Patients’ perspectives on the medical primary-secondary care interface : systematic review and synthesis of qualitative research

Funding NHS Highland Research, Development & Innovation Department, Aberdeen University, and Stirling University provided funds to meet publication costs.Peer reviewedPublisher PD

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

Effects of Measurement Duration on the Determination of Basal Metabolic and Evaporative Water Loss of Small Marsupials: How Long is Long Enough

We examined the time course for measurement of basal metabolic rate (BMR; measured as O2 consumption and CO2 production) and standard evaporative water loss (EWL) for six species of small marsupial to determine the minimum time required to achieve basal/standard values. There was a highly significant effect of measurement duration on measured physiological variables with values for O2 consumption, CO2 production, and EWL decreasing with time for all species. The time required to attain values statistically indistinguishable from minimal differed significantly between species, but in general O2 consumption rate reached basal values after 4.3 h, CO2 production after 4.5 h, and evaporative water loss after 5.2 h. For 16 BMR measurements of small marsupial species in the literature, with experimental duration provided, 10 were for less than 4 h, suggesting that their BMR values might be overestimates. For EWL, three of the four published values for small marsupials may be overestimates. It is clear that appropriate experimental duration is an important component of the measurement protocol for both BMR and standardized water loss, which needs to be rigorously observed in future studies

Using A Priori Contrasts for Multivariate Repeated-Measures ANOVA to Analyze Thermoregulatory Responses of the Dibbler (Parantechinus apicalis; Marsupialia, Dasyuridae)

Physiological studies often involve the repeated measurement of individuals over a range of ordered categorical conditions, for example, varying ambient temperature. We illustrate here the use of a priori contrasts for multivariate repeated-measures ANOVA by analyzing the thermal responses of various physiological variables for a small marsupial, the dibbler (Parantechinus apicalis). Our analyses showed that dibblers conform closely to the Scholander-Irving model of endothermy. Body temperature was constant at low air temperatures, was 36.3 +/- 0.24 degrees C at thermoneutrality (30 degrees C), and increased at 35 degrees C. Metabolic rate decreased with increasing ambient temperature to a basal rate of 0.619 +/- 0.036 mL O(2) g(-1) h(-1) at 30 degrees C; it extrapolated closely to thermoneutral body temperature. Increased oxygen demand at lower ambient temperature was met by increased respiratory minute volume, achieved by increased respiratory frequency and tidal volume; oxygen extraction was constant at about 19%. Evaporative water loss and wet and dry thermal conductance increased markedly at high ambient temperatures but not sufficiently to maintain constant body temperature. Relative water economy was similar to that of other small marsupials, increasing linearly at lower air temperatures with a point of relative water economy of 20.3 degrees C. We conclude that a priori contrasts provide a statistically appropriate and powerful analysis that can be used routinely to statistically describe the pattern of response of physiological variables to a categorical factor and are especially useful for repeated-measures ANOVA designs common to many physiological studies

Reflective practice undertaken by healthcare and medical trainees and practitioners: so what’s all the fuss about?

Having worked with healthcare and medical trainees and practitioners for a number of years as medical educators, we have often noticed a glazed, irritated or frustrated look in the eyes of many of them when the terms reflective practice or reflection are used. These two sets of words have come to be known as the ‘R’ words. This has prompted us to consider the modern origins of the concept of reflective practice and also the etymological roots and philosophical foundation of the meaning of the term ‘practice’. At the same time, this has raised issues of who owns the process and product of reflective practice (e.g. individuals; peers; tutors; assessors) and whether the outcomes should be formally assessed given the associated ethical and authenticity dilemmas that often seem to arise from such assessment

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

New Approaches to St Stephen's Chapel, Palace of Westminster

Introduction to a group of articles in this edition, on 'One Object', St Stephen's Chape

Observation of Motion Dependent Nonlinear Dispersion with Narrow Linewidth Atoms in an Optical Cavity

As an alternative to state-of-the-art laser frequency stabilisation using ultra-stable cavities, it has been proposed to exploit the non-linear effects from coupling of atoms with a narrow transition to an optical cavity. Here we have constructed such a system and observed non-linear phase shifts of a narrow optical line by strong coupling of a sample of strontium-88 atoms to an optical cavity. The sample temperature of a few mK provides a domain where the Doppler energy scale is several orders of magnitude larger than the narrow linewidth of the optical transition. This makes the system sensitive to velocity dependent multi-photon scattering events (Dopplerons) that affect the cavity field transmission and phase. By varying the number of atoms and the intra-cavity power we systematically study this non-linear phase signature which displays roughly the same features as for much lower temperature samples. This demonstration in a relatively simple system opens new possibilities for alternative routes to laser stabilization at the sub 100 mHz level and superradiant laser sources involving narrow line atoms. The understanding of relevant motional effects obtained here has direct implications for other atomic clocks when used in relation with ultranarrow clock transitions.Comment: 9 pages (including 4 pages of Supplemental Information), 6 figures. Updated to correspond to the published versio