Estimating the effect of healthcare-associated infections on excess length of hospital stay using inverse probability-weighted survival curves

Background: Studies estimating excess length of stay (LOS) attributable to nosocomial infections have failed to address time-varying confounding, likely leading to overestimation of their impact. We present a methodology based on inverse probability–weighted survival curves to address this limitation. Methods: A case study focusing on intensive care unit–acquired bacteremia using data from 2 general intensive care units (ICUs) from 2 London teaching hospitals were used to illustrate the methodology. The area under the curve of a conventional Kaplan-Meier curve applied to the observed data was compared with that of an inverse probability–weighted Kaplan-Meier curve applied after treating bacteremia as censoring events. Weights were based on the daily probability of acquiring bacteremia. The difference between the observed average LOS and the average LOS that would be observed if all bacteremia cases could be prevented was multiplied by the number of admitted patients to obtain the total excess LOS. Results: The estimated total number of extra ICU days caused by 666 bacteremia cases was estimated at 2453 (95% confidence interval [CI], 1803–3103) days. The excess number of days was overestimated when ignoring time-varying confounding (2845 [95% CI, 2276–3415]) or when completely ignoring confounding (2838 [95% CI, 2101–3575]). Conclusions: ICU-acquired bacteremia was associated with a substantial excess LOS. Wider adoption of inverse probability–weighted survival curves or alternative techniques that address time-varying confounding could lead to better informed decision making around nosocomial infections and other time-dependent exposures

Preclinical detection of infectivity and disease-specific PrP in blood throughout the incubation period of prion disease.

Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder characterised by accumulation of pathological isoforms of the prion protein, PrP. Although cases of clinical vCJD are rare, there is evidence there may be tens of thousands of infectious carriers in the United Kingdom alone. This raises concern about the potential for perpetuation of infection via medical procedures, in particular transfusion of contaminated blood products. Accurate biochemical detection of prion infection is crucial to mitigate risk and we have previously reported a blood assay for vCJD. This assay is sensitive for abnormal PrP conformers at the earliest stages of preclinical prion disease in mice and precedes the maximum infectious titre in blood. Not only does this support the possibility of screening asymptomatic individuals, it will also facilitate the elucidation of the complex relationship that exists between the ensemble of abnormal PrP conformers present in blood and the relationship to infectivity

Double marking revisited

In 2002, the Qualifications and Curriculum Authority (QCA) published the report of an independent panel of experts into maintaining standards at Advanced Level (A-Level). One of its recommendations was for: ‘limited experimental double marking of scripts in subjects such as English to determine whether the strategy would signi-ficantly reduce errors of measurement’ (p. 24). This recommendation provided the impetus for this paper which reviews the all but forgotten literature on double marking and considers its relevance now

Intensive care unit (ICU)-acquired bacteraemia and ICU mortality and discharge:Addressing time-varying confounding using appropriate methodology

Background: Studies often ignore time-varying confounding or may use inappropriate methodology to adjust for time-varying confounding. Aim: To estimate the effect of intensive care unit (ICU)-acquired bacteraemia on ICU mortality and discharge using appropriate methodology. Methods: Marginal structural models with inverse probability weighting were used to estimate the ICU mortality and discharge associated with ICU-acquired bacteraemia among patients who stayed more than two days at the general ICU of a London teaching hospital and remained bacteraemia-free during those first two days. For comparison, the same associations were evaluated with (i) a conventional Cox model, adjusting only for baseline confounders and (ii) a Cox model adjusting for baseline and time-varying confounders. Findings: Using the marginal structural model with inverse probability weighting, bacteraemia was associated with an increase in ICU mortality (cause-specific hazard ratio (CSHR): 1.29; 95% confidence interval (CI): 1.02-1.63)and a decrease in discharge (CSHR: 0.52; 95% CI: 0.45-0.60). By 60 days, among patients still in the ICU after two days and without prior bacteraemia, 8.0% of ICU deaths could be prevented by preventing all ICU-acquired bacteraemia cases. The conventional Cox model adjusting for time-varying confounders gave substantially different results [for ICU mortality, CSHR: 1.08 (95% CI: 0.88-1.32); for discharge, CSHR: 0.68 (95% CI: 0.60-0.77)]. Conclusion: In this study, even after adjusting for the timing of acquiring bacteraemia and time-varying confounding using inverse probability weighting for marginal structura

Planet Formation in the Outer Solar System

This paper reviews coagulation models for planet formation in the Kuiper Belt, emphasizing links to recent observations of our and other solar systems. At heliocentric distances of 35-50 AU, single annulus and multiannulus planetesimal accretion calculations produce several 1000 km or larger planets and many 50-500 km objects on timescales of 10-30 Myr in a Minimum Mass Solar Nebula. Planets form more rapidly in more massive nebulae. All models yield two power law cumulative size distributions, N_C propto r^{-q} with q = 3.0-3.5 for radii larger than 10 km and N_C propto r^{-2.5} for radii less than 1 km. These size distributions are consistent with observations of Kuiper Belt objects acquired during the past decade. Once large objects form at 35-50 AU, gravitational stirring leads to a collisional cascade where 0.1-10 km objects are ground to dust. The collisional cascade removes 80% to 90% of the initial mass in the nebula in roughly 1 Gyr. This dust production rate is comparable to rates inferred for alpha Lyr, beta Pic, and other extrasolar debris disk systems.Comment: invited review for PASP, March 2002. 33 pages of text and 12 figure

Electrochemistry at nanoscale electrodes : individual single-walled carbon nanotubes (SWNTs) and SWNT-templated metal nanowires

Individual nanowires (NWs) and native single-walled carbon nanotubes (SWNTs) can be readily used as well-defined nanoscale electrodes (NSEs) for voltammetric analysis. Here, the simple photolithography-free fabrication of submillimeter long Au, Pt, and Pd NWs, with sub-100 nm heights, by templated electrodeposition onto ultralong flow-aligned SWNTs is demonstrated. Both individual Au NWs and SWNTs are employed as NSEs for electron-transfer (ET) kinetic quantification, using cyclic voltammetry (CV), in conjunction with a microcapillary-based electrochemical method. A small capillary with internal diameter in the range 30–70 μm, filled with solution containing a redox-active mediator (FcTMA+ ((trimethylammonium)methylferrocene), Fe(CN)64–, or hydrazine) is positioned above the NSE, so that the solution meniscus completes an electrochemical cell. A 3D finite-element model, faithfully reproducing the experimental geometry, is used to both analyze the experimental CVs and derive the rate of heterogeneous ET, using Butler–Volmer kinetics. For a 70 nm height Au NW, intrinsic rate constants, k0, up to ca. 1 cm s–1 can be resolved. Using the same experimental configuration the electrochemistry of individual SWNTs can also be accessed. For FcTMA+/2+ electrolysis the simulated ET kinetic parameters yield very fast ET kinetics (k0 > 2 ± 1 cm s–1). Some deviation between the experimental voltammetry and the idealized model is noted, suggesting that double-layer effects may influence ET at the nanoscale

A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant staphylococcus aureus pandemic

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens

Accretion in the Early Kuiper Belt I. Coagulation and Velocity Evolution

We describe planetesimal accretion calculations in the Kuiper Belt. Our evolution code simulates planetesimal growth in a single annulus and includes velocity evolution but not fragmentation. Test results match analytic solutions and duplicate previous simulations at 1 AU. In the Kuiper Belt, simulations without velocity evolution produce a single runaway body with a radius of 1000 km on a time scale inversely proportional to the initial mass in the annulus. Runaway growth occurs in 100 Myr for 10 earth masses and an initial eccentricity of 0.001 in a 6 AU annulus centered at 35 AU. This mass is close to the amount of dusty material expected in a minimum mass solar nebula extrapolated into the Kuiper Belt. Simulations with velocity evolution produce runaway growth on a wide range of time scales. Dynamical friction and viscous stirring increase particle velocities in models with large (8 km radius) initial bodies. This velocity increase delays runaway growth by a factor of two compared to models without velocity evolution. In contrast, collisional damping dominates over dynamical friction and viscous stirring in models with small (80--800 m radius) initial bodies. Collisional damping decreases the time scale to runaway growth by factors of 4--10 relative to constant velocity calculations. Simulations with minimum mass solar nebulae, 10 earth masses, reach runaway growth on time scales of 20-40 Myr with 80 m initial bodies, 50-100 Myr with 800 m bodies, and 75-250 Myr for 8 km initial bodies. These growth times vary linearly with the mass of the annulus but are less sensitive to the initial eccentricity than constant velocity models.Comment: 45 pages of text (including 5 tables), 31 pages of figur

The TAOS Project Stellar Variability II. Detection of 15 Variable Stars

The Taiwanese-American Occultation Survey (TAOS) project has collected more than a billion photometric measurements since 2005 January. These sky survey data-covering timescales from a fraction of a second to a few hundred days-are a useful source to study stellar variability. A total of 167 star fields, mostly along the ecliptic plane, have been selected for photometric monitoring with the TAOS telescopes. This paper presents our initial analysis of a search for periodic variable stars from the time-series TAOS data on one particular TAOS field, No. 151 (RA = 17^{\rm h}30^{\rm m}6\fs67, Dec = 27\degr17\arcmin 30\arcsec, J2000), which had been observed over 47 epochs in 2005. A total of 81 candidate variables are identified in the 3 square degree field, with magnitudes in the range 8 < R < 16. On the basis of the periodicity and shape of the lightcurves, 29 variables, 15 of which were previously unknown, are classified as RR Lyrae, Cepheid, delta Scuti, SX Phonencis, semi-regular and eclipsing binaries.Comment: 20 pages, 6 figures, accepted in The Astronomical Journa

The use of happiness research for public policy

Research on happiness tends to follow a "benevolent dictator" approach where politicians pursue people's happiness. This paper takes an antithetic approach based on the insights of public choice theory. First, we inquire how the results of happiness research may be used to improve the choice of institutions. Second, we show that the policy approach matters for the choice of research questions and the kind of knowledge happiness research aims to provide. Third, we emphasize that there is no shortcut to an optimal policy maximizing some happiness indicator or social welfare function since governments have an incentive to manipulate this indicator