Assessment innovation and student experience: a new assessment challenge and call for a multi-perspective approach to assessment research

The impact of innovative assessment on student experience in higher education is a neglected research topic. This represents an important gap in the literature given debate around the marketization of higher education, international focus on student satisfaction measurement tools and political calls to put students at the heart of higher education in the UK. This paper reports on qualitative findings from a research project examining the impact of assessment preferences and familiarity on student attainment and experience. It argues that innovation is defined by the student, shaped by diverse assessment experiences and preferences and therefore its impact is difficult to predict. It proposes that future innovations must explore assessment choice mechanisms which allow students to shape their own assessments. Cultural change and staff development will be required to achieve this. To be accepted, assessment for student experience must be viewed as a complementary layer within a complex multi perspective model of assessment which also embraces assessment of learning, assessment for learning and assessment for life long learning. Further research is required to build a meta theory of assessment to enhance the synergies between these alternative approaches and to minimise tensions between them

A kinetic model of single and clustered IP3 receptors in the absence of Ca2+ feedback

Ca2+ liberation through inositol 1,4,5- trisphosphate receptor (IP3R) channels generates complex patterns of spatiotemporal cellularCa(2+) signals owing to the biphasic modulation of channel gating by Ca2+ itself. These processes have been extensively studied in Xenopus oocytes, where imaging studies have revealed local Ca2+ signals ("puffs'') arising from clusters of IP3R, and patch-clamp studies on isolated oocyte nuclei have yielded extensive data on IP3R gating kinetics. To bridge these two levels of experimental data, we developed an IP3R model and applied stochastic simulation and transition matrix theory to predict the behavior of individual and clustered IP(3)Rchannels. The channel model consists of four identical, independent subunits, each of which has an IP3- binding site together with one activating and one inactivating Ca2+- binding site. The channel opens when at least three subunits undergo a conformational change to an "active'' state after binding IP3 and Ca2+. The model successfully reproduces patch- clamp data; including the dependence of open probability, mean open duration, and mean closed duration on [IP3] and [Ca2+]. Notably, the biexponential distribution of open- time duration and the dependence of mean open time on [Ca2+] are explained by populations of openings involving either three or four active subunits. As a. rst step toward applying the single IP3R model to describe cellular responses, we then simulated measurements of puff latency after step increases of [IP3]. Assuming that stochastic opening of a single IP3R at basal cytosolic [Ca2+] and any given [IP3] has a high probability of rapidly triggering neighboring channels by calcium- induced calcium release to evoke a puff, optimal correspondence with experimental data of puff latencies after photorelease of IP3 was obtained when the cluster contained a total of 40 - 70 IP(3)Rs

The mitochondrial Ca2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation

Introduction: The mitochondrial uniporter (MCU) Ca2+ ion channel represents the primary means for Ca2+ uptake by mitochondria. Mitochondrial matrix Ca2+ plays critical roles in mitochondrial bioenergetics by impinging upon respiration, energy production and flux of biochemical intermediates through the TCA cycle. Inhibition of MCU in oncogenic cell lines results in an energetic crisis and reduced cell proliferation unless media is supplemented with nucleosides, pyruvate or α-KG. Nevertheless, the roles of MCU-mediated Ca2+ influx in cancer cells remain unclear, in part because of a lack of genetic models.Methods: MCU was genetically deleted in transformed murine fibroblasts for study in vitro and in vivo. Tumor formation and growth were studied in murine xenograft models. Proliferation, cell invasion, spheroid formation and cell cycle progression were measured in vitro. The effects of MCU deletion on survival and cell-death were determined by probing for live/death markers. Mitochondrial bioenergetics were studied by measuring mitochondrial matrix Ca2+ concentration, membrane potential, global dehydrogenase activity, respiration, ROS production and inactivating-phosphorylation of pyruvate dehydrogenase. The effects of MCU rescue on metabolism were examined by tracing of glucose and glutamine utilization for fueling of mitochondrial respiration.Results: Transformation of primary fibroblasts in vitro was associated with increased MCU expression, enhanced MCU-mediated Ca2+ uptake, altered mitochondrial matrix Ca2+ concentration responses to agonist stimulation, suppression of inactivating-phosphorylation of pyruvate dehydrogenase and a modest increase of mitochondrial respiration. Genetic MCU deletion inhibited growth of HEK293T cells and transformed fibroblasts in mouse xenograft models, associated with reduced proliferation and delayed cell-cycle progression. MCU deletion inhibited cancer stem cell-like spheroid formation and cell invasion in vitro, both predictors of metastatic potential. Surprisingly, mitochondrial matrix [Ca2+], membrane potential, global dehydrogenase activity, respiration and ROS production were unaffected. In contrast, MCU deletion elevated glycolysis and glutaminolysis, strongly sensitized cell proliferation to glucose and glutamine limitation, and altered agonist-induced cytoplasmic Ca2+ signals.Conclusion: Our results reveal a dependence of tumorigenesis on MCU, mediated by a reliance on MCU for cell metabolism and Ca2+ dynamics necessary for cell-cycle progression and cell proliferation

Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer

BACKGROUND: Drug resistance in breast cancer is a major obstacle to successful chemotherapy. In this study we used cDNA microarray technology to examine gene expression profiles obtained from fine needle aspiration (FNA) of primary breast tumors before and after systemic chemotherapy. Our goal was to determine the feasibility of obtaining representative expression array profiles from limited amounts of tissue and to identify those expression profiles that correlate with treatment response. METHODS: Repeat presurgical FNA samples were taken from six patients who were to undergo primary surgical treatment. Additionally, a group of 10 patients who were to receive neoadjuvant chemotherapy underwent two FNAs before chemotherapy (adriamycin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)) followed by another FNA on day 21 after the first cycle. Total RNA was amplified with T7 Eberwine's procedure and labeled cDNA was hybridized onto a 7600-feature glass cDNA microarray. RESULTS: We identified candidate gene expression profiles that might distinguish tumors with complete response to chemotherapy from tumors that do not respond, and found that the number of genes that change after one cycle of chemotherapy was 10 times greater in the responding group than in the non-responding group. CONCLUSION: This study supports the suitability of FNA-derived cDNA microarray expression profiling of breast cancers as a comprehensive genomic approach for studying the mechanisms of drug resistance. Our findings also demonstrate the potential of monitoring post-chemotherapy changes in expression profiles as a measure of pharmacodynamic effect and suggests that these approaches might yield useful results when validated by larger studies

The epidemiology of polymyalgia rheumatica in primary care: a research protocol

BACKGROUND: Polymyalgia Rheumatica (PMR) is the commonest inflammatory condition seen in older patients in primary care. To date, however, research has been focused on secondary care cohorts rather than primary care where many patients are exclusively managed. This two year prospective inception cohort study of PMR patients will enable us to understand the full spectrum of this condition. METHODS: Patients diagnosed with PMR in primary care will be identified via Read codes and mailed a series of postal questionnaires over a two-year period to assess their levels of pain, stiffness and functioning, as well as medication usage and other health-related and socio-demographic characteristics. In addition, participants will be asked for permission to link their survey data to their general practice electronic medical record and to national mortality and cancer registers. DISCUSSION: This will be the first large-scale, prospective, observational cohort of PMR patients in primary care. The combination of survey data with medical records and national registers will allow for a full investigation of the natural history and prognosis of this condition in the primary care setting, in which the majority of patients are treated, but where little research on the treatment and outcome of consultation has been undertaken. This will provide information that may lead to improved primary care management of PMR

Sprouty Proteins Inhibit Receptor-mediated Activation of Phosphatidylinositol-specific Phospholipase C

PLCγ03B3 binds Spry1 and Spry2. Overexpression of Spry decreased PLCγ03B3 activity and IP3 and DAG production, whereas Spry-deficient cells yielded more IP3. Spry overexpression inhibited T-cell receptor signaling and Spry1 null T-cells hyperproliferated with TCR ligation. Through action of PLCγ03B3, Spry may influence signaling through multiple receptors

The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours

Little literature exists on the safety of early pregnancy following chemotherapy. Here we assess the rate of relapse and foetal outcome in women who have completed single and multi-agent chