Current syndromic surveillance systems utilize centralized databases that are neither scalable in storage space nor in computing power. Such systems are limited in the amount of syndromic data that may be collected and analyzed for the early detection of infectious disease outbreaks. However, with the increased prevalence of international travel, public health monitoring must extend beyond the borders of municipalities or states which will require the ability to store vasts amount of data and significant computing power for analyzing the data. Intelligent mobile agents may be used to create a distributed surveillance system that will utilize the hard drives and computer processing unit (CPU) power of the hosts on the agent network where the syndromic information is located. This thesis proposes the design of a mobile agent-based syndromic surveillance system and an agent decision model for outbreak detection. Simulation results indicate that mobile agents are capable of detecting an outbreak that occurs at all hosts the agent is monitoring. Further study of agent decision models is required to account for localized epidemics and variable agent movement rates.

Orientador: Jair Cortez Montovani / Banca: Victor Nakajima / Banca: Luciana Paula Maximo / Resumo: A deficiência auditiva é o déficit sensorial mais comum e tem dentre as suas diferentes etiologias as alterações genéticas. Mutações na conexina 26 são comuns, e uma mutação específica no gene GJB2 é a 35delG, a mais encontrada na deficiência auditiva hereditária não sindrômica. Investigar a ocorrência da mutação 35delG, em pacientes com deficiência auditiva sensorioneural não sindrômica (DASNNS) e de seus parentes em primeiro grau com o mesmo tipo de disacusia assim como naqueles com audição dentro dos padrões de normalidade. Participaram do estudo 72 indivíduos, atendidos no Serviço de Saúde Auditiva do Centro de Reabilitação dos Distúrbios da Audição e Comunicação (CERDAC), do Hospital das Clínicas da Faculdade de Medicina de Botucatu‐ UNESP. Estes indivíduos foram divididos em três grupos ‐ Grupo A: 58 casos com DASNNS; Grupo B: 09 casos (parentes em primeiro grau do grupo A) com DASNNS e Grupo C: 05 indivíduos parentes em primeiro grau do grupo A com audição dentro dos padrões de normalidade. Todos foram submetidos à avaliação audiológica e investigação genética para o rastreamento da mutação 35delG. 67 casos apresentaram deficiência auditiva sensorioneural não sindrômica (DASNNS) ‐ Grupos A e B, e 05 indivíduos com audição dentro dos padrões de normalidade (Grupo C). Quanto às mutações 35delG encontradas, quatro foram mutações em heterozigose, três delas encontradas em uma mesma família: pai (38anos), mãe (28 anos) e filho (05 anos) afetados. Nesta família, os pais eram ouvintes normais e o filho apresentou DASNNS pré‐lingual de grau grave bilateral. A outra mutação em heterozigose foi encontrada em paciente do sexo feminino, 38 anos, com DASNNS pré‐lingual de grau moderado bilateral. A única mutação em homozigose foi em um paciente do sexo masculino... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Hearing impairment is the most common sensory deficit and has among its different etiologies the genetic disorders. Mutations in connexin 26 are common and a specific mutation in the gene GJB2 is the 35delG, the most commonly found in hereditary non‐syndromic deafness. To investigate the occurrence of the 35delG mutation in patients with non‐syndromic sensorineural hearing loss (NS‐SNHL) and their first‐degree relatives with the same type of hearing loss as well as those with normal hearing. The study included 72 patients from the Division of Hearing Health of the Hearing and Communication Disorders Rehabilitation Center (CERDAC), Botucatu Medical School Hospital, UNESP. These individuals were divided into three groups ‐ Group A: 58 cases with NS‐SNHL, Group B: 09 cases (first‐degree relatives of group A) with NS‐SNHL and Group C: 05 cases with normal hearing, first‐degree relatives of patients from group A. All patients were submitted to audiologic evaluation and genetic testing of the 35delG mutation. 67 patients had non‐syndromic sensorineural hearing loss (NS‐SNHL) ‐ Groups A and B, and 05 individuals had normal hearing (Group C). As for 35delG mutations found, four were heterozygous mutations, three of them found in the same family: father (38 years old), mother (28 years old) and son (05 years old) affected. In this family, the parents had normal hearing and the child had severe prelingual NS‐SNHL. The other heterozygous mutation was found in a female patient, 38 years old, with bilateral moderate pre‐lingual NS‐SNHL. A single homozygous mutation was found in a male patient, 20 years old, with a severe pre‐lingual SNHL in his right ear and a profound SNHL in his left ear. The study of the 35delG mutation was found to be easy to perform and inexpensive; it was possible to determine the... (Complete abstract click electronic access below) / Mestre

Background: The burden of Sexually transmitted infections (STIs) is high globally. The World Health Organisation (WHO) recommends syndromic management of these STIs, based on presentation with signs and symptoms, in resource-limited countries. Due to this syndromic approach, there is little current data on STI prevalence, including asymptomatic STIs, in high risk populations. Methods: We reviewed secondary data collected as part of the screening procedures of 6 clinical trials between 2012 and 2017 in Cape Town, South Africa. These trials recruited populations of different sexual orientation and gender, mostly key populations at risk of HIV and STI acquisition. Routine screening for STI symptoms and testing for Chlamydia, Gonorrhoea, Trichomonas, Syphilis and HIV was performed for all of the studies at screening/enrollment. Results: A total of 639 participants were screened; 411 (64.3%) self-identifying as female, 198 (31%) males, 29 (4.5%) transgender women and 01 (0.2%) transvestite. Median age was 20 years (IQR: 18-24), with the 15-24-year age category contributing 77% to the cohort. Laboratory testing diagnosed 239 (37.4%) people with STI infections in this cohort; only 28 (11.7%) people were symptomatic. 119 (88.8%) of Chlamydial, 64 (82.1%) of Gonorrhoeal, 23 (92%) of Trichomonal and 31(79.5%) of Syphilis infections elicited no signs and/or symptoms. Conclusion: A vast majority of STIs in this high-risk population were asymptomatic. Laboratory testing of causal organism was more reliable in diagnosing STIs than the use of signs and/or symptoms as recommended by WHO.

No description available.

As alterações cromossômicas estruturais associadas a fenótipos clínicos oferecem a oportunidade de identificação de genes cujas mutações possam estar determinando essas patologias, tendo em vista a possibilidade de que esses genes podem ter sido alterados pelas quebras ou ter o número de cópias modificado. Um número cada vez maior de evidências aponta para a participação de certas seqüências do genoma na formação de rearranjos cromossômicos recorrentes e não recorrentes. Neste trabalho, estudamos duas deleções cromossômicas detectadas em indivíduos com retardo mental associado a sinais clínicos. O objetivo foi determinar que mecanismos originaram esses rearranjos e como a perda ou quebra dos segmentos cromossômicos está relacionada com o fenótipo dos portadores. A caracterização das seqüências nos pontos de quebra e junção desses rearranjos é fundamental para a compreensão dos mecanismos de formação das alterações cromossômicas. A delimitação precisa dos segmentos deletados é necessária para a correlação com o quadro clínico. Para isso, este trabalho aliou o estudo cromossômico por hibridação in situ fluorescente (FISH) à análise do DNA. / Structural chromosomal alterations related to clinical phenotypes bring the opportunity to identify gene mutations determining the pathologies, because the causative genes may have been disrupted by the breaks or may have an altered number of copies. The delimitation of the segments involved in the chromosomal rearrangements is necessary for these genotype-phenotype correlations. The characterization of breakpoint and junction sequences in these chromosome alterations enables the identification of mechanisms originating them, and evidence has been produced pointing to the participation of particular genomic sequences in their formation. In this work, we studied two chromosomal deletions in patients with syndromic mental retardation, combining chromosomal analysis by fluorescent in situ hybridization (FISH) to DNA analysis. Our aim was to determine the mechanisms that originated these aberrations and how they were involved with the clinical phenotypes.

