Retaining the general practitioner workforce in England : what matters to GPs? A cross-sectional study

Background: The general practice (GP) workforce in England is in crisis, reflected in increasing rates of early retirement and intentions to reduce hours of working. This study aimed to investigate underlying factors and how these might be mitigated. Methods: GPs in central England were invited to participate in an on-line survey exploring career plans and views and experiences of work-related pressures. Quantitative data were analysed using logistic regression analysis and principal components analysis. Qualitative data were analysed using a thematic framework approach. Results: Of 1,192 GPs who participated, 978 (82.0 %) stated that they intend to leave general practice, take a career break and/or reduce clinical hours of work within the next five years. This included 488 (41.9 %) who intend to leave practice, and almost a quarter (279; 23.2 %) intending to take a career break. Only 67 (5.6 %) planned to increase their hours of clinical work. For participants planning to leave practice, the issues that most influenced intentions were volume and intensity of workload, time spent on “unimportant tasks”, introduction of seven-day working and lack of job satisfaction. Four hundred fifty five participants responded to open questions (39128 words in total). The main themes were the cumulative impact of work-related pressures, the changing and growing nature of the workload, and the consequent stress. Reducing workload intensity, workload volume, administrative activities, with increased time for patient care, no out-of-hour commitments, more flexible working conditions and greater clinical autonomy were identified as the most important requirements to address the workforce crisis. In addition, incentive payments, increased pay and protected time for education and training were also rated as important. Conclusions: New models of professionalism and organisational arrangements may be needed to address the issues described here. Without urgent action, the GP workforce crisis in England seems set to worsen

ELMO1 has an essential role in the internalization of Salmonella Typhimurium into enteric macrophages that impacts disease outcome.

Backgrounds and aims4-6 million people die of enteric infections each year. After invading intestinal epithelial cells, enteric bacteria encounter phagocytes. However, little is known about how phagocytes internalize the bacteria to generate host responses. Previously, we have shown that BAI1 (Brain Angiogenesis Inhibitor 1) binds and internalizes Gram-negative bacteria through an ELMO1 (Engulfment and cell Motility protein 1)/Rac1-dependent mechanism. Here we delineate the role of ELMO1 in host inflammatory responses following enteric infection.MethodsELMO1-depleted murine macrophage cell lines, intestinal macrophages and ELMO1 deficient mice (total or myeloid-cell specific) was infected with Salmonella enterica serovar Typhimurium. The bacterial load, inflammatory cytokines and histopathology was evaluated in the ileum, cecum and spleen. The ELMO1 dependent host cytokines were detected by a cytokine array. ELMO1 mediated Rac1 activity was measured by pulldown assay.ResultsThe cytokine array showed reduced release of pro-inflammatory cytokines, including TNF-α and MCP-1, by ELMO1-depleted macrophages. Inhibition of ELMO1 expression in macrophages decreased Rac1 activation (~6 fold) and reduced internalization of Salmonella. ELMO1-dependent internalization was indispensable for TNF-α and MCP-1. Simultaneous inhibition of ELMO1 and Rac function virtually abrogated TNF-α responses to infection. Further, activation of NF-κB, ERK1/2 and p38 MAP kinases were impaired in ELMO1-depleted cells. Strikingly, bacterial internalization by intestinal macrophages was completely dependent on ELMO1. Salmonella infection of ELMO1-deficient mice resulted in a 90% reduction in bacterial burden and attenuated inflammatory responses in the ileum, spleen and cecum.ConclusionThese findings suggest a novel role for ELMO1 in facilitating intracellular bacterial sensing and the induction of inflammatory responses following infection with Salmonella

School physical activity intervention effect on adolescents' performance in mathematics

