657 research outputs found
Prevalence of Gram-negative bacilli resistance in adult critically ill patients at admission screening
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
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: âlimited experimental double marking of scripts in subjects such as English to determine whether the strategy would signi-ficantly reduce errors of measurementâ (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
Global and Local Conformation of Human IgG Antibody Variants Rationalizes Loss of Thermodynamic Stability.
Immunoglobulinâ
G (IgG) monoclonal antibodies (mAbs) are a major class of medicines, with high specificity and affinity towards targets spanning many disease areas. The antibody Fc (fragment crystallizable) region is a vital component of existing antibody therapeutics, as well as many next generation biologic medicines. Thermodynamic stability is a critical property for the development of stable and effective therapeutic proteins. Herein, a combination of ion-mobility mass spectrometry (IM-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) approaches have been used to inform on the global and local conformation and dynamics of engineered IgG Fc variants with reduced thermodynamic stability. The changes in conformation and dynamics have been correlated with their thermodynamic stability to better understand the destabilising effect of functional IgG Fc mutations and to inform engineering of future therapeutic proteins.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20150722
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
Healthcare-associated outbreak of meticillin-resistant Staphylococcus aureus bacteraemia: role of a cryptic variant of an epidemic clone
BACKGROUND
New strains of meticillin-resistant Staphylococcus aureus (MRSA) may be associated with changes in rates of disease or clinical presentation. Conventional typing techniques may not detect new clonal variants that underlie changes in epidemiology or clinical phenotype.
AIM
To investigate the role of clonal variants of MRSA in an outbreak of MRSA bacteraemia at a hospital in England.
METHODS
Bacteraemia isolates of the major UK lineages (EMRSA-15 and -16) from before and after the outbreak were analysed by whole-genome sequencing in the context of epidemiological and clinical data. For comparison, EMRSA-15 and -16 isolates from another hospital in England were sequenced. A clonal variant of EMRSA-16 was identified at the outbreak hospital and a molecular signature test designed to distinguish variant isolates among further EMRSA-16 strains.
FINDINGS
By whole-genome sequencing, EMRSA-16 isolates during the outbreak showed strikingly low genetic diversity (P < 1 Ă 10(-6), Monte Carlo test), compared with EMRSA-15 and EMRSA-16 isolates from before the outbreak or the comparator hospital, demonstrating the emergence of a clonal variant. The variant was indistinguishable from the ancestral strain by conventional typing. This clonal variant accounted for 64/72 (89%) of EMRSA-16 bacteraemia isolates at the outbreak hospital from 2006.
CONCLUSIONS
Evolutionary changes in epidemic MRSA strains not detected by conventional typing may be associated with changes in disease epidemiology. Rapid and affordable technologies for whole-genome sequencing are becoming available with the potential to identify and track the emergence of variants of highly clonal organisms
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 30â70 ÎŒm, filled with solution containing a redox-active mediator (FcTMA+ ((trimethylammonium)methylferrocene), Fe(CN)64â, 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 ButlerâVolmer kinetics. For a 70 nm height Au NW, intrinsic rate constants, k0, up to ca. 1 cm sâ1 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 sâ1). Some deviation between the experimental voltammetry and the idealized model is noted, suggesting that double-layer effects may influence ET at the nanoscale
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
The Physics of the Colloidal Glass Transition
As one increases the concentration of a colloidal suspension, the system
exhibits a dramatic increase in viscosity. Structurally, the system resembles a
liquid, yet motions within the suspension are slow enough that it can be
considered essentially frozen. This kinetic arrest is the colloidal glass
transition. For several decades, colloids have served as a valuable model
system for understanding the glass transition in molecular systems. The spatial
and temporal scales involved allow these systems to be studied by a wide
variety of experimental techniques. The focus of this review is the current
state of understanding of the colloidal glass transition. A brief introduction
is given to important experimental techniques used to study the glass
transition in colloids. We describe features of colloidal systems near and in
glassy states, including tremendous increases in viscosity and relaxation
times, dynamical heterogeneity, and ageing, among others. We also compare and
contrast the glass transition in colloids to that in molecular liquids. Other
glassy systems are briefly discussed, as well as recently developed synthesis
techniques that will keep these systems rich with interesting physics for years
to come.Comment: 56 pages, 18 figures, Revie
Oxidation resistance of graphene-coated Cu and Cu/Ni alloy
The ability to protect refined metals from reactive environments is vital to
many industrial and academic applications. Current solutions, however,
typically introduce several negative effects, including increased thickness and
changes in the metal physical properties. In this paper, we demonstrate for the
first time the ability of graphene films grown by chemical vapor deposition to
protect the surface of the metallic growth substrates of Cu and Cu/Ni alloy
from air oxidation. SEM, Raman spectroscopy, and XPS studies show that the
metal surface is well protected from oxidation even after heating at 200
\degree C in air for up to 4 hours. Our work further shows that graphene
provides effective resistance against hydrogen peroxide. This protection method
offers significant advantages and can be used on any metal that catalyzes
graphene growth
- âŠ