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Genome-wide association studies (GWAS) have now been conducted for hundreds of phenotypes of relevance to human health. Many such GWAS involve multiple closely-related phenotypes collected on the same samples. However, the vast majority of these GWAS have been analyzed using simple univariate analyses, which consider one phenotype at a time. This is despite the fact that, at least in simulation experiments, multivariate analyses have been shown to be more powerful at detecting associations. Here, we conduct multivariate association analyses on 13 different publicly-available GWAS datasets that involve multiple closely-related phenotypes. These data include large studies of anthropometric traits (GIANT), plasma lipid traits (GlobalLipids), and red blood cell traits (HaemgenRBC). Our analyses identify many new associations (433 in total across the 13 studies), many of which replicate when follow-up samples are available. Overall, our results demonstrate that multivariate analyses can help make more effective use of data from both existing and future GWAS. [ABSTRACT FROM AUTHOR]

We examined the influence of linear perspective cues and texture gradients in the perceptual rescaling of stimuli over a highly-salient Ponzo illusion of a corridor. We performed two experiments using the Method of Constant Stimuli where participants judged the size of one of two rings. In experiment 1, one ring was presented in the upper visual-field at the end of the corridor and the other in the lower visual-field at the front of the corridor. The perceived size of the top and bottom rings changed as a function of the availability of linear perspective and textures. In experiment 2, only one ring was presented either at the top or the bottom of the image. The perceived size of the top but not the bottom ring changed as a function of the availability of linear perspective and textures. In both experiments, the effects of the cues were additive. Perceptual rescaling was also stronger for the top compared to the bottom ring. Additional eye-tracking revealed that participants tended to gaze more in the upper than the lower visual-field. These findings indicate that top-down mechanisms provide an important contribution to the Ponzo illusion. Nonetheless, additional maximum likelihood estimation analyses revealed that linear perspective fulfilled a greater contribution in experiment 2, which is suggestive of a bottom-up mechanism. We conclude that both top-down and bottom-up mechanisms play important roles. However, the former seems to fulfil a more prominent role when both stimuli are presented in the image. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the dependability and accuracy of midkine (MK) in the diagnosis of hepatocellular carcinoma (HCC). Methods: PubMed, EMBASE, Web of Science, China Biology Medicine disc and grey literature sources were searched from the date of database inception to January 2019. Two authors (B-H.Z. and B.L.) independently extracted the data and evaluated the study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR−) were estimated using a bivariate model. Moreover, hierarchical summary receiver operating characteristic curves were generated. The diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled using a univariate model. Results: Nine articles (11 studies) were included (1941 participants). The bivariate analysis revealed that the sensitivity and specificity of MK for HCC diagnosis were 0.85 (95% CI 0.78–0.91) and 0.83 (95% CI 0.76–0.88), respectively. We also found a LR+ of 5.05 (95% CI 3.33–7.40), a LR− of 0.18 (95% CI 0.11–0.28), a DOR of 31.74 (95% CI 13.98–72.09) and an AUC of 0.91 (95% CI 0.84–0.99). Subgroup analyses showed that MK provided the best efficiency for HCC diagnosis when the cutoff value was greater than 0.5 ng/mL. Conclusions: MK has an excellent diagnostic value for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to examine the effects of physical exercise cum cognitive-behavioural therapy (CBT) on alleviating pain intensity, functional disabilities, and mood/mental symptoms in those suffering with chronic musculoskeletal pain. MEDLINE, EMBASE, PubMEd, PsycINFO and CINAHL were searched to identify relevant randomised controlled trials from inception to 31 December 2018. The inclusion criteria were: (a) adults ≥18 years old with chronic musculoskeletal pain ≥3 months, (b) randomised controlled design, (c) a treatment arm consisting of physical intervention and CBT combined, (d) the comparison arm being waitlist, usual care or other non-pharmacological interventions such as physical exercise or CBT alone, and (e) outcomes including pain intensity, pain-related functional disabilities (primary outcomes), or mood/mental symptoms (secondary outcome). The exclusion criteria were: (a) the presence of comorbid mental illnesses other than depression and anxiety and (b) non-English publication. The search resulted in 1696 records and 18 articles were selected for review. Results varied greatly across studies, with most studies reporting null or small effects but a few studies reporting very large effects up to 2-year follow-up. Pooled effect sizes (Hedges' g) were ~1.00 for pain intensity and functional disability, but no effect was found for mood/mental symptoms. The effects were mainly driven by several studies reporting unusually large differences between the exercise cum CBT intervention and exercise alone. When these outliers were removed, the effect on pain intensity disappeared at post-intervention while a weak effect (g = 0.21) favouring the combined intervention remained at follow-up assessment. More consistent effects were observed for functional disability, though the effects were small (g = 0.26 and 0.37 at post-intervention and follow-up respectively). More importantly, the value of adding CBT to exercise interventions is questionable, as consistent benefits were not seen. The clinical implications and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

Fertility in Ghana has declined steadily since 1980, however, a slight increase was observed between 2008 and 2014. While several factors may account for this pattern, research on the contribution of type of union is limited. This study examined differentials in the fertility of women in different types of union. Secondary data from 6,285 (weighted) ever-married women aged 15–49 years were analysed using compare means, t-test, analysis of variance, Poisson and binary logistic regression analyses. The findings indicate that, independent of other factors, fertility among remarried women is higher compared to first-time married women but this does not hold true when other factors are controlled for. Additionally, there was no significant difference in the fertility of remarried women who were in union and women who were in union in a first-time marriage. However, compared to remarried women who were currently in a union, fertility was significantly lower among remarried women who were not currently in union (β = -0.121, p<0.01) and women who have been married only once but were not currently in union (β = -0.212, p<0.001). Further analysis revealed that remarried women were significantly more likely to desire more children and less likely to use any method of contraception compared to first-time married women. There is the need for further research to better understand the fertility needs of remarried women. [ABSTRACT FROM AUTHOR]

The practice of early marriage, although acknowledged as a human rights violation, continues to occur in many countries. Different studies have identified the associated factors in many developing countries. However, these factors often assume no geographical variation in these factors within countries. Again, cultural practices and beliefs which strongly influence the acceptance and practices of early marriage vary geographically. In addition, geographic clusters of high rates of early marriage and union formation are also unknown. Thus, area specific correlates of early child marriage are required for the development of location specific policies to aid the eradication of early child marriage. Using data from the 2010 Ghana Population and Housing Census, this study examines the extent of geospatial clustering in early marriage amongst girls and their spatially-varying associated factors at the district level. The findings reveal strong clustering of high early marriage amongst districts in the Upper West, Northern and Volta regions. Nationally, 6.96% (CI = 6.83, 7.08) of girls are married or in union before their 18th birthday. The estimates range from 2.7% in the Jaman North district in Brong Ahafo region to 19.0% in the Gushiegu district in Northern region. Economic factors were observed as important spatially-varying associated factors. The findings suggest that targeted interventions are required in the effort to eradicate the practice in Ghana. [ABSTRACT FROM AUTHOR]

Context: Whether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment. Objective: To determine the impact of PVL and PIVH in the incidence of cerebral palsy, sensorineural impairment and development scores in preterm neonates. Registered in PROSPERO (CRD42017073113). Data sources: PubMed, Embase, SciELO, LILACS, and Cochrane databases. Study selection: Prospective cohort studies evaluating neurodevelopment in children born preterm which performed brain imaging in the neonatal period. Data extraction: Two independent researchers extracted data using a predesigned data extraction sheet. Statistical methods: A random-effects model was used, with Mantel-Haenszel approach and a Sidik-Jonkman method for the estimation of variances, combined with Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed through the I2 statistic and sensitivity analysis were performed when possible. No funnel plots were generated but publication bias was discussed as a possible limitation. Results: Our analysis concluded premature children with any degree of PIVH are at increased risk for cerebral palsy (CP) when compared to children with no PIVH (3.4, 95% CI 1.60–7.22; 9 studies), a finding that persisted on subgroup analysis for studies with mean birth weight of less than 1000 grams. Similarly, PVL was associated with CP, both in its cystic (19.12, 95% CI 4.57–79.90; 2 studies) and non-cystic form (9.27, 95% CI 5.93–14.50; 2 studies). We also found children with cystic PVL may be at risk for visual and hearing impairment compared to normal children, but evidence is weak. Limitations: Major limitations were the lack of data for PVL in general, especially for the outcome of neurodevelopment, the high heterogeneity among methods used to assess neurodevelopment and the small number of studies, which led to meta-analysis with high heterogeneity and wide confidence intervals. Conclusions: There was no evidence supporting the hypothesis that PIVH causes impairment in neuropsychomotor development in our meta-analysis, but review of newer studies show an increased risk for lower intelligence scores in children with severe lesions, both PIVH and PVL. There is evidence to support the hypothesis that children with any degree of PIVH, especially those born below 1000 grams and those with severe haemorrhage, are at increased risk of developing CP, as well as children with PVL, both cystic and non-cystic. [ABSTRACT FROM AUTHOR]

Background: In patients with left heart failure, micro-RNAs (miRNAs) have been shown to be of diagnostic and prognostic value. The present study aims to identify those miRNAs in patients with univentricular heart (UVH) disease that may be associated with overt heart failure. Methods: A large panel of human miRNA arrays were used to determine miRNA expression profiles in the blood of 48 UVH patients and 32 healthy controls. For further selection, the most abundantly expressed miRNA arrays were related to clinical measures of heart failure and selected miRNAs validated by polymerase chain reaction were used for the prediction of overt heart failure and all-cause mortality. Results: According to microarray analysis, 50 miRNAs were found to be significantly abundant in UVH patients of which miR-150-5p was best related to heart failure parameters. According to ROC analysis, NT-proBNP levels (AUC 0.940, 95% CI 0.873–1.000; p = 0.001), miR-150-5p (AUC 0.905, 95% CI 0.779–1.000; p = 0.001) and a higher NYHA class ≥ III (AUC 0.893, 95% CI 0.713–1.000; p = 0.002) were the 3 most significant predictors of overt heart failure. Using a combined biomarker model, AUC increased to 0.980 indicating an additive value of miR-150-5p. Moreover, in the multivariate analysis, a higher NYHA class ≥ III (p = 0.005) and miR-150-5p (p = 0.006) turned out to be independent predictors of overt heart failure. Conclusion: In patients with UVH, miR-150-5p is an independent predictor of overt heart failure and thus may be used in the risk assessment of these patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate effects of postural changes and bladder distention on intrabladder pressure whilst estimating intra-abdominal pressure in horses. Design: Two-year cohort study. Patients admitted for elective surgical procedures unrelated to gastrointestinal or genitourinary tract. Setting: School of Agricultural and Veterinarian Sciences, Jaboticabal, SP, Brazil. Animals: 20 adult horses, 11 males (stallions and geldings) and 9 females; between 3.5 and 12 years, weighing 350 to 500 kg. Interventions: Intra-abdominal pressure was directly-recorded through abdominocentesis at the ventral midline with a fluid-filled system. Intrabladder pressure was obtained from a bladder catheter with the fluid-filled system zeroed at the level of the tuber ischia with patients in dorsal recumbency or pubic symphysis if in lateral recumbency. Measurements and main results: Body position directly influenced intra-abdominal pressure. In dorsal recumbency, intra-abdominal pressure differed (p < 0.05) from intrabladder pressure at end-inspiration and end-expiration regardless of whether the bladder was empty or distended. There was no correlation nor association between the two pressures in this body position. In lateral recumbency a difference (p <0.05) between intra-abdominal pressure and intrabladder pressure was recorded at end-inspiration with the bladder distended with 25 ml, and at end-expiration for distension volumes of 25 ml and 50 ml. There was a strong correlation between both pressures for left and right lateral recumbency, regardless of the distension volume. Ordinary least product (OLP) regression analysis showed no fixed or proportional bias between both pressures for distension volume of 50 ml, at both end-inspiration and end-expiration. Conclusions: Indirect assessment of equine intra-abdominal pressure cannot be made in dorsal recumbency. For that purpose, patients should be in left lateral recumbency with the bladder distended with 50 ml. Values can be recorded at end-inspiration or end-expiration. Restriction: Occlusion of the catheter tip by the bladder wall when minimally distended. [ABSTRACT FROM AUTHOR]

Background: Dietary management is highly important for the maintenance of renal function in patients with chronic kidney disease (CKD). Cerebral oxygen saturation (rSO2) was reportedly associated with the estimated glomerular filtration rate (eGFR) and cognitive function. However, data concerning the association between cerebral rSO2 and dietary intake of CKD patients is limited. Methods: This was a single-center observational study. We recruited 67 CKD patients not undergoing dialysis. Cerebral rSO2 was monitored using the INVOS 5100c oxygen saturation monitor. Energy intake was evaluated by dietitians based on 3-day meal records. Daily protein and salt intakes were calculated from 24-h urine collection. Results: Multivariable regression analysis showed that cerebral rSO2 was independently associated with energy intake (standardized coefficient: 0.370) and serum albumin concentration (standardized coefficient: 0.236) in Model 1 using parameters with p < 0.10 in simple linear regression analysis (body mass index, Hb level, serum albumin concentration, salt and energy intake) and confounding factors (eGFR, serum sodium concentration, protein intake), and the energy/salt index (standardized coefficient: 0.343) and Hb level (standardized coefficient: 0.284) in Model 2 using energy/protein index as indicated by energy intake/protein intake and energy/salt index by energy intake/salt intake in place of salt, protein and energy intake. Conclusions: Cerebral rSO2 is affected by energy intake, energy/salt index, serum albumin concentration and Hb level. Sufficient energy intake and adequate salt restriction is important to prevent deterioration of cerebral oxygenation, which might contribute to the maintenance of cognitive function in addition to the prevention of renal dysfunction in CKD patients. [ABSTRACT FROM AUTHOR]

The problem of handling non-ignorable non-response has been typically addressed under the design-based approach using the well-known sub-sampling technique introduced by Hansen and Hurwitz [1946, Journal of the American Statistical Association, Vol 41(236), Page 517- 529]. Alternatively, the model-based paradigm emphasizes on utilizing the underlying model relationship between the outcome variable and one or more covariate(s) whose population values are known prior to the survey. This article utilizes the model relationship between the study variable and covariate(s) for handling non-ignorable non-response and obtaining an unbiased estimator for the population total under the sub-sampling technique. The main idea is to combine the estimates obtained from the sample on first call and the sub-sample from second call using separate model relationships. The contribution of this paper helps us in providing unbiased estimates with an improved efficiency under model-based paradigm in presence of non-ignorable non-response. The provided method is more economical than the available estimators under callback methods as we are working sub-sampling and also increase response rate as a stronger mode of interview is employed for data collection. A numerical study using Monte Carlo is presented to illustrate the behavior of the proposed and the efficiency comparison. [ABSTRACT FROM AUTHOR]

Social scientists have been interested in measuring the prosperity, well-being, and quality of life of nations, which has resulted in a multiplicity of country-level indicators. However, little is known about the factor structure of these indicators. We explored the structure of quality of life, using country-level data on tens of subjective and objective indicators. Applying factor analysis, we identified three distinct factors that exhibited both overlap and complementarity. This structure was replicated in data from previous years and with a partially different set of variables. The first factor, ‘socio-economic progress’, is dominated by socio-political and economic indicators but also includes life satisfaction, which thus appears to reflect objective living conditions. The second factor, ‘psycho-social functioning’, consists of subjective indicators, such as eudaimonic well-being and positive affective states. The third, ‘negative affectivity’, comprises negatively-valenced affective states. The three macro-factors of societal quality of life demonstrated moderate intercorrelations and differential associations with cultural and ecological variables, providing support for their discriminant validity. Finally, country and regional rankings based on the three societal factors revealed a complex picture that cautions against over-reliance on any single indicator such as life satisfaction. The results underline the need for a broadly-based approach to the measurement of societal quality of life, and provide an empirically-derived multidimensional framework for conceptualizing and measuring quality of life and well-being at country level. This study is thus an initial empirical step towards systematizing the multiple approaches to societal quality of life. [ABSTRACT FROM AUTHOR]

Background: Postural orthostatic tachycardia syndrome is a disorder of the autonomic nervous system. Approximately 30% of patients experience orthostatic headaches. Orthostatic headaches also are a hallmark symptom in spontaneous intracranial hypotension. While the cause of orthostatic headaches in spontaneous intracranial hypotension can be linked to the cerebrospinal fluid loss at the spinal level and consecutively reduced intracranial pressure in the upright position, the cause of orthostatic headaches in postural orthostatic tachycardia syndrome still remains unknown. The present study examined orthostatic changes of intracranial pressure using dynamic ultrasound of the optic nerve and optic nerve sheath diameter in postural orthostatic tachycardia syndrome, spontaneous intracranial hypotension and healthy subjects. Methods: Data was obtained from postural orthostatic tachycardia syndrome patients with (n = 7) and without orthostatic headaches (n = 7), spontaneous intracranial hypotension patients (n = 5) and healthy subjects (n = 8). All participants underwent high-resolution transorbital ultrasound in the supine and upright position to assess optic nerve and optic nerve sheath diameter. Results: Group differences were found in percentage deviations when changing position of optic nerve sheath diameter (p < 0.01), but not regarding the optic nerve diameter. Pairwise comparisons indicated differences in optic nerve sheath diameter only between spontaneous intracranial hypotension and the other groups. No differences were found between postural orthostatic tachycardia syndrome patients with and without orthostatic headaches. Conclusion: This study shows that the size of the optic nerve sheath diameter dynamically decreases during orthostatic stress in spontaneous intracranial hypotension, but not in postural orthostatic tachycardia syndrome with or without orthostatic headaches, which indicates different underlying causes. [ABSTRACT FROM AUTHOR]

