Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study

Background. The role of stress in the onset of chronic fatigue syndrome is unclear. Our objectives in this study were first, to determine the relation between the onset of chronic fatigue syndrome and stressful life events and difficulties. Secondly, we examined the role of a particular type of problem, dilemmas, in the onset of chronic fatigue syndrome. Method. We used a case–control design with 64 consecutive referrals from an Infectious Diseases/Liaison Psychiatry Fatigue clinic and 64 age- and sex-matched controls from a general practice population control group in Leeds. We had two main outcome measures; the odds ratios of the risk of developing chronic fatigue syndrome after experiencing a severe life event, severe difficulties or both in the year and 3 months preceding onset; and the proportion of subjects in each group who experienced a dilemma prior to onset. Results. Patients with chronic fatigue syndrome were more likely to experience severe events and difficulties in the 3 months (OR=9, 95% CI 3·2 to 25·1) and year (OR=4·3, 95% CI 1·8 to 10·2) prior to onset of their illness than population controls. In the 3 months prior to onset 19 of the 64 patients (30%) experienced a dilemma compared to none of the controls. Conclusions. Chronic fatigue syndrome is associated with stressful events and difficulties prior to onset. Those events and difficulties characterized as being dilemmas seem to be particularly important

Orbit Spaces of Gradient Vector Fields

We study orbit spaces of generalized gradient vector fields for Morse functions. Typically, these orbit spaces are non-Hausdorff. Nevertheless, they are quite structured topologically and are amenable to study. We show that these orbit spaces are locally contractible. We also show that the quotient map associated to each such orbit space is a weak homotopy equivalence and has the path lifting property.Comment: 16 pages, 4 figures; strengthened a main result (Corollary 3.5) and updated the introduction and the conclusio

Evolutionary rates and gene dispensability associate with replication timing in the Archaeon Sulfolobus islandicus

In bacterial chromosomes, the position of a gene relative to the single origin of replication generally reflects its replication timing, how often it is expressed, and consequently, its rate of evolution. However, because some archaeal genomes contain multiple origins of replication, bias in gene dosage caused by delayed replication should be minimized and hence the substitution rate of genes should associate less with chromosome position. To test this hypothesis, six archaeal genomes from the genus Sulfolobus containing three origins of replication were selected, conserved orthologs were identified, and the evolutionary rates (dN and dS) of these orthologs were quantified. Ortholog families were grouped by their consensus position and designated by their proximity to one of the three origins (O1, O2, O3). Conserved orthologs were concentrated near the origins and most variation in genome content occurred distant from the origins. Linear regressions of both synonymous and nonsynonymous substitution rates on distance from replication origins were significantly positive, the rates being greatest in the region furthest from any of the origins and slowest among genes near the origins. Genes near O1 also evolved faster than those near O2 and O3, which suggest that this origin may fire later in the cell cycle. Increased evolutionary rates and gene dispensability are strongly associated with reduced gene expression caused in part by reduced gene dosage during the cell cycle. Therefore, in this genus of Archaea as well as in many Bacteria, evolutionary rates and variation in genome content associate with replication timing

Why genes evolve faster on secondary chromosomes in bacteria

In bacterial genomes composed of more than one chromosome, one replicon is typically larger, harbors more essential genes than the others, and is considered primary. The greater variability of secondary chromosomes among related taxa has led to the theory that they serve as an accessory genome for specific niches or conditions. By this rationale, purifying selection should be weaker on genes on secondary chromosomes because of their reduced necessity or usage. To test this hypothesis we selected bacterial genomes composed of multiple chromosomes from two genera, Burkholderia and Vibrio, and quantified the evolutionary rates (dN and dS) of all orthologs within each genus. Both evolutionary rate parameters were faster among orthologs found on secondary chromosomes than those on the primary chromosome. Further, in every bacterial genome with multiple chromosomes that we studied, genes on secondary chromosomes exhibited significantly weaker codon usage bias than those on primary chromosomes. Faster evolution and reduced codon bias could in turn result from global effects of chromosome position, as genes on secondary chromosomes experience reduced dosage and expression due to their delayed replication, or selection on specific gene attributes. These alternatives were evaluated using orthologs common to genomes with multiple chromosomes and genomes with single chromosomes. Analysis of these ortholog sets suggested that inherently fast-evolving genes tend to be sorted to secondary chromosomes when they arise; however, prolonged evolution on a secondary chromosome further accelerated substitution rates. In summary, secondary chromosomes in bacteria are evolutionary test beds where genes are weakly preserved and evolve more rapidly, likely because they are used less frequently

Machine dependence and reproducibility for coupled climate simulations: the HadGEM3-GC3.1 CMIP Preindustrial simulation

When the same weather or climate simulation is run on different high-performance computing (HPC) platforms, model outputs may not be identical for a given initial condition. While the role of HPC platforms in delivering better climate projections is to some extent discussed in the literature, attention is mainly focused on scalability and performance rather than on the impact of machine-dependent processes on the numerical solution. Here we investigate the behaviour of the Preindustrial (PI) simulation prepared by the UK Met Office for the forthcoming CMIP6 (Coupled Model Intercomparison Project Phase 6) under different computing environments. Discrepancies between the means of key climate variables were analysed at different timescales, from decadal to centennial. We found that for the two simulations to be statistically indistinguishable, a 200-year averaging period must be used for the analysis of the results. Thus, constant-forcing climate simulations using the HadGEM3-GC3.1 model are reproducible on different HPC platforms provided that a sufficiently long duration of simulation is used. In regions where El Niño–Southern Oscillation (ENSO) teleconnection patterns were detected, we found large sea surface temperature and sea ice concentration differences on centennial timescales. This indicates that a 100-year constant-forcing climate simulation may not be long enough to adequately capture the internal variability of the HadGEM3-GC3.1 model, despite this being the minimum simulation length recommended by CMIP6 protocols for many MIP (Model Intercomparison Project) experiments. On the basis of our findings, we recommend a minimum simulation length of 200 years whenever possible

Comparative genomics of Burkholderia multivorans, a ubiquitous pathogen with a highly conserved genomic structure

The natural environment serves as a reservoir of opportunistic pathogens. A well-established method for studying the epidemiology of such opportunists is multilocus sequence typing, which in many cases has defined strains predisposed to causing infection. Burkholderia multivorans is an important pathogen in people with cystic fibrosis (CF) and its epidemiology suggests that strains are acquired from non-human sources such as the natural environment. This raises the central question of whether the isolation source (CF or environment) or the multilocus sequence type (ST) of B. multivorans better predicts their genomic content and functionality. We identified four pairs of B. multivorans isolates, representing distinct STs and consisting of one CF and one environmental isolate each. All genomes were sequenced using the PacBio SMRT sequencing technology, which resulted in eight high-quality B. multivorans genome assemblies. The present study demonstrated that the genomic structure of the examined B. multivorans STs is highly conserved and that the B. multivorans genomic lineages are defined by their ST. Orthologous protein families were not uniformly distributed among chromosomes, with core orthologs being enriched on the primary chromosome and ST-specific orthologs being enriched on the second and third chromosome. The ST-specific orthologs were enriched in genes involved in defense mechanisms and secondary metabolism, corroborating the strain-specificity of these virulence characteristics. Finally, the same B. multivorans genomic lineages occur in both CF and environmental samples and on different continents, demonstrating their ubiquity and evolutionary persistence