Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012

Introduction A decrease in disease-specific mortality over the last twenty years has been reported for patients admitted to United States (US) hospitals, but data for intensive care patients are lacking. The aim of this study was to describe changes in hospital mortality and case-mix using clinical data for patients admitted to multiple US ICUs over the last 24 years. Methods We carried out a retrospective time series analysis of hospital mortality using clinical data collected from 1988 to 2012. We also examined the impact of ICU admission diagnosis and other clinical characteristics on mortality over time. The potential impact of hospital discharge destination on mortality was also assessed using data from 2001 to 2012. Results For 482,601 ICU admissions there was a 35% relative decrease in mortality from 1988 to 2012 despite an increase in age and severity of illness. This decrease varied greatly by diagnosis. Mortality fell by \u3e60% for patients with chronic obstructive pulmonary disease, seizures and surgery for aortic dissection and subarachnoid hemorrhage. Mortality fell by 51% to 59% for six diagnoses, 41% to 50% for seven diagnoses, and 10% to 40% for seven diagnoses. The decrease in mortality from 2001 to 2012 was accompanied by an increase in discharge to post-acute care facilities and a decrease in discharge to home. Conclusions Hospital mortality for patients admitted to US ICUs has decreased significantly over the past two decades despite an increase in the severity of illness. Decreases in mortality were diagnosis specific and appear attributable to improvements in the quality of care, but changes in discharge destination and other confounders may also be responsible

Creating an "enabling environment" for taking insecticide treated nets to national scale: the Tanzanian experience

INTRODUCTION: Malaria is the largest cause of health services attendance, hospital admissions and child deaths in Tanzania. At the Abuja Summit in April 2000 Tanzania committed itself to protect 60% of its population at high risk of malaria by 2005. The country is, therefore, determined to ensure that sustainable malaria control using insecticide-treated nets is carried out on a national scale. CASE DESCRIPTION: Tanzania has been involved for two decades in the research process for developing insecticide-treated nets as a malaria control tool, from testing insecticides and net types, to assessing their efficacy and effectiveness, and exploring new ways of distribution. Since 2000, the emphasis has changed from a project approach to that of a concerted multi-stakeholder action for taking insecticide-treated nets to national scale (NATNETS). This means creating conditions that make insecticide-treated nets accessible and affordable to all those at risk of malaria in the country. This paper describes Tanzania's experience in (1) creating an enabling environment for insecticide-treated nets scale-up, (2) promoting the development of a commercial sector for insecticide-treated nets, and (3) targeting pregnant women with highly subsidized insecticide-treated nets through a national voucher scheme. As a result, nearly 2 million insecticide-treated nets and 2.2 million re-treatment kits were distributed in 2004. CONCLUSION: National upscaling of insecticide-treated nets is possible when the programme is well designed, coordinated and supported by committed stakeholders; the Abuja target of protecting 60% of those at high risk is feasible, even for large endemic countries

Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation

Advances in sequencing technology allow researchers to map genome-wide changes in DNA methylation in development and disease. However, there is a lack of experimental tools to site-specifically manipulate DNA methylation to discern the functional consequences. We developed a CRISPR/Cas9 DNA methyltransferase 3A (DNMT3A) fusion to induce DNA methylation at specific loci in the genome. We induced DNA methylation at up to 50% of alleles for targeted CpG dinucleotides. DNA methylation levels peaked within 50 bp of the short guide RNA (sgRNA) binding site and between pairs of sgRNAs. We used our approach to target methylation across the entire CpG island at the CDKN2A promoter, three CpG dinucleotides at the ARF promoter, and the CpG island within the Cdkn1a promoter to decrease expression of the target gene. These tools permit mechanistic studies of DNA methylation and its role in guiding molecular processes that determine cellular fate

Large N Phases, Gravitational Instantons and the Nuts and Bolts of AdS Holography

Recent results in the literature concerning holography indicate that the thermodynamics of quantum gravity (at least with a negative cosmological constant) can be modeled by the large N thermodynamics of quantum field theory. We emphasize that this suggests a completely unitary evolution of processes in quantum gravity, including black hole formation and decay; and even more extreme examples involving topology change. As concrete examples which show that this correspondence holds even when the space-time is only locally asymptotically AdS, we compute the thermodynamical phase structure of the AdS-Taub-NUT and AdS-Taub-Bolt spacetimes, and compare them to a 2+1 dimensional conformal field theory (at large N) compactified on a squashed three sphere, and on the twisted plane.Comment: 20 pages, three figures. (uses harvmac.tex and epsf.tex

