Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

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.

Estimation of cosmological parameters using adaptive importance sampling

We present a Bayesian sampling algorithm called adaptive importance sampling or population Monte Carlo (PMC), whose computational workload is easily parallelizable and thus has the potential to considerably reduce the wall-clock time required for sampling, along with providing other benefits. To assess the performance of the approach for cosmological problems, we use simulated and actual data consisting of CMB anisotropies, supernovae of type Ia, and weak cosmological lensing, and provide a comparison of results to those obtained using state-of-the-art Markov chain Monte Carlo (MCMC). For both types of data sets, we find comparable parameter estimates for PMC and MCMC, with the advantage of a significantly lower wall-clock time for PMC. In the case of WMAP5 data, for example, the wall-clock time scale reduces from days for MCMC to hours using PMC on a cluster of processors. Other benefits of the PMC approach, along with potential difficulties in using the approach, are analyzed and discussed.

Bayesian model comparison in cosmology with Population Monte Carlo

We use Bayesian model selection techniques to test extensions of the standard flat LambdaCDM paradigm. Dark-energy and curvature scenarios, and primordial perturbation models are considered. To that end, we calculate the Bayesian evidence in favour of each model using Population Monte Carlo (PMC), a new adaptive sampling technique which was recently applied in a cosmological context. The Bayesian evidence is immediately available from the PMC sample used for parameter estimation without further computational effort, and it comes with an associated error evaluation. Besides, it provides an unbiased estimator of the evidence after any fixed number of iterations and it is naturally parallelizable, in contrast with MCMC and nested sampling methods. By comparison with analytical predictions for simulated data, we show that our results obtained with PMC are reliable and robust. The variability in the evidence evaluation and the stability for various cases are estimated both from simulations and from data. For the cases we consider, the log-evidence is calculated with a precision of better than 0.08. Using a combined set of recent CMB, SNIa and BAO data, we find inconclusive evidence between flat LambdaCDM and simple dark-energy models. A curved Universe is moderately to strongly disfavoured with respect to a flat cosmology. Using physically well-motivated priors within the slow-roll approximation of inflation, we find a weak preference for a running spectral index. A Harrison-Zel'dovich spectrum is weakly disfavoured. With the current data, tensor modes are not detected; the large prior volume on the tensor-to-scalar ratio r results in moderate evidence in favour of r=0.

Native Phloem and Wood Borers in Australian Mediterranean Forest Trees

Native Mediterranean forests in Australia are dominated by two tree genera, Eucalyptus and Acacia, while Pinus and Eucalyptus dominate plantation forestry. In native forests, there is a high diversity of phloem and wood borers across several families in the Coleoptera and Lepidoptera. In the Coleoptera, cerambycid beetles (Cerambycidae), jewel beetles (Buprestidae), bark, ambrosia and pinhole beetles (Curculionidae) and pinworms (Lymexelidae) are some of the most commonly found beetles attacking eucalypts and acacias. In the Lepidoptera, wood moths (Cossidae), ghost moths (Hepialidae) and borers in the Xyloryctidae (subfamily Xyloryctinae) are most common. In contrast to native forests, there is a much more limited range of native insects present in Australian plantations, particularly in exotic Pinus spp. plantations, although eucalypt plantations do share some borers in common with native forests. This chapter reviews the importance of these borers in Australian forests primarily from an economic perspective (i.e. those species that cause damage to commercial tree species) and highlights a paucity of native forest species that commonly kill trees relative to the large scales regularly seen in North America and Europe.

Editorial: In 2035, will all bacteria be multidrug-resistant? No

The spread of multidrug-resistant (MDR) bacteria has reached a threatening level. Extended-spectrum betalactamase- producing enterobacteriaceae (ESBLE) are now endemic in many hospitals worldwide as well as in the community, while resistance rates continue to rise steadily in Acinetobacter baumannii and Pseudomonas aeruginosa [1]. Even more alarming is the dissemination of carbapenemase-producing enterobacteriaceae (CPE), causing therapeutic and organizational problems in hospitals facing outbreaks or endemicity. This context could elicit serious concerns for the coming two decades; nevertheless, effective measures exist to stop the amplification of the problem and several axes of prevention remain to be fully exploited, leaving room for realistic hopes, at least for many parts of the world...

Semi-similar solutions of the unsteady compressible second-order boundary layer flow at the stagnation point

Semi-similar solutions of the unsteady compressible laminar boundary layer flow over two-dimensional and axisymmetric bodies at the stagnation point with mass transfer are studied for all the second-order boundary layer effects when the free stream velocity varies arbitrarily with time. The set of partial differential equations governing the unsteady compressible second-order boundary layers representing all the effects are derived for the first time. These partial differential equations are solved numerically using an implicit finite-difference scheme. The results are obtained for two particular unsteady free stream velocity distributions: (a) an accelerating stream and (b) a fluctuating stream. It is observed that the total skin friction and heat transfer are strongly affected by the surface mass transfer and wall temperature. However, their variation with time is significant only for large times. The second-order boundary layer effects are found to be more pronounced in the case of no mass transfer or injection as compared to that for suction. Résumé Des solutions semi-similaires d'écoulement variable compressible de couche limite sur des corps bi-dimensionnels thermique, sont étudiées pour tous les effets de couche limite du second ordre, lorsque la vitesse de l'écoulement libre varie arbitrairement avec le temps. Le systéme d'équations aux dérivées partielles représentant tous les effets est écrit pour la premiére fois. On le résout numériquement á l'aide d'un schéma implicite aux différences finies. Les résultats sont obtenus pour deux cas de vitesse variable d'écoulement libre: (a) un écoulement accéléré et (b) un écoulement fluctuant. On observe que le frottement pariétal total et le transfert de chaleur sont fortement affectés par le transfert de masse et la température pariétaux. Néanmoins, leur variation avec le temps est sensible seulement pour des grandes durées. Les effets sont trouvés plus prononcés dans le cas de l'absence du transfert de masse ou de l'injection par rapport au cas de l'aspiration.

Multifractal analysis, a method to investigate the morphology of materials

Using the multifractal formalism, we discuss the results obtained to characterized the morphology of polymer alloys and granular discontinuous metallic thin films. In the first case we have found a correlation between the multifractality and the mechanical properties of the alloys. In the second case, we have found that it is possible to measure the differences between the morphology of thin films induced by a growth process on a subtrate and that of percolation clusters of the classical theory of percolation.

Estudios de Historia de España, 2008, vol. 10 (número completo)

Contenido: El regadío sostenible en al-Andalus / José Roldán Cañas ; María Fátima Moreno Pérez ; José Luis del Pino García – Presencia jurídica femenina a través de los Ordenamientos de Cortes (Castilla – León, Siglos XII-XIV) / Diana Arauz Mercado – Santo Domingo de Caleruega. Estudio iconológico / María Jesús Baquero Martín – Un ejemplo de poder monástico femenino: las relaciones entre la villa de Tordesillas y el convento de Santa Clara / Cecilia Bahr – La exposición de la doctrina de la “Guerra Justa” en El Victorial de Gutierre Díaz de Games / Santiago Agustín Pérez – Algunas notas sobre el patrimonio de la boticaria Elvira Pérez (Santiago, 1348) / Carlos Calderón – The price of Charles V’S protection in Italy: the example of Lucca / Christine Shaw – El Imperio y las Cortes de Santiago de Compostela de 1520, la base ideológica del Absolutismo español / István Szászdi – The extradition treaties of the Spanish and Portuguese Inquisitions (1500-1700) / François Soyer – Las “Memorias” del general argentino Tomás de Iriarte sobre la Guerra de la Independencia Española / Miguel Ángel De Marco – Los viajes a Alemania de Ramiro de Maeztu / Ángeles Castro Montero -- Reseñas

Sapientia, 2004, Vol. LIX, nº 216 (número completo)

