Differences in level of confidence in diabetes care between different groups of trainees: the TOPDOC diabetes study

Background There is an increasing prevalence of diabetes. Doctors in training, irrespective of specialty, will have patients with diabetes under their care. The aim of this further evaluation of the TOPDOC Diabetes Study data was to identify if there was any variation in confidence in managing diabetes depending on the geographical location of trainees and career aspirations. Methods An online national survey using a pre-validated questionnaire was administered to trainee doctors. A 4-point confidence rating scale was used to rate confidence in managing aspects of diabetes care and a 6-point scale used to quantify how often trainees would contribute to the management of patients with diabetes. Responses were grouped depending on which UK country trainees were based and their intended career choice. Results Trainees in Northern Ireland reported being less confident in IGT diagnosis, use of IV insulin and peri-operative management and were less likely to adjust oral treatment, contact specialist, educate lifestyle, and optimise treatment. Trainees in Scotland were less likely to contact a specialist, but more likely to educate on lifestyle, change insulin, and offer follow-up advice. In Northern Ireland, Undergraduate (UG) and Postgraduate (PG) training in diagnosis was felt less adequate, PG training in emergencies less adequate, and reporting of need for further training higher. Trainees in Wales felt UG training to be inadequate. In Scotland more trainees felt UG training in diagnosis and optimising treatment was inadequate. Physicians were more likely to report confidence in managing patients with diabetes and to engage in different aspects of diabetes care. Aspiring physicians were less likely to feel the need for more training in diabetes care; however a clear majority still felt they needed more training in all aspects of care. Conclusions Doctors in training have poor confidence levels dealing with diabetes related care issues. Although there is variability between different groups of trainees according to geographical location and career aspirations, this is a UK wide issue. There should be a UK wide standardised approach to improving training for junior doctors in diabetes care with local training guided by specific needs.</p

Acid and inflammatory sensitisation of naked mole-rat colonic afferent nerves.

Acid sensing in the gastrointestinal tract is required for gut homeostasis and the detection of tissue acidosis caused by ischaemia, inflammation and infection. In the colorectum, activation of colonic afferents by low pH contributes to visceral hypersensitivity and abdominal pain in human disease including during inflammatory bowel disease. The naked mole-rat (Heterocephalus glaber) shows no pain-related behaviour to subcutaneous acid injection and cutaneous afferents are insensitive to acid, an adaptation thought to be a consequence of the subterranean, likely hypercapnic, environment in which it lives. As such we sought to investigate naked mole-rat interoception within the gastrointestinal tract and how this differed from the mouse (Mus Musculus). Here, we show the presence of calcitonin gene-related peptide expressing extrinsic nerve fibres innervating both mesenteric blood vessels and the myenteric plexi of the smooth muscle layers of the naked mole-rat colorectum. Using ex vivo colonic-nerve electrophysiological recordings, we show differential sensitivity of naked mole-rat, compared to mouse, colonic afferents to acid and the prototypic inflammatory mediator bradykinin, but not direct mechanical stimuli. In naked mole-rat, but not mouse, we observed mechanical hypersensitivity to acid, whilst both species sensitised to bradykinin. Collectively, these findings suggest that naked mole-rat colonic afferents are capable of detecting acidic stimuli; however, their intracellular coupling to downstream molecular effectors of neuronal excitability and mechanotransduction likely differs between species.The authors declare no competing financial interests. This work was supported by Rosetrees Postdoctoral Grant (A1296; JRFH and EStJS), BBSRC grant (BB/R006210/1; JRFH and EStJS), Versus Arthritis Pain Challenge Grant (RG21973; GC and EStJS), AstraZeneca PhD studentshipt (KHB), EMBO Long-Term Fellowship (ALTF1565-2015; ZH) and University of Cambridge Vice Chancellor’s Award (TST)

