Whole-genome sequencing of patients with rare diseases in a national health system.

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.

Emergency nursing in Malta: past and present with a vision for the future.

Every other year, the International Council of Nurses convenes a conference. In 2011 it was held in Malta, and Diane Gurney, RN, MS, CEN, ENA Past President, attended to represent ENA. In this article Diane and Paul Calleja, MSc(Manchester) Nurs, BSc (Hons) Nurs, Dip Nurs, Malta Emergency Nurses Association (MENA) International Relationship Officer, describe this visit, the significant nursing history in Malta, emergency nursing, and MENA.

Global benchmarking of children's exposure to television advertising of unhealthy foods and beverages across 22 countries.

Restricting children's exposures to marketing of unhealthy foods and beverages is a global obesity prevention priority. Monitoring marketing exposures supports informed policymaking. This study presents a global overview of children's television advertising exposure to healthy and unhealthy products. Twenty-two countries contributed data, captured between 2008 and 2017. Advertisements were coded for the nature of foods and beverages, using the 2015 World Health Organization (WHO) Europe Nutrient Profile Model (should be permitted/not-permitted to be advertised). Peak viewing times were defined as the top five hour timeslots for children. On average, there were four times more advertisements for foods/beverages that should not be permitted than for permitted foods/beverages. The frequency of food/beverages advertisements that should not be permitted per hour was higher during peak viewing times compared with other times (P < 0.001). During peak viewing times, food and beverage advertisements that should not be permitted were higher in countries with industry self-regulatory programmes for responsible advertising compared with countries with no policies. Globally, children are exposed to a large volume of television advertisements for unhealthy foods and beverages, despite the implementation of food industry programmes. Governments should enact regulation to protect children from television advertising of unhealthy products that undermine their health.

Enantioselective Silver-Catalyzed Cascade Synthesis of Fused Lactone and Lactam Oxazolines.

A new and highly stereoselective cascade reaction between isocyanoacetate esters and α-hydroxy and α-amino ketones has been developed. A cinchona alkaloid derived aminophosphine/silver(I) catalyst complex promoted the reaction and enabled the ready synthesis of fused bicyclic γ-lactone and γ-lactam oxazolines with high enantiocontrol (up to 99% ee).