Genetic Screening of LCA in Belgium: Predominance of CEP290 and Identification of Potential Modifier Alleles in AHI1 of CEP290-Related Phenotypes

Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91 LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the cohort, with major involvement of CEP290 (30%). In addition, 11 patients with early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS) were included. Exhaustive re-inspection of the overall phenotypes in our LCA cohort revealed novel insights mainly regarding the CEP290-related phenotype. The AHI1 gene was screened as a candidate modifier gene in three patients with the same CEP290 genotype but different neurological involvement. Interestingly, a heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely affected patient. Moreover, AHI1 screening in five other patients with CEP290-related disease and neurological involvement revealed a second novel missense variant, p.His758Pro, in one LCA patient with mild mental retardation and autism. These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease.

Spill-over effects in multi-partner loyalty programs

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Chagas' disease: an algorithm for donor screening and positive donor counseling

Classical serological screening assays for Chagas' disease are time consuming and subjective. The objective of the present work is to evaluate the enzyme immuno-assay (ELISA) methodology and to propose an algorithm for blood banks to be applied to Chagas' disease. Seven thousand, nine hundred and ninety nine blood donor samples were screened by both reverse passive hemagglutination (RPHA) and indirect immunofluorescence assay (IFA). Samples reactive on RPHA and/or IFA were submitted to supplementary RPHA, IFA and complement fixation (CFA) tests. This strategy allowed us to create a panel of 60 samples to evaluate the ELISA methodology from 3 different manufacturers. The sensitivity of the screening by IFA and the 3 different ELISA's was 100%. The specificity was better on ELISA methodology. For Chagas disease, ELISA seems to be the best test for blood donor screening, because it showed high sensitivity and specificity, it is not subjective and can be automated. Therefore, it was possible to propose an algorithm to screen samples and confirm donor results at the blood bank.

Maintaining the correctness of transactional memory programs

Dissertação para obtenção do Grau de Doutor em Engenharia Informática

Revision based total semantics for extended normal logic programs

Dissertação para obtenção do Grau de Doutor em Matemática - Lógica e Fundamentos da Matemática

Fast screening for diagnostic of heart ischemic episodes

Dissertação para obtenção do Grau de Doutor em Química Sustentável

Lightweight monitoring of transactional memory programs

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

Promoting healthy eating standards on children through CSR educational programs: An evaluation of impact on eating preferences, attitude towards the brand and perceived brand reputation

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Positioning of Ontario University Business Programs - Guelph-Humber

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Serological screening and toxoplasmosis exposure factors among pregnant women in South of Brazil

Serological screening and evaluation of exposure factors for Toxoplasma gondii transmission were conducted in 2126 pregnant women from southern Brazil. Specific antibodies against Toxoplasma gondii were presented by 74.5% (n=1583) of the pregnant women evaluated. Contact with soil was found to be the major factor for infection.

Development of novel benzimidazole- based COX Inhibitors new synthetic strategies and screening of heterocyclic structures

Dissertação para obtenção do Grau de Doutor em Química, especialidade Química Orgânica

Evaluation of the use of real-time PCR for human T cell lymphotropic virus 1 and 2 as a confirmatory test in screening for blood donors

INTRODUCTION: HTLV-1/2 screening among blood donors commonly utilizes an enzyme-linked immunosorbent assay (EIA), followed by a confirmatory method such as Western blot (WB) if the EIA is positive. However, this algorithm yields a high rate of inconclusive results, and is expensive. METHODS: Two qualitative real-time PCR assays were developed to detect HTLV-1 and 2, and a total of 318 samples were tested (152 blood donors, 108 asymptomatic carriers, 26 HAM/TSP patients and 30 seronegative individuals). RESULTS: The sensitivity and specificity of PCR in comparison with WB results were 99.4% and 98.5%, respectively. PCR tests were more efficient for identifying the virus type, detecting HTLV-2 infection and defining inconclusive cases. CONCLUSIONS: Because real-time PCR is sensitive and practical and costs much less than WB, this technique can be used as a confirmatory test for HTLV in blood banks, as a replacement for WB.

Standardization of an ELISA test using a recombinant nucleoprotein from the Junin virus as the antigen and serological screening for arenavirus among the population of Nova Xavantina, State of Mato Grosso

INTRODUCTION: Arenavirus hemorrhagic fever is a severe emerging disease. METHODS: Considering that the levels of antibodies against arenavirus in the Brazilian population are completely unknown, we have standardized an ELISA test for detecting IgG antibodies using a recombinant nucleoprotein from the Junin virus as the antigen. This protein was obtained by inserting the gene of the Junin virus nucleoprotein into the genome of Autographa californica nucleopolyhedrovirus, using the Bac-to-Bac baculovirus expression system. This recombinant baculovirus was used to infect S. frugiperda cells (SF9). RESULTS: The infection resulted in synthesis of high concentrations of recombinant protein. This protein was detected on 12.5% polyacrylamide gel and by means of Western blot. Using the standardized ELISA test, 343 samples from the population of Nova Xavantina were analyzed. We observed that 1.4% of the serum samples (five samples) presented antibody titers against arenavirus. CONCLUSIONS: These results show the population studied may present exposure to arenavirus infection.

Incidence of congenital toxoplasmosis in the city of Belém, state of Pará, northern Brazil, determined by a neonatal screening program: preliminary results

INTRODUCTION: The aim of this study was to determinate the incidence of congenital toxoplasmosis among a group of newborns (NBs) from Belém using neonatal screening. METHODS: Among the 6,000 newborns referred for investigation of genetic and metabolic diseases, 1,000 were selected for screening for congenital toxoplasmosis by determining the amount of IgM in the eluates of blood collected on filter paper. Positive tests were confirmed using paired serology of the NB and his mother. RESULTS: Out of the 1,000 NBs assessed, one had a positive screening result that was confirmed by paired serology. CONCLUSIONS: The incidence of congenital toxoplasmosis in Belém was 10/10,000 live NBs.

The Impact of income support programs on transitions to employment

The income support programs are created with the purpose of fighting both, the poverty trap and the inactivity trap. The balance between both is fragile and hard to find. Thus, the goal of this work is to contribute to solve this issue by finding how income support programs, particularly the Portuguese RSI, affect transitions to employment. This is made through duration analysis, namely using Cox and Competing Risks models. A particular feature is introduced in this work as it incorporates the possibility of Defective Risks. The estimated hazard elasticity with respect to the amount of RSI received for individuals who move to employment is -0,41. More than a half of RSI receivers stays for more than a year and the probability of never leaving to employment is 44%. The results appear to indicate that RSI has affected negatively transitions to employment.