Single-handed versus multiple-handed General practices: A cross-sectional study of quality outcomes in England.

OBJECTIVES: As general practice increasingly moves towards large group practices, there is debate about the relative benefits, safety and sustainability of different care delivery models. This study investigates the performance of single-handed practices compared to practices with multiple doctors in England, UK. METHODS: Practices in England with more than 1000 patients were included. Workforce data and a quality control process classified practices as single-handed or multiple-handed. Outcomes were (i) GP patient survey scores measuring access, continuity, confidence in health professional and overall satisfaction; (ii) reported diabetes and hypertension outcomes; and (iii) emergency department presentation rates and cancer detection (percentage of cancers diagnosed by a 2-week wait). Generalised linear models, controlling for patient and practice characteristics, compared outcomes in single and multiple-handed practices and assessed the effect of GP age in single-handed practices. RESULTS: Single-handed practices were more commonly found in areas of high deprivation (41% compared to 20% of multiple-handed practices). Single-handed practices had higher patient-reported access, continuity and overall satisfaction but slightly lower diabetes management and cancer detection rates. Emergency department presentations were higher when controlling for patient characteristics in single-handed practices but not when also controlling for practice rurality and size. Increased deprivation was associated with lower performance in seven out of eight outcomes. CONCLUSIONS: We found single-handed practices to be associated with high patient satisfaction while performing slightly less well on selected clinical outcomes. Further research is required to better understand the association between practice size, including increasing multidisciplinary working, on patient experience and outcomes.

Screening tools for sepsis identification in paramedicine and other emergency contexts: a rapid systematic review.

BACKGROUND: Sepsis is a life-threatening condition that contributes significantly to protracted hospitalisations globally. The unique positioning of paramedics and other emergency care cadres in emergency contexts enable the prospect of early identification and management of sepsis, however, a standardised screening tool still does not exist in the emergency setting. The objective of this review was to identify and recommend the most clinically ideal sepsis screening tool for emergency contexts such as emergency departments and out-of-hospital emergency contexts. METHODS: A rapid review of five databases (Medline, Embase, the Cochrane Library, CINAHL, and ProQuest Central) was undertaken, with searches performed on February 10, 2022. Covidence software was used by two authors for initial screening, and full text review was undertaken independently by each reviewer, with conflicts resolved by consensus-finding and a mediator. Systematic reviews, meta-analyses, randomised controlled trials, and prospective observational studies were eligible for inclusion. Data extraction used an a priori template and focused on sensitivity and specificity, with ROBINS-I and ROBIS bias assessment tools employed to assess risk of bias in included studies. Study details and key findings were summarised in tables. The a priori review protocol was registered on Open Science Framework ( https://doi.org/10.17605/OSF.IO/3XQ5T ). RESULTS: The literature search identified 362 results. After review, 18 studies met the inclusion criteria and were included for analysis. There were five systematic reviews, with three including meta-analysis, eleven prospective observational studies, one randomised controlled trial, and one validation study. CONCLUSIONS: The review recognised that a paucity of evidence exists surrounding standardised sepsis screening tools in the emergency context. The use of a sepsis screening tool in the emergency environment may be prudent, however there is currently insufficient evidence to recommend a single screening tool for this context. A combination of the qSOFA and SIRS may be employed to avoid 'practice paralysis' in the interim. The authors acknowledge the inherent potential for publication and selection bias within the review due to the inclusion criteria.

An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity.

The molecular mechanisms by which the endosomal sorting complexes required for transport (ESCRT) proteins contribute to the integrity of the nuclear envelope (NE) barrier are not fully defined. We leveraged the single NE hole generated by mitotic extrusion of the Schizosaccharomyces pombe spindle pole body to reveal two modes of ESCRT function executed by distinct complements of ESCRT-III proteins, both dependent on CHMP7/Cmp7. A grommet-like function is required to restrict the NE hole in anaphase B, whereas replacement of Cmp7 by a sealing module ultimately closes the NE in interphase. Without Cmp7, nucleocytoplasmic compartmentalization remains intact despite NE discontinuities of up to 540 nm, suggesting mechanisms to limit diffusion through these holes. We implicate spindle pole body proteins as key components of a diffusion barrier acting with Cmp7 in anaphase B. Thus, NE remodelling mechanisms cooperate with proteinaceous diffusion barriers beyond nuclear pore complexes to maintain the nuclear compartment.

Non-random distribution of vacuoles in Schizosaccharomyces pombe.

A central question in eukaryotic cell biology asks, during cell division, how is the growth and distribution of organelles regulated to ensure each daughter cell receives an appropriate amount. For vacuoles in budding yeast, there are well described organelle-to-cell size scaling trends as well as inheritance mechanisms involving highly coordinated movements. It is unclear whether such mechanisms are necessary in the symmetrically dividing fission yeast, Schizosaccharomyces pombe, in which random partitioning may be utilized to distribute vacuoles to daughter cells. To address the increasing need for high-throughput analysis, we are augmenting existing semi-automated image processing by developing fully automated machine learning methods for locating vacuoles and segmenting fission yeast cells from brightfield and fluorescence micrographs. All strains studied show qualitative correlations in vacuole-to-cell size scaling trends, i.e. vacuole volume, surface area, and number all increase with cell size. Furthermore, increasing vacuole number was found to be a consistent mechanism for the increase in total vacuole size in the cell. Vacuoles are not distributed evenly throughout the cell with respect to available cytoplasm. Rather, vacuoles show distinct peaks in distribution close to the nucleus, and this preferential localization was confirmed in mutants in which nucleus position is perturbed. Disruption of microtubules leads to quantitative changes in both vacuole size scaling trends and distribution patterns, indicating the microtubule cytoskeleton is a key mechanism for maintaining vacuole structure.

Triggering of eruptions at Axial Seamount, Juan de Fuca Ridge.

The submarine volcano Axial Seamount has exhibited an inflation predictable eruption cycle, which allowed for the successful forecast of its 2015 eruption. However, the exact triggering mechanism of its eruptions remains ambiguous. The inflation predictable eruption pattern suggests a magma reservoir pressure threshold at which eruptions occur, and as such, an overpressure eruption triggering mechanism. However, recent models of volcano unrest suggest that eruptions are triggered when conditions of critical stress are achieved in the host rock surrounding a magma reservoir. We test hypotheses of eruption triggering using 3-dimensional finite element models which track stress evolution and mechanical failure in the host rock surrounding the Axial magma reservoir. In addition, we provide an assessment of model sensitivity to various temperature and non-temperature-dependent rheologies and external tectonic stresses. In this way, we assess the contribution of these conditions to volcanic deformation, crustal stress evolution, and eruption forecasts. We conclude that model rheology significantly impacts the predicted timing of through-going failure and eruption. Models consistently predict eruption at a reservoir pressure threshold of 12-14 MPa regardless of assumed model rheology, lending support to the interpretation that eruptions at Axial Seamount are triggered by reservoir overpressurization.

Inflation-predictable behavior and co-eruption deformation at Axial Seamount.

Deformation of the ground surface at active volcanoes provides information about magma movements at depth. Improved seafloor deformation measurements between 2011 and 2015 documented a fourfold increase in magma supply and confirmed that Axial Seamount's eruptive behavior is inflation-predictable, probably triggered by a critical level of magmatic pressure. A 2015 eruption was successfully forecast on the basis of this deformation pattern and marked the first time that deflation and tilt were captured in real time by a new seafloor cabled observatory, revealing the timing, location, and volume of eruption-related magma movements. Improved modeling of the deformation suggests a steeply dipping prolate-spheroid pressure source beneath the eastern caldera that is consistent with the location of the zone of highest melt within the subcaldera magma reservoir determined from multichannel seismic results.

Causes of variation in malaria infection dynamics: insights from theory and data.

