942 resultados para as comparing diseased to non-diseased subjects while minimizing bias is of epidemiologic importance. We estimate essentially non-parametric piecewise constant hazards and smooth them


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This paper proposes Poisson log-linear multilevel models to investigate population variability in sleep state transition rates. We specifically propose a Bayesian Poisson regression model that is more flexible, scalable to larger studies, and easily fit than other attempts in the literature. We further use hierarchical random effects to account for pairings of individuals and repeated measures within those individuals, as comparing diseased to non-diseased subjects while minimizing bias is of epidemiologic importance. We estimate essentially non-parametric piecewise constant hazards and smooth them, and allow for time varying covariates and segment of the night comparisons. The Bayesian Poisson regression is justified through a re-derivation of a classical algebraic likelihood equivalence of Poisson regression with a log(time) offset and survival regression assuming piecewise constant hazards. This relationship allows us to synthesize two methods currently used to analyze sleep transition phenomena: stratified multi-state proportional hazards models and log-linear models with GEE for transition counts. An example data set from the Sleep Heart Health Study is analyzed.

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This doctoral thesis was published in printed form in 1987. It was digitized from paper copy in 2013. Unfortunately on some pages the digitizaion process has not been complete, i.e there are some minor typographic erros on some pages.

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Workshop Overview The use of special effects (moulage) is a way to augment the authenticity of a scenario in simulation. This workshop will introduce different techniques of moulage (oil based cream colors, watercolors, transfer tattoos and 3D Prosthetics). The participants will have the opportunity to explore these techniques by applying various moulages. They will compare the techniques and discuss their advantages and disadvantages. Moreover, strategies for standardization and quality assurance will be discussed. Workshop Rationale Moulage supports the sensory perception in an scenario (1). It can provide evaluation clues (2) and help learners (and SPs) to engage in the simulation. However, it is of crucial importance that the simulated physical pathologies are represented accurate and reliable. Accuracy is achieved by using the appropriate technique, which requires knowledge and practice . With information about different moulage techniques, we hope to increases the knowledge of moulage during the workshop. By applying moulages in various techniques we will practice together. As standardization is critical for simulation scenarios in assessment (3, 4) strategies for standardization of moulage will be introduced and discussed. Workshop Objectives During the workshop participants will: - gain knowledge about different techniques of moulages - practice moulages in various techniques - discuss the advantages and disadvantages of moulage techniques - describe strategies for standardization and quality assurance of moulage Planned Format 5 min Introduction 15 min Overview â Background & Theory (presentation) 15 min Application of moulage for ankle sprain in 4 different techniques (oil based cream color, water color, temporary tatoo, 3D prosthetic) in small groups 5 min Comparing the results by interactive viewing of prepared moulages 15 min Application of moulages for burn in different techniques in small groups 5 min Comparing results the results by interactive viewing of prepared moulages 5 min Sharing experiences with different techniques in small groups 20 min Discussion of the techniques including standardization and quality assurance strategies (plenary discussion) 5 min Summary / Take home points

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Neutrophils (PMN) play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM), which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. The goal of the study was to use low-level laser therapy (LLLT) to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan), and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point) on alternate days at two points on each hind leg. The aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. The number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS) and their fungicidal activity. The highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. The kinetics of neutrophil protein production also correlated with a more activated state. LLLT may be a safe and non-invasive approach to deal with PCM infection.

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In embedded systems, the timing behaviour of the control mechanisms are sometimes of critical importance for the operational safety. These high criticality systems require strict compliance with the offline predicted task execution time. The execution of a task when subject to preemption may vary significantly in comparison to its non-preemptive execution. Hence, when preemptive scheduling is required to operate the workload, preemption delay estimation is of paramount importance. In this paper a preemption delay estimation method for floating non-preemptive scheduling policies is presented. This work builds on [1], extending the model and optimising it considerably. The preemption delay function is subject to a major tightness improvement, considering the WCET analysis context. Moreover more information is provided as well in the form of an extrinsic cache misses function, which enables the method to provide a solution in situations where the non-preemptive regions sizes are small. Finally experimental results from the implementation of the proposed solutions in Heptane are provided for real benchmarks which validate the significance of this work.

