Educational attainment: A genome wide association study in 9538 Australians

BACKGROUND Correlations between Educational Attainment (EA) and measures of cognitive performance are as high as 0.8. This makes EA an attractive alternative phenotype for studies wishing to map genes affecting cognition due to the ease of collecting EA data compared to other cognitive phenotypes such as IQ. METHODOLOGY In an Australian family sample of 9538 individuals we performed a genome-wide association scan (GWAS) using the imputed genotypes of approximately 2.4 million single nucleotide polymorphisms (SNP) for a 6-point scale measure of EA. Top hits were checked for replication in an independent sample of 968 individuals. A gene-based test of association was then applied to the GWAS results. Additionally we performed prediction analyses using the GWAS results from our discovery sample to assess the percentage of EA and full scale IQ variance explained by the predicted scores. RESULTS The best SNP fell short of having a genome-wide significant p-value (p = 9.77x10(-7)). In our independent replication sample six SNPs among the top 50 hits pruned for linkage disequilibrium (r(2)<0.8) had a p-value<0.05 but only one of these SNPs survived correction for multiple testing--rs7106258 (p = 9.7*10(-4)) located in an intergenic region of chromosome 11q14.1. The gene based test results were non-significant and our prediction analyses show that the predicted scores explained little variance in EA in our replication sample. CONCLUSION While we have identified a polymorphism chromosome 11q14.1 associated with EA, further replication is warranted. Overall, the absence of genome-wide significant p-values in our large discovery sample confirmed the high polygenic architecture of EA. Only the assembly of large samples or meta-analytic efforts will be able to assess the implication of common DNA polymorphisms in the etiology of EA.

The use of genetic correlations to evaluate associations between SNP markers and quantitative traits

Open-pollinated progeny of Corymbia citriodora established in replicated field trials were assessed for stem diameter, wood density, and pulp yield prior to genotyping single nucleotide polymorphisms (SNP) and testing the significance of associations between markers and assessment traits. Multiple individuals within each family were genotyped and phenotyped, which facilitated a comparison of standard association testing methods and an alternative method developed to relate markers to additive genetic effects. Narrow-sense heritability estimates indicated there was significant additive genetic variance within this population for assessment traits ( h ˆ 2 =0.28to0.44 ) and genetic correlations between the three traits were negligible to moderate (r G = 0.08 to 0.50). The significance of association tests (p values) were compared for four different analyses based on two different approaches: (1) two software packages were used to fit standard univariate mixed models that include SNP-fixed effects, (2) bivariate and multivariate mixed models including each SNP as an additional selection trait were used. Within either the univariate or multivariate approach, correlations between the tests of significance approached +1; however, correspondence between the two approaches was less strong, although between-approach correlations remained significantly positive. Similar SNP markers would be selected using multivariate analyses and standard marker-trait association methods, where the former facilitates integration into the existing genetic analysis systems of applied breeding programs and may be used with either single markers or indices of markers created with genomic selection processes.

Ecological condition of coastal ocean waters along the U.S. Western Continental Shelf: 2003

Executive Summary: The western National Coastal Assessment (NCA-West) program of EPA, in conjunction with the NOAA National Ocean Service (NOS), conducted an assessment of the status of ecological condition of soft sediment habitats and overlying waters along the western U.S. continental shelf, between the target depths of 30 and 120 m, during June 2003. NCA-West and NOAA/NOS partnered with the West Coast states (Washington (WA), Oregon (OR), and California (CA)), and the Southern California Coastal Water Research Project (SCCWRP) Bight ’03 program to conduct the survey. A total of 257 stations were sampled from Cape Flattery, WA to the Mexican border using standard methods and indicators applied in previous coastal NCA projects. A key study feature was the incorporation of a stratified-random sampling design with stations stratified by state and National Marine Sanctuary (NMS) status. Each of the three states was represented by at least 50 random stations. There also were a total of 84 random stations located within NOAA’s five NMSs along the West Coast including the Olympic Coast NMS (OCNMS), Cordell Bank NMS (CBNMS), Gulf of Farallones NMS (GFNMS), Monterey Bay NMS (MBNMS), and Channel Islands NMS (CINMS). Collection of flatfish via hook-and-line for fish-tissue contaminant analysis was successful at 50 EMAP/NCA-West stations. Through a collaboration developed with the FRAM Division of the Northwest Fisheries Science Center, fish from an additional 63 stations in the same region and depth range were also analyzed for fish-tissue contaminants. Bottom depth throughout the region ranged from 28 m to 125 m for most stations. Two slightly deeper stations from the Southern California Bight (SCB) (131, 134 m) were included in the data set. About 44% of the survey area had sediments composed of sands (< 20% silt-clay), about 47% was composed of intermediate muddy sands (20-80% silt-clay), and about 9% was composed of muds (> 80% silt-clay). The majority of the survey area (97%) had relatively low percent total organic carbon (TOC) levels of < 2%, while a small portion (< 1%) had high TOC levels (> 5%), in a range potentially harmful to benthic fauna. Salinity of surface waters for 92% of the survey area were > 31 psu, with most stations < 31 psu associated with the Columbia River plume. Bottom salinities ranged only between 31.6 and 34.4 psu. There was virtually no difference in mean bottom salinities among states or between NMS and non-NMS stations. Temperatures of surface water (range 8.5 -19.9 °C) and bottom water (range 5.8 -14.7 °C) averaged several degrees higher in CA in comparison to WA and OR. The Δσt index of watercolumn stratification indicated that about 31% of the survey area had strong vertical stratification of the water column. The index was greatest for waters off WA and lowest for CA waters. Only about 2.6 % of the survey area had surface dissolved oxygen (DO) concentrations ≤ 4.8 mg/L, and there were no values below the lower threshold (2.3 mg/L) considered harmful to the survival and growth of marine animals. Surface DO concentrations were higher in WA and OR waters than in CA, and higher in the OC NMS than in the CA sanctuaries. An estimated 94.3% of the area had bottom-water DO concentrations ≤ 4.8 mg/L and 6.6% had concentrations ≤ 2.3 mg/L. The high prevalence of DO from 2.3 to 4.8 mg/L (85% of survey area) is believed to be associated with the upwelling of naturally low DO water across the West Coast shelf. Mean TSS and transmissivity in surface waters (excluding OR due to sample problems) were slightly higher and lower, respectively, for stations in WA than for those in CA. There was little difference in mean TSS or transmissivity between NMS and non-NMS locations. Mean transmissivity in bottom waters, though higher in comparison to surface waters, showed little difference among geographic regions or between NMS and non-NMS locations. Concentrations of nitrate + nitrite, ammonium, total dissolved inorganic nitrogen (DIN) and orthophosphate (P) in surface waters tended to be highest in CA compared to WA and OR, and higher in the CA NMS stations compared to CA non-sanctuary stations. Measurements of silicate in surface waters were limited to WA and CA (exclusive of the SCB) and showed that concentrations were similar between the two states and approximately twice as high in CA sanctuaries compared to OCNMS or nonsanctuary locations in either state. The elevated nutrient concentrations observed at CA NMS stations are consistent with the presence of strong upwelling at these sites at the time of