888 research outputs found
Brightness temperature and attenuation statistics at 20.6 and 31.65 GHz
Attenuation and brightness temperature statistics at 20.6 and 31.65 GHz are analyzed for a year's worth of data. The data were collected in 1988 at Denver and Platteville, Colorado. The locations are separated by 49 km. Single-station statistics are derived for the entire year. Quality control procedures are discussed and examples of their application are given
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
Global and Local Conformation of Human IgG Antibody Variants Rationalizes Loss of Thermodynamic Stability.
Immunoglobulin 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 × 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
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
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
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