South Korea is ranked as 4th among 34 nations of the Organization for Economic Cooperation and Development with 102 deaths in road accidents per one million population. This paper aims to investigate the factors associated with road accidents in South Korea. The rainfall data of the Korea Meteorological Administration and road accidents data of Traffic Accident Analysis System of Korea Road Traffic Authority is analyzed for this purpose. In this connection, multivariate regression analysis and ratio analysis with the descriptive analysis are performed to uncover the catastrophic factors involved. In turn, the results reveal that traffic volume is the leading factor in road accidents. The limited road extension of 1.47% compared to the 4.14% per annum growth of the vehicles is resulting in road accidents at such a large scale. The increasing proportion of passenger cars accelerate road accidents as well. 56% of accidents occur by the infringement of safety driving violations. The drivers with higher driving experience tend to have a higher accident ratio. The collected data is analyzed in terms of gender, driver experience, type of violations and accidents as well as the associated time of the accidents when they happen. The results indicate that 36.29% and 53.01% of accidents happen by male drivers in the day and night time, respectively. 29.15% of crashes happen due to safety infringement and violations of 41 to 60 years old drivers. The results demonstrate that population density is associated with the accidents frequency and lower density results in an increased number of accidents. The necessity of the state-of-the-art regulations to govern the urban road traffic is beyond dispute, and it becomes even more crucial for citizens’ relief since in our daily lives road accidents are getting more diverse. [ABSTRACT FROM AUTHOR]

Background: Previous studies of radiological damage in rheumatoid arthritis (RA) have used candidate-gene approaches, or evaluated single genome-wide association studies (GWAS). We undertook the first meta-analysis of GWAS of RA radiological damage to: (1) identify novel genetic loci for this trait; and (2) test previously validated variants. Methods: Seven GWAS (2,775 RA cases, of a range of ancestries) were combined in a meta-analysis. Radiological damage was assessed using modified Larsen scores, Sharp van Der Heijde scores, and erosive status. Single nucleotide polymophsim (SNP) associations with radiological damage were tested at a single time-point using regression models. Primary analyses included age and disease duration as covariates. Secondary analyses also included rheumatoid factor (RF). Meta-analyses were undertaken in trans-ethnic and European-only cases. Results: In the trans-ethnic primary meta-analysis, one SNP (rs112112734) in close proximity to HLA-DRB1, and strong linkage disequilibrium with the shared-epitope, attained genome-wide significance (P = 4.2x10-8). In the secondary analysis (adjusting for RF) the association was less significant (P = 1.7x10-6). In both trans-ethnic primary and secondary meta-analyses 14 regions contained SNPs with associations reaching P<5x10-6; in the European primary and secondary analyses 13 and 10 regions contained SNPs reaching P<5x10-6, respectively. Of the previously validated SNPs for radiological progression, only rs660895 (tagging HLA-DRB1*04:01) attained significance (P = 1.6x10-5) and had a consistent direction of effect across GWAS. Conclusions: Our meta-analysis confirms the known association between the HLA-DRB1 shared epitope and RA radiological damage. The lack of replication of previously validated non-HLA markers highlights a requirement for further research to deliver clinically-useful prognostic genetic markers. [ABSTRACT FROM AUTHOR]

Even though classic job design theories have evolved over the years and become more focused on employees’ ability to autonomously change their job characteristics, tools to assess job crafting are still limited. The purpose of this study was to analyze the psychometric properties of the Spanish version of the Job Crafting Questionnaire (JCQ), taking into account the valuable contribution made by Wrzesniewski and Dutton’s model to the understanding of the job crafting concept. The total sample consisted of 768 employees (participants’ mean age was 41.63 and 49.7% of them were women). The sample was randomly divided into two halves in order to conduct two factor analyses (Exploratory Factor Analysis and Confirmatory Factor Analysis). Concurrent and convergent validity was assessed by computing correlations with validated questionnaires for measuring job crafting (Job Crafting Scale, JCS), engagement (Utrecht Work Engagement Scale, UWES-9) and job burnout (Maslach Burnout Inventory-General Survey, MBI-GS). The results indicated a high level of internal consistency (Cronbach’s alpha = .880) which was similar to the original scale, and provided a good fit to the three-dimensional model tested. Appropriate evidence of construct validity was also shown (r = .45 with total JCS; r = .52 with total UWES-9 and r-values between -.33 and .45 with MBI dimensions). The results confirmed that the Spanish translation of the JCQ is a suitable tool for measuring job crafting and enabling practitioners and researchers to further expand the existing knowledge of this concept. [ABSTRACT FROM AUTHOR]

Early mobilization has been proven to be an effective and safe intervention for preventing complications in mechanically ventilated patients; however, there is currently no unified definition of the optimal mobilization initiation time, hindering widespread clinical implementation. As clinicians are increasingly aware of the benefits of early mobilization, the definition of early mobilization is important. The purpose of this study was to evaluate the effects of different early mobilization initiation times on mechanically ventilated patients and rank these times for practical consideration. The Chinese Biomedical Literature Database, the Chinese Knowledge Infrastructure, Wanfang Data, PubMed, Cochrane Library, Web of Science, and Embase databases, along with grey literature and reference lists, were searched for randomized control trials (RCTs) that evaluated the effects of early mobilization for improving patient outcomes; databases were searched from inception to October 2018. Two authors extracted data independently, using a predesigned Excel form, and assessed the quality of included RCTs according to the Cochrane Handbook (v5.1.0). Data were analyzed using Stata (v13.0) and Review Manager (v5.3.0). A total of 15 RCTs involving 1726 patients and seven mobilization initiation times (which were all compared to usual care) were included in our analysis. Network meta-analysis showed that mechanical ventilation for 48–72 h may be optimal to improve intensive care unit acquired weakness (ICU-AW) and reduce the duration of mechanical ventilation; however, there were no significant differences in length of ICU stay according to mobilization initiation time. The results of this study indicate that initiation of mobilization within 48–72 h of mechanical ventilation may be optimal for improving clinical outcomes for mechanically ventilated patients. [ABSTRACT FROM AUTHOR]

Deficiency in several of the classical human RAD51 paralogs [RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3] is associated with cancer predisposition and Fanconi anemia. To investigate their functions, isogenic disruption mutants for each were generated in non-transformed MCF10A mammary epithelial cells and in transformed U2OS and HEK293 cells. In U2OS and HEK293 cells, viable ablated clones were readily isolated for each RAD51 paralog; in contrast, with the exception of RAD51B, RAD51 paralogs are cell-essential in MCF10A cells. Underlining their importance for genomic stability, mutant cell lines display variable growth defects, impaired sister chromatid recombination, reduced levels of stable RAD51 nuclear foci, and hyper-sensitivity to mitomycin C and olaparib. Altogether these observations underscore the contributions of RAD51 paralogs in diverse DNA repair processes, and demonstrate essential differences in different cell types. Finally, this study will provide useful reagents to analyze patient-derived mutations and to investigate mechanisms of chemotherapeutic resistance deployed by cancers. [ABSTRACT FROM AUTHOR]

Introduction: Epidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016–2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible, and actionable the information produced by these studies was. Methods: To improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE, and grey literature review, we identified studies that forecasted, predicted, or simulated ecological or epidemiological phenomena related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility, and clarity by independent reviewers. Results: 2034 studies were identified, of which n = 73 met the eligibility criteria. Spatial spread, R0 (basic reproductive number), and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barré Syndrome burden (4%), sexual transmission risk (4%), and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%), and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions, and 54% provided sufficient methodological detail to allow complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median of 119 days sooner than journal publication dates, they were used in only 30% of studies. Conclusions: Many ZIKV predictions were published during the 2016–2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics, and pandemics. [ABSTRACT FROM AUTHOR]

Background: Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax.Methods and Findings: Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups.Conclusions: In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis. [ABSTRACT FROM AUTHOR]

Background: This study investigated the incidence and predictors of retreatment after discontinuation of either entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment in Taiwan. Methods: A total of 535 non-cirrhotic chronic hepatitis B (CHB) patients undergoing either ETV (n = 358) or TDF (n = 177) treatment were enrolled. Patients were followed for at least 12 months after stopping ETV or TDF treatment. Most patients (86.3%) fulfilled the retreatment criteria of Taiwan's National Health Plan. Results: The 5-year cumulative rates of clinical relapse and retreatment were 52.1% and 47%, respectively, in 160 hepatitis B e antigen (HBeAg)-positive patients, and were 62% and 54.8%, respectively, in 375 HBeAg-negative patients. The median duration from the end of treatment until clinical relapse and retreatment was 40 and 57 weeks, respectively, for all patients. Multivariate Cox regression analysis revealed that discontinuing TDF treatment, old age, male gender, and higher baseline HBsAg levels were independent factors of retreatment in HBeAg-positive patients; old age, HBV genotype B, and higher baseline and end-of-treatment HBsAg levels were independent factors in HBeAg-negative patients. A total of 18.8% of retreated patients satisfied the retreatment criteria of hepatic decompensation according to Taiwan's National Health Plan. Of the 64 patients who had clinical relapse without retreatment, 17 achieved sustained virological remission and 26 did not experience clinical relapse until their last visit after clinical relapse. Four patients developed HBsAg loss. Conclusions: The 5-year retreatment rate was about 50% in HBeAg-positive and HBeAg-negative patients. Discontinuing TDF treatment was an independent factor of retreatment in HBeAg-positive patients. [ABSTRACT FROM AUTHOR]

