Summer Atmospheric Circulation Anomalies over the Arctic Ocean and Their Influences on September Sea Ice Extent: A Cautionary Tale

Numerous studies have addressed links between summer atmospheric circulation patterns and inter-annual variability and the downward trend in total September Arctic sea ice extent. In general, low extent is favored when the preceding summer is characterized by positive sea level pressure (SLP) anomalies over the central Arctic Ocean north of Alaska. High extent is favored when low pressure dominates. If such atmospheric patterns could be predicted several months out, these links provide an avenue for improved seasonal predictability of total September extent. We analyze de-trended September extent time series (1979-2015), atmospheric reanalysis fields, ice age and motion, and AIRS data, to show that while there is merit to this summer circulation framework, it has limitations. Large departures in total September extent relative to the trend line are preceded by a wide range of summer circulation patterns. While patterns for the four years with the largest positive departures in September extent have below average SLP over the central Arctic Ocean, they differ markedly in the magnitude and location of pressure and air temperature anomalies. Differences in circulation for the four years with the largest negative departures are equally prominent. Circulation anomalies preceding Septembers with ice extent close to the trend also have a wide range of patterns. In turn, years (such as 2013 and 2014) with almost identical total September extent, were preceded by very different summer circulation patterns. September ice conditions can also be strongly shaped by events as far back as the previous winter or spring

Variability, trends and predictability of seasonal sea ice retreat and advance in the Chukchi Sea

As assessed over the period 1979–2014, the date that sea ice retreats to the shelf break (150 m contour) of the Chukchi Sea has a linear trend of −0.7 days per year. The date of seasonal ice advance back to the shelf break has a steeper trend of about +1.5 days per year, together yielding an increase in the open water period of 80 days. Based on detrended time series, we ask how interannual variability in advance and retreat dates relate to various forcing parameters including radiation fluxes, temperature and wind (from numerical reanalyses), and the oceanic heat inflow through the Bering Strait (from in situ moorings). Of all variables considered, the retreat date is most strongly correlated (r ∼ 0.8) with the April through June Bering Strait heat inflow. After testing a suite of statistical linear models using several potential predictors, the best model for predicting the date of retreat includes only the April through June Bering Strait heat inflow, which explains 68% of retreat date variance. The best model predicting the ice advance date includes the July through September inflow and the date of retreat, explaining 67% of advance date variance. We address these relationships by discussing heat balances within the Chukchi Sea, and the hypothesis of oceanic heat transport triggering ocean heat uptake and ice-albedo feedback. Developing an operational prediction scheme for seasonal retreat and advance would require timely acquisition of Bering Strait heat inflow data. Predictability will likely always be limited by the chaotic nature of atmospheric circulation patterns

Uncovering Blind Spots in Urban Carbon Management: The Role of Consumption-Based Carbon Accounting in Bristol, UK

The rapid urbanisation of the twentieth century, along with the spread of high-consumption urban lifestyles, has led to cities becoming the dominant drivers of global anthropogenic greenhouse gas emissions. Reducing these impacts is crucial, but production-based frameworks of carbon measurement and mitigation—which encompass only a limited part of cities’ carbon footprints—are much more developed and widely applied than consumption-based approaches that consider the embedded carbon effectively imported into a city. Frequently, therefore, cities are left blind to the importance of their wider consumption-related climate impacts, while at the same time left lacking effective tools to reduce them. To explore the relevance of these issues, we implement methodologies for assessing production- and consumption-based emissions at the city-level and estimate the associated emissions trajectories for Bristol, a major UK city, from 2000 to 2035. We develop mitigation scenarios targeted at reducing the former, considering potential energy, carbon and financial savings in each case. We then compare these mitigation potentials with local government ambitions and Bristol’s consumption-based emissions trajectory. Our results suggest that the city’s consumption-based emissions are three times the production-based emissions, largely due to the impacts of imported food and drink. We find that low-carbon investments of circa £3 billion could reduce production-based emissions by 25% in 2035. However, we also find that this represents <10% of Bristol’s forecast consumption-based emissions for 2035 and is approximately equal to the mitigation achievable by eliminating the city’s current levels of food waste. Such observations suggest that incorporating consumption-based emission statistics into cities’ accounting and decision-making processes could uncover largely unrecognised opportunities for mitigation that are likely to be essential for achieving deep decarbonisation

Evaluation of the London Measure of Unplanned Pregnancy in a United States population of women

Copyright @ 2012 Morof et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Objective: To evaluate the reliability and validity of the London Measure of Unplanned Pregnancy (a U.K.-developed measure of pregnancy intention), in English and Spanish translation, in a U.S. population of women. Methods: A psychometric evaluation study of the London Measure of Unplanned Pregnancy (LMUP), a six-item, self-completion paper measure was conducted with 346 women aged 15–45 who presented to San Francisco General Hospital for termination of pregnancy or antenatal care. Analyses of the two language versions were carried out separately. Reliability (internal consistency) was assessed using Cronbach’s alpha and item-total correlations. Test-retest reliability (stability) was assessed using weighted Kappa. Construct validity was assessed using principal components analysis and hypothesis testing. Results: Psychometric testing demonstrated that the LMUP was reliable and valid in both U.S. English (alpha = 0.78, all item-total correlations .0.20, weighted Kappa = 0.72, unidimensionality confirmed, hypotheses met) and Spanish translation (alpha = 0.84, all item-total correlations .0.20, weighted Kappa = 0.77, unidimensionality confirmed, hypotheses met). Conclusion: The LMUP was reliable and valid in U.S. English and Spanish translation and therefore may now be used with U.S. women.The study was funded by an anonymous donation

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P &lt; 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Genetic Complexity of Crohn’s Disease in Two Large Ashkenazi Jewish Families

Background & Aims Crohn’s disease (CD) is a highly heritable disease that is particularly common in the Ashkenazi Jewish population. We studied 2 large Ashkenazi Jewish families with a high prevalence of CD in an attempt to identify novel genetic risk variants. Methods Ashkenazi Jewish patients with CD and a positive family history were recruited from the University College London Hospital. We used genome-wide, single-nucleotide polymorphism data to assess the burden of common CD-associated risk variants and for linkage analysis. Exome sequencing was performed and rare variants that were predicted to be deleterious and were observed at a high frequency in cases were prioritized. We undertook within-family association analysis after imputation and assessed candidate variants for evidence of association with CD in an independent cohort of Ashkenazi Jewish individuals. We examined the effects of a variant in DUOX2 on hydrogen peroxide production in HEK293 cells. Results We identified 2 families (1 with >800 members and 1 with >200 members) containing 54 and 26 cases of CD or colitis, respectively. Both families had a significant enrichment of previously described common CD-associated risk variants. No genome-wide significant linkage was observed. Exome sequencing identified candidate variants, including a missense mutation in DUOX2 that impaired its function and a frameshift mutation in CSF2RB that was associated with CD in an independent cohort of Ashkenazi Jewish individuals. Conclusions In a study of 2 large Ashkenazi Jewish with multiple cases of CD, we found the genetic basis of the disease to be complex, with a role for common and rare genetic variants. We identified a frameshift mutation in CSF2RB that was replicated in an independent cohort. These findings show the value of family studies and the importance of the innate immune system in the pathogenesis of CD

Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Evolving DNA motifs to predict GeneChip probe performance

Background: Affymetrix High Density Oligonuclotide Arrays (HDONA) simultaneously measure expression of thousands of genes using millions of probes. We use correlations between measurements for the same gene across 6685 human tissue samples from NCBI's GEO database to indicated the quality of individual HG-U133A probes. Low correlation indicates a poor probe. Results: Regular expressions can be automatically created from a Backus-Naur form (BNF) context-free grammar using strongly typed genetic programming. Conclusion: The automatically produced motif is better at predicting poor DNA sequences than an existing human generated RE, suggesting runs of Cytosine and Guanine and mixtures should all be avoided. © 2009 Langdon and Harrison; licensee BioMed Central Ltd

Appropriate disclosure of a diagnosis of dementia : identifying the key behaviours of 'best practice'

Background: Despite growing evidence that many people with dementia want to know their diagnosis, there is wide variation in attitudes of professionals towards disclosure. The disclosure of the diagnosis of dementia is increasingly recognised as being a process rather than a one-off behaviour. However, the different behaviours that contribute to this process have not been comprehensively defined. No intervention studies to improve diagnostic disclosure in dementia have been reported to date. As part of a larger study to develop an intervention to promote appropriate disclosure, we sought to identify important disclosure behaviours and explore whether supplementing a literature review with other methods would result in the identification of new behaviours. Methods: To identify a comprehensive list of behaviours in disclosure we conducted a literature review, interviewed people with dementia and informal carers, and used a consensus process involving health and social care professionals. Content analysis of the full list of behaviours was carried out. Results: Interviews were conducted with four people with dementia and six informal carers. Eight health and social care professionals took part in the consensus panel. From the interviews, consensus panel and literature review 220 behaviours were elicited, with 109 behaviours over-lapping. The interviews and consensus panel elicited 27 behaviours supplementary to the review. Those from the interviews appeared to be self-evident but highlighted deficiencies in current practice and from the panel focused largely on balancing the needs of people with dementia and family members. Behaviours were grouped into eight categories: preparing for disclosure; integrating family members; exploring the patient's perspective; disclosing the diagnosis; responding to patient reactions; focusing on quality of life and well-being; planning for the future; and communicating effectively. Conclusion: This exercise has highlighted the complexity of the process of disclosing a diagnosis of dementia in an appropriate manner. It confirms that many of the behaviours identified in the literature (often based on professional opinion rather than empirical evidence) also resonate with people with dementia and informal carers. The presence of contradictory behaviours emphasises the need to tailor the process of disclosure to individual patients and carers. Our combined methods may be relevant to other efforts to identify and define complex clinical practices for further study.This project is funded by UK Medical Research Council, Grant reference number G0300999