Subclinical hypothyroidism and the risk of coronary heart disease and mortality: an individual participant data analysis from nine prospective cohort studies

Texte intégral: http://www.springerlink.com/content/3q68180337551r47/fulltext.pdf

A general model to predict individual exposure to solar UV by using ambient irradiance data

Excessive exposure to solar ultraviolet (UV) is the main cause of skin cancer. Specific prevention should be further developed to target overexposed or highly vulnerable populations. A better characterisation of anatomical UV exposure patterns is however needed for specific prevention. To develop a regression model for predicting the UV exposure ratio (ER, ratio between the anatomical dose and the corresponding ground level dose) for each body site without requiring individual measurements. A 3D numeric model (SimUVEx) was used to compute ER for various body sites and postures. A multiple fractional polynomial regression analysis was performed to identify predictors of ER. The regression model used simulation data and its performance was tested on an independent data set. Two input variables were sufficient to explain ER: the cosine of the maximal daily solar zenith angle and the fraction of the sky visible from the body site. The regression model was in good agreement with the simulated data ER (R(2)=0.988). Relative errors up to +20% and -10% were found in daily doses predictions, whereas an average relative error of only 2.4% (-0.03% to 5.4%) was found in yearly dose predictions. The regression model predicts accurately ER and UV doses on the basis of readily available data such as global UV erythemal irradiance measured at ground surface stations or inferred from satellite information. It renders the development of exposure data on a wide temporal and geographical scale possible and opens broad perspectives for epidemiological studies and skin cancer prevention.

Cognitive and Emotional Deficits Associated with Minor and Serious Delinquency in High-Risk Adolescents

This study aims at evaluating how minor and serious delinquency relates to cognitive and emotional functioning in high-risk adolescents, taking problematic substance use into account. In 80 high-risk adolescent males (13-19 years), the frequency of minor and serious offences committed over the last year was predicted, in multiple regression analyses, from problematic substance use, intellectual efficiency, trait impulsivity, alexithymia (inability to express feelings in words), and cognitive coping strategies. Both minor and serious delinquency were more frequent in adolescents with more problematic substance use and higher intellectual efficacy. Minor delinquency was further related to a tendency to act out when experiencing negative emotions, and difficulties in focusing energy on instrumental action when under stress; while serious delinquency was predominantly and strongly related to rigid and dichotomous thinking. The results underline the heterogeneous nature of delinquency, minor offences being primarily associated with emotional regulation deficits, while major offences are related with a lack of cognitive flexibility.

Effects of different Incentives on Attrition and Fieldwork Effort in Telephone Household Panel Surveys

Little is known about sample behavior and fieldwork effects of different incentives introduced in a household panel survey. This is especially true for telephone surveys. In a randomized experiment, the Swiss Household Panel implemented one prepaid and two promised nonmonetary incentives in the range of 10 to 15 Swiss Francs (7-10 e), plus a no incentive control group. The aim of the paper is to compare effects of these incentives especially on cooperation, but also on sample selection and fieldwork effort, separated by the household and the subsequent individual level. We find small positive cooperation effects of the prepaid incentive on both the household and the individual level especially in larger households. Sample composition is affected to a very minor extent. Finally, incentives tend to save fieldwork time and partially the number of contacts needed on the individual level.

Collective victimisation and collective guilt in the former Yugoslavia : the interplay between individual, local and societal levels

The thesis examines the impact of collective war victimization on individuals' readiness to accept or assign collective guilt for past war atrocities. As a complement to previous studies, its aim is to articulate an integrated approach to collective victimization, which distinguishes between individual-, communal-, and societal-level consequences of warfare. Building on a social representation approach, it is guided by the assumption that individuals form beliefs about a conflict through their personal experiences of victimization, communal experiences of warfare that occur in their proximal surrounding, and the mass- mediatised narratives that circulate in a society's public sphere. Four empirical studies test the hypothesis that individuals' beliefs about the conflict depend on the level and type of war experiences to which they have been exposed, that is, on informative and normative micro and macro contexts in which they are embedded. The studies have been conducted in the context of the Yugoslav wars that attended the breakup of Yugoslavia, a series of wars fought between 1991 and 2001 during which numerous war atrocities were perpetrated causing a massive victimisation of population. To examine the content and impact of war experiences at each level of analysis, the empirical studies employed various methodological strategies, from quantitative analyses of a representative public opinion survey, to qualitative analyses of media content and political speeches. Study 1 examines the impact of individual- and communal- level war experiences on individuals' acceptance and assignment of collective guilt. It further examines the impact of the type of communal level victimization: exposure to symmetric (i.e., violence that similarly affects members of different ethnic groups, including adversaries) and asymmetric violence. The main goal of Study 2 is to examine the structural and political circumstances that enhance collective guilt assignment. While the previous studies emphasize the role of past victimisation, Study 2 tests the assumption that the political demobilisation strategy employed by elites facing public discontent in the collective system-threatening circumstances can fuel out-group blame. Studies 3 and 4 have been conducted predominantly in the context of Croatia and examine rhetoric construction of the dominant politicized narrative of war in a public sphere (Study 3) and its maintenance through public delegitimization of alternative (critical) representations (Study 4). Study 4 further examines the likelihood that highly identified group members adhere to publicly delegitimized critical stances on war. - Cette thèse étudie l'impact de la victimisation collective de guerre sur la capacité des individus à accepter ou à attribuer une culpabilité collective liée à des atrocités commises en temps de guerre. En compléments aux recherches existantes, le but de ce travail est de définir une approche intégrative de la victimisation collective, qui distingue les conséquences de la guerre aux niveaux individuel, régional et sociétal. En partant de l'approche des représentations sociales, cette thèse repose sur le postulat que les individus forment des croyances sur un conflit au travers de leurs expériences personnelles de victimisation, de leurs expériences de guerre lorsque celle-ci se déroule près d'eux, ainsi qu'au travers des récits relayés par les mass media. Quatre études testent l'hypothèse que les croyances des individus dépendent des niveaux et des types d'expériences de guerre auxquels ils ont été exposés, c'est-à-dire, des contextes informatifs et normatifs, micro et macro dans lesquels ils sont insérés. Ces études ont été réalisées dans le contexte des guerres qui, entre 1991 et 2001, ont suivi la dissolution de la Yougoslavie et durant lesquelles de nombreuses atrocités de guerre ont été commises, causant une victimisation massive de la population. Afin d'étudier le contenu et l'impact des expériences de guerre sur chaque niveau d'analyse, différentes stratégies méthodologiques ont été utilisées, des analyses quantitatives sur une enquête représentative d'opinion publique aux analyses qualitatives de contenu de médias et de discours politiques. L'étude 1 étudie l'impact des expériences de guerre individuelles et régionales sur l'acceptation et l'attribution de la culpabilité collective par les individus. Elle examine aussi l'impact du type de victimisation régionale : exposition à la violence symétrique (i.e., violence qui touche les membres de différents groupes ethniques, y compris les adversaires) et asymétrique. L'étude 2 se penche sur les circonstances structurelles et politiques qui augmentent l'attribution de culpabilité collective. Alors que les recherches précédentes ont mis l'accent sur le rôle de la victimisation passée, l'étude 2 teste l'hypothèse que la stratégie de démobilisation politique utilisée par les élites pour faire face à l'insatisfaction publique peut encourager l'attribution de la culpabilité à l'exogroupe. Les études 3 et 4 étudient, principalement dans le contexte croate, la construction rhétorique du récit de guerre politisé dominant (étude 3) et son entretien à travers la délégitimation publique des représentations alternatives (critiques] (étude 4). L'étude 4 examine aussi la probabilité qu'ont les membres de groupe fortement identifiés d'adhérer à des points de vue sur la guerre critiques et publiquement délégitimés.

Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data

BACKGROUND: Individually, randomised trials have not shown conclusively whether adjuvant chemotherapy benefits adult patients with localised resectable soft-tissue sarcoma.METHODS: A quantitative meta-analysis of updated data from individual patients from all available randomised trials was carried out to assess whether adjuvant chemotherapy improves overall survival, recurrence-free survival, and local and distant recurrence-free intervals (RFI) and whether chemotherapy is differentially effective in patients defined by age, sex, disease status at randomisation, disease site, histology, grade, tumour size, extent of resection, and use of radiotherapy.FINDINGS: 1568 patients from 14 trials of doxorubicin-based adjuvant chemotherapy were included (median follow-up 9.4 years). Hazard ratios of 0.73 (95% CI 0.56-0.94, p = 0.016) for local RFI, 0.70 (0.57-0.85, p = 0.0003) for distant RFI, and 0.75 (0.64-0.87, p = 0.0001) for overall recurrence-free survival, correspond to absolute benefits from adjuvant chemotherapy of 6% (95% CI 1-10), 10% (5-15), and 10% (5-15), respectively, at 10 years. For overall survival the hazard ratio of 0.89 (0.76-1.03) was not significant (p = 0.12), but represents an absolute benefit of 4% (1-9) at 10 years. These results were not affected by prespecified changes in the groups of patients analysed. There was no consistent evidence that the relative effect of adjuvant chemotherapy differed for any subgroup of patients for any endpoint. However, the best evidence of an effect of adjuvant chemotherapy for survival was seen in patients with sarcomas of the extremities.INTERPRETATION: The meta-analysis provides evidence that adjuvant doxorubicin-based chemotherapy significantly improves the time to local and distant recurrence and overall recurrence-free survival. There is a trend towards improved overall survival.

Coronary heart disease in primary care: accuracy of medical history and physical findings in patients with chest pain - a study protocol for a systematic review with individual patient data.

BACKGROUND: Chest pain is a common complaint in primary care, with coronary heart disease (CHD) being the most concerning of many potential causes. Systematic reviews on the sensitivity and specificity of symptoms and signs summarize the evidence about which of them are most useful in making a diagnosis. Previous meta-analyses are dominated by studies of patients referred to specialists. Moreover, as the analysis is typically based on study-level data, the statistical analyses in these reviews are limited while meta-analyses based on individual patient data can provide additional information. Our patient-level meta-analysis has three unique aims. First, we strive to determine the diagnostic accuracy of symptoms and signs for myocardial ischemia in primary care. Second, we investigate associations between study- or patient-level characteristics and measures of diagnostic accuracy. Third, we aim to validate existing clinical prediction rules for diagnosing myocardial ischemia in primary care. This article describes the methods of our study and six prospective studies of primary care patients with chest pain. Later articles will describe the main results. METHODS/DESIGN: We will conduct a systematic review and IPD meta-analysis of studies evaluating the diagnostic accuracy of symptoms and signs for diagnosing coronary heart disease in primary care. We will perform bivariate analyses to determine the sensitivity, specificity and likelihood ratios of individual symptoms and signs and multivariate analyses to explore the diagnostic value of an optimal combination of all symptoms and signs based on all data of all studies. We will validate existing clinical prediction rules from each of the included studies by calculating measures of diagnostic accuracy separately by study. DISCUSSION: Our study will face several methodological challenges. First, the number of studies will be limited. Second, the investigators of original studies defined some outcomes and predictors differently. Third, the studies did not collect the same standard clinical data set. Fourth, missing data, varying from partly missing to fully missing, will have to be dealt with.Despite these limitations, we aim to summarize the available evidence regarding the diagnostic accuracy of symptoms and signs for diagnosing CHD in patients presenting with chest pain in primary care. REVIEW REGISTRATION: Centre for Reviews and Dissemination (University of York): CRD42011001170.

Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease (PR) and reverse transcriptase (RT) inhibitors may display impaired infectivity and replication capacity. The individual contributions of mutated HIV-1 PR and RT to infectivity, replication, RT activity, and protein maturation (herein referred to as "fitness") in recombinant viruses were investigated by separately cloning PR, RT, and PR-RT cassettes from drug-resistant mutant viral isolates into the wild-type NL4-3 background. Both mutant PR and RT contributed to measurable deficits in fitness of viral constructs. In peripheral blood mononuclear cells, replication rates (means +/- standard deviations) of RT recombinants were 72.5% +/- 27.3% and replication rates of PR recombinants were 60.5% +/- 33.6% of the rates of NL4-3. PR mutant deficits were enhanced in CEM T cells, with relative replication rates of PR recombinants decreasing to 15.8% +/- 23.5% of NL4-3 replication rates. Cloning of the cognate RT improved fitness of some PR mutant clones. For a multidrug-resistant virus transmitted through sexual contact, RT constructs displayed a marked infectivity and replication deficit and diminished packaging of Pol proteins (RT content in virions diminished by 56.3% +/- 10.7%, and integrase content diminished by 23.3% +/- 18.4%), a novel mechanism for a decreased-fitness phenotype. Despite the identified impairment of recombinant clones, fitness of two of the three drug-resistant isolates was comparable to that of wild-type, susceptible viruses, suggestive of extensive compensation by genomic regions away from PR and RT. Only limited reversion of mutated positions to wild-type amino acids was observed for the native isolates over 100 viral replication cycles in the absence of drug selective pressure. These data underscore the complex relationship between PR and RT adaptive changes and viral evolution in antiretroviral drug-resistant HIV-1.

Assessing ageing of individual T lymphocytes: mission impossible?

Effector T lymphocytes are the progeny of a limited number of antigen-specific precursor cells and it has been estimated that clonotypic human T cells may expand million fold on their way reaching high cell numbers that are sufficient for immune protection. Moreover, memory T cell responses are characterized by repetitive expansion of antigen-specific T cell clonotypes, and limitations in the proliferative capacity could lead to immune senescence. Because telomeres progressively shorten as a function of cell division, telomere length is a powerful indicator of the replicative in vivo history of human T lymphocytes. In this review, we summarize observations made over the last decade on telomere length dynamics of well-defined T cell populations derived from healthy donors and patients with infectious disease or cancer. We focus on T cell differentiation, T cell ageing, and natural and vaccine induced immune responses. We also discuss the scientific evidence for in vivo replicative senescence of antigen-specific T cells, and evaluate the available methods for measuring telomere lengths and telomerase activity, and their potential and limitations to increase our understanding of T cell physiology.

Change in individual growth rate and its link to gill-net fishing in two sympatric whitefish species

Size-selective fishing is expected to affect traits such as individual growth rate, but the relationship between the fishery-linked selection differentials and the corresponding phenotypic changes is not well understood. We analysed a 25-year monitoring survey of sympatric populations of the two Alpine whitefish Coregonus albellus and C. fatioi. We determined the fishing-induced selection differentials on growth rates, the actual change of growth rates over time, and potential indicators of reproductive strategies that may change over time. We found marked declines in adult growth rate and significant selection differentials that may partly explain the observed declines. However, when comparing the two sympatric species, the selection differentials on adult growth were stronger in C. albellus while the decline in adult growth rate seemed more pronounced in C. fatioi. Moreover, the selection differential on juvenile growth was significant in C. albellus but not in C. fatioi, while a significant reduction in juvenile growth over the last 25 years was only found in C. fatioi. Our results suggest that size-selective fishing affects the genetics for individual growth in these whitefish, and that the link between selection differentials and phenotypic changes is influenced by species-specific factors.