sampling. Approximately 93% of the area had DIN/P values ≤ 16, indicative of nitrogen limitation. Mean DIN/P ratios were similar among the three states, although the mean for the OCNMS was less than half that of the CA sanctuaries or nonsanctuary locations. Concentrations of chlorophyll a in surface waters ranged from 0 to 28 μg L-1, with 50% of the area having values < 3.9 μg L-1 and 10% having values > 14.5 μg L-1. The mean concentration of chlorophyll a for CA was less than half that of WA and OR locations, and concentrations were lowest in non-sanctuary sites in CA and highest at the OCNMS. Shelf sediments throughout the survey area were relatively uncontaminated with the exception of a group of stations within the SCB. Overall, about 99% of the total survey area was rated in good condition (<5 chemicals measured above corresponding effect range low (ERL) concentrations). Only the pesticides 4,4′-DDE and total DDT exceeded corresponding effect range-median (ERM) values, all at stations in CA near Los Angeles. Ten other contaminants including seven metals (As, Cd, Cr, Cu, Hg, Ag, Zn), 2-methylnaphthalene, low molecular weight PAHs, and total PCBs exceeded corresponding ERLs. The most prevalent in terms of area were chromium (31%), arsenic (8%), 2-methylnaphthalene (6%), cadmium (5%), and mercury (4%). The chromium contamination may be related to natural background sources common to the region. The 2-methylnaphthalene exceedances were conspicuously grouped around the CINMS. The mercury exceedances were all at non-sanctuary sites in CA, particularly in the Los Angeles area. Concentrations of cadmium in fish tissues exceeded the lower end of EPA’s non-cancer, human-health-risk range at nine of 50 EMAP/NCA-West and nine of 60 FRAM groundfish-survey stations, including a total of seven NMS stations in CA and two in the OCNMS. The human-health guidelines for all other contaminants were only exceeded for total PCBs at one station located in WA near the mouth of the Columbia River. Benthic species richness was relatively high in these offshore assemblages, ranging from 19 to 190 taxa per 0.1-m2 grab and averaging 79 taxa/grab. The high species richness was reflected over large areas of the shelf and was nearly three times greater than levels observed in estuarine samples along the West Coast (e.g NCA-West estuarine mean of 26 taxa/grab). Mean species richness was highest off CA (94 taxa/grab) and lower in OR and WA (55 and 56 taxa/grab, respectively). Mean species richness was very similar between sanctuary vs. non-sanctuary stations for both the CA and OR/WA regions. Mean diversity index H′ was highest in CA (5.36) and lowest in WA (4.27). There were no major differences in mean H′ between sanctuary vs. nonsanctuary stations for both the CA and OR/WA regions. A total of 1,482 taxa (1,108 to species) and 99,135 individuals were identified region-wide. Polychaetes, crustaceans and molluscs were the dominant taxa, both by percent abundance (59%, 17%, 12% respectively) and percent species (44%, 25%, 17%, respectively). There were no major differences in the percent composition of benthic communities among states or between NMSs and corresponding non-sanctuary sites. Densities averaged 3,788 m-2, about 30% of the average density for West Coast estuaries. Mean density of benthic fauna in the present offshore survey, averaged by state, was highest in CA (4,351 m-2) and lowest in OR (2,310 m-2). Mean densities were slightly higher at NMS stations vs. non-sanctuary stations for both the CA and OR/WA regions. The 10 most abundant taxa were the polychaetes Mediomastus spp., Magelona longicornis, Spiophanes berkeleyorum, Spiophanes bombyx, Spiophanes duplex, and Prionospio jubata; the bivalve Axinopsida serricata, the ophiuroid Amphiodia urtica, the decapod Pinnixa occidentalis, and the ostracod Euphilomedes carcharodonta. Mediomastus spp. and A. serricata were the two most abundant taxa overall. Although many of these taxa have broad geographic distributions throughout the region, the same species were not ranked among the 10 most abundant taxa consistently across states. The closest similarities among states were between OR and WA. At least half of the 10 most abundant taxa in NMSs were also dominant in corresponding nonsanctuary waters. Many of the abundant benthic species have wide latitudinal distributions along the West Coast shelf, with some species ranging from southern CA into the Gulf of Alaska or even the Aleutians. Of the 39 taxa on the list of 50 most abundant taxa that could be identified to species level, 85% have been reported at least once from estuaries of CA, OR, or WA exclusive of Puget Sound. Such broad latitudinal and estuarine distributions are suggestive of wide habitat tolerances. Thirteen (1.2%) of the 1,108 identified species are nonindigenous, with another 121 species classified as cryptogenic (of uncertain origin), and 208 species unclassified with respect to potential invasiveness. Despite uncertainties of classification, the number and densities of nonindigenous species appear to be much lower on the shelf than in the estuarine ecosystems of the Pacific Coast. Spionid polychaetes and the ampharetid polychaete Anobothrus gracilis were a major component of the nonindigenous species collected on the shelf. NOAA’s five NMSs along the West Coast of the U.S. appeared to be in good ecological condition, based on the measured indicators, with no evidence of major anthropogenic impacts or unusual environmental qualities compared to nearby nonsanctuary waters. Benthic communities in sanctuaries resembled those in corresponding non-sanctuary waters, with similarly high levels of species richness and diversity and low incidence of nonindigenous species. Most oceanographic features were also similar between sanctuary and non-sanctuary locations. Exceptions (e.g., higher concentrations of some nutrients in sanctuaries along the CA coast) appeared to be attributable to natural upwelling events in the area at the time of sampling. In addition, sediments within the sanctuaries were relatively uncontaminated, with none of the samples having any measured chemical in excess of ERM values. The ERL value for chromium was exceeded in sediments at the OCNMS, but at a much lower percentage of stations (four of 30) compared to WA and OR non-sanctuary areas (31 of 70 stations). ERL values were exceeded for arsenic, cadmium, chromium, 2- methylnaphthalene, low molecular weight PAHs, total DDT, and 4,4′-DDE at multiple sites within the CINMS. However, cases where total DDT, 4,4′-DDE, and chromium exceeded the ERL values were notably less prevalent at CINMS than in non-sanctuary waters of CA. In contrast, 2-methylnaphthalene above the ERL was much more prevalent in sediments at the CINMS compared to non-sanctuary waters off the coast of CA. While there are natural background sources of PAHs from oil seeps throughout the SCB, this does not explain the higher incidence of 2-methylnaphthalene contamination around CINMS. Two stations in CINMS also had levels of TOC (> 5%) potentially harmful to benthic fauna, though none of these sites exhibited symptoms of impaired benthic condition. This study showed no major evidence of extensive biological impacts linked to measured stressors. There were only two stations, both in CA, where low numbers of benthic species, diversity, or total faunal abundance co-occurred with high sediment contamination or low DO in bottom water. Such general lack of concordance suggests that these offshore waters are currently in good condition, with the lower-end values of the various biological attributes representing parts of a normal reference range controlled by natural factors. Results of multiple linear regression, performed using full model procedures to test for effects of combined abiotic environmental factors, suggested that latitude and depth had significant influences on benthic variables regionwide. Latitude had a significant inverse influence on all three of the above benthic variables, i.e. with values increasing as latitude decreased (p< 0.01), while depth had a significant direct influence on diversity (p < 0.001) and inverse effect on density (p <0.01). None of these variables varied significantly in relation to sediment % fines (at p< 0.1), although in general there was a tendency for muddier sediments (higher % fines) to have lower species richness and diversity and higher densities than coarser sediments. Alternatively, it is possible that for some of these sites the lower values of benthic variables reflect symptoms of disturbance induced by other unmeasured stressors. The indicators in this study included measures of stressors (e.g., chemical contaminants, eutrophication) that are often associated with adverse biological impacts in shallower estuarine and inland ecosystems. However, there may be other sources of humaninduced stress in these offshore systems (e.g., bottom trawling) that pose greater risks to ambient living resources and which have not been captured. Future monitoring efforts in these offshore areas should include indicators of such alternative sources of disturbance. (137pp.) (PDF contains 167 pages)

Molecular bases of classic galactosemia : searching for new therapeutic strategies

Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2014

Statistical hypothesis testing and common misinterpretations: should we abandon p-value in forensic science applications?

Many people regard the concept of hypothesis testing as fundamental to inferential statistics. Various schools of thought, in particular frequentist and Bayesian, have promoted radically different solutions for taking a decision about the plausibility of competing hypotheses. Comprehensive philosophical comparisons about their advantages and drawbacks are widely available and continue to span over large debates in the literature. More recently, controversial discussion was initiated by an editorial decision of a scientific journal [1] to refuse any paper submitted for publication containing null hypothesis testing procedures. Since the large majority of papers published in forensic journals propose the evaluation of statistical evidence based on the so called p-values, it is of interest to expose the discussion of this journal's decision within the forensic science community. This paper aims to provide forensic science researchers with a primer on the main concepts and their implications for making informed methodological choices.

Análise da efetividade do transplante renal na qualidade de vida dos receptores no estado do Rio Grande do Norte

This study was developed with the aim of analyzing the effectiveness of renal transplantation on quality of life of kidney recipients in the Rio Grande do Norte State. This is a descriptive study with longitudinal design, panel type with quantitative approach to data analysis. The Quality of Life (QoL) of chronic disease kidney patients before and after kidney transplantation was assessed by the WHOQOL-bref, The population consisted of patients in pre and post-renal transplantation, the sample had 63 patients older than 18 years. The study was conducted after approval by the Research Ethics Committee of the Onofre Lopes University Hospital, Federal University of Rio Grande do Norte, No. CAAE 0008.0.294.000-10. Data collection was performed at a referral center for renal transplantation in Rio Grande do Norte, from May 2010 to May 2013. Data were analyzed using descriptive statistics and presented in tables and graphs. For statistical analyzes, Microsoft Excel XP and SPSS 15.0 software were used. The tests used were simple variance (ANOVA), t-test, Mann-Whitney and Wilcoxon test to compare means, and Spearman correlations. P values <0.05 were considered significant. The demographic data showed a predominance of people between 18 and 45 years (68.2%) with a mean age of 39.9 years (SD 12.2), male (63.5%), married (58.7%), with children (51.0%). Regarding the education level was observed that 49.2% of participants had completed primary school, and most did not engage in any work activity (90.4%) during the study period. Hemodialysis was the predominant renal replacement therapy (96.8%) and the average waiting time for execution of transplantation was 1.9 years (SD 1.9). Comparison of QoL before and after transplantation showed significant differences in all areas analyzed, demonstrating that kidney transplantation had a positive impact on QoL in chronic renal patients undergoing kidney transplantation. Sociodemographic factors did not influence the quality of life in this group of patients, indicating that transplantation was the main factor to explain the improvement in quality of life. Thus, the alternative hypothesis of the study was accept, that there is a significant difference in quality of life before and after kidney transplant. It is expected that the results of this study may contribute to the development of strategies to encourage organ donation and kidney transplantation process

Associação entre o nível de atividade física habitual e a prática de atividade física realizada na infância em escolares do ensino fundamental de João Pessoa - PB

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Produção de progesterona pelas células luteínicas esteroidogênicas bovina cultivadas e co-cultivadas in vitro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Human Bone Morphogenetic Protein-2 Use for Maxillary Reconstruction in Cleft Lip and Palate Patients

Background: The conventional methods of maxillary alveolar reconstruction in patient with cleft are the periosteoplasty and autologous bone grafting. As an important alternative of bone substitution, there is the recombinant human bone morphogenetic protein-2 (rhBMP-2). This study compares the rhBMP-2 with periosteoplasty and autologous bone grafting. Methods: Patients with cleft and alveolar defect were divided into 3 groups of 6 patients who underwent to autologous iliac crest bone grafting, resorbable collagen sponge with rhBMP2, and periosteoplasty, respectively. The analysis was performed through computed tomographic scan preoperatively and at months 3, 6, and 12 postoperatively. The variables analyzed were the alveolar defect volume, formed bone volume, bone formation rate, maxillary height repair rate, and the formed bone density mean. Results: The formed bone volume was similar comparing the bone graft and BMP groups at 1-year postoperative analysis (P = 0.58). Both of them had the formed bone volume significantly larger than the periosteoplasty group at 3 and 6 months postoperatively. In this last group, the 1-year follow-up was canceled because the bone formation was insufficient. The bone formation rate, the maxillary height repair rate, and the mean of density of the formed bone were similar in the bone graft and BMP groups at 1-year follow-up with P values of 0.93, 0.90, and 0.81, respectively. Conclusions: The amount of formed bone in the periosteoplasty group was insufficient. There was no difference among the bone graft and rhBMP-2 therapy considering the parameters analyzed.

