Quitting patient care and career break intentions among general practitioners in South West England: findings of a census survey of general practitioners

Objective: Given recent concerns regarding general practitioner (GP) workforce capacity, we aimed to describe GPs’ career intentions, especially those which might impact on GP workforce availability over the next 5 years. Design: Census survey, conducted between April and June 2016 using postal and online responses , of all GPs on the National Health Service performers list and eligible to practise in primary care. Two reminders were used as necessary. Setting: South West England (population 3.5  million), a region with low overall socioeconomic deprivation. Participants: Eligible GPs were 2248 out of 3370 (67 % response rate). Main outcome measures: Reported likelihood of permanently leaving or reducing hours spent in direct patient care or of taking a career break within the next 5 years and present morale weighted for non-response. Results: Responders included 217 7 GPs engaged in patient care. Of these, 863 (37% weighted, 95%  CI 35 % to 39 %) reported a high likelihood of quitting direct patient care within the next 5 years. Overall, 1535 (70% weighted, 95%  CI 68 % to 72 %) respondents reported a career intention that would negatively impact GP workforce capacity over the next 5 years, through permanently leaving or reducing hours spent in direct patient care, or through taking a career break. GP age was an important predictor of career intentions; sharp increases in the proportion of GPs intending to quit patient care were evident from 52 years. Only 305 (14% weighted, 95%  CI 13 % to 16 %) reported high morale, while 1195 ( 54 % weighted, 95%  CI 52 % to 56 %) reported low morale. Low morale was particularly common among GP partners. Current morale strongly predicted GPs’ career intentions; those with very low morale were particularly likely to report intentions to quit patient care or to take a career break. Conclusions: A substantial majority of GPs in South West England report low morale. Many are considering career intentions which, if implemented, would adversely impact GP workforce capacity within a short time period. Study registration: NIHR HS&DR - 14/196/02, UKCRN ID 20700

Agnosia for accents in primary progressive aphasia.

As an example of complex auditory signal processing, the analysis of accented speech is potentially vulnerable in the progressive aphasias. However, the brain basis of accent processing and the effects of neurodegenerative disease on this processing are not well understood. Here we undertook a detailed neuropsychological study of a patient, AA with progressive nonfluent aphasia, in whom agnosia for accents was a prominent clinical feature. We designed a battery to assess AA's ability to process accents in relation to other complex auditory signals. AA's performance was compared with a cohort of 12 healthy age and gender matched control participants and with a second patient, PA, who had semantic dementia with phonagnosia and prosopagnosia but no reported difficulties with accent processing. Relative to healthy controls, the patients showed distinct profiles of accent agnosia. AA showed markedly impaired ability to distinguish change in an individual's accent despite being able to discriminate phonemes and voices (apperceptive accent agnosia); and in addition, a severe deficit of accent identification. In contrast, PA was able to perceive changes in accents, phonemes and voices normally, but showed a relatively mild deficit of accent identification (associative accent agnosia). Both patients showed deficits of voice and environmental sound identification, however PA showed an additional deficit of face identification whereas AA was able to identify (though not name) faces normally. These profiles suggest that AA has conjoint (or interacting) deficits involving both apperceptive and semantic processing of accents, while PA has a primary semantic (associative) deficit affecting accents along with other kinds of auditory objects and extending beyond the auditory modality. Brain MRI revealed left peri-Sylvian atrophy in case AA and relatively focal asymmetric (predominantly right sided) temporal lobe atrophy in case PA. These cases provide further evidence for the fractionation of brain mechanisms for complex sound analysis, and for the stratification of progressive aphasia syndromes according to the signature of nonverbal auditory deficits they produce

Evolutionary distances in the twilight zone -- a rational kernel approach

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.Comment: to appear in PLoS ON

Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: Different boosting intervals and implications for efficacy trials

Objectives. To investigate the safety and immunogenicity of boosting BCG with modified vaccinia Ankara expressing antigen 85A (MVA85A), shortly after BCG vaccination, and to compare this first with the immunogenicity of BCG vaccination alone and second with a previous clinical trial where MVA85A was administered more than 10 years after BCG vaccination. Design. There are two clinical trials reported here: a Phase I observational trial with MVA85A; and a Phase IV observational trial with BCG. These clinical trials were all conducted in the UK in healthy, HIV negative, BCG naı¨ve adults. Subjects were vaccinated with BCG alone; or BCG and then subsequently boosted with MVA85A four weeks later (short interval). The outcome measures, safety and immunogenicity, were monitored for six months. The immunogenicity results from this short interval BCG prime–MVA85A boost trial were compared first with the BCG alone trial and second with a previous clinical trial where MVA85A vaccination was administered many years after vaccination with BCG. Results. MVA85A was safe and highly immunogenic when administered to subjects who had recently received BCG vaccination. When the short interval trial data presented here were compared with the previous long interval trial data, there were no significant differences in the magnitude of immune responses generated when MVA85A was administered shortly after, or many years after BCG vaccination. Conclusions. The clinical trial data presented here provides further evidence of the ability of MVA85A to boost BCG primed immune responses. This boosting potential is not influenced by the time interval between prior BCG vaccination and boosting with MVA85A. These findings have important implications for the design of efficacy trials with MVA85A. Boosting BCG induced anti-mycobacterial immunity in either infancy or adolescence are both potential applications for this vaccine, given the immunological data presented here. Trial Registration. ClinicalTrials.Oxford University was the sponsor for all the clinical trials reported here

Understanding why primary care doctors leave direct patient care: a systematic review of qualitative research

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement: All data relevant to the study are included in the article or uploaded as supplementary information. No additional data available.Background UK general practitioners (GPs) are leaving direct patient care in significant numbers. We undertook a systematic review of qualitative research to identify factors affecting GPs’ leaving behaviour in the workforce as part of a wider mixed methods study (ReGROUP). Objective To identify factors that affect GPs’ decisions to leave direct patient care. Methods Qualitative interview-based studies were identified and their quality was assessed. A thematic analysis was performed and an explanatory model was constructed providing an overview of factors affecting UK GPs. Non-UK studies were considered separately. Results Six UK interview-based studies and one Australian interview-based study were identified. Three central dynamics that are key to understanding UK GP leaving behaviour were identified: factors associated with low job satisfaction, high job satisfaction and those linked to the doctor–patient relationship. The importance of contextual influence on job satisfaction emerged. GPs with high job satisfaction described feeling supported by good practice relationships, while GPs with poor job satisfaction described feeling overworked and unsupported with negatively impacted doctor–patient relationships. Conclusions Many GPs report that job satisfaction directly relates to the quality of the doctor–patient relationship. Combined with changing relationships with patients and interfaces with secondary care, and the gradual sense of loss of autonomy within the workplace, many GPs report a reduction in job satisfaction. Once job satisfaction has become negatively impacted, the combined pressure of increased patient demand and workload, together with other stress factors, has left many feeling unsupported and vulnerable to burn-out and ill health, and ultimately to the decision to leave general practice

Physiological phenotyping of dementias using emotional sounds.

INTRODUCTION: Emotional behavioral disturbances are hallmarks of many dementias but their pathophysiology is poorly understood. Here we addressed this issue using the paradigm of emotionally salient sounds. METHODS: Pupil responses and affective valence ratings for nonverbal sounds of varying emotional salience were assessed in patients with behavioral variant frontotemporal dementia (bvFTD) (n = 14), semantic dementia (SD) (n = 10), progressive nonfluent aphasia (PNFA) (n = 12), and AD (n = 10) versus healthy age-matched individuals (n = 26). RESULTS: Referenced to healthy individuals, overall autonomic reactivity to sound was normal in Alzheimer's disease (AD) but reduced in other syndromes. Patients with bvFTD, SD, and AD showed altered coupling between pupillary and affective behavioral responses to emotionally salient sounds. DISCUSSION: Emotional sounds are a useful model system for analyzing how dementias affect the processing of salient environmental signals, with implications for defining pathophysiological mechanisms and novel biomarker development

Whole Earth Telescope discovery of a strongly distorted quadrupole pulsation in the largest amplitude rapidly oscillating Ap star

We present a new analysis of the rapidly oscillating Ap (roAp) star, 2MASS J19400781 − 4420093 (J1940; V = 13.1). The star was discovered using SuperWASP broadband photometry to have a frequency of 176.39 d−1 (2041.55 µHz; P = 8.2 min; Holdsworth et al. 2014a) and is shown here to have a peak-to-peak amplitude of 34 mmag. J1940 has been observed during three seasons at the South African Astronomical Ob- servatory, and has been the target of a Whole Earth Telescope campaign. The observations reveal that J1940 pulsates in a distorted quadrupole mode with unusual pulsational phase variations. A higher signal-to-noise ratio spectrum has been obtained since J1940’s first announcement, which allows us to classify the star as A7 Vp Eu(Cr). The observing campaigns presented here reveal no pulsations other than the initially detected frequency. We model the pulsation in J1940 and conclude that the pulsation is distorted by a magnetic field of strength 1.5 kG. A difference in the times of rotational maximum light and pulsation maximum suggests a significant offset between the spots and pulsation axis, as can be seen in roAp stars

Associations between health-related quality of life, physical function and fear of falling in older fallers receiving home care

Falls and injuries in older adults have significant consequences and costs, both personal and to society. Although having a high incidence of falls, high prevalence of fear of falling and a lower quality of life, older adults receiving home care are underrepresented in research on older fallers. The objective of this study is to determine the associations between health-related quality of life (HRQOL), fear of falling and physical function in older fallers receiving home care

A physiological signature of sound meaning in dementia.

The meaning of sensory objects is often behaviourally and biologically salient and decoding of semantic salience is potentially vulnerable in dementia. However, it remains unclear how sensory semantic processing is linked to physiological mechanisms for coding object salience and how that linkage is affected by neurodegenerative diseases. Here we addressed this issue using the paradigm of complex sounds. We used pupillometry to compare physiological responses to real versus synthetic nonverbal sounds in patients with canonical dementia syndromes (behavioural variant frontotemporal dementia - bvFTD, semantic dementia - SD; progressive nonfluent aphasia - PNFA; typical Alzheimer's disease - AD) relative to healthy older individuals. Nonverbal auditory semantic competence was assessed using a novel within-modality sound classification task and neuroanatomical associations of pupillary responses were assessed using voxel-based morphometry (VBM) of patients' brain MR images. After taking affective stimulus factors into account, patients with SD and AD showed significantly increased pupil responses to real versus synthetic sounds relative to healthy controls. The bvFTD, SD and AD groups had a nonverbal auditory semantic deficit relative to healthy controls and nonverbal auditory semantic performance was inversely correlated with the magnitude of the enhanced pupil response to real versus synthetic sounds across the patient cohort. A region of interest analysis demonstrated neuroanatomical associations of overall pupil reactivity and differential pupil reactivity to sound semantic content in superior colliculus and left anterior temporal cortex respectively. Our findings suggest that autonomic coding of auditory semantic ambiguity in the setting of a damaged semantic system may constitute a novel physiological signature of neurodegenerative diseases