Night-sky brightness monitoring in Hong Kong - a city-wide light pollution assessment

Results of the first comprehensive light pollution survey in Hong Kong are presented. The night-sky brightness was measured and monitored around the city using a portable light sensing device called the Sky Quality Meter over a 15-month period beginning in March 2008. A total of 1,957 data sets were taken at 199 distinct locations, including urban and rural sites covering all 18 Administrative Districts of Hong Kong. The survey shows that the environmental light pollution problem in Hong Kong is severe - the urban night-skies (sky brightness at 15.0 mag per arcsec square) are on average ~100 times brighter than at the darkest rural sites (20.1 mag per arcsec square), indicating that the high lighting densities in the densely populated residential and commercial areas lead to light pollution. In the worst polluted urban location studied, the night-sky at 13.2 mag per arcsec square can be over 500 times brighter than the darkest sites in Hong Kong. The observed night-sky brightness is found to be affected by human factors such as land utilization and population density of the observation sites, together with meteorological and/or environmental factors. Moreover, earlier night-skies (at 9:30pm local time) are generally brighter than later time (at 11:30pm), which can be attributed to some public and commercial lightings being turned off later at night. On the other hand, no concrete relationship between the observed sky brightness and air pollutant concentrations could be established with the limited survey sampling. Results from this survey will serve as an important database for the public to assess whether new rules and regulations are necessary to control the use of outdoor lightings in Hong Kong.Comment: 33 pages, 13 figures, Environmental Monitoring and Assessment, in pres

The Value of Preseason Screening for Injury Prediction: The Development and Internal Validation of a Multivariable Prognostic Model to Predict Indirect Muscle Injury Risk in Elite Football (Soccer) Players

© 2020, The Author(s). Background: In elite football (soccer), periodic health examination (PHE) could provide prognostic factors to predict injury risk. Objective: To develop and internally validate a prognostic model to predict individualised indirect (non-contact) muscle injury (IMI) risk during a season in elite footballers, only using PHE-derived candidate prognostic factors. Methods: Routinely collected preseason PHE and injury data were used from 152 players over 5 seasons (1st July 2013 to 19th May 2018). Ten candidate prognostic factors (12 parameters) were included in model development. Multiple imputation was used to handle missing values. The outcome was any time-loss, index indirect muscle injury (I-IMI) affecting the lower extremity. A full logistic regression model was fitted, and a parsimonious model developed using backward-selection to remove factors that exceeded a threshold that was equivalent to Akaike’s Information Criterion (alpha 0.157). Predictive performance was assessed through calibration, discrimination and decision-curve analysis, averaged across all imputed datasets. The model was internally validated using bootstrapping and adjusted for overfitting. Results: During 317 participant-seasons, 138 I-IMIs were recorded. The parsimonious model included only age and frequency of previous IMIs; apparent calibration was perfect, but discrimination was modest (C-index = 0.641, 95% confidence interval (CI) = 0.580 to 0.703), with clinical utility evident between risk thresholds of 37–71%. After validation and overfitting adjustment, performance deteriorated (C-index = 0.589 (95% CI = 0.528 to 0.651); calibration-in-the-large = − 0.009 (95% CI = − 0.239 to 0.239); calibration slope = 0.718 (95% CI = 0.275 to 1.161)). Conclusion: The selected PHE data were insufficient prognostic factors from which to develop a useful model for predicting IMI risk in elite footballers. Further research should prioritise identifying novel prognostic factors to improve future risk prediction models in this field. Trial registration: NCT03782389

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, transethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N = 78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P < 5 x 10(-8)), we found suggestive evidence (P < 5 x 10(-6)) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions

Clinicopathological and immunohistochemical findings in an autopsy case of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder caused by mutations in either the TSC1 or TSC2 genes and characterized by developmental brain abnormalities. In the present study we discuss the neuropathological findings of a 32-year-old patient with a germ-line mutation in the TSC2 gene. Post mortem MRI combined with histology and immunocytochemical analysis was applied to demonstrate widespread anatomical abnormalities of gray and white matter structure. TSC brain lesions were analyzed for loss of heterozygosity (LOH) on chromosome 16p13. The neuropathological supratentorial abnormalities were represented by multiple subependymal nodules (SENs) and cortical tubers. In addition to cerebral cortical lesions, cerebellar lesions and hippocampal sclerosis were also observed. LOH was not found in the cortical tubers and SENs of this patient. Immunocytochemical analysis of the TSC brain lesions confirmed the cell-specific activation of the mTOR pathway in cortical tubers, SENs and cerebellum, as well as differential cellular localization of hamartin and tuberin, the TSC1 and TSC2 gene products. Examination of the pathological brain regions revealed activated microglial cells and disruption of blood-brain barrier permeability. Predominant intralesional cell-specific distribution was also detected for the multidrug transporter protein P-gp, possibly explaining the mechanisms underlying the pharmacoresistance to antiepileptic drugs. Autopsy findings confirm the complexity of the brain abnormalities encountered in TSC patients and proved useful in clarifying certain aspects of the pathogenesis, epileptogenesis and pharmacoresistance of TSC lesion