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BACKGROUND AND PURPOSE: Accurate placement of an external ventricular drain (EVD) for the treatment of hydrocephalus is of paramount importance for its functionality and in order to minimize morbidity and complications. The aim of this study was to compare two different drain insertion assistance tools with the traditional free-hand anatomical landmark method, and to measure efficacy, safety and precision. METHODS: Ten cadaver heads were prepared by opening large bone windows centered on Kocher's points on both sides. Nineteen physicians, divided in two groups (trainees and board certified neurosurgeons) performed EVD insertions. The target for the ventricular drain tip was the ipsilateral foramen of Monro. Each participant inserted the external ventricular catheter in three different ways: 1) free-hand by anatomical landmarks, 2) neuronavigation-assisted (NN), and 3) XperCT-guided (XCT). The number of ventricular hits and dangerous trajectories; time to proceed; radiation exposure of patients and physicians; distance of the catheter tip to target and size of deviations projected in the orthogonal plans were measured and compared. RESULTS: Insertion using XCT increased the probability of ventricular puncture from 69.2 to 90.2 % (p&#8201;=&#8201;0.02). Non-assisted placements were significantly less precise (catheter tip to target distance 14.3&#8201;±&#8201;7.4 mm versus 9.6&#8201;±&#8201;7.2 mm, p&#8201;=&#8201;0.0003). The insertion time to proceed increased from 3.04&#8201;±&#8201;2.06 min. to 7.3&#8201;±&#8201;3.6 min. (p&#8201;<&#8201;0.001). The X-ray exposure for XCT was 32.23 mSv, but could be reduced to 13.9 mSv if patients were initially imaged in the hybrid-operating suite. No supplementary radiation exposure is needed for NN if patients are imaged according to a navigation protocol initially. CONCLUSION: This ex vivo study demonstrates a significantly improved accuracy and safety using either NN or XCT-assisted methods. Therefore, efforts should be undertaken to implement these new technologies into daily clinical practice. However, the accuracy versus urgency of an EVD placement has to be balanced, as the image-guided insertion technique will implicate a longer preparation time due to a specific image acquisition and trajectory planning.

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Colistin is a last resort's antibacterial treatment in critically ill patients with multi-drug resistant Gram-negative infections. As appropriate colistin exposure is the key for maximizing efficacy while minimizing toxicity, individualized dosing optimization guided by therapeutic drug monitoring is a top clinical priority. Objective of the present work was to develop a rapid and robust HPLC-MS/MS assay for quantification of colistin plasma concentrations. This novel methodology validated according to international standards simultaneously quantifies the microbiologically active compounds colistin A and B, plus the pro-drug colistin methanesulfonate (colistimethate, CMS). 96-well micro-Elution SPE on Oasis Hydrophilic-Lipophilic-Balanced (HLB) followed by direct analysis by Hydrophilic Interaction Liquid Chromatography (HILIC) with Ethylene Bridged Hybrid - BEH - Amide phase column coupled to tandem mass spectrometry allows a high-throughput with no significant matrix effect. The technique is highly sensitive (limit of quantification 0.014 and 0.006&#956;g/mL for colistin A and B), precise (intra-/inter-assay CV 0.6-8.4%) and accurate (intra-/inter-assay deviation from nominal concentrations -4.4 to +6.3%) over the clinically relevant analytical range 0.05-20&#956;g/mL. Colistin A and B in plasma and whole blood samples are reliably quantified over 48h at room temperature and at +4°C (<6% deviation from nominal values) and after three freeze-thaw cycles. Colistimethate acidic hydrolysis (1M H2SO4) to colistin A and B in plasma was completed in vitro after 15min of sonication while the pro-drug hydrolyzed spontaneously in plasma ex vivo after 4h at room temperature: this information is of utmost importance for interpretation of analytical results. Quantification is precise and accurate when using serum, citrated or EDTA plasma as biological matrix, while use of heparin plasma is not appropriate. This new analytical technique providing optimized quantification in real-life conditions of the microbiologically active compounds colistin A and B offers a highly efficient tool for routine therapeutic drug monitoring aimed at individualizing drug dosing against life-threatening infections.

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Land cover classification is a key research field in remote sensing and land change science as thematic maps derived from remotely sensed data have become the basis for analyzing many socio-ecological issues. However, land cover classification remains a difficult task and it is especially challenging in heterogeneous tropical landscapes where nonetheless such maps are of great importance. The present study aims to establish an efficient classification approach to accurately map all broad land cover classes in a large, heterogeneous tropical area of Bolivia, as a basis for further studies (e.g., land cover-land use change). Specifically, we compare the performance of parametric (maximum likelihood), non-parametric (k-nearest neighbour and four different support vector machines - SVM), and hybrid classifiers, using both hard and soft (fuzzy) accuracy assessments. In addition, we test whether the inclusion of a textural index (homogeneity) in the classifications improves their performance. We classified Landsat imagery for two dates corresponding to dry and wet seasons and found that non-parametric, and particularly SVM classifiers, outperformed both parametric and hybrid classifiers. We also found that the use of the homogeneity index along with reflectance bands significantly increased the overall accuracy of all the classifications, but particularly of SVM algorithms. We observed that improvements in producerâs and userâs accuracies through the inclusion of the homogeneity index were different depending on land cover classes. Earlygrowth/degraded forests, pastures, grasslands and savanna were the classes most improved, especially with the SVM radial basis function and SVM sigmoid classifiers, though with both classifiers all land cover classes were mapped with producerâs and userâs accuracies of around 90%. Our approach seems very well suited to accurately map land cover in tropical regions, thus having the potential to contribute to conservation initiatives, climate change mitigation schemes such as REDD+, and rural development policies.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Background: Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention. Methods: This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-alpha -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype. Results: In the entire sample (66.7% women; mean age 56.5 +/- 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-alpha -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL-6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention. Conclusion: The TNF alpha -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.

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The identification of clinical risk factors for AIDS in patients with preserved immune function is of significant interest. We examined whether patients with fungal infection (FI) and CD4 cell count &gt;or=200/microl were at higher risk of disease progression in the era of cART. 11,009 EuroSIDA patients were followed from their first CD4 cell count &gt;or=200/microl after 1 January 1997 until progression to any non-azoles/amphotericin B susceptible (AAS) AIDS disease, last visit or death. Initiation of antimycotic therapy (AMT) was used as a marker of FI and was modelled as a time-updated covariate using Poisson regression. After adjustment for current CD4 cell count, HIV-RNA, starting cART and diagnosis of AAS-AIDS, AMT was significantly associated with an increased incidence of non-AAS-AIDS (IRR=1.55, 95% CI 1.17-2.06, p=0.0024). Despite low incidence of AIDS in the cART era, FI in patients with a CD4 cell count &gt;or=200/microl is associated with a 55% higher risk of non-AAS-AIDS (95% confidence interval 1.17-2.06, p=0.0024). These data suggest that patients with FI are more immune compromized than would be expected from their CD4 cell count alone. FI can be used as a clinical marker for disease progression and indirect indicator for initiation/changing cART in settings where laboratory facilities are limited.