Contenido: Josef Pieper en el centenario de su nacimiento / Héctor J. Delbosco – Misterio filosófico y misterio teológico en Josef Pieper y en Santo Tomás de Aquino / Ignacio Andereggen – El status de la filosofía en la posciencia. Respuestas desde Josef Pieper / Miriam Dolly Arancibía de Calmels – “Miseria y esplendor de la interpretación”. En torno a los límites de la hermenéutica en Pieper y en Ortega / Roberto E. Aras – Si sí : la condicionalidad metafísica de una afirmación absoluta / Santiago Argüello – Una perspectiva del saber y de la fortaleza en el héroe unamuniano a la luz de Josef Pieper / Angélica S. Arza de Bousquet – Manía, mito y conmoción erótica / Luis Baliña ; Juan Torbidoni – Juventud, fiesta y esperanza en la obra de Josef Pieper : una respuesta a la cultura posmoderna / Santiago Bellomo – Pieper y Guardini en Rothenfels : un encuentro fecundo / Alberto Berro – La afirmación real del amor / María José Binetti – Josef Pieper al encuentro de Platón : una relectura de las relaciones entre mito y filosofía / Claudio Calabrese – Orientación y pautas de discernimiento en el ámbito poético-literario : la doctrina de la contemplación terrena enunciada por Josef Pieper e ilustrada en Albert Camus / Inés de Cassagne – La imposibilidad de una filosofía no cristiana según Josef Pieper / Agustín Ignacio Echavarría – Ética y psicoterapia según Josef Pieper / Martín Echavarría – Enseñanzas de un gran maestro : la corruptibilidad de la palabra / María del Carmen Fernández – La inspiración platónica de la filosofía de Josef Pieper / Juan Francisco Franck – Método y lenguaje en el pensamiento de Josef Pieper / Jean Lauand – Josef Pieper y Peter Wust / Juan Andrés Levermann – Aprobación creadora : un aspecto de la dimensión social del bien de la persona / Marisa Mosto – Josef Pieper y la reflexión sobre el mito y la cultura / Héctor Jorge Padrón – Josef Pieper y el tomismo medieval : la controversia sobre la creación / François-Xavier Putallaz – Algunas consideraciones sobre J. Pieper y el tema del mal en la problemática filosófica contemporánea / Juan Pablo Roldán – Josef Pieper y la acedia : la causa afectiva de ciertas deformaciones intelectuales / El hombre de ocio : parásito o transformador del mundo / Bernard N. Schumacher – La templanza en Josef Pieper y Santo Tomás / Zelmira Seligmann – El ideal del trabajo en Josef Pieper / Ludovico Antonio Videla – Valor para la realidad – Valor para la persona : reafirmación cristiana como crítica de la cultura en la obra temprana de Josef Pieper / Berthold Wald – Notas y comentarios -- Bibliografía

Comprometimento organizacional afetivo : um estudo na Câmara dos Deputados

Avalia o grau de comprometimento afetivo dos funcionários de alguns setores da Câmara dos Deputados, tendo por base uma pesquisa de campo com aplicação de questionário. Identifica os diferentes padrões de comprometimento, segundo os dados biográficos e funcionais dos servidores, e analisa em que medida o comportamento afetivo prevalece sobre os demais.

Diário da Constituinte [gravação de vídeo] : [programa n. 226]

A Comissão de Sistematização da Assembleia Nacional Constituinte (ANC) debate emenda sobre a criação da Defensoria Pública. A Defensoria defende o cidadão contra ações ou omissões praticadas por empresas públicas. O Senador Nelson Carneiro (PMDB-RJ) apoia a Defensoria, assinalando que se trata de uma carreira composta por elementos escolhidos por concurso público e orientados por um Procurador-Geral da Defensoria, que deverão defender os pobres contra os mais poderosos. Plenário discute a representação política. O novo projeto eleva de sessenta para oitenta o número máximo de deputados federais por Estado, beneficiando apenas o Estado de São Paulo. A medida é polêmica porque, mantido o número atual de cadeiras na Câmara, os Estados pequenos teriam sua representação diminuída. O Deputado Victor Fontana (PFL-SC) propõe diminuir o número de deputados na Câmara, afirmando que o último aumento para quatrocentos e oitenta e sete (487) deputados não trouxe mais eficiência e nem conseguiu recuperar a credibilidade dos políticos perante o eleitor. O Deputado Antônio Salim Curiati (PDS-SP) defende a redução para duzentos e vinte e cinco (225) deputados. Os Deputados Celso Dourado (PMDB-BA) e Roberto Rollemberg (PMDB-SP) querem ampliar o número de representantes. Senadores franceses visitaram o Congresso para conhecer os trabalhos da Assembleia Nacional Constituinte (ANC). O presidente da ANC, Deputado Ulysses Guimarães (PMDB-SP) explicou aos senadores que, no Brasil, preferiu-se a organização da Constituinte dividida em comissões temáticas, com a participação de todos os representantes. Os parlamentares franceses também queriam saber sobre a discussão do tema "sistema de governo". O Deputado Ulysses Guimarães declara que esse é um dos temas mais polêmicos e que as negociações ainda não foram concluídas. O Senador Jean François Pintat afirmou que os franceses vêm com bons olhos o trabalho desenvolvido, porque a Constituinte representa a promessa de uma verdadeira democracia.