A complexidade da fisiologia da audição resulta da participação e interação de produtos de grande número de genes, razão pela qual a surdez hereditária exibe enorme heterogeneidade genética. Estudos moleculares nas duas últimas décadas permitiram a identificação de vários genes responsáveis por surdez; entretanto, muitos ainda restam ser identificados. A maioria dos estudos de mapeamento de genes de surdez até então conduzidos privilegiou estratégias que buscavam mutações de ponto. Outros mecanismos mutacionais, como deleções e duplicações, foram pouco investigados. Portanto, a contribuição das CNVs (Copy Number Variations) na surdez hereditária é pouco conhecida. O objetivo desse trabalho foi identificar novos genes que possam ter papel na etiologia da surdez sindrômica ou não-sindrômica por meio da investigação de microdeleções e microduplicações em pacientes com perda auditiva. Selecionamos 25 genes candidatos (CTTN, FGF3, FGF19, FOXC1, FOXF2, FOXQ1, IMMP2L, KIF5C, LRRN3, MAP1A, MYLK4, PPP3CA, SHANK2, SLC5A7, STRC, TMC1, TMC2, TMC3, TMC4, TMC5, TMC6, TMC7, TMC8, TPCN2 e TUBB2A) para a triagem de microrrearranjos por meio da técnica de MLPA (Multiplex Ligation-dependent Probe Amplification). Os genes candidatos foram selecionados a partir de rearranjos detectados em um estudo prévio realizado por meio de array-CGH (array-based Comparative Genomic Hybridization) em indivíduos com surdez sindrômica estudados em nosso laboratório, e também a partir de dados da literatura. Nossa casuística foi composta por 163 indivíduos, dos quais 74 são pacientes com surdez associada a outros sinais (sindrômicos), a maioria casos isolados, e 89 são pacientes com surdez não-sindrômica, propósitos de famílias em que segrega surdez de herança autossômica dominante ou recessiva. Desenhamos uma sonda sintética intragênica de MLPA para cada um dos genes candidatos. Foram detectadas seis deleções em TMC6 (3,7%), seis deleções e uma duplicação em STRC (4,3%) e uma duplicação em IMMP2L (0,6%). A triagem de alterações nesses três genes em 189 indivíduos fenotipicamente normais revelou quatro deleções em TMC6 (2,1%), oito deleções e três duplicações em STRC (5,8%) e três deleções em IMMP2L (1,6%). Todas as alterações em TMC6, tanto nos casos de surdez como nos controles, eram na realidade artefatos devidos a problemas de hibridação da sonda correspondente. No gene STRC, previamente já relacionado à surdez, os rearranjos nos indivíduos afetados devem se tratar de polimorfismos sem efeito fenotípico por serem muito frequentes na população. Contudo, é possível que haja nesses pacientes mutações adicionais que não puderam ser rastreadas e que poderiam contribuir ao fenótipo, em combinação com o rearranjo detectado, como já descrito em um caso da literatura. A duplicação em IMMP2L em uma paciente com surdez não-sindrômica, herdada da mãe igualmente afetada, mostrou-se a mais provavelmente relacionada ao fenótipo, pois o estudo complementar por meio de array-CGH revelou que o rearranjo inclui uma duplicação parcial da porção 3 de outro gene, DOCK4. O produto desse gene possui uma isoforma que se localiza nos estereocílios das células ciliadas e se liga a uma importante proteína relacionada à audição, a harmonina. Portanto, nossa hipótese é a de que a duplicação seja a causa da surdez na família e que DOCK4 seja um novo gene responsável por surdez. A associação de IMMP2L com surdez é menos provável devido ao grande número de CNVs não patogênicas já descritas que incluem partes desse gene. Estudos complementares são necessários para mapear a duplicação com mais precisão. Além disso, o rastreamento de mutações em DOCK4 em outras famílias