An inter-comparison of Arctic synoptic scale storms between four global reanalysis datasets

The Arctic is becoming more accessible as sea ice extent continues to decline, resulting in higher human exposure to Arctic storms. This study compares Arctic storm characteristics between the ECMWF-Interim Reanalysis, 55-year Japanese Reanalysis, NASA-Modern Era Retrospective Analysis for Research and Applications Version 2 and National Centre for Environmental Prediction-Climate Forecast System Reanalysis datasets between 1980 and 2017, in winter (DJF) and summer (JJA). It is shown that Arctic storm characteristics are sensitive to the variable used for storm tracking. Arctic storm frequency is found to be similar in summer and winter when using sea level pressure minima to track Arctic storms, whereas, the storm frequency is found to be higher in winter than summer when using 850 hPa relative vorticity to track storms, based on using the same storm tracking algorithm. It is also found that there are no significant trends in Arctic storm characteristics between 1980 and 2017. Given the sparsity of observations in the Arctic, it might be expected that there are large differences in Arctic storm characteristics between the reanalysis datasets. Though, some similar Arctic storm characteristics are found between the reanalysis datasets, it is found that the differences in Arctic storm characteristics between the reanalysis datasets are generally higher in winter than in summer. Overall, the results show that there are differences in Arctic storm characteristics between reanalysis datasets, but even larger differences can arise between using 850 hPa relative vorticity or mean sea level pressure as the storm tracking variable, which adds to the uncertainty associated with current Arctic storm characteristics

Comparative Analysis of mRNA Targets for Human PUF-Family Proteins Suggests Extensive Interaction with the miRNA Regulatory System

Genome-wide identification of mRNAs regulated by RNA-binding proteins is crucial to uncover post-transcriptional gene regulatory systems. The conserved PUF family RNA-binding proteins repress gene expression post-transcriptionally by binding to sequence elements in 3′-UTRs of mRNAs. Despite their well-studied implications for development and neurogenesis in metazoa, the mammalian PUF family members are only poorly characterized and mRNA targets are largely unknown. We have systematically identified the mRNAs associated with the two human PUF proteins, PUM1 and PUM2, by the recovery of endogenously formed ribonucleoprotein complexes and the analysis of associated RNAs with DNA microarrays. A largely overlapping set comprised of hundreds of mRNAs were reproducibly associated with the paralogous PUM proteins, many of them encoding functionally related proteins. A characteristic PUF-binding motif was highly enriched among PUM bound messages and validated with RNA pull-down experiments. Moreover, PUF motifs as well as surrounding sequences exhibit higher conservation in PUM bound messages as opposed to transcripts that were not found to be associated, suggesting that PUM function may be modulated by other factors that bind conserved elements. Strikingly, we found that PUF motifs are enriched around predicted miRNA binding sites and that high-confidence miRNA binding sites are significantly enriched in the 3′-UTRs of experimentally determined PUM1 and PUM2 targets, strongly suggesting an interaction of human PUM proteins with the miRNA regulatory system. Our work suggests extensive connections between the RBP and miRNA post-transcriptional regulatory systems and provides a framework for deciphering the molecular mechanism by which PUF proteins regulate their target mRNAs

Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58 515 women with invasive breast cancer and 95 067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19–1.45, P<0.00001) for an intake of 35–44 g per day alcohol, and 1.46 (1.33–1.61, P<0.00001) for ⩾45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5–8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98–1.07, and for current smokers=0.99, 0.92–1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver

The risk of synoptic-scale Arctic cyclones to shipping

The risk posed by Arctic cyclones to ships has seldom been quantified due to the lack of publicly available historical Arctic ship track data. This study investigates Automated Identification System (AIS) transponder derived Arctic ship tracksfrom September 2009 to December 2016. These are analysed with historical synoptic-scale cyclone tracks derived from ERA-5 and reports of past Arctic shipping incidents, to determine the 5 number of ship tracks intersected by intense Arctic cyclones tracks, and how many of these intersections resulted in a reported shipping incident. The number of ships operating in the Arctic has increased year-on-year from 2010 to 2016. The highest density of ships occurs year-round in the Barents Sea. Trans-Arctic shipping transits via theNorthern Sea Route and theNorth-West Passage are limited to summer and autumn months when sea ice extent has sufficiently retreated from the coastlines. Ship track 10 density along these trans-Arctic routes is far less than the thousands of ships travelling in the Barents Sea year-round. Between 2010 and 2016, 158 Arctic shipping incidents were reported, but only 6% of these reported incidents occurred following the passage of an intense Arctic cyclone. Arctic cyclones with significant wave heights greater than 6 metres are found to frequently intersect ships, but only 0.1% of these intersections resulted in a reported shipping incident. Results from this study indicate that ships are frequently impacted by Arctic cyclones, but cyclones have not been a dominant cause of reported Arctic shipping incidents between 2010 and 2016. This suggests that ships are resilient to the rough sea conditions that past Arctic cyclones have caused, therefore mitigating, and reducing risk

Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver

Maternal hormonal contraceptive use and offspring overweight or obesity

OBJECTIVE: Experiments in animal models have shown a positive association between in utero exposure to pharmacologic sex hormones and offspring obesity. The developmental effects of such hormones on human obesity are unknown. METHODS: Using data from a large, prospective pregnancy cohort study (n=19,652), with linkage to a national prescription registry, we evaluated the association between use of hormonal contraceptives before and after conception (defined from dispensed prescription data and characterized by last date of use relative to conception, 12 – >4 months before (n=3,392), 4 – >1 months before (n=2,541), 1 – > 0 months before (n=2,997), and 0–12 weeks after (n=567)) in relation to offspring overweight or obesity at age 3 years. RESULTS: We observed a weak, inverse association between early pregnancy use of a combination oral contraceptive and offspring overweight or obesity at age 3 (adjusted OR: 0.75, 95% CI: 0.53, 1.08) and a positive, but imprecise, association with use of a progestin-only oral contraceptive in early pregnancy (adjusted OR: 1.26, 95% CI: 0.79, 2.02). In general, no association was observed between use of a hormonal contraceptive before conception and offspring overweight or obesity. A sensitivity analysis comparing combination oral contraceptive users in early pregnancy to other unplanned pregnancies without hormonal contraceptive use further strengthened the inverse association (adjusted OR: 0.70, 95% CI: 0.48, 1.02). Other sensitivity analyses were conducted to evaluate the robustness of the associations observed given varying assumptions. CONCLUSION: Pharmacologic sex hormones in early pregnancy may be inversely or positively associated with offspring overweight or obesity at age 3, depending on the specific formulation used. The present study provides support for the potential for environmental sources of hormonally active agents to exert developmental effects