Submitted by admin tede (tede@pucgoias.edu.br) on 2018-06-19T18:06:59Z No. of bitstreams: 1 SAMARA SOCORRO SILVA PEREIRA.pdf: 764936 bytes, checksum: 434a8cd13e6701c05b6ea08edda95150 (MD5) / Made available in DSpace on 2018-06-19T18:06:59Z (GMT). No. of bitstreams: 1 SAMARA SOCORRO SILVA PEREIRA.pdf: 764936 bytes, checksum: 434a8cd13e6701c05b6ea08edda95150 (MD5) Previous issue date: 2018-03-14 / Copy Number Variation (CNV) has been associated with intelectual disability (ID) and this condition occur in approximately 2% of world population. Chromosomal Microarray Analysis (CMA) is being indicated as first-tier test for individuals with ID and has also helped to understand the mechanisms of CNV formation, classification of these rearrangements, type of recurrence, and its origin. The aim of this study was to infer the parental chromosome origin of de novo pathogenic CNV in patients with ID and their mechanisms of formation. Patients with clinical indications of ID were referred to Replicon Research Group/LaGene for G-band karyotyping. CMA approach was done for patients without numerical and/or structural rearrangements results in karyotype. After performing CMA and classification of CNVs, the parental origin of pathogenic CNVs was done using Mendelian error check based on SNPs markers available by ChAs software. In addition, the UCSC Genome Browser website was used to detect Low Copy Repeats (LCR) surrounding the CNVs to infer the mechanisms of their formation. In the period from 2013 to 2015 was performed G-band karyotyping in 290 patients with clinical indication of ID and a total of 193/290 (66.5%) were diagnosed by Karyotype. The group of patients who were not diagnosed using the karyotype, only 76/97 (78.3%) agreed to continue the investigation by CMA’s approach. After performing CMA, a total of 15 de novo pathogenic CNVs were observed, 10 CNV of loss and 5 CNV of gain, in 13/76 (17.1%) patients. The analysis of the parental origin showed 60% of CNVs are of maternal origin and 40% of paternal origin. It was not possible to detect the influence of parental age in the formation of CNVs. After analyzing the presence of surrounding LCRs, it was observed that 46.7% are recurrent CNVs and the mechanism of formation was Non- Allelic Homologous Recombination (NAHR), and 71.4% of these recurrent CNVs are of maternal origin. These data are in agreement with studies that affirm that the majority of CNVs of paternal origin are nonrecurrent due to germ cells replicate many times their genetic material in the pre-meiotic phase, being possible to infer the mechanism of formation of CNV that may have been by Microhomology-mediated break-induced replication (MMBIR) or Non-homologous end joining (NHEJ). / A variação no número de cópias (CNV) no genoma é um dos fatores etiológicos que pode desencadear a condição da deficiência intelectual (DI), sendo que esta condição atinge cerca de 2% da população mundial. A metodologia de análise cromossômica por microarranjo (CMA) além de ser indicada como teste de primeira escolha para pacientes com DI, tem ajudado também na compreensão da formação de CNVs e classificação destes rearranjos, quanto à patogenicidade, o tipo de recorrência e sua origem. E este estudo objetivou inferir a origem cromossômica parental das CNVs de novo patogênicas em pacientes com DI e seu mecanismo de formação. Os pacientes com indicação clínica de DI foram encaminhados ao Núcleo de Pesquisas Replicon/LaGene para realização do cariótipo com bandeamento GTG, e subsequentemente, os que não tiveram alteração numérica e/ou estrutural no cariótipo foram convidados a continuar a investigação em nível genômico, pela metodologia de CMA. Após realização do CMA e classificação das CNVs, foram realizadas a análise da origem parental das CNVs de novo patogênicas pela análise do erro mendeliano usando os marcadores de SNPs disponibilizado pelo software ChAS. Adicionalmente, foi usado o UCSC Genome Browser para detectar Repetições De Poucas Cópias (LCR) circundantes as CNVs para inferir o mecanismo de formação das mesmas. Foi realizado o cariótipo em 290 pacientes com indicação clínica de DI entre os anos de 2013 a 2015 e em 193/290 (66,5%) foram diagnosticados pelo cariótipo. Do conjunto de pacientes que não foram diagnosticados usando o cariótipo, apenas 76/97 (78,3%) aceitaram continuar a investigação pelo CMA. Após realizar o CMA, foi observado 15 CNVs de novo patogênicas, 10 CNVs de perda e 5 CNVs de ganho, em 13/76 (17,1%) pacientes. Na análise da origem parental, observou-se que 60% das CNVs são de origem materna e 40% de origem paterna. Não foi possível detectar a influência da idade parental na formação das CNVs. Ao analisar a presença de LCRs circundantes, observou-se que 46,7% das CNVs de novo patogênicas são recorrentes e o mecanismo de formação foi a Recombinação Homologa Não Alélica (NAHR), e 71,4% dessas CNVs recorrentes são de origem materna. Esses dados corroboram com os estudos que afirmam que a maioria das CNVs de origem paterna são não recorrentes devido às células germinativas replicarem inúmeras vezes o seu material genético na fase pré-meiótica, sendo possível inferir sobre o mecanismo de formação que pode ter sido por Replicação Induzida por Quebra e Mediada por Microhomologia (MMBIR) ou Junção de Extremidade Não Alélica (NHEJ).

Objetivo: Avaliar a prevalência, a gravidade e os fatores de risco associados à sibilância recorrente em crianças nos primeiros dois anos de vida em uma coorte de nascimentos. Métodos: Estudo de coorte prospectivo de 3167 crianças nascidas em Ribeirão Preto, SP, no ano de 2010 e avaliadas para esse estudo entre 12 e 24 meses. Os responsáveis pelos lactentes participantes responderam a questionários padronizados com questões referentes às características maternas, condições gestacionais, perinatais e pós-natais, antecedentes pessoais e familiares de doenças alérgicas, ocorrência e número de episódios de sibilância, ida a serviços de emergência, uso de medicações, diagnóstico de pneumonia e internações. O estudo das associações entre os desfechos e as variáveis independentes de interesse foi feito por meio de análise univariada e por modelos log-binomiais ajustados, obtendose medidas de risco relativo (RR) e seus intervalos de confiança (IC). Resultados: A prevalência de pelo menos um episódio de sibilância nos dois primeiros anos de vida foi de 56,3% (1785/3167), sendo que 35,8% (1136/3167) lactentes apresentaram sibilância ocasional (até dois episódios) e 20,1% (639/3167) apresentaram sibilância recorrente (três ou mais episódios). Sibilância recorrente grave (mais de 6 episódios) foi relatada em 8,7% lactentes (277/3167). Os fatores de risco independentes para apresentar de 3 a 6 episódios de sibilância foram: prematuridade (RR=1,46), tabagismo passivo (RR= 1,72, se menos de 10 cigarros/dia e RR=2,04. se mais de 10 cigarros/dia), frequentar a creche após os 6 meses (RR= 1,31), diagnóstico médico de rinite alérgica (RR= 1,52) e presença de carpete no domicílio (RR= 1,59). Os principais fatores de risco associados à sibilância grave foram: tabagismo passivo (RR= 2,89 para mais de 10 cigarros/dia), frequentar creche (RR= 2,43, se início até os 6 meses e RR: 1,49, se início após os 6 meses), resfriados nos 3 primeiros meses de vida (RR= 2,17), asma (RR= 1,50) e dermatite atópica na família (RR= 1,49) e diagnóstico de rinite alérgica (RR= 1,93). Lactentes brancos apresentaram prevalência menor de sibilância recorrente não grave (RR=0,68). Não houve associação entre o tempo de aleitamento materno e sibilância recorrente. Conclusões: Crianças nascidas em Ribeirão Preto apresentam alta prevalência de sibilância recorrente nos dois primeiros anos de vida. Nessa fase precoce da vida, medidas ambientais visando a diminuição da exposição à fumaça do cigarro e a prevenção de infeções virais poderiam resultar na redução dos casos de sibilância recorrente grave nesta população. / Objective: To evaluate the prevalence, severity and risk factors associated with recurrent wheezing in children in early years of life. Methods: Prospective cohort study of 3167 children born in Ribeirão Preto, São Paulo, in 2010, and evaluated for this study at 12-24 months of age. A standardized questionnaire with questions regarding maternal characteristics, gestational, perinatal and postnatal conditions, family and children allergy, occurrence of wheezing, number of wheezing episodes, daycare attendance, visits to emergency, medication use, diagnosis of pneumonia and hospitalizations was applied to caregivers . Associations between outcomes and the independent variables of interest were done through univariate analysis and adjusted log-binomial models. Relative risks (RR) and confidence intervals (CI) were calculated. Results: The prevalence of at least one episode of wheezing in the first two years of life was 56.3% (1785/3167), 35.8% (1136/3167) infants had occasional wheezing (up to two episodes) and 20,1% (639/3167) had recurrent wheezing (three or more episodes). Severe recurrent wheeze (more than 6 episodes) was reported in 8.7% infants (277/3167). The independent risk factors for presenting 3 to 6 episodes of wheezing were prematurity (RR = 1.46), passive smoking (RR = 1.72 for less than 10 cigarettes / day, RR = 2.04 for more than 10 cigarettes / day), daycare attendance after 6 months (RR = 1.31), medical diagnosis of allergic rhinitis (RR = 1.52) and the presence of carpet at home (RR = 1.59). The main risk factors associated with severe wheezing were passive smoking (RR = 2.89 for more than 10 cigarettes / day), daycare attendance (RR = 2.43 if was started before 6 months and RR=1.49, if started after 6 months), acute upper respiratory infections during the first 3 months of life (RR = 2.17), asthma (RR = 1.50) and atopic dermatitis in the family (RR = 1.49) and diagnosis of allergic rhinitis (RR = 1.93). White infants have a lower prevalence of non-severe recurrent wheezing (RR = 0.68). There was no association between duration of breastfeeding and recurrent wheeze Conclusions: Children born in Ribeirão Preto have a high prevalence of recurrent wheezing in the first two years of life. In this early stage of life, environmental measures to reduce the exposure to cigarette smoke and prevention of viral infections could result in the reduction of severe recurrent wheezing in this population.

This thesis adopts a survival model to analyze China’s stock market. The data used are the capitalization-weighted stock market index (CSI 300) and the 300 stocks for creating the index. We define the recurrent events using the daily return of the selected stocks and the index. A shared frailty model which incorporates the random effects is then used for analyses since the survival times of individual stocks are correlated. Maximization of penalized likelihood is presented to estimate the parameters in the model. The covariates are selected using the Akaike information criterion (AIC) and the variance inflation factor (VIF) to avoid multicollinearity. The result of analyses show that the general capital, total amount of a stock traded in a day, turnover rate and price book ratio are significant in the shared frailty model for daily stock data.

The recurrent laryngeal nerve (RLN) innervates all the intrinsic muscles of the larynx that are responsible for human vocalization and language. The RLN runs along the tracheoesophageal groove bilaterally and is often accidentally damaged or transected during head and neck surgical procedures. RLN palsy and vocal cord paralysis are the most common and serious post op complications of thyroid surgeries. Patients who suffer from RLN injury can develop unilateral or bilateral vocal fold paralysis (BVFP). Theoretically, selective reinnervation of the posterior cricoarytenoid muscle would be the best treatment for BVFP. The phrenic nerve has been shown in several studies to be the best candidate to anastomose to the distal end of a severed RLN to restore glottal abduction. Successful PCA reinnervation has been sporadically achieved in both human patients and in animal models. Another notable ramification of recurrent laryngeal nerve injury is vocal instability caused by the alteration of mechanical properties within the larynx. In phonosurgery, alterations to the position and framework of the laryngeal apparatus are made to improve voice quality. Accurate and realistic synthetic models are greatly needed to predict the outcome of various adjustments to vocal cord tension and position that could be made surgically. Despite the sporadically successful attempts at PCA reinnervation, thus far, there are still several deficits in our anatomical familiarity and technological capability, which hinder the regularity of successful PCA reinnervation surgeries and our capacity to generate synthetic models of the human larynx that are both realistic and functional. We will address three of these deficits in this project using the porcine larynx as a model. Firstly, we will identify the anatomical variations of the porcine recurrent laryngeal nerve branches. A microscribe digitizer will be used to create three-dimensional mapping of the recurrent laryngeal nerve branches that are relevant to the posterior cricoarytenoid muscle and the abduction of the vocal folds. Secondly, we will develop a magnetic resonance imaging technique to correlate recurrent laryngeal nerve branching patterns with high-resolution MR images that can be used to determine the branching patterns present in a given specimen without surgery. Lastly, we will determine the distribution and composition of different tissue types found within human vocal folds. High resolution MRI, and Mallory's trichrome and H&E histological staining will be used to distinguish and identify the tissue composition of the vocal folds and surrounding laryngeal structures. Detailed information regarding vocal fold tissue composition and histological geometry will enable laryngeal modelers to select more sophisticated and life-like materials with which to construct synthetic vocal fold models.

African American men in their late teens to early 20s account for nearly half the victims of violent crimes. This mixed methods social epidemiological study was designed to identify the social determinants of violence as described by a purposive sample of young adult African American men (n=353) who have experience as a victim or witness to any type of violence to determine the impact post traumatic stress disorder (PTSD) symptoms have on recurrent violent injury. The pathways to recurrence model shaped the theoretical framework of this study. Quantitative data were collected using the Past Feelings and Acts of Violence (PFAV) instrument and the PTSD checklist civilian version (PCL-C). Logistic regression and Pearson correlation analysis techniques were used to examine correlations between the variables. The results showed that with higher levels of past violent behaviors there is an increase in PTSD symptoms. Qualitative data regarding exposure to and experiences with violence were collected from a subgroup of participants using open-ended, semistructured interviews (n=5) that were later analyzed using a phenomenological approach. Weapon-carrying, living in urban settings, and gang presence were themes identified by those interviewed as being related to recurrent injury. These findings will encourage social change by stimulating new strategies aimed at long-range systems changes by those who shape policies and influence community investment and engagement in resource -poor communities where violence is prevalent. More research is needed to determine if early identification and treatment for PTSD among African American men who have been exposed to violence may reduce the incidence of future violence and injury.

Thesis (M.Sc. (Physics))--North-West University, Potchefstroom Campus, 2008.

<p>The effectiveness of foreign aid in bringing economic and social development is mired in controversy. However, despite the controversial debates on its effectiveness, poor countries of the world have been receiving and using aid as a leverage to relieve themselves from development constraints they faced. Ethiopia is no exception amongst developing countries. Since the time it joined the World Bank group in 1945, foreign capital inflow has remained an important source of revenue for the government. This paper examines the fiscal impact of aid inflow into Ethiopia using time series data for the period 1975-2005. The empirical findings reveal that inflow of foreign aid influences public decision on revenue and expenditure patterns. The result shows that a larger proportion of aid is allocated to capital expenditure and that only a small proportion goes to recurrent expenditure. There is a strong positive association between aid inflow and capital expenditure. The finding also shows that, while a very weak negative association exists between aid and taxation effort, aid and borrowing are used as alternative source of finance.</p>

The aim of this study was to establish the factors associated with sports injuries among first division Rwandan female soccer players. Conclusion: Advocacy about the safety and improvement of Rwandan female soccer through workshops and trainings involving players, coaches and team owners need to be emphasised.

Let (b$_{i,j}$) be a bounded matrix on extit{ l}$^{2}$, $Bbb T={zinBbb C:|z|=1}$, and A be a bounded matrix on L$^{ 2}(mathbb{T)}$ satisfying the conditions 1.$langle Az^{2j},z^{2i} angle =sigma ^{-1}b_{ij}+|alpha |^{2}sigma ^{-1}langle Az^{j},z^{i} angle $; 2.$langle Az^{2j},z^{2i-1} angle =-alpha sigma ^{-1}b_{ij}+alpha sigma ^{-1}langle Az^{j},z^{i} angle $; 3.$langle Az^{2j-1},z^{2i} angle =-overline{alpha }sigma ^{-1}b_{ij}+overline{alpha }sigma ^{-1}langle Az^{j},z^{i} angle$; 4.$langle Az^{2j-1},z^{2i-1} angle =|alpha |^{2}sigma ^{-1}b_{ij}+sigma ^{-1}langle Az^{j},z^{i} angle $ hspace{-0.76cm} for all $i,jin mathbb{Z}$, where $sigma =1+|alpha |^{2},,alpha in mathbb{C},alpha eq0$. The above conditions evidently suggests that there is a "dyadic" relation in the entries of $A$. Here in the following picture illustrates how each $ij-$th entry of $A$ generates the 2 by 2 block in $A$ with entries ${a_{2i 2j}, a_{2i-1 2j}, a_{2i 2j-1}, a_{2i-1 2j-1}}.$ vspace{-0.3cm} egin{figure}[hp] egin{center} includegraphics[scale=0.42]{cubic.pdf} end{center} vspace{-0.8cm}caption{The dyadic recurrent form} end{figure} It has been shown [2] that $displaystyle A=sum_{n=0}^{infty }S^{n}BS^{ast n}$, where $Sz^i=sigma ^{-1/2}(overline{alpha }z^{2i}+z^{2i-1})$ and $$B=sumlimits_{i=-infty}^infty sumlimits_{j=-infty}^infty b_{ij}(u_{i}otimes u_{j}), u_{i}(z)=sigma ^{-1/2}z^{2i-1}(alpha -z).$$ In this paper, we shall use the above relations to compute $langle a_{i,j} angle $ explicitly. ewline Key words: shift operator, bounded matrix, dyadic recurrent formula, slant Toeplitz operator, separable Hilbert space 2.$langle Az^{2j},z^{2i-1} angle =-alpha sigma ^{-1}b_{ij}+alpha sigma ^{-1}langle Az^{j},z^{i} angle $ 3.$langle Az^{2j-1},z^{2i} angle =-overline{alpha }sigma ^{-1}b_{ij}+overline{alpha }sigma ^{-1}langle Az^{j},z^{i} angle $ 4.$langle Az^{2j-1},z^{2i-1} angle =|alpha |^{2}sigma ^{-1}b_{ij}+sigma ^{-1}langle Az^{j},z^{i} angle $ for all $i,jin mathbb{Z}$, where $sigma =1+|alpha |^{2},,alpha in mathbb{C},alpha eq0$ egin{figure}[hp] egin{center} includegraphics[scale=0.42]{cubic.pdf} end{center} caption{The dyadic recurrent form} end{figure} Since it has been shown [2] that $displaystyle A=sum_{n=0}^{infty }S^{n}BS^{ast n}$, where $ Sz^i=sigma ^{-1/2}(overline{alpha }z^{2i}+z^{2i-1})$ $ B=sum sum b_{ij}(u_{i}otimes u_{j})$ ;;; which $u_{i}(z)=sigma ^{-1/2}z^{2i-1}(alpha -z)$ Then we can use it to compute $langle Az^{j},z^{i} angle $ explicity if A satisfies the previous condition. ewline Key words: shift operator, bounded matrix, dyadic recurrent formula, slant Toeplitz operator, separable Hilbert space

Recurrent corneal erosions are a common complication of superficial corneal wounds. They most commonly arise following a trauma, in association with various corneal dystrophies, or are idiopathic. The main aim of this thesis was to investigate two hereditary corneal diseases with recurrent erosions in order to find out if they had been described before, and more specifically to describe the clinical picture and the morphological changes, differentiate them from other known autosomal dominant corneal dystrophies with a clinical resemblance, and to exclude genetic linkage to known corneal dystrophies with autosomal-dominant inheritance and a clinical resemblance. The thesis is based on two families of subjects belonging to different phenotypes. The subjects from Småland (Dystrophia Smolandiensis) belonged to a six-generation family, which included 171 individuals of whom 44 were affected individuals, and the family from Hälsingland (Dystrophia Helsinglandica) included sevengenerations of 342 individuals, of whom 84 were affected. The individuals in both families were investigated by collection of medical history through medical records and questionnaires assessing different aspects of the diseases, pedigree analysis, and from clinical examination. Haplotype analysis was used to exclude genetic linkage of both diseases to known autosomal-dominant corneal dystrophies with a clinical resemblance. The morphological changes in Dystrophia Smolandiensis were investigated by examining affected individuals with in-vivo confocal microscopy and/or slit-lamp biomicroscopy, and examining corneal tissue samples using histopathology and immunohistochemistry. In Dystrophia Helsinglandica, the morphological changes were described using in-vivo confocal microscopy and/or slit-lamp biomicroscopy, but also using videokeratography and corneal sensitivity measurement. The main results were the findings of two new corneal disorders with autosomal dominant inheritance, characterized by recurrent corneal erosions. In Dystrophia Smolandiensis the symptoms often started within the first year of life. The number of recurrences per year was highest from the onset and for about 30-40 years, and the duration of recurrence could stretch up to 21 days. The frequency of recurrences was variable in the disease from continuous symptoms to once a year and tended to decrease later in life. The risk of having recurrences did not disappear completely with age. Typical precipitating factors of recurrence were draught and a common cold. About two thirds of the affected individuals responded well to oral vitamin B treatment, but no other therapy has so far been successful. In Dystrophia Smolandiensis development of corneal opacifications or secondary scarring of varying type and degree was seen in about half of the subjects. Opacifications were first noted at the age of about 7 years, but usually first seen at the age of 20-40 years. Corneal grafting was performed in nine individuals, and recurrences were seen in all grafts. The corneal buttons showed epithelial hyperplasia, partial or total loss of Bowman’s layer, and subepithelial fibrosis in the light microscope. The deeper stroma, Descement’s membrane, and endothelium were normal. Confocal microscopy confirmed loss of Bowman’s layer and revealed that the corneal nerves either were normal in their sub-basal plexa or showed signs of regeneration. None of the morphological findings were specific. We believe that the opacifications are reactive corneal changes to repeated erosive events. The onset in Dystrophia Helsinglandica was usually at the age of 4-7 years and late-developing subepithelial fibrosis not significantly affecting visual acuity was seen in all affected individuals over the age of 37 years. The number of recurrences per year was highest from the onset and for about 20-30 years, and the duration of recurrence was usually up to about a week. The frequency of recurrences tended to decrease in the disease with increasing age, but did not cease completely. The precipitating factor of recurrence was typically a minor trauma. No therapy has so far been successful in the family. The corneal changes of affected individuals were classified into different stages from a nearly normal cornea to progressive fairly discrete subepithelial fibrosis of the central cornea. Discrete localized Subepithelial fibrosis in the periphery or mid-periphery (stage I) was the sole finding in 12% of the individuals. A more widespread subepithelial fibrosis, mainly in the mid-periphery, was found in 31% of the individuals (stage II). In stage III, the subepithelial fibrosis engaged the central cornea but did not affect the vision to a significant degree. In late phases of stage III small jellylike corneal irregularities could be seen. We believe that the opacifications are reactive changes to repeated erosive events. In conclusion this thesis describes two new corneal disorders – Dystrophia Smolandiensis and Dystrophia Helsinglandica.