EFSUMB clinical practice guidelines for point-of-care ultrasound: Part one (Common heart and pulmonary applications) SHORT VERSION

Objective: To evaluate the evidence and produce a summary and recommendations for the most common heart and lung point-of-care ultrasound (PoCUS). Methods: We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendations were produced, including assigning levels of evidence (LoE) and grading of recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement of the summary and recommendation for each question (using a 5-point Likert scale), which was approved in the case of a level of agreement of greater than 75 %. A level of agreement was defined as a summary of strongly agree and agree on the Likert scale responses. Findings and recommendations: One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1), the remaining 9 questions achieved broad agreement with an assigned LoE of 4 and a weak GRADE recommendation (question 2), three achieved an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8) and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10). Conclusion: These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings

Post Occupancy Analysis of nZEB implementation via the PH standard

The 34th International Passive and Low Energy Architecture (PLEA 2018), The Chinese University of Hong Kong, Hong Kong, 10-12 December 2018Building regulations are currently under development across Europe in advance of the implementation of the nearly Zero Energy Buildings (nZEB) standard at national member state level. However, when revising the national building regulations to improve energy efficiency, few examples exist of the monitored performance of such dwellings, making informed decision-making difficult. This paper reports on the monitored performance of nZEB compliant dwellings which were built to the Passive House (PH) Standard. It finds that the PH bedroom CO2 concentrations are significantly better than in houses built to the current building regulations which use natural ventilation.Sustainable Energy Authority of Ireland (SEAI

Achieving schooling for All in Africa: Costs, Commitments and Gender

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Identification of 21 novel glucokinase (GCK) mutations in UK and European Caucasians with maturity-onset diabetes of the young (MODY).

Maturity-onset diabetes of the young (MODY) resulting from mutations in the glucokinase (GCK) gene accounts for approximately 20% of MODY in the UK. We have performed fluorescent single stranded conformation polymorphism (F-SSCP) analysis or direct sequencing of the GCK gene in 212 patients referred as part of a research cohort or for diagnostic molecular genetic testing. Mutation screening has identified 43 different mutations in 61 individuals, of which 21 are novel. This report details the mutations identified and their associated clinical features

Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

Glucokinase is a key regulatory enzyme in the pancreatic beta-cell. It plays a crucial role in the regulation of insulin secretion and has been termed the glucose sensor in pancreatic beta-cells. Given its central role in the regulation of insulin release it is understandable that mutations in the gene encoding glucokinase (GCK) can cause both hyper- and hypoglycemia. Heterozygous inactivating mutations in GCK cause maturity-onset diabetes of the young (MODY) subtype glucokinase (GCK), characterized by mild fasting hyperglycemia, which is present at birth but often only detected later in life during screening for other purposes. Homozygous inactivating GCK mutations result in a more severe phenotype presenting at birth as permanent neonatal diabetes mellitus (PNDM). A growing number of heterozygous activating GCK mutations that cause hypoglycemia have also been reported. A total of 620 mutations in the GCK gene have been described in a total of 1,441 families. There are no common mutations, and the mutations are distributed throughout the gene. The majority of activating mutations cluster in a discrete region of the protein termed the allosteric activator site. The identification of a GCK mutation in patients with both hyper- and hypoglycemia has implications for the clinical course and clinical management of their disorder

Homozygous hypomorphic HNF1A alleles are a novel cause of young-onset diabetes and result in sulphonylurea sensitive diabetes

OBJECTIVE Heterozygous loss-of-function mutations in HNF1A cause maturity-onset diabetes of the young (MODY). Affected individuals can be treated with low-dose sulphonylureas. Individuals with homozygous HNF1A mutations causing MODY have not been reported. RESEARCH DESIGN AND METHODS We phenotyped a kindred with young-onset diabetes and performed molecular genetic testing, a mixed meal tolerance test, a sulphonylurea challenge, and in vitro assays to assess variant protein function. RESULTS A homozygous HNF1A variant (p.A251T) was identified in three insulin-treated family members diagnosed with diabetes before 20 years of age. Those with the homozygous variant had low hs-CRP levels (0.2–0.8 mg/L), and those tested demonstrated sensitivity to sulphonylurea given at a low dose, completely transitioning off insulin. In silico modeling predicted a variant of unknown significance; however, in vitro studies supported a modest reduction in transactivation potential (79% of that for the wild type; P CONCLUSIONS Homozygous hypomorphic HNF1A variants are a cause of HNF1A-MODY. We thus expand the allelic spectrum of variants in dominant genes causing diabetes.</p

A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.

Neonatal diabetes is a genetically heterogeneous disorder with nine different genetic aetiologies reported to date. Heterozygous activating mutations in the KCNJ11 gene encoding Kir6.2, the pore-forming subunit of the ATP-sensitive potassium (K(ATP)) channel, are the most common cause of permanent neonatal diabetes. The sulphonylurea receptor (SUR) SUR1 serves as the regulatory subunit of the K(ATP) channel in pancreatic beta cells. We therefore hypothesized that activating mutations in the ABCC8 gene, which encodes SUR1, might cause neonatal diabetes. We identified a novel heterozygous mutation, F132L, in the ABCC8 gene of a patient with severe developmental delay, epilepsy and neonatal diabetes (DEND syndrome). This mutation had arisen de novo and was not present in 150 control chromosomes. Residue F132 shows evolutionary conservation across species and is located in the first set of transmembrane helices (TMD0) of SUR1, which is proposed to interact with Kir6.2. Functional studies of recombinant K(ATP) channels demonstrated that F132L markedly reduces the sensitivity of the K(ATP) channel to inhibition by MgATP and this increases the whole-cell K(ATP) current. The functional consequence of this ABCC8 mutation mirrors that of KCNJ11 mutations causing neonatal diabetes and provides new insights into the interaction of Kir6.2 and SUR1. As SUR1 is expressed in neurones as well as in beta cells, this mutation can account for both neonatal diabetes and the neurological phenotype. Our results demonstrate that SUR1 mutations constitute a new genetic aetiology for neonatal diabetes and that they act by reducing the K(ATP) channel's ATP sensitivity