Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota

The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio. Supplementary video and information availabl

Critical analysis of information security culture definitions

This article aims to advance the understanding of information security culture through a critical reflection on the wide-ranging definitions of information security culture in the literature. It uses the hermeneutic approach for conducting literature reviews. The review identifies 16 definitions of information security culture in the literature. Based on the analysis of these definitions, four different views of culture are distinguished. The shared values view highlights the set of cultural value patterns that are shared across the organization. An action-based view highlights the behaviors of individuals in the organization. A mental model view relates to the abstract view of the individual’s thinking on how information security culture must work. Finally, a problem-solving view emphasizes a combination of understanding from shared value-based and action-based views. The paper analyzes and presents the limitations of these four views of information security culture definitions

Access to myocardial revascularization procedures: Closing the gap with time?

BACKGROUND: Early access to revascularization procedures is known to be related to a more favorable outcome in myocardial infarction (MI) patients, but access to specialized care varies widely amongst the population. We aim to test if the early gap found in the revascularization rates, according to distance between patients' location and the closest specialized cardiology center (SCC), remains on a long term basis. METHODS: We conducted a population-based cohort study using data from the Quebec's hospital discharge register (MED-ECHO). The study population includes all patients 25 years and older living in the province of Quebec, who were hospitalized for a MI in 1999 with a follow up time of one year after the index hospitalization. The main variable is revascularization (percutaneous transluminal coronary angioplasty or a coronary artery bypass graft). The population is divided in four groups depending how close they are from a SCC (<32 km, 32–64 km, 64–105 km and ≥105 km). Revascularization rates are adjusted for age and sex. RESULTS: The study population includes 11,802 individuals, 66% are men. The one-year incidence rate of MI is 244 individuals per 100,000 inhabitants. At index hospitalization, a significant gap is found between patients living close (< 32 km) to a SCC and patients living farther (≥32 km). During the first year, a gap reduction can be observed but only for patients living at an intermediate distance from the specialized center (64–105 km). CONCLUSION: The gap observed in revascularization rates at the index hospitalization for MI is in favour of patients living closer (< 32 km) to a SCC. This gap remains unchanged over the first year after an MI except for patients living between 64 and 105 km, where a closing of the gap can be noticed

Present day greenhouse gases could cause more frequent and longer Dust Bowl heatwaves

Substantial warming occurred across North America, Europe and the Arctic over the early twentieth century1, including an increase in global drought2, that was partially forced by rising greenhouse gases (GHGs)3. The period included the 1930s Dust Bowl drought4,5,6,7 across North America’s Great Plains that caused widespread crop failures4,8, large dust storms9 and considerable out-migration10. This coincided with the central United States experiencing its hottest summers of the twentieth century11,12 in 1934 and 1936, with over 40 heatwave days and maximum temperatures surpassing 44 °C at some locations13,14. Here we use a large-ensemble regional modelling framework to show that GHG increases caused slightly enhanced heatwave activity over the eastern United States during 1934 and 1936. Instead of asking how a present-day heatwave would behave in a world without climate warming, we ask how these 1930s heatwaves would behave with present-day GHGs. Heatwave activity in similarly rare events would be much larger under today’s atmospheric GHG forcing and the return period of a 1-in-100-year heatwave summer (as observed in 1936) would be reduced to about 1-in-40 years. A key driver of the increasing heatwave activity and intensity is reduced evaporative cooling and increased sensible heating during dry springs and summers

A systematic review of intravenous gamma globulin for therapy of acute myocarditis

