Clinical evaluation and COL2A1 gene analysis in 21 Brazilian families with Stickler syndrome: Identification of novel mutations, further genotype/phenotype correlation, and its implications for the diagnosis

We present clinical and molecular evaluation from a large cohort of patients with Stickler syndrome: 78 individuals from 21 unrelated Brazilian families. The patients were selected in a Hospital with a craniofacial dysmorphology assistance service and clinical diagnosis was based on the presence of cleft palate associated to facial and ocular anomalies of Stickler syndrome. Analysis of COL2A1 gene revealed 9 novel and 4 previously described pathogenic mutations. Except for the mutation c.556G>T (p.Gly186X), all the others were located in the triple helical domain. We did not find genotype/phenotype correlation in relation to type and position of the mutation in the triple helical domain. However, a significantly higher proportion of myopia in patients with mutations located in this domain was observed in relation to those with the mutation in the non-tripe helical domain (c.556G>T; P < 0.04). A trend towards a higher prevalence of glaucoma, although not statistically significant, was observed in the presence of the mutation c.556G>T. It is possible. that this mutation alters the splicing of the mRNA instead of only creating a premature stop codon and therefore it can lead to protein products of different ocular effects. One novel DNA variation (c.1266+7G>C) occurs near a splice site and it was observed to co-segregate with the phenotype in one of the two families with this DNA variation. As in silico analysis predicted that the c.1266+7G>C DNA variation can affect the efficiency of the splicing, we still cannot rule it out as non-pathogenic. Our study also showed that ascertainment through cleft palate associated to other craniofacial signs can be very efficient for identification of Stickler syndrome patients. Still, high frequency of familial cases and high frequency of underdevelopment of distal lateral tibial epiphyses observed in our patients suggested that the inclusion of this information can improve the clinical diagnosis of Stickler syndrome. (C) 2008 Elsevier Masson SAS. All rights reserved.

Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome

Purpose: Interferon regulatory factor 6 encodes a member of the IRF family of transcription factors. Mutations in interferon regulatory factor 6 cause Van der Woude and popliteal pterygium syndrome, two related orofacial clefting disorders. Here, we compared and contrasted the frequency and distribution of exonic Mutations in interferon regulatory factor 6 between two large geographically distinct collections of families with Van der Woude and between one collection of families with popliteal pterygium syndrome. Methods: We performed direct sequence analysis of interferon regulatory factor 6 exons oil samples from three collections, two with Van der Woude and one with popliteal pterygium syndrome. Results: We identified mutations in interferon regulatory factor 6 exons in 68% of families in both Van der Woude collections and in 97% of families with popliteal pterygium syndrome. In sum, 106 novel disease-causing variants were found. The distribution of mutations in the interferon regulatory factor 6 exons in each collection was not random; exons 3, 4, 7, and 9 accounted for 80%. In the Van der Woude collections, the mutations were evenly divided between protein truncation and missense, whereas most mutations identified in the popliteal pterygium syndrome collection were missense. Further, the missense mutations associated with popliteal pterygium syndrome were localized significantly to exon 4, at residues that are predicted to bind directly to DNA. Conclusion: The nonrandom distribution of mutations in the interferon regulatory factor 6 exons suggests a two-tier approach for efficient mutation screens for interferon regulatory factor 6. The type and distribution of mutations are consistent with the hypothesis that Van der Woude is caused by haploinsufficiency of interferon regulatory factor 6. Oil the other hand, the distribution of popliteal pterygium syndrome-associated mutations suggests a different, though not mutually exclusive, effect oil interferon regulatory factor 6 function. Genet Med 2009:11(4):241-247.

The old metal-poor open cluster ESO 92-SC05: accreted from a dwarf galaxy ?

The study of old open clusters outside the solar circle can bring constraints on formation scenarios of the outer disc. In particular, accretion of dwarf galaxies has been proposed as a likely mechanism in the area. We use BVI photometry for determining fundamental parameters of the faint open cluster ESO 92-SC05. Colour-magnitude diagrams are compared with Padova isochrones, in order to derive age, reddening and distance. We derive a reddening E(B - V) = 0.17, and an old age of similar to 6.0 Gyr. It is one of the rare open clusters known to be older than 5 Gyr. A metallicity of Z similar to 0.004 or [M/H] similar to -0.7 is found. The rather low metallicity suggests that this cluster might be the result of an accretion episode of a dwarf galaxy.

Searching for s-Process-Enhanced Metal-Poor Stars

We present preliminary results for the estimation of barium [Ba/Fe], and strontium [Sr/Fe], abundances ratios using medium-resolution spectra (1-2 angstrom). We established a calibration between the abundance ratios and line indices for Ba and Sr, using multiple regression and artificial neural network techniques. A comparison between the two techniques (showing the advantage of the latter), as well as a discussion of future work, is presented.

