The stratigraphic basis of the Anthropocene Event

This paper outlines the stratigraphic basis of a proposed Anthropocene Event. It considers a diachronous event framework to be more appropriate for understanding the Anthropocene than treating it as a new geological series/epoch. Four general categories of material evidence are identified as of particular relevance: ‘artificial’ strata with natural constituents; humanly modified ground; legacy sediments; and ‘natural’ geo-deposits containing artefactual material. All these arise from the interaction and mixing of human, natural, and hybrid human-natural forces. Taken together, such stratigraphic evidence supports the case for recognising the Anthropocene as an unfolding event

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

Genetic Diversity of norA, Coding for a Main Efflux Pump of Staphylococcus aureus

Funding Information: This work was partially supported by Fundação para a Ciência e a Tecnologia (FCT, Portugal), through funds to GHTM – UID/Multi/04413/2013. SC was supported by grant SFRH/BPD/97508/2013 from FCT, Portugal. TC was funded by the Medical Research Council United Kingdom (Grant Nos. MR/K000551/1, MR/M01360X/1, MR/N010469/1, and MR/R020973/1) and BBSRC United Kingdom (BB/R013063/1). BS was funded by the Medical Research Council United Kingdom (Grant No. MR/N010469/1). Publisher Copyright: © 2007 - 2019 Frontiers Media S.A. All Rights Reserved.NorA is the best studied efflux system of Staphylococcus aureus and therefore frequently used as a model for investigating efflux-mediated resistance in this pathogen. NorA activity is associated with resistance to fluoroquinolones, several antiseptics and disinfectants and several reports have pointed out the role of efflux systems, including NorA, as a first-line response to antimicrobials in S. aureus. Genetic diversity studies of the gene norA have described three alleles; norAI, norAII and norAIII. However, the epidemiology of these alleles and their impact on NorA activity remains unclear. Additionally, increasing studies do not account for norA variability when establishing relations between resistance phenotypes and norA presence or reported absence, which actually corresponds, as we now demonstrate, to different norA alleles. In the present study we assessed the variability of the norA gene present in the genome of over 1,000 S. aureus isolates, corresponding to 112 S. aureus strains with whole genome sequences publicly available; 917 MRSA strains sourced from a London-based study and nine MRSA isolates collected in a major Hospital in Lisbon, Portugal. Our analyses show that norA is part of the core genome of S. aureus. It also suggests that occurrence of norA variants reflects the population structure of this major pathogen. Overall, this work highlights the ubiquitous nature of norA in S. aureus which must be taken into account when studying the role played by this important determinant on S. aureus resistance to antimicrobials.publishersversionpublishe

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

Screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus in intensive care units: cost effectiveness evaluation

Objective To assess the cost effectiveness of screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus (MRSA) in intensive care units

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

Frequent Undetected Ward-Based Methicillin-Resistant Staphylococcus aureus Transmission Linked to Patient Sharing Between Hospitals.

Background: Recent evidence suggests that hospital transmission of methicillin-resistant Staphylococcus aureus (MRSA) is uncommon in UK centers that have implemented sustained infection control programs. We investigated whether a healthcare-network analysis could shed light on transmission paths currently sustaining MRSA levels in UK hospitals. Methods: A cross-sectional observational study was performed in 2 National Health Service hospital groups and a general district hospital in Southeast London. All MRSA patients identified at inpatient, outpatient, and community settings between 1 November 2011 and 29 February 2012 were included. We identified genetically defined MRSA transmission clusters in individual hospitals and across the healthcare network, and examined genetic differentiation of sequence type (ST) 22 MRSA isolates within and between hospitals and inpatient or outpatient and community settings, as informed by average and median pairwise single-nucleotide polymorphisms (SNPs) and SNP-based proportions of nearly identical isolates. Results: Two hundred forty-eight of 610 (40.7%) MRSA patients were linked in 90 transmission clusters, of which 27 spanned multiple hospitals. Analysis of a large 32 patient ST22-MRSA cluster showed that 26 of 32 patients (81.3%) had multiple contacts with one another during ward stays at any hospital. No residential, outpatient, or significant community healthcare contacts were identified. Genetic differentiation between ST22 MRSA inpatient isolates from different hospitals was less than between inpatient isolates from the same hospitals (P ≤ .01). Conclusions: There is evidence of frequent ward-based transmission of MRSA brought about by frequent patient admissions to multiple hospitals. Limiting in-ward transmission requires sharing of MRSA status data between hospitals