National health reform needs strategic investment in health services research

• With new funding for the National Health and Medical Research Council (NHMRC) to provide an evidence base for policy and practice reform, it is timely to revisit Australia's recent experiences with health services research and policy development. • We provide a broad review of the contribution of Australian health services research to the development of health policy over the past 20 years. • We conclude that three preconditions are necessary to influence policy: political will; sustained funding to encourage methodological rigour and build decisionmakers' confidence; and the development of sufficient capacity and skills

VenSAR: A multi-functional S-band radar for the EnVision mission to Venus

The EnVision science case requires an instrument capable of providing global stereo images at 10-50 m resolution, phase information from at least 20% of the surface for interferometry, as well as the ability to provide 1-10 m resolution images of specific targets in the C- to S-band range (X-band does not penetrate through the atmosphere to the surface of Venus). VenSAR is adapted from the individual phase centre design of NovaSAR-S, which offers much greater flexibility that can be optimised for Venus science. In addition, its S-band wavelength offers an acceptable compromise between InSAR resolution and atmospheric stability. The use of an off-the-shelf system, adapted for use at Venus, saves cost and provides for directly comparable data from Venus and Earth at a resolution two orders of magnitude better than Magellan, for the first time allowing the direct measurement of rates of tectonic and volcanic processes on another planet

A Bayesian Approach to Graphical Record Linkage and Deduplication

© 2016 American Statistical Association.We propose an unsupervised approach for linking records across arbitrarily many files, while simultaneously detecting duplicate records within files. Our key innovation involves the representation of the pattern of links between records as a bipartite graph, in which records are directly linked to latent true individuals, and only indirectly linked to other records. This flexible representation of the linkage structure naturally allows us to estimate the attributes of the unique observable people in the population, calculate transitive linkage probabilities across records (and represent this visually), and propagate the uncertainty of record linkage into later analyses. Our method makes it particularly easy to integrate record linkage with post-processing procedures such as logistic regression, capture–recapture, etc. Our linkage structure lends itself to an efficient, linear-time, hybrid Markov chain Monte Carlo algorithm, which overcomes many obstacles encountered by previously record linkage approaches, despite the high-dimensional parameter space. We illustrate our method using longitudinal data from the National Long Term Care Survey and with data from the Italian Survey on Household and Wealth, where we assess the accuracy of our method and show it to be better in terms of error rates and empirical scalability than other approaches in the literature. Supplementary materials for this article are available online

SMERED: A Bayesian Approach to Graphical Record Linkage and De-duplication

We propose a novel unsupervised approach for linking records across arbitrarily many files, while simultaneously detecting duplicate records within files. Our key innovation is to represent the pattern of links between records as a {\em bipartite} graph, in which records are directly linked to latent true individuals, and only indirectly linked to other records. This flexible new representation of the linkage structure naturally allows us to estimate the attributes of the unique observable people in the population, calculate $k$-way posterior probabilities of matches across records, and propagate the uncertainty of record linkage into later analyses. Our linkage structure lends itself to an efficient, linear-time, hybrid Markov chain Monte Carlo algorithm, which overcomes many obstacles encountered by previously proposed methods of record linkage, despite the high dimensional parameter space. We assess our results on real and simulated data

VenSAR on EnVision: taking Earth Observation radar to Venus

Venus should be the most Earth-like of all our planetary neighbours: its size, bulk composition and distance from the Sun are very similar to those of Earth. How and why did it all go wrong for Venus? What lessons can be learned about the life story of terrestrial planets in general, in this era of discovery of Earth-like exoplanets? Were the radically different evolutionary paths of Earth and Venus driven solely by distance from the Sun, or do internal dynamics, geological activity, volcanic outgassing and weathering also play an important part? EnVision is a proposed ESA Medium class mission designed to take Earth Observation technology to Venus to measure its current rate of geological activity, determine its geological history, and the origin and maintenance of its hostile atmosphere, to understand how Venus and Earth could have evolved so differently. EnVision will carry three instruments: the Venus Emission Mapper (VEM); the Subsurface Radar Sounder (SRS); and VenSAR, a world-leading European phased array synthetic aperture radar that is the subject of this article. VenSAR will obtain images at a range of spatial resolutions from 30 m regional coverage to 1 m images of selected areas; an improvement of two orders of magnitude on Magellan images; measure topography at 15 m resolution vertical and 60 m spatially from stereo and InSAR data; detect cm-scale change through differential InSAR, to characterise volcanic and tectonic activity, and estimate rates of weathering and surface alteration; and characterise of surface mechanical properties and weathering through multi-polar radar data. These data will be directly comparable with Earth Observation radar data, giving geoscientists unique access to an Earth-sized planet that has evolved on a radically different path to our own, offering new insights on the Earth-sized exoplanets across the galaxy

Inhibition of Sec61-dependent translocation by mycolactone uncouples the integrated stress response from ER stress, driving cytotoxicity via translational activation of ATF4

Mycolactone is the exotoxin virulence factor of Mycobacterium ulcerans that causes the neglected tropical disease Buruli ulcer. We recently showed it to be a broad spectrum inhibitor of Sec61-dependent co-translational translocation of proteins into the endoplasmic reticulum (ER). An outstanding question is the molecular pathway linking this to its known cytotoxicity. We have now used translational profiling to better understand the reprogramming that occurs in cells exposed to mycolactone. Gene ontology identified enrichment in genes involved in cellular response to stress, and apoptosis signalling among those showing enhanced translation. Validation of these results supports a mechanism by which mycolactone activates an integrated stress response meditated by phosphorylation of eIF2α via multiple kinases (PERK, GCN, PKR) without activation of the ER stress sensors IRE1 or ATF6. The response therefore uncouples the integrated stress response from ER stress, and features translational and transcriptional modes of genes expression that feature the key regulatory transcription factor ATF4. Emphasising the importance of this uncoupled response in cytotoxicity, downstream activation of this pathway is abolished in cells expressing mycolactone-resistant Sec61α variants. Using multiple genetic and biochemical approaches, we demonstrate that eIF2α phosphorylation is responsible for mycolactone-dependent translation attenuation, which initially protects cells from cell death. However, chronic activation without stress remediation enhances autophagy and apoptosis of cells by a pathway facilitated by ATF4 and CHOP. Our findings demonstrate that priming events at the ER can result in the sensing of stress within different cellular compartmentsWellcome Trus

Evaluation of a strict protocol approach in managing women with severe disease due to hypertension in pregnancy: A before and after study

BACKGROUND: To evaluate whether the introduction of a strict protocol based on the systemic evaluation of critically ill pregnant women with complications of hypertension affected the outcome of those women. METHOD: Study group: Indigent South African women managed in the tertiary hospitals of the Pretoria Academic Complex. Since 1997 a standard definition of women with severe acute maternal morbidity (SAMM), also referred to as a Nearmiss, has been used in the Pretoria Academic Complex. All cases of SAMM and maternal deaths (MD) were entered on the Maternal Morbidity and Mortality Audit System programme (MaMMAS). A comparison of outcome of severely ill women who had complications of hypertension in pregnancy was performed between 1997–1998 (original protocol) and 2002–2003 (strict protocol). Data include women referred from outside the Pretoria Academic Complex area to the tertiary hospitals. RESULTS: Between 1997–1998 there were 79 women with SAMM and 18 maternal deaths due to complications of hypertension, compared with 91 women with SAMM and 13 maternal deaths in 2002–2003. The mortality index (MI) declined from 18.6% to 12.5% (OR 0.62, 95% CI 0.27–1.45). Statistically significant fewer women had renal failure (RR 0.37, 95% CI 0.21 – 0.66) and cerebral complications (RR 0.52, 95%CI 0.34 – 0.81) during the second period, and liver dysfunction (RR 0.27 95%CI 0.06 – 1.25) tended to be lower. However, there tended to be an increase in the number of women, who had immune system failure (RR 4.2 95%CI 0.93 – 18.94) and respiratory failure (RR 1.42 95%CI 0.88 – 2.29) although it did not reach significance. Cardiac failure remained constant (RR 0.84 95%CI 0.54 – 1.30). CONCLUSION: The strict protocol approach based on the systemic evaluation of severely ill pregnant women with complications of hypertension and an intensive, regular feedback mechanism has been associated with a reduction in the number of patients with renal failure and cerebral compromise

Minsky machines and algorithmic problems

This is a survey of using Minsky machines to study algorithmic problems in semigroups, groups and other algebraic systems.Comment: 19 page