The collective impact of rare diseases in Western Australia: an estimate using a population-based cohort.

PURPOSE: It has been argued that rare diseases should be recognized as a public health priority. However, there is a shortage of epidemiological data describing the true burden of rare diseases. This study investigated hospital service use to provide a better understanding of the collective health and economic impacts of rare diseases. METHODS: Novel methodology was developed using a carefully constructed set of diagnostic codes, a selection of rare disease cohorts from hospital administrative data, and advanced data-linkage technologies. Outcomes included health-service use and hospital admission costs. RESULTS: In 2010, cohort members who were alive represented approximately 2.0% of the Western Australian population. The cohort accounted for 4.6% of people discharged from hospital and 9.9% of hospital discharges, and it had a greater average length of stay than the general population. The total cost of hospital discharges for the cohort represented 10.5% of 2010 state inpatient hospital costs. CONCLUSIONS: This population-based cohort study provides strong new evidence of a marked disparity between the proportion of the population with rare diseases and their combined health-system costs. The methodology will inform future rare-disease studies, and the evidence will guide government strategies for managing the service needs of people living with rare diseases.Genet Med advance online publication 22 September 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.143

Use of mechanical airway clearance devices in the home by people with neuromuscular disorders: effects on health service use and lifestyle benefits

Background; People with neuromuscular disorders (NMD) exhibit weak coughs and are susceptible to recurrent chest infections and acute respiratory complications, the most frequent reasons for their unplanned hospital admissions. Mechanical insufflation-exsufflation (MI-E) devices are a non-invasive method of increasing peak cough flow, improving cough efficacy, the clearance of secretion and overcoming atelectasis. There is limited published evidence on the impact of home use MI-E devices on health service utilisation. The aims of the study were: to assess the self-reported health and lifestyle benefits experienced as a result of home use of MI-E devices; and evaluate the effects of in-home use of MI-E devices on Emergency Department (ED) presentations, hospital admissions and inpatient length of stay (LOS). Methods: Individuals with NMD who were accessing a home MI-E device provided through Muscular Dystrophy Western Australia were invited to participate in a quantitative survey to obtain information on their experiences and self-assessed changes in respiratory health. An ad-hoc record linkage was performed to extract hospital, ED and mortality data from the Western Australian Department of Health (DOHWA). The main outcome measures were ED presentations, hospital separations and LOS, before and after commencement of home use of an MI-E device.Results: Thirty seven individuals with NMD using a MI-E device at home consented to participate in this study. The majority (73%) of participants reported using the MI-E device daily or weekly at home without medical assistance and 32% had used the machine to resolve a choking episode. The survey highlighted benefits to respiratory function maintenance and the ability to manage increased health care needs at home. Not using a home MI-E device was associated with an increased risk of ED presentations (RR = 1.76, 95% CI 1.1-2.84). The number of hospital separations and LOS reduced after the use of MI-E device, but not significantly. No deaths were observed in participants using the MI-E device at home. Conclusions: Home use of a MI-E device by people living with NMD may have a potential impact on reducing their health service utilisation and risk of death. Future research with greater subject numbers and longer follow-up periods is recommended to enhance this field of study

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery

The TESS Objects of Interest Catalog from the TESS Prime Mission

We present 2241 exoplanet candidates identified with data from the Transiting Exoplanet Survey Satellite (TESS) during its 2 yr Prime Mission. We list these candidates in the TESS Objects of Interest (TOI) Catalog, which includes both new planet candidates found by TESS and previously known planets recovered by TESS observations. We describe the process used to identify TOIs, investigate the characteristics of the new planet candidates, and discuss some notable TESS planet discoveries. The TOI catalog includes an unprecedented number of small planet candidates around nearby bright stars, which are well suited for detailed follow-up observations. The TESS data products for the Prime Mission (sectors 1-26), including the TOI catalog, light curves, full-frame images, and target pixel files, are publicly available at the Mikulski Archive for Space Telescopes

A Handbook to literature./ Holman

vii, 603 hal. ; 24 cm

A Handbook to literature./ Holman

vii, 603 hal. ; 24 cm

A Handbook to literature./ Holman

vii, 603 hal. ; 24 cm