Echocardiography, as a noninvasive hemodynamic evaluation technique, is frequently used in critically ill patients. Different opinions exist regarding whether it can be interchanged with traditional invasive means, such as the pulmonary artery catheter thermodilution (TD) technique. This systematic review aimed to analyze the consistency and interchangeability of cardiac output measurements by ultrasound (US) and TD. Five electronic databases were searched for studies including clinical trials conducted up to June 2019 in which patients’ cardiac output was measured by ultrasound techniques (echocardiography) and TD. The methodological quality of the included studies was evaluated by two independent reviewers who used the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), which was tailored according to our systematic review in Review Manager 5.3. A total of 68 studies with 1996 patients were identified as eligible. Meta-analysis and subgroup analysis were used to compare the cardiac output (CO) measured using the different types of echocardiography and different sites of Doppler use with TD. No significant differences were found between US and TD (random effects model: mean difference [MD], -0.14; 95% confidence interval, -0.30 to 0.02; P = 0.08). No significant differences were observed in the subgroup analyses using different types of echocardiography and different sites except for ascending aorta (AA) (random effects model: mean difference [MD], -0.37; 95% confidence interval, -0.74 to -0.01; P = 0.05) of Doppler use. The median of bias and limits of agreement were -0.12 and ±0.94 L/min, respectively; the median of correlation coefficient was 0.827 (range, 0.140–0.998). Although the difference in CO between echocardiography by different types or sites and TD was not entirely consistent, the overall effect of meta-analysis showed that no significant differences were observed between US and TD. The techniques may be interchangeable under certain conditions. [ABSTRACT FROM AUTHOR]

Background: Quality improvement collaboratives (QICs) have been used to improve health care for decades. Evidence on QIC effectiveness has been reported, but systematic reviews to date have little information from low- and middle-income countries (LMICs). Objective: To assess the effectiveness of QICs in LMICs. Methods: We conducted a systematic review following Cochrane methods, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for quality of evidence grading, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement for reporting. We searched published and unpublished studies between 1969 and March 2019 from LMICs. We included papers that compared usual practice with QICs alone or combined with other interventions. Pairs of reviewers independently selected and assessed the risk of bias and extracted data of included studies. To estimate strategy effectiveness from a single study comparison, we used the median effect size (MES) in the comparison for outcomes in the same outcome group. The primary analysis evaluated each strategy group with a weighted median and interquartile range (IQR) of MES values. In secondary analyses, standard random-effects meta-analysis was used to estimate the weighted mean MES and 95% confidence interval (CI) of the mean MES of each strategy group. This review is registered with PROSPERO (International Prospective Register of Systematic Reviews): CRD42017078108. Results: Twenty-nine studies were included; most (21/29, 72.4%) were interrupted time series studies. Evidence quality was generally low to very low. Among studies involving health facility-based health care providers (HCPs), for “QIC only”, effectiveness varied widely across outcome groups and tended to have little effect for patient health outcomes (median MES less than 2 percentage points for percentage and continuous outcomes). For “QIC plus training”, effectiveness might be very high for patient health outcomes (for continuous outcomes, median MES 111.6 percentage points, range: 96.0 to 127.1) and HCP practice outcomes (median MES 52.4 to 63.4 percentage points for continuous and percentage outcomes, respectively). The only study of lay HCPs, which used “QIC plus training”, showed no effect on patient care-seeking behaviors (MES -0.9 percentage points), moderate effects on non-care-seeking patient behaviors (MES 18.7 percentage points), and very large effects on HCP practice outcomes (MES 50.4 percentage points). Conclusions: The effectiveness of QICs varied considerably in LMICs. QICs combined with other invention components, such as training, tended to be more effective than QICs alone. The low evidence quality and large effect sizes for QIC plus training justify additional high-quality studies assessing this approach in LMICs. [ABSTRACT FROM AUTHOR]

Background: Previous studies have documented that disordered eating is associated with a wide range of impaired physical and mental health conditions among children and adolescents. The relationship between disordered eating and health-related quality of life (HRQOL) has been predominantly examined in children and adolescents who are overweight or obese or suffer from chronic illnesses. In the last decade, several studies have been conducted to investigate the relationship between disordered eating and HRQOL among school and community children and adolescents. No systematic review or meta-analysis has synthesized the findings from these population-based studies. The purpose of this systematic review and meta-analysis was to synthesize the relationship between disordered eating and HRQOL among the general population of children and adolescents. Methods: We performed a computer search for the English language literature using the databases PUBMED, EMBASE and PSYCINFO to retrieve eligible studies published between 1946 and August 9, 2018. We also searched the relevant articles using PubMed related article search features and manually examined the reference lists of the retrieved full text articles selected from the database search. The association between disordered eating and HRQOL was synthesized using both a qualitative method and a meta-analysis. The review was conducted adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Results: We identified eight studies that met the inclusion criteria and were included in the final synthesis. The studies included six cross-sectional studies and two longitudinal studies. The systematic review found that disordered eating attitudes and behaviors were associated with lower HRQOL among children and adolescents. Children and adolescents with bulimia nervosa (BN), binge eating disorder (BED), purging disorder (PD) and other eating disorder symptoms had poorer HRQOL than their healthy peers without the eating disorder conditions. The meta-analysis using four out of the eight studies showed that disordered eating was significantly associated with poor psychosocial health and lower overall HRQOL among children and adolescents. Conclusion: The present review reveals that disordered eating behaviors and eating disorders are associated with decreased HRQOL in children and adolescents. More prospective studies are needed to ascertain the directions in the relationship between disordered eating and HRQOL among children and adolescents. The findings of this review suggest that health programs for promoting healthy eating and reducing disordered eating behaviors among school children and adolescents may help to enhance the HRQOL and overall health status of these individuals. [ABSTRACT FROM AUTHOR]

Background/Aim: The aim of this study is to determine the relationship between stromal types, PD-L1 status and clinicopathological characteristics in patients with different molecular subtypes of breast cancer. Materials and methods: Protein expression levels of PD-L1 were determined by immunohistochemistry assay. Stromal type was classified based on the maturity of the tumor stroma. Results: Different subtypes of breast cancer had distinct stromal types. Tumors from patients with mature stroma had lower pathological N stage and AJCC stage, more frequent high p53 expression and positive stromal PD-L1 staining. Hormone receptor negative patients had higher frequency of positive stromal PD-L1 staining. Stromal PD-L1 status was also associated with different breast cancer subtypes and EGFR expression level. Importantly, our data revealed that stromal types and stromal PD-L1 status were independent prognostic factors. Conclusion: This study highlighted the importance of stromal types and stromal PD-L1 status in determining clinical outcomes in patients with breast cancer, and suggested that stromal type classification might be readily incorporated into routine clinical risk assessment following curative resection or optimal therapeutic design. [ABSTRACT FROM AUTHOR]

The cochlear nucleus (CN) transforms the spike trains of spiral ganglion cells into a set of sensory representations that are essential for auditory discriminations and perception. These transformations require the coordinated activity of different classes of neurons that are embryologically derived from distinct sets of precursors. Decades of investigation have shown that the neurons of the CN are differentiated by their morphology, neurotransmitter receptors, ion channel expression and intrinsic excitability. In the present study we have used linear discriminant analysis (LDA) to perform an unbiased analysis of measures of the responses of CN neurons to current injections to objectively categorize cells on the basis of both morphology and physiology. Recordings were made from cells in brain slices from CBA/CaJ mice and a transgenic mouse line, NF107, crossed against the Ai32 line. For each cell, responses to current injections were analyzed for spike rate, spike shape, input resistance, resting membrane potential, membrane time constant, hyperpolarization-activated sag and time constant. Cells were filled with dye for morphological classification, and visually classified according to published accounts. The different morphological classes of cells were separated with the LDA. Ventral cochlear nucleus (VCN) bushy cells, planar multipolar (T-stellate) cells, and radiate multipolar (D-stellate) cells were in separate clusters and separate from all of the neurons from the dorsal cochlear nucleus (DCN). Within the DCN, the pyramidal cells and tuberculoventral cells were largely separated from a distinct cluster of cartwheel cells. principal axes, whereas VCN cells were in 3 clouds approximately orthogonal to this plane. VCN neurons from the two mouse strains overlapped but were slightly separated, indicating either a strain dependence or differences in slice preparation methods. We conclude that cochlear nucleus neurons can be objectively distinguished based on their intrinsic electrical properties, but such distinctions are still best aided by morphological identification. [ABSTRACT FROM AUTHOR]

Lutzomyia longipalpis is the main vector of Leishmania infantum, the causative agent of visceral leishmaniasis in the Neotropical realm. Its taxonomic status has been widely discussed once it encompasses a complex of species. The knowledge about the genetic structure of insect vector populations helps the elucidation of components and interactions of the disease ecoepidemiology. Thus, the objective of this study was to genotypically analyze populations of the Lu. longipalpis complex from a macrogeographic perspective using Next Generation Sequencing. Polymorphism analysis of three molecular markers was used to access the levels of population genetic structure among nine different populations of sand flies. Illumina Amplicon Sequencing Protocol® was used to identify possible polymorphic sites. The library was sequenced on paired-end Illumina MiSeq platform. Significant macrogeographical population differentiation was observed among Lu. longipalpis populations via PCA and DAPC analyses. Our results revealed that populations of Lu. longipalpis from the nine municipalities were grouped into three clusters. In addition, it was observed that the levels of Lu. longipalpis population structure could be associated with distance isolation. This new sequencing method allowed us to study different molecular markers after a single sequencing run, and to evaluate population and inter-species differences on a macrogeographic scale. [ABSTRACT FROM AUTHOR]

