1,504 research outputs found
Hedgehog Signalling in Androgen Independent Prostate Cancer
Objectives: Androgen-deprivation therapy effectively shrinks hormone-naĆÆve 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
Exchange of Higher Education Teaching and Learning Practices Between UK and Thailand: A Case Study of RailExchange Courses
The RailExchange project has been developed in collaboration between two universities, one UK-based and one Thailand-based, to work on educational ideas for rail to benefit the rail industry in Thailand. At the same time, a new rail Master programme has been designed with a strong input from the rail industry in terms of technical and interpersonal skills necessary for a formation of a successful rail graduate. The new programme has been established at the Thai university and aligned with Thai and international higher education frameworks (AUN-QA and TQF). As part of the activities listed in the exchange project, the lecturers from the UK have been invited to conduct short experimental classes to teach on three different subjects, which are part of the new rail Masterās curriculum. The paper presents feedback received from participants of the three courses in terms of learning activities, academic activities and personal experience. The analyses of the feedback reveal that the UK visiting lecturers helped in broadening the perspective of the Thai academics and students in terms of educational content and active learning style, such as a hands-on approach and applied learning style with real-life scenarios and student-led learning. The English language was used to deliver the experimental classes to Thai participants, who represented academia and industry, and for majority of the participants, it was not a barrier in actively participating in a course. Feedback received highlighted differences between the UK and Thai approaches to higher education learning, but also suggested improvements, listed in recommendations, which should be taken into account in the delivery of the Master programme in rail in the near future
Analysis of auditory functions in grades one, two, and three.
Thesis (Ed.M.)--Boston Universit
Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice
Purpose: Acute, severe asthma exacerbations can be difficult to predict and thus prevent. Patients who have frequent exacerbations are of particular concern. Practical exacerbation predictors are needed for these patients in the primary-care setting.Patients and methods: Medical records of 130,547 asthma patients aged 12ā80 years from the UK Optimum Patient Care Research Database and Clinical Practice Research Datalink, 1990ā2013, were examined for 1 year before (baseline) and 1 year after (outcome) their most recent blood eosinophil count. Baseline variables predictive (P<0.05) of exacerbation in the outcome year were compared between patients who had two or more exacerbations and those who had no exacerbation or only one exacerbation, using uni- and multivariable logistic regression models. Exacerbation was defined as asthma-related hospital attendance/admission (emergency or inpatient) or acute oral corticosteroid (OCS) course.Results: Blood eosinophil count >400/ĀµL (versus ?400/ĀµL) increased the likelihood of two or more exacerbations >1.4-fold (odds ratio [OR]: 1.48 (95% confidence interval [CI]: 1.39, 1.58); P<0.001). Variables that significantly increased the odds by up to 1.4-fold included increasing age (per year), female gender (versus male), being overweight or obese (versus normal body mass index), being a smoker (versus nonsmoker), having anxiety/depression, diabetes, eczema, gastroesophageal reflux disease, or rhinitis, and prescription for acetaminophen or nonsteroidal anti-inflammatory drugs. Compared with treatment at British Thoracic Society step 2 (daily controller Ā± reliever), treatment at step 0 (none) or 1 (as-needed reliever) increased the odds by 1.2- and 1.6-fold, respectively, and treatment at step 3, 4, or 5 increased the odds by 1.3-, 1.9-, or 3.1-fold, respectively (all P<0.05). Acute OCS use was the single best predictor of two or more exacerbations. Even one course increased the odds by more than threefold (OR: 3.75 [95% CI: 3.50, 4.01]; P<0.001), and three or more courses increased the odds by >25-fold (OR: 25.7 [95% CI: 23.9, 27.6]; P<0.001).Conclusion: Blood eosinophil count and several other variables routinely available in patient records may be used to predict frequent asthma exacerbations
The EvoDevoCI: A Concept Inventory for Gauging Studentsā Understanding of Evolutionary Developmental Biology