Knowledge gaps in economic costs of invasive alien fish worldwide

Peer reviewe

Attributing scientific and technical progress: the case of holography

Holography, the three-dimensional imaging technology, was portrayed widely as a paradigm of progress during its decade of explosive expansion 1964–73, and during its subsequent consolidation for commercial and artistic uses up to the mid 1980s. An unusually seductive and prolific subject, holography successively spawned scientific insights, putative applications and new constituencies of practitioners and consumers. Waves of forecasts, associated with different sponsors and user communities, cast holography as a field on the verge of success—but with the dimensions of success repeatedly refashioned. This retargeting of the subject represented a degree of cynical marketeering, but was underpinned by implicit confidence in philosophical positivism and faith in technological progressivism. Each of its communities defined success in terms of expansion, and anticipated continual progressive increase. This paper discusses the contrasting definitions of progress in holography, and how they were fashioned in changing contexts. Focusing equally on reputed ‘failures’ of some aspects of the subject, it explores the varied attributes by which success and failure were linked with progress by different technical communities. This important case illuminates the peculiar post-World War II environment that melded the military, commercial and popular engagement with scientific and technological subjects, and the competing criteria by which they assessed the products of science

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey)

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal ofmellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, \u3e1 g proteinuria, heart failure, estimated glomerular filtration ratemL·min RESULTS: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. CONCLUSIONS: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events

Nucleation and Growth of the Superconducting Phase in the Presence of a Current

We study the localized stationary solutions of the one-dimensional time-dependent Ginzburg-Landau equations in the presence of a current. These threshold perturbations separate undercritical perturbations which return to the normal phase from overcritical perturbations which lead to the superconducting phase. Careful numerical work in the small-current limit shows that the amplitude of these solutions is exponentially small in the current; we provide an approximate analysis which captures this behavior. As the current is increased toward the stall current J*, the width of these solutions diverges resulting in widely separated normal-superconducting interfaces. We map out numerically the dependence of J* on u (a parameter characterizing the material) and use asymptotic analysis to derive the behaviors for large u (J* ~ u^-1/4) and small u (J -> J_c, the critical deparing current), which agree with the numerical work in these regimes. For currents other than J* the interface moves, and in this case we study the interface velocity as a function of u and J. We find that the velocities are bounded both as J -> 0 and as J -> J_c, contrary to previous claims.Comment: 13 pages, 10 figures, Revte

Biological invasion costs reveal insufficient proactive management worldwide

Funding Information: The authors thank the French National Research Agency (ANR-14-CE02-0021) and the BNP-Paribas Foundation Climate Initiative for funding the InvaCost project and the work on InvaCost database development. The present work was conducted in the frame of InvaCost workshop carried in November 2019 (Paris, France) and funded by the AXA Research Fund Chair of Invasion Biology and is part of the AlienScenario project funded by BiodivERsA and Belmont-Forum call 2018 on biodiversity scenarios. RNC was funded through a Leverhulme Early Career Fellowship (ECF-2021-001) from the Leverhulme Trust and a Humboldt Postdoctoral Fellowship from the Alexander von Humboldt Foundation. DAA is funded by the Kuwait Foundation for the Advancement of Sciences (KFAS) (PR1914SM-01) and the Gulf University for Science and Technology (GUST) internal seed funds (187092 & 234597). CA was funded by the French National Centre for Scientific Research (CNRS). TWB acknowledges funding from the European Union's Horizon 2020 research and innovation programme Marie Skodowska-Curie fellowship (Grant No. 747120). FE was funded through the 2017?2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND programme, and with the funding organisation Austrian Science Foundation FWF (grant I 4011-B32). NK is funded by the basic project of Sukachev Institute of Forest SB RAS, Russia (Project No. 0287-2021-0011; data mining) and the Russian Science Foundation (project No. 21-16-00050; data analysis).Peer reviewedPublisher PD