Epidemiology of cleft palate in Europe: implications for genetic research.

OBJECTIVE: To describe the epidemiology of cleft palate (CP) in Europe. DESIGN AND SETTING: A descriptive epidemiological study on 3852 cases of CP, identified (1980 through 1996) from more than 6 million births from the EUROCAT network of 30 registers in 16 European countries. RESULTS: Significant differences in prevalence in Europe between registries and within countries were observed. A total of 2112 (54.8%) CP cases occurred as isolated, 694 (18.0%) were associated with other defects such as multiple congenital anomalies, and 1046 (27.2%) were in recognized conditions. The study confirmed the tendency toward female prevalence (sex ratio [SR] = 0.83), particularly among isolated cases (SR = 0.78) even if SR inversion is reported in some registries. A specific association with neural tube defects (NTDs) in some registers is reported. CONCLUSION: The differences identified in Europe (prevalence, sex, associated anomalies) can be only partially explained by methodological reasons because a common methodology was shared among all registries for case ascertainment and collection, and CP is an easy detectable condition with few induced abortions. The complex model of inheritance and the frequently conflicting results in different populations on the role of genes that constitute risk factors suggest the presence of real biological differences. The association of CP/NTD in an area with a high prevalence of NTDs can identify a group of conditions that can be considered etiologically homogeneous. The epidemiological evaluation can guide genetic research to specify the role of etiological factors in each different population

Prevalence, prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe.

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990-2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100,000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.

The role of geography and ecology in shaping repeated patterns of morphological and genetic differentiation between European minnows (Phoxinus phoxinus) from the Pyrenees and the Alps

Neutral and selective processes c an drive repeated patterns of evolu tion in dif ferent groups of populationsexp eriencing similar ecol ogica l gradients. In this paper, we used a combinat ion of nucl ear and mitochondrialDNA markers, as well as geometric morphometrics, to investigate repeated patterns of morphological andgenetic divergence of E uropean minnows in two mountain ranges : the Pyrenees and the Al ps. Europeanminnows (Phoxinus phoxinus) are cyprinid fish i nha bitin g most freshwater bodies in Europe, including those indifferent mountain r anges that could act as major geographical barriers to gene flow. We explored patterns ofP. phoxinus phenotypic and genetic di versi fication along a gradi ent of alti tude common to the two mountainranges, and tested for isolation by distance (IBD), isolation by environment (IBE) and isolation by adaptation(IBA). The results indicated that populations from the Pyr enees a nd the Alps bel ong to two well differentiated,reciprocally monophyletic mt DNA lineages. Substantial genetic differentiation due to geographical isolationwithin and between populations from the Pyrenees and the Alps was also found using rapidly evolving AFLPsmarkers (isolation by distance or IBD), as well as morphological differences between mountain ranges. Als o,morphology varied strong ly with elevation and so did genetic differentiation to a lower extent. Despitemoderate evidence for IBE and IBA, and therefore of repeated evolution, substantial population heterogeneitywas found at the genetic level, suggesting that selection and population specific genetic drift act in concert toaffect genetic divergence.

Tracing the Origin and Spread of Agriculture in Europe

The origins of early farming and its spread to Europe have been the subject of major interest for some time. The main controversy today is over the nature of the Neolithic transition in Europe: the extent to which the spread was, for the most part, indigenous and animated by imitatio (cultural diffusion) or else was driven by an influx of dispersing populations (demic diffusion). We analyze the spatiotemporal dynamics of the transition using radiocarbon dates from 735 early Neolithic sites in Europe, the Near East, and Anatolia. We compute great-circle and shortest-path distances from each site to 35 possible agricultural centers of origin—ten are based on early sites in the Middle East and 25 arehypothetical locations set at 58 latitude/longitude intervals. We perform a linear fit of distance versus age (and viceversa) for each center. For certain centers, high correlation coefficients (R . 0.8) are obtained. This implies that a steady rate or speed is a good overall approximation for this historical development. The average rate of the Neolithic spread over Europe is 0.6–1.3 km/y (95% confidence interval). This is consistent with the prediction of demic diffusion(0.6–1.1 km/y). An interpolative map of correlation coefficients, obtained by using shortest-path distances, shows thatthe origins of agriculture were most likely to have occurred in the northern Levantine/Mesopotamian area

Molecular detection of enteropathogenic Escherichia coli in asymptomatic captive psittacines