Psychometric characteristics of the Brunel Mood Scale in a Singaporean context

Mood profiling serves several functions in the sporting domain, including monitoring of athlete mindset, early problem identification, performance prediction, and screening for pathogenic behaviours. The 24-item Brunel Mood Scale (BRUMS; Terry, Lane, Lane, & Keohane, 1999) is yet to be validated or researched extensively in a Singaporean context, and hence the current investigation provided a cross-cultural re-validation of the BRUMS. The six-factor measurement model was tested on a sample of 1,444 English-speaking Singaporean participants (age range = 18– 56+ yr., median = 22–25 yr.; male = 991, female = 440, unspecified = 13), including 954 involved in sport and 490 non-sport participants. In addition, a subgroup of 243 participants completed the BRUMS and concurrent measures of affect and psychological distress. A subgroup of 141 participants completed the BRUMS on two occasions to assess test-retest reliability. Structural equation modelling showed a good fit of the data to the measurement model (CFI = .937, TLI = .927, RMSEA = .062). Multi-sample modelling (sport vs non-sport, ≤ 25 yr. vs 26+ yr.) further supported the factorial validity of the measure. Relationships between BRUMS subscales and concurrent measures were consistent with theoretical predictions. Internal consistency and test-retest reliability coefficients were acceptable. Findings supported the psychometric integrity of the BRUMS for use in a Singaporean context, providing opportunities for further investigation of the antecedents, correlates and behavioural consequences of mood responses among Singaporean sport and non-sport participants

Single-cell RNAseq reveals seven classes of colonic sensory neuron.

OBJECTIVE: Integration of nutritional, microbial and inflammatory events along the gut-brain axis can alter bowel physiology and organism behaviour. Colonic sensory neurons activate reflex pathways and give rise to conscious sensation, but the diversity and division of function within these neurons is poorly understood. The identification of signalling pathways contributing to visceral sensation is constrained by a paucity of molecular markers. Here we address this by comprehensive transcriptomic profiling and unsupervised clustering of individual mouse colonic sensory neurons. DESIGN: Unbiased single-cell RNA-sequencing was performed on retrogradely traced mouse colonic sensory neurons isolated from both thoracolumbar (TL) and lumbosacral (LS) dorsal root ganglia associated with lumbar splanchnic and pelvic spinal pathways, respectively. Identified neuronal subtypes were validated by single-cell qRT-PCR, immunohistochemistry (IHC) and Ca2+-imaging. RESULTS: Transcriptomic profiling and unsupervised clustering of 314 colonic sensory neurons revealed seven neuronal subtypes. Of these, five neuronal subtypes accounted for 99% of TL neurons, with LS neurons almost exclusively populating the remaining two subtypes. We identify and classify neurons based on novel subtype-specific marker genes using single-cell qRT-PCR and IHC to validate subtypes derived from RNA-sequencing. Lastly, functional Ca2+-imaging was conducted on colonic sensory neurons to demonstrate subtype-selective differential agonist activation. CONCLUSIONS: We identify seven subtypes of colonic sensory neurons using unbiased single-cell RNA-sequencing and confirm translation of patterning to protein expression, describing sensory diversity encompassing all modalities of colonic neuronal sensitivity. These results provide a pathway to molecular interrogation of colonic sensory innervation in health and disease, together with identifying novel targets for drug development

Spitzer Observations of Var Her 04: Possible Detection of Dust Formation in a Super-Outbursting TOAD

We present four MIPS (24 \micron) and two IRAC (3.6, 4.5, 5.8, and 8.0 \micron) Spitzer observations of the newly discovered Tremendous Outburst Amplitude Dwarf nova (TOAD) Var Her 04 during decline from super-outburst. The four MIPS observations span 271 days and the two IRAC observations span 211 days. Along the line-of-sight to Var Her 04, there is a foreground M-star within 1\arcsec of the variable; as a result, all of the Spitzer photometry presented in this paper is a blend of the foreground M-star and Var Her 04. We estimate the quiescent level of the TOAD to be $\Delta V=4-5$ magnitudes below that of the M-star. Based upon the spectral energy distribution and the 2MASS colors, we find the M-star to be an M3.5V dwarf at a distance of 80-130 pc. Based upon its outburst amplitude and quiescent apparent magnitude, we estimate the distance to Var Her 04 to be 200-400 pc, suggesting that the line-of-sight foreground star is physically unrelated to the cataclysmic variable. All of the Spitzer photometry is consistent with the photospheric emission of the line-of-sight M3.5V star, except for one 24 \micron observation obtained after the variable re-brightened. This 24 \micron flux density is 75 $\mu$Jy ($4\sigma$) above the preceding and following MIPS observations. We tentatively suggest that the mid-infrared brightening of 75 $\mu$Jy may be associated with a dust formation event in the super-outburst ejecta. Assuming a dust temperature of 100-400 K, we have estimated the amount of dust required. We find $10^{-13}-10^{-11}$ M$_\odot$ of dust is needed, consistent with amounts of mass ejection in TOADs expected during super-outburst, and possibly making TOADs important contributors to the recycling of the interstellar medium.Comment: Accepted for publication in The Astronomical Journa

Vagus nerve stimulation paired with upper limb rehabilitation after chronic stroke

Background and Purpose: We assessed safety, feasibility, and potential effects of vagus nerve stimulation (VNS) paired with rehabilitation for improving arm function after chronic stroke. Methods: We performed a randomized, multisite, double-blinded, sham-controlled pilot study. All participants were implanted with a VNS device and received 6-week in-clinic rehabilitation followed by a home exercise program. Randomization was to active VNS (n=8) or control VNS (n=9) paired with rehabilitation. Outcomes were assessed at days 1, 30, and 90 post-completion of in-clinic therapy. Results: All participants completed the course of therapy. There were 3 serious adverse events related to surgery. Average FMA-UE scores increased 7.6 with active VNS and 5.3 points with control at day 1 post–in-clinic therapy (difference, 2.3 points; CI, −1.8 to 6.4; P=0.20). At day 90, mean scores increased 9.5 points from baseline with active VNS, and the control scores improved by 3.8 (difference, 5.7 points; CI, −1.4 to 11.5; P=0.055). The clinically meaningful response rate of FMA-UE at day 90 was 88% with active VNS and 33% with control VNS (P&lt;0.05). Conclusions: VNS paired with rehabilitation was acceptably safe and feasible in participants with upper limb motor deficit after chronic ischemic stroke. A pivotal study of this therapy is justified

Design management: changing roles of the professions

This paper sets out to explore how recent changes in procurement in construction have affected the roles that professions play in the design process. It discusses how professions that traditionally took the role of design manager now find themselves participating within previously unforeseen contexts, working in multidisciplinary teams led by contractors and with changed responsibilities at the design stage. Supply chain members who were not previously involved during the early project phases are being engaged at the earliest phases of the project life cycle and even taking leadership roles while designers sometimes work as supply chain partners. A study of design in construction and other sectors shows that in dealing with design management issues it is critical to deepen appreciation for the unique characteristics of design and the design process. The paper argues that contractors and designers taking on design management roles in a dynamic industry seeking to explore best practice and innovative approaches to procurement and in the delivery of projects need to acquire new skills, management education and develop the necessary qualities

Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit.

By studying healthy women who do not request analgesia during their first delivery, we investigate genetic effects on labor pain. Such women have normal sensory and psychometric test results, except for significantly higher cuff pressure pain. We find an excess of heterozygotes carrying the rare allele of SNP rs140124801 in KCNG4. The rare variant KV6.4-Met419 has a dominant-negative effect and cannot modulate the voltage dependence of KV2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, Kcng4 (KV6.4) expression occurs in 40% of retrograde-labeled mouse uterine sensory neurons, all of which express KV2.1, and over 90% express the nociceptor genes Trpv1 and Scn10a. In neurons overexpressing KV6.4-Met419, the voltage dependence of inactivation for KV2.1 is more depolarized compared with neurons overexpressing KV6.4. Finally, KV6.4-Met419-overexpressing neurons have a higher action potential threshold. We conclude that KV6.4 can influence human labor pain by modulating the excitability of uterine nociceptors.MCL, DKM, DW, and CGW acknowledge funding from Addenbrooke’s Charitable Trust and the NIHR Cambridge Biomedical Research Centre. MN was funded by the Wellcome Trust (200183/Z/15/Z); JH and ESS by a Rosetrees Postdoctoral Grant (A1296) and the BBSRC (BB/R006210/1); GC and ESS by Versus Arthritis Grants (RG21973); VBL and FR by the Wellcome Trust (106262/Z/14/Z and 106263/Z/14/Z) and a joint MRC programme within the Metabolic Diseases Unit (MRC_MC_UU_12012/3). EF, GI and CB were funded by the Cambridge NIHR Biomedical Research Centre Integrative Genomics theme and LAP by a BBSRC-funded studentship (BB/M011194/1)

The new global governors: Globalization, civil society, and the rise of private philanthropic foundations

One of the important drivers of change within contemporary global civil society is the growing power and influence of private philanthropic foundations (PPFs). In the analysis below, I consider the cases of the Bill and Melinda Gates Foundation (BMGF) and the Open Society Foundations (OSF), the largest and fourth largest PPFs in the world today by wealth or assets, and, especially, their founders. I consider their influence within global civil society, within the context of international development, and the consequences of their activities for a range of international actors. I do so in the context of debate within the literature on the activities of PPFs and I side with advocates of critical scrutiny. In developing my argument, I draw on a range of sources including the financial statements and audited accounts of PPFs, of other non-governmental organizations and of selected inter-governmental organizations. I argue that the BMGF and OSF are engines of neoliberalism and potent symbols of a second distinct ‘gilded age’ and that their influence must be restrained through anti-trust measures and through greater taxation and regulation