Exercising ‘bad faith’ in the asylum policy arena

This article uses a ‘scoping’ methodology to identify the different ways in which asylum policy and practice fall short of policymakers’ stated aims, are counter-evidential and are inhumane in their effects. It highlights how asylum seekers, commonly constructed as undeserving economic migrants, are impacted by these powerful ‘othering’ narratives, before drawing on a breadth of research evidence to challenge dominant claims and expose the particular weaknesses of the asylum system. In doing so, it asks why, if asylum policy is not informed by the evidence, does not achieve its stated objectives and yet causes suffering for those seeking asylum, such an approach persists. The article then develops the concept of ‘bad faith’ as an exercise of power, in order to theorise the actions of powerful agents in the shaping of asylum policy and practice with reference to hidden collective interests. It contends that the asylum policymaking community, in failing to acknowledge the suffering resulting from the diminishment of asylum seekers into a ‘typified other’, are engaging in an oppressive power operation, concealed by the political narratives underpinning policy reforms from the 1999 Immigration and Asylum Act to the 2016 Immigration Act.</jats:p

Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/ hyperactivity disorder

Objective: The primary objective of this study was to assess the impact of atomoxetine in combination with psychoeducation, compared with placebo and psychoeducation, on health-related quality of life (HRQL) in Swedish stimulant-naïve pediatric patients with attention deficit/ hyperactivity disorder (ADHD). HRQL results will be presented elsewhere. Here, psychoeducation as well as efficacy and safety of the treatment are described. Patients and methods: A total of 99 pediatric ADHD patients were randomized to a 10-week double-blind treatment with atomoxetine (49 patients) or placebo (50 patients). Parents of all patients received four sessions of psychoeducation. Atomoxetine was dosed up to approximately 1.2 mg/kg day (≤70 kg) or 80 mg/day (>70 kg). Improvement of ADHD symptoms was evaluated using the ADHD rating scale (ADHD-RS) and clinical global impression (CGI) rating scales. Safety was assessed based on adverse events (AEs). Results: The study population was predominantly male (80.8%) and diagnosed with the combined ADHD subtype (77.8%). The least square mean (lsmean) change from baseline to endpoint in total ADHD-RS score was −19.0 for atomoxetine patients and −6.3 for placebo patients, resulting in an effect size (ES) of 1.3 at endpoint. Treatment response (reduction in ADHD-RS score of ≥25 or ≥40%) was achieved in 71.4 or 63.3% of atomoxetine patients and 28.6 or 14.3% of placebo patients. The lsmean change from baseline to endpoint in CGI-Severity was −1.8 in the atomoxetine group compared with −0.3 in the placebo group. The difference between treatments in CGI-Improvement at endpoint was −1.4 in favor of atomoxetine. No serious AEs occurred. The safety profile of atomoxetine was in line with the current label. Conclusions: Atomoxetine combined with psychoeducation was superior to placebo and psychoeducation in ADHD core symptoms improvement. The large ES might be a result of including stimulant-naïve patients only, but also may indicate a positive interaction between atomoxetine treatment and psychoeducation, possibly by increased compliance

Periodontal bone loss and risk of epithelial ovarian cancer

PURPOSE: Periodontitis, a chronic inflammatory response to pathogenic bacteria in the oral microbiome, is common among adults. It is associated with several medical conditions, including cardiovascular diseases, and potentially with esophageal, lung, oral, and pancreatic cancer. One of the proposed mechanisms behind these associations is systemic inflammation, which has also been implicated in ovarian cancer etiology. The aim of this study was to evaluate association between ovarian cancer and periodontal bone loss. METHODS: The association between periodontal bone loss, a marker of periodontitis, and risk of epithelial ovarian cancer was estimated among 60,560 participants of the prospective Nurses' Health Study using Cox proportional hazards analysis. Competing risks analysis was used to estimate association by histologic subtype. RESULTS: We did not observe an increased risk of ovarian cancer among participants with periodontal bone loss (HR 0.86, 95% CI 0.64-1.15). Among women younger than 69 years, periodontal bone loss was associated with a 40 % (HR 0.60, 95% CI 0.36-0.98) decreased ovarian cancer risk, while there was no association in women older than 69 (HR 1.09, 95% CI 0.75-1.58), although this difference did not reach statistical significance (p-heterogeneity = 0.06). We observed a suggestive decreased risk for serous tumors (HR 0.76, 95% CI 0.53-1.09). The number of natural teeth and root canals, other metrics of oral health, were not associated with ovarian cancer risk. CONCLUSION: Our results do not support an increased ovarian cancer risk in women with periodontal bone loss; however, there was a significant decrease in risk in women younger than 69. Given the unexpected association between periodontal bone loss and ovarian cancer risk in younger women, further research is warranted.Other Research Uni

Multiple interactions between the alpha2C- and beta1-adrenergic receptors influence heart failure survival

<p>Abstract</p> <p>Background</p> <p>Persistent stimulation of cardiac β₁-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the α_2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (<it>ADRB1 </it>and <it>ADRA2C</it>, respectively) on the risk of death/transplant in heart failure patients.</p> <p>Methods</p> <p>Sixteen sequence variations in <it>ADRA2C </it>and 17 sequence variations in <it>ADRB1 </it>were genotyped in a longitudinal study of 655 white heart failure patients. Eleven sequence variations in each gene were polymorphic in the heart failure cohort. Cox proportional hazards modeling was used to identify polymorphisms and potential intra- or intergenic interactions that influenced risk of death or cardiac transplant. A leave-one-out cross-validation method was utilized for internal validation.</p> <p>Results</p> <p>Three polymorphisms in <it>ADRA2C </it>and five polymorphisms in <it>ADRB1 </it>were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks ranging from 3.02 to 9.23. There was no evidence of intragenic epistasis. Combining high risk genotype classes across epistatic pairs to take into account linkage disequilibrium, the relative risk of death or transplant was 3.35 (1.82, 6.18) relative to all other genotype classes.</p> <p>Conclusion</p> <p>Multiple polymorphisms act synergistically between the <it>ADRA2C </it>and <it>ADRB1 </it>genes to increase risk of death or cardiac transplant in heart failure patients.</p

Ovarian cancer risk factors by tumor aggressiveness : An analysis from the Ovarian Cancer Cohort Consortium

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in = 35 vs. 20 to <25 kg/m(2), 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.Peer reviewe

Common variants at theCHEK2gene locus and risk of epithelial ovarian cancer

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.Other Research Uni

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.Other Research Uni

rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology.

Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3' gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97⁻1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03⁻1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10-28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small

Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research