Impact of ultraviolet radiation on marine crustacean zooplankton and ichthyoplankton: a synthesis of results from the estuary and Gulf of St. Lawrence, Canada

The objectives of the research program reported upon here were (1) to measure ambient levels of UV radiation and determine whichvariables most strongly affected its attenuation in the waters of the estuary and Gulf of St. Lawrence, Canada; and (2) to investigate the potential direct impacts of W radiation on species of crustacean zooplankton and fish whose early life stages are planktonic. In this geographic region, productivity-determining biophysical interactions occur in the upper 0 to 30 m of the water column. Measurements of the diffuse attenuation coefficients for ultraviolet-B radiation (W-B, 280 to 320 nm) at various locations in this region indicated maximum 10% depths (the depth to which 10% of the surface energy penetrates at a given wavelength) of 3 to 4 m at a wavelength of 310 nm. Organisms residing in this layer-including the eggs and larvae of Calanus finmarchicus and Atlantic cod Gadus morhua-are exposed to biologically damaging levels of W radiation. As a result of these physical and biological characteristics, this system offered a relevant opportunity to assess the impacts of UV on subarctic marine ecosystems. Eggs of C. finmarchicus were incubated under the sun, with and without the W-B and/or UV-A (320 to 400 nm) wavebands. W-exposed eggs exhibited low percent hatchmg compared to those protected from W : W radiation had a strong negative impact on C. finmarchicus eggs. Further, percent hatching in W-B-exposed eggs was not significantly lower than that in eggs exposed to UV-A only: under natural sunlight, UV-A radiation appeared to be more detrimental to C. finmarchicus embryos than was UV-B. In analogous experiments with Atlantic cod eggs, exposure to UV-B produced a significant negative effect. However, UV-A had no negative effect on cod eggs. Additional experiments using a solar simulator (SS) revealed high wavelength-dependent mortality in both C. finmarchicus and cod embryos exposed to UV. The strongest effects occurred under exposures to wavelengths below 312 nm. At the shorter wavelengths (<305 nm) UV-B-induced mortality was strongly dose-dependent, but (for both C. finmarchicus and cod) not significantly influenced by dose-rate. Thus, at least within the limits of the exposures under which the biological weighting functions (BWFs) were generated, reciprocity held. The BWFs derived for UV-B-induced mortality in C. finmarchicus and cod eggs were similar in shape to the action spectrum for UV-B effects on naked DNA. Further, the wavelengthdependence of DNA damage was similar to that for the mortality effect. These observations suggest that W-induced mortality in C. finmarchicus and cod eggs is a direct result of DNA damage. There was no evidence of a detrimental effect of UV-A radiation in these SS-derived results. A mathematical model that includes the BWFs, vertical mixing of eggs, meteorological and hydrographic conditions, and ozone depletion, indicates that W-induced mortality in the C. finmarchicus egg population could be as high as 32.5 %, while the impact on the cod egg population was no more than 1.2%. Variability in cloud cover, water transparency (and the variables that affect it), and vertical distribution and displacement of planktonic organisms within the mixed layer can all have a greater effect on the flux of UV-B radiation to which they are exposed than will ozone layer depletion at these latitudes. Our observations indicate that C, finmarchicus and cod eggs present in the first meter of the water column (likely only a small percentage of the total egg populations) are susceptible to W radiation. However, although exposure to UV can negatively impact crustacean zooplankton and ichthyoplankton populations, these direct effects are likely minimal within the context of all the other environmental factors that produce the very high levels of mortality typically observed in their planktonic early life stages. The impact of indnect effects-which may well be of much greater import-has yet to be evaluated

The Relationship Between Physical Activity and Cardiorespiratory Fitness Among People Living With Human Immunodeficiency Virus Throughout The Life Span

BACKGROUND: People living with human immunodeficiency virus (PLHIV) are at an increased risk for developing cardiovascular disease (CVD). Physical activity and cardiorespiratory fitness in PLHIV are poorly understood. OBJECTIVE: The aims of this study were to describe physical activity and cardiorespiratory fitness by sex and age and to examine the association between physical activity and cardiorespiratory fitness in PLHIV, controlling for covariates. METHODS: Seven hundred two PLHIV participated in a cross-sectional study and completed validated measures of self-reported physical activity (7-day Physical Activity Recall) and cardiorespiratory fitness (6-minute walk test). Participants were recruited from 7 diverse sites in the United States and Thailand, and data were analyzed using descriptive statistics and multiple regression to examine the relationship between physical activity and cardiorespiratory fitness. RESULTS: On average, participants self-reported engaging in 115 minutes of, mostly light (75%), physical activity. Men reported twice the amount of physical activity as women (155 vs 73 minutes, P = .01). Participants\u27 ability to achieve their predicted 6-minute walk test distances was similar between men (68%) and women (69%) (P \u3e .01). For women, vigorous physical activity was associated with a 6.6% increase in cardiorespiratory fitness and being temporarily unemployed was associated with an 18% decline in cardiorespiratory fitness. Cardiorespiratory fitness increased with age (P \u3c .01). CONCLUSIONS: Weekly physical activity of people living with human immunodeficiency virus averaged 85 minutes of mostly light activity, well below the recommended 150 minutes of moderate activity. Vigorous physical activity was associated with improved cardiorespiratory fitness in women, but not men. Although PLHIV would benefit from interventions to increase physical activity, our data suggest a need to develop sex-specific physical activity strategies

Randomised Controlled Trial of Real-Time Feedback and Brief Coaching to Reduce Indoor Smoking

Background: Previous secondhand smoke (SHS) reduction interventions have provided only delayed feedback on reported smoking behaviour, such as coaching, or presenting results from child cotinine assays or air particle counters. Design: This SHS reduction trial assigned families at random to brief coaching and continuous real-time feedback (intervention) or measurement-only (control) groups. Participants: We enrolled 298 families with a resident tobacco smoker and a child under age 14. Intervention: We installed air particle monitors in all homes. For the intervention homes, immediate light and sound feedback was contingent on elevated indoor particle levels, and up to four coaching sessions used prompts and praise contingent on smoking outdoors. Mean intervention duration was 64 days. Measures: The primary outcome was \u27particle events\u27 (PEs) which were patterns of air particle concentrations indicative of the occurrence of particle-generating behaviours such as smoking cigarettes or burning candles. Other measures included indoor air nicotine concentrations and participant reports of particle-generating behaviour. Results: PEs were significantly correlated with air nicotine levels (r=0.60) and reported indoor cigarette smoking (r=0.51). Interrupted time-series analyses showed an immediate intervention effect, with reduced PEs the day following intervention initiation. The trajectory of daily PEs over the intervention period declined significantly faster in intervention homes than in control homes. Pretest to post-test, air nicotine levels, cigarette smoking and e-cigarette use decreased more in intervention homes than in control homes. Conclusions: Results suggest that real-time particle feedback and coaching contingencies reduced PEs generated by cigarette smoking and other sources

The quality of different types of child care at 10 and 18 months. A comparison between types and factors related to quality.

The quality of care offered in four different types of non-parental child care to 307 infants at 10 months old and 331 infants at 18 months old was compared and factors associated with higher quality were identified. Observed quality was lowest in nurseries at each age point, except that at 18 months they offered more learning activities. There were few differences in the observed quality of care by child-minders, grandparents and nannies, although grandparents had somewhat lower safety and health scores and offered children fewer activities. Cost was largely unrelated to quality of care except in child-minding, where higher cost was associated with higher quality. Observed ratios of children to adults had a significant impact on quality of nursery care; the more infants or toddlers each adult had to care for, the lower the quality of the care she gave them. Mothers' overall satisfaction with their child's care was positively associated with its quality for home-based care but not for nursery settings

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Five endometrial cancer risk loci identified through genome-wide association analysis.

We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.I.T. is supported by Cancer Research UK and the Oxford Comprehensive Biomedical Research Centre. T.H.T.C. is supported by the Rhodes Trust and the Nuffield Department of Medicine. Funding for iCOGS infrastructure came from the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565), the US National Institutes of Health (R01 CA128978, U19 CA148537, U19 CA148065 and U19 CA148112), the US Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Susan G. Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund. SEARCH recruitment was funded by a programme grant from Cancer Research UK (C490/A10124). Stage 1 and stage 2 case genotyping was supported by the NHMRC (552402 and 1031333). Control data were generated by the WTCCC, and a full list of the investigators who contributed to the generation of the data is available from the WTCCC website. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by UK Medical Research Council grant G0000934 and Wellcome Trust grant 068545/Z/02; funding for this project was provided by the Wellcome Trust under award 085475. NSECG was supported by the European Union's Framework Programme 7 CHIBCHA grant and Wellcome Trust Centre for Human Genetics Core Grant 090532/Z/09Z, and CORGI was funded by Cancer Research UK. BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014). OCAC 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) and the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.356

Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

BACKGROUND: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. METHODS: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types. RESULTS: We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P \u3c .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P \u3c .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. CONCLUSIONS: CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention

Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

BACKGROUND: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. METHODS: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types. RESULTS: We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. CONCLUSIONS: CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention