Functional filter for whole genome sequencing data identifies HHT and stress-associated non-coding SMAD4 polyadenylation site variants >5kb from coding DN

Acknowledgments: This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The work was cofounded by the National Institute for Health Research Imperial Biomedical Research Centre, the D’Almeida Charitable Trust, and Imperial College Healthcare NHS Trust. AA was supported by Prince Sultan Military Medical City, Saudi Arabia. MAA was supported by the National Institutes of Health (grant R35HL140019). The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. We thank the National Health Service staff of the UK Genomic Medicine Centres and the participants for their willing participation; the Genomics England Clinical Research Interface team, specifically Susan Walker, for separately reviewing bam file variant sequences; Charlotte Bevan, Michael Hubank and Santiago Vernia for helpful discussions and manuscript review; and our academic and public partners within the NIHR Imperial BRC’s Social Genetic and Environmental Determinants of Health (SGE) theme. We specifically thank the presented families for confirmation of their clinical phenotypes and consent to share in this manuscript. The views expressed are those of the authors and not necessarily those of funders, the NHS, the NIHR, or the Department of Health and Social Care.Peer reviewedPublisher PD

Classification of haematopoietic and lymphoid tumors: WHO, standardization of nomenclature in Portuguese, 4th edition

INTRODUCTION: The World Health Organization (WHO) classification of hematopoietic and lymphoid tissue (4th edition, 2008) tumors constitutes an updated review of the 3rd edition published in 2001. The translation of the nomenclature used to describe the entities should be clear, precise and uniform so that clinicians, pathologists and researchers involved in the onco-hematopathological area may identify them accurately. OBJECTIVE: With this purpose, the authors present an updated proposal and a terminological standardization in Portuguese based on WHO/2008INTRODUÇÃO: A classificação da Organização Mundial da Saúde (OMS) para os tumores do tecido hematopoético e linfoide (4ª edição, 2008) representa uma revisão atualização da 3ª edição publicada em 2001. A tradução da nomenclatura utilizada para identificar as entidades descritas deve ser clara, precisa e uniforme no sentido de reproduzir de forma correta as diversas entidades clinicopatológicas para clínicos, patologistas e pesquisadores envolvidos na área da onco-hematopatologia. OBJETIVO: Os autores apresentam uma proposta de atualização e padronização terminológica em língua portuguesa, com base na OMS/200864364

Genetic counselling and testing in pulmonary arterial hypertension:a consensus statement on behalf of the International Consortium for Genetic Studies in PAH

Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.</p

Behavioural and Developmental Interventions for Autism Spectrum Disorder: A Clinical Systematic Review

Background: Much controversy exists regarding the clinical efficacy of behavioural and developmental interventions for improving the core symptoms of autism spectrum disorders (ASD). We conducted a systematic review to summarize the evidence on the effectiveness of behavioural and developmental interventions for ASD. Methods and Findings: Comprehensive searches were conducted in 22 electronic databases through May 2007. Further information was obtained through hand searching journals, searching reference lists, databases of theses and dissertations, and contacting experts in the field. Experimental and observational analytic studies were included if they were written in English and reported the efficacy of any behavioural or developmental intervention for individuals with ASD. Two independent reviewers made the final study selection, extracted data, and reached consensus on study quality. Results were summarized descriptively and, where possible, meta-analyses of the study results were conducted. One-hundred-and-one studies at predominantly high risk of bias that reported inconsistent results across various interventions were included in the review. Meta-analyses of three controlled clinical trials showed that Lovaas treatment was superior to special education on measures of adaptive behaviour, communication and interaction, comprehensive language, daily living skills, expressive language, overall intellectual functioning and socialization. High-intensity Lovaas was superior to low-intensity Lovaas on measures of intellectual functioning in two retrospective cohort studies. Pooling the results of two randomized controlle

Recent progress in low-carbon binders

The development of low-carbon binders has been recognized as a means of reducing the carbon footprint of the Portland cement industry, in response to growing global concerns over CO2 emissions from the construction sector. This paper reviews recent progress in the three most attractive low-carbon binders: alkali-activated, carbonate, and belite-ye'elimite-based binders. Alkali-activated binders/materials were reviewed at the past two ICCC congresses, so this paper focuses on some key developments of alkali-activated binders/materials since the last keynote paper was published in 2015. Recent progress on carbonate and belite-ye'elimite-based binders are also reviewed and discussed, as they are attracting more and more attention as essential alternative low-carbon cementitious materials. These classes of binders have a clear role to play in providing a sustainable future for global construction, as part of the available toolkit of cements

Common variants near CAV1 and CAV2 are associated with primary openangle glaucoma.

l e t t e r s We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[A], odds ratio (OR) = 1.36, P = 5.0 × 10 −10 ). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG. Glaucoma is the leading cause of irreversible blindness worldwide, affecting approximately 70 million people 1 . It is a chronic degenerative optic neuropathy with progressive loss of retinal ganglion cells and axons resulting in a corresponding thinning of the neuroretinal rim of the optic nerve and a characteristic visual field defect. It is distinct from other forms of optic neuropathy in that the neuro retinal rim of the optic nerve retains its normal pink color as it becomes progressively thinner, leading to an enlarged opticnerve cup. POAG is the most common form of glaucoma. Excluding rare primary juvenile glaucoma with age of onset between 10 and 35 years, POAG is arbitrarily divided into highpressure glaucoma (defined as ≥22 mmHg) and normalpressure glaucoma. POAG is thought to have a multifactorial etiology, with the main risk factors being age, elevated intraocular (IOP) pressure, family history, race, central corneal thickness (CCT), hypertension, diabetes and myopia. The familiality of POAG has been known for decades, and studies have revealed three to ninefold greater risk of POAG in firstdegree relatives of POAG cases than in the population in general 2 . Common variants near CAV1 and CAV2 are associated with primary openangle glaucom

18 Eye Clinic

We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in ,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q3 (rs423660[A], odds ratio (OR) = .36, P = 5.0 × 0 −0 ). We then replicated the association in sample sets of 2,75 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = .8, P = 0.005) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.002). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG. Glaucoma is the leading cause of irreversible blindness worldwide, affecting approximately 70 million people 1 . It is a chronic degenerative optic neuropathy with progressive loss of retinal ganglion cells and axons resulting in a corresponding thinning of the neuroretinal rim of the optic nerve and a characteristic visual field defect. It is distinct from other forms of optic neuropathy in that the neuro retinal rim of the optic nerve retains its normal pink color as it becomes progressively thinner, leading to an enlarged opticnerve cup. POAG is the most common form of glaucoma. Excluding rare primary juvenile glaucoma with age of onset between 10 and 35 years, POAG is arbitrarily divided into highpressure glaucoma (defined as ≥22 mmHg) and normalpressure glaucoma. POAG is thought to have a multifactorial etiology, with the main risk factors being age, elevated intraocular (IOP) pressure, family history, race, central corneal thickness (CCT), hypertension, diabetes and myopia. The familiality of POAG has been known for decades, and studies have revealed three to ninefold greater risk of POAG in firstdegree relatives of POAG cases than in the population in general 2 . Common variants near CAV1 and CAV2 are associated with primary openangle glaucom

Varieties of capitalism, governance, and high-tech export performance: A fuzzy-set analysis of the new EU member states

PurposeThis paper aims to assess the extent to which convergence in institutional regimes is likely to occur, by examining all ten new EU member states in Central and Eastern Europe in terms of their development of comparative advantages in high‐tech export markets either by drawing on foreign investors in the form of multinational companies or by making use of domestic institutional resources.Design/methodology/approachThe article uses fuzzy sets and qualitative comparative analysis to examine both necessary and sufficient causes of success in high‐tech export markets. By doing so, it can address the important issue of institutional complementarity.FindingsWhile it finds that countries that have stronger records in such markets share common features, there are also important differences between them – not least in the areas of employee relations. This, together with other evidence presented in the paper, suggests that convergence around a specific institutional model is unlikely to happen.Originality/valueAnalysing, unlike many previous studies, all ten new EU member states in Central and Eastern Europe enables conclusions to be drawn that apply to the whole region. The novel method used in this article means that the extent of any complementarity between different institutions can be addressed, and ensures that issues relating to convergence/divergence are explored. The article, therefore, contributes to a number of important debates on the convergence among types of capitalism, the dependency of the new EU member states on foreign investors, and the institutional foundations for success in high‐tech export markets.</jats:sec