Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.

The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2-29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05-0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits

Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis.

BACKGROUND: Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M. tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of influence in the pathogenesis of a number of infectious diseases, including tuberculosis. METHODS AND FINDINGS: We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (-871G and -336A) and decreased risk of developing tuberculosis. By looking at the geographical distribution of these variants, we observed that their allelic combination is mainly confined to Eurasian populations. CONCLUSIONS: Our observations suggest that the two -871G and -336A variants confer protection against tuberculosis. In addition, the geographic distribution of these two alleles, together with their phylogenetic status, suggest that they may have increased in frequency in non-African populations as a result of host genetic adaptation to a longer history of exposure to tuberculosis. Further characterization of the biological consequences of DC-SIGN variation in tuberculosis will be crucial to better appreciate the role of this lectin in interactions between the host immune system and the tubercle bacillus as well as other pathogens

Assessing the knowledge of the potential harm to others caused by second-hand smoke and its impact on protective behaviours at home

BACKGROUND: Smokers' knowledge of the risks of second-hand smoke (SHS) and the role this plays in implementing behaviours to reduce the SHS exposure of others have not been thoroughly explored. Mass media health promotion is used to promote behaviour change partly by providing information on the consequences of behaviour. In England, between 2003 and 2006, frequent mass media campaigns highlighted the toxicity of SHS. OBJECTIVES: To examine peoples' knowledge of SHS-related illnesses in England over time, identify the determinants of good knowledge and to assess its importance in predicting SHS-protective behaviours. METHODS: Statistical analysis of repeat cross-sectional data (1996–2008) from the Omnibus Survey to explore the trends and determinants of knowledge of SHS-related illnesses and the determinants of SHS-protective behaviours. RESULTS: Only 40% of smokers had ‘good’ knowledge of SHS-related illnesses compared with 65% of never smokers. Knowledge increased markedly when frequent SHS-related mass media campaigns (2003–06) ran, compared with earlier years (1996–2002). Smokers with better knowledge were more likely to have smoke-free homes [odds ratio (OR): 1.10, 1.04–1.16] and abstain from smoking in a room with children (OR: 1.11, 1.09–1.14). CONCLUSIONS: The low levels of knowledge of some SHS-related conditions, especially among smokers, and the relationship between knowledge and SHS-protective behaviours, suggest that greater efforts to educate smokers about the risks associated with SHS are worthwhile

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

A new species of Chaetaglaea (Lepidoptera, Noctuidae, Noctuinae, Xylenini), from eastern North America

Chaetaglaea tremula (Harvey) occurs through the Gulf States, from southern Florida, west to eastern Texas. Coastal populations, previously referred to Chaetaglaea tremula occurring from the Carolinas, at least as far north as Massachusetts and shoreline dunes in southwestern Ontario are recognized as distinct and described here as Chaetaglaea rhonda. Adults and genitalia are illustrated for Chaetaglaea rhonda and Chaetaglaea tremula

Rediscovery of Anacampsis lupinella Busck (Lepidoptera: Gelechiidae) in Ontario

We rediscovered populations of Anacampsis lupinella Busck (Lepidoptera: Gelechiidae) in three remnant populations of sundial lupines (Lupinus perennis L. (Fabaceae)) in southern Ontario. Here we provide a detailed description of the species and illustrate it with figures of adult moths and both male and female genitalia. Photographs of the moths taken recently in High Park, Toronto, match photos of the type specimen that was collected at High Park in 1901. The male genitalia of contemporary males match those of a male from the original series of specimens collected in Toronto. CO1DNA barcodes of eight contemporary specimens were very similar to the CO1barcode recovered from a specimen from the original series. The CO1sequences demonstrated slight genetic differentiation of the three Ontario populations, but collectively were clearly delimited from the seven congeneric species known from Ontario

Annotated checklist of the moths and butterflies (Lepidoptera) of Canada and Alaska

The first comprehensive checklist of the Lepidoptera of Canada and Alaska is presented. Taxonomic papers, historical regional checklists, and many collections were consulted to prepare the list. The known distributions of species are listed for the provinces and territories of Canada and the state of Alaska in the USA. The province of Newfoundland and Labrador is further divided into separate listings. A total of 5431 species belonging to 82 families are confirmed as occurring in Canada and Alaska, as well as 53 species that have been reported from the region but not yet verified, 19 species listed as interceptions or unsuccessful introductions, and 52 species listed as probably occurring in the region. A total of 318 species have been reported in error in historical works, and they are listed as well, clearly indicated as erroneous records. All erroneous records and uncertain listings are detailed with notes. All Nearctic subspecies and synonyms are included in the list, except for butterfly subspecies (and their synonyms) that do not occur in the region