Caminhos para o empreendedorismo: uma tipologia de acesso à atividade empreendedora

Este artigo tem por objetivo central analisar os fatores sociais que, de forma articulada, explicam a decisão de uma pessoa se tornar empreendedora. Para o efeito é mobilizada informação recolhida no âmbito de um projeto de investigação realizado em Portugal direcionado para o estudo dos padrões, contextos e experiências de empreendedorismo. Com base na componente qualitativa da pesquisa, relativa à análise de entrevistas aprofundadas a mulheres e homens empreendedores sobre os seus trajetos individuais, foi elaborada uma tipologia de acesso à empresarialidade. Esta categorização expressa diferentes combinações de fatores, dando particular destaque aos efeitos que o género e as qualificações têm na opção de trabalhar por conta própria, sem deixar de enfatizar a interligação com as inserções socioeconômicas, as redes interpessoais e as relações familiares

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport

Tiina Paunio on työryhmän UK10K jäsen.The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.Peer reviewe

Whole-genome sequence-based analysis of thyroid function

Tiina Paunio on työryhmän UK10K Consortium jäsen.Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N = 2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF >= 1%) associated with TSH and FT4 (N = 16,335). For TSH, we identify a novel variant in SYN2 (MAF = 23.5%, P = 6.15 x 10(-9)) and a new independent variant in PDE8B (MAF = 10.4%, P = 5.94 x 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/ SLC25A52 (MAF = 3.2%, P = 1.27 x 10(-9)) tagging a rare TTR variant (MAF = 0.4%, P = 2.14 x 10(-11)). All common variants explain >= 20% of the variance in TSH and FT4. Analysis of rare variants (MAFPeer reviewe

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Hemangioma Gigante na Criança — Tratamento com Interferon Alfa 2A — Um Caso Clínico

O hemangioma é uma das malformações congénitas mais comuns na infância, habitualmente benigna e de involução expontânea.Em casos raros,pelo seu volume ou pela sua localização em estruturas vitais, pode causar graves problemas e ser de dificil controle.Os autores apresentam o caso clínico de uma criança do sexo feminino, com um hemangioma gigante localizado no hemitórax esquerdo, braço eantebraço esquerdo, que pela sua grande extensão e volume condionava uma insuficiência cardíaca de alto débito, com deficiente crescimento estatoponderai.A gravidade da situação, a ausência de resposta aos 2 ciclos de prednisolona (4 mg/kg/d) e o insucesso da embolização realizada por cateterismocardíaco, levaram à medicação com interferon a-2A (3 milhões de unidades por m2 de superfície corporal, em injecção subcutânea diária). Após o iníciodesta terapêutica, que foi mantida durante um ano, assistiu-se a uma redução rápida e progressiva da massa angiomatosa, com desaparecimento dainsuficiência cardíaca e pronta recuperação do crescimento. À excepção de neutropenia transitória, que não se associou a qualquer infecção, não seregistaram outros efeitos secundários. Actualmente a criança com 3,5 anos de idade, terminou há um ano o tratamento, encontrando-se clinicamente beme com excelente evolução estato-ponderal

Mine-influenced waters: the relationship between Total Dissolved Solids/Electrical Conductivity and Total Dissolved Solids/Acidity

Total dissolved solids (TDS) are usually estimated from electrical conductivity (EC) by applying a conversion factor f, which results relatively well for natural waters. However, in the case of mine waters defining a conversion factor is not as simple since this type of water is highly mineralized and has complex chemical matrices. So, the present work aims to establish a conversion factor from the classic parameters usually analyzed for the hydrochemical characterization of these waters. The mine water samples were collected in three different mining areas: Valdarcas, São Domingos, and Campanario. Valcarcas is an old W-mine (N of Portugal) associated with skarn deposit, where acid mine drainage (AMD) problems remained even after the remediation project. São Domingos and Campanario are abandoned Cu-mines in the Iberian Pyrite Belt (IPB). IPB is one of the largest metallogenic provinces of the world, with an extension from the Alentejo region (SW of Portugal) to Sevilla (SW of Spain). These two mines also show AMD problems, and the remediation project started only in São Domingos. A total of 124 samples of mine-influenced waters were taken from AMD streams, acidic lagoons, and pit lakes. In the field, pH and EC were measured using a multi-parameter instrument. Total acidity was analyzed by volumetric titration, while sulfates and TDS were analyzed by turbidimetric and gravimetric methods, respectively. The range for each parameter analyzed was pH 0.44 to 5.13, EC 251 to 42 560 µS cm -1, TDS of 296 to 640086 mg L -1, sulfates of 153 to 2 684 963 mg L -1, and acidity of 96 to 429 250 mg L -1 of CaCO3. The TDS/EC ratio showed a nonlinear relationship. In contrast, TDS/Acidity reveals a high and positive linear correlation (r>0.97). Therefore, hierarchical cluster analysis (using Ward's method) was applied for grouping the diversity of samples based on their characteristics (pH, EC, sulfates, and acidity). This analysis allowed to clustering the data by their contamination degree. The classification obtained from the dendrogram supported the establishment of a conversion factor f that was calculated using the TDS and Acidity correlation. Such a procedure allows estimating TDS in a more accurate way than usually done by EC.This work was funded by FCT—Fundação para a Ciência e a Tecnologia through projects UIDB/04683/2020 and UIDP/04683/2020 and Nano-MINENV 029259 (PTDC/CTAAMB/29259/2017)