Background: The high chances of getting latent tuberculosis infection (LTBI) among health care workers (HCWs) will an enormous problem in low and upper-middle-income countries. Method: Search strategies were done through both national and international databases include SID, Barakat knowledge network system, Irandoc, Magiran, Iranian national library, web of science, Scopus, PubMed/MEDLINE, OVID, EMBASE, the Cochrane library, and Google Scholar search engine. The Persian and the English languages were used as the filter in national and international databases, respectively. Medical Subject Headings (MeSH) terms was used to controlling comprehensive vocabulary. The search terms were conducted without time limitation till January 01, 2019. Results: The prevalence of LTBI in Iranian’s HCWs, based on the PPD test was 27.13% [CI95%: 18.64–37.7]. The highest prevalence of LTBI in Iranian’s HCWs were estimated 41.4% [CI95%: 25.4–59.5] in the north, and 33.8% [CI95%: 21.1–49.3] in the west. The lowest prevalence of LTBI was evaluated 18.2% [CI95%: 3.4–58.2] in the south of Iran. The prevalence of LTBI in Iranian’s HCWs who had work-experience more than 20 years old were estimated 20.49% [CI95%: 11–34.97]. In the PPD test, the prevalence of LTBI in Iranian’s HCWs who had received the Bacille Calmette–Guérin (BCG) was estimated 15% [CI95%: 3.6–47.73]. While, in the QFT, the prevalence of LTBI in Iranian’s HCWs in non-vaccinated was estimated 25.71% [CI95%: 13.96–42.49]. Conclusions: This meta-analysis shows the highest prevalence of LTBI in Iranian’s HCWs in the north and the west probably due to neighboring countries like Azerbaijan and Iraq, respectively. It seems that Iranian’s HCWs have not received the necessary training to prevent of TB. We also found that BCG was not able to protect Iranian’s HCWs from TB infections, completely. [ABSTRACT FROM AUTHOR]

The need for a validated set of emotional clips to elicit emotions in more ecological experiments is increasing. Here we present the validation of a new database of emotional films, named E-MOVIE, which includes, in this first validation phase, 39 excerpts arranged in six categories, three negative (Fear, Sadness and Compassion), two positive (Erotic and Scenery) and a Neutral category. Notably, Compassion and Scenery are new in the field as they were not included in other databases. The clips in E-MOVIE are characterized by homogenous durations of approximately two minutes, which make them suitable for psychophysiological research. In order to study the affective profile prompted by each category 174 participants (112 women) rated the movies on multiple dimensions, namely valence and arousal, intensity and discreteness of the induction of one of the six basic emotions and, finally, intensity of the experience of the emotional states defined by a series of emotional adjectives. Erotic clips were effective in the elicitation of a positive emotional state, characterized by high levels of arousal and excitement. On the other hand, Fear clips (selected without blood to avoid disgust reaction) prompted an affect characterized by high arousal, low valence and high levels of reported fear and anxiety. Women reported greater unpleasantness, distress, anxiety and jittery than men to the three negative categories. Compassion clips, characterized by the depiction of crying characters, were able to induce an affective state dominated by sadness and feeling touched, consistent with an empathic reaction to emotional sufferance. Sadness clips, instead, elicited an affective state characterized by sadness together with distress and angst. We also demonstrated that clips depicting natural environments (i.e. Scenery) prompted in the viewer a surprised, inspired affective state, characterized by high valence and arousal (especially in males), a result which suggests that their past categorization as neutral stimuli was inaccurate and problematic. [ABSTRACT FROM AUTHOR]

The transport and distribution of charged molecules in polyelectrolyte solutions are of both fundamental and practical importance. A practical example, which is the specific subject addressed in the present paper, is the transport and distribution of charged species into cartilage. The charged species could be a contrast agent or a drug molecule involved in diagnosis or treatment of the widespread degenerative disease osteoarthritis, which leads to degradation of articular cartilage. Associated scientific issues include the rate of transport and the equilibrium concentrations of the charged species in the cartilage and the synovial fluid. To address these questions, we present results from magnetic resonance micro-imaging experiments on a model system of articular cartilage. The experiments yield temporally and spatially resolved data on the transport of a negatively charged contrast agent (charge = -2), used in medical examinations of cartilage, into a polyelectrolyte solution, which is designed to capture the electrostatic interactions in cartilage. Also presented is a theoretical analysis of the transport where the relevant differential equations are solved using finite element techniques as well as treated with approximate analytical expressions. In the analysis, non-ideal effects are included in the treatment of the mobile species in the system. This is made possible by using results from previous Monte Carlo simulations. The results demonstrate the importance of taking non-idealities into account when data from measurements of transport of charged solutes in a system with fixed charges from biological polyelectrolytes are analyzed. [ABSTRACT FROM AUTHOR]

Background: Physical therapy can prevent functional impairments and improve the quality of life of patients after hospital discharge. However, the effect of early mobilization on patients with a critical illness remains unclear. This study was performed to assess the evidence available regarding the effect of early mobilization on critically ill patients in the intensive care unit (ICU). Methods: Electronic databases were searched from their inception to March 21, 2019. Randomized controlled trials (RCTs) comprising critically ill patients who received early mobilization were included. The methodological quality and risk of bias of each eligible trial were assessed using the Cochrane Collaboration tool. Data were extracted using a standard collection form each included study, and processed using the Mantel-Haenszel (M-H) or inverse-variance (I-V) test in the STATA v12.0 statistical software. Results: A total of 1,898 records were screened. Twenty-three RCTs comprising 2,308 critically ill patients were ultimately included. Early mobilization decreased the incidence of ICU-acquired weakness (ICU-AW) at hospital discharge (three studies, 190 patients, relative risk (RR): 0.60, 95% confidence interval (CI) [0.40, 0.90]; p = 0.013, I2 = 0.0%), increased the number of patients who were able to stand (one study, 50 patients, 90% vs. 62%, p = 0.02), increased the number of ventilator-free days (six studies, 745 patients, standardized mean difference (SMD): 0.17, 95% CI [0.02, 0.31]; p = 0.023, I2 = 35.5%) during hospitalization, increased the distance the patient was able to walk unassisted (one study, 104 patients, 33.4 (0–91.4) meters vs. 0 (0–30.4) meters, p = 0.004) at hospital discharge, and increased the discharged-to-home rate (seven studies, 793 patients, RR: 1.16, 95% CI [1.00, 1.34]; p = 0.046). The mortality (28-day, ICU and hospital) and adverse event rates were moderately increased by early mobilization, but the differences were statistically non-significant. However, due to the substantial heterogeneity among the included studies, and the low quality of the evidence, the results of this study should be interpreted with caution. Publication bias was not identified. Conclusions: Early mobilization appears to decrease the incidence of ICU-AW, improve the functional capacity, and increase the number of ventilator-free days and the discharged-to-home rate for patients with a critical illness in the ICU setting. [ABSTRACT FROM AUTHOR]

Background: It remains unknown which is the optimal first-line treatment regimen for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue. Methods: PubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs). Results: 25 RCTs with a total of 5005 patients randomized to receive seven treatments were included in the meta-analysis. Third-generation tyrosine kinase inhibitor (TKI) (osimertinib) and first-generation TKIs (F-TKIs) in combination with chemotherapy (F-TKIs+CT) were more effective than F-TKIs alone in terms of PFS (HR = 0.46, 95% CI: 0.22–0.93; P = 0.031 and HR = 0.62, 95% CI: 0.39–0.98; P = 0.041) and OS (HR = 0.63, 95% CI: 0.43–0.91; P = 0.014 and HR = 0.73, 95% CI: 0.57–0.92; P = 0.008). Second-generation TKIs (S-TKIs) showed significant OS advantage over F-TKIs (HR = 0.83, 95% CI: 0.70–0.99; P = 0.04). Based on treatment ranking in terms of PFS and OS, osimertinib had the highest probability of being the most effective treatment (89% and 86%) and with the best tolerability. F-TKIs+CT was ranked the second-most effective regimen, but with relatively high risk of SAEs. Conclusions: Osimertinib seemed to be the most preferable first-line treatment in advanced EGFR-mutated NSCLC. However, limitations of the study including a single RCT investigating osimertinib and immature OS data need to be considered. [ABSTRACT FROM AUTHOR]

Seasonal influenza is a sometimes surprisingly impactful disease, causing thousands of deaths per year along with much additional morbidity. Timely knowledge of the outbreak state is valuable for managing an effective response. The current state of the art is to gather this knowledge using in-person patient contact. While accurate, this is time-consuming and expensive. This has motivated inquiry into new approaches using internet activity traces, based on the theory that lay observations of health status lead to informative features in internet data. These approaches risk being deceived by activity traces having a coincidental, rather than informative, relationship to disease incidence; to our knowledge, this risk has not yet been quantitatively explored. We evaluated both simulated and real activity traces of varying deceptiveness for influenza incidence estimation using linear regression. We found that deceptiveness knowledge does reduce error in such estimates, that it may help automatically-selected features perform as well or better than features that require human curation, and that a semantic distance measure derived from the Wikipedia article category tree serves as a useful proxy for deceptiveness. This suggests that disease incidence estimation models should incorporate not only data about how internet features map to incidence but also additional data to estimate feature deceptiveness. By doing so, we may gain one more step along the path to accurate, reliable disease incidence estimation using internet data. This capability would improve public health by decreasing the cost and increasing the timeliness of such estimates. [ABSTRACT FROM AUTHOR]

Cognitive models suggest that social anxiety disorder (SAD) is maintained through the use of safety behaviours. Previous reports propose that these safety behaviours can be subdivided into two main categories: avoidance and impression management. Study 1 investigates whether certain safety behaviours are specific to SAD. The social behaviour questionnaire was administered to individuals with SAD (N = 106), post-traumatic stress disorder (N = 28) and non-patient controls (N = 59). A factor analysis (N = 164) replicated the previously reported avoidance and impression management subtypes. Scores for both subtypes were significantly higher in individuals with SAD than in individuals with post-traumatic stress disorder or non-patient controls. Study 2 investigated the causal role of such safety behaviours using an experimental design in a non-clinical population (N = 96). Pairs of participants each engaged in two conversations. In one of the conversations, a randomly selected participant performed either avoidance or impression management safety behaviours. In the other conversation, neither participant was instructed to use safety behaviours. Each participant rated their own anxiety and performance as well as rating the other person. Videos of the conversations were also rated. Both types of safety behaviour increased anxiety in the person performing the safety behaviour. The avoidance subtype also had broader effects on the other person that were largely absent from the impression management subtype. Taken together the studies provide support for the distinction between safety behaviour subtypes and have implications for the treatment of SAD. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes are at high risk of drug therapy problems (DTPs), as they are receiving multiple medications. To date, studies regarding DTPs in patients with diabetes in Ethiopia are limited. The aim of this study was to assess prevalence of DTPs, medication adherence and treatment satisfaction of patients with diabetes at Tikur Anbessa Specialized Hospital (TASH). Method: A cross-sectional study was conducted on randomly selected 418 participants who fulfilled the inclusion criteria. Data were collected using structured questionnaire and patients’ chart review. Cipolle’s classification system was used to determine DTPs. Modified Morisky’s Adherence Scale (MMAS-8) was used to measure patients’ adherence to their medication. Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) patient satisfaction assessment questionnaire was used to assess patients’ treatment satisfaction. Results: A total of 207 DTPs in 177 (42.3%) of participants were identified. Commonly identified DTPs were dosage too low (58, 28.0%), ineffective drug therapy (54, 26.1%), and need additional drug therapy (52, 25.1%). Factors associated with DTPs were female gender (Adjusted Odds Ratio [AOR] = 2.31,95% CI:1.30–4.12); ≥3comorbidities (AOR = 3.61, 95% CI:1.19–10.96); ever married (AOR = 2.58,95% CI:1.23–5.48); type 2 diabetes (AOR = 5.62, 95% CI:1.21–26.04); non-adherence (AOR = 5.26,95% CI:2.51–11.04) and residence out of Addis Ababa (AOR = 0.30, 95% CI:0.12–0.73). Twenty four percent of participants were non-adherent to their drug therapies. Factors associated with non-adherence were diabetes complications (AOR = 2.00, 95% CI: 1.2–3.32), the female gender (AOR = 1.67, 95%CI: 1.01–2.8) and level of education (AOR = 0.42, 95%CI: 0.18–0.96). Eighty one percent of participants were satisfied with the current treatment. Conclusion: A significant proportion of patients were satisfied with their treatment and a quarter of the study participants were non-adherent to their medications at TASH diabetic clinic. However, DTPs were considerably higher among the study participants. Hence, future interventions targeting prevention and resolution of DTPs deemed to be necessary. [ABSTRACT FROM AUTHOR]

In order to support decision making on how to most effectively improve broiler welfare an innovative expert survey was conducted based on principles derived from semantic modelling. Twenty-seven experts, mainly broiler welfare scientists (n = 20; and 7 veterinarians), responded (response rate 38%) by giving welfare scores (GWS, scale 0–10) to 14 benchmarking housing systems (HSs), and explaining these overall scores by selecting, weighing and scoring main welfare parameters, including both input and output measures. Data exploration followed by REML (Linear Mixed Model) and ALM (Automatic Linear Modelling) analyses revealed 6 clusters of HSs, sorted from high to low welfare, i.e. mean GWS (with superscripts indicating significant differences): 1. (semi-natural backyard) Flock (8.8a); 2. Nature (7.7ab), Label Rouge II (7.4ab), Free range EU (7.2ab), Better Life (7.2ab); 3. Organic EU (7.0bc), Freedom Food (6.2bc); 4. Organic US (5.8bcd), Concepts NL (5.6abcdef), GAP 2 (4.9bcd); 5. Conventional EU (3.7de), Conventional US (2.9ef), Modern cage (2.9abcdef); 6. Battery cage (1.3f). Mean weighting factors (WF, scale 0–10) of frequently (n> = 15) scored parameters were: Lameness (8.8), Health status (8.6), Litter (8.3), Density (8.2), Air quality (8.1), Breed (8.0), Enrichment (7.0) and Outdoor (6.6). These did not differ significantly, and did not have much added value in explaining GWS. Effects of Role (Scientist/Vet), Gender (M/F) and Region (EU/non-EU) did not significantly affect GWS or WF, except that women provided higher WF than men (7.2 vs 6.4, p<0.001). The contribution of welfare components to overall welfare has been quantified in two ways: a) using the beta-coefficients of statistical regression (ALM) analyses, and b) using a semantic-modelling type (weighted average) calculation of overall scores (CalcWS) from parameter level scores (PLS) and WF. GWS and CalcWS were highly correlated (R = ~0.85). CalcWS identified Lameness, Health status, Density, Breed, Air quality and Litter as main parameters contributing to welfare. ALM showed that the main parameters which significantly explained the variance in GWS based on all PLS, were the output parameter Health status (with a beta-coefficient of 0.38), and the input parameters (stocking) Density (0.42), Litter (0.14) and Enrichment (0.27). The beta-coefficients indicated how much GWS would improve from 1 unit improvement in PLS for each parameter, thus the potential impact on GWS ranged from 1.4 welfare points for Litter to 4.2 points for Density. When all parameters were included, 81% of the variance in GWS was explained (77% for inputs alone; 39% for outputs alone). From this, it appears that experts use both input and output parameters to explain overall welfare, and that both are important. The major conventional systems and modern cages for broilers received low welfare scores (2.9–3.7), well below scores that may be considered acceptable (5.5). Also, several alternatives like GAP 2 (4.9), Concepts NL (5.6), Organic US (5.8) and Freedom Food (6.2) are unacceptable, or at risk of being unacceptable due to individual variation between experts and farms. Thus, this expert survey provides a preliminary semi-quantified decision-support tool to help determine how to most effectively improve broiler welfare in a wide range of HSs. [ABSTRACT FROM AUTHOR]

Background: In this research, an meta-analysis was performed for assessment of the associations between O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation possessing low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), cervical cancer (CC), and clinicopathological characters of CC. Methods: Literature selection were conducted through searching PubMed, Web of science, EMBASE, China National Knowledge Infrastructure and Wanfang databases (up to November 2018). An assessment of associations between MGMT methylation and LSIL, HSIL, CC risk and clinicopathological characteristics was performed through pooled odds ratios (ORs) with relevant 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and Galbraith plots were conducted to conduct an exploration on the possible sources of heterogeneity. The genome-wide DNA methylation array studies were extracted from Gene Expression Omnibus (GEO) databases for validation of these outcomes. Results: In this meta-analysis of 25 published articles, MGMT hypermethylation gradually elevated the rates among control group (12.16%), LSIL (20.92%), HSIL (36.33%) and CC (41.50%) specimens. MGMT promoter methylation was significant associated with the increased risk of LSIL by 1.74-fold (P<0.001), HSIL by 3.71-fold (P<0.001) and CC by 7.08-fold (P<0.001) compared with control. A significant association between MGMT promoter methylation with FIGO stage was also found (OR = 2.81, 95% CI: 1.79–4.41, p<0.001). The results of GEO datasets showed that 5 CpG sites in MGMT with a great diagnostic value for the screening of cervical cancer. Conclusion: The meta-analysis indicated the association between MGMT promoter hypermethylation and squamous intraepithelial lesion and cervical cancer. MGMT methylation detection might have a potential value to be an epigenetic marker for the clinical diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: To identify risk factors associated with unfavorable outcomes in children with IgA vasculitis with nephritis (Henoch-Schőnlein purpura nephritis)(IgA-VN) Methods: PubMed, Embase, and Web of Science databases were searched for studies, published in English through February 2019. The data were extracted to perform pooled analysis, heterogeneity testing, subgroup analysis, sensitivity analysis, and publication bias analysis. Results: This meta-analysis showed that, older age at onset (WMD 1.77, 95% CI 0.35–3.18, p = 0.014), lower glomerular filtration rate (GFR; WMD -23.93, 95% CI -33.78- -14.09, p<0.0001), initial renal manifestations with nephrotic syndrome (OR 1.74, 95% CI 1.12–2.70, p = 0.013), with nephritic-nephrotic syndrome (OR 4.55, 95% CI 2.89–7.15, p<0.0001) and renal biopsy with crescentic nephritis (International Study of Kidney Disease in Children [ISKDC] grades III-V) (OR 3.85, 95% CI 2.37–6.28, p<0.0001) were significant risk factors associated with poor outcomes in IgA-VN, whereas initial clinical features with hematuria (OR 0.33, 95% CI 0.16–0.69, p = 0.003) and mild proteinuria±hematuria (OR 0.46, 95% CI 0.28–0.75, p<0.0001) were associated with progression to good outcomes. By contrast, gender, hypertension and initial renal manifestations of acute nephritic syndrome were not significantly associated with poor outcomes in IgA-VN. Conclusion: This meta-analysis showed that older age at onset, lower GFR, initial renal features of nephrotic syndrome and nephritic-nephrotic syndrome and renal biopsy with crescentic nephritis (ISKDC grades III-V) were predictive of poor prognosis in children with IgA-VN. [ABSTRACT FROM AUTHOR]

