Can Monkeys (Macaca mulatta) Represent Invisible Displacement?

Four experiments were conducted to assess whether or not rhesus macaques (Macaca mulatta) could represent the unperceived movements of a stimulus. Subjects were tested on 2 computerized tasks, HOLE (monkeys) and LASER (humans and monkeys), in which subjects needed to chase or shoot at, respectively, a moving target that either remained visible or became invisible for a portion of its path of movement. Response patterns were analyzed and compared between target-visible and target-invisible conditions. Results of Experiments 1, 2, and 3 demonstrated that the monkeys are capable of extrapolating movement. That this extrapolation involved internal representation of the target's invisible movement was suggested but not confirmed. Experiment 4, however, demonstrated that the monkeys are capable of representing the invisible displacements of a stimulus

p21WAF1/CIP1 Upregulation through the Stress Granule-Associated Protein CUGBP1 Confers Resistance to Bortezomib-Mediated Apoptosis

p21(WAF1/CIP1) is a well known cyclin-dependent kinase inhibitor induced by various stress stimuli. Depending on the stress applied, p21 upregulation can either promote apoptosis or prevent against apoptotic injury. The stress-mediated induction of p21 involves not only its transcriptional activation but also its posttranscriptional regulation, mainly through stabilization of p21 mRNA levels. We have previously reported that the proteasome inhibitor MG132 induces the stabilization of p21 mRNA, which correlates with the formation of cytoplasmic RNA stress granules. The mechanism underlying p21 mRNA stabilization, however, remains unknown.We identified the stress granules component CUGBP1 as a factor required for p21 mRNA stabilization following treatment with bortezomib ( =  PS-341/Velcade). This peptide boronate inhibitor of the 26S proteasome is very efficient for the treatment of myelomas and other hematological tumors. However, solid tumors are sometimes refractory to bortezomib treatment. We found that depleting CUGBP1 in cancer cells prevents bortezomib-mediated p21 upregulation. FISH experiments combined to mRNA stability assays show that this effect is largely due to a mistargeting of p21 mRNA in stress granules leading to its degradation. Altering the expression of p21 itself, either by depleting CUGBP1 or p21, promotes bortezomib-mediated apoptosis.We propose that one key mechanism by which apoptosis is inhibited upon treatment with chemotherapeutic drugs might involve upregulation of the p21 protein through CUGBP1

Student-led development and evaluation of a community pharmacy-based cardiovascular risk assessment

Robert Gordon Universitys key strength is employability (reflecting close liaison with the professions) and courses must therefore offer opportunities for work-based learning, which can be challenging in the current financial climate. This is a particular problem for Pharmacy: opportunities for placement are extremely limited and tend to be focused on the later years of the course. This late and limited exposure to practice is thought to be responsible for significant failures in the ability of students and newly-qualified pharmacists to take their knowledge of science and medicines and apply it in the context of solving clinical problems. Furthermore, a lack of engagement with practice makes it difficult for the theoretical learning (especially the underpinning science) to be effectively contextualised, leading to an artificial segregation of the science and practice sections of the course. While pharmacists must be technically capable, success depends on a broader range of non-technical skills, including communication and empathy as well the ability to deal with the unexpected. Simulation is used as a partial alternative to the practice environment, but there are often vast differences between these highly-managed scenarios and the real situations encountered in practice. Since there is no ideal setting for a pharmacist, students should be educated and trained with an understanding, at the forefront of their minds, of human factors - something which challenges existing course design. Teaching and learning activities must allow students to explore the differences between the ideal and real clinical environments and to recognise when deviations from the ideal are likely to affect patient safety. This paper discusses a piece of action research by MPharm undergraduate students, exploring ways in which such activities may be developed. These new activities are based upon an existing cardiovascular risk assessment, currently used to deliver scientific theory and develop technical skills, and involving the identification of modifiable and non-modifiable risk factors and the use of these to calculate the ten-year risk of cardiovascular disease.The approach involved the building of two simulated scenarios, one representing an ideal risk assessment and the other reflecting adverse outcomes arising as a result of practice-based problems. Developing the simulations required an in-depth analysis of factors contributing to outcomes, and a combination of interviews with healthcare professionals and peer-peer focus groups were used to explore this. This paper discusses the challenges and learning points arising from this work, as well as an evaluation of the ways in which the work was used to enhance teaching in the academic session 2013-14

Tumor volume-adapted dosing in stereotactic ablative radiotherapy of lung tumors.

PURPOSE: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. METHODS AND MATERIALS: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume \u3c12 \u3emL) received single-fraction regimens with biologically effective doses (BED)(total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume ≥12 mL) received multifraction regimens with BED ≥100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2). RESULTS: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). CONCLUSION: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity