Anal acoustic reflectometry (AAR) is a technique that is currently under investigation for the assessment of faecal incontinence. It uses reflected sounds waves to measure cross sectional area at different pressures leading to a profile of the anal canal, and in particular the high pressure zone of the anal sphincters. The cross sectional area from the high pressure zone is then plotted on a graph to give seven characteristic parameters. AAR has been shown to be reproducible and reliable, able to distinguish between continence and incontinence, correlate with the severity of incontinence and able to discriminate between the three patterns of incontinence (urge, passive and mixed). Opening pressure has been shown to be an independent predictor of success with peripheral nerve evaluation, the trial period before sacral nerve stimulation. This thesis aimed to validate AAR against manometry and explore its physiological and clinical potential. A retrospective analysis of 265 patients who had undergone AAR was undertaken in order to develop a surrogate marker for anal canal length. The surrogate marker did find the expected difference between men and women but this was not clinically significant. Furthermore, the surrogate marker was unable to differentiate between incontinence and continence. A technical limitation (Gibbs phenomenon) of AAR was subsequently shown to explain this unexpected result. Prior manometry could possibly interfere with the interpretation of AAR, and therefore a prospective randomised cohort study of 30 patients was conducted to assess two orders of data collection. Reassuringly it does not matter which one of these investigations is undertaken first. In order to test the hypothesis that the greater the challenge to the anal sphincter, the greater the response, the effect of two rates of anal canal stretch was investigated in a prospective randomised cohort study of 50 patients with faecal incontinence. No difference was found between normal or fast rates of AAR. This study has validated a faster method of AAR that can be used alongside manometry in any order. A pudendal nerve block was used to investigate whether AAR assesses primarily internal or external sphincter function in a prospective cohort study of 15 patients using both AAR and manometry. Bilateral pudendal nerve block reduced the function of the external anal sphincter but had no effect on the internal sphincter using both techniques. This study suggests that AAR at rest is predominately an investigation of the internal anal sphincter. A prospective study of 30 patients with faecal incontinence was carried out to establish if AAR can predict the outcome from posterior tibial nerve stimulation. Posterior tibial nerve stimulation improved rectal sensation, manometry squeeze pressures, quality of life, severity of incontinence and was more effective for patients with urge incontinence. A variety of demographic, clinical and physiological measures were unable to predict the success of posterior tibial nerve stimulation. The results presented in this thesis suggest that the full clinical potential of AAR has yet to be realised and it will be necessary to compare it with high resolution anal manometry in the future. Progress in this field would be greatly facilitated by establishing the normal values for this technique and the development of a robust AAR assessment of the external anal sphincter.

The aetiology of autoimmune disease is a complex interplay between genetics, environment and immunological regulation. Our understanding of the genetic aspects of autoimmunity has increased with recent findings from Genome Wide Association Studies (GWAS). There is now a movement towards meta-analyses of GWA studies in order to increase the number of genetic loci detected. There are also efforts to detect common genetic risk factors amongst groups of diseases that potentially share common aetiopathogenic pathways. Animal models have formed the basis of many genetic discoveries and the domestic dog presents a spontaneous model for many diseases, including autoimmunity. Through man’s efforts to create specific breeds, the dog has acquired a genomic architecture consisting of long haplotype blocks and extensive linkage disequilibrium. This means that a GWAS can be conducted in dog breeds with fewer samples and fewer markers than an equivalent study in humans, reducing costs, cohort collection times, and data handling/storage considerations. Successful canine GWA studies are now starting to be published. Building upon this success, the findings from GWA studies in three canine autoimmune diseases (across six different breeds), with equivalent human pathologies, are presented. Dogs with diabetes mellitus (similar to latent autoimmune diabetes of adulthood in man), lymphocytic thyroiditis (similar to Hashimoto’s thyroiditis), and anal furunculosis (similar to perianal Crohn’s disease) were compared to control dogs to identify genetic susceptibility loci underlying disease. Follow-up genotyping of the top hits from the GWAS analyses were conducted to replicate findings and to better characterise the diseases across a number of dog breeds. Typing of MHC class II genes, important in the immune response, was also undertaken in canine diabetes mellitus and canine lymphocytic thyroiditis. In anal furunculosis, high-throughput, next-generation sequencing was utilised to identify novel mutations and fine-map associations at discovered loci. Several genes were identified in all of these canine autoimmune diseases, many with good candidate function. Some of these genes indicated common genetic susceptibility loci and pathways between canine autoimmune diseases. Breed-specific genetic effects underlying canine diabetes mellitus and canine lymphocytic thyroiditis were identified, which has implications for disease diagnosis and clinical management. Novel loci for investigation in the corresponding human disease studies have been identified and future work will begin to genetically link the conditions in dog and man.

O Peptídeo Liberador de Gastrina é um peptídeo neuroendócrino que tem importante atividade como fator de crescimento em diferentes tipos de cânceres. A expressão aumentada do GRP tem sido documentada em várias neoplasias, e estudos sobre uso terapêutico do bloqueio dos receptores do GRP (GRPR) têm apresentado resultados promissores. Nosso objetivo foi determinar a expressão do GRPR no carcinoma epidermóide de canal anal e discutir suas potenciais aplicações clínicas. Foi realizada análise imunoistoquímica em blocos de parafina com amostras tumorais de 35 pacientes com câncer anal. Como grupo controle não maligno, analisamos 24 amostras de tecidos anais (anatomopatológicos de hemorroidectomias). A expressão do GRPR foi avaliada utilizando uma abordagem semi-quantitativa de acordo com a intensidade e distribuição da coloração. Todos os tecidos analisados, com exceção de uma amostra controle, apresentaram imunoexpressão positiva do GRPR. O GRPR teve forte expressão em 54% das amostras tumorais e em somente 12% das amostras do grupo controle (P < 0.003). Nos tumores, o receptor demonstrou um padrão de distribuição difuso e homogêneo Em contraste, as amostras do grupo controle apresentaram um padrão de coloração focal restrito à metade mais profunda da camada basal do epitélio. Em conclusão, demonstramos que o GRPR é altamente expresso no carcinoma epidermóide do canal anal, o que sugere que este receptor possa desempenhar um papel na carcinogênese anal. Nossos resultados fornecem uma base para a exploração do receptor de gastrina como um alvo diagnóstico e terapêutico no carcinoma anal.

Men who have sex with men continue to be at highest risk of HIV infection, with Black and Latino men who have sex with men [BLMSM] disproportionately at risk. The impact of alcohol consumption on condomless anal intercourse [CAI] is compounded for BLMSM by unique risk factors like internalized homophobia and racial stigma, reinforcing barriers to treatment. The traditional formats of existing HIV interventions fail to address heightened confidentiality concerns of BLMSM and few target both CAI and alcohol use. Existing interventions may be modified with mobile health [mhealth] technologies to improve outcomes for BLMSM. The current study examined the feasibility and acceptability of a novel mhealth intervention to reduce heavy drinking episodes [HDE], reduce CAI, and increase intentions to use pre-exposure prophylaxis medication [PrEP]. METHODS: Enrollment criteria included (1) Black and/or Latino man, (2) at least one episode of CAI with another man in the past six months, (3) at least one HDE in the past month and (4) no current PrEP use. Twelve participants completed a brief videoconferencing session then four weeks of interactive mobile messages. Outcome assessment was completed 8-weeks post-baseline. To assess feasibility and acceptability (primary outcomes), message response rates, ratings of intervention satisfaction (Client Satisfaction Questionnaire-8, CSQ), and ratings from a 10-item acceptability measure were used. RESULTS: Message response rates (M= 96%, SD = 0.04, Mdn = 98%) indicated high engagement. Ratings at follow-up indicated high acceptability (item rating M = 1.77, SD = 0.73, Mdn = 1.45; scores range from 1-5, lower ratings indicate higher acceptability) and high satisfaction (CSQ M = 26.7, SD = 4.08, Mdn = 27.5; scores range from 8-32, higher scores indicate higher satisfaction). Descriptive statistics were used to characterize post-intervention outcomes. HDEs decreased by 45% from baseline while PrEP use intentions remained largely unchanged (decreased by 5%). Only three of twelve participants reported CAI at post-intervention. DISCUSSION: Results show high engagement, acceptability, and satisfaction with the mhealth modality and support the feasibility of this approach to address HDE among BLMSM. Future efficacy testing of this novel mhealth intervention via randomized controlled trial is warranted.

Limited data exists on intimate partner violence (IPV) among transgender women (TW), though global trends suggest IPV is associated with HIV risk in this population. We describe the prevalence of verbal, physical, and/or sexual violence as well as participant- and partner-level correlates of IPV among TW in Lima, Peru. Among 389 respondents, 15.2% reported IPV with one or more of their last three sexual partners: 9.2% verbal, 8.2% physical, and 2.3% sexual violence. Physical and verbal violence were more common with stable partners (aPR 3.46, 95% CI 1.17–10.25, aPR 2.46, 95% CI 1.14–5.28, respectively). Physical violence was associated with condomless receptive anal intercourse (cRAI) (aPR 2.22, 95% CI 1.19–4.13) and partner alcohol use (aPR 4.38, 95% CI 1.56–12.33) while verbal violence correlated with participant inebriation (aPR 4.86, 95% CI 1.63–14.46). Our results link IPV with stable partnerships, alcohol use, and cRAI, suggesting TW in Peru may benefit from multidimensional IPV prevention strategies to foster supportive relationships and reduce HIV transmission. / amfAR, The Foundation for AIDS Research / Revisión por pares

No description available.

