How do medical schools influence their students' career choices? A realist evaluation.

INTRODUCTION: The career choices of medical graduates vary widely between medical schools in the UK and elsewhere and are generally not well matched with societal needs. Research has found that experiences in medical school including formal, informal and hidden curricula are important influences. We conducted a realist evaluation of how and why these various social conditions in medical school influence career thinking. METHODS: We interviewed junior doctors at the point of applying for speciality training. We selected purposively for a range of career choices. Participants were asked to describe points during their medical training when they had considered career options and how their thinking had been influenced by their context. Interview transcripts were coded for context-mechanism-outcome (CMO) configurations to test initial theories of how career decisions are made. RESULTS: A total of 26 junior doctors from 12 UK medical schools participated. We found 14 recurring CMO configurations in the data which explained influences on career choice occurring during medical school. DISCUSSION: Our initial theories about career decision-making were refined as follows: It involves a process of testing for fit of potential careers. This process is asymmetric with multiple experiences needed before deciding a career fits ('easing in') but sometimes only a single negative experience needed for a choice to be ruled out. Developing a preference for a speciality aligns with Person-Environment-Fit decision theories. Ruling out a potential career can however be a less thought-through process than rationality-based decision theories would suggest. Testing for fit is facilitated by longer and more authentic undergraduate placements, allocation of and successful completion of tasks, being treated as part of the team and enthusiastic role models. Informal career guidance is more influential than formal. We suggest some implications for medical school programmes.

How well do UK assistantships equip medical students for graduate practice? Think EPAs.

The goal of better medical student preparation for clinical practice drives curricular initiatives worldwide. Learning theory underpins Entrustable Professional Activities (EPAs) as a means of safe transition to independent practice. Regulators mandate senior assistantships to improve practice readiness. It is important to know whether meaningful EPAs occur in assistantships, and with what impact. Final year students at one UK medical school kept learning logs and audio-diaries for six one-week periods during a year-long assistantship. Further data were also obtained through interviewing participants when students and after three months as junior doctors. This was combined with data from new doctors from 17 other UK schools. Realist methods explored what worked for whom and why. 32 medical students and 70 junior doctors participated. All assistantship students reported engaging with EPAs but gaps in the types of EPAs undertaken exist, with level of entrustment and frequency of access depending on the context. Engagement is enhanced by integration into the team and shared understanding of what constitutes legitimate activities. Improving the shared understanding between student and supervisor of what constitutes important assistantship activity may result in an increase in the amount and/or quality of EPAs achieved.

Transcranial Direct Current Stimulation Modulates Connectivity of Left Dorsolateral Prefrontal Cortex with Distributed Cortical Networks.

Studies have shown that transcranial direct current stimulation increases neuronal excitability of the targeted region and general connectivity of relevant functional networks. However, relatively little is understood of how the stimulation affects the connectivity relationship of the target with regions across the network structure of the brain. Here, we investigated the effects of transcranial direct current stimulation on the functional connectivity of the targeted region using resting-state fMRI scans of the human brain. Anodal direct current stimulation was applied to the left dorsolateral prefrontal cortex (lDLPFC; cathode on the right bicep), which belongs to the frontoparietal control network (FPCN) and is commonly targeted for neuromodulation of various cognitive functions including short-term memory, long-term memory, and cognitive control. lDLPFC's connectivity characteristics were quantified as graph theory measures, from the resting-state fMRI scans obtained prior to and following the stimulation. Critically, we tested pre- to poststimulation changes of the lDLPFC connectivity metrics following an active versus sham stimulation. We found that the stimulation had two distinct effects on the connectivity of lDLPFC: for Brodmann's area (BA) 9, it increased the functional connectivity between BA 9 and other nodes within the FPCN; for BA 46, net connectivity strength was not altered within FPCN, but connectivity distribution across networks (participation coefficient) was decreased. These findings provide insights that the behavioral changes as the functional consequences of stimulation may come about because of the increased role of lDLPFC in the FPCN.

Intensity-Dependent Changes in Quantified Resting Cerebral Perfusion With Multiple Sessions of Transcranial DC Stimulation.

Transcranial direct current stimulation (tDCS) to the left prefrontal cortex has been shown to produce broad behavioral effects including enhanced learning and vigilance. Still, the neural mechanisms underlying such effects are not fully understood. Furthermore, the neural underpinnings of repeated stimulation remain understudied. In this work, we evaluated the effects of the repetition and intensity of tDCS on cerebral perfusion [cerebral blood flow (CBF)]. A cohort of 47 subjects was randomly assigned to one of the three groups. tDCS of 1- or 2-mA was applied to the left prefrontal cortex on three consecutive days, and resting CBF was quantified before and after stimulation using the arterial spin labeling MRI and then compared with a group that received sham stimulation. A widespread decreased CBF was found in a group receiving sham stimulation across the three post-stimulation measures when compared with baseline. In contrast, only slight decreases were observed in the group receiving 2-mA stimulation in the second and third post-stimulation measurements, but more prominent increased CBF was observed across several brain regions including the locus coeruleus (LC). The LC is an integral region in the production of norepinephrine and the noradrenergic system, and an increased norepinephrine/noradrenergic activity could explain the various behavioral findings from the anodal prefrontal tDCS. A decreased CBF was observed in the 1-mA group across the first two post-stimulation measurements, similar to the sham group. This decreased CBF was apparent in only a few small clusters in the third post-stimulation scan but was accompanied by an increased CBF, indicating that the neural effects of stimulation may persist for at least 24 h and that the repeated stimulation may produce cumulative effects.

Cervical transcutaneous vagal nerve stimulation (ctVNS) improves human cognitive performance under sleep deprivation stress.

Fatigue is a pervasive public health and safety issue. Common fatigue countermeasures include caffeine or other chemical stimulants. These can be effective in limited circumstances but other non-pharmacological fatigue countermeasures such as non-invasive electrical neuromodulation have shown promise. It is reasonable to suspect that other types of non-invasive neuromodulation may be similarly effective or perhaps even superior. The objective of this research was to evaluate the efficacy of cervical transcutaneous vagal nerve stimulation (ctVNS) to mitigate the negative effects of fatigue on cognition and mood. Two groups (active or sham stimulation) of twenty participants in each group completed 34 h of sustained wakefulness. The ctVNS group performed significantly better on arousal, multi-tasking, and reported significantly lower fatigue ratings compared to sham for the duration of the study. CtVNS could be a powerful fatigue countermeasure tool that is easy to administer, long-lasting, and has fewer side-effects compared to common pharmacological interventions.

The Effects of Anodal Transcranial Direct Current Stimulation on Sleep Time and Efficiency.

A single session of anodal transcranial direct current stimulation (tDCS) has been shown to increase arousal in healthy participants for up to 24 h post-stimulation. However, little is known about the effects of tDCS on subsequent sleep in this population. Based on previous clinical studies, we hypothesized that anodal stimulation to the left dorsolateral prefrontal cortex (lDLPFC) would produce higher arousal with decreased sleep time and stimulation to the primary motor cortex (M1) would have the converse effect. Thirty-six active duty military were randomized into one of three groups (n = 12/group); active anodal tDCS over the lDLPFC, active anodal tDCS over left M1, or sham tDCS. Participants answered questionnaires 3 times a day and wore a wrist activity monitor (WAM) to measure sleep time and efficiency for 3 weeks. On weeks 2 and 3 (order counterbalance), participants received stimulation at 1800 h before 26 h of sustained wakefulness testing (sleep deprived) and at 1800 h without sleep deprivation (non-sleep deprived). There were no significant effects for the non-sleep deprived portion of testing. For the sleep deprived portion of testing, there were main effects of group and night on sleep time. The DLPFC group slept less than the other groups on the second and third night following stimulation. There is no negative effect on mood or sleep quality from a single dose of tDCS when participants have normal sleep patterns (i.e., non-sleep deprived portion of testing). The results suggest that stimulation may result in faster recovery from fatigue caused by acute periods of sleep deprivation, as their recovery sleep periods were less.

