Are local guidelines on investigations in children admitted with acute gastroenteritis being adhered to?

The aim of this article is to assess adherence to local guidelines on the investigation of children admitted with acute gastroenteritis. Children admitted to Mater Dei Hospital with a diagnosis of gastroenteritis between December 2012 and February 2013 were selected. Their investigations were retrospectively assessed in relation to the degree of dehydration and the type of management given. Hospital guidelines relating to investigations performed in children admitted with gastroenteritis were reviewed and compliance was assessed. A total of 411 investigations were carried out in 76 children with the most common investigations being serum electrolytes, urea and creatinine and random blood glucose. Guidelines were met in 4/76 (5.3%) of the study population. Serum electrolytes had the greatest impact on management. The conclusion is that the local guideline on gastroenteritis is not being adhered to in the vast majority of cases. There is an urgent need to raise awareness about the availability and utilisation of this guideline amongst doctors working in paediatrics.peer-reviewe

The distribution implications of selected policy measures of the 2018 budget for Malta

This note provides an assessment of the redistributive impact of some of the main measures announced in the 2018 Budget for Malta. The four main policy measures included in this study are increase in pension rates, introduction of a tax rebate on all persons in employment, tax credit for elderly persons and extension of in-work benefit scheme. Through the utilisation of EUROMOD, a tax-benefit micro-simulation model, we analyse the impact of these policy measures on income distribution and their respective source of income. The overall results indicate that the implementation of these measures contributes to a redistribution of income from higher to lower and middle-income groups whilst lowering the at-risk-of-poverty rate. Increase in pension rates positively affects, and mostly, the bottom three decile groups while the income tax reform leads to an increase in disposable income for the fourth, fifth and sixth decile groups.peer-reviewe

Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages.

The establishment of the embryonic and trophoblast lineages is a developmental decision underpinned by dramatic differences in the epigenetic landscape of the two compartments. However, it remains unknown how epigenetic information and transcription factor networks map to the 3D arrangement of the genome, which in turn may mediate transcriptional divergence between the two cell lineages. Here, we perform promoter capture Hi-C experiments in mouse trophoblast (TSC) and embryonic (ESC) stem cells to understand how chromatin conformation relates to cell-specific transcriptional programmes. We find that key TSC genes that are kept repressed in ESCs exhibit interactions between H3K27me3-marked regions in ESCs that depend on Polycomb repressive complex 1. Interactions that are prominent in TSCs are enriched for enhancer-gene contacts involving key TSC transcription factors, as well as TET1, which helps to maintain the expression of TSC-relevant genes. Our work shows that the first developmental cell fate decision results in distinct chromatin conformation patterns establishing lineage-specific contexts involving both repressive and active interactions

Social impact assessment : Reġjun Lvant

The scope of a Social Impact Assessment is to analyse, better monitor the intended and unintended social consequences from policies, programs and project concluded or planned, and the social changes these would have had or might bring about.Obviously, the conclusion from such a study - which all of Malta’s Regional Councils are obliged to conduct within the initial years of each new legislature - has the primary purpose to help gauge the present social status within each. In the light of the findings hereby being presented by the Faculty for Social Wellbeing within the University of Malta, the Eastern Regional Council, is now in a more knowledgeable position to mitigate for, address and plan adequate interventions to maximise benefits towards the Social Wellbeing and best interest of our communities.We feel our Region is rich in contrasts of different aspects. Ours, is the most populous region and assembles, smaller, quaint localities steeped in tradition, amassed over many centuries. A few of more recent development, and which are still evolving at a very fast pace, totally away from previously early identifiable characteristics of a more traditional way of life. Others larger, ever expanding - mostly upwards! quite cosmopolitan, vibrant and bustling with commercial, entertainment and tourism activities! So, matters of social concerns abound.This report’s conclusions provide us with the opportunity to test how near or far off correct are our perceptions.This scientific snapshot is most needed and welcome; conclusions need to be very carefully studied and assessed, so the right policies may be set in place at the earliest.Times change, and our Islands have and still are experiencing a great deal of this. Are we adapting to change? Surely forever -a bone of contention-, we have to learn to adapt to change if we are to move forward. Does however the old saying “When in Rome do like the Romans do”! still hold water? This report should enlighten us further. I am of the opinion that there’s still a great deal to debate on this!Let’s thrive towards building a Society that embraces every person irrespective; one based on ‘common understanding’ and one that will always hold dear to its heart the ‘Wellbeing of All’.peer-reviewe

Social impact assessment Southern region

It is incredible how complex our communities are. No wonder getting people together at times is so complex. This study which has been commissioned by the regional councils is an important loop in helping us conceptualize the nuances that tug on the way we operate and function as a society. The variables are increasingly composite but with the right type of social and political governance we are sure to find a way how to untangle this multiplexity and learn to not only live ‘with each other’ but ‘together’. However, as we know, communities cannot just happen. Having neighbourhoods where people are living sideby- side is not enough. We are at a transition stage which calls for active engagement for people to come together. We hope that this courageous act from the regional councils to take the bull by the horns and try to understand the transformations that are happening in this region are vindicated by a report led by a team of RSOs (Stephanie Bugeja, Maria Giulia Borg and Ruth Mifsud) and an academic (Dr Maria Brown) that will help with understanding the complex dynamics and propose recommendations.peer-reviewe

A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS

HLA-A*11:01-restricted CD8+ T cell immunity against influenza A and influenza B viruses in Indigenous and non-Indigenous people

HLA-A*11:01 is one of the most prevalent human leukocyte antigens (HLAs), especially in East Asian and Oceanian populations. It is also highly expressed in Indigenous people who are at high risk of severe influenza disease. As CD8+ T cells can provide broadly cross-reactive immunity to distinct influenza strains and subtypes, including influenza A, B and C viruses, understanding CD8+ T cell immunity to influenza viruses across prominent HLA types is needed to rationally design a universal influenza vaccine and generate protective immunity especially for high-risk populations. As only a handful of HLA-A*11:01-restricted CD8+ T cell epitopes have been described for influenza A viruses (IAVs) and epitopes for influenza B viruses (IBVs) were still unknown, we embarked on an epitope discovery study to define a CD8+ T cell landscape for HLA-A*11:01-expressing Indigenous and non-Indigenous Australian people. Using mass-spectrometry, we identified IAV- and IBV-derived peptides presented by HLA-A*11:01 during infection. 79 IAV and 57 IBV peptides were subsequently screened for immunogenicity in vitro with peripheral blood mononuclear cells from HLA-A*11:01-expressing Indigenous and non-Indigenous Australian donors. CD8+ T cell immunogenicity screening revealed two immunogenic IAV epitopes (A11/PB2320-331 and A11/PB2323-331) and the first HLA-A*11:01-restricted IBV epitopes (A11/M41-49, A11/NS1186-195 and A11/NP511-520). The immunogenic IAV- and IBV-derived peptides were >90% conserved among their respective influenza viruses. Identification of novel immunogenic HLA-A*11:01-restricted CD8+ T cell epitopes has implications for understanding how CD8+ T cell immunity is generated towards IAVs and IBVs. These findings can inform the development of rationally designed, broadly cross-reactive influenza vaccines to ensure protection from severe influenza disease in HLA-A*11:01-expressing individuals

BMJ Open

INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients

Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative : study protocol and rationale of a multicentre retrospective individual patient data meta-analysis

Introduction Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. Methods and analysis The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.Peer reviewe

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe