Immunological Signatures Identifying Different Stages of Latent Mycobacterium tuberculosis Infection and Discriminating Latent from Active Tuberculosis in Humans

Objectives: One third of the world population is considered latently infected with Mycobacterium tuberculosis(LTBI) and sterilizing this reservoir of bacteria that may reactivate is required for tuberculosis (TB) elimination. Thegroup of individuals with LTBI is heterogeneous with some of them being more at risk to develop TB disease thanothers. Improved diagnosis of subjects with LTBI is needed, allowing to differentiate subjects with LTBI from thosewith active TB, and to select among LTBI subjects those who are more at risk to develop active TB. We havecharacterized at the cellular level both the quantitative and qualitative T cell responses to different mycobacterialantigens in selected populations of infected subjects in order to identify new biomarkers that could help to identify M.tuberculosis-infected subjects and to stratify them in risk groups for reactivation of the infection.Methods: Lymphoblast frequencies and cytokine production (IFN-γ, TNF-α, IL-2) among CD4+ and CD8+ T cellswere analyzed by flow cytometry after in vitro stimulation with the latency antigen heparin-binding haemagglutinin(HBHA) or early-secreted antigen Target-6 (ESAT-6) of peripheral blood mononuclear cells from clinically wellcharacterized M. tuberculosis-infected humans (28 LTBI, 22 TB disease,12 controls). The LTBI group definedaccording to the Center for Disease Control guidelines was subdivided into QuantiFERON-TB Gold in-Tube (QFT)positive and negative subgroups.Results: Similar to TB patients, QFT+ LTBI subjects had higher proportions of HBHA-induced TNF-αsingle+ CD4+lymphocytes than QFT- LTBI subjects (p<0.05). Compared to LTBI subjects, TB patients had higher frequencies ofESAT-6-induced CD8+ lymphoblasts (p<0.001), higher proportions of ESAT-6-induced IFN-γ+TNF-α+ CD4+ Tlymphocytes (p<0.05), and lower proportions of HBHA-induced IFN-γ+TNF-α+IL-2+ (p<0.05) CD4+ T lymphocytes.Conclusions: These data provide new biomarkers to discriminate active TB from LTBI, and more interestingly,help to identify LTBI subjects with increased likelihood to develop TB disease.

Violence Exposure and Welfare over Time: Evidence from the Burundi Civil War

We investigate the relationship between exposure to conflict and poverty dynamics over time, using original three-waves panel data for Burundi which tracked individuals and reported local-level violence exposure from 1998 to 2012. Firstly, the data reveal that headcount poverty has not changed since 1998 while we observe multiple transitions into and out of poverty. Moreover, households exposed to the war exhibit a lower level of welfare than non-exposed households, with the difference between the two groups predicted to remain significant at least until 2017, i.e. twelve years after the conflict termination. The correlation between violence exposure and deprivation over time is confirmed in a household-level panel setting. Secondly, our empirical investigation shows how violence exposure over different time spans interacts with households' subsequent welfare. Our analysis of the determinants of households' likelihood to switch poverty status (i.e. to fall into poverty or escape poverty) combined with quantile regressions suggest that, (i) exposure during the first phase of the conflict has affected the entire distribution, and (ii) exposure during the second phase of the conflict has mostly affected the upper tail of the distribution: initially non-poor households have a higher propensity to fall into poverty while initially poor households see their propensity to pull through only slightly decrease with recent exposure to violence. Although not directly testable with the data at hand, these results are consistent with the changing nature of violence in the course of the Burundi civil war, from relatively more labour-destructive to relatively more capital-destructive.

Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis.

Aims/hypothesis Glomerular hyperfiltration is a well established phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR.

Methods A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement
of GFR and presence or absence of hyperfiltration.

Results We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum
of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20–6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p=0.05, measure of degree of inconsistency=48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min-1 1.73 m-2 (95% CI 5.0–22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p<0.01).

Conclusions/interpretation In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.

Country-wise differences in perception of health-related messages in cereal-based food products

The objective of the present study was to explore the impact of health-related messages on the perceived overall healthiness and consumers' likelihood to buy cereal-based products or non-cereal products containing beneficial compounds from grains, across four European countries. The data were collected from a sample of 2392 members of the public in Finland, Germany, Italy and the UK. The results from a conjoint task with a main effects additive model were reported. In general, the presence of a verbal health claim on foods had positive influence on respondents perception of healthiness and on likelihood to buy the products, whereas the pictorial health claims were found to have a weak influence on the two dependent variables. However, the findings showed that health-related information on food labels differently influenced the healthiness perception and the likelihood to buy the product across the four countries, suggesting that different cultures, traditions, and eating habits have to be taken into account before positioning cereal-based products containing beneficial compounds from grains on the market. (C) 2009 Elsevier Ltd. All rights reserved.

Job strain as a risk factor for coronary heart disease:a collaborative meta-analysis of individual participant data

BACKGROUND: Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. METHODS: We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. FINDINGS: 30?214 (15%) of 197?473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10-1·37). This effect estimate was higher in published (1·43, 1·15-1·77) than unpublished (1·16, 1·02-1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15-1·48) and 5 years (1·30, 1·13-1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%. INTERPRETATION: Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. FUNDING: Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.

PTGS2 (Cyclooxygenase-2) expression and survival among colorectal cancer patients: A systematic review

Background: Studies have examined whether tumor expression of PTGS2 (also known as COX-2), an enzyme inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, is associated with prognosis in patients with colorectal cancer. However, results to date have been mixed. Methods: Using terms for PTGS2 and colorectal cancer, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until December 2011. Random effects meta-analyses were used to calculate pooled HRs [95% confidence intervals (CI)] for the association between PTGS2 expression and tumor recurrence, colorectal cancer-specific survival, and overall survival. Results: In total, 29 studies, which had prognostic data on 5,648 patients, met the inclusion criteria. PTGS2- positive patients were at an increased risk of tumor recurrence (n = 9 studies; HR, 2.79; 95% CI, 1.76-4.41; P <0.001) and had poorer colorectal cancer-specific survival (n = 7; HR, 1.36; 95% CI, 1.02-1.82; P = 0.04). However, there was funnel plot asymmetry, possibly due to publication bias, for the association with cancerspecific survival but less so for recurrence. PTGS2 expression was not associated with overall survival [(n= 16; pooled unadjusted HR, 1.30; 95% CI, 0.94-1.79; P=0.11) and (n=9; pooled adjusted HR, 1.02; 95% CI, 0.72-1.45; P = 0.91)]. Conclusions: PTGS2 expression was associated with an increased risk of tumor recurrence and poorer colorectal cancer-specific survival but not overall survival among patients with colorectal cancer. However, confounding by tumor characteristics such as tumor stage seems likely. Impact: There is insufficient evidence to recommend PTGS2 expression as a prognostic marker in patients with colorectal cancer. Furthermore, studies providing adjusted results are required. © 2013 AACR.

Ethical leadership and unethical pro-organizational behavior: A moderated mediation model of affective commitment and authenticity at work

Recently, unethical conduct in the workplace has been a focus of literature and media. Unethical pro-organizational behavior (UPB) refers to unethical conduct that employees engage in to benefit the organization. Given the complexity of UPB, there is an increasing need to understand how and under what conditions this attitude originates within organizations. Based on a sample of 167 employees and seven organizations, results support the moderated mediation model. An ethical leader increases employees’ organizational affective commitment which increases the likelihood to engage in UPB. However, the indirect relationship diminishes when employees feel authentic at work.

Establishing an association between a peri-operative perfusion score system (PerfSCORE) and post-operative patient morbidity/mortality during CPB cardiac surgery.