Parasite strategies for exploiting host resources are key determinants of disease severity (i.e., virulence) and infectiousness (i.e., transmission between hosts). By iterating the development of theory and empirical tests, we investigated whether variation in parasite traits across two genetically distinct clones of the rodent malaria parasite, Plasmodium chabaudi, explains differences in within-host infection dynamics and virulence. First, we experimentally tested key predictions of our earlier modeling work. As predicted, the more virulent genotype produced more progeny parasites per infected cell (burst size), but in contrast to predictions, invasion rates of red blood cells (RBCs) did not differ between the genotypes studied. Second, we further developed theory by confronting our earlier model with these new data, testing a new set of models that incorporate more biological realism, and developing novel theoretical tools for identifying differences between parasite genotypes. Overall, we found robust evidence that differences in burst sizes contribute to variation in dynamics and that differential interactions between parasites and host immune responses also play a role. In contrast to previous work, our model predicts that RBC age structure is not important for explaining dynamics. Integrating theory and empirical tests is a potentially powerful way of progressing understanding of disease biology.

Quantitative analysis of mechanisms that govern red blood cell age structure and dynamics during anaemia.

Mathematical modelling has proven an important tool in elucidating and quantifying mechanisms that govern the age structure and population dynamics of red blood cells (RBCs). Here we synthesise ideas from previous experimental data and the mathematical modelling literature with new data in order to test hypotheses and generate new predictions about these mechanisms. The result is a set of competing hypotheses about three intrinsic mechanisms: the feedback from circulating RBC concentration to production rate of immature RBCs (reticulocytes) in bone marrow, the release of reticulocytes from bone marrow into the circulation, and their subsequent ageing and clearance. In addition we examine two mechanisms specific to our experimental system: the effect of phenylhydrazine (PHZ) and blood sampling on RBC dynamics. We performed a set of experiments to quantify the dynamics of reticulocyte proportion, RBC concentration, and erythropoietin concentration in PHZ-induced anaemic mice. By quantifying experimental error we are able to fit and assess each hypothesis against our data and recover parameter estimates using Markov chain Monte Carlo based Bayesian inference. We find that, under normal conditions, about 3% of reticulocytes are released early from bone marrow and upon maturation all cells are released immediately. In the circulation, RBCs undergo random clearance but have a maximum lifespan of about 50 days. Under anaemic conditions reticulocyte production rate is linearly correlated with the difference between normal and anaemic RBC concentrations, and their release rate is exponentially correlated with the same. PHZ appears to age rather than kill RBCs, and younger RBCs are affected more than older RBCs. Blood sampling caused short aperiodic spikes in the proportion of reticulocytes which appear to have a different developmental pathway than normal reticulocytes. We also provide evidence of large diurnal oscillations in serum erythropoietin levels during anaemia.

Long-term eruptive activity at a submarine arc volcano.

Three-quarters of the Earth's volcanic activity is submarine, located mostly along the mid-ocean ridges, with the remainder along intraoceanic arcs and hotspots at depths varying from greater than 4,000 m to near the sea surface. Most observations and sampling of submarine eruptions have been indirect, made from surface vessels or made after the fact. We describe here direct observations and sampling of an eruption at a submarine arc volcano named NW Rota-1, located 60 km northwest of the island of Rota (Commonwealth of the Northern Mariana Islands). We observed a pulsating plume permeated with droplets of molten sulphur disgorging volcanic ash and lapilli from a 15-m diameter pit in March 2004 and again in October 2005 near the summit of the volcano at a water depth of 555 m (depth in 2004). A turbid layer found on the flanks of the volcano (in 2004) at depths from 700 m to more than 1,400 m was probably formed by mass-wasting events related to the eruption. Long-term eruptive activity has produced an unusual chemical environment and a very unstable benthic habitat exploited by only a few mobile decapod species. Such conditions are perhaps distinctive of active arc and hotspot volcanoes.

A parasite-mediated life-history shift in Daphnia magna.

The impact of parasitism on host populations will be modulated by both genetic variation for susceptibility, and phenotypically plastic-life-history traits that are altered to lessen the fitness consequences of infection. In this study we tested for life-history shifts in the crustacean Daphnia magna following exposure to the horizontally transmitted microsporidian, Glugoides intestinalis. In two separate experiments, we exposed hosts to parasite spores and measured their fecundity relative to controls. We show that host exposed G. intestinalis show fecundity compensation, i.e. hosts shift their life-history strategy towards early production. Our experiments included multiple host genotypes, and subtle differences among them indicated that fecundity compensation could be subject to parasite-mediated natural selection.