Background: Delirium is the most common postoperative complication of the central nervous system (CNS) that can trigger long-term cognitive impairment. Its underlying mechanism is not fully understood, but the dysfunction of the blood-brain barrier (BBB) has been implicated. The serum levels of the axonal damage biomarker, phosphorylated neurofilament heavy subunit (pNF-H) increase in moderate to severe delirium patients, indicating that postoperative delirium can induce irreversible CNS damage. Here, we investigated the relationship among postoperative delirium, CNS damage and BBB dysfunction, using pNF-H as reference. Methods: Blood samples were collected from 117 patients within 3 postoperative days. These patients were clinically diagnosed with postoperative delirium using the Confusion Assessment Method for the Intensive Care Unit. We measured intercellular adhesion molecule-1, platelet and endothelial cell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin as biomarkers for BBB disruption, pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6), and pNF-H. We conducted logistic regression analysis including all participants to identify independent biomarkers contributing to serum pNF-H detection. Next, by multiple regression analysis with a stepwise method we sought to determine which biomarkers influence serum pNF-H levels, in pNF-H positive patients. Results: Of the 117 subjects, 41 were clinically diagnosed with postoperative delirium, and 30 were positive for serum pNF-H. Sensitivity and specificity of serum pNF-H detection in the patients with postoperative delirium were 56% and 90%, respectively. P-selectin was the only independent variable to associate with pNF-H detection (P < 0.0001) in all 117 patients. In pNF-H positive patients, only PECAM-1 was associated with serum pNF-H levels (P = 0.02). Conclusions: Serum pNF-H could be an objective delirium biomarker, superior to conventional tools in clinical settings. In reference to pNF-H, P-selectin may be involved in the development of delirium-related CNS damage and PECAM-1 may contribute to the progression of delirium- related CNS damage. [ABSTRACT FROM AUTHOR]

Aim: To assess the effect of Lactobacillus supplementation on Helicobacter pylori eradication rates and side effects of the triple therapy. Methods: PubMed, Embase, Web of Science and Cochrane Library were searched for articles published up to July, 2019. Review Manager 5.3 and Stata 12.0 were used for statistical analyses. Results: The initial database search resulted in 852 articles. Through exclusion and screening, 11 randomized controlled trials involving a total of 724 patients were finally included in this meta-analysis. The H. pylori elimination rate in the Lactobacillus supplement group was significantly higher than that in the control group (RR 1.16, 95% CI 1.08–1.25, P<0.0001). Subgroup analysis showed that the eradication rates were significantly enhanced in both adults and children group, and no significant difference was detected between Asia and Europe group. In addition, sub-analysis based on duration of Lactobacillus supplementation showed the pooled RRs in the long-term and short-term groups were 1.17 (95%CI 1.06–1.30) and 1.16 (95% CI 1.04–1.30), respectively. Regarding the Lactobacillus strains, the pooled RR was 1.33 (95% CI 1.10–1.62) in the L. casei group, 1.18 (95% CI 1.03–1.34) in the L. reuteri group while 1.02 (95% CI 0.87–1.21) in the Lactobacillus GG group. As for the total side effects, Lactobacillus supplementation significantly reduced the incidence of taste disturbance (RR = 0.36, 95% CI 0.17–0.74, P = 0.005). Conclusions: Lactobacillus supplementation during the treatment of Helicobacter pylori infection can effectively improve the eradication rates, and reduce the incidence of therapy-related taste disturbance. [ABSTRACT FROM AUTHOR]

Humans and other animals effortlessly identify natural sounds and categorize them into behaviorally relevant categories. Yet, the acoustic features and neural transformations that enable sound recognition and the formation of perceptual categories are largely unknown. Here, using multichannel neural recordings in the auditory midbrain of unanesthetized female rabbits, we first demonstrate that neural ensemble activity in the auditory midbrain displays highly structured correlations that vary with distinct natural sound stimuli. These stimulus-driven correlations can be used to accurately identify individual sounds using single-response trials, even when the sounds do not differ in their spectral content. Combining neural recordings and an auditory model, we then show how correlations between frequency-organized auditory channels can contribute to discrimination of not just individual sounds but sound categories. For both the model and neural data, spectral and temporal correlations achieved similar categorization performance and appear to contribute equally. Moreover, both the neural and model classifiers achieve their best task performance when they accumulate evidence over a time frame of approximately 1–2 seconds, mirroring human perceptual trends. These results together suggest that time-frequency correlations in sounds may be reflected in the correlations between auditory midbrain ensembles and that these correlations may play an important role in the identification and categorization of natural sounds. [ABSTRACT FROM AUTHOR]

Background: The Sequential Organ Failure Assessment (SOFA) score is commonly used in ICUs around the world, designed to assess the severity of the patient's clinical state based on function/dysfunction of six major organ systems. The goal of this work is to build a computational model to predict mortality based on a series of SOFA scores. In addition, we examined the possibility of improving the prediction by incorporating a new component designed to measure the performance of the gastrointestinal system, added to the other six components. Methods: In this retrospective study, we used patients’ three latest SOFA scores recorded during an individual ICU stay as input to different machine learning models and ensemble learning models. We added three validated parameters representing gastrointestinal failure. Among others, we used classification models such as Support Vector Machines (SVMs), Neural Networks, Logistic Regression and a penalty function used to increase model robustness in regard to certain extreme cases, which may be found in ICU population. We used the Area under Curve (AUC) performance metric to examine performance. Results: We found an ensemble model of linear and logistic regression achieves a higher AUC compared related works in past years. After incorporating the gastrointestinal failure score along with the penalty function, our best performing ensemble model resulted in an additional improvement in terms of AUC metrics. We implemented and compared 36 different models that were built using both the information from the SOFA score as well as that of the gastrointestinal system. All compared models have approximately similar and relatively large AUC (between 0.8645 and 0.9146) with the best results are achieved by incorporating the gastrointestinal parameters into the prediction models. Conclusions: Our findings indicate that gastrointestinal parameters carry significant information as a mortality predictor in addition to the conventional SOFA score. This information improves the predictive power of machine learning models by extending the SOFA to include information related to gastrointestinal organ system. The described method improves mortality prediction by considering the dynamics of the extended SOFA score. Although tested on a limited data set, the results' stability across different models suggests robustness in real-time use. [ABSTRACT FROM AUTHOR]

Background: Portugal has one of the most severe HIV-1 epidemics in Western Europe. Two subtypes circulate in parallel since the beginning of the epidemic. Comparing their transmission patterns and its association with transmitted drug resistance (TDR) is important to pinpoint transmission hotspots and to develop evidence-based treatment guidelines. Methods: Demographic, clinical and genomic data were collected from 3599 HIV-1 naive patients between 2001 and 2014. Sequences obtained from drug resistance testing were used for subtyping, TDR determination and transmission clusters (TC) analyses. Results: In Portugal, transmission of subtype B was significantly associated with young males, while transmission of subtype G was associated with older heterosexuals. In Portuguese originated people, there was a decreasing trend both for prevalence of subtype G and for number of TCs in this subtype. The active TCs that were identified (i.e. clusters originated after 2008) were associated with subtype B-infected males residing in Lisbon. TDR was significantly different when comparing subtypes B (10.8% [9.5–12.2]) and G (7.6% [6.4–9.0]) (p = 0.001). Discussion: TC analyses shows that, in Portugal, the subtype B epidemic is active and fueled by young male patients residing in Lisbon, while transmission of subtype G is decreasing. Despite similar treatment rates for both subtypes in Portugal, TDR is significantly different between subtypes. [ABSTRACT FROM AUTHOR]

Background: Pulmonary embolism (PE) is correlated with increased mortality among patients with lung cancer (LC). The characteristics of patients with LC presenting with PE have not been fully established, and our meta-analysis aims to comprehensively investigate the clinical characteristics associated with PE in patients with LC to help physicians identify PE earlier in these patients. Methods: Multiple databases were searched, including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Wanfang. Odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were used as effect measures for dichotomous and continuous variables, respectively. Moreover, Egger’s test, Begg’s test and a sensitivity analysis were performed to assess the publication bias and reliability of the articles. Results: In total, 16 studies were included in our meta-analysis. The results indicated that history of chronic obstructive pulmonary disease (OR = 2.59, 95% CI: 1.09, 6.15; P = 0.03), adenocarcinoma (OR = 2.28, 95% CI: 1.88, 2.77; P < 0.01), advanced tumour stage (TNM III-IV vs. I-II, OR = 2.38, 95% CI: 1.99, 2.86; P < 0.01), history of central venous catheter (OR = 1.95, 95% CI: 1.36, 2.78; P < 0.01), history of chemotherapy (OR = 2.32, 95% CI: 1.80, 2.99, P < 0.01), high levels of D-dimer (WMD = 4.31, 95% CI: 2.53, 6.10; P < 0.01) and carcinoembryonic antigen (WMD = 10.30, 95% CI: 9.95, 10.64; P < 0.01) and a low level of partial pressure of oxygen (WMD = -25.97, 95% CI: -31.31, -20.62; P < 0.01) were clinical features of LC patients with PE compared to those without PE. Conclusions: These results reveal that LC patients with PE have specific clinical features, including but not limited to several cancer- and treatment-related factors, that may help their early identification. [ABSTRACT FROM AUTHOR]

Raman chemometric urinalysis (Rametrix™) was used to analyze 235 urine specimens from healthy individuals. The purpose of this study was to establish the “range of normal” for Raman spectra of urine specimens from healthy individuals. Ultimately, spectra falling outside of this range will be correlated with kidney and urinary tract disease. Rametrix™ analysis includes direct comparisons of Raman spectra but also principal component analysis (PCA), discriminant analysis of principal components (DAPC) models, multivariate statistics, and it is available through GitHub as the Rametrix™ LITE Toolbox for MATLAB®. Results showed consistently overlapping Raman spectra of urine specimens with significantly larger variances in Raman shifts, found by PCA, corresponding to urea, creatinine, and glucose concentrations. A 2-way ANOVA test found that age of the urine specimen donor was statistically significant (p < 0.001) and donor sex (female or male identification) was less so (p = 0.0526). With DAPC models and blind leave-one-out build/test routines using the Rametrix™ PRO Toolbox (also available through GitHub), an accuracy of 71% (sensitivity = 72%; specificity = 70%) was obtained when predicting whether a urine specimen from a healthy unknown individual was from a female or male donor. Finally, from female and male donors (n = 4) who contributed first morning void urine specimens each day for 30 days, the co-occurrence of menstruation was found statistically insignificant to Rametrix™ results (p = 0.695). In addition, Rametrix™ PRO was able to link urine specimens with the individual donor with an average of 78% accuracy. Taken together, this study established the range of Raman spectra that could be expected when obtaining urine specimens from healthy individuals and analyzed by Rametrix™ and provides the methodology for linking results with donor characteristics. [ABSTRACT FROM AUTHOR]

Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare and typically aggressive malignancy with poor prognosis. This study developed a nomogram model to predict the overall survival (OS) of patients with LCNEC. Methods: LCNEC patients were identified from the Surveillance, Epidemiology, and End Results database between 2004–2014. Univariate and multivariate Cox regression models were used to determine demographic and clinicopathological features associated with OS. A nomogram model was generated to predict OS and its performance was assessed by Harrell’s concordance index (C-index), calibration plots, and subgroup analysis by risk scores. Results: Of 3048 eligible patients with LCNEC, 2138 were randomly grouped into the training set and 910 into the validation set. Age at diagnosis, gender, tumor stage, N stage, tumor size, and surgery of primary site were independent prognostic factors of OS. C-index values of the nomogram were 0.75 (95% CI, 0.74–0.76) and 0.76 (95% CI, 0.74–0.77) in the training and validation sets, respectively. In both cohorts, the calibration plots showed good concordance between the predicted and observed OS at 3 and 5 years. Kaplan-Meier curves revealed significant differences in OS in patients stratified by nomogram-based risk score, and patients with a higher-than-median risk score had poorer OS. Conclusion: This is the first nomogram developed and validated in a large population-based cohort for predicting OS in patients with LCNEC, and it shows favorable discrimination and calibration abilities. Use of this proposed nomogram has the potential to improve prediction of survival risk, and lead to individualized clinical decisions for LCNEC. [ABSTRACT FROM AUTHOR]

Cognitive behavioral therapy is an effective treatment for improving mental health problems among university students. However, intervention components have different effects on mental health problems. This paper is a meta-analysis of the data concerning the relationship between cognitive behavioral variables and mental health status among university students. A total of five electronic databases were reviewed, and 876 articles met the initial selection criteria. Reviewers applied standardized coding schemes to extract the correlational relationship between cognitive behavioral variables and mental health status. A total of 55 articles were included in the meta-analysis. Correlations were found for three cognitive behavioral variables (attention, thought, and behavior) across nine mental health domains (negative affect, positive affect, happiness, social function, stress response, psychological symptom, quality of life, well-being, and general health). Across each cognitive behavioral process and all mental health domains, the estimated mean correlation was medium (r = .32 - .46), and varied by the domain of mental health. [ABSTRACT FROM AUTHOR]

Purpose: During resections of brain tumors, neurosurgeons have to weigh the risk between residual tumor and damage to brain functions. Different perspectives on these risks result in practice variation. We present statistical methods to localize differences in extent of resection between institutions which should enable to reveal brain regions affected by such practice variation. Methods: Synthetic data were generated by simulating spheres for brain, tumors, resection cavities, and an effect region in which a likelihood of surgical avoidance could be varied between institutions. Three statistical methods were investigated: a non-parametric permutation based approach, Fisher’s exact test, and a full Bayesian Markov chain Monte Carlo (MCMC) model. For all three methods the false discovery rate (FDR) was determined as a function of the cut-off value for the q-value or the highest density interval, and receiver operating characteristic and precision recall curves were created. Sensitivity to variations in the parameters of the synthetic model were investigated. Finally, all these methods were applied to retrospectively collected data of 77 brain tumor resections in two academic hospitals. Results: Fisher’s method provided an accurate estimation of observed FDR in the synthetic data, whereas the permutation approach was too liberal and underestimated FDR. AUC values were similar for Fisher and Bayes methods, and superior to the permutation approach. Fisher’s method deteriorated and became too liberal for reduced tumor size, a smaller size of the effect region, a lower overall extent of resection, fewer patients per cohort, and a smaller discrepancy in surgical avoidance probabilities between the different surgical practices. In the retrospective patient data, all three methods identified a similar effect region, with lower estimated FDR in Fisher’s method than using the permutation method. Conclusions: Differences in surgical practice may be detected using voxel statistics. Fisher’s test provides a fast method to localize differences but could underestimate true FDR. Bayesian MCMC is more flexible and easily extendable, and leads to similar results, but at increased computational cost. [ABSTRACT FROM AUTHOR]

Background: Torture and other forms of ill treatment have been reported in at least 141 countries, exposing a global crisis. Survivors face multiple physical, psychological, and social difficulties. Psychological consequences for survivors are varied, and evidence on treatment is mixed. We conducted a systematic review and meta-analysis to estimate the benefits and harms of psychological, social, and welfare interventions for torture survivors.Methods and Findings: We updated a 2014 review with published randomised controlled trials (RCTs) for adult survivors of torture comparing any psychological, social, or welfare intervention against treatment as usual or active control from 1 January 2014 through 22 June 2019. Primary outcome was post-traumatic stress disorder (PTSD) symptoms or caseness, and secondary outcomes were depression symptoms, functioning, quality of life, and adverse effects, after treatment and at follow-up of at least 3 months. Standardised mean differences (SMDs) and odds ratios were estimated using meta-analysis with random effects. The Cochrane tool was used to derive risk of bias. Fifteen RCTs were included, with data from 1,373 participants (589 females and 784 males) in 10 countries (7 trials in Europe, 5 in Asia, and 3 in Africa). No trials of social or welfare interventions were found. Compared to mostly inactive (waiting list) controls, psychological interventions reduced PTSD symptoms by the end of treatment (SMD -0.31, 95% confidence interval [CI] -0.52 to -0.09, p = 0.005), but PTSD symptoms at follow-up were not significantly reduced (SMD -0.34, 95% CI -0.74 to 0.06, p = 0.09). No significant improvement was found for PTSD caseness at the end of treatment, and there was possible worsening at follow-up from one study (n = 28). Interventions showed no benefits for depression symptoms at end of treatment (SMD -0.23, 95% CI -0.50 to 0.03, p = 0.09) or follow-up (SMD -0.23, 95% CI -0.70 to 0.24, p = 0.34). A significant improvement in functioning for psychological interventions compared to control was found at end of treatment (SMD -0.38, 95% CI -0.58 to -0.18, p = 0.0002) but not at follow-up from only one study. No significant improvement emerged for quality of life at end of treatment (SMD 0.38, 95% CI -0.28 to 1.05, p = 0.26) with no data available at follow-up. The main study limitations were the difficulty in this field of being certain of capturing all eligible studies, the lack of modelling of maintenance of treatment gains, and the low precision of most SMDs making findings liable to change with the addition of further studies as they are published.Conclusions: Our findings show evidence that psychological interventions improve PTSD symptoms and functioning at the end of treatment, but it is unknown whether this is maintained at follow-up, with a possible worsening of PTSD caseness at follow-up from one study. Further interventions in this population should address broader psychological needs beyond PTSD while taking into account the effect of multiple daily stressors. Additional studies, including social and welfare interventions, will improve precision of estimates of effect, particularly over the longer term. [ABSTRACT FROM AUTHOR]