HTR1B and HTR2C in autism spectrum disorders in Brazilian families

Autism spectrum disorders (ASD) is a group of behaviorally defined neuro developmental disabilities characterized by multiple genetic etiologies and a complex presentation. Several studies suggest the involvement of the serotonin system in the development of ASD, but only few have investigated serotonin receptors. We have performed a case-control and a family-based study with 9 polymorphisms mapped to two serotonin receptor genes (HTR1B and HTR2C) in 252 Brazilian male ASD patients of European ancestry. These analyses showed evidence of undertransmission of the HTR1B haplotypes containing alleles -161G and -261A at HTR1B gene to ASD (P=0.003), but no involvement of HTR2C to the predisposition to this disease. Considering the relatively low level of statistical significance and the power of our sample, further studies are required to confirm the association of these serotonin-related genes and ASD. (C) 2008 Elsevier B.V. All rights reserved.

Education and Earnings for Poverty Reduction : Short-Term Evidence of Pro-Poor Growth from the Mexican Oportunidades Program

Education, as an indispensable component of human capital, has been acknowledged to play a critical role in economic growth, which is theoretically elaborated by human capital theory and empirically confirmed by evidence from different parts of the world. The educational impact on growth is especially valuable and meaningful when it is for the sake of poverty reduction and pro-poorness of growth. The paper re-explores the precious link between human capital development and poverty reduction by investigating the causal effect of education accumulation on earnings enhancement for anti-poverty and pro-poor growth. The analysis takes the evidence from a well-known conditional cash transfer (CCT) program — Oportunidades in Mexico. Aiming at alleviating poverty and promoting a better future by investing in human capital for children and youth in poverty, this CCT program has been recognized producing significant outcomes. The study investigates a short-term impact of education on earnings of the economically disadvantaged youth, taking the data of both the program’s treated and untreated youth from urban areas in Mexico from 2002 to 2004. Two econometric techniques, i.e. difference-in-differences and difference-in-differences propensity score matching approach are applied for estimation. The empirical analysis first identifies that youth who under the program’s schooling intervention possess an advantage in educational attainment over their non-intervention peers; with this identification of education discrepancy as a prerequisite, further results then present that earnings of the education advantaged youth increase at a higher rate about 20 percent than earnings of their education disadvantaged peers over the two years. This result indicates a confirmation that education accumulation for the economically disadvantaged young has a positive impact on their earnings enhancement and thus inferring a contribution to poverty reduction and pro-poorness of growth.

Vård i livets slut av personer med demens. Personal och anhörigas upplevelse av given vård : En metasyntes

Palliativt förhållningssätt kännetecknas av helhetssyn av människan och uppnås genom stöttning av individen att leva med värdighet och största möjliga välbefinnande till livets slut oavsett diagnos eller ålder. Demens är en sjukdom som är svårt handikappande för den som drabbas och för de anhöriga är sjukdomen förödande. Den palliativa vården av personer med demens är inte optimerad. Studier visar att det dels beror på demenssjukdomen som är svår att vårda och dels för att stöd till de personer som vårdar sina anhöriga och det sociala kommunala nätverket har brister. Syfte: Att analysera upplevelsen av given vård i livets slutskede hos personer med demensdiagnos ur personalens och anhörigas perspektiv. Metod: Metasyntes utförd med Howell Major och Savin-Badins analysmodell, Qualitative Research Synthesis. Resultat: Kunskap och personcentrering var de två begrepp som blev produkten av syntesen. Begreppen fungerar som motsatser, om det finns kunskap och personcentrering så finns en bra upplevelse av given vård hos personal och anhöriga och om det brister i kunskap och personcentrering blir upplevelsen sämre. Diskussion: Kunskap om demens bland personal har i syntesen visats vara en indikator för god vård vid livets slut. Utbildning i demenssjukdom bör ske kontinuerligt och på olika nivåer beroende på vilken personalkategori som utbildas. Konklusion: Palliativ vård och demens måste få utrymme i utbildningarna av all personal, från undersköterska till specialistläkare.

Voices of the Poor: Poverty and Growth in Albania

This paper uses three waves of panel surveys at the household level to study growth and poverty in Albania over the period 2002-2004. It attempts to answer two main questions. The first question is directed at finding the micro determinants of growth and aims to expose the obstacles households face to improve their economic situation. The main focus of the analysis is to investigate the importance of health, education, and infrastructure indicators for income growth. The second question asks whether growth in Albania during the period 2002-2004 has been pro-poor. I find that there is some evidence for a convergence of incomes and a pro-poor growth, which has led to a substantial decrease in the number of people living under the poverty line. I also find that infrastructure has not been an important determinant for income mobility, and neither has health. Only the higher education of poor urban households seems to have affected prospects for growing out of poverty, and unexpectedly, the relationship is negative.

Pro-poor growth and social programmes in Brazil

From a methodological point of view, this paper makes two contributions to the literature. One contribution is the proposal of a new measure of pro-poor growth. This new measure provides the linkage between growth rates in mean income and in income inequality. In this context, growth is defined as propoor (or anti-poor) if there is a gain (or loss) in the growth rate due to a decrease (or increase) in inequality. The other contribution is a decomposition methodology that explores linkages between growth patterns and social policies. Through the decomposition analysis, we assess the contribution of different income sources to growth patterns. The proposed methodologies are then applied to the Brazilian National Household Survey (PNAD) covering the period 1995-2004. The paper analyzes the evolution of Brazilian social indicators based on per capita income exploring links with adverse labour market performance and social policy change, with particular emphasis on the expansion of targeted cash transfers and devising more pro-poor social security benefits.

Income and bargaining effects on education and health

In this paper, we examine the impacts of the reform in the rural pension system in Brazil in 1991 on schooling and health indicators. In addition, we use the reform to investigate the validity of the unitary model of household allocation by testing if there were uneven impacts on those indicators depending on the gender of the recipient. The main conclusion of the paper is that the reform had significantly positive effects on the outcomes of interest, especially on those co-residing with a male pensioner, indicating that the unitary model is not a well-specified framework to understand family allocation decisions. The highest impacts were on school attendance for boys, literacy for girls and illness for middle-age people. We explore a collective model as defined by Chiappori (1992) as one possible alternative representation for the decision-making process of the poor rural Brazilian families. In the cooperative Nash equilibrium, the reform effects can be divided into two pieces: a direct income effect and bargaining power effect. The data support the existence of these two different effects

Targeting the poor: a macroeconomic analysis of cash transfer programs

This paper introduces cash transfers targeting the poor in an incomplete markets model with heterogeneous agents facing idiosyncratic risk. These transfers change the degree of insurance in the economy and affect precautionary motives asymmetrically, leading the poorest households to decrease savings proportionally more than their richer counterparts. In a model economy calibrated to Brazil, once the cash transfer program is adopted, wealth inequality and social welfare increase, poverty decreases, while employment and income inequality remain about the same. Imperfect access to financial markets is important for these results, whereas whether the program is funded with lump sum or distortive taxes is not.

Neighborhood feedbacks, endogenous stratification, and income inequality

This paper explores the evolution of the cross-section income distribution in economies where endogenous neighborhood formation interacts with positive within-neighborhood feedback effects. We study an economy in which the economic success of adults is determined by the characteristics of the families in the neighborhood in which a person grows up. These feedbacks take two forms. First, the tax base of a neighborhood affects the leveI of education investment in offspring. Second, the effectiveness of education investment is affected by a neighborhood's in come distribution, reflecting factors such as role model or labor market connection effects. Conditions are developed under which endogenous stratification, defined as the tendency for families wi th similar incomes to choose to form common communities, will occur. When families are allowed to choose their neighborhoods, wealthy families will have an incentive to segregate themselves from the rest of the population. This resulting stratification is supported by house price differences between ricli and poor communities. Endogenous stratification can lead to pronounced intertemporal inequality as different families provide very different interaction environments for offspring. When the transformation of human capital into in come exhibits constant retums to scale, cross-section in come differences may also grow across time. As a result, endogenous stratification and neighborhood feedbacks can interact to produce long run inequality.

Linkages between pro-poor growth, social programmes and labour market : the recent Brazilian experience

From a methodological point of view, this paper makes two contlibutions to the literature. One contribution is the proposal of a new measure of pro-poor growth. This new measure provides the linkage between growth rates in mean income and in income inequality. In this context, growth is defined as pro-poor (or anti-poor) if there is a gain (or loss) in the growth rate due to a decrease (or increase) in inequality. The other contribution is a decomposition methodology that explores linkages between three dimensions: growth pattems, labour market performances. and social policies. Through the decomposition analysis, growth in per capita income is explained in terms of four labour market components: the employment rate. hours of work, the labour force participation rate. and productivity. We also assess the contribution of different nonlabour income sources to growth patterns. The proposed methodologies are then applied to the Brazilian National Household Survey (PNAD) covering the period 1995-2004. The paper analyzes the evolution of Brazilian social indicators based on per capita income exploring links with adverse labour market performance and social policy change, with particular emphasis on the expansion of targeted cash transfers and devising more propoor social security benefits.