Background: The JAK-STAT pathway is a cellular signaling pathway, which acts normally in humans and animals in the control of multiple important functions. Dysregulation of this pathway has been identified in human cancers, as well as a limited number of veterinary cancers. Objectives: The aims of this study were to identify the presence and tentative activity of components of the JAK-STAT pathway in selected canine tumors. Methods: Formalin-fixed, paraffin-embedded samples from mast cell tumors (MCT), hemangiosarcomas (HSA), thyroid carcinomas, and apocrine gland anal sac adenocarcinomas (AGASACA) were obtained from the Diagnostic Histopathology Laboratory at the Virginia Maryland College of Veterinary Medicine. Immunohistochemistry was performed to evaluate protein levels of JAK1, phospho-JAK1, JAK2, phospho-JAK2, STAT3, and phospho-STAT3. Signalment, treatment information, and survival information was obtained from the medical record for each case. Results: Tumor samples were scored for percent positive neoplastic cells. Positive staining was seen for all antibodies in all tumor types, with expression of JAK1, STAT3, and pSTAT3 being highest overall for all tumor types. Significant associations were seen between JAK1 and survival time in MCT (p = 0.03), pJAK1 and survival time in HSA (p = 0.009) and MCT (p = 0.04), and pSTAT3 and metastasis in MCT (p = 0.0008). Conclusions: The finding of positive staining for the components of the JAK-STAT pathway in the tumor samples evaluated indicates presence and tentative activity of this pathway in the studied cancers. Further study of JAK1, pJAK1, and pSTAT3 should be pursued to evaluate their potential as therapeutic targets. / MS

Obstetrical intervantion`s goal is to normalize an abnormal or pathological course of labour. In a certain case (e.g. fetal distress) this is not fully achievable. Then the goal is to accelerate the delivery without inadequate increase of risk of maternal or neonatal trauma. The aim of this dizertation thesis was to offer an up-to-date definition and to outline a proper performance of these interventions. Therefore, it was necessary to properly and timely describe the labour layout in which the accoucheur and/or the parturient happen to occurr when an intervention is to take place. It was essential to describe the quantity of perineal loading as well as to define the main vector of perineal strain and deformation. Based on the range of this deformation it was subsequently possible to adequately describe and execute some obstetrical interventions (e.g. a variety of types of episiotomy) or to evaluate a variety of modifications by means of computational modelling (e.g. manual perineal protection) that might have so tiny nuances between each other or differences that are difficult to measure because the clinical evaluation is impossible due to interindividual imprecision or very short duration of the intervention. We described the maximum strain on the perineal surface during vaginal delivery that...

Made available in DSpace on 2015-04-14T14:12:24Z (GMT). No. of bitstreams: 1 402017.pdf: 892539 bytes, checksum: 77b9e139d7b2d5143a6077814f4b2eba (MD5) Previous issue date: 2008-03-31 / Este estudo teve como objetivo investigar os conte?dos matem?ticos aprendidos pelos alunos de tr?s turmas do 3o ano do Ensino M?dio de uma escola particular, da cidade de Porto Alegre/RS, ap?s a realiza??o de uma Unidade de Aprendizagem (UA) sobre geometria anal?tica. O problema desta pesquisa tem por base a seguinte pergunta: Como os alunos aplicam a linguagem matem?tica na interpreta??o de quest?es sobre geometria anal?tica em uma escola do ensino m?dio? Por conseq??ncia, o objetivo central do trabalho foi identificar e analisar conte?dos matem?ticos lembrados e n?o lembrados pelos alunos ap?s a realiza??o da UA sobre geometria anal?tica, bem como compreender o modo como aplicam a linguagem matem?tica na resolu??o de quest?es. Para isso, foram analisados os dados coletados por meio de relat?rios elaborados pelos alunos sobre a resolu??o de quest?es sobre geometria anal?tica, identificando os conte?dos presentes e comparando-os com os esperados pelo professor. A meta foi desenvolver uma metodologia para o desenvolvimento do conte?do de geometria anal?tica, identificando ap?s os conte?dos matem?ticos presentes em quest?es relacionadas ao tema, extra?das de concursos vestibulares. Ao t?rmino do trabalho, foi poss?vel identificar que conte?dos est?o mais presentes na aprendizagem dos alunos, bem como quais s?o os mais complexos, principais respons?veis pelas dificuldades de aprendizagem. Foi poss?vel tamb?m constatar que, ap?s a UA, os alunos passaram a utilizar linguagem matem?tica com maior autonomia e com mais significado na resolu??o de outras quest?es de conte?dos matem?ticos.

Submitted by PPG Direito (ppgdir@pucrs.br) on 2017-12-13T17:26:39Z No. of bitstreams: 1 VIN?CIUS_JOS?_ROCKENBACH_PORTELA_DIS.pdf: 1297929 bytes, checksum: 62d6c68d277e555a2ac184919275176e (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-12-19T13:04:00Z (GMT) No. of bitstreams: 1 VIN?CIUS_JOS?_ROCKENBACH_PORTELA_DIS.pdf: 1297929 bytes, checksum: 62d6c68d277e555a2ac184919275176e (MD5) / Made available in DSpace on 2017-12-19T13:35:48Z (GMT). No. of bitstreams: 1 VIN?CIUS_JOS?_ROCKENBACH_PORTELA_DIS.pdf: 1297929 bytes, checksum: 62d6c68d277e555a2ac184919275176e (MD5) Previous issue date: 2017-03-30 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / With the advent of the new Code of Civil Procedure (Law no. 13.105/2015), it emerged the obligation of analytical reasoning in judgments, laid down in article 489, paragraph 1, of the CPC, which sets forth the hypothesis in which will be not considered, for all legal purposes, reasoned the judgments. It turns out that part of the doctrine and the jurisprudence opposed barriers to the application of the referred legal dispositive to the procedural labor law, for they understand that it would not be fulfilled the requirements set out in article 769 of the CLT. In other words, under the arguments that there is no gap in the labor process ordinance and that the analytical reasoning would be incompatible with the procedural labor law. On the other hand, the other part of the doctrine and jurisprudence holds that the analytical reasoning is an important legal mechanism in combating judicial activism present in the labor courts, supporting the completion of the requirements set out in the law for implementation of common standards in labor process. Therefore, the doctrinal and jurisprudential debate, it abides to this work to address scientifically the question inherent in the requirement of analytical reasoning of judicial decisions in the labor process, mainly aiming to submit a proposal of a solution to this problem. After long research stabilized in doctrine and jurisprudence, it reaches two main conclusions. The first is that the article 489 of the CPC is not incompatible with the systematic and principiology of the procedural labor law, which is, therefore, perfectly applicable supplementarily to the labor process, before the existence of partial regulatory gap in CLT. Finally, the second conclusion is that it is essential that they are committed to efforts for the creation of a Code of Labor Procedure that contains sufficient mechanisms for the solution of the problems that plague labor relations in the present days, because, only that way, the labor process will return to have its vanguard status of a rapid, simple and effective process model, pursued by other procedural systems. / Com o advento do novo C?digo de Processo Civil (Lei n? 13.105/2015), surgiu o dever de fundamenta??o anal?tica das decis?es judiciais, previsto no artigo 489, par?grafo 1?, do CPC, o qual elenca as hip?teses em que n?o ser?o consideradas, para todos os efeitos legais, fundamentadas as decis?es judiciais. Ocorre que parte da doutrina e da jurisprud?ncia op?s entraves a aplica??o do referido dispositivo legal ao Processo do Trabalho, por entenderem que n?o estariam preenchidos os requisitos previstos no artigo 769 da CLT, isto ?, sob os argumentos de que n?o h? lacuna no ordenamento processual trabalhista e de que a fundamenta??o anal?tica seria incompat?vel com o Processo do Trabalho. De outro lado, a outra parte da doutrina e jurisprud?ncia defende que a fundamenta??o anal?tica ? um importante mecanismo legal no combate ao protagonismo judicial presente na Justi?a do Trabalho, sustentando o preenchimento dos requisitos fixados na lei para aplica??o da norma comum ao processo laboral. Posta, pois, a celeuma doutrin?ria e jurisprudencial, cumpre ao presente trabalho abordar cientificamente a quest?o inerente ? obrigatoriedade de fundamenta??o anal?tica das decis?es judiciais no Processo do Trabalho, objetivando-se, principalmente, apresentar uma proposta de solu??o para esse problema. Ap?s longa pesquisa lastreada na doutrina e jurisprud?ncia, chega-se a duas principais conclus?es. A primeira ? de que o artigo 489, caput e par?grafos, do CPC, n?o s?o incompat?veis com a sistem?tica e a principiologia processual trabalhista, sendo, por conseguinte, perfeitamente aplic?veis supletivamente ao Processo do Trabalho, ante a exist?ncia de lacuna normativa parcial na CLT. Por fim, a segunda conclus?o ? de que ? imprescind?vel que sejam empenhados esfor?os para a cria??o de um C?digo de Processo do Trabalho que contenha mecanismos suficientes para a solu??o dos problemas que assolam as rela??es de trabalho nos dias atuais, pois, s? assim, o Processo do Trabalho voltar? a ter seu status de vanguarda e de modelo de processo c?lere, simples e efetivo, perseguido pelos demais sistemas processuais.