BACKGROUND: Intravenous gamma globulin (IVGG) is commonly used in the management of acute myocarditis. The objective of this study was to systematically review the literature evaluating this practice. METHODS: We conducted a comprehensive search (electronic databases, trials registries, conference proceedings, reference lists, contact with authors) to identify studies evaluating the use of IVGG in adults and children with a clinical or histologically proven diagnosis of myocarditis of possible viral etiology and symptoms of less than six months duration. Two reviewers independently screened the searches, applied inclusion criteria, and graded the evidence. RESULTS: Results were described qualitatively; data were not pooled because only one randomized controlled trial (RCT) with 62 patients was identified. The RCT showed no benefit with respect to cardiac function, functional outcome, or event-free survival. A small, uncontrolled trial (n = 10) showed significant improvement in LVEF from a mean of 24% to 41% 12 months after IVGG in nine survivors. A retrospective cohort study of pediatric patients showed improvement in cardiac function and a trend towards improved survival in patients receiving IVGG (n = 21) versus historic controls (n = 25). Ten case reports and two case series (total n = 21) described improvement in cardiac function after administration of IVGG; two case reports showed no benefit of IVGG. One case of hemolytic anemia was attributed to IVGG. CONCLUSION: There is insufficient data from methodologically strong studies to recommend routine use of IVGG for acute myocarditis. Future randomized studies that take into account the etiology of acute myocarditis will be required to determine the efficacy of IVGG

The inference of gray whale (Eschrichtius robustus) historical population attributes from whole-genome sequences

Commercial whaling caused extensive demographic declines in many great whale species, including gray whales that were extirpated from the Atlantic Ocean and dramatically reduced in the Pacific Ocean. The Eastern Pacific gray whale has recovered since the 1982 ban on commercial whaling, but the Western Pacific gray whale-once considered possibly extinct-consists of only about 200 individuals and is considered critically endangered by some international authorities. Herein, we use whole-genome sequencing to investigate the demographic history of gray whales from the Pacific and use environmental niche modelling to make predictions about future gene flow.Our sequencing efforts and habitat niche modelling indicate that: i) western gray whale effective population sizes have declined since the last glacial maximum; ii) contemporary gray whale genomes, both eastern and western, harbor less autosomal nucleotide diversity than most other marine mammals and megafauna; iii) the extent of inbreeding, as measured by autozygosity, is greater in the Western Pacific than in the Eastern Pacific populations; and iv) future climate change is expected to open new migratory routes for gray whales.Our results indicate that gray whale genomes contain low nucleotide diversity and have been subject to both historical and recent inbreeding. Population sizes over the last million years likely peaked about 25,000 years before present and have declined since then. Our niche modelling suggests that novel migratory routes may develop within the next century and if so this could help retain overall genetic diversity, which is essential for adaption and successful recovery in light of global environmental change and past exploitation

Stable Cytotoxic T Cell Escape Mutation in Hepatitis C Virus Is Linked to Maintenance of Viral Fitness

Mechanisms by which hepatitis C virus (HCV) evades cellular immunity to establish persistence in chronically infected individuals are not clear. Mutations in human leukocyte antigen (HLA) class I-restricted epitopes targeted by CD8+ T cells are associated with persistence, but the extent to which these mutations affect viral fitness is not fully understood. Previous work showed that the HCV quasispecies in a persistently infected chimpanzee accumulated multiple mutations in numerous class I epitopes over a period of 7 years. During the acute phase of infection, one representative epitope in the C-terminal region of the NS3/4A helicase, NS31629-1637, displayed multiple serial amino acid substitutions in major histocompatibility complex (MHC) anchor and T cell receptor (TCR) contact residues. Only one of these amino acid substitutions at position 9 (P9) of the epitope was stable in the quasispecies. We therefore assessed the effect of each mutation observed during in vivo infection on viral fitness and T cell responses using an HCV subgenomic replicon system and a recently developed in vitro infectious virus cell culture model. Mutation of a position 7 (P7) TCR-contact residue, I1635T, expectedly ablated the T cell response without affecting viral RNA replication or virion production. In contrast, two mutations at the P9 MHC-anchor residue abrogated antigen-specific T cell responses, but additionally decreased viral RNA replication and virion production. The first escape mutation, L1637P, detected in vivo only transiently at 3 mo after infection, decreased viral production, and reverted to the parental sequence in vitro. The second P9 variant, L1637S, which was stable in vivo through 7 years of follow-up, evaded the antigen-specific T cell response and did not revert in vitro despite being less optimal in virion production compared to the parental virus. These studies suggest that HCV escape mutants emerging early in infection are not necessarily stable, but are eventually replaced with variants that achieve a balance between immune evasion and fitness for replication