Purpose: The primary aim of this study was to test the effect of a school-based physical activity intervention on adolescents’ performance in mathematics. A secondary aim was to explore potential mechanisms that might explain the intervention effect. Methods: The Activity and Motivation in Physical EDucation intervention was evaluated using a two-arm cluster randomized controlled trial in 14 secondary schools located in low socioeconomic areas of Western Sydney, Australia. Study participants (n = 1173) were grade 8 students (mean age = 12.94 yr, SD = 0.54). The multicomponent intervention was designed to help teachers maximize students’ opportunities for moderate-to-vigorous physical activity (MVPA) during physical education (PE) and enhance students’ motivation toward PE. Mathematics performance was assessed as part of national testing in grade 7, which was the year before the trial began and then again in grade 9. Potential mediators were: (i) proportion of PE lesson time that students spent in MVPA and leisure time MVPA (%), measured using Actigraph GT3X+ accelerometers, and (ii) students’ self-reported engagement (behavioral, emotional, and cognitive) during mathematics lessons. Mediators were assessed at baseline (grade 8) and follow-up (grade 9, 14–15 months after baseline). Results: The effect of the intervention on mathematics performance was small-to-medium (β = 0.16, P < 0.001). An intervention effect was observed for MVPA% in PE (β = 0.59, P < 0.001), but not for leisure time MVPA or any of the engagement mediators. There were no significant associations between changes in potential mediators and mathematics performance. Conclusions: The Activity and Motivation in Physical EDucation intervention had a significant positive effect on mathematics performance in adolescents. However, findings should be interpreted with caution as the effect was small and not associated with changes in hypothesized mediators

Formation of Super-Earths

Super-Earths are the most abundant planets known to date and are characterized by having sizes between that of Earth and Neptune, typical orbital periods of less than 100 days and gaseous envelopes that are often massive enough to significantly contribute to the planet's overall radius. Furthermore, super-Earths regularly appear in tightly-packed multiple-planet systems, but resonant configurations in such systems are rare. This chapters summarizes current super-Earth formation theories. It starts from the formation of rocky cores and subsequent accretion of gaseous envelopes. We follow the thermal evolution of newly formed super-Earths and discuss their atmospheric mass loss due to disk dispersal, photoevaporation, core-cooling and collisions. We conclude with a comparison of observations and theoretical predictions, highlighting that even super-Earths that appear as barren rocky cores today likely formed with primordial hydrogen and helium envelopes and discuss some paths forward for the future.Comment: Invited review accepted for publication in the 'Handbook of Exoplanets,' Planet Formation section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Ed

Distributed Subnetworks of Depression Defined by Direct Intracranial Neurophysiology

Major depressive disorder is a common and disabling disorder with high rates of treatment resistance. Evidence suggests it is characterized by distributed network dysfunction that may be variable across patients, challenging the identification of quantitative biological substrates. We carried out this study to determine whether application of a novel computational approach to a large sample of high spatiotemporal resolution direct neural recordings in humans could unlock the functional organization and coordinated activity patterns of depression networks. This group level analysis of depression networks from heterogenous intracranial recordings was possible due to application of a correlational model-based method for inferring whole-brain neural activity. We then applied a network framework to discover brain dynamics across this model that could classify depression. We found a highly distributed pattern of neural activity and connectivity across cortical and subcortical structures that was present in the majority of depressed subjects. Furthermore, we found that this depression signature consisted of two subnetworks across individuals. The first was characterized by left temporal lobe hypoconnectivity and pathological beta activity. The second was characterized by a hypoactive, but hyperconnected left frontal cortex. These findings have applications toward personalization of therapy

The inevitable youthfulness of known high-redshift radio galaxies

Radio galaxies can be seen out to very high redshifts, where in principle they can serve as probes of the early evolution of the Universe. Here we show that for any model of radio-galaxy evolution in which the luminosity decreases with time after an initial rapid increase (that is, essentially all reasonable models), all observable high-redshift radio-galaxies must be seen when the lobes are less than 10^7 years old. This means that high-redshift radio galaxies can be used as a high-time-resolution probe of evolution in the early Universe. Moreover, this result helps to explain many observed trends of radio-galaxy properties with redshift [(i) the `alignment effect' of optical emission along radio-jet axes, (ii) the increased distortion in radio structure, (iii) the decrease in physical sizes, (iv) the increase in radio depolarisation, and (v) the increase in dust emission] without needing to invoke explanations based on cosmology or strong evolution of the surrounding intergalactic medium with cosmic time, thereby avoiding conflict with current theories of structure formation.Comment: To appear in Nature. 4 pages, 2 colour figures available on request. Also available at http://www-astro.physics.ox.ac.uk/~km