com surdez pode vir a confirmar o possível papel desse gene na etiologia da surdez. / Several genes contribute to the complexity of physiology of hearing. Consequently, hereditary deafness is extremely heterogeneous from the genetic point of view. In the last two decades, several genes responsible for hereditary hearing loss have been identified, but a large number of genes remains to be found, as evidenced by the unexplained cases of inherited deafness. The search for point mutations in candidate genes after mapping based on linkage studies has been the main strategy in the identification of such genes. Other mutation mechanisms, such as deletions and duplications, have been rarely investigated, and the contribution of DNA copy number variants (CNVs) to hearing loss is not well known. This study aimed at identifying novel genes, which might play a role in the etiology of syndromic and non-syndromic deafness, through the search of gene microdeletions and microduplications. We selected 25 candidate genes (CTTN, FGF3, FGF19, FOXC1, FOXF2, FOXQ1, IMMP2L, KIF5C, LRRN3, MAP1A, MYLK4, PPP3CA, SHANK2, SLC5A7, STRC, TMC1, TMC2, TMC3, TMC4, TMC5, TMC6, TMC7, TMC8, TPCN2 and TUBB2A) based on their involvement in microimbalances detected by Array-based Comparative Genomic Hybridization (aCGH) in a previous study of a Brazilian sample of individuals with syndromic hearing loss from our laboratory and others reported in the literature. We studied 163 subjects, 74 of them presenting syndromic deafness, the majority were isolated cases, and 89 being probands of families in which nonsyndromic deafness had an autosomal dominant or recessive mode of inheritance. Gene deletions or duplications were screened by Multiplex Ligant-dependent Probe Amplification (MLPA) using one synthetic intragenic probe designed for each candidate gene. We detected six deletions in TMC6 (3,7%), six deletions and one duplication in STRC (4,3%), and one duplication in IMMP2L (0,6%). The screening of imbalances in these genes in a control sample of 189 hearing individuals revealed four deletions in TMC6 (2,1%), eight deletions and three duplications in STRC (5,8%) and three deletions in IMMP2L (1,6%). The imbalances found in TMC6, both in affected and control individuals, were in fact artifacts due to problems in the hybridization of the corresponding probe. As to the STRC gene, previously related to deafness, the imbalances are more likely to be 4 polymorphisms with no phenotypic effect. However, the possibility remains that additional undetected mutations in affected individuals contribute to their phenotype, in combination with the microrearrangement, as already reported in the literature. The duplication in IMMP2L in a non-syndromic patient, and also present in her affected mother, is most likely causative of deafness, since a complementary study performed with aCGH revealed that the rearrangement included a partial duplication of the 3 end of another gene, DOCK4. An isoform of the DOCK4 protein localizes to the stereocilia in the inner ear and interacts with harmonin, a protein already known to be involved in hearing. We hypothesize that this duplication may be the cause of deafness in the family and, this being the case, DOCK4 appears as a novel deafness gene. The causal association between IMMP2L and deafness is less plausible, because of the large number of reported non-pathogenic CNVs that include parts of this gene. Further studies are required to precisely map this duplication. In addition, the screening of mutations in DOCK4 in other families with hearing impairment is required to evaluate its possible role in the etiology of deafness.

La surveillance des maladies abortives chez les bovins actuellement absentes du territoire (dites maladies exotiques), parmi lesquelles figure la brucellose, constitue un cas emblématique de système de surveillance à faire évoluer. Cette surveillance n'est réellement organisée que pour la brucellose. Pour cette maladie, la surveillance évènementielle basée sur la déclaration obligatoire de tout avortement (DA) constitue la pierre angulaire de la surveillance, mais souffre de l'avis de l'ensemble des acteurs, d'une forte sous-déclaration, sans que cela ait été évalué. Dans le cadre de cette thèse, l'évaluation approfondie du dispositif de DA a permis de quantifier la faible sensibilité de ce dispositif et d'identifier l'influence de différents facteurs, structurels, humains et sanitaires, sur le processus de déclaration. En parallèle, des données démographiques et de reproduction, collectées respectivement à des fins de traçabilité des animaux et d'amélioration des performances génétiques, ont été utilisées pour élaborer des indicateurs indirects de survenue d'avortements. La modélisation des variations temporelles et spatio-temporelles de ces indicateurs a souligné la capacité d'outils de surveillance syndromique à identifier la survenue d'évènements abortifs à l'échelle individuelle et des élevages. Au vu de ces travaux, l'amélioration de la surveillance des maladies exotiques abortives passe par le renforcement du dispositif de DA et le développement d'outils de surveillance syndromique. Plus globalement, dans un contexte où les risques d'apparition de maladies exotiques ou émergentes et les formes épidémio-cliniques qu'elles revêtiraient sont très difficilement prévisibles, il apparaît nécessaire de revisiter la surveillance des maladies exotiques et émergentes en définissant des systèmes de surveillance intégrée, déclinés par filière de production, associant différentes modalités de surveillance. De tels systèmes, en couvrant des maladies connues ou non, présentes sous forme clinique ou asymptomatique, et sous forme sporadique, épizootique ou diffuse, optimiseraient les chances de détecter les maladies exotiques ou émergentes / The surveillance system for exotic abortive diseases in French cattle (i.e. abortive diseases that are not currently found in France), such as brucellosis, is a typical example of a surveillance system that is in need of improvement. This type of surveillance only actually exists for brucellosis. Clinical surveillance is the cornerstone of brucellosis surveillance and consists in the mandatory notification of each bovine abortion. However, while no quantitatively assessments have been made, it is common knowledge that this type of surveillance suffers from high levels of under-reporting. By providing an in-depth assessment of the bovine abortion notification surveillance system, we quantified its low sensitivity and identified the influence of structural, human and health factors on how decisions to report abortions are taken. In addition, demographic and reproductive data, collected for purposes of traceability and for genetic performance improvement, were used to devise indirect indicators of abortion occurrence. By modeling the temporal and spatio-temporal variations of these indicators, we highlighted the ability for syndromic surveillance systems to identify the occurrence of abortive events at individual and herd scale. Based on these studies, improving exotic abortive disease surveillance requires revising the mandatory notification surveillance system and developing syndromic surveillance systems. More generally, considering the difficulties in predicting the occurrence of exotic or emerging diseases and their clinical and epidemiological forms, it is necessary to reorganize the surveillance of exotic diseases by setting up integrated surveillance systems that would include different surveillance modalities. Such surveillance systems, implemented by production sector, would focus on known or unknown diseases, showing clinical or subclinical forms, and sporadic, epizootic or diffuse patterns, and would thus maximize the ability to detect exotic or emerging diseases

<p>The aims of this thesis were to expand the knowledge about sexual and reproductive health among urban Ugandan youths, living in a slum, and to evaluate the national flow-chart for management of the abnormal vaginal discharge (AVD) syndrome in adolescent girls. Data collection included individual interviews, focus-group discussions and clinical investigations with tests for chlamydia trachomatis (CT), neisseria gonorrhoea (NG), trichomonas vaginalis (TV), syphilis, and HIV infection. Poverty, peer pressure and gender power imbalance were obstacles to safe sexual practices: to abstain from sex, be faithful or to use condoms. Prevalence among the 199 female and 107 male adolescents for CT, NG, TV, syphilis and HIV was 4.5%, 9.0%, 8.0%, 4.0% and 15.2% for females and 4.7%, 5.7%, 0%, 2.8% and 5.8% for males. The national AVD flow-chart had a sensitivity of 61%, a specificity of 38.5% and a positive predictive value (PPV) of 11.6%. A flow-chart using risk factors, rather than symptoms, implicated a sensitivity/specificity and PPV of 82.6%/47% and 17.3% respectively. Socially disadvantaged females had a high risk to be HIV infected and HIV infection was associated to other STIs. Females were more likely than males to have any of the infections studied. Voluntary counselling and testing (VCT) for HIV was considered as helpful in preventing the spread of HIV. Obstacles for testing were: lack of time and money, fear of stigmatisation and fear that the knowledge of HIV positive status could shorten someone's life. An alternative flow-chart for management of AVD among adolescent girls should be evaluated. Girl's opportunities for education and income generating work should be a priority. VCT services for young people should be made accessible in terms of cost, time and quality of counselling.</p>

The aims of this thesis were to expand the knowledge about sexual and reproductive health among urban Ugandan youths, living in a slum, and to evaluate the national flow-chart for management of the abnormal vaginal discharge (AVD) syndrome in adolescent girls. Data collection included individual interviews, focus-group discussions and clinical investigations with tests for chlamydia trachomatis (CT), neisseria gonorrhoea (NG), trichomonas vaginalis (TV), syphilis, and HIV infection. Poverty, peer pressure and gender power imbalance were obstacles to safe sexual practices: to abstain from sex, be faithful or to use condoms. Prevalence among the 199 female and 107 male adolescents for CT, NG, TV, syphilis and HIV was 4.5%, 9.0%, 8.0%, 4.0% and 15.2% for females and 4.7%, 5.7%, 0%, 2.8% and 5.8% for males. The national AVD flow-chart had a sensitivity of 61%, a specificity of 38.5% and a positive predictive value (PPV) of 11.6%. A flow-chart using risk factors, rather than symptoms, implicated a sensitivity/specificity and PPV of 82.6%/47% and 17.3% respectively. Socially disadvantaged females had a high risk to be HIV infected and HIV infection was associated to other STIs. Females were more likely than males to have any of the infections studied. Voluntary counselling and testing (VCT) for HIV was considered as helpful in preventing the spread of HIV. Obstacles for testing were: lack of time and money, fear of stigmatisation and fear that the knowledge of HIV positive status could shorten someone's life. An alternative flow-chart for management of AVD among adolescent girls should be evaluated. Girl's opportunities for education and income generating work should be a priority. VCT services for young people should be made accessible in terms of cost, time and quality of counselling.

Deep penetration of personal computers, data communication networks, and the Internet has created a massive platform for data collection, dissemination, storage, and retrieval. Large amounts of textual data are now available at a very low cost. Valuable information, such as consumer preferences, new product developments, trends, and opportunities, can be found in this large collection of textual data. Growing worldwide competition, new technology development, and the Internet contribute to an increasingly turbulent business environment. Conducting surveillance on this growing collection of textual data could help a business avoid surprises, identify threats and opportunities, and gain competitive advantages.Current text mining approaches, nonetheless, provide limited support for conducting surveillance using textual data. In this dissertation, I develop novel text quantification approaches to identify useful information in textual data, effective anomaly detection approaches to monitor time series data aggregated based on the text quantification approaches, and empirical evaluation approaches that verify the effectiveness of text mining approaches using external numerical data sources.In Chapter 2, I present free-text chief complaint classification studies that aim to classify incoming emergency department free-text chief complaints into syndromic categories, a higher level of representation that facilitates syndromic surveillance. Chapter 3 presents a novel detection algorithm based on Markov switching with jumps models. This surveillance model aims at detecting different types of disease outbreaks based on the time series generated from the chief complaint classification system.In Chapters 4 and 5, I studied the surveillance issue under the context of business decision making. Chapter 4 presents a novel text-based risk recognition design framework that can be used to monitor the changing business environment. Chapter 5 presents an empirical evaluation study that looks at the interaction between news sentiment and numerical accounting earnings information. Chapter 6 concludes this dissertation by highlighting major research contributions and the relevance to MIS research.