Transcranial Direct Current Stimulation Optimization - From Physics-Based Computer Simulations to High-Fidelity Head Phantom Fabrication and Measurements.

BACKGROUND: Transcranial direct current stimulation (tDCS) modulates neural networks. Computer simulations, while used to identify how currents behave within tissues of different conductivity properties, still need to be complemented by physical models. OBJECTIVE/HYPOTHESIS: To better understand tDCS effects on biology-mimicking tissues by developing and testing the feasibility of a high-fidelity 3D head phantom model that has sensing capabilities at different compartmental levels. METHODS: Models obtained from MRI images generated 3D printed molds. Agar phantoms were fabricated, and 18 monitoring electrodes were placed on specific phantom brain areas. RESULTS: When using rectangular electrodes, the measured and simulated voltages at the monitoring electrodes agreed reasonably well, except at excitation locations. The electric field distribution in different phantom layers appeared better confined with circular electrodes compared to rectangular electrodes. CONCLUSION: The high-fidelity 3D head model was found to be feasible and comparable with computer-based electrical simulations, with high correlation between simulated and measured brain voltages. This feasibility study supports testing to further assess the reliability of this model.

Repetitive Transcranial Electrical Stimulation Induces Quantified Changes in Resting Cerebral Perfusion Measured from Arterial Spin Labeling.

The use of transcranial electrical stimulation (TES) as a method to augment neural activity has increased in popularity in the last decade and a half. The specific application of TES to the left prefrontal cortex has been shown to produce broad cognitive effects; however, the neural mechanisms underlying these effects remain unknown. In this work, we evaluated the effect of repetitive TES on cerebral perfusion. Stimulation was applied to the left prefrontal cortex on three consecutive days, and resting cerebral perfusion was quantified before and after stimulation using arterial spin labeling. Perfusion was found to decrease significantly more in a matched sham stimulation group than in a group receiving active stimulation across many areas of the brain. These changes were found to originate in the locus coeruleus and were broadly distributed in the neocortex. The changes in the neocortex may be a direct result of the stimulation or an indirect result via the changes in the noradrenergic system produced from the altered activity of the locus coeruleus. These findings indicate that anodal left prefrontal stimulation alters the activity of the locus coeruleus, and this altered activity may excite the noradrenergic system producing the broad behavioral effects that have been reported.

Transcranial direct current stimulation versus caffeine as a fatigue countermeasure.

BACKGROUND: To assess the efficacy of using transcranial direct current stimulation (tDCS) to remediate the deleterious effects of fatigue induced by sleep deprivation and compare these results to caffeine, a commonly used fatigue countermeasure. OBJECTIVE/HYPOTHESIS: Based on previous research, tDCS of the dorsolateral prefrontal cortex (DLPFC) can modulate attention and arousal. The authors hypothesize that tDCS can be an effective fatigue countermeasure. METHODS: Five groups of ten participants each received either active tDCS and placebo gum at 1800, caffeine gum with sham tDCS at 1800, active tDCS and placebo gum at 0400, caffeine gum with sham tDCS at 0400, or sham tDCS with placebo gum at 1800 and 0400 during 36-h of sustained wakefulness. Participants completed a vigilance task, working memory task, psychomotor vigilance task (PVT), and a procedural game beginning at 1800 h and continued every two hours throughout the night until 1900 the next day. RESULTS: tDCS dosed at 1800 provided 6 h of improved attentional accuracy and reaction times compared to the control group. Caffeine did not produce an effect. Both tDCS groups also had an improved effect on mood. Participants receiving tDCS reported feeling more vigor, less fatigue, and less bored throughout the night compared to the control and caffeine groups. CONCLUSIONS: We believe tDCS could be a powerful fatigue countermeasure. The effects appear to be comparable or possibly more beneficial than caffeine because they are longer lasting and mood remains more positive.

Safety parameter considerations of anodal transcranial Direct Current Stimulation in rats.

A commonly referenced transcranial Direct Current Stimulation (tDCS) safety threshold derives from tDCS lesion studies in the rat and relies on electrode current density (and related electrode charge density) to support clinical guidelines. Concerns about the role of polarity (e.g. anodal tDCS), sub-lesion threshold injury (e.g. neuroinflammatory processes), and role of electrode montage across rodent and human studies support further investigation into animal models of tDCS safety. Thirty-two anesthetized rats received anodal tDCS between 0 and 5mA for 60min through one of three epicranial electrode montages. Tissue damage was evaluated using hemotoxylin and eosin (H&E) staining, Iba-1 immunohistochemistry, and computational brain current density modeling. Brain lesion occurred after anodal tDCS at and above 0.5mA using a 25.0mm2 electrode (electrode current density: 20.0A/m2). Lesion initially occurred using smaller 10.6mm2 or 5.3mm2 electrodes at 0.25mA (23.5A/m2) and 0.5mA (94.2A/m2), respectively. Histological damage was correlated with computational brain current density predictions. Changes in microglial phenotype occurred in higher stimulation groups. Lesions were observed using anodal tDCS at an electrode current density of 20.0A/m2, which is below the previously reported safety threshold of 142.9A/m2 using cathodal tDCS. The lesion area is not simply predicted by electrode current density (and so not by charge density as duration was fixed); rather computational modeling suggests average brain current density as a better predictor for anodal tDCS. Nonetheless, under the assumption that rodent epicranial stimulation is a hypersensitive model, an electrode current density of 20.0A/m2 represents a conservative threshold for clinical tDCS, which typically uses an electrode current density of 2A/m2 when electrodes are placed on the skin (resulting in a lower brain current density).

Mechanisms and Effects of Transcranial Direct Current Stimulation.

The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing research in the field of transcranial direct current stimulation (tDCS) and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical populations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising applications include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models) can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose-response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light) therapy, can be prudently leveraged.

A Par-1-Par-3-Centrosome Cell Polarity Pathway and Its Tuning for Isotropic Cell Adhesion.

To form regulated barriers between body compartments, epithelial cells polarize into apical and basolateral domains and assemble adherens junctions (AJs). Despite close links with polarity networks that generate single polarized domains, AJs distribute isotropically around the cell circumference for adhesion with all neighboring cells [1-3]. How AJs avoid the influence of polarity networks to maintain their isotropy has been unclear. In established epithelia, trans cadherin interactions could maintain AJ isotropy [4], but AJs are dynamic during epithelial development and remodeling [5, 6], and thus specific mechanisms may control their isotropy. In Drosophila, aPKC prevents hyper-polarization of junctions as epithelia develop from cellularization to gastrulation [7]. Here, we show that aPKC does so by inhibiting a positive feedback loop between Bazooka (Baz)/Par-3, a junctional organizer [5, 8-10], and centrosomes. Without aPKC, Baz and centrosomes lose their isotropic distributions and recruit each other to single plasma membrane (PM) domains. Surprisingly, our loss- and gain-of-function analyses show that the Baz-centrosome positive feedback loop is driven by Par-1, a kinase known to phosphorylate Baz and inhibit its basolateral localization [8, 11, 12]. We find that Par-1 promotes the positive feedback loop through both centrosome microtubule effects and Baz phosphorylation. Normally, aPKC attenuates the circuit by expelling Par-1 from the apical domain at gastrulation. The combination of local activation and global inhibition is a common polarization strategy [13-16]. Par-1 seems to couple both effects for a potent Baz polarization mechanism that is regulated for the isotropy of Baz and AJs around the cell circumference.

A new quality of life consultation template for patients with venous leg ulceration.

OBJECTIVE: Chronic venous leg ulcers (CVLUs) are common and recurrent, however, care for patients predominantly has a focus which overlooks the impact of the condition on quality of life. The aim of this study was to develop a simple, evidence-based consultation template, with patients and practitioners, which focuses consultations on quality of life themes. METHOD: A nominal group was undertaken to develop a new consultation template for patients with CVLUs based on the findings of earlier qualitative study phases. RESULTS: A user-friendly two-sided A4 template was designed to focus nurse-patient consultations on the quality of life challenges posed by CVLUs. CONCLUSION: CVLUs impact negatively on the quality of life of the patient but this receives inadequate attention during current consultations. This new template will help to ensure that key concerns are effectively raised, explored and addressed during each consultation. DECLARATION OF INTEREST: The NHS West Midlands Strategic Health Authority funded this study. The authors have no conflicts of interest to declare.

The impact of chronic venous leg ulcers: a systematic review.

OBJECTIVE: Chronic venous leg ulcers are common, intractable and often recurrent, but care tends to be wound focused, potentially overlooking the significant impact the condition has on patients' lives. A systematic review was undertaken to explore the factors that impact on the quality of life of patients with chronic venous leg ulceration. METHOD: Eligible articles published between 1990 and 2013 were identified via electronic searches of research databases (MEDLINE, CINAHL, BNI, EMBASE, PsycINFO, AMED and HMIC, Cochrane Collaboration database and Google Scholar). RESULTS: There were 23 studies (11 qualitative and 12 quantitative) that met the inclusion criteria. There were then the subject of a full review. The qualitative studies were collapsed into four core themes: physical, psychological, social implications and the nurse-patient relationship. The quantitative studies were grouped according to the tool applied. The review demonstrated that chronic venous leg ulcers impact negatively upon all areas of daily living. Pain, exudate, odour and the impact on mobility were daily challenges. The ability to engage with everyday functioning was restricted either owing to the ulcer, the dressing or to a self-imposed isolation in response to the impact of symptoms. Depression and low mood were common and yet, despite this, some studies reported that participants remained hopeful. CONCLUSION: Studies suggest that chronic venous leg ulceration negatively affects the quality of life of the patient and that such issues receive inadequate attention during current consultations. If such negative implications are to be effectively addressed, key issues need to be considered during every consultation. DECLARATION OF INTEREST: This study was funded by West Midlands Strategic Health Authority. The authors have no conflicts of interest to declare.

Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask.

There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine). Non-invasive brain stimulation-specifically transcranial Direct Current Stimulation (tDCS)-has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks) were seen with a right parietal (C4, reference to left shoulder) montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008). No effects were seen with anodes over sites that stimulated only dorsal (C3) or only ventral (F10) attention networks. The speed subtask (update memory for symbols) benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical.

A comparison of the effects of transcranial direct current stimulation and caffeine on vigilance and cognitive performance during extended wakefulness.

BACKGROUND: Sleep deprivation from extended duty hours is a common complaint for many occupations. Caffeine is one of the most common countermeasures used to combat fatigue. However, the benefits of caffeine decline over time and with chronic use. OBJECTIVE: Our objective was to evaluate the efficacy of anodal transcranial direct current stimulation (tDCS) applied to the pre-frontal cortex at 2 mA for 30 min to remediate the effects of sleep deprivation and to compare the behavioral effects of tDCS with those of caffeine. METHODS: Three groups of 10 participants each received either active tDCS with placebo gum, caffeine gum with sham tDCS, or sham tDCS with placebo gum during 30 h of extended wakefulness. RESULTS: Our results show that tDCS prevented a decrement in vigilance and led to better subjective ratings for fatigue, drowsiness, energy, and composite mood compared to caffeine and control in sleep-deprived individuals. Both the tDCS and caffeine produced similar improvements in latencies on a short-term memory task and faster reaction times in a psychomotor task when compared to the placebo group. Interestingly, changes in accuracy for the tDCS group were not correlated to changes in mood; whereas, there was a relationship for the caffeine and sham groups. CONCLUSION: Our data suggest that tDCS could be a useful fatigue countermeasure and may be more beneficial than caffeine since boosts in performance and mood last several hours.

