Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

Background: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (<135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration >10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was >3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care

Mood following emotional crying : effects of differential processing

Includes bibliographical references (pages [58]-62)This thesis assessed three hypotheses regarding emotional behavior: (1) emotional expression effects the character of subsequent mood, (2) emotional expression effects the ability to access emotional material in oneself, and (3) women and men demonstrate different patterns of emotional expression. There is a discussion of the background/theoretical underpinnings of each of these hypotheses. This study was a three-group analog pre- and post-measure design, including an experimental, placebo, and control condition. Data were collected on 61 participants, aged 18 to 31 years, matched to condition according to sex. Participants in all groups completed a battery of questionnaires, including the Subjective Units of Discomfort (SUD), the Depression Adjective Check Lists (DACL), and the Trait Meta-Mood Scale (TMMS). Next, all participants watched an (18-minute) emotionally provocative video. Participants were then placed in one of three conditions: (1) in the experimental, persons expressed thoughts and feelings through a specially designed interview with a researcher (5-10 minutes), (2) in the placebo, persons read aloud an unrelated passage (8-10 minutes), and (3) in the control, persons waited alone in a room for the experimenter to return (8 minutes). Participants in all groups returned approximately one week later, \ watched an abbreviated (5-minute) version of the original video, and again completed a battery of questionnaires (SUD, DACL, and TMMS). Hypotheses 1 was assessed through ANCOVAs and t tests, with null findings for ANCOVAs, and one t test indicating decreased negative mood at postmeasurement (t.025 (19) = 2. 13, £ < .05). Hypothesis 2 was assessed through ANCOVAs, resulting in null findings. For hypothesis 3, interview data were transcribed and scored using the Experiencing Scale. The average inter-rater reliability between three independent raters was .99, and the data were assessed using one-way ANOVA. Results were statistically significant such that F(l, 18) = 4.87, £ < .05, with females posting higher scores than males. This suggests that while emotional expression may differentially effect subsequent mood but not the ability to access emotional information from oneself, women tend to process emotional events at a more self-referential level than do men.M.A. (Master of Arts

Gender and Modality Differences in Experiencing and Emotional Expression

This study investigated gender and modality differences in experiencing and emotional expression. The factorial design included two levels of gender, and two levels of expression modality (public and private). All 47 participants watched and responded to questions about an emotionally provocative video. Participant responses were assessed using the Experiencing Scale, and for use of emotional words. Analyses revealed a higher level of experiencing, and more use of emotional words by women than men. Additionally, experiencing judgments of private responses were significantly higher than those of public responses. Implications for facilitation of experiencing are discussed.Cette étude examine les différentes façons dont les hommes et les femmes ressentent et expriment leurs émotions. Le plan factoriel a été conçu avec deux niveaux de genre et de modalités d'expression (publique et privée). Les 47 participants ont, tous, regardé un vidéo émotionnellement chargé au sujet duquel des questions leur ont été posées. Leurs réponses ont été évaluées à l'aide de l'échelle d'expérience [Experiencing Scale] et selon leur usage de mots émotionnels. Les analyses révèlent, chez les femmes, des expériences plus intenses ainsi qu'une utilisation plus importante des mots affectifs. De plus, on a pu conclure que l'intensité des réponses privées était plus élevée que celle des réponses publiques. Les implications quant à la facilitation des expériences sont étudiées par les auteurs

The Treatment of the Carmack’s Copper-Gold Ore by Acid Leaching and Cyanide Leaching with SART Recovery of Copper and Cyanide from Barren Cyanide Solution

Western Copper's Carmacks copper-gold deposit in the Yukon Territory, Canada contains copper and gold values. The copper mineralization is oxidized and acid soluble, and the gold is free milling and may be extracted by cyanidation. The current treatment plan is to recover the copper by heap leaching, and SX/EW. The challenge of this deposit is to be able to economically extract the remaining gold. In this work, a series of tests were conducted to process a mineral sample for copper extraction by acid column leaching followed by cyanidation for gold extraction. The barren gold solution was then treated by the SART process (sulfidization, acidification, recycle, thickening) for copper recovery as copper sulfide and cyanide recycle. The results of this work were very encouraging with 65% direct copper extraction with acid and 76-82% Au extraction from the copper leach residue by cyanidation. Approximately 21-27% of the copper was co-extracted in cyanidation. SART treatment of the cyanide solution (after carbon adsorption) recovered greater than 95% of the copper as a synthetic copper sulfide precipitate. Additionally, a significant portion of the molybdenum in the ore also leached and was precipitated in the SART process. After filtration and re-neutralization, the recovered cyanide solution was suitable for recycling