BACKGROUND: To date, there is no quality assurance program that correlates patient outcome to perfusion service provided during cardiopulmonary bypass (CPB). A score was devised, incorporating objective parameters that would reflect the likelihood to influence patient outcome. The purpose was to create a new method for evaluating the quality of care the perfusionist provides during CPB procedures and to deduce whether it predicts patient morbidity and mortality. METHODS: We analysed 295 consecutive elective patients. We chose 10 parameters: fluid balance, blood transfused, Hct, ACT, PaO2, PaCO2, pH, BE, potassium and CPB time. Distribution analysis was performed using the Shapiro-Wilcoxon test. This made up the PerfSCORE and we tried to find a correlation to mortality rate, patient stay in the ICU and length of mechanical ventilation. Univariate analysis (UA) using linear regression was established for each parameter. Statistical significance was established when p < 0.05. Multivariate analysis (MA) was performed with the same parameters. RESULTS: The mean age was 63.8 +/- 12.6 years with 70% males. There were 180 CABG, 88 valves, and 27 combined CABG/valve procedures. The PerfSCORE of 6.6 +/- 2.4 (0-20), mortality of 2.7% (8/295), CPB time 100 +/- 41 min (19-313), ICU stay 52 +/- 62 hrs (7-564) and mechanical ventilation of 10.5 +/- 14.8 hrs (0-564) was calculated. CPB time, fluid balance, PaO2, PerfSCORE and blood transfused were significantly correlated to mortality (UA, p < 0.05). Also, CPB time, blood transfused and PaO2 were parameters predicting mortality (MA, p < 0.01). Only pH was significantly correlated for predicting ICU stay (UA). Ultrafiltration (UF) and CPB time were significantly correlated (UA, p < 0.01) while UF (p < 0.05) was the only parameter predicting mechanical ventilation duration (MA). CONCLUSIONS: CPB time, blood transfused and PaO2 are independent risk factors of mortality. Fluid balance, blood transfusion, PaO2, PerfSCORE and CPB time are independent parameters for predicting morbidity. PerfSCORE is a quality of perfusion measure that objectively quantifies perfusion performance.

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study.

BACKGROUND: The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. METHODS: Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. RESULTS: EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). CONCLUSIONS: In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

“Weathering a Hidden Storm”: An Application of Andersen’s Behavioral Model of Health, and Health Services Use for Those with Diagnosable Anxiety Disorder

Abstract: Research has primarily focused on depression and mood disorders, but little research has been devoted to an examination of mental health services use amongst those with diagnosable anxiety disorder (Wittchen et al., 2002; Bergeron et al., 2005). This study examined the possible predicting factors for mental health services utilization amongst those with identifiable anxiety disorder in the Canadian population. The methods used for this study was the application of Andersen’s Behavioral Model of Health Services Use, where predisposing, need and enabling characteristics were regressed on the dependent variable of mental health services use. This study used the Canadian Community Health Survey (cycle 1.2: Mental Health and Well-Being) in a secondary data analysis. Several multiple logistics models predicted the likelihood to seek and use mental health services. Predisposing characteristics of gender and age, Enabling characteristics of education and geographical location, and those with co-occurring mood disorders were at the greatest increased likelihood to seek and use mental health services.

"Weathering a hidden storm" : an application of Andersen's behavioral model of health, and health services use for those with diagnosable anxiety disorder

"Weathering a Hidden Storm": An App~ication of Andersen's Behaviora~ Mode~ of Hea~th, and Hea~th Services Use for Those With Diagnosab~e Anxiety Disorder Research has primarily focused on depression and mood disorders, but little research has been devoted to an examination of mental health services use amongst those with diagnosable anxiety disorder (Wittchen et al., 2002; Bergeron et al., 2005). This study examined the possible predicting factors for mental health services utilization amongst those with identifiable anxiety disorder in the Canadian population. The methods used for this study was the application of Andersen's Behavioral Model of Health Services Use, where predisposing, need and enabling 111 characteristics were regressed on the dependent variable of mental health services use. This study used the Canadian Community Health Survey (cycle 1.2: Mental Health and Well- Being) in a secondary data analysis. Several multiple logistics models predicted the likelihood to seek and use mental health services. Predisposing characteristics of gender and age, Enabling characteristics of education and geographical location, and those with co-occurring mood disorders were at the greatest increased likelihood to seek and use mental health services.

Forgiveness in Two Minds: Understanding Forgiveness Through Dual-Process Theory

In this thesis, I examined the relevance of dual-process theory to understanding forgiveness. Specifically, I argued that the internal conflict experienced by laypersons when forgiving (or finding themselves unable to forgive) and the discrepancies between existing definitions of forgiveness can currently be best understood through the lens of dual-process theory. Dual-process theory holds that individuals engage in two broad forms of mental processing corresponding to two systems, here referred to as System 1 and System 2. System 1 processing is automatic, unconscious, and operates through learned associations and heuristics. System 2 processing is effortful, conscious, and operates through rule-based and hypothetical thinking. Different definitions of forgiveness amongst both lay persons and scholars may reflect different processes within each system. Further, lay experiences with internal conflict concerning forgiveness may frequently result from processes within each system leading to different cognitive, affective, and behavioural responses. The study conducted for this thesis tested the hypotheses that processing within System 1 can directly affect one's likelihood to forgive, and that this effect is moderated by System 2 processing. I used subliminal conditioning to manipulate System 1 processing by creating positive or negative conditioned attitudes towards a hypothetical transgressor. I used working memory load (WML) to inhibit System 2 processing amongst half of the participants. The conditioning phase of the study failed and so no conclusions could be drawn regarding the roles of System 1 and System 2 in forgiveness. The implications of dual-process theory for forgiveness research and clinical practice, and directions for future research are discussed.

Étude de la sensibilité baroréceptive en sommeil et à l’éveil dans l’insomnie primaire chronique

L’insomnie, une condition fréquemment retrouvée dans la population, se caractérise d’abord par une difficulté à initier ou à maintenir le sommeil et/ou par des éveils précoces le matin ou encore par un sommeil non-réparateur. Lorsqu’elle n’est pas accompagnée par des troubles psychiatriques ou médicaux ou un autre trouble de sommeil et qu’elle perdure plus de 6 mois on parle alors d’insomnie primaire chronique. Selon certains, cette condition serait associée à un état d’hyperéveil caractérisé par une augmentation de l’activité autonome sympathique durant le sommeil et l’éveil. Le baroréflexe est un important mécanisme de contrôle à court terme des fluctuations de la tension artérielle (TA) et de la fréquence cardiaque agissant sur le cœur et les vaisseaux sanguins par l’entremise du système nerveux autonome. On appelle sensibilité baroréceptive (SBR) la capacité du baroréflexe de réagir et de contrôler les fluctuations de TA en modulant le rythme cardiaque. De manière générale, la SBR serait augmentée durant la nuit par rapport à la journée. Aussi, il semblerait que le baroréflexe soit impliqué dans le phénomène de baisse physiologique de la TA pendant la nuit. Or, des données de notre laboratoire ont démontré une augmentation de la TA systolique au cours de la nuit ainsi qu’une atténuation de la baisse nocturne de TA systolique chez des sujets avec insomnie primaire chronique comparé à des témoins bons dormeurs. De plus, il a été démontré que le baroréflexe était altéré de façon précoce dans plusieurs troubles cardiovasculaires et dans l’hypertension artérielle. Or, il semblerait que l’insomnie soit accompagnée d’un risque accru de développement de l’hypertension artérielle. Ces études semblent aller dans le sens d’une altération des mécanismes de régulation de la TA dans l’insomnie. Par ailleurs, une réduction de la SBR serait aussi impliquée dans des états associés à une augmentation de l’activité autonome sympathique. Ainsi, nous nous sommes demandé si le baroréflexe pouvait constituer un des mécanismes de contrôle de la TA qui serait altéré dans l’insomnie et pourrait être impliqué dans l’augmentation de l’activité sympathique qui semble accompagner l’insomnie. Jusqu’à présent, le baroréflexe reste inexploré dans l’insomnie. L’objectif principal de ce mémoire était d’évaluer de façon non-invasive la SBR à l’éveil et en sommeil chez 11 sujets atteints d’insomnie primaire chronique comparé à 11 témoins bons dormeurs. L’évaluation du baroréflexe a été effectuée de façon spontanée par la méthode de l’analyse en séquence et par le calcul du coefficient alpha obtenu par l’analyse spectrale croisée de l’intervalle RR et de la TA systolique. De façon concomitante, les paramètres de la variabilité de l’intervalle RR en sommeil et à l’éveil ont aussi été comparés chez ces mêmes sujets. Aucune différence significative n’a été notée au niveau des index de la SBR entre le groupe d’insomniaques et celui des bons dormeurs, à l’éveil ou en sommeil. Cependant, on observe des valeurs légèrement plus faibles de la SBR chez les insomniaques ayant mal dormi (efficacité de sommeil (ES) < 85%) comparés aux insomniaques ayant bien dormi (ES≥ 85%) à la nuit expérimentale durant l’éveil et en sommeil. Par ailleurs, aucune différence n’a été notée entre le groupe d’insomniaques et celui des bons dormeurs au niveau des paramètres de la variabilité RR considérés (intervalle RR, PNN50, LF et HF en valeurs normalisées). En effet, les insomniaques tout comme les bons dormeurs semblent présenter une variation normale de l’activité autonome en sommeil, telle que représentée par les paramètres de la variabilité RR. Ces résultats préliminaires semblent suggérer que les mécanismes du baroréflexe sont préservés chez les sujets atteints d’insomnie primaire chronique tels que diagnostiqués de manière subjective. Cependant, il est possible qu’une altération des mécanismes du baroréflexe ne se révèle chez les insomniaques que lorsque les critères objectifs d’une mauvaise nuit de sommeil sont présents.

Participation des immigrants à la formation liée à un emploi au Canada

L’essor continu de l’économie canadienne repose grandement sur l’immigration. Toutefois, le Canada a encore du chemin à faire pour assurer l’intégration des nouveaux arrivants sur le marché du travail. Notre recherche porte sur un moyen souvent considéré comme essentiel pour accomplir cette intégration : la formation liée à l’emploi. L’expression « formation liée à l’emploi » fait référence aux activités d’apprentissage en lien avec un emploi et parrainées par l’employeur. Nous avons deux objectifs. Le premier est de déterminer si les immigrants et les Canadiens de naissance ont les mêmes chances de participer à des activités de formation liée à l’emploi. Le deuxième est d’examiner l’effet du sexe et de la durée depuis l’immigration sur la probabilité qu’un immigrant participe à la formation liée à l’emploi. Notre analyse est de type quantitatif et utilise les données de l’Enquête sur l’éducation et la formation des adultes de l’année 2003, menée par Statistiques Canada. Concernant le premier objectif, il ressort de nos analyses que les travailleurs immigrants sont moins susceptibles que les Canadiens de naissance de participer à la formation liée à l’emploi. Même si d'autres études ont remarqué un écart semblable entre ces deux groupes, notre recherche a la particularité de contrôler l'impact de six variables qui, selon la littérature, affectent le niveau de participation à la formation liée à l’emploi. Cette particularité réduit la probabilité que la différence observée entre les immigrants et les Canadiens de naissance puisse être le résultat d'un facteur autre que le statut d'immigrant. Quant au deuxième objectif, notre étude montre que la durée depuis l'immigration augmente les chances qu'un immigrant participe à la formation liée à l’emploi. Néanmoins, la question concernant l'impact du sexe de l’immigrant demeure ouverte. En effet, à l’encontre de nos attentes, nous n’avons pas observé d’effet statistiquement significatif du sexe sur la relation entre le statut d’immigrant et la participation à la formation liée à l’emploi. Notre recherche permet d'attirer le regard sur un possible facteur modérateur qui mérite plus de réflexion de la part des chercheurs.

Modelling risk perception and trust in food safety information within the theory of planned behaviour

This study suggests a statistical strategy for explaining how food purchasing intentions are influenced by different levels of risk perception and trust in food safety information. The modelling process is based on Ajzen's Theory of Planned Behaviour and includes trust and risk perception as additional explanatory factors. Interaction and endogeneity across these determinants is explored through a system of simultaneous equations, while the SPARTA equation is estimated through an ordered probit model. Furthermore, parameters are allowed to vary as a function of socio-demographic variables. The application explores chicken purchasing intentions both in a standard situation and conditional to an hypothetical salmonella scare. Data were collected through a nationally representative UK wide survey of 533 UK respondents in face-to-face, in-home interviews. Empirical findings show that interactions exist among the determinants of planned behaviour and socio-demographic variables improve the model's performance. Attitudes emerge as the key determinant of intention to purchase chicken, while trust in food safety information provided by media reduces the likelihood to purchase. (C) 2006 Elsevier Ltd. All rights reserved.