Towards a formative assessment of classroom competencies (FACCs) for postgraduate medical trainees

Background An assumption of clinical competency is no longer acceptable or feasible in routine clinical practice. We sought to determine the feasibility, practicability and efficacy of undertaking a formal assessment of clinical competency for all postgraduate medical trainees in a large NHS foundation trust. Methods FY1 doctors were asked to complete a questionnaire to determine prior experience and self reported confidence in performing the GMC core competencies. From this a consensus panel of key partners considered and developed an 8 station Objective Structured Clinical Examination (OSCE) circuit to assess clinical competencies in all training grade medical staff... The OSCE was then administered to all training grade doctors as part of their NHS trust induction process. Results 106 (87.6% of all trainees) participated in the assessment during the first 14 days of appointment. Candidates achieved high median raw percentage scores for the majority of stations however analysis of pre defined critical errors and omissions identified important areas for concern. Performance of newly qualified FY1 doctor was significantly better than other grades for the arterial blood gas estimation and nasogastric tube insertion stations. Discussion Delivering a formal classroom assessment of clinical competencies to all trainees as part of the induction process was both feasible and useful. The assessment identified areas of concern for future training and also served to reassure as to the proficiency of trainees in undertaking the majority of core competencies

Perspectives: Entrepreneurship Training Can Empower Students Being Left Behind

Entrepreneurial self-employment, however, would hold great promise for business-minded students, if they learn entrepreneurship in high school and can test out their innovative business plans on consumers in their own neighborhoods and beyond — especially Internet start-up ideas. The social and community networking success of MySpace opens a wide door for anyone to market a new idea or product to a myriad of potential customers instantly

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema

A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unrelated donor SCT, or autologous SCT. Blood samples were taken following conditioning and prior to transplant on day 0 and the plasma was comprehensively characterized with respect to its lipidome and metabolome via liquid chromatography/mass spectrometry (LCMS) and gas chromatography/mass spectrometry (GCMS). A pro-inflammatory metabolic profile was observed in patients who eventually developed GVHD. Five potential pre-transplant biomarkers, 2-aminobutyric acid, 1-monopalmitin, diacylglycerols (DG 38:5, DG 38:6), and fatty acid FA 20:1 demonstrated high sensitivity and specificity towards predicting post-transplant GVHD. The resulting predictive model demonstrated an estimated predictive accuracy of risk stratification of 100%, with area under the curve of the ROC of 0.995. The likelihood ratio of 1-monopalmitin (infinity), DG 38:5 (6.0), and DG 38:6 (6.0) also demonstrated that a patient with a positive test result for these biomarkers following conditioning and prior to transplant will be at risk of developing GVHD. Collectively, the data suggest the possibility that pre-transplant metabolic signature may be used for risk stratification of SCT recipients with respect to development of alloreactivity

Which imaging modality is superior for prediction of response to neoadjuvant chemotherapy in patients with triple negative breast cancer?

Background and Objectives. Triple negative breast cancer (TNBC) has been shown to be generally chemosensitive. We sought to investigate the utility of mammography (MMG), ultrasonography (US), and breast magnetic resonance imaging (MRI) in predicting residual disease following neoadjuvant chemotherapy for TNBC. Methods. We identified 148 patients with 151 Stage I–III TNBC treated with neoadjuvant chemotherapy. Residual tumor size was estimated by MMG, US, and/or MRI prior to surgical intervention and compared to the subsequent pathologic residual tumor size. Data were compared using chi-squared test. Results. Of 151 tumors, 44 (29%) did not have imaging performed prior to surgical treatment. Thirty-eight (25%) tumors underwent a pathologic complete response (pCR), while 113 (75%) had residual invasive disease. The imaging modality was accurate to within 1 cm of the final pathologic residual disease in 74 (69%) cases and within 2 cm in 94 (88%) cases. Groups were similar with regards to patient age, race, tumor size and grade, and clinical stage (). Accuracy to within 1 cm was the highest for US (83%) and the lowest for MMG (56%) (). Conclusions. Breast US and MRI were more accurate than MMG in predicting residual tumor size following neoadjuvant chemotherapy in patients with TNBC. None of the imaging modalities were predictive of a pCR

Validation of a New Predictive Risk Model: Measuring the Impact of the Major Modifiable Risks of Death for Patients and Populations

Background: Modifiable risks account for a large fraction of disease and death, but clinicians and patients lack tools to identify high risk populations or compare the possible benefit of different interventions. Methods: We used data on the distribution of exposure to 12 major behavioral and biometric risk factors inthe US population, mortality rates by cause, and estimates of the proportional hazards of risk factor exposure from published systematic reviews to develop a risk prediction model that estimates an adult\u27s 10 year mortality risk compared to a population with optimum risk factors. We compared predicted risk to observed mortality in 8,241 respondents in NHANES 1988-1994 and NHANES 1999-2004 with linked mortality data up to the end of 2006

