An Examination of Motivation to Change and Neural Alcohol Cue Reactivity Following a Brief Intervention.

Background: Brief interventions represent a promising psychological intervention targeting individuals with heavy alcohol use. Motivation to change represents an individual's openness to engage in a behavior change strategy and is thought to be a crucial component of brief interventions. Neuroimaging techniques provide a translational tool to investigate the neurobiological mechanisms underlying potential mediators of treatment response, including motivation to change. Therefore, this study aimed to examine the effect of a brief intervention on motivation to change drinking behavior and neural alcohol taste cue reactivity. Methods: Non-treatment-seeking heavy drinkers were randomized to receive a brief drinking intervention (n = 22) or an attention-matched control (n = 24). Three indices of motivation to change were assessed at baseline and after the intervention or control session: importance, confidence, and readiness. Immediately following the intervention or control session, participants also underwent an functional magnetic resonance imaging (fMRI) during which they completed an alcohol taste cues paradigm. Results: There was a significant effect of the brief intervention on increasing ratings of importance of changing drinking behavior, but not on ratings of confidence or readiness to change. Ratings of importance after the intervention or control session were associated with neural alcohol taste cue reactivity, but notably, this effect was only significant for participants who received the intervention. Individuals in the intervention condition showed a positive association between ratings of importance and activation in the precuneus, posterior cingulate, and insula. Conclusions: The brief drinking intervention was successful at improving one dimension of motivation to change among non-treatment-seeking heavy drinkers. The brief intervention moderated the relationship between ratings of importance and brain activation in circuitry associated with interoceptive awareness and self-reflection. Together, findings represent an initial step toward understanding the neurobiological mechanisms through which a brief intervention may improve motivation to change

Clinical and cognitive correlates of employment among patients with schizophrenia: a cross-sectional study in Malaysia

<p>Abstract</p> <p>Background</p> <p>Gainful employment is one major area of functioning which is becoming an important goal in psychiatric rehabilitation of patients with schizophrenia. Studies in western countries are pointing to evidence that certain sociodemographic and clinical factors may contribute to employment outcomes in this group of people. However, the area is still largely unexplored in Malaysia. The aim of this study was to examine the sociodemographic, clinical and cognitive correlates of employment status among patients with Schizophrenia.</p> <p>Methods</p> <p>This was a cross-sectional study. All participants who fulfilled the requirements of the study according to the inclusion and exclusion criteria were enrolled. Study instruments included a demographic data questionnaire, Positive and Negative Symptom Scale (PANSS), Trail Making Tests, Rey's Auditory Verbal Learning Test (RAVLT) and Digit Span. Bivariate analyses were done using chi-square for categorical data and t-test for continuous data and multiple logistic regression analysis was done to identify predictors of employment status.</p> <p>Results</p> <p>A total of 95 participants who fulfilled the inclusion criteria were enrolled into the study. Among the sociodemographic, clinical and cognitive variables studied marital status, educational level, mean scores of negative symptoms, Digit Span and RAVLT and Trail Making Tests were found to show significant association with employment status on bivariate analyses. However, when entered into a logistic regression model, only cognitive variables ie. Trail A and B, Digit Span and RAVLT were significant predictors of employment status.</p> <p>Conclusions</p> <p>The results from this study support the role of cognitive function, particularly, attention, working memory and executive functioning on attaining and maintaining employment in persons with schizophrenia as measured by the RAVLT, Digit Span and Trail Making Tests. These findings may act as preliminary evidence suggesting the importance of integrating cognitive rehabilitation in the psychosocial rehabilitation program for patients with schizophrenia in Malaysia.</p

Synergistic drug combinations from electronic health records and gene expression.