Modulation of cellular innate immunity by Lepeophtheirus salmonis secretory products.

Lepeophtheirus salmonis produces pharmacologically active substances that have been shown to modify genetic expression of inflammatory mediators in SHK-1 cells and head kidney macrophages of salmon. Differences in genetic expression among genera of Oncorhynchus and Salmo reflect different susceptibilities to L. salmonis. This study was conducted to determine if the presence of L. salmonis secretory products (SEPs)(1) alters the cellular innate immune response (specifically macrophage function) among several salmonids. Phagocytic assays were performed using SHK-1 cells and macrophages isolated from pink (Oncorhynchus gorbuscha), chum (Oncorhynchus keta) and Atlantic (Salmo salar) salmon following incubation with SEPs and Aeromonas salmonicida. Respiratory burst assays were analyzed using pink, chum and Atlantic salmon macrophages after exposure to SEPs. For SHK-1 cells, incubation with SEPS led to dose-dependent increases in phagocytosis. Following incubation with SEPs, chum salmon macrophages had the highest phagocytic index (55.1%) followed by Atlantic (26.4%) and pink (15.8%) salmon. In contrast, respiratory burst response was greatest in pink salmon and minimal in the other two species. Our results suggest that the cellular innate immune response of salmon is modified in the presence of L. salmonis secretions and differences observed among species provide insight into species-specific consequences of sea lice infection.

Development and face validation of strategies for improving consultation skills.

While formative workplace based assessment can improve learners' skills, it often does not because the procedures used do not facilitate feedback which is sufficiently specific to scaffold improvement. Provision of pre-formulated strategies to address predicted learning needs has potential to improve the quality and automate the provision of written feedback. To systematically develop, validate and maximise the utility of a comprehensive list of strategies for improvement of consultation skills through a process involving both medical students and their clinical primary and secondary care tutors. Modified Delphi study with tutors, modified nominal group study with students with moderation of outputs by consensus round table discussion by the authors. 35 hospital and 21 GP tutors participated in the Delphi study and contributed 153 new or modified strategies. After review of these and the 205 original strategies, 265 strategies entered the nominal group study to which 46 year four and five students contributed, resulting in the final list of 249 validated strategies. We have developed a valid and comprehensive set of strategies which are considered useful by medical students. This list can be immediately applied by any school which uses the Calgary Cambridge Framework to inform the content of formative feedback on consultation skills. We consider that the list could also be mapped to alternative skills frameworks and so be utilised by schools which do not use the Calgary Cambridge Framework.

Detection of vigilance performance using eye blinks.

Research has shown that sustained attention or vigilance declines over time on task. Sustained attention is necessary in many environments such as air traffic controllers, cyber operators, and imagery analysts. A lapse of attention in any one of these environments can have harmful consequences. The purpose of this study was to determine if eye blink metrics from an eye-tracker are related to changes in vigilance performance and cerebral blood flow velocities. Nineteen participants performed a vigilance task while wearing an eye-tracker on four separate days. Blink frequency and duration changed significantly over time during the task. Both blink frequency and duration increased as performance declined and right cerebral blood flow velocity declined. These results suggest that eye blink information may be an indicator of arousal levels. Using an eye-tracker to detect changes in eye blinks in an operational environment would allow preventative measures to be implemented, perhaps by providing perceptual warning signals or augmenting human cognition through non-invasive brain stimulation techniques.