A mega-analysis of genome-wide association studies for major depressive disorder

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 x 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 x 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

Combining meta- and mega-analytic approaches for multi-site diffusion imaging based genetic studies: From the enigma-DTI working group

Meta-analyses estimate a statistical effect size for a test or an analysis by combining results from multiple studies without necessarily having access to each individual study's raw data. Multi-site meta-analysis is crucial for imaging genetics, as single sites rarely have a sample size large enough to pick up effects of single genetic variants associated with brain measures. However, if raw data can be shared, combining data in a "mega-analysis" is thought to improve power and precision in estimating global effects. As part of an ENIGMA-DTI investigation, we use fractional anisotropy (FA) maps from 5 studies (total N=2, 203 subjects, aged 9-85) to estimate heritability. We combine the studies through meta-and mega-analyses as well as a mixture of the two - combining some cohorts with mega-analysis and meta-analyzing the results with those of the remaining sites. A combination of mega-and meta-approaches may boost power compared to meta-analysis alone.

Polygenic Interactions with Environmental Adversity in the Aetiology of Major Depressive Disorder

Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.

Analysis of traffic injury severity in a mega city of a developing country

Despite a considerable amount of research on traffic injury severities, relatively little is known about the factors influencing traffic injury severity in developing countries, and in particular in Bangladesh. Road traffic crashes are a common headline in daily newspapers of Bangladesh. It has also recorded one of the highest road fatality rates in the world. This research identifies significant factors contributing to traffic injury severity in Dhaka – a mega city and capital of Bangladesh. Road traffic crash data of 5 years from 2007 to 2011 were collected from the Dhaka Metropolitan Police (DMP), which included about 2714 traffic crashes. The severity level of these crashes was documented in a 4-point ordinal scale: no injury (property damage), minor injury, severe injury, and death. An ordered Probit regression model has been estimated to identify factors contributing to injury severities. Results show that night time influence is associated with a higher level injury severity as is for individuals involved in single vehicle crashes. Crashes on highway sections within the city are found to be more injurious than crashes along the arterial and feeder roads. There is a lower likelihood of injury severity, however, if the road sections are monitored and enforced by the traffic police. The likelihood of injuries is lower on two-way traffic arrangements than one-way, and at four-legged intersections and roundabouts compare to road segments. The findings are compared with those from developed countries and the implications of this research are discussed in terms of policy settings for developing countries.

The Panama canal expansion mega project : a case study and stakeholder´s analysis

As globalization increases integration, a new playing field is emerging which is driving the need for operational efficiencies and alignment of complementary capabilities among countries to build sustainable models and integrated offerings. As demands increase, companies are turning to effective project management as means to control operations and countries are increasing the amount of mega projects to boost their competitiveness and global footprint. Given the scale, complexity, political nature, multicultural makeup, and high level of visibility; mega projects rely on successful stakeholder management to effectively manage its operational, tactical, and strategic levels to execute their mission. This paper examines the success drivers of mega projects and presents an in depth stakeholder assessment of the Panama Canal Expansion mega project to identify the perceived value to its stakeholder community. The stakeholder categories include: the Panama Canal Authority, subcontractors executing the expansion project, customers of the canal in Panama and U.S., as well as the communities surrounding the Panama Canal and ports in the U.S. East Coast. The conclusion of this paper captures the relationship between the effective stakeholder engagement from the Panama Canal Authority, the perceived value of the Panamanian stakeholders, and compares it to U.S. based mega projects being executed simultaneously to allow the U.S. East Coast ports to accommodate increased cargo volumes.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA-DTI working group

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/).

Tree-ring based hydroclimate reconstruction over northern Vietnam from Fokienia hodginsii: eighteenth century mega-drought and tropical Pacific influence

We present here the first statistically calibrated and verified tree-ring reconstruction of climate from continental Southeast Asia.The reconstructed variable is March-May (MAM) Palmer Drought Severity Index (PDSI) based on ring widths from 22 trees (42 radial cores) of rare and long-lived conifer, Fokienia hodginsii (Po Mu as locally called) from northern Vietnam. This is the first published tree ring chronology from Vietnam as well as the first for this species. Spanning 535 years, this is the longest cross-dated tree-ring series yet produced from continental Southeast Asia. Response analysis revealed that the annual growth of Fokienia at this site was mostly governed by soil moisture in the pre-monsoon season. The reconstruction passed the calibration-verification tests commonly used in dendroclimatology, and revealed two prominent periods of drought in the mid-eighteenth and late-nineteenth enturies. The former lasted nearly 30 years and was concurrent with a similar drought over northwestern Thailand inferred from teak rings, suggesting a ``mega-drought'' extending across Indochina in the eighteenth century. Both of our reconstructed droughts are consistent with the periods of warm sea surface temperature (SST)anomalies in the tropical Pacific. Spatial correlation analyses with global SST indicated that ENSO-like anomalies might play a role in modulating droughts over the region, with El Nio (warm) phases resulting in reduced rainfall. However, significant correlation was also seen with SST over the Indian Ocean and the north Pacific,suggesting that ENSO is not the only factor affecting the climate of the area. Spectral analyses revealed significant peaks in the range of 53.9-78.8 years as well as in the ENSO-variability range of 2.0 to 3.2 years.

An analysis of a microfabricated solenoid inductor

A microscale solenoid inductor is manufactured using electrodeposition method. The inductor is designed for switching mode DC-DC converters operating at switching frequencies in the mega-Hertz range. Two magnetic core materials, electroformed permalloy Ni80 Fe20 film and Vitrovac 6025 which is a commercial magnetic film, have been analyzed using experimental and computer modeling techniques

Land cover mapping analysis and urban growth modeling using remote sensing techniques

The rapid growth of big cities has been noticed since 1950s when the majority of world population turned to live in urban areas rather than villages, seeking better job opportunities and higher quality of services and lifestyle circumstances. This demographic transition from rural to urban is expected to have a continuous increase. Governments, especially in less developed countries, are going to face more challenges in different sectors, raising the essence of understanding the spatial pattern of the growth for an effective urban planning. The study aimed to detect, analyse and model the urban growth in Greater Cairo Region (GCR) as one of the fast growing mega cities in the world using remote sensing data. Knowing the current and estimated urbanization situation in GCR will help decision makers in Egypt to adjust their plans and develop new ones. These plans should focus on resources reallocation to overcome the problems arising in the future and to achieve a sustainable development of urban areas, especially after the high percentage of illegal settlements which took place in the last decades. The study focused on a period of 30 years; from 1984 to 2014, and the major transitions to urban were modelled to predict the future scenarios in 2025. Three satellite images of different time stamps (1984, 2003 and 2014) were classified using Support Vector Machines (SVM) classifier, then the land cover changes were detected by applying a high level mapping technique. Later the results were analyzed for higher accurate estimations of the urban growth in the future in 2025 using Land Change Modeler (LCM) embedded in IDRISI software. Moreover, the spatial and temporal urban growth patterns were analyzed using statistical metrics developed in FRAGSTATS software. The study resulted in an overall classification accuracy of 96%, 97.3% and 96.3% for 1984, 2003 and 2014’s map, respectively. Between 1984 and 2003, 19 179 hectares of vegetation and 21 417 hectares of desert changed to urban, while from 2003 to 2014, the transitions to urban from both land cover classes were found to be 16 486 and 31 045 hectares, respectively. The model results indicated that 14% of the vegetation and 4% of the desert in 2014 will turn into urban in 2025, representing 16 512 and 24 687 hectares, respectively.

As práticas de supervisão e liderança dos coordenadores do departamento de Matemática e Ciências Experimentais na harmonização de um emergente mega departamento

A escola é uma organização cuja missão se traduz no aperfeiçoamento das práticas pedagógicas e na melhoria da qualidade do ensino e da aprendizagem (Lima, 2008) muito embora se veja confrontada diariamente com vários desafios de ordem política, social, económica e ideológica que obrigam todos os agentes educativos a encontrar formas para os ultrapassar (Nóvoa, 2009). Atualmente, o sucesso dos mega agrupamentos recentemente criados pela tutela emerge como um enorme desafio quanto à organização e nova dinâmica da escola como instituição, realçando o papel fundamental dos promotores e harmonizadores da mudança que constituem os órgãos de gestão e nomeadamente os de gestão intermédia, representados pelos coordenadores dos departamentos curriculares. Com efeito, é a eles que cabe o difícil e delicado papel de unir realidades diferentes coordenando-as, orientando-as e harmonizando-as respeitando simultaneamente as diferentes ambições e expetativas dos alunos quanto ao seu futuro, as culturas escolares e os professores que de um momento para o outro são obrigados a adaptarem-se a contextos sociais ainda mais heterogéneos. Desta forma, a tarefa dos coordenadores de departamento vê-se substancialmente acrescida e dificultada não só pelo aumento do número de docentes que constitui o departamento mas, mais ainda pela explosão das diferenças que surgem entre os vários docentes, as suas práticas e o universo de alunos do mega agrupamento que se deve constituir numa única comunidade escolar (Sergiovanni, 2004). No intuito de realçar o papel dos coordenadores na promoção da integração das duas escolas e na implementação da efetiva colaboração entre coordenadores e grupos disciplinares, objetivo geral deste trabalho, é proposta uma ação de formação na modalidade de projeto. Esta proposta resulta da análise das entrevistas realizadas aos coordenadores do mega departamento de Matemática e Ciências Experimentais do mega agrupamento onde a autora deste estudo exerce funções, e através das quais se procurava responder à questão: qual o papel dos coordenadores na promoção de integração das duas escolas e na implementação da efetiva colaboração entre os coordenadores e grupos disciplinares.

Meta-analysis of individual patient data from randomised trials: a review of methods used in practice

Background: Meta-analyses based on individual patient data (IPD) are regarded as the gold standard for systematic reviews. However, the methods used for analysing and presenting results from IPD meta-analyses have received little discussion. Methods We review 44 IPD meta-analyses published during the years 1999–2001. We summarize whether they obtained all the data they sought, what types of approaches were used in the analysis, including assumptions of common or random effects, and how they examined the effects of covariates. Results: Twenty-four out of 44 analyses focused on time-to-event outcomes, and most analyses (28) estimated treatment effects within each trial and then combined the results assuming a common treatment effect across trials. Three analyses failed to stratify by trial, analysing the data is if they came from a single mega-trial. Only nine analyses used random effects methods. Covariate-treatment interactions were generally investigated by subgrouping patients. Seven of the meta-analyses included data from less than 80% of the randomized patients sought, but did not address the resulting potential biases. Conclusions: Although IPD meta-analyses have many advantages in assessing the effects of health care, there are several aspects that could be further developed to make fuller use of the potential of these time-consuming projects. In particular, IPD could be used to more fully investigate the influence of covariates on heterogeneity of treatment effects, both within and between trials. The impact of heterogeneity, or use of random effects, are seldom discussed. There is thus considerable scope for enhancing the methods of analysis and presentation of IPD meta-analysis.

Genetic analysis of heat tolerance at anthesis in rice

Genetic analysis of heat tolerance will help breeders produce rice (Oryza sativa L.) varieties adapted to future climates. An F6 population of 181 recombinant inbred lines of Bala (tolerant) × Azucena (susceptible) was screened for heat tolerance at anthesis by measuring spikelet fertility at 30°C (control) and 38°C (high temperature) in experiments conducted in the Philippines and the United Kingdom. The parents varied significantly for absolute spikelet fertility under control (79–87%) and at high temperature (2.9–47.1%), and for relative spikelet fertility (high temperature/control) at high temperature (3.7–54.9%). There was no correlation between spikelet fertility in control and high-temperature conditions and no common quantitative trait loci (QTLs) were identified. Two QTLs for spikelet fertility under control conditions were identified on chromosomes 2 and 4. Eight QTLs for spikelet fertility under high-temperature conditions were identified on chromosomes 1, 2, 3, 8, 10, and 11. The most significant heat-responsive QTL, contributed by Bala and explaining up to 18% of the phenotypic variation, was identified on chromosome 1 (38.35 mega base pairs on the rice physical genome map). This QTL was also found to influence plant height, explaining 36.6% of the phenotypic variation. A comparison with other studies of abiotic (drought, cold, salinity) stresses showed QTLs at similar positions on chromosomes 1, 3, 8, and 10, suggesting common underlying stress-responsive regions of the genome.

Acoustic Design in Urban Development : analysis of urban soundscapes and acoustic ecology research in New York City

The world is urbanizing rapidly with more than half of the global population now living in cities. Improving urban environments for the well-being of the increasing number of urban citizens is becoming one of the most important challenges of the 21st century. Even though it is common that city planners have visions of a ’good urban milieu’, those visions are concerning visual aesthetics or practical matters. The qualitative perspective of sound, such as sonic diversity and acoustic ecology are neglected aspects in architectural design. Urban planners and politicians are therefore largely unaware of the importance of sounds for the intrinsic quality of a place. Whenever environmental acoustics is on the agenda, the topic is noise abatement or noise legislation – a quantitative attenuation of sounds. Some architects may involve acoustical aspects in their work but sound design or acoustic design has yet to develop to a distinct discipline and be incorporated in urban planning.My aim was to investigate to what extent the urban soundscape is likely to improve if modern architectural techniques merge with principles of acoustics. This is an important, yet unexplored, research area. My study explores and analyses the acoustical aspects in urban development and includes interviews with practitioners in the field of urban acoustics, situated in New York City. My conclusion is that to achieve a better understanding of the human living conditions in mega-cities, there is a need to include sonic components into the holistic sense of urban development.

5th BRICS Trade and Economic Research Network (TERN) meeting: the impact of mega agreements on BRICS

The BRICS TERN – BRICS Trade and Economics Research Network is a group of independent research institutes established four years ago by five think tanks from Brazil, Russia, India, China and South Africa. The main objective of the network is to study different aspects of trade and economic relations amongst these five countries. The purpose of the V BRICS TERN Meeting was to analyze and debate the effects of the negotiations of the Mega Agreements, mainly those initiated by the US and the EU, already in negotiation, to each of the BRICS Trade Policies. Both Mega Agreements were examined – the Trans Pacific Partnership (TPP) and the Transatlantic Trade and Investment Partnership (TTIP). The studies included the main impacts on trade flows and on the international trade rules system, respecting the perspective of each of the countries concerned. This workshop was an initiative of the Center for Global Trade and Investments (CGTI), a think-tank on International Trade held by FGV Sao Paulo School of Economics. Its main objective is the research on trade regulation, preferential trade agreements, trade and currency, trade and global value chains, through legal analysis and economic modelling. One of its main researches, now, is on the potential economic and legal impacts of the Mega Agreements on Brazil and WTO rules. This meeting was organized in March14, 2014, in Rio de Janeiro, in a perfect timing for introducing such issues in the international agenda, in advance of the 6th BRICS Summit scheduled to be held in Brazil in July 2014.

Efeitos da dieta suplementada com ômega-3 no músculo sóleo de ratos submetidos à natação: análise histológica e morfométrica

As lesões musculares têm sido observadas como as mais frequentes nos esportes. Considerando a produção de espécies reativas de oxigênio como um fator de risco para instalação de lesões e características antioxidantes e anti-inflamatórias do ômega-3, o objetivo deste trabalho foi verificar as alterações histológicas e morfométricas do músculo sóleo de ratos que realizaram natação, associado a uma dieta suplementada com ômega-3. Para sua realização foram utilizados 31 ratos Wistar divididos em quatro grupos, sendo os grupos A e C suplementados com azeite de oliva e B e D com 3g/dia de ômega-3 por quatro semanas. Os grupos C e D foram submetidos à natação cinco dias/semana por 28 dias, com acréscimo de 5% do peso corporal a partir da segunda semana, enquanto que os grupos A e B não realizaram treinamento. Após este período os animais foram sacrificados, o músculo sóleo retirado e corado com Hematoxilina-eosina para avaliação morfológica. Análise de variância bifatorial, com nível de significância de 5%, foi utilizada para análise dos valores do menor diâmetro das fibras musculares. Os grupos A e B (sedentários) apresentaram padrões histológicos de normalidade. O grupo C apresentou aumento do tecido endomisial e do número de núcleos, presença de fibras fagocitadas e de contornos poligonais não mantidos, enquanto que o grupo D apresentou poucas fibras fagocitadas e de contornos poligonais preservados. Com relação à medida do menor diâmetro das fibras musculares, as análises mostraram diferenças para o fator treinamento, mas não para o fator suplementação e a interação entre eles. As alterações histológicas induzidas pelo exercício foram atenuadas no grupo suplementado com ômega-3, sugerindo um efeito protetor da suplementação, contudo, o aumento do diâmetro das fibras para os grupos expostos ao exercício está relacionado ao efeito do treinamento e não à suplementação.