>b </it>= -0.073, <it>p < 0.01</it>), organizational management satisfaction (<it>b </it>= -0.146, <it>p < 0.01</it>), and emotional exhaustion (<it>b </it>= 0.135, <it>p < 0.01</it>) were identified as significant direct predictors of the turnover intention of physicians, with 41.2% of the variance explained unitedly, under the control of sociodemographic variables, among which gender, age, and years of service were always significant. However, job-itself satisfaction no longer became significant, with the estimated parameter on job rewards satisfaction smaller after burnout syndrome variables were included. As congregated latent concepts, job satisfaction had both significant direct effects (gamma₂₁= -0.32, <it>p < 0.01</it>) and indirect effects (gamma₁₁× beta₂₁= -0.13, <it>p < 0.01</it>) through occupational burnout (62% explained) as a mediator on turnover intention (47% explained).</p> <p>Conclusions</p> <p>Our study reveals that several, but not all dimensions of both job satisfaction and burnout syndrome are relevant factors affecting physicians' turnover intention, and there may be partial mediation effects of occupational burnout, mainly through emotional exhaustion, within the impact of job satisfaction on turnover intention. This suggests that enhancements in job satisfaction can be expected to reduce physicians' intentions to quit by the intermediary role of burnout as well as the direct path. It is hoped that these findings will offer some clues for health-sector managers to keep their physician resource motivated and stable.</p