Is stroke early supported discharge still effective in practice? A prospective comparative study

Objective: Randomised controlled trials have shown the benefits of Early Supported Discharge (ESD) of stroke survivors. Our aim was to evaluate whether ESD is still beneficial when operating in the complex context of frontline healthcare provision. Design: We conducted a cohort study with quasi experimental design. A total of 293 stroke survivors (transfer independently or with assistance of one, identified rehabilitation goals) within two naturally formed groups were recruited from two acute stroke units: ‘ESD’ n=135 and ‘Non ESD’ n=158 and 84 caregivers. The ‘ESD’ group accessed either of two ESD services operating in Nottinghamshire, UK. The ‘Non ESD’ group experienced standard practices for discharge and onward referral. Outcome measures (primary: Barthel Index) were administered at baseline, 6 weeks, 6 months and 12 months. Results: The ESD group had a significantly shorter length of hospital stay (P=0.029) and reported significantly higher levels of satisfaction with services received (P<0.001). Following adjustment for age differences at baseline, participants in the ESD group (n=71) had significantly higher odds (compared to the Non ESD group, n=85) of being in the ⩾90 Barthel Index category at 6 weeks (OR = 1.557, 95% CI 2.579 to 8.733), 6 months (OR = 1.541, 95% CI 2.617 to 8.340) and 12 months (OR 0.837, 95% CI 1.306 to 4.087) respectively in relation to baseline. Carers of patients accessing ESD services showed significant improvement in mental health scores (P<0.01). Conclusion: The health benefits of ESD are still evident when evidence based models of these services are implemented in practice

NUVA: A Naming Utterance Verifier for Aphasia Treatment

Anomia (word-finding difficulties) is the hallmark of aphasia, an acquired language disorder most commonly caused by stroke. Assessment of speech performance using picture naming tasks is a key method for both diagnosis and monitoring of responses to treatment interventions by people with aphasia (PWA). Currently, this assessment is conducted manually by speech and language therapists (SLT). Surprisingly, despite advancements in automatic speech recognition (ASR) and artificial intelligence with technologies like deep learning, research on developing automated systems for this task has been scarce. Here we present NUVA, an utterance verification system incorporating a deep learning element that classifies 'correct' versus' incorrect' naming attempts from aphasic stroke patients. When tested on eight native British-English speaking PWA the system's performance accuracy ranged between 83.6% to 93.6%, with a 10-fold cross-validation mean of 89.5%. This performance was not only significantly better than a baseline created for this study using one of the leading commercially available ASRs (Google speech-to-text service) but also comparable in some instances with two independent SLT ratings for the same dataset

Mapping the structural path for allosteric inhibition of a short-form ATP phosphoribosyltransferase by histidine

Funding: This work was supported by a Wellcome Trust Institutional Strategic Support Fund to the University of St Andrews and the Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BB/M010996/1] via an EASTBIO Doctoral Training Partnership studentship to GF. X-ray diffraction data were collected at Diamond Light Source in the UK.ATP phosphoribosyltransferase (ATPPRT) catalyses the first step of histidine biosynthesis, being allosterically inhibited by the final product of the pathway. Allosteric inhibition of long-form ATPPRTs by histidine has been extensively studied, but inhibition of short-form ATPPRTs is poorly understood. Short-form ATPPRTs are hetero-octamers formed by four catalytic subunits (HisGS) and four regulatory subunits (HisZ). HisGS alone is catalytically active and insensitive to histidine. HisZ enhances catalysis by HisGS in the absence of histidine but mediates allosteric inhibition in its presence. Here, steady-state and pre-steady-state kinetics establish that histidine is a non-competitive inhibitor of short-form ATPPRT, and that inhibition does not occur by dissociating HisGS from the hetero-octamer. The crystal structure of ATPPRT in complex with histidine and the substrate 5-phospho-α-D-ribosyl-1-pyrophosphate (PRPP) was solved, showing histidine bound solely to HisZ, with four histidine molecules per hetero-octamer. Histidine binding involves the repositioning of two HisZ loops. The histidine-binding loop moves closer to histidine to establish polar contacts. This leads to a hydrogen bond between its Tyr263 and His104 in the Asp101–Leu117 loop. The Asp101–Leu117 loop leads to the HisZ/HisGS interface, and in the absence of histidine its motion prompts HisGS conformational changes responsible for catalytic activation. Following histidine binding, interaction with the histidine-binding loop may prevent the Asp101–Leu117 loop from efficiently sampling conformations conducive to catalytic activation. Tyr263Phe-PaHisZ-containing PaATPPRT, however, is less susceptible though not insensitive to histidine inhibition, suggesting the Tyr263-His104 interaction may be relevant to, yet not solely responsible for transmission of the allosteric signal.Publisher PDFPeer reviewe