Further results in J and CTOD estimation procedures for SE(T) fracture specimens - Part I: Homogeneous materials

This study provides further developments of the evaluation procedure for J and CTOD in SE(T) fracture specimens based on plastic eta-factors and load separation analysis. Non-linear finite element analyses for plane-strain and 3-D models provide the relationship between plastic work and crack driving forces which define the eta-values. Further analyses based on the load separation method define alternative eta-values for the analyzed specimen configurations. Overall, the present results provide improved estimation equations for J and CTOD as a function of loading condition (pin load vs. clamp ends), crack geometry and strain hardening properties. (C) 2011 Elsevier Ltd. All rights reserved.

Multiple testing in spatial epidemiology: a Bayesian approach

In this work we aim to propose a new approach for preliminary epidemiological studies on Standardized Mortality Ratios (SMR) collected in many spatial regions. A preliminary study on SMRs aims to formulate hypotheses to be investigated via individual epidemiological studies that avoid bias carried on by aggregated analyses. Starting from collecting disease counts and calculating expected disease counts by means of reference population disease rates, in each area an SMR is derived as the MLE under the Poisson assumption on each observation. Such estimators have high standard errors in small areas, i.e. where the expected count is low either because of the low population underlying the area or the rarity of the disease under study. Disease mapping models and other techniques for screening disease rates among the map aiming to detect anomalies and possible high-risk areas have been proposed in literature according to the classic and the Bayesian paradigm. Our proposal is approaching this issue by a decision-oriented method, which focus on multiple testing control, without however leaving the preliminary study perspective that an analysis on SMR indicators is asked to. We implement the control of the FDR, a quantity largely used to address multiple comparisons problems in the eld of microarray data analysis but which is not usually employed in disease mapping. Controlling the FDR means providing an estimate of the FDR for a set of rejected null hypotheses. The small areas issue arises diculties in applying traditional methods for FDR estimation, that are usually based only on the p-values knowledge (Benjamini and Hochberg, 1995; Storey, 2003). Tests evaluated by a traditional p-value provide weak power in small areas, where the expected number of disease cases is small. Moreover tests cannot be assumed as independent when spatial correlation between SMRs is expected, neither they are identical distributed when population underlying the map is heterogeneous. The Bayesian paradigm oers a way to overcome the inappropriateness of p-values based methods. Another peculiarity of the present work is to propose a hierarchical full Bayesian model for FDR estimation in testing many null hypothesis of absence of risk.We will use concepts of Bayesian models for disease mapping, referring in particular to the Besag York and Mollié model (1991) often used in practice for its exible prior assumption on the risks distribution across regions. The borrowing of strength between prior and likelihood typical of a hierarchical Bayesian model takes the advantage of evaluating a singular test (i.e. a test in a singular area) by means of all observations in the map under study, rather than just by means of the singular observation. This allows to improve the power test in small areas and addressing more appropriately the spatial correlation issue that suggests that relative risks are closer in spatially contiguous regions. The proposed model aims to estimate the FDR by means of the MCMC estimated posterior probabilities b i's of the null hypothesis (absence of risk) for each area. An estimate of the expected FDR conditional on data (\FDR) can be calculated in any set of b i's relative to areas declared at high-risk (where thenull hypothesis is rejected) by averaging the b i's themselves. The\FDR can be used to provide an easy decision rule for selecting high-risk areas, i.e. selecting as many as possible areas such that the\FDR is non-lower than a prexed value; we call them\FDR based decision (or selection) rules. The sensitivity and specicity of such rule depend on the accuracy of the FDR estimate, the over-estimation of FDR causing a loss of power and the under-estimation of FDR producing a loss of specicity. Moreover, our model has the interesting feature of still being able to provide an estimate of relative risk values as in the Besag York and Mollié model (1991). A simulation study to evaluate the model performance in FDR