Observational and Dynamical Characterization of Main-belt Comet P/2010 R2 (La Sagra)

We present observations of the recently discovered comet-like main-belt object P/2010 R2 (La Sagra) obtained by Pan-STARRS1 and the Faulkes Telescope-North on Haleakala in Hawaii, the University of Hawaii 2.2 m, Gemini-North, and Keck I telescopes on Mauna Kea, the Danish 1.54 m telescope (operated by the MiNDSTEp consortium) at La Silla, and the Isaac Newton Telescope on La Palma. An antisolar dust tail is observed to be present from 2010 August through 2011 February, while a dust trail aligned with the object's orbit plane is also observed from 2010 December through 2011 August. Assuming typical phase darkening behavior, P/La Sagra is seen to increase in brightness by >1 mag between 2010 August and December, suggesting that dust production is ongoing over this period. These results strongly suggest that the observed activity is cometary in nature (i.e., driven by the sublimation of volatile material), and that P/La Sagra is therefore the most recent main-belt comet to be discovered. We find an approximate absolute magnitude for the nucleus of HR = 17.9 ± 0.2 mag, corresponding to a nucleus radius of ~0.7 km, assuming an albedo of p = 0.05. Comparing the observed scattering surface areas of the dust coma to that of the nucleus when P/La Sagra was active, we find dust-to-nucleus area ratios of Ad /AN = 30-60, comparable to those computed for fellow main-belt comets 238P/Read and P/2008 R1 (Garradd), and one to two orders of magnitude larger than for two other main-belt comets (133P/Elst-Pizarro and 176P/LINEAR). Using optical spectroscopy to search for CN emission, we do not detect any conclusive evidence of sublimation products (i.e., gas emission), finding an upper limit CN production rate of Q CN 100 Myr, suggesting that it is likely native to its current location and that its composition is likely representative of other objects in the same region of the main belt, though the relatively close proximity of the 13:6 mean-motion resonance with Jupiter and the (3,-2,-1) three-body mean-motion resonance with Jupiter and Saturn mean that dynamical instability on larger timescales cannot be ruled out.

Job strain as a risk factor for coronary heart disease:a collaborative meta-analysis of individual participant data

BACKGROUND: Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. METHODS: We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. FINDINGS: 30?214 (15%) of 197?473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10-1·37). This effect estimate was higher in published (1·43, 1·15-1·77) than unpublished (1·16, 1·02-1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15-1·48) and 5 years (1·30, 1·13-1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%. INTERPRETATION: Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. FUNDING: Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.

Plasma HDL cholesterol and risk of myocardial infarction: A mendelian randomisation study

Background: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian random isation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.
Methods: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20 913 myocardial infarction cases, 95 407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12 482 cases of myocardial infarction and 41 331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.
Findings: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher p=8×10-13) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with noncarriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13 95% CI 1·69-2·69, p=2×10 -10).
Interpretation: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.

Novel susceptibility locus at 22q11 for diabetic nephropathy in type 1 diabetes

Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21-q25 region has repeatedly been indicated as a susceptibility region for DN. The aim of this study was to search for new DN susceptibility loci in Finnish, Danish and French T1D families.

Large-scale association analysis identifies new risk loci for coronary artery disease

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2)

Explaining the Stunted Rise of Macroprudential Regulatory Philosophies

In the aftermath of the financial crash of 2008, policy makers operating in international financial regulatory networks discovered macroprudential regulation (MPR), but macroprudential regulation has had a stunted or arrested development that can be explained with reference to five factors that are recounted in this article

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Genetically Determined Height and Coronary Artery Disease

Background: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. 
Methods: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. 
Results: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. 
Conclusions: There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.)