Psittaciformes are one of the most endangered groups of birds, and several Brazilian species are classified between vulnerable and critically endangered. It is thus necessary to identify agents that cause infections in captive wild animals and to assess the risks posed thereof and to design interventions to minimize the possibility of disease outbreaks, leading to the conservation of endangered species. The purpose of this study was to identify enteropathogenic Escherichia coli (EPEC) cloacal isolates from asymptomatic psittacines in captivity and evaluate the distribution of the EPEC pathotype. Cloacal swabs were obtained from 46 asymptomatic birds, and resulting isolates were tested by polymerase chain reaction (PCR) for the presence of the attaching and effacing gene (eae) and bundle-forming pilus structural gene (bfpA) of EPEC. Samples from several species were tested, and three samples were found to be positive for the eae and bfpA genes and characterized as typical EPEC. This is the first report of this pathotype in asymptomatic psittacines. Although certain E. coli strains are more pathogenic than others, various factors should be considered when determining the potential of E. coli isolates to cause disease in captive psittacines. Birds that are positive for the EPEC (typical) strain could be zoonotic sources of infection, and may have acquired these strains through contact with humans or domestic animals. These findings may also be valuable for the long-term management of endangered species ex situ as one EPEC sample was isolated from a Red-tailed Amazon (Amazona brasiliensis).

Tracing the Origin and Spread of Agriculture in Europe

The origins of early farming and its spread to Europe have been the subject of major interest for some time. The main controversy today is over the nature of the Neolithic transition in Europe: the extent to which the spread was, for the most part, indigenous and animated by imitatio (cultural diffusion) or else was driven by an influx of dispersing populations (demic diffusion). We analyze the spatiotemporal dynamics of the transition using radiocarbon dates from 735 early Neolithic sites in Europe, the Near East, and Anatolia. We compute great-circle and shortest-path distances from each site to 35 possible agricultural centers of origin—ten are based on early sites in the Middle East and 25 are hypothetical locations set at 58 latitude/longitude intervals. We perform a linear fit of distance versus age (and vice versa) for each center. For certain centers, high correlation coefficients (R . 0.8) are obtained. This implies that a steady rate or speed is a good overall approximation for this historical development. The average rate of the Neolithic spread over Europe is 0.6–1.3 km/y (95% confidence interval). This is consistent with the prediction of demic diffusion(0.6–1.1 km/y). An interpolative map of correlation coefficients, obtained by using shortest-path distances, shows that the origins of agriculture were most likely to have occurred in the northern Levantine/Mesopotamian area

Molecular detection of enteropathogenic Escherichia coli in asymptomatic captive psittacines

Psittaciformes are one of the most endangered groups of birds, and several Brazilian species are classified between vulnerable and critically endangered. It is thus necessary to identify agents that cause infections in captive wild animals and to assess the risks posed thereof and to design interventions to minimize the possibility of disease outbreaks, leading to the conservation of endangered species. The purpose of this study was to identify enteropathogenic Escherichia coli (EPEC) cloacal isolates from asymptomatic psittacines in captivity and evaluate the distribution of the EPEC pathotype. Cloacal swabs were obtained from 46 asymptomatic birds, and resulting isolates were tested by polymerase chain reaction (PCR) for the presence of the attaching and effacing gene (eae) and bundle-forming pilus structural gene (bfpA) of EPEC. Samples from several species were tested, and three samples were found to be positive for the eae and bfpA genes and characterized as typical EPEC. This is the first report of this pathotype in asymptomatic psittacines. Although certain E. coli strains are more pathogenic than others, various factors should be considered when determining the potential of E. coli isolates to cause disease in captive psittacines. Birds that are positive for the EPEC (typical) strain could be zoonotic sources of infection, and may have acquired these strains through contact with humans or domestic animals. These findings may also be valuable for the long-term management of endangered species ex situ as one EPEC sample was isolated from a Red-tailed Amazon (Amazona brasiliensis).

HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis

BACKGROUND: Highly active antiretroviral therapy (HAART) for the treatment of HIV infection was introduced a decade ago. We aimed to examine trends in the characteristics of patients starting HAART in Europe and North America, and their treatment response and short-term prognosis. METHODS: We analysed data from 22,217 treatment-naive HIV-1-infected adults who had started HAART and were followed up in one of 12 cohort studies. The probability of reaching 500 or less HIV-1 RNA copies per mL by 6 months, and the change in CD4 cell counts, were analysed for patients starting HAART in 1995-96, 1997, 1998, 1999, 2000, 2001, and 2002-03. The primary endpoints were the hazard ratios for AIDS and for death from all causes in the first year of HAART, which were estimated using Cox regression. RESULTS: The proportion of heterosexually infected patients increased from 20% in 1995-96 to 47% in 2002-03, and the proportion of women from 16% to 32%. The median CD4 cell count when starting HAART increased from 170 cells per muL in 1995-96 to 269 cells per muL in 1998 but then decreased to around 200 cells per muL. In 1995-96, 58% achieved HIV-1 RNA of 500 copies per mL or less by 6 months compared with 83% in 2002-03. Compared with 1998, adjusted hazard ratios for AIDS were 1.07 (95% CI 0.84-1.36) in 1995-96 and 1.35 (1.06-1.71) in 2002-03. Corresponding figures for death were 0.87 (0.56-1.36) and 0.96 (0.61-1.51). INTERPRETATION: Virological response after starting HAART improved over calendar years, but such improvement has not translated into a decrease in mortality.

Genetic diversity of the cestode Echinococcus multilocularis in red foxes at a continental scale in Europe

BACKGROUND: Alveolar echinococcosis (AE) is a severe helminth disease affecting humans, which is caused by the fox tapeworm Echinococcus multilocularis. AE represents a serious public health issue in larger regions of China, Siberia, and other regions in Asia. In Europe, a significant increase in prevalence since the 1990s is not only affecting the historically documented endemic area north of the Alps but more recently also neighbouring regions previously not known to be endemic. The genetic diversity of the parasite population and respective distribution in Europe have now been investigated in view of generating a fine-tuned map of parasite variants occurring in Europe. This approach may serve as a model to study the parasite at a worldwide level. METHODOLOGY/PRINCIPAL FINDINGS: The genetic diversity of E. multilocularis was assessed based upon the tandemly repeated microsatellite marker EmsB in association with matching fox host geographical positions. Our study demonstrated a higher genetic diversity in the endemic areas north of the Alps when compared to other areas. CONCLUSIONS/SIGNIFICANCE: The study of the spatial distribution of E. multilocularis in Europe, based on 32 genetic clusters, suggests that Europe can be considered as a unique global focus of E. multilocularis, which can be schematically drawn as a central core located in Switzerland and Jura Swabe flanked by neighbouring regions where the parasite exhibits a lower genetic diversity. The transmission of the parasite into peripheral regions is governed by a "mainland-island" system. Moreover, the presence of similar genetic profiles in both zones indicated a founder event.

First Record of Freshwater Fish on the Cape Verdean Archipelago

The Cape Verdean islands form a distinct aquatic freshwater ecoregion characterized mainly by temporal water bodies with an adapted invertebrate community. Freshwater fish were not previously recorded from the archipelago. During a non-exhaustive survey of freshwater bodies on five islands of the archipelago, the first presence of a freshwater fish was recorded. Using barcoding sequences, the species was identified as the guppy (Poecilia reticulata), a highly invasive species alien to the Cape Verdean Islands.

Comparison of rural and urban attitudes to the conservation of Asian elephants in Sri Lanka: empirical evidence

There has been little study of economic and general attitudes towards the conservation of the Asian elephant. This paper reports and analyses results from surveys conducted in Sri Lanka of attitudes of urban dwellers and farmers towards nature conservation in general and the elephant conservation in particular. The analyses are based on urban and a rural sample. Contingent valuation techniques are used as survey instruments. Multivariate logit regression analysis is used to analyse the respondents' attitudes towards conservation of elephants. It is found that, although some variations occurred between the samples, the majority of the respondents (both rural and urban) have positive attitudes towards nature conservation in general. However, marked differences in attitudes toward elephant conservation are evident between these two samples: the majority of urban respondents were in favour of elephant conservation; rural respondents expressed a mixture of positive and negative attitudes. Overall, considerable unrecorded and as yet unutilised economic support for conservation of wild elephants exists in Sri Lanka. (C) 2002 Elsevier Science Ltd. All rights reserved.

Alliance behaviour, absorptive capacity and competitive advantage: a comparative study of biopharmaceutical firms in Europe and the US

In this thesis, we explore the relationship between absorptive capacity and alliances, and their influence on firms’ competitive advantage in the US and European biopharmaceutical sectors. The study undertaken in this thesis is based on data from a large-scale international survey of over 2,500 biopharmaceutical firms in the US, the UK, Germany, France and Ireland. The thesis advanced a conceptual framework, which integrated the multi-dimensions of absorptive capacity, exploration-exploitation alliances, and competitive advantage, into a biopharmaceutical firm’s new product development process. The proposed framework is then tested in the empirical analysis, using truncated models to estimate firms’ sales growth, with zero-inflated negative binominal models capturing the number of alliances in which firms engage, and aspects of realised absorptive capacity analysed by ordinal probit models. The empirical results suggest that both skill-based and exploitation-based absorptive capacity play crucial roles in shaping firms’ competitive advantage, while neither exploratory nor exploitation alliances contribute to the improvement in firms’ competitive position. In terms of the interaction between firms’ absorptive capacity and alliance behaviour, the results suggest that engagement with exploratory alliances depends more strongly on firms’ assimilation capability (skills levels and continuity of R&D activities), while participation in exploitation alliances is more conditional on firms’ relevant knowledge monitoring capability. The results highlight the major differences between the determinants of firms’ alliance behaviour, and competitive advantage in the US and Europe – in the US firms’ skill levels prove more significant in determining firms’ engagement with exploratory alliances, whereas in Europe continuity of R&D proves more important. Correspondingly, while US firms’ engagement with exploitation alliances depends on market monitoring capability, that in Europe is more strongly linked to exploitation-based absorptive capacity. In respect of the determinants of firms’ competitive advantage – in Europe, market monitoring capability, engagement with exploitation alliances, and continuous R&D activities, prove more important, while in the US, it is firms’ market characteristics that matter most.

The evolution of lactase persistence in Europe. A synthesis of archaeological and genetic evidence

Lactase persistence, the ability to digest the milk sugar lactose in adulthood, is highly associated with a T allele situated 13,910 bp upstream from the actual lactase gene in Europeans. The frequency of this allele rose rapidly in Europe after transition from hunter–gatherer to agriculturalist lifestyles and the introduction of milkable domestic species from Anatolia some 8000 years ago. Here we first introduce the archaeological and historic background of early farming life in Europe, then summarize what is known of the physiological and genetic mechanisms of lactase persistence. Finally, we compile the evidence for a co-evolutionary process between dairying culture and lactase persistence. We describe the different hypotheses on how this allele spread over Europe and the main evolutionary forces shaping this process. We also summarize three different computer simulation approaches, which offer a means of developing a coherent and integrated understanding of the process of spread of lactase persistence and dairying.

Geographical distribution and conservation of Cucurbita in Brazil.

The collection and conservation of the Cucurbita genus in Brazil happened in so dispersed institutions, an assessment of the storage conditions and the genetic diversity is needed, making it possible to identify new priorities for the genus. This work constitutes diagnosis of geographical distribution, storage conditions in situ and ex situ and on genetic diversity of the Cucurbita genus in Brazil. Research was done in herbariums, databases, literature and in situ (expeditions to rural areas and (markets) to map the areas of occurrence of the species. During these expeditions, questionnaires were applied to obtain information about the property and genus Cucurbita. Questionnaires were sent to 173 Brazilian institutions regarding the preservation conditions ex situ. A genetic variability of the Cucurbita genus was found in traditional Brazilian agriculture. Collections must be prioritized in the northern and southern regions (all states); the southeastern region, all states, except Minas Gerais; central-west, in Mato Grosso do Sul and Mato Grosso; the northeastern region, the states of Alagoas, Maranhão, Paraíba, Pernambuco, Piauí and Sergipe. Currently 5.545 entries are being conserved in the Germplasm banks, however, C. pepo, C. ficifolia, C. argyrosperma and wild species are poorly represented. The characterization level of conserved entries is low in the ex situcollections. Participative research projects must be financed as a way to stimulate the farmers to continue planting their local varieties. A coleta e conservação do gênero Cucurbita no Brasil aconteceu de forma dispersa pelas instituições, sendo necessário um diagnóstico sobre as condições de conservação e sobre a diversidade genética, tornando possível identificar novas prioridades para o gênero. Este trabalho realizou diagnóstico sobre distribuição geográfica, condições de conservação in situ e ex situ e sobre diversidade genética do gênro Cucurbita no Brasil. Para mapear as áreas de ocorrência das espécies, foram realizados levantamentos de informações em herbários, banco de dados, literatura e levantamentos in situ (expedições para áreas rurais, feiras livres e CEASAs). Nessas expedições foram aplicados questionários, buscando informações sobre a propriedade e o gênero Cucurbita. Em relação as condições de conservação ex situ, foram enviados questionários para 173 instituições brasileiras. Foi constatado que existe variabilidade genética do gênero Cucurbita na agricultura tradicional brasileira. Devem ser priorizadas coletas nas regiões Norte e Sul (todos os estados); região Sudeste, todos os estados, exceto Minas Gerais; região Centro-Oeste, no Mato Grosso do Sul e Mato Grosso; região Nordeste, os estados de Alagoas, Maranhão, Paraíba, Pernambuco, Piauí e Sergipe. Atualmente estão sendo conservados nos Bancos de Germoplasma 5.545 acessos, no entanto C. pepo, C ficifolia, C. argyrosperma e espécies silvestres estão pouco representadas. É baixa a taxa de caracterização dos acessos conservados nas coleções ex situ. Devem ser financiados projetos de pesquisa participativa como uma forma de estimular e dar condições aos agricultores de continuarem cultivado suas variedades locais.

Geographical distribution and conservation of Cucurbita in Brazil.

The collection and conservation of the Cucurbita genus in Brazil happened in so dispersed institutions, an assessment of the storage conditions and the genetic diversity is needed, making it possible to identify new priorities for the genus. This work constitutes diagnosis of geographical distribution, storage conditions in situ and ex situ and on genetic diversity of the Cucurbita genus in Brazil. Research was done in herbariums, databases, literature and in situ (expeditions to rural areas and (markets) to map the areas of occurrence of the species. During these expeditions, questionnaires were applied to obtain information about the property and genus Cucurbita. Questionnaires were sent to 173 Brazilian institutions regarding the preservation conditions ex situ. A genetic variability of the Cucurbita genus was found in traditional Brazilian agriculture. Collections must be prioritized in the northern and southern regions (all states); the southeastern region, all states, except Minas Gerais; central-west, in Mato Grosso do Sul and Mato Grosso; the northeastern region, the states of Alagoas, Maranhão, Paraíba, Pernambuco, Piauí and Sergipe. Currently 5.545 entries are being conserved in the Germplasm banks, however, C. pepo, C. ficifolia, C. argyrosperma and wild species are poorly represented. The characterization level of conserved entries is low in the ex situcollections. Participative research projects must be financed as a way to stimulate the farmers to continue planting their local varieties. A coleta e conservação do gênero Cucurbita no Brasil aconteceu de forma dispersa pelas instituições, sendo necessário um diagnóstico sobre as condições de conservação e sobre a diversidade genética, tornando possível identificar novas prioridades para o gênero. Este trabalho realizou diagnóstico sobre distribuição geográfica, condições de conservação in situ e ex situ e sobre diversidade genética do gênro Cucurbita no Brasil. Para mapear as áreas de ocorrência das espécies, foram realizados levantamentos de informações em herbários, banco de dados, literatura e levantamentos in situ (expedições para áreas rurais, feiras livres e CEASAs). Nessas expedições foram aplicados questionários, buscando informações sobre a propriedade e o gênero Cucurbita. Em relação as condições de conservação ex situ, foram enviados questionários para 173 instituições brasileiras. Foi constatado que existe variabilidade genética do gênero Cucurbita na agricultura tradicional brasileira. Devem ser priorizadas coletas nas regiões Norte e Sul (todos os estados); região Sudeste, todos os estados, exceto Minas Gerais; região Centro-Oeste, no Mato Grosso do Sul e Mato Grosso; região Nordeste, os estados de Alagoas, Maranhão, Paraíba, Pernambuco, Piauí e Sergipe. Atualmente estão sendo conservados nos Bancos de Germoplasma 5.545 acessos, no entanto C. pepo, C ficifolia, C. argyrosperma e espécies silvestres estão pouco representadas. É baixa a taxa de caracterização dos acessos conservados nas coleções ex situ. Devem ser financiados projetos de pesquisa participativa como uma forma de estimular e dar condições aos agricultores de continuarem cultivado suas variedades locais.