The American Association for the Advancement of Science 2011 report Vision and Change in Undergraduate Biology Education encourages the teaching of developmental biology as an important part of teaching evolution. Recently, however, we found that biology majors often lack the developmental knowledge needed to understand evolutionary developmental biology, or āevo-devo.ā To assist in efforts to improve evo-devo instruction among undergraduate biology majors, we designed a concept inventory (CI) for evolutionary developmental biology, the EvoDevoCI. The CI measures student understanding of six core evo-devo concepts using four scenarios and 11 multiple-choice items, all inspired by authentic scientific examples. Distracters were designed to represent the common conceptual difficulties students have with each evo-devo concept. The tool was validated by experts and administered at four institutions to 1191 students during preliminary (n = 652) and final (n = 539) field trials. We used student responses to evaluate the readability, difficulty, discriminability, validity, and reliability of the EvoDevoCI, which included items ranging in difficulty from 0.22ā0.55 and in discriminability from 0.19ā0.38. Such measures suggest the EvoDevoCI is an effective tool for assessing student understanding of evo-devo concepts and the prevalence of associated common conceptual difficulties among both novice and advanced undergraduate biology majors
The EvoDevoCI: A Concept Inventory for Gauging Studentsā Understanding of Evolutionary Developmental Biology
The American Association for the Advancement of Science 2011 report Vision and Change in Undergraduate Biology Education encourages the teaching of developmental biology as an important part of teaching evolution. Recently, however, we found that biology majors often lack the developmental knowledge needed to understand evolutionary developmental biology, or āevo-devo.ā To assist in efforts to improve evo-devo instruction among undergraduate biology majors, we designed a concept inventory (CI) for evolutionary developmental biology, the EvoDevoCI. The CI measures student understanding of six core evo-devo concepts using four scenarios and 11 multiple-choice items, all inspired by authentic scientific examples. Distracters were designed to represent the common conceptual difficulties students have with each evo-devo concept. The tool was validated by experts and administered at four institutions to 1191 students during preliminary (n = 652) and final (n = 539) field trials. We used student responses to evaluate the readability, difficulty, discriminability, validity, and reliability of the EvoDevoCI, which included items ranging in difficulty from 0.22ā0.55 and in discriminability from 0.19ā0.38. Such measures suggest the EvoDevoCI is an effective tool for assessing student understanding of evo-devo concepts and the prevalence of associated common conceptual difficulties among both novice and advanced undergraduate biology majors
Getting to Evo-Devo: Concepts and Challenges for Students Learning Evolutionary Developmental Biology
To examine how well biology majors have achieved the necessary foundation in evolution, numerous studies have examined how students learn natural selection. However, no studies to date have examined how students learn developmental aspects of evolution (evo-devo). Although evo-devo plays an increasing role in undergraduate biology curricula, we find that instruction often addresses development cursorily, with most of the treatment embedded within instruction on evolution. Based on results of surveys and interviews with students, we suggest that teaching core concepts (CCs) within a framework that integrates supporting concepts (SCs) from both evolutionary and developmental biology can improve evo-devo instruction. We articulate CCs, SCs, and foundational concepts (FCs) that provide an integrative framework to help students master evo-devo concepts and to help educators address specific conceptual difficulties their students have with evo-devo. We then identify the difficulties that undergraduates have with these concepts. Most of these difficulties are of two types: those that are ubiquitous among students in all areas of biology and those that stem from an inadequate understanding of FCs from developmental, cell, and molecular biology
The Genetic Drift Inventory: A Tool for Measuring What Advanced Undergraduates Have Mastered about Genetic Drift
Understanding genetic drift is crucial for a comprehensive understanding of biology, yet it is difficult to learn because it combines the conceptual challenges of both evolution and randomness. To help assess strategies for teaching genetic drift, we have developed and evaluated the Genetic Drift Inventory (GeDI), a concept inventory that measures upper-division studentsā understanding of this concept. We used an iterative approach that included extensive interviews and field tests involving 1723 students across five different undergraduate campuses. The GeDI consists of 22 agreeādisagree statements that assess four key concepts and six misconceptions. Student scores ranged from 4/22 to 22/22. Statements ranged in mean difficulty from 0.29 to 0.80 and in discrimination from 0.09 to 0.46. The internal consistency, as measured with Cronbach\u27s alpha, ranged from 0.58 to 0.88 across five iterations. Testāretest analysis resulted in a coefficient of stability of 0.82. The trueāfalse format means that the GeDI can test how well students grasp key concepts central to understanding genetic drift, while simultaneously testing for the presence of misconceptions that indicate an incomplete understanding of genetic drift. The insights gained from this testing will, over time, allow us to improve instruction about this key component of evolution
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