Gestão curricular da língua cabo-verdiana : sua integração nos curricula

Com esta investigação pretendemos analisar as perspectivas e opiniões dos professores de Portugugs, relativamente A questáo da Gestão Curricular da Língua Cabo-vediana e sua integração nos curficula. O trabalho divide-se em duas partes, sendo a primeira parte abrangendo a coniextualizaç~od o problema e objecto de estudo, e o enquadramento tebrico, com base nos suportes te6ricos de referência e a segunda parte abarca a enquadramento metodológico de um estudo prospectivo, concretizado através da realização de um inquérito por questionário aplicado a uma amostra dos professores de Português de Cabo Verde. Na primeira parte do trabalho, para além do conceito de curriculo. que foi largamente descrito a nível teórico, o estudo centra-se no conceito de gesfão cvrricular da Ccv e as suas inter-relaçáes com os conceitos de adequaçio, diferenciação e integra@ curricuiares, a luz das novas tendemias curriculares e de inovação educativa. Um outro ponto que tem merecido destaque, nesta primeira parte diz respeito aos conceitos de crioulo e pidgin e a formação do Ccv e a sua conversão em Ccv. Assim, atribuímos A política linguística ai legiiimaçào da criação de estruturas e meios indispensáveis para a afirmação e valorizaç8a da Lcv e sua integração nos curricula. A concepção da nossa investigação situa-se dentro do paradigma construtívista, conforme definido por Guba & Lincoln (19941, que permite a compreensão da realidade sob a forma de construções mentais e sociais, baseadas na interpretação e analise de conteúdo de dados obtidos junto dos sujeitos, Para a abordagem metodológica utilizada nesta pesquisa utilizou-se o inquérito por question8rio1 com recurso ao método quantitativdqualitativo, visto que se trata de um estudo descritivolinterpretativo de natureza exploratória, que se preocupa mais com o processo do que com os prdutos. A síntese dos resultados demonstra que os professores têm a noção dos conceitos de currículo e de gestão curricular, embora haja algumas divergências na conceptualização dos mesmos. No tocante à Lcv, é clara a ansiedade que os professores deixam transparecer de ver a sua Ilngua materna valorizada, no sentido da sua ascensão A língua oficial em paridade com a Lp. Assim, advoga-se a criação de estruturas e de gestão de meios materiais a humanos para a oficialiração da Lcv e sua integração nos çurricula escolares.

The Long Range Transport of Birch (Betula) Pollen from Poland and Germany Causes Significant Pre-season Concentrations in Denmark

Background Birch pollen is highly allergic and has the potential for episodically long range transport. Such episodes will in general occur out of the main pollen season. During that time allergy patients are unprotected and high pollen concentrations will therefore have a full allergenic impact. Objective To show that Denmark obtains significant quantities of birch pollen from Poland or Germany before the local trees start to flower. Methods Simultaneous observations of pollen concentrations and phenology in the potential source area in Poland as well as in Denmark were performed in 2006. The Danish pollen records from 2000-2006 were analysed for possible long range transport episodes and analysed with trajectories in combination with a birch tree source map. Results In 2006 high pollen concentrations were observed in Denmark with bi-hourly concentrations above 500 grains/ m3 before the local trees began to flower. Poland was identified as a source region. The analysis of the historical pollen record from Copenhagen shows significant pre-seasonal pollen episodes almost every year from 2000-2006. In all episodes trajectory analysis identified Germany or Poland as source regions. Conclusion Denmark obtains significant pre-seasonal quantities of birch pollen from either Poland or Germany almost every year. Forecasting of birch pollen quantities relevant to allergy patients must therefore take into account long-range transport. This cannot be based on measured concentrations in Denmark. The most effective way to improve the current Danish pollen forecasts is to extend the current forecasts with atmospheric transport models that take into account pollen emission and transport from countries such as Germany and Poland. Unless long range transport is taken into account pre-seasonal pollen episodes will have a full allergic impact, as the allergy patients in general will be unprotected during that time.

Seasonal Variation in Diurnal Atmospheric Grass Pollen Concentration Profiles

In this study, the diurnal atmospheric grass pollen concentration profile within the Danish city of Aarhus was shown to change in a systematic manner as the pollen season progressed. Although diurnal grass pollen profiles can differ greatly from day-to-day, it is common practice to establish the time of day when peak concentrations are most likely to occur using seasonally averaged diurnal profiles. Atmospheric pollen loads are highly dependent upon emissions, and different species of grass are known to flower and emit pollen at different times of the day and during different periods of the pollen season. Pollen concentrations are also influenced by meteorological factors – directly through those parameters that govern pollen dispersion and transport, and indirectly through the weather-driven flowering process. We found that three different profiles dominated the grass pollen season in Aarhus – a twin peak profile during the early season, a single evening profile during the middle of the season, and a single midday peak during the late season. Whilst this variation could not be explained by meteorological factors, no inconsistencies were found with the theory that it was driven by a succession of different grass species with different diurnal flowering patterns dominating atmospheric pollen loads as the season progressed. The potential for exposure was found to be significantly greater during the late-season period than during either the early- or mid-season periods.