estimation accuracy, sensitivity and specificity of the decision rule, and goodness of estimation of relative risks, was set up. We chose a real map from which we generated several spatial scenarios whose counts of disease vary according to the spatial correlation degree, the size areas, the number of areas where the null hypothesis is true and the risk level in the latter areas. In summarizing simulation results we will always consider the FDR estimation in sets constituted by all b i's selected lower than a threshold t. We will show graphs of the\FDR and the true FDR (known by simulation) plotted against a threshold t to assess the FDR estimation. Varying the threshold we can learn which FDR values can be accurately estimated by the practitioner willing to apply the model (by the closeness between\FDR and true FDR). By plotting the calculated sensitivity and specicity (both known by simulation) vs the\FDR we can check the sensitivity and specicity of the corresponding\FDR based decision rules. For investigating the over-smoothing level of relative risk estimates we will compare box-plots of such estimates in high-risk areas (known by simulation), obtained by both our model and the classic Besag York Mollié model. All the summary tools are worked out for all simulated scenarios (in total 54 scenarios). Results show that FDR is well estimated (in the worst case we get an overestimation, hence a conservative FDR control) in small areas, low risk levels and spatially correlated risks scenarios, that are our primary aims. In such scenarios we have good estimates of the FDR for all values less or equal than 0.10. The sensitivity of\FDR based decision rules is generally low but specicity is high. In such scenario the use of\FDR = 0:05 or\FDR = 0:10 based selection rule can be suggested. In cases where the number of true alternative hypotheses (number of true high-risk areas) is small, also FDR = 0:15 values are well estimated, and \FDR = 0:15 based decision rules gains power maintaining an high specicity. On the other hand, in non-small areas and non-small risk level scenarios the FDR is under-estimated unless for very small values of it (much lower than 0.05); this resulting in a loss of specicity of a\FDR = 0:05 based decision rule. In such scenario\FDR = 0:05 or, even worse,\FDR = 0:1 based decision rules cannot be suggested because the true FDR is actually much higher. As regards the relative risk estimation, our model achieves almost the same results of the classic Besag York Molliè model. For this reason, our model is interesting for its ability to perform both the estimation of relative risk values and the FDR control, except for non-small areas and large risk level scenarios. A case of study is nally presented to show how the method can be used in epidemiology.

ASSOCIATON TESTS THAT ACCOMMODATE GENOTYPING ERRORS

High-throughput SNP arrays provide estimates of genotypes for up to one million loci, often used in genome-wide association studies. While these estimates are typically very accurate, genotyping errors do occur, which can influence in particular the most extreme test statistics and p-values. Estimates for the genotype uncertainties are also available, although typically ignored. In this manuscript, we develop a framework to incorporate these genotype uncertainties in case-control studies for any genetic model. We verify that using the assumption of a “local alternative” in the score test is very reasonable for effect sizes typically seen in SNP association studies, and show that the power of the score test is simply a function of the correlation of the genotype probabilities with the true genotypes. We demonstrate that the power to detect a true association can be substantially increased for difficult to call genotypes, resulting in improved inference in association studies.

GENE SET ENRICHMENT ANALYSIS MADE SIMPLE

Among the many applications of microarray technology, one of the most popular is the identification of genes that are differentially expressed in two conditions. A common statistical approach is to quantify the interest of each gene with a p-value, adjust these p-values for multiple comparisons, chose an appropriate cut-off, and create a list of candidate genes. This approach has been criticized for ignoring biological knowledge regarding how genes work together. Recently a series of methods, that do incorporate biological knowledge, have been proposed. However, many of these methods seem overly complicated. Furthermore, the most popular method, Gene Set Enrichment Analysis (GSEA), is based on a statistical test known for its lack of sensitivity. In this paper we compare the performance of a simple alternative to GSEA.We find that this simple solution clearly outperforms GSEA.We demonstrate this with eight different microarray datasets.

