Bacterial-induced protection against allergy through a novel multi-component immunoregulatory mechanism

Airborne microbial products have been reported to promote immune responses that suppress asthma, yet how these beneficial effects take place remains controversial and poorly understood. We have found that pulmonary exposure with the bacterium Escherichia coli leads to a suppression of allergic airway inflammation, characterized by reduced airway-hyperresponsiveness, eosinophilia and cytokine production by T cells in the lung. This immune modulation was neither mediated by the induction of a Th1 response nor regulatory T cells; was dependent on TLR-4 but did not involve TLR-desensitization. Dendritic cell migration to the draining lymph nodes and subsequent activation of T cells was unaffected by prior exposure to E.coli indicating that the immunomodulation was limited to the lung environment. In non-treated control mice ovalbumin was primarily presented by airway CD11b+ CD11c+ DCs expressing high levels of MHC class II molecules whilst the DCs in E.coli-treated mice displayed a less activated phenotype and had impaired antigen presentation capacity. Consequently, in situ Th2 cytokine production by ovalbuminspecific effector T cells recruited to the airways was significantly reduced. The suppression of airways hyper responsiveness was mediated through the recruitment of IL-17-producing gd-T cells; however, the suppression of dendritic cells and T cells was mediated through a distinct mechanism that could not be overcome by the local administration of activated dendritic cells, or by the in vivo administration of TNF-alpha. Taken together, these data reveal a novel multi-component immunoregulatory pathway that acts to protect the airways from allergic inflammation.

A multi-center study: intra-scan and inter-scan variability of diffusion spectrum imaging.

The objective of this study was to investigate whether it is possible to pool together diffusion spectrum imaging data from four different scanners, located at three different sites. Two of the scanners had identical configuration whereas two did not. To measure the variability, we extracted three scalar maps (ADC, FA and GFA) from the DSI and utilized a region and a tract-based analysis. Additionally, a phantom study was performed to rule out some potential factors arising from the scanner performance in case some systematic bias occurred in the subject study. This work was split into three experiments: intra-scanner reproducibility, reproducibility with twin-scanner settings and reproducibility with other configurations. Overall for the intra-scanner and twin-scanner experiments, the region-based analysis coefficient of variation (CV) was in a range of 1%-4.2% and below 3% for almost every bundle for the tract-based analysis. The uncinate fasciculus showed the worst reproducibility, especially for FA and GFA values (CV 3.7-6%). For the GFA and FA maps, an ICC value of 0.7 and above is observed in almost all the regions/tracts. Looking at the last experiment, it was found that there is a very high similarity of the outcomes from the two scanners with identical setting. However, this was not the case for the two other imagers. Given the fact that the overall variation in our study is low for the imagers with identical settings, our findings support the feasibility of cross-site pooling of DSI data from identical scanners.

Contexts and typologies in the analysis of welfare state legitimacy : a social psychological approach to political opinion formation

This dissertation analyses public opinion towards the welfare state across 29 European countries. Based on an interdisciplinary approach combining social psychological, sociological, and public opinion approaches to political opinion formation, it investigates how social position and shared beliefs shape perceived legitimacy of welfare institutions, and how social contexts impact on the processes of opinion formation. Drawing on social representations theory, as well as socialization and self-interest approaches, the dissertation analyses the role of social position in lay support for institutional solidarity. Normative beliefs-defined as preferred views regarding the organisation of social relations-mediate the effect of social position on welfare support. In addition, drawing on public opinion literature, the dissertation analyses opinion formation as a function of country-level structural (e.g., level of social spending, unemployment) and ideological factors (e.g., level of meritocracy). The dissertation comprises two theoretical and four empirical chapters. Three of the empirical chapters use data from the European Social Survey 2008. Using multilevel and typological approaches, the dissertation contributes to welfare attitude literature by showing that normative beliefs, such as distrust or egalitarianism, function as underlying mechanisms that link social position to policy attitudes (Chapter 3), and that characteristics of the national contexts influence the processes of political opinion formation (Chapters 3 and 4). Chapter 5 proposes and predicts a typology of the relationship between attitudes towards solidarity and attitudes towards control, reflecting the two central domains of government intervention. Finally, Chapter 6 examines welfare support in the realm of action and social protest, using data from a survey on Spanish Indigados activists. The findings of this dissertation inform contemporary debates about welfare state legitimacy and retrenchment. - Cette thèse avait pour but d'analyser l'opinion publique envers l'Etat social dans 29 pays européens. Basée sur une approche interdisciplinaire qui combine des perspectives psycho-sociales, sociologiques et d'opinion publique sur la formation d'opinion politique, la thèse étudie comment la position sociale et les croyances partagées façonnent la légitimité perçue des institutions de l'Etat social, et comment les contextes sociaux influencent les processus de formation d'opinion. Basée sur la théorie des représentations sociales, ainsi qu'une approche de socialisation et d'intérêt propre, cette thèse analyse le rôle des positions sociales dans le soutien envers la solidarité institutionnelle. Les croyances normatives-définies comme les visions préférées de l'organisation des rapports sociaux-médiatisent l'effet de la position sociale sur le soutien pour l'Etat social. De plus, s'inspirant de la littérature sur l'opinion publique, la thèse analyse la formation d'opinion en fonction des facteurs structurels (ex. le taux de dépenses sociales, le chômage) et idéologiques (ex. le degré de méritocratie). Cette thèse est composée de deux chapitres théoriques et quatre chapitres empiriques. Trois chapitres empiriques utilisent des données provenant de l'enquête European Social Survey 2008. Appliquant des approches multi-niveux et typoloqiques, la thèse contribue à la littérature sur les attitudes envers l'Etat social en montrant que les croyances normatives, telles que la méfiance ou l'égalitarisme, fonctionnent comme des mécanismes sous-jacents qui relient la position sociale aux attitudes politiques (Chapitre 3), et que les caractéristiques des contextes nationaux influencent les processus de formation d'opinion politique (Chapitres 3 et 4). Le chapitre 5 propose et prédit une typologie sur le rapport entre les attitudes envers la solidarité et celles envers le contrôle, renvoyant à deux domaines centraux de régulation étatique. Enfin, le chapitre 6 examine le soutien à l'Etat social dans le domaine de l'action protestataire, utilisant des données d'une enquête menée auprès des militants espagnols du mouvement des Indignés. Les résultats de cette thèse apportent des éléments qui éclairent les débats contemporains sur la légitimité de l'Etat social et son démantèlement.

Multi-Atlas based Segmentation of Head and Neck CT Images using Active Contour

This paper presents the segmentation of bilateral parotid glands in the Head and Neck (H&N) CT images using an active contour based atlas registration. We compare segmentation results from three atlas selection strategies: (i) selection of "single-most-similar" atlas for each image to be segmented, (ii) fusion of segmentation results from multiple atlases using STAPLE, and (iii) fusion of segmentation results using majority voting. Among these three approaches, fusion using majority voting provided the best results. Finally, we present a detailed evaluation on a dataset of eight images (provided as a part of H&N auto segmentation challenge conducted in conjunction with MICCAI-2010 conference) using majority voting strategy.

Association between smoking and total energy expenditure in a multi-country study.

BACKGROUND: The association between smoking and total energy expenditure (TEE) is still controversial. We examined this association in a multi-country study where TEE was measured in a subset of participants by the doubly labeled water (DLW) method, the gold standard for this measurement. METHODS: This study includes 236 participants from five different African origin populations who underwent DLW measurements and had complete data on the main covariates of interest. Self-reported smoking status was categorized as either light (<7 cig/day) or high (≥7 cig/day). Lean body mass was assessed by deuterium dilution and physical activity (PA) by accelerometry. RESULTS: The prevalence of smoking was 55% in men and 16% in women with a median of 6.5 cigarettes/day. There was a trend toward lower BMI in smokers than non-smokers (not statistically significant). TEE was strongly correlated with fat-free mass (men: 0.70; women: 0.79) and with body weight (0.59 in both sexes). Using linear regression and adjusting for body weight, study site, age, PA, alcohol intake and occupation, TEE was larger in high smokers than in never smokers among men (difference of 298 kcal/day, p = 0.045) but not among women (162 kcal/day, p = 0.170). The association became slightly weaker in men (254 kcal/day, p = 0.058) and disappeared in women (-76 kcal/day, p = 0.380) when adjusting for fat-free mass instead of body weight. CONCLUSION: There was an association between smoking and TEE among men. However, the lack of an association among women, which may be partly related to the small number of smoking women, also suggests a role of unaccounted confounding factors.

Identification of different heart tissues from MRI C-SENC images using an unsupervised multi-stage fuzzy clustering technique.

PURPOSE: To objectively characterize different heart tissues from functional and viability images provided by composite-strain-encoding (C-SENC) MRI. MATERIALS AND METHODS: C-SENC is a new MRI technique for simultaneously acquiring cardiac functional and viability images. In this work, an unsupervised multi-stage fuzzy clustering method is proposed to identify different heart tissues in the C-SENC images. The method is based on sequential application of the fuzzy c-means (FCM) and iterative self-organizing data (ISODATA) clustering algorithms. The proposed method is tested on simulated heart images and on images from nine patients with and without myocardial infarction (MI). The resulting clustered images are compared with MRI delayed-enhancement (DE) viability images for determining MI. Also, Bland-Altman analysis is conducted between the two methods. RESULTS: Normal myocardium, infarcted myocardium, and blood are correctly identified using the proposed method. The clustered images correctly identified 90 +/- 4% of the pixels defined as infarct in the DE images. In addition, 89 +/- 5% of the pixels defined as infarct in the clustered images were also defined as infarct in DE images. The Bland-Altman results show no bias between the two methods in identifying MI. CONCLUSION: The proposed technique allows for objectively identifying divergent heart tissues, which would be potentially important for clinical decision-making in patients with MI.

Indicators of therapeutic effect in FIT-06, a Phase II trial of a DNA vaccine, GTU(®)-Multi-HIVB, in untreated HIV-1 infected subjects.

BACKGROUND: Combination highly active antiretroviral therapy (HAART) has significantly decreased HIV-1 related morbidity and mortality globally transforming HIV into a controllable condition. HAART has a number of limitations though, including limited access in resource constrained countries, which have driven the search for simpler, affordable HIV-1 treatment modalities. Therapeutic HIV-1 vaccines aim to provide immunological support to slow disease progression and decrease transmission. We evaluated the safety, immunogenicity and clinical effect of a novel recombinant plasmid DNA therapeutic HIV-1 vaccine, GTU(®)-multi-HIVB, containing 6 different genes derived from an HIV-1 subtype B isolate. METHODS: 63 untreated, healthy, HIV-1 infected, adults between 18 and 40 years were enrolled in a single-blinded, placebo-controlled Phase II trial in South Africa. Subjects were HIV-1 subtype C infected, had never received antiretrovirals, with CD4 ≥ 350 cells/mm(3) and pHIV-RNA ≥ 50 copies/mL at screening. Subjects were allocated to vaccine or placebo groups in a 2:1 ratio either administered intradermally (ID) (0.5mg/dose) or intramuscularly (IM) (1mg/dose) at 0, 4 and 12 weeks boosted at 76 and 80 weeks with 1mg/dose (ID) and 2mg/dose (IM), respectively. Safety was assessed by adverse event monitoring and immunogenicity by HIV-1-specific CD4+ and CD8+ T-cells using intracellular cytokine staining (ICS), pHIV-RNA and CD4 counts. RESULTS: Vaccine was safe and well tolerated with no vaccine related serious adverse events. Significant declines in log pHIV-RNA (p=0.012) and increases in CD4+ T cell counts (p=0.066) were observed in the vaccine group compared to placebo, more pronounced after IM administration and in some HLA haplotypes (B*5703) maintained for 17 months after the final immunisation. CONCLUSIONS: The GTU(®)-multi-HIVB plasmid recombinant DNA therapeutic HIV-1 vaccine is safe, well tolerated and favourably affects pHIV-RNA and CD4 counts in untreated HIV-1 infected individuals after IM administration in subjects with HLA B*57, B*8101 and B*5801 haplotypes.

Female adolescents' views on a youth-friendly clinic

Rapport de synthèse : La satisfaction des patients concernant leur prise en charge fait maintenant partie intégrante de la qualité des soins. Elle a été évaluée à maintes reprises chez des patients adultes ou pédiatriques, mais rarement chez des patients adolescents. Les attentes des adolescents par rapport aux services de soins ont par contre été souvent étudiées et certains facteurs semblent particulièrement importants. Parmi ceux-ci, citons la confidentialité, le respect, l'honnêteté, l'écoute, l'accès aux soins ou le fait d'avoir des informations compréhensibles. L'Organisation Mondiale de la Santé a développé le concept de 'Youth-friendly health services' pour répondre aux besoins et attentes particuliers des adolescents. Il est basé sur sept principes : l'accessibilité, l'équité, l'efficience, l'efficacité, le fait d'être approprié et compréhensible. Notre objectif était d'évaluer la satisfaction des adolescentes consultant dans une clinique multidisciplinaire pour adolescents basée sur le modèle 'Youth-friendly health services' et de déterminer les facteurs qui y sont associés. Nous avons fait une enquête transversale dans une clinique pour adolescents à Lausanne entre mars et mai 2008 moyennant un questionnaire anonyme auto-administré. Tous les patients qui avaient consulté au moins une fois auparavant étaient éligibles. Nous avons ensuite éliminé les garçons, en très petit nombre et donc de faible valeur statistique. Trois cents onze patientes âgées de 12 à 22 ans ont été inclues dans l'étude. Nous avons effectué des analyses bivariées pour comparer les patientes satisfaites et non satisfaites puis avons construit un modèle log- linéaire afin de déterminer les facteurs directement ou indirectement liés à la satisfaction des patientes. Nonante-quatre pourcent des patientes étaient satisfaites. Les facteurs significativement associés à la satisfaction des adolescentes étaient les suivants : Les jeunes filles se sentaient plus écoutées en ce qui concerne leurs plaintes, et avaient plus l'impression que le soignant les comprenait. Elles avaient aussi moins changé de soignant durant le suivi, avaient plus l'impression d'avoir bénéficié du traitement adéquat et pensaient avoir plus suivi les conseils du soignant. Le modèle log-linéaire que nous avons effectué a mis en avant quatre facteurs directement liés à la satisfaction des patientes, qui sont la continuité des soins, le résultat de la prise en charge, l'adhérence au traitement et le sentiment d'être comprise par le soignant. Ces résultats mettent en avant l'importance de la relation interpersonnelle entre le soignant et le patient, mais rendent aussi attentif à des aspects qui pourraient être améliorés, en ce qui concerne par exemple la continuité des soins. En effet, une clinique comme la nôtre fait partie d'un hôpital de formation et le tournus fréquent des soignants est inévitable. Les changements de médecins et autres soignants devraient alors être préparés et expliqués aux patients avec la plus grande attention. L'adhérence au traitement semble être fortement liée à la satisfaction des patients, mais la nature de notre étude ne permet pas de conclure à une relation de cause à effet. Nous pouvons tout de même supposer qu'elle est une conséquence de la satisfaction des patients. Enfin, la confidentialité et l'accès aux soins souvent cités comme essentiels à la satisfaction des patients dans la littérature étaient secondaires dans notre étude. En conclusion, la satisfaction des adolescentes était principalement basée sur une relation de confiance de longue durée avec leurs soignants. Les pédiatres occupent une place privilégiée pour répondre à ces besoins parce qu'ils connaissent leurs patients depuis l'enfance. Ils devraient cependant garder à l'esprit que la relation avec le patient change au moment de l'adolescence et que les jeunes sont très sensibles à la relation de confiance interpersonnelle qu'ils ont avec leur médecin.

Detection of coronary thrombosis after multi-phase postmortem CT-angiography.

The aim of this study was to compare postmortem angiography-based, autopsy-based and histology-based diagnoses of acute coronary thrombosis in a series of medicolegal cases that underwent postmortem angiographies according to multiphase CT-angiography protocol. Our study included 150 medicolegal cases. All cases underwent native CT-scan, postmortem angiography, complete conventional autopsy and histological examination of the main organs and coronary arteries. In 10 out of the 150 investigated cases, postmortem angiographies revealed coronary arterial luminal filling defects and the absence of collateral vessels, suggesting acute coronary thromboses. Radiological findings were confirmed by autopsy and histological examinations in all cases. In 40 out of 150 cases, angiograms revealed complete or incomplete coronary arterial luminal filling defects and the presence of collateral vessels. Histological examinations did not reveal free-floating or non-adherent thrombi in the coronary arteries in any of these cases. Though postmortem angiography examination has not been well-established for the diagnosis of acute coronary thrombosis, luminal filling defects in coronary arteries suggesting acute thromboses can be observed through angiography and subsequently confirmed by autopsy and histological examinations.

Classification of urban multi-angular image sequences by aligning their manifolds

When dealing with multi-angular image sequences, problems of reflectance changes due either to illumination and acquisition geometry, or to interactions with the atmosphere, naturally arise. These phenomena interplay with the scene and lead to a modification of the measured radiance: for example, according to the angle of acquisition, tall objects may be seen from top or from the side and different light scatterings may affect the surfaces. This results in shifts in the acquired radiance, that make the problem of multi-angular classification harder and might lead to catastrophic results, since surfaces with the same reflectance return significantly different signals. In this paper, rather than performing atmospheric or bi-directional reflection distribution function (BRDF) correction, a non-linear manifold learning approach is used to align data structures. This method maximizes the similarity between the different acquisitions by deforming their manifold, thus enhancing the transferability of classification models among the images of the sequence.

CT dose optimization when changing to CT multi-detector row technology

The purpose of this article was to review the strategies to control patient dose in adult and pediatric computed tomography (CT), taking into account the change of technology from single-detector row CT to multi-detector row CT. First the relationships between computed tomography dose index, dose length product, and effective dose in adult and pediatric CT are revised, along with the diagnostic reference level concept. Then the effect of image noise as a function of volume computed tomography dose index, reconstructed slice thickness, and the size of the patient are described. Finally, the potential of tube current modulation CT is discussed.