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Cette thèse de doctorat se situe dans le contexte des préoccupations des autorités nationales et des organisations internationales relatives à lâefficacité des organisations publiques dans les pays en développement, dans le cadre des Objectifs du Millénaire pour le développement (OMD) et du programme Ãducation pour tous (ÃPT). Lâargument du manque de ressources est de plus en plus remis en cause par le constat que certaines organisations disposant de ressources moindres que dâautres de même nature, obtiennent de meilleurs résultats (Barney, 1991; Durand, 1996; Isckia, 2008). Autrement dit, la quantité de ressources nâexplique pas tout; il faut considérer dâautres éléments, dont la mobilisation organisationnelle, câest-à-dire le mouvement obtenu dâune masse critique dâemployés qui adoptent des actions positives dans le sens de lâatteinte des objectifs de leur organisation. Cette mobilisation suppose un climat positif auquel contribue la présence de certains états psychologiques ressentis par les employés, notamment les perceptions de soutien et de reconnaissance de la part de lâorganisation de même quâun sentiment dâhabilitation psychologique (Tremblay et Simard, 2005). Ces perceptions et ce sentiment constituent les points focaux de la recherche que nous avons menée au sein du Ministère de lâéducation nationale et de lâalphabétisation (MÃNA) du Burkina Faso. Lâobjectif principal de notre recherche est de décrire ces trois états psychologiques. Le soutien organisationnel perçu (SOP), lâhabilitation psychologique (HP) et la reconnaissance perçue ont été explorés à partir des travaux de Eisenberger et al. (1986), de Spreitzer (1995) et de Brun et Dugas (2005) respectivement. Nous avons délibérément choisi la perspective des employés plutôt que celle des pratiques de gestion observées ou déclarées de leurs supérieurs et avons entrepris de connaître leurs perceptions. Ces dernières méritent que lâon sâen préoccupe car aucune politique, mesure ou pratique visant à instaurer un climat organisationnel mobilisant ne peut être efficace si elle nâest pas perçue comme telle par les employés. Utilisant une méthodologie mixte, nous avons recueilli auprès de cadres et de directions dâécole, des données sur les trois états psychologiques retenus, à lâaide dâun questionnaire comportant 37 énoncés (65 répondants); dâentrevues individuelles visant à enrichir, compléter, expliciter ou illustrer les informations obtenues par le questionnaire (18 participants); et de deux groupes de discussion autour des résultats de lâanalyse préliminaire des réponses au questionnaire (7 participants). Au total, les données ont été recueillies auprès de 73 personnes, certaines dâentre elles ayant à la fois répondu au questionnaire et participé à une entrevue individuelle. Les données ont été traitées par état psychologique à lâaide des logiciels SPSS Statistics 20 (pour les questionnaires) et QDA Miner 4.0.11 (pour les entretiens individuels). Pour chaque énoncé, chaque variable créée et chacune des caractéristiques (fonction, genre et milieu de travail), nous avons dâabord obtenu des mesures de tendances centrales; nous avons poursuivi en ajoutant un second niveau de traitement en combinant les caractéristiques, par exemple : la fonction (cadre ou direction dâécole) et le genre (femme ou homme). Nous avons ensuite procédé au codage des verbatims des entretiens en vue dâen extraire des éléments qui corroborent, précisent ou nuancent les résultats de lâanalyse des données obtenues par le questionnaire pour chaque état psychologique. Lâexploitation des données dâentretiens visait également à identifier des éléments portant sur le thème de la mobilisation au MÃNA. Les résultats des analyses des données issues des questionnaires indiquent globalement que le soutien organisationnel est perçu de façon négative au sein du MÃNA, seule la valorisation du travail réalisé recueillant un sentiment un peu moins négatif. Les répondants se perçoivent habilités psychologiquement; des quatre composantes de lâhabilitation psychologique, câest lâautonomie qui recueille la perception la plus négative. En ce qui concerne la reconnaissance, on observe une perception positive des éléments reliés à la communication et négative lorsquâil sâagit de lâappréciation du système dâattribution des récompenses. En complément à ces résultats obtenus de lâanalyse des données issues du questionnaire, les entretiens ont permis de mettre en lumière le fait que des pratiques efficaces de gestion (par exemple la rapidité des réponses aux demandes, lâapplication des normes de ponctualité et dâassiduité, la réception régulière du salaire) sont considérées comme des marques de soutien organisationnel. Ces entretiens ont également permis de découvrir un fort potentiel dâimplication personnelle et professionnelle des participants rencontrés qui affichaient une disposition favorable à lâaugmentation de leur contribution tout en souhaitant une plus grande reconnaissance de leur potentiel. La prise en compte de la fonction, du genre et du milieu de travail a permis de raffiner les analyses. à titre dâexemple: le soutien organisationnel est perçu plus positivement en milieu urbain quâen milieu rural; les cadres perçoivent positivement la valorisation que le ministère accorde à leur contribution; alors que les directrices dâécole ont une appréciation négative de cette valorisation. Le sentiment de compétence est éprouvé de façon plus positive chez les cadres alors que le sentiment dâautonomie est plus positif chez les directions dâécole. En milieu urbain, la transmission de lâinformation, les rencontres avec les supérieurs et les témoignages dâappréciation sont plus présents quâen milieu rural. Dans cette recherche, qui sâest déroulée dans un contexte subsaharien, nous avons affiché un parti pris pour une approche universaliste plutôt que culturaliste. Tout en reconnaissant que les traditions et la culture font partie de lâenvironnement organisationnel, nous pensons quâelles ne sont pas les principaux facteurs explicatifs des comportements des employés dans une organisation. Les propos tenus par certains des participants que nous avons rencontrés renforcent notre conviction que les pratiques de gestion généralement perçues positivement par les employés le sont également dans ce contexte.