Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Accuracy Assessment of the ESA CCI 20M Land Cover Map: Kenya, Gabon, Ivory Coast and South Africa

This working paper presents the overall and spatial accuracy assessment of the European Space Agency (ESA) 20 m prototype land cover map for Africa for four countries: Kenya, Gabon, Ivory Coast and South Africa. This accuracy assessment was undertaken as part of the ESA-funded CrowdVal project. The results varied from 44% (for South Africa) to 91% (for Gabon). In the case of Kenya (56% overall accuracy) and South Africa, these values are largely caused by the confusion between grassland and shrubland. However, if a weighted confusion matrix is used, which diminishes the importance of the confusion between grassland and shrubs, the overall accuracy for Kenya increases to 79% and for South Africa, 75%. The overall accuracy for Ivory Coast (47%) is a result of a highly fragmented land cover, which makes it a difficult country to map with remote sensing. The exception was Gabon with a high overall accuracy of 91%, but this can be explained by the high amount of tree cover across the country, which is a relatively easy class to map

Pathogenic Germline Variants in 10,389 Adult Cancers

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effectiveness of motion scaling procedures for the seismic assessment of concrete gravity dams for near field motions

With the advent of the time domain analyses, preferred over the design methods based on the response spectrum idea, the use of time histories in the seismic analysis of dams is common practice. Selection of the ground motions to be used in time history analysis is a crucial task as the seismic demands show large variance depending on the chosen records. In order to reduce this variability and predict the true' demand related to the seismic hazard conditions of the site, the selected ground motions are usually scaled and/or modified. Commonly utilised ground motion scaling techniques (i.e. scaling to the target spectrum, maximum incremental velocity and spectrum matching) are evaluated in this study for determining the efficiency and accuracy of the scaling technique in predicting the target demands on the concrete gravity dams. Different canyon geometries and moduli ratios were considered in a robust soil-structure-reservoir interaction framework including the ground motion variability through the use of a large ensemble of motions. The minimum number of required motions for consistent estimation of seismic demands on gravity dams was determined to be higher than current practice. Demand parameters corresponding to the non-linear response were determined to be underestimated by the scaled sets

Assessment of the impact of abattoir effluent on the quality of groundwater in a residential area of Omu-Aran, Nigeria

Background: Water pollution from abattoir efuents may create substantial environmental and public health hazards. Available literature is scanty on the quality of groundwater located near abattoirs in tropical developing countries like Nigeria. This study, therefore, accessed the impact of abattoir activities on the quality of groundwater in Omu-Aran Nigeria. Methods: A total of eighteen water samples were taken from fve privately own wells and one control well located at varying distances and elevations to the abattoir. The physicochemical characteristics of the water were determined using the standard methods. Data were analyzed using descriptive statistics and ANOVA. Results: The mean values of parameters in the water samples collected from the studied wells ranged from 5.80±0.20 to 7.23±0.55 mg/L, 12.0±1.0 to 26.0±2.0 mg/L, 0.06±0.02 to 0.16±0.02 mg/L and 208.0±24.25 to 254.67±12.22 cfu/mL for dissolved oxygen, biological oxygen demand, lead and total coliforms, respectively. There was a signifcant diference in the quality of water from the studied and control wells in the parameters except that of total coliform. The quality of the groundwater improved with increasing distance from the abattoir. Conclusions: Findings revealed that abattoirs have the potential to impact the quality of groundwater. Therefore, careful consideration is required when choosing a location for siting new abattoirs. For existing ones, particularly those close to residential areas, efective pollution control measures should be put in place to protect groundwater. Keywords: Ground water quality, Water pollution, Omu-Aran and abattoir efuent

Why U.S. health care expenditure and ranking on health care indicators are so different from Canada’s

Health care expenditure, United States, Canada, I10, I12,