ObjectiveUsing electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.MethodWe applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.ResultsFrom EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.ConclusionsThis is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing

Ant colony optimization for design of water distribution systems

During the last decade, evolutionary methods such as genetic algorithms have been used extensively for the optimal design and operation of water distribution systems. More recently, ant colony optimization algorithms ~ACOAs!, which are evolutionary methods based on the foraging behavior of ants, have been successfully applied to a number of benchmark combinatorial optimization problems. In this paper, a formulation is developed which enables ACOAs to be used for the optimal design of water distribution systems. This formulation is applied to two benchmark water distribution system optimization problems and the results are compared with those obtained using genetic algorithms ~GAs!. The findings of this study indicate that ACOAs are an attractive alternative to GAs for the optimal design of water distribution systems, as they outperformed GAs for the two case studies considered both in terms of computational efficiency and their ability to find near global optimal solutions.Holger R. Maier, Angus R. Simpson, Aaron C. Zecchin, Wai Kuan Foong, Kuang Yeow Phang, Hsin Yeow Seah and Chan Lim Ta

A Brief Smoking Cessation Intervention for Heavy Drinking Smokers: Treatment Feasibility and Acceptability

Approximately 20–25% of regular smokers report heavy drinking. Abstinent smokers are five times as likely to experience a smoking lapse during drinking episodes. Current efforts seek to improve treatments for this subgroup of heavy-drinking smokers. This study tested the feasibility and acceptability of addressing alcohol use in a brief, single session smoking cessation intervention (SMK+A) compared to smoking cessation counseling only (SMK); these interventions were grounded in a motivational interview framework and included personalized feedback, decisional balance, quit day setting, and tailored skills building (e.g., breathing techniques, coping with urges, dealing with social pressures) to maintain abstinence. Descriptive outcomes included reported helpfulness of intervention skills, readiness to change scores, and feasibility of participant recruitment and retention. We also assessed 7-day point prevalence of smoking cessation, and smoking and drinking reduction at 1-month follow-up. Participants (N = 22) were community-based treatment-seeking daily smokers (≥5 cigarettes/day) who were also heavy drinkers (≥14 drinks/week for men, ≥ 7 drinks/week for women; or ≥5 drinks on one episode in past week for men, ≥4 for women). Twenty five percent of interested individuals were eligible after initial phone screen, and all randomized participants were retained through follow up. All skills demonstrated high acceptability (i.e., rated between moderately and very helpful), and a significant proportion of participants in each condition reported taking action to reduce cigarette smoking and/or alcohol use at 1-month post-quit. Three participants in each condition (27.3%) attained bioverified (CO ≤ 4 parts per million and cotinine ≤ 3 ng/mL) smoking quit at follow-up. Given the modified intervention's acceptability and flexibility, larger studies may help to elucidate this intervention's effects on readiness to change, smoking cessation, and alcohol reduction

The SXS Collaboration catalog of binary black hole simulations

Accurate models of gravitational waves from merging black holes are necessary for detectors to observe as many events as possible while extracting the maximum science. Near the time of merger, the gravitational waves from merging black holes can be computed only using numerical relativity. In this paper, we present a major update of the Simulating eXtreme Spacetimes (SXS) Collaboration catalog of numerical simulations for merging black holes. The catalog contains 2018 distinct configurations (a factor of 11 increase compared to the 2013 SXS catalog), including 1426 spin-precessing configurations, with mass ratios between 1 and 10, and spin magnitudes up to 0.998. The median length of a waveform in the catalog is 39 cycles of the dominant $\ell=m=2$ gravitational-wave mode, with the shortest waveform containing 7.0 cycles and the longest 351.3 cycles. We discuss improvements such as correcting for moving centers of mass and extended coverage of the parameter space. We also present a thorough analysis of numerical errors, finding typical truncation errors corresponding to a waveform mismatch of $\sim 10^{-4}$. The simulations provide remnant masses and spins with uncertainties of 0.03% and 0.1% ($90^{\text{th}}$ percentile), about an order of magnitude better than analytical models for remnant properties. The full catalog is publicly available at https://www.black-holes.org/waveforms .Comment: 33+18 pages, 13 figures, 4 tables, 2,018 binaries. Catalog metadata in ancillary JSON file. v2: Matches version accepted by CQG. Catalog available at https://www.black-holes.org/waveform

Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015

Background Exposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden. We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels. Methods We estimated global population-weighted mean concentrations of particle mass with aerodynamic diameter less than 2·5 μm (PM2·5) and ozone at an approximate 11 km × 11 km resolution with satellite-based estimates, chemical transport models, and ground-level measurements. Using integrated exposure–response functions for each cause of death, we estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using non-linear exposure–response functions spanning the global range of exposure. Findings Ambient PM2·5 was the fifth-ranking mortality risk factor in 2015. Exposure to PM2·5 caused 4·2 million (95% uncertainty interval [UI] 3·7 million to 4·8 million) deaths and 103·1 million (90·8 million 115·1 million) disability-adjusted life-years (DALYs) in 2015, representing 7·6% of total global deaths and 4·2% of global DALYs, 59% of these in east and south Asia. Deaths attributable to ambient PM2·5 increased from 3·5 million (95% UI 3·0 million to 4·0 million) in 1990 to 4·2 million (3·7 million to 4·8 million) in 2015. Exposure to ozone caused an additional 254 000 (95% UI 97 000–422 000) deaths and a loss of 4·1 million (1·6 million to 6·8 million) DALYs from chronic obstructive pulmonary disease in 2015. Interpretation Ambient air pollution contributed substantially to the global burden of disease in 2015, which increased over the past 25 years, due to population ageing, changes in non-communicable disease rates, and increasing air pollution in low-income and middle-income countries. Modest reductions in burden will occur in the most polluted countries unless PM2·5 values are decreased substantially, but there is potential for substantial health benefits from exposure reduction

Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations

Measurement of three-jet differential cross sections d sigma-3jet / d M-3jet in p anti-p collisions at sqrt(s)=1.96 TeV

We present the first measurement of the inclusive three-jet differential cross section as a function of the invariant mass of the three jets with the largest transverse momenta in an event in p anti-p collisions at sqrt(s) = 1.96 TeV. The measurement is made in different rapidity regions and for different jet transverse momentum requirements and is based on a data set corresponding to an integrated luminosity of 0.7 fb^{-1} collected with the D0 detector at the Fermilab Tevatron Collider. The results are used to test the three-jet matrix elements in perturbative QCD calculations at next-to-leading order in the strong coupling constant. The data allow discrimination between parametrizations of the parton distribution functions of the proton.Comment: 10 pages, 4 figures, 2 tables, submitted to Phys. Lett. B, corrected chi2 values for NNPD

Pharmacokinetics of enteric coated mycophenolate sodium in lupus nephritis (POEMSLUN)

Mycophenolate mofetil (MMF) or enteric coated mycophenolate sodium (EC-MPS) and steroids are used for induction and maintenance therapy in severe lupus nephritis (LN). Blood concentrations of mycophenolic acid (MPA), the active metabolite of these drugs varies among LN patients. The objective of this study was to examine whether concentration controlled (CC) dosing (via therapeutic drug monitoring) of EC-MPS result in a higher proportion of participants achieving target exposure of MPA compared to fixed dosing (FD). An additional aim of the study was to evaluate the influence of CC dosing on clinical outcomes.Nineteen participants were randomly assigned either to FD or CC group. All the participants were eligible to have free and total measurements of MPA over a period of 8-12 hours on three different occasions. Area under the concentration-time curve between 0 and 12 hours (AUC0-12) was calculated using non-compartmental method. Dose of EC-MPS was titrated according to AUC0-12 in the CC group.Thirty-two AUC0-12 measurements were obtained from 9 FD and 9 CC participants. Large interpatient variability was observed in both groups but was more pronounced in FD group. There were no significant differences between FD and CC participants in any pharmacokinetic parameters across the study visits except for total C0 (FD 2.0 ± 0.3 mg/L vs. CC 1.1 ± 0.3; p = 0.01) and dose-normalised C0 (FD 2.9 ± 0.2 mg/L/g vs. CC 2.1 ± 0.7 mg/L/g; p = 0.04) at the second visit and total AUC0-12 (FD 66.6 ± 6.0 mg[BULLET OPERATOR]h/L vs. CC 35.2 ± 11.4 mg[BULLET OPERATOR]h/L; p = 0.03) at the third visit. At the first study visit, 33.3% of the FD and 11.1% of the CC participants achieved the target AUC (p = 0.58). From the second visit, none of the FD participants, compared to all the CC participants, achieved target AUC0-12 (p = 0.01). More CC participants achieved remission compared to FD participants (absolute difference of -22.2, 95% confidence interval -0.19-0.55; p = 0.62). The mean free MPA AUC0-12 was significantly lower in those who had complete remission.CC participants reached target AUC0-12 quicker. Larger studies are required to test clinical efficacy.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal