817 research outputs found

    Student outcomes from diverse undergraduate research experiences - findings from a multi-disciplinary study

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    Undergraduate research experiences (UREs) provide students with opportunities to engage in high impact experiential learning. UREs have been especially prevalent in the sciences, but there are now extensive banks of case studies demonstrating the use of UREs as an educationally enriching activity in nearly all disciplines. This study investigated the diversity of UREs available across a wide range of disciplines at a large Australian research-intensive university and examined the perceived benefits. Through group interviews with 68 academics, we gathered detailed information about 81 URE activities, across 28 Schools within the institution (representing 77.8% of Schools), ranging from archaeology to political science, from biology to social work and from law to journalism. The most common URE model observed was that of activities embedded in courses. Across disciplines the most common feature was the requirement for students to engage with the research literature in their field. A smaller number of models incorporated features which allowed students to engage in other high impact learning activities such as community-based activities and internships. Although we identified a large ‘set’ of perceived student outcomes across the varied URE models the generic graduate attributes attained by students through these UREs appeared to be independent of the discipline itself. In most cases, the UREs were available to all students rather than an elite or specialist cohort. This leads us to believe that across a range of disciplinary contexts, there are many ways to use UREs to achieve high levels of engagement of large cohorts of students

    Immunological and Clinical Effects of Vaccines Targeting p53-Overexpressing Malignancies

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    Approximately 50% of human malignancies carry p53 mutations, which makes it a potential antigenic target for cancer immunotherapy. Adoptive transfer with p53-specific cytotoxic T-lymphocytes (CTL) and CD4+ T-helper cells eradicates p53-overexpressing tumors in mice. Furthermore, p53 antibodies and p53-specific CTLs can be detected in cancer patients, indicating that p53 is immunogenic. Based on these results, clinical trials were initiated. In this paper, we review immunological and clinical responses observed in cancer patients vaccinated with p53 targeting vaccines. In most trials, p53-specific vaccine-induced immunological responses were observed. Unfortunately, no clinical responses with significant reduction of tumor-burden have occurred. We will elaborate on possible explanations for this lack of clinical effectiveness. In the second part of this paper, we summarize several immunopotentiating combination strategies suitable for clinical use. In our opinion, future p53-vaccine studies should focus on addition of these immunopotentiating regimens to achieve clinically effective therapeutic vaccination strategies for cancer patients

    Life at school in Australia and Japan: the impact of stress and support on bullying and adaptation to school

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    In this international, comparative study, path analysis was used to examine eight different aspects of Japanese and Australian students' experiences of school life in relation to their effect on adaptation to school. Adaptation was constructed to include information on enjoyment of school, feelings of belonging to school, and relationships with other students. Two separate path models were tested to compare questionnaire data from over 3000 Australian and 6000 Japanese students across Years 5-10. The questionnaire was developed collaboratively by the authors to examine issues of common concern in both countries. Issues that related to the impact on adaptation to school of stress and support: family teachers, peers and school work, as well as bullying were of particular interest. Lack of support and the influential effect of stress were found to exert direct negative effects on adaptation to school, especially for high school students in Japan and Australia. The path results also confirmed the stressful effects of bullying in both countries. The finding of a strong relationship between bullying others and being victimised is discussed in the paper. Finally, the differences and similarities between Japanese and Australian students' perceptions of school life are extrapolated

    Enhanced antitumour immunity following neoadjuvant chemoradiotherapy mediates a favourable prognosis in women with resected pancreatic cancer

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    Background This study investigates sex disparities in clinical outcomes and tumour immune profiles in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection preceded by gemcitabine-based neoadjuvant chemoradiotherapy (nCRT).Methods Patients originated from the PREOPANC randomised controlled trial. Upfront surgery was performed in 82 patients, and 66 received nCRT before resection. The impact of sex on overall survival (OS) was investigated using Cox proportional hazards models. The immunological landscape within the tumour microenvironment (TME) was mapped using transcriptomic and spatial proteomic profiling.Results The 5-year OS rate differed between the sexes following resection preceded by nCRT, with 43% for women compared with 22% for men. In multivariate analysis, the female sex was a favourable independent prognostic factor for OS only in the nCRT group (HR 0.19; 95% CI 0.07 to 0.52). Multivariate heterogeneous treatment effects analysis revealed a significant interaction between sex and treatment, implying increased nCRT efficacy among women with resected PDAC. The TME of women contained fewer protumoural CD163+MRC1+M2 macrophages than that of men after nCRT, as indicated by transcriptomic and validated using spatial proteomic profiling.Conclusion PDAC tumours of women are more sensitive to gemcitabine-based nCRT, resulting in longer OS after resection compared with men. This may be due to enhanced immunity impeding the infiltration of protumoral M2 macrophages into the TME. Our findings highlight the importance of considering sex disparities and mitigating immunosuppressive macrophage polarisation for personalised PDAC treatment

    Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

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    Background: Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods: We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results: We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m(2) with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions: We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation

    Prospects for high-z cluster detections with Planck, based on a follow-up of 28 candidates using MegaCam@CFHT

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    The Planck catalogue of SZ sources limits itself to a significance threshold of 4.5 to ensure a low contamination rate by false cluster candidates. This means that only the most massive clusters at redshift z>0.5, and in particular z>0.7, are expected to enter into the catalogue, with a large number of systems in that redshift regime being expected around and just below that threshold. In this paper, we follow-up a sample of SZ sources from the Planck SZ catalogues from 2013 and 2015. In the latter maps, we consider detections around and at lower significance than the threshold adopted by the Planck Collaboration. To keep the contamination rate low, our 28 candidates are chosen to have significant WISE detections, in combination with non-detections in SDSS/DSS, which effectively selects galaxy cluster candidates at redshifts z0.5z\gtrsim0.5. By taking r- and z-band imaging with MegaCam@CFHT, we bridge the 4000A rest-frame break over a significant redshift range, thus allowing accurate redshift estimates of red-sequence cluster galaxies up to z~0.8. After discussing the possibility that an overdensity of galaxies coincides -by chance- with a Planck SZ detection, we confirm that 16 of the candidates have likely optical counterparts to their SZ signals, 13 (6) of which have an estimated redshift z>0.5 (z>0.7). The richnesses of these systems are generally lower than expected given the halo masses estimated from the Planck maps. However, when we follow a simplistic model to correct for Eddington bias in the SZ halo mass proxy, the richnesses are consistent with a reference mass-richness relation established for clusters detected at higher significance. This illustrates the benefit of an optical follow-up, not only to obtain redshift estimates, but also to provide an independent mass proxy that is not based on the same data the clusters are detected with, and thus not subject to Eddington bias.Comment: 13 pages, 7 figures. Accepted for publication in A&

    Identification of major dioxin-like compounds and androgen receptor antagonist in acid-treated tissue extracts of high trophic-level animals

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    We evaluated the applicability of combining in vitro bioassays with instrument analyses to identify potential endocrine disrupting pollutants in sulfuric acid-treated extracts of liver and/or blubber of high trophic-level animals. Dioxin-like and androgen receptor (AR) antagonistic activities were observed in Baikal seals, common cormorants, raccoon dogs, and finless porpoises by using a panel of rat and human cell-based chemical-activated luciferase gene expression (CALUX) reporter gene bioassays. On the other hand, no activity was detected in estrogen receptor α (ERα)-, glucocorticoid receptor (GR)-, progesterone receptor (PR)-, and peroxisome proliferator-activated receptor γ2 (PPARγ2)-CALUX assays with the sample amount applied. All individual samples (n = 66) showed dioxin-like activity, with values ranging from 21 to 5500 pg CALUX-2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (TEQ)/g-lipid. Because dioxins are expected to be strong contributors to CALUX-TEQs, the median theoretical contribution of dioxins calculated from the result of chemical analysis to the experimental CALUX-TEQs was estimated to explain up to 130% for all the tested samples (n = 54). Baikal seal extracts (n = 31), but not other extracts, induced AR antagonistic activities that were 8-150 μg CALUX-flutamide equivalent (FluEQ)/g-lipid. p,p′-DDE was identified as an important causative compound for the activity, and its median theoretical contribution to the experimental CALUX-FluEQs was 59% for the tested Baikal seal tissues (n = 25). Our results demonstrate that combining in vitro CALUX assays with instrument analysis is useful for identifying persistent organic pollutant-like compounds in the tissue of wild animals on the basis of in vitro endocrine disruption toxicity. © 2011 American Chemical Society
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