Response of Nodularia spumigena to pCO2 - Part 3: Turnover of phosphorus compounds

Diazotrophic cyanobacteria often form extensive summer blooms in the Baltic Sea driving their environment into phosphate limitation. One of the main species is the heterocystous cyanobacterium Nodularia spumigena. N. spumigena exhibits accelerated uptake of phosphate through the release of the exoenzyme alkaline phosphatase that also serves as an indicator of the hydrolysis of dissolved organic phosphorus (DOP). The present study investigated the utilization of DOP and its compounds (e.g. ATP) by N. spumigena during growth under varying CO2 concentrations, in order to estimate potential consequences of ocean acidification on the cell's supply with phosphorus. Cell growth, phosphorus pool fractions, and four DOP-compounds (ATP, DNA, RNA, and phospholipids) were determined in three set-ups with different CO2 concentrations (341, 399, and 508 µatm) during a 15-day batch experiment. The results showed rapid depletion of dissolved inorganic phosphorus (DIP) in all pCO2 treatments while DOP utilization increased with elevated pCO2, in parallel with the growth stimulation of N. spumigena. During the growth phase, DOP uptake was enhanced by a factor of 1.32 at 399 µatm and of 2.25 at 508 µatm compared to the lowest pCO2 concentration. Among the measured DOP compounds, none was found to accumulate preferentially during the incubation or in response to a specific pCO2 treatment. However, at the beginning 61.9 ± 4.3% of the DOP were not characterized but comprised the most highly utilized fraction. This is demonstrated by the decrement of this fraction to 27.4 ± 9.9% of total DOP during the growth phase, especially in response to the medium and high pCO2 treatment. Our results indicate a stimulated growth of diazotrophic cyanobacteria at increasing CO2 concentrations that is accompanied by increasing utilization of DOP as an alternative P source.

Métodos de máxima verosimilitud en ecología y su aplicación en modelos de vecindad

Los métodos de máxima verosimilitud (MMV) ofrecen un marco alternativo a la estadística frecuentista convencional, alejándose del uso del p-valor para el rechazo de una única hipótesis nula y optando por el uso de las verosimilitudes para evaluar el grado de apoyo en los datos a un conjunto de hipótesis alternativas (o modelos) de interés para el investigador. Estos métodos han sido ampliamente aplicados en ecología en el marco de los modelos de vecindad. Dichos modelos usan una aproximación espacialmente explícita para describir procesos demográficos de plantas o procesos ecosistémicos en función de los atributos de los individuos vecinos. Se trata por tanto de modelos fenomenológicos cuya principal utilidad radica en funcionar como herramientas de síntesis de los múltiples mecanismos por los que las especies pueden interactuar e influenciar su entorno, proporcionando una medida del efecto per cápita de individuos de distintas características (ej. tamaño, especie, rasgos fisiológicos) sobre los procesos de interés. La gran ventaja de aplicar los MMV en el marco de los modelos de vecindad es que permite ajustar y comparar múltiples modelos que usen distintos atributos de los vecinos y/o formas funcionales para seleccionar aquel con mayor soporte empírico. De esta manera, cada modelo funcionará como un “experimento virtual” para responder preguntas relacionadas con la magnitud y extensión espacial de los efectos de distintas especies coexistentes, y extraer conclusiones sobre posibles implicaciones para el funcionamiento de comunidades y ecosistemas. Este trabajo sintetiza las técnicas de implementación de los MMV y los modelos de vecindad en ecología terrestre, resumiendo su uso hasta la fecha y destacando nuevas líneas de aplicación.