Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.

OBJECTIVE: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. DATA EXTRACTION AND SYNTHESIS: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥ 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. CONCLUSIONS: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

Background: We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. Results: Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1) highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. Conclusion: Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3). Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer.

Study of tergal glands morphogenesis through an integrative analysis of genomic data

About 50% of living species are holometabolan insects. Therefore, unraveling the ori- gin of insect metamorphosis from the hemimetabolan (gradual metamorphosis) to the holometabolan (sudden metamorphosis at the end of the life cycle) mode is equivalent to explaining how all this biodiversity originated. One of the problems with studying the evolution from hemimetaboly to holometaboly is that most information is available only in holometabolan species. Within the hemimetabolan group, our model, the cock- roach Blattella germanica, is the most studied species. However, given that the study of adult morphogenesis at organismic level is still complex, we focused on the study of the tergal gland (TG) as a minimal model of metamorphosis. The TG is formed in tergites 7 and 8 (T7-8) in the last days of the last nymphal instar (nymph 6). The comparative study of four T7-T8 transcriptomes provided us with crucial keys of TG formation, but also essential information about the mechanisms and circuitry that allows the shift from nymphal to adult morphogenesis.

Is there any association between Hashimoto’s thyroiditis and thyroid cancer? A retrospective data analysis

AbstractObjective:To evaluate the association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC).Materials and Methods:The patients were evaluated by ultrasonography-guided fine needle aspiration cytology. Typical cytopathological aspects and/or classical histopathological findings were taken into consideration in the diagnosis of HT, and only histopathological results were considered in the diagnosis of PTC.Results:Among 1,049 patients with multi- or uninodular goiter (903 women and 146 men), 173 (16.5%) had cytopathological features of thyroiditis. Thirty-three (67.4%) out of the 49 operated patients had PTC, 9 (27.3%) of them with histopathological features of HT. Five (31.3%) out of the 16 patients with non-malignant disease also had HT. In the groups with HT, PTC, and PCT+HT, the female prevalence rate was 100%, 91.6%, and 77.8%, respectively. Mean age was 41.5, 43.3, and 48.5 years, respectively. No association was observed between the two diseases in the present study where HT occurred in 31.1% of the benign cases and in 27.3% of malignant cases (p = 0.8).Conclusion:In spite of the absence of association between HT and PCT, the possibility of malignancy in HT should always be considered because of the coexistence of the two diseases already reported in the literature.

Analysis of space-time environmental data in complex regions

This thesis develops a comprehensive and a flexible statistical framework for the analysis and detection of space, time and space-time clusters of environmental point data. The developed clustering methods were applied in both simulated datasets and real-world environmental phenomena; however, only the cases of forest fires in Canton of Ticino (Switzerland) and in Portugal are expounded in this document. Normally, environmental phenomena can be modelled as stochastic point processes where each event, e.g. the forest fire ignition point, is characterised by its spatial location and occurrence in time. Additionally, information such as burned area, ignition causes, landuse, topographic, climatic and meteorological features, etc., can also be used to characterise the studied phenomenon. Thereby, the space-time pattern characterisa- tion represents a powerful tool to understand the distribution and behaviour of the events and their correlation with underlying processes, for instance, socio-economic, environmental and meteorological factors. Consequently, we propose a methodology based on the adaptation and application of statistical and fractal point process measures for both global (e.g. the Morisita Index, the Box-counting fractal method, the multifractal formalism and the Ripley's K-function) and local (e.g. Scan Statistics) analysis. Many measures describing the space-time distribution of environmental phenomena have been proposed in a wide variety of disciplines; nevertheless, most of these measures are of global character and do not consider complex spatial constraints, high variability and multivariate nature of the events. Therefore, we proposed an statistical framework that takes into account the complexities of the geographical space, where phenomena take place, by introducing the Validity Domain concept and carrying out clustering analyses in data with different constrained geographical spaces, hence, assessing the relative degree of clustering of the real distribution. Moreover, exclusively to the forest fire case, this research proposes two new methodologies to defining and mapping both the Wildland-Urban Interface (WUI) described as the interaction zone between burnable vegetation and anthropogenic infrastructures, and the prediction of fire ignition susceptibility. In this regard, the main objective of this Thesis was to carry out a basic statistical/- geospatial research with a strong application part to analyse and to describe complex phenomena as well as to overcome unsolved methodological problems in the characterisation of space-time patterns, in particular, the forest fire occurrences. Thus, this Thesis provides a response to the increasing demand for both environmental monitoring and management tools for the assessment of natural and anthropogenic hazards and risks, sustainable development, retrospective success analysis, etc. The major contributions of this work were presented at national and international conferences and published in 5 scientific journals. National and international collaborations were also established and successfully accomplished. -- Cette thèse développe une méthodologie statistique complète et flexible pour l'analyse et la détection des structures spatiales, temporelles et spatio-temporelles de données environnementales représentées comme de semis de points. Les méthodes ici développées ont été appliquées aux jeux de données simulées autant qu'A des phénomènes environnementaux réels; nonobstant, seulement le cas des feux forestiers dans le Canton du Tessin (la Suisse) et celui de Portugal sont expliqués dans ce document. Normalement, les phénomènes environnementaux peuvent être modélisés comme des processus ponctuels stochastiques ou chaque événement, par ex. les point d'ignition des feux forestiers, est déterminé par son emplacement spatial et son occurrence dans le temps. De plus, des informations tels que la surface bru^lée, les causes d'ignition, l'utilisation du sol, les caractéristiques topographiques, climatiques et météorologiques, etc., peuvent aussi être utilisées pour caractériser le phénomène étudié. Par conséquent, la définition de la structure spatio-temporelle représente un outil puissant pour compren- dre la distribution du phénomène et sa corrélation avec des processus sous-jacents tels que les facteurs socio-économiques, environnementaux et météorologiques. De ce fait, nous proposons une méthodologie basée sur l'adaptation et l'application de mesures statistiques et fractales des processus ponctuels d'analyse global (par ex. l'indice de Morisita, la dimension fractale par comptage de boîtes, le formalisme multifractal et la fonction K de Ripley) et local (par ex. la statistique de scan). Des nombreuses mesures décrivant les structures spatio-temporelles de phénomènes environnementaux peuvent être trouvées dans la littérature. Néanmoins, la plupart de ces mesures sont de caractère global et ne considèrent pas de contraintes spatiales com- plexes, ainsi que la haute variabilité et la nature multivariée des événements. A cet effet, la méthodologie ici proposée prend en compte les complexités de l'espace géographique ou le phénomène a lieu, à travers de l'introduction du concept de Domaine de Validité et l'application des mesures d'analyse spatiale dans des données en présentant différentes contraintes géographiques. Cela permet l'évaluation du degré relatif d'agrégation spatiale/temporelle des structures du phénomène observé. En plus, exclusif au cas de feux forestiers, cette recherche propose aussi deux nouvelles méthodologies pour la définition et la cartographie des zones périurbaines, décrites comme des espaces anthropogéniques à proximité de la végétation sauvage ou de la forêt, et de la prédiction de la susceptibilité à l'ignition de feu. A cet égard, l'objectif principal de cette Thèse a été d'effectuer une recherche statistique/géospatiale avec une forte application dans des cas réels, pour analyser et décrire des phénomènes environnementaux complexes aussi bien que surmonter des problèmes méthodologiques non résolus relatifs à la caractérisation des structures spatio-temporelles, particulièrement, celles des occurrences de feux forestières. Ainsi, cette Thèse fournit une réponse à la demande croissante de la gestion et du monitoring environnemental pour le déploiement d'outils d'évaluation des risques et des dangers naturels et anthro- pogéniques. Les majeures contributions de ce travail ont été présentées aux conférences nationales et internationales, et ont été aussi publiées dans 5 revues internationales avec comité de lecture. Des collaborations nationales et internationales ont été aussi établies et accomplies avec succès.

An update on EMU sovereign yield spread drivers in times of crisis: A panel data analysis

We empirically investigate the determinants of EMU sovereign bond yield spreads with respect to the German bund. Using panel data techniques, we examine the role of a wide set of potential drivers. To our knowledge, this paper presents one of the most exhaustive compilations of the variables used in the literature to study the behaviour of sovereign yield spreads and, in particular, to gauge the effect on these spreads of changes in market sentiment and risk aversion. We use a sample of both central and peripheral countries from January 1999 to December 2012 and assess whether there were significant changes after the outbreak of the euro area debt crisis. Our results suggest that the rise in sovereign risk in central countries can only be partially explained by the evolution of local macroeconomic variables in those countries.

An update on EMU sovereign yield spread drivers in times of crisis: A panel data analysis

We empirically investigate the determinants of EMU sovereign bond yield spreads with respect to the German bund. Using panel data techniques, we examine the role of a wide set of potential drivers. To our knowledge, this paper presents one of the most exhaustive compilations of the variables used in the literature to study the behaviour of sovereign yield spreads and, in particular, to gauge the effect on these spreads of changes in market sentiment and risk aversion. We use a sample of both central and peripheral countries from January 1999 to December 2012 and assess whether there were significant changes after the outbreak of the euro area debt crisis. Our results suggest that the rise in sovereign risk in central countries can only be partially explained by the evolution of local macroeconomic variables in those countries.

Analysis of laboratory intercomparison data: a matter of independence

When laboratory intercomparison exercises are conducted, there is no a priori dependence of the concentration of a certain compound determined in one laboratory to that determined by another(s). The same applies when comparing different methodologies. A existing data set of total mercury readings in fish muscle samples involved in a Brazilian intercomparison exercise was used to show that correlation analysis is the most effective statistical tool in this kind of experiments. Problems associated with alternative analytical tools such as mean or paired 't'-test comparison and regression analysis are discussed.

Panel Data Stochastic Convergence Analysis of the Mexican Regions

The stochastic convergence amongst Mexican Federal entities is analyzed in panel data framework. The joint consideration of cross-section dependence and multiple structural breaks is required to ensure that the statistical inference is based on statistics with good statistical properties. Once these features are accounted for, evidence in favour of stochastic convergence is found. Since stochastic convergence is a necessary, yet insufficient condition for convergence as predicted by economic growth models, the paper also investigates whether-convergence process has taken place. We found that the Mexican states have followed either heterogeneous convergence patterns or divergence process throughout the analyzed period.

Compositional data analysis of vote shares in the 2001 Australian Federal election

First application of compositional data analysis techniques to Australian election data

Regression analysis of compositional data when both the dependent variable and independent variable are components

It is well known that regression analyses involving compositional data need special attention because the data are not of full rank. For a regression analysis where both the dependent and independent variable are components we propose a transformation of the components emphasizing their role as dependent and independent variables. A simple linear regression can be performed on the transformed components. The regression line can be depicted in a ternary diagram facilitating the interpretation of the analysis in terms of components. An exemple with time-budgets illustrates the method and the graphical features

The single principle of compositional data analysis, continuing fallacies, confusionsand misunderstandings and some suggested remedies

In any discipline, where uncertainty and variability are present, it is important to haveprinciples which are accepted as inviolate and which should therefore drive statisticalmodelling, statistical analysis of data and any inferences from such an analysis.Despite the fact that two such principles have existed over the last two decades andfrom these a sensible, meaningful methodology has been developed for the statisticalanalysis of compositional data, the application of inappropriate and/or meaninglessmethods persists in many areas of application. This paper identifies at least tencommon fallacies and confusions in compositional data analysis with illustrativeexamples and provides readers with necessary, and hopefully sufficient, arguments topersuade the culprits why and how they should amend their ways

Labour segregation and immigrant and native-born wage distributions in Spain: an analysis using matched employer-employee data

This article carries out an empirical examination of the origin of the differences between immigrant and native-born wage structures in the Spanish labour market. Especial attention is given in the analysis to the role played by occupational and workplace segregation of immigrants. Legal immigrants from developing countries exhibit lower mean wages and a more compressed wage structure than native-born workers. By contrast, immigrants from developed countries display higher mean wages and a more dispersed wage structure. The main empirical finding is that the disparities in the wage distributions for the native-born and both groups of immigrants are largely explained by their different observed characteristics, with a particularly important influence in this context of workplace and, particularly, occupational segregation.