Cosmogenic ^(10)Be and ^(36)Cl geochronology of offset alluvial fans along the northern Death Valley fault zone: Implications for transient strain in the eastern California shear zone

The northern Death Valley fault zone (NDVFZ) has long been recognized as a major right-lateral strike-slip fault in the eastern California shear zone (ECSZ). However, its geologic slip rate has been difficult to determine. Using high-resolution digital topographic imagery and terrestrial cosmogenic nuclide dating, we present the first geochronologically determined slip rate for the NDVFZ. Our study focuses on the Red Wall Canyon alluvial fan, which exposes clean dextral offsets of seven channels. Analysis of airborne laser swath mapping data indicates ∼297 ± 9 m of right-lateral displacement on the fault system since the late Pleistocene. In situ terrestrial cosmogenic ^(10)Be and ^(36)Cl geochronology was used to date the Red Wall Canyon fan and a second, correlative fan also cut by the fault. Beryllium 10 dates from large cobbles and boulders provide a maximum age of 70 +22/−20 ka for the offset landforms. The minimum age of the alluvial fan deposits based on ^(36)Cl depth profiles is 63 ± 8 ka. Combining the offset measurement with the cosmogenic ^(10)Be date yields a geologic fault slip rate of 4.2 +1.9/−1.1 mm yr^(−1), whereas the ^(36)Cl data indicate 4.7 +0.9/−0.6 mm yr^(−1) of slip. Summing these slip rates with known rates on the Owens Valley, Hunter Mountain, and Stateline faults at similar latitudes suggests a total geologic slip rate across the northern ECSZ of ∼8.5 to 10 mm yr^(−1). This rate is commensurate with the overall geodetic rate and implies that the apparent discrepancy between geologic and geodetic data observed in the Mojave section of the ECSZ does not extend north of the Garlock fault. Although the overall geodetic rates are similar, the best estimates based on geology predict higher strain rates in the eastern part of the ECSZ than to the west, whereas the observed geodetic strain is relatively constant

A Rapid Electronic Cognitive Assessment Measure for Multiple Sclerosis: Validation of Cognitive Reaction, an Electronic Version of the Symbol Digit Modalities Test

Background: incorporating cognitive testing into routine clinical practice is a challenge in multiple sclerosis (MS), given the wide spectrum of both cognitive and physical impairments people can have and the time that testing requires. Shortened paper and verbal assessments predominate but still are not used routinely. Computer-based tests are becoming more widespread; however, changes in how a paper test is implemented can impact what exactly is being assessed in an individual. The Symbol Digit Modalities Test (SDMT) is one validated test that forms part of the cognitive batteries used in MS and has some computer-based versions. We developed a tablet-based SDMT variant that has the potential to be ultimately deployed to patients' own devices.Objective: this paper aims to develop, validate, and deploy a computer-based SDMT variant, the Cognition Reaction (CoRe) test, that can reliably replicate the characteristics of the paper-based SDMT.Methods: we carried out analysis using Pearson and intraclass correlations, as well as a Bland-Altman comparison, to examine consistency between the SDMT and CoRe tests and for test-retest reliability. The SDMT and CoRe tests were evaluated for sensitivity to disability levels and age. A novel metric in CoRe was found: question answering velocity could be calculated. This was evaluated in relation to disability levels and age for people with MS and compared with a group of healthy control volunteers.Results: SDMT and CoRe test scores were highly correlated and consistent with 1-month retest values. Lower scores were seen in patients with higher age and some effect was seen with increasing disability. There was no learning effect evident. Question answering velocity demonstrated a small increase in speed over the 90-second duration of the test in people with MS and healthy controls.Conclusions: this study validates a computer-based alternative to the SDMT that can be used in clinics and beyond. It enables accurate recording of elements of cognition relevant in MS but offers additional metrics that may offer further value to clinicians and people with MS