8,480 research outputs found

    Curated Collections for Educators: Eight Key Papers about Feedback in Medical Education

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    Feedback is an essential part of learning, growth, and academic success. Junior faculty members are often unfamiliar with the grounding literature that defines feedback. Many times they receive little education on providing and receiving feedback, resulting in unhelpful "feedback" for both learners and program leadership alike. This article aims to summarize eight key papers on feedback, to outline relevant information for emerging clinician educators, and identify ways to use these resources for the faculty development. In order to generate a list of key papers that describes the importance and significance of feedback, the authors conducted a consensus-building process to identify the top papers. In August and September, 2018, the 2018-2019 Academic Life in Emergency Medicine (ALiEM) Faculty Incubator program discussed the topic of feedback in medical education. A number of papers on the topic was highlighted. This list of papers was further augmented using the suggestions and expertise of guest experts who are leaders in the field of medical education and feedback. The authors also used social media to conduct an open call on Twitter for important papers regarding feedback (utilizing #meded, #Feedback hashtags). Via this process, a list of 88 key papers was identified on the topic of feedback in medical education. After compiling these papers, the authorship group engaged in a modified Delphi approach to build consensus on the top eight papers on feedback. These papers were deemed essential by the authors and have been summarized with respect to their relevance to junior faculty members and to faculty developers. In this manuscript, we present eight key papers addressing feedback in medical education with discussions and applications for junior faculty members and faculty developers. This list of articles that can serve to help junior clinician educators grow in their ability to give effective feedback and also serve as resources upon which senior faculty can design the faculty development sessions

    Inhibition of androgen-independent prostate cancer cell growth is enhanced by combination therapy targeting Hedgehog and ErbB signalling

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    <p>Abstract</p> <p>Background</p> <p>Prostate cancer is a leading cause of male cancer specific mortality. When cure by radical prostatectomy is not possible the next line of prostate cancer treatment is androgen deprivation. However prolonged androgen deprivation often results in relapse and androgen-independent prostate cancer that is inevitably fatal despite optimal chemotherapy. The Hedgehog signalling pathway has recently been implicated in prostate cancer development and metastasis. EGFR or ErbB2 expression has been also correlated with androgen independence, shorter survival and metastasis.</p> <p>Results</p> <p>We determined that the Hedgehog and ErbB signalling pathways are active in circulating tumour cells isolated from androgen-independent prostate cancer patients and in the androgen-independent prostate cancer cell line LNCaP C4-2B. As a basis for synergistic chemotherapy protocols combinations of the Hedgehog specific inhibitor cyclopamine and the ErbB signalling inhibitors gefitinib or lapatinib were tested in this study. Androgen-independent prostate cancer cell growth was inhibited by a SMO inhibitor (cyclopamine) which blocks Hedgehog signalling and by ErbB inhibitors (gefitinib and lapatinib). The isobologram and combination index method of Chou and Talalay was used to evaluate drug interactions. Synergistic antiproliferation effects were observed when the Hedgehog and ErbB inhibitors were combined.</p> <p>Conclusion</p> <p>Androgen-independent prostate cancer cell proliferation was associated with activity of the Hedgehog and ErbB signalling pathways. Cyclopamine, gefitinib or lapatinib treatment significantly decreased the proliferation of androgen-independent prostate cancer cells. The Hedgehog pathway therefore represents a promising new therapeutic target in androgen-independent prostate cancer. Synergistic effects were observed when Hedgehog and ErbB inhibitors were used together. This study may have clinical implications for improving the treatment of advanced prostate cancer.</p

    Sea-level variations at Iceland and Bermuda

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    Data from tide gauges at Iceland and Bermuda combined with data on atmospheric pressure at both stations plus hydrographic serial observations at Bermuda are utilized to analyze sea-level variations in both regions. Residual sea-level anomalies (raw sea-level anomaly minus barometric and steric effects) are computed and discussed for Bermuda. The analysis, which indicates a periodicity of four months, is regarded as very tentative...

    Perfluorocarbon Enhanced Glasgow Oxygen Level Dependent (GOLD) magnetic resonance metabolic imaging identifies the penumbra following acute ischemic stroke

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    The ability to identify metabolically active and potentially salvageable ischaemic penumbra is crucial for improving treatment decisions in acute stroke patients. Our solution involves two complementary novel MRI techniques (Glasgow Oxygen Level Dependant (GOLD) Metabolic Imaging), which when combined with a perfluorocarbon (PFC) based oxygen carrier and hyperoxia can identify penumbra due to dynamic changes related to continued metabolism within this tissue compartment. Our aims were (i) to investigate whether PFC offers similar enhancement of the second technique (Lactate Change) as previously demonstrated for the T2*OC technique (ii) to demonstrate both GOLD metabolic imaging techniques working concurrently to identify penumbra, following administration of Oxycyte® (O-PFC) with hyperoxia. Methods: An established rat stroke model was utilised. Part-1: Following either saline or PFC, magnetic resonance spectroscopy was applied to investigate the effect of hyperoxia on lactate change in presumed penumbra. Part-2; rats received O-PFC prior to T2*OC (technique 1) and MR spectroscopic imaging, which was used to identify regions of tissue lactate change (technique 2) in response to hyperoxia. In order to validate the techniques, imaging was followed by [14C]2-deoxyglucose autoradiography to correlate tissue metabolic status to areas identified as penumbra. Results: Part-1: PFC+hyperoxia resulted in an enhanced reduction of lactate in the penumbra when compared to saline+hyperoxia. Part-2: Regions of brain tissue identified as potential penumbra by both GOLD metabolic imaging techniques utilising O-PFC, demonstrated maintained glucose metabolism as compared to adjacent core tissue. Conclusion: For the first time in vivo, enhancement of both GOLD metabolic imaging techniques has been demonstrated following intravenous O-PFC+hyperoxia to identify ischaemic penumbra. We have also presented preliminary evidence of the potential therapeutic benefit offered by O-PFC. These unique theranostic applications would enable treatment based on metabolic status of the brain tissue, independent of time from stroke onset, leading to increased uptake and safer use of currently available treatment options

    Mitofusins and OPA1 Mediate Sequential Steps in Mitochondrial Membrane Fusion

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    Mitochondrial fusion requires the coordinated fusion of the outer and inner membranes. Three large GTPases—OPA1 and the mitofusins Mfn1 and Mfn2—are essential for the fusion of mammalian mitochondria. OPA1 is mutated in dominant optic atrophy, a neurodegenerative disease of the optic nerve. In yeast, the OPA1 ortholog Mgm1 is required for inner membrane fusion in vitro; nevertheless, yeast lacking Mgm1 show neither outer nor inner membrane fusion in vivo, because of the tight coupling between these two processes. We find that outer membrane fusion can be readily visualized in OPA1-null mouse cells in vivo, but these events do not progress to inner membrane fusion. Similar defects are found in cells lacking prohibitins, which are required for proper OPA1 processing. In contrast, double Mfn-null cells show neither outer nor inner membrane fusion. Mitochondria in OPA1-null cells often contain multiple matrix compartments bounded together by a single outer membrane, consistent with uncoupling of outer versus inner membrane fusion. In addition, unlike mitofusins and yeast Mgm1, OPA1 is not required on adjacent mitochondria to mediate membrane fusion. These results indicate that mammalian mitofusins and OPA1 mediate distinct sequential fusion steps that are readily uncoupled, in contrast to the situation in yeast

    Transatlantic Issues: Report from Scotland

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    Several bioethical topics received a great deal of news coverage here in Scotland in 2009. Three important issues with transatlantic connections are the swine flu outbreak, which was handled very differently in Scotland, England, and America; the U.S. debate over healthcare reform, which drew the British National Health Service (NHS) into the controversy; and the release to Libya of the Lockerbie bomber, which at first glance might not seem particularly bioethical, but which actually hinged on the very public discussion of the prisoner’s medical records. On a national level, there have been attempts in both Scotland and England to change the law on assisted suicide, where success looks more likely than ever. This paper discusses each of these issues and hopefully will raise awareness of how these issues were dealt with in the United Kingdom and its component countries

    Hedgehog Signalling in Androgen Independent Prostate Cancer

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    Objectives: Androgen-deprivation therapy effectively shrinks hormone-naïve prostate cancer, both in the prostate and at sites of distant metastasis. However prolonged androgen deprivation generally results in relapse and androgen-independent tumour growth, which is inevitably fatal. The molecular events that enable prostate cancer cells to proliferate in reduced androgen conditions are poorly understood. Here we investigate the role of Hedgehog signalling in androgen-independent prostate cancer (AIPC). Methods: Activity of the Hedgehog signalling pathway was analysed in cultured prostate cancer cells, and circulating prostate tumour cells were isolated from blood samples of patients with AIPC. Results: AIPC cells were derived through prolonged culture in reduced androgen conditions, modelling hormone therapy in patients, and expressed increased levels of Hedgehog signalling proteins. Exposure of cultured AIPC cells to cyclopamine, which inhibits Hedgehog signalling, resulted in inhibition of cancer cell growth. The expression of the Hedgehog receptor PTCH and the highly prostate cancer-specific gene DD3PCA3 was significantly higher in circulating prostate cancer cells isolated from patients with AIPC compared with samples prepared from normal individuals. There was an association between PTCH and DD3PCA3 expression and the length of androgen-ablation therapy. Conclusions: Our data are consistent with reports implicating overactivity of Hedgehog signalling in prostate cancer and suggest that Hedgehog signalling contributes to the androgen-independent growth of prostate cancer cells. As systemic anti-Hedgehog medicines are developed, the Hedgehog pathway will become a potential new therapeutic target in advanced prostate cancer.Peer reviewedFinal Accepted Versio

    Epidemic spreading in evolving networks

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    A model for epidemic spreading on rewiring networks is introduced and analyzed for the case of scale free steady state networks. It is found that contrary to what one would have naively expected, the rewiring process typically tends to suppress epidemic spreading. In particular it is found that as in static networks, rewiring networks with degree distribution exponent γ>3\gamma >3 exhibit a threshold in the infection rate below which epidemics die out in the steady state. However the threshold is higher in the rewiring case. For 2<γ≤32<\gamma \leq 3 no such threshold exists, but for small infection rate the steady state density of infected nodes (prevalence) is smaller for rewiring networks.Comment: 7 pages, 7 figure

    International study into the use of intermittent hormone therapy in the treatment of carcinoma of the prostate : A meta-analysis of 1446 patients

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    OBJECTIVE: To review pooled phase II data to identify features of different regimens of intermittent hormone therapy (IHT), developed to reduce the morbidity of treating metastatic prostate cancer, and which carries a theoretical advantage of delaying the onset of androgen-independent prostate cancer, (AIPC) that are associated with success, highlighting features which require exploration with prospective trials to establish the best strategies for using this treatment. METHODS: Individual data were collated on 1446 patients with adequate information, from 10 phase II studies with >50 cases, identified through Pubmed. RESULTS: Univariate and multivariate Cox proportional hazard models were developed to predict treatment success with a high degree of statistical success. The prostate-specific antigen (PSA) nadir, the PSA threshold to restart treatment, and medication type and duration, were important predictors of outcome. CONCLUSIONS: The duration of biochemical remission after a period of HT is a durable early indicator of how rapidly AIPC and death will occur, and will make a useful endpoint in future trials to investigate the best ways to use IHT based on the important treatment cycling variables described above. Patients spent a mean of 39% of the time off treatment. The initial PSA level and PSA nadir allow the identification of patients with prostate cancer in whom it might be possible to avoid radical therapy.Peer reviewe
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