Australia\u27s health 2000 : the seventh biennial report of the Australian Institute of Health and Welfare

Australia\u27s Health 2000 is the seventh biennial health report of the Australian Institute of Health and Welfare. It is the nation\u27s authoritative source of information on patterns of health and illness, determinants of health, the supply and use of health services, and health services costs and performance.This 2000 edition serves as a summary of Australia\u27s health record at the end of the twentieth century. In addition, a special chapter is presented on changes in Australia\u27s disease profile over the last 100 years.Australia\u27s Health 2000 is an essential reference and information source for all Australians with an interest in health

Highly efficient serum-free manipulation of miRNA in human NK cells without loss of viability or phenotypic alterations is accomplished with TransIT-TKO.

Natural killer (NK) cells are innate lymphocytes with functions that include target cell killing, inflammation and regulation. NK cells integrate incoming activating and inhibitory signals through an array of germline-encoded receptors to gauge the health of neighbouring cells. The reactive potential of NK cells is influenced by microRNA (miRNA), small non-coding sequences that interfere with mRNA expression. miRNAs are highly conserved between species, and a single miRNA can have hundreds to thousands of targets and influence entire cellular programs. Two miRNA species, miR-155-5p and miR-146a-5p are known to be important in controlling NK cell function, but research to best understand the impacts of miRNA species within NK cells has been bottlenecked by a lack of techniques for altering miRNA concentrations efficiently and without off-target effects. Here, we describe a non-viral and straightforward approach for increasing or decreasing expression of miRNA in primary human NK cells. We achieve >90% transfection efficiency without off-target impacts on NK cell viability, education, phenotype or function. This opens the opportunity to study and manipulate NK cell miRNA profiles and their impacts on NK cellular programs which may influence outcomes of cancer, inflammation and autoimmunity

The Apertif Radio Transient System (ARTS): Design, commissioning, data release, and detection of the first five fast radio bursts

Fast radio bursts (FRBs) must be powered by uniquely energetic emission mechanisms. This requirement has eliminated a number of possible source types, but several remain. Identifying the physical nature of FRB emitters arguably requires good localisation of more detections, as well as broad-band studies enabled by real-time alerting. In this paper, we present the Apertif Radio Transient System (ARTS), a supercomputing radio-telescope instrument that performs real-time FRB detection and localisation on the Westerbork Synthesis Radio Telescope (WSRT) interferometer. It reaches coherent-addition sensitivity over the entire field of the view of the primary-dish beam. After commissioning results verified that the system performed as planned, we initiated the Apertif FRB survey (ALERT). Over the first 5 weeks we observed at design sensitivity in 2019, we detected five new FRBs, and interferometrically localised each of them to 0.4–10 sq. arcmin. All detections are broad band, very narrow, of the order of 1 ms in duration, and unscattered. Dispersion measures are generally high. Only through the very high time and frequency resolution of ARTS are these hard-to-find FRBs detected, producing an unbiased view of the intrinsic population properties. Most localisation regions are small enough to rule out the presence of associated persistent radio sources. Three FRBs cut through the halos of M31 and M33. We demonstrate that Apertif can localise one-off FRBs with an accuracy that maps magneto-ionic material along well-defined lines of sight. The rate of one every ~7 days ensures a considerable number of new sources are detected for such a study. The combination of the detection rate and localisation accuracy exemplified by the first five ARTS FRBs thus marks a new phase in which a growing number of bursts can be used to probe our Universe

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease