Post-traumatic stress disorder (PTSD) is a heterogenous psychiatric condition that affects thousands of individuals each year. Of those who experience this condition, military members including members of the Canadian Armed Forces (CAF) are particularly vulnerable, demonstrating high prevalence rates of PTSD-related symptoms. Moreover, individuals with PTSD are at increased risk for comorbid conditions and are at greater risk for suicide due to the overwhelming, debilitating nature of PTSD symptoms. In previous research, hyperarousal symptoms associated with PTSD have been linked to dysregulation in the locus coeruleus norepinephrine (LC-NE) system, a vast neuromodulatory system responsible for regulating arousal, attention, autonomic and memory-related functions. Advancements in neuroimaging methods have advanced our ability to study connectivity in vivo such that small structures like the LC can be further studied in human samples. Specifically, neuromelanin-sensitive MRI (NM-MRI), a novel, non-invasive neuroimaging method has been shown to detect changes in neuromelanin (NM)-related signal in both the LC and substantia nigra (SN). NM is a dark pigment that accumulates over the lifespan in catecholamine-dominant centers such as the LC and SN and is the by-product of catecholamine oxidation. NM-MRI can be used to image these centers in vivo due to the paramagnetic properties offered by NM. Furthermore, when excess cytosolic catecholamine levels are present in select neurons, NM production is thought to be increased, resulting in increased NM signal from the LC. This could potentially be a marker for dysregulation as many conditions have been associated with variability of this system. Previously, NM-MRI has been used in other clinical settings such as in Parkinson’s disease (PD), Alzheimer’s disease (AD), schizophrenia and depression; however, this current investigation is the first to utilize this imaging modality in the context of PTSD. Specifically, we hypothesized that increased NM-MRI signal in the LC would correlate with increasing severity of hyperarousal symptoms in individuals with PTSD. We also predicted that the opposite would be true for comorbid depression symptom severity, as reduced LC signal has been previously correlated with clinical measures of comorbid depression using NM-MRI. As per our primary hypothesis, we observed a significant positive correlation between NM-MRI signals in the caudal elements of the LC with hyperarousal symptom severity in 22 PTSD subjects (r= 0.54, p= 0.017; partial correlation controlling for depression symptom severity, age, and sex). In contrast, we did not find any evidence to support our secondary hypothesis, because a non-significant trend correlating LC NM-MRI signal and depression symptom severity was obtained (r= -0.30, p=0.22; partial correlation controlling for hyperarousal severity, age, and sex). Based on these results, we were able to build on previously conducted work to further investigate the utility of NM-MRI in the detection of variability in LC-NE system as it pertains to psychiatric conditions known to show dysregulation of this system such as PTSD. In addition, this thesis provides further evidence to support the automation of NM-MRI analytical methods, thus supporting their potential utility for future clinical research. Our findings also provide support for the use of NM-MRI as a potential measure of NE activity; further, this work provided preliminary evidence supporting the use of NM-MRI in a clinical, psychiatric setting, where the technique may serve as a biomarker of PTSD pathology. With these findings in mind, additional validation studies can be conducted to verify the use of NM-MRI as a biomarker for NE system dysregulation. This would potentially allow for advancements in targeted treatment options for PTSD, particularly those targeting the LC-NE system, thus potentially increasing patient stratification and treatment efficacy.

This study explores Working from Home (WFH) as a model of work in a public organisation in London, which operates in the clinical-trials sector. It argues that WFH is used as a strategy that offers benefits both to the organisation and its employees. WFH is offered to all Clinical Research Associates (CRAs) who work as monitors of the whole process of a clinical trial. Based on a qualitative approach, using semi-structured interviews of 29 CRAs, managers and administrative staff and secondary data, this single-case study focuses on five topics that are part of the CRAs’ everyday life. These are work-life balance (WLB), cost reduction, the Information and Communications Technology (ICT) factor, the performance of the CRAs and the management of remote workers. In particular, the study identified that WFH had a positive effect on CRAs’ WLB. Moreover, it argues that WFH may offer significant assistance to organisational budgets and may reduce personal expenses. It found that existing ICT could cover all employees’ technological needs and reduce the requirement of managers to keep them physically present at a centralised workplace. Additionally, this thesis also identified that WFH improved CRAs’ performance, whilst it also highlighted that results-oriented management was the main managerial approach towards employees who work from a distance. The key contribution of the thesis is the examination of the CRA occupation through a contemporary perspective on the WFH phenomenon.

There is increasing recognition of the relationship between depression and obesity in the pediatric population and recently, there has been a focus on inflammation as a potential link. Both conditions are considered to be pro-inflammatory states, and certain inflammatory markers are linked to depression in obese adults and vice versa. Leptin has also been implicated in depression as a potential mediator between inflammation and depression. Brain derived neurotrophic factor (BDNF), which is associated with depression and obesity, is influenced by inflammation and leptin in animal models as well. Few studies have examined the interactions between depression, adiposity, and biological markers in obese youth and therefore, our objective was to explore the determinants of depression in obese youth in a clinical setting. We studied 244 youth aged 8-17 years (125 girls, 119 boys) at the time of entry to a weight management program, as part of a prospective, longitudinal study. The CES-DC depression-screening tool was used to assess depressive symptoms, and a participant was classified as having high depressive symptoms if the CES-DC score ≥15 or taking antidepressants. Questionnaires assessed socio-demographic factors and puberty while adiposity was measured using dual-energy X-ray absorptiometry (DXA). Inflammatory markers (IL-6, TNFα, CRP, IL-10), leptin, and BDNF were quantified by immunoassays. Of the 244 participants, 8 were on antidepressants and 88 (36.4%) met the criteria for high depressive symptoms. We confirmed previous findings that household income and body fat were important determinants of depressive symptoms. However for the first time, it was identified that leptin levels predicted CES-DC score independent of body fat. Neither inflammatory markers nor BDNF were significantly related to depression scores. Our findings suggest that leptin may mediate the relationship of adiposity and depression but it is uncertain if this is related to direct action or to the phenomenon of leptin resistance. / Thesis / Master of Science (MSc) / Obesity has a significant impact on depression in children and adolescents. Inflammation – the body’s response to injury – is measured through markers in the blood and leptin – the marker of body fat – have shown to be related to depression. Research indicates that depression influences these factors to act on obesity. However, research on the interactions of biological and socio-demographic factors with depression in youth with obesity is lacking. Therefore, our objective was to explore the impact of these factors on depression in obese youth entering into a weight management program. Using a depression-screening tool, we studied 244 youth under 18 years and confirmed that household income and body fat were important factors of depression. However for the first time, we found leptin influenced depression regardless of the amount of fat present suggesting that depression acts on obesity through leptin but it is uncertain how this occurs and further research is warranted.

No description available.

Les informations médicales recueillies dans le cadre du soin doivent être utilisables pour répondre à d’autres objectifs plus collectifs. Dans ce contexte de réutilisation des données d’un système d’information clinique pour de la recherche en épidémiologie, l’objectif de ce travail est d’étudier l’apport de l'intéropérabilité sémantique à travers un certain nombre de situations concrêtes que nous avons rencontrées et étudiées et qui illustrent la nature des problèmes de cohérence sémantiques liés au traitement des données médicales et de santé.La coexistence, à un moment donné, de plusieurs référentiels sémantiques ne doit pas être considéré comme un obstacle à l'interopérabilité. Des outils génériques peuvent être conçus et développés pour passer de façon transparente d'un composant à un autre avec aussi peu de perte d’information que possible. L’Unified Medical Language System (UMLS) est un de ses outils d’intégration sémantique. Son usage dans le cadre de ces travaux montre le caractère général de cette méthode et son potentiel pour résoudre cette classe de problèmes d’intéropérabilité sémantique.La richesse de chacune des terminologies permet, lorsqu’elles sont associées dans un même référentiel sémantique pivot, d’enrichir l’ensemble des terminologies prises individuellement pour une meilleur représentation des connaissances.L’interopérabilité sémantique améliore la disponibilité et la qualité des données réutilisables pour des recherches en santé publique. Elle permet d’enrichir les données existantes. Elle fournit les moyens d'accéder à de nouvelles sources de données, agrégées de manière valide, permettant des analyses comparatives ou des analyses plus riches. / Medical information collected during clinical care must be re-used to address other more collective goals. In this context of re-using data from a clinical information system for epidemiological research, the objective of this work is to study the contribution of semantic interoperability across a number of practical situations we have met and discussed which illustrate the nature of semantic consistency problems associated with processing of medical data.Coexistence at a given time, of several semantic repositories should not be considered as an obstacle to interoperability. Generic tools can be designed and developed to move seamlessly from one component to another with as little loss of information as possible. The Unified Medical Language System (UMLS) is one of the semantic integration tools. Its use in this work shows the generality of this method and its potential for solving this class of semantic interoperability problems.The richness of each of the terminology can, when combined into a single pivot semantic repository, enrich the set of terminologies individually for a better representation of knowledge.Semantic interoperability improves the availability and quality of reusable data for public health research. It also enriches existing data. It provides access to new sources of data, aggregated in a valid manner, allowing benchmarking or richer analysis.

O objetivo deste estudo foi investigar variações no planejamento pré-cirúrgico para tratamento com implantes dentários entre cirurgiões dentistas com diferentes níveis de experiência profissional utilizando-se apenas a radiografia panorâmica (PAN), ou associando-a a tomografia computadorizada de feixe cônico (PAN+TCFC). Materiais e métodos: seis cirurgiões-dentistas, de dois diferentes níveis de experiência (sênior: Sr e júnior: Jr) executaram planejamentos pré-cirúrgicos simulados em PANs e após um mês em PAN+TCFCs, considerando os parâmetros: comprimento do implante (CI); largura do implante (LI); necessidade de enxerto ósseo (EO); necessidade de outros procedimentos cirúrgicos (PC). Para observar a concordância entre os planejamentos usando PAN e PAN+TCFC em relação a CI e LI, foi utilizado o teste estatístico de Bland-Altman. O coeficiente de kappa foi usado para observar a concordância entre os examinadores em relação a indicação de EO e PC. Os dados foram analisados por meio do software GraphPad Prism, versão 6.0. Resultados: O teste de Bland-Altman mostrou boa concordância nos planejamentos para os valores de CI e LI interexaminadores (Srs x Jrs) e intraexaminadores (PAN x TCFC). A estatística descritiva mostrou que examinadores Jrs indicam implantes dentários de maior largura quando planejam a partir da PAN em comparação com a TCFC. O teste de kappa mostrou forte (k>0,75) concordância entre examinadores Jrs e Srs nos planejamentos para tratamento com implantes em relação a indicação de outros procedimentos (PAN e TCFC). Na indicação de enxertos ósseos o nível de concordância entre os examinadores foi forte (k>0,75) quando o planejamento foi feito com PAN e regular quando o planejamento foi feito com TCFC. Conclusão: de acordo com a interpretação de nossos dados, há variações no planejamento pré-cirúrgico para tratamento com implantes dentários relacionadas a experiência profissional e o tipo de exame de imagem utilizado para o planejamento. / The purpose of this study was to investigate variations in pre-surgical planning for dental implant treatment among dental surgeons with different levels of professional experience using panoramic radiography (PAN) or associating it with computed cone beam tomography (PAN + TCFC). Materials and methods: Six dentists, from two different levels of experience (Senior: Sr and Junior: Jr) performed simulated pre-surgical planning in PANs and after one month in PANs + TCFCs, considering the parameters: implant length (CI); Implant width (LI); Need for bone graft (EO); Need for other surgical procedures (PC). In order to observe the agreement between the planning using PAN and PAN + TCFC in relation to IC and LI, the Bland-Altman test was used. The kappa coefficient was used to observe agreement between the examiners regarding the indication of OE and PC. Data were analyzed using GraphPad Prism software, version 6.0. Results: The Bland-Altman test showed good agreement in the plans for inter-examiner (Sr x Jr) and intra-examiner (PAN x TCFC) values. Descriptive statistics have shown that Jr examiners indicate larger dental implants when planning from PAN compared to TCFC. The kappa test showed strong (k> 0.75) agreement between Jr and Sr examiners in the plans for treatment with implants in relation to the indication of other procedures (PAN and TCFC). In the indication of bone grafts the level of concordance between the examiners was strong (k> 0.75) when planning was done with PAN and regular when planning was done with TCFC. Conclusion: according to the interpretation of our data, there are variations in the pre-surgical planning for treatment with dental implants related to professional experience and the type of imaging test used for the planning.

Este trabalho tem por escopo analisar o procedimento de experimentação de novos tratamentos médicos e farmacêuticos em seres humanos, mais especificamente, crianças e adolescentes. A partir da ideia da condição do menor de pessoa em formação e da proteção especial garantida pela ordem jurídica, busca-se, constatando a necessidade de realização de pesquisas clínicas com este grupo, analisar de que modo a doutrina dos denominados direitos humanos e fundamentais e a regulamentação bioética devem atuar no sentido de estabelecer normativamente os requisitos que garantam o desenvolvimento científico sem o sacrifício das prerrogativas humanas mais comezinhas, como a integridade física e psíquica, bem como a autonomia. Por fim, tendo em vista os conceitos de risco e precaução, são estabelecidos os pressupostos para o nascimento da responsabilidade civil, de pesquisadores, patrocinadores e responsáveis legais pelo menor, inclusive pais, com a abordagem, também, dos reflexos no poder familiar, quando eventuais danos venham a ser produzidos contra as crianças e adolescentes sujeitos de pesquisa. / This work has as scope the analysis of the procedure regarding new medical and pharmaceutical treatments testing in humans, more specifically children and teenagers. From the idea of the minors status as person under development and the special protection guaranteed by law, it is intended with this work, considering the need of clinical researches involving this group, an examination of how the so-called human and fundamental rights as well as bioethics regulation must act to standardize the requirements that ensure the scientific development without sacrificing the most basic human prerogatives, such as physic and psychological integrity and independence. Finally, in view of risk and precautions concepts, the assumptions are set to the arise of researchers, sponsors and guardians liability, including parents, also regarding the repercussion of such liability on parental authority, in the event of damages occurrence in children and teenagers in the context of clinical trials.

Contexto: Modificações químicas da superfície dos implantes dentários com o objetivo de aumentar a molhabilidade resultam em uma osseointegração mais rápida e melhor. Objetivo: O objetivo deste estudo foi avaliar o quociente de estabilidade do implante (ISQ) (implant stability quotient) de implantes com geometria idêntica, mas com tratamentos de superfície diferentes: jateamento de areia e ataque ácido (SAE) e a mesma superfície com uma modificação química para aumento da hidrofilia, dentro das primeiras 16 semanas de cicatrização. Materiais e Método: neste estudo clínico randomizado um total de 64 implantes (32 SAE - Grupo Controle e 32 SAE modificado - Grupo Teste) com o mesmo desenho geométrico, comprimento e diâmetro (cônico e compressivo, 4,3x10 mm) foram colocados na maxila posterior de 21 pacientes parcialmente desdentados. Os valores de ISQ foram coletados no pós - cirúrgico imediato (T0), com 1 semana (T1), 2 (T2), 3 (T3), 5 ( T4), 8 (T5), 12 (T6) e 16 semanas (T7). Os resultados foram comparados por meio do ANOVA de medidas repetidas. Resultados: O grupo teste apresentou valores de ISQ mais altos que o grupo controle (ANOVA - p<0,01) a partir da 5a semana. Quando comparados os grupos em relação ao tempo necessário para se atingir o ISQ >= 70 como uma referência, houve uma diferença estatisticamente significante (p<0,01) e um Hazard Ratio de 2,24 (IC 1,62-3,11). No acompanhamento de um ano um paciente com 2 implantes abandonou a pesquisa, e estes não puderam mais ser avaliados. A taxa de sobrevida de ambos grupos foi de 100% após um ano de acompanhamento. Conclusão: O presente estudo sugere que implantes com superfície hidrofílica osseointegram mais rápido que implantes com superfície SAE convencional. O ganho de estabilidade do grupo teste foi 2,24 vezes mais rápido que do grupo controle após 5 semanas de avaliação em leitos na maxila posterior. / Background: Chemical modifications of dental implant surface, to improve the wettability, results in a faster and better osseointegration. Purpose: The aim of this study was to evaluate the implant stability quotient (ISQ) of implants with the same design, treated with two different surfaces: Sandblasted Acid-Etched (SAE) and hydrophilic SAE, within the initial 16 weeks of healing. Materials and Method: For this RCT a total of 64 implants (32 SAE - Control Group and 32 modified SAE - Test Group) with the same design, length and diameter (conical and compressive, 4.3x10 mm) were inserted in the posterior maxillae of 21 patients partially edentulous. The ISQ values were collected at the post-surgery (T0), 1-week (T1), 2-weeks (T2), 3- weeks (T3), 5-weeks (T4), 8-weeks (T5), 12-weeks (T6) and 16-weeks (T7). The statistic test was ANOVA. Results: Test group presented ISQ values higher than the Control group (ANOVA - p<0.01) from 5th week. When comparing groups regarding the amount of time required to achieve ISQ >= 70 as a reference, there was a statistically significant difference (p <0.01), and a HR (Hazard Ratio) of 2.24 (CI 1.62- 3.11). At the one-year follow up, there was a drop out of one patient and two implants were no longer evaluated. Survival rate for both groups was of 100% after one year of follow up. Conclusion: The current study suggests that implants with hydrophilic surface (modified SAE) integrates faster than implants with SAE surface. Stability gain of the tested group was 2.24 times faster than the control group after five weeks of evaluation at the posterior region of maxillae.

A hanseníase causada pelo Mycobacterium leprae é a infecção que mais gera danos ao sistema nervoso periférico. Este microrganismo tem como alvo a célula de Schwann, o qual se liga à laminina, um dos constituintes da lâmina basal. Através desta ligação o Mycobacterium leprae penetra nas células de Schwann onde se multiplica, infectando o sistema nervoso periférico e desse modo comprometendo sua estrutura e funções. Provavelmente tal como ocorre em outras neuropatias degenerativas, inflamatórias ou neoplásicas, no processo de agressão nervosa na hanseníase, participam outras moléculas como a integrina beta1 e a proteína S-100. O presente trabalho estudou 44 doentes de hanseníase, classificados de acordo com Ridley e Jopling, distribuídos em: 12 doentes indeterminados, 7 doentes tuberculóides, 17 doentes dimorfo-tuberculóides, 2 doentes dimorfo-dimorfos, 2 doentes dimorfo virchowianos e 4 doentes virchowianos. Os propósitos foram estudar o dano nervoso nas terminações nervosas da pele por meio da expressão da integrina beta1 e da proteína S100; e ainda a análise da relação entre as manifestações dermatológica, neurológica, reação de Mitsuda, bacterioscopia e os achados imunohistoquímicos. A alteração da expressão da integrina beta1 nas terminações nervosas da pele foi variável, precoce e constante em 100% dos doentes. A alteração da proteína S-100 nas terminações nervosas da pele nos doentes foi de 88,6%. Apesar da significativa correlação entre elas, a sensibilidade da integrina beta1 foi maior. Encontrou-se correlação entre a clínica dermatológica e neurológica, bem como com a bacteriscopia e a reação intradérmica de Mitsuda. Não houve correlação das reações imunohistoquímicas com os dados clínicos, provavelmente em decorrência das alterações moleculares ocorrerem antes das manifestações clínicas / Leprosy caused by Mycobacterium Leprae is the infection that most causes damage to the peripheral nervous system. This microorganism has its principal target in the Schwann cells, which bind themselves to laminin, one of the constituints of the basic lamina. The Mycobacterium Leprae, by way of this link, penetrates the Schwann cells, where they multiply, infecting the peripheral nervous system and thus compromising its structure and functions. Probably, as happens in other degenerative neuropathies, inflammatory or neoplastic, other molecules participate in the process of nervous aggression of leprosy, such as beta1 integrin and S-100 protein. This paper studied 44 patients with leprosy, classified according to Ridley and Jopling, distributed as: 12 indetermined patients, 7 tuberculoid patients, 17 borderline-tuberculoid patients, 2 mid-borderline patients, 2 borderline-lepromatous patients and 4 lepromatous patients. The aims were to study the damage to the skin nerve endings by way of the levels of beta1-integrin and S-100 protein; and also the analysis of relation between dermatological, neurological clinical manifestations, the Mitsuda reactions, bacterioscopical and the immunohistochemical findings. The alterations in the amounts of beta1 integrin in the skin nerve endings were variable, premature and constant in 100 % of the patients. The alteration in the S-100 level in the skin nerve endings in the patients was 88,6 %. In spite of the correlation between them, the sensibility of the beta1 integrin was greater. There was found to be correlation between dermatological and neurological clinical manifestations as well as with the bacterioscopy and the Mitsuda intradermal reactions. There was no correlation between immunohistochemical reactions with the clinical data, probably because of the molecular alterations that occur before the clinical manifestations

Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1–324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.