Meta-analysis of regional white matter volume in bipolar disorder with replication in an independent sample using coordinates, T-maps, and individual MRI data

Converging evidence suggests that bipolar disorder (BD) is associated with white matter (WM) abnormalities. Meta-analyses of voxel based morphometry (VBM) data is commonly performed using published coordinates, however this method is limited since it ignores non-significant data. Obtaining statistical maps from studies (T-maps) as well as raw MRI datasets increases accuracy and allows for a comprehensive analysis of clinical variables. We obtained coordinate data (5-studies), T-Maps (12-studies, including unpublished data) and raw MRI datasets (5-studies) and analysed the 24 studies using Seed-based d Mapping (SDM). A VBM analysis was conducted to verify the results in an independent sample. The meta-analysis revealed decreased WM volume in the posterior corpus callosum extending to WM in the posterior cingulate cortex. This region was significantly reduced in volume in BD patients in the independent dataset (p=0.003) but there was no association with clinical variables. We identified a robust WM volume abnormality in BD patients that may represent a trait marker of the disease and used a novel methodology to validate the findings

Discrete Roles for Impulsivity and Compulsivity in Gambling Disorder

Background and Objective: Complex associations between gambling disorder (GD) and impulsivity have been identified. However, little is known regarding how compulsivity associates with different impulsivity domains in GD. In this study, we examined associations between self-reported and behavioral measures of impulsivity-assessed through the Barratt Impulsiveness Scale (BIS-11) and the Experiential Discounting Task (EDT), respectively- and compulsivity-measured using the Padua Inventory and the Wisconsin Card Sorting Test (WCST), respectively-, in an adult sample with GD (N = 132, 94 men and 38 women, ages ranging from 18 to 69 years). GD severity was assessed using the South Oaks Gambling Screen. Methods: Structural Equation Modeling was used to examine relationships between impulsivity and compulsivity measures, age, and GD severity. Results: BIS-11 non-planning and BIS-11 total scores positively correlated with GD severity. The standardized coefficients for the SEM showed direct positive contributions of BIS-11 non-planning, Padua and EDT scores to GD severity. Only participants' ages directly contributed to WCST perseverative errors, and no direct or indirect effects were found with respect to GD severity. Conclusion: The findings suggest that specific aspects of impulsivity and compulsivity contribute to GD severity. Interventions specifically targeting domains that are most relevant to GD severity may improve treatment outcomes

The driver landscape of sporadic chordoma.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma

A Population of X-ray Weak Quasars: PHL 1811 Analogs at High Redshift

We report the results from Chandra and XMM-Newton observations of a sample of 10 type 1 quasars selected to have unusual UV emission-line properties (weak and blueshifted high-ionization lines; strong UV Fe emission) similar to those of PHL 1811, a confirmed intrinsically X-ray weak quasar. These quasars were identified by the Sloan Digital Sky Survey at high redshift (z~2.2); eight are radio quiet while two are radio intermediate. All of the radio-quiet PHL 1811 analogs are notably X-ray weak by a mean factor of ~13. These sources lack broad absorption lines and have blue UV/optical continua, suggesting they are intrinsically X-ray weak. However, their average X-ray spectrum appears to be harder than those of typical quasars, which may indicate the presence of heavy intrinsic X-ray absorption. Our radio-quiet PHL 1811 analogs support a connection between an X-ray weak spectral energy distribution and PHL 1811-like UV emission lines; this connection provides an economical way to identify X-ray weak type 1 quasars. The fraction of radio-quiet PHL 1811 analogs in the radio-quiet quasar population is estimated to be < 1.2%. We have investigated correlations between relative X-ray brightness and UV emission-line properties for a sample combining radio-quiet PHL 1811 analogs, PHL 1811, and typical type 1 quasars. These correlation analyses suggest that PHL 1811 analogs may have extreme wind-dominated broad emission-line regions. Observationally, radio-quiet PHL 1811 analogs appear to be a subset (~30%) of radio-quiet weak-line quasars. The existence of a subset of quasars in which high-ionization "shielding gas" covers most of the BELR, but little more than the BELR, could potentially unify the PHL 1811 analogs and WLQs. The two radio-intermediate PHL 1811 analogs are X-ray bright. One of them appears to have jet-dominated X-ray emission, while the nature of the other remains unclear.Comment: ApJ accepted; 25 pages, 11 figures and 8 table

Alterations in functional networks during cue-reactivity in Internet gaming disorder

Background: Cue-induced brain reactivity has been suggested to be a fundamental and important mechanism explaining the development, maintenance, and relapse of addiction, including Internet gaming disorder (IGD). Altered activity in addiction-related brain regions has been found during cue-reactivity in IGD using functional magnetic resonance imaging (fMRI), but less is known regarding the alterations of coordinated whole brain activity patterns in IGD. Methods: To investigate the activity of temporally coherent, large-scale functional brain networks (FNs) during cue-reactivity in IGD, independent component analysis was applied to fMRI data from 29 male subjects with IGD and 23 matched healthy controls (HC) performing a cue-reactivity task involving Internet gaming stimuli (i.e., game cues) and general Internet surfing-related stimuli (i.e., control cues). Results: Four FNs were identified that were related to the response to game cues relative to control cues and that showed altered engagement/disengagement in IGD compared with HC. These FNs included temporo-occipital and temporo-insula networks associated with sensory processing, a frontoparietal network involved in memory and executive functioning, and a dorsal-limbic network implicated in reward and motivation processing. Within IGD, game versus control engagement of the temporo-occipital and frontoparietal networks were positively correlated with IGD severity. Similarly, disengagement of temporo-insula network was negatively correlated with higher game-craving. Discussion: These findings are consistent with altered cue-reactivity brain regions reported in substance-related addictions, providing evidence that IGD may represent a type of addiction. The identification of the networks might shed light on the mechanisms of the cue-induced craving and addictive Internet gaming behaviors

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Institutional trust and alcohol consumption in Sweden: The Swedish National Public Health Survey 2006

<p>Abstract</p> <p>Background</p> <p>Trust as a measure of social capital has been documented to be associated with health. Mediating factors for this association are not well investigated. Harmful alcohol consumption is believed to be one of the mediating factors. We hypothesized that low social capital defined as low institutional trust is associated with harmful alcohol consumption.</p> <p>Methods</p> <p>Data from the 2006 Swedish National Survey of Public Health were used for analyses. The total study population comprised a randomly selected representative sample of 26.305 men and 30.584 women aged 16–84 years. Harmful alcohol consumption was measured using a short version the Alcohol Use Disorders Identification Test (AUDIT), developed and recommended by the World Health Organisation. Low institutional trust was defined based on trust in ten main welfare institutions in Sweden.</p> <p>Results</p> <p>Independent of age, country of birth and socioeconomic circumstances, low institutional trust was associated with increased likelihood of harmful alcohol consumption (OR (men) = 1.52, 95% CI 1.34–1.70) and (OR (women) = 1.50, 95% CI 1.35–1.66). This association was marginally altered after adjustment for interpersonal trust.</p> <p>Conclusion</p> <p>Findings of the present study show that lack of trust in institutions is associated with increased likelihood of harmful alcohol consumption. We hope that findings in the present study will inspire similar studies in other contexts and contribute to more knowledge on the association between institutional trust and lifestyle patterns. This evidence may contribute to policies and strategies related to alcohol consumption.</p

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology