Polymorphisms in folate-metabolizing genes, chromosome damage, and risk of Down syndrome in Italian women: identification of key factors using artificial neural networks

<p>Abstract</p> <p>Background</p> <p>Studies in mothers of Down syndrome individuals (MDS) point to a role for polymorphisms in folate metabolic genes in increasing chromosome damage and maternal risk for a Down syndrome (DS) pregnancy, suggesting complex gene-gene interactions. This study aimed to analyze a dataset of genetic and cytogenetic data in an Italian group of MDS and mothers of healthy children (control mothers) to assess the predictive capacity of artificial neural networks assembled in TWIST system in distinguish consistently these two different conditions and to identify the variables expressing the maximal amount of relevant information to the condition of being mother of a DS child.</p> <p>The dataset consisted of the following variables: the frequency of chromosome damage in peripheral lymphocytes (BNMN frequency) and the genotype for 7 common polymorphisms in folate metabolic genes (<it>MTHFR </it>677C>T and 1298A>C, <it>MTRR </it>66A>G, <it>MTR </it>2756A>G, <it>RFC1 </it>80G>A and <it>TYMS </it>28bp repeats and 1494 6bp deletion). Data were analysed using TWIST system in combination with supervised artificial neural networks, and a semantic connectivity map.</p> <p>Results</p> <p>TWIST system selected 6 variables (BNMN frequency, <it>MTHFR </it>677TT, <it>RFC1 </it>80AA, <it>TYMS </it>1494 6bp +/+, <it>TYMS </it>28bp 3R/3R and <it>MTR </it>2756AA genotypes) that were subsequently used to discriminate between MDS and control mothers with 90% accuracy. The semantic connectivity map provided important information on the complex biological connections between the studied variables and the two conditions (being MDS or control mother).</p> <p>Conclusions</p> <p>Overall, the study suggests a link between polymorphisms in folate metabolic genes and DS risk in Italian women.</p

Polymorphic variants of genes involved in homocysteine metabolism in celiac disease

Celiac disease (CD) is a polygenic chronic enteropathy conferring an increased risk for various nutrient deficiency states. Hyperhomocysteinemia is a frequent finding in CD and may be related to the development of venous thrombosis, cardiovascular disease, and stroke in untreated CD patients. Recently, a possible excess in the frequency of the MTHFR c.677C>T (rs1801133) gene variant in CD patients was reported. The purpose of this study was to determine if there exist differences in the distribution of polymorphic variants of genes involved in homocysteine/methyl group metabolism between CD patients and the general population. A set of 10 gene polymorphisms (MTHFR rs1801133, MTR rs1805087, MTHFD1 rs2236225, MTRR rs1801394, CBS 844ins68, BHMT1 rs7356530 and rs3733890, BHMT2 rs526264 and rs625879, and TCN2 rs1801198) was tested in 134 patients with CD and 160 matched healthy controls. The frequency of the MTR rs1805087 GG genotype in CD patients was lower than in controls (0.01 and 0.06, respectively), although statistical significance was not achieved (P = 0.06). For the other analyzed polymorphisms, there was no evidence of difference in both allelic and genotypic distribution between cases and controls. The exhaustive Multifactor Dimensionality Reduction analysis revealed no combination of interactive polymorphisms predicting the incidence of CD. In contrast to the well-documented clinical observations of increased risks of vascular disease in patients with longstanding untreated CD, in our group of patients no significant association with CD was found for all tested polymorphic variants of genes involved in homocysteine metabolism. These findings should be replicated in studies with a larger sample size

The changing face of cartographic education and training

This paper discusses the issue faced by many cartographic departments and programs around the world. That is the weakening of cartography as a discipline in its own right and the dispersal of cartographic theory and practice into many and varied education programs representing allied disciplines. The general public has little awareness of the connection between the study of cartography and the new spatial information technology that they use daily. The GISciences industry had become fragmented as it searched for identity in this rapidly changing environment. University programs were feeling the impact of these changes through the reduction in those seeking careers in cartography. This paper first discusses the growth of digital cartography. Second, the impact of changes on the GISciences industry is discussed. Third, the impact of the changes on cartographic education and training is discussed and specific points are emphasised using case study examples for individual programs from Hungary, Brazil and Australia

Defining standard symbols for street network maps for urban planning based on user requirements

This paper describes the first step of a research project that aims to establish a standard set of symbols for the cartographic representation of urban regions. This first step is a case study that focuses on street network symbol design as part of a municipal master plan. In Brazil, the Federal Law 10.257 of 2001 demands that a municipal master plan is the basic instrument for political policies for the development of urban areas. According to the Brazilian Federal Constitution every municipality that has over 20,000 inhabitants is obliged to have a municipal master plan. In the state of Parana, Brazil, 3 groups of professionals are involved in establishing and implementing a master plan: state government technicians, municipality technicians, and urban planners. Commonly, to propose a master plan, the municipal executive government needs to contract a commercial enterprise, which is employing urban planners. Their plan proposal is then analyzed by municipality technicians and sent to the council of representatives to be approved as a set of laws. The state government technicians, who are the users we focus on in this case study, work for an institution called ParanaCidade that is responsible to provide knowledge support to municipality technicians who have to review a master plan. According to ParanaCidade a municipal master plan is developed in five stages, where three of them are directly dependent on spatial analysis. They are the analysis of the regional, municipal and urban reality; the master plan guidelines and proposal; and the draft of a set of laws. In these stages it is important that every cartographic representation of different aspects of urban reality be perfectly understood by the 3 groups of professionals. However, that is currently not the case in the state of Parana. Today, in different municipalities, urban planners use different classifications for the same phenomena, and those differences are not always based on the specifics of the geographic region. As every classification is depicted by a unique set of symbols, there are also different symbols for representing the same phenomenon. This fact can affect the efficiency of the decision making by state government and municipality technicians in the field of urban planning. Our proposed solution to this problem is a standard for map symbolization which is the result of this case study. The street network was chosen as a research starting point because its design and construction depend on most of the geographic characteristics that must be part of the analysis of the municipal reality. At the same time, the proposals for all of the other aspects of an urban plan, e.g. land use zoning and public transportation, are dependent on the street network. The user requirement analysis is executed through scientific methodology and reference is also made to research into the cartographic design of interactive land use planning maps in the Netherlands. The steps of the methodology are (1) understanding the geographic knowledge based on which users will accomplish tasks for proposing a municipal master plan, (2) defining the street network classification that can be suitable for every map scale necessary for decision making based on spatial analysis, (3) designing a proposed standard symbology for the street system network, (4) designing and implementing qualitative user tests. The tests are based on tasks related to scenarios that represent some actual situations in urban planning. Representatives of the users perform the tasks using maps designed with the proposed standard symbolization. They are also encouraged to 'think aloud' while performing the tasks. And a 'focus group' activity will be prepared based on the results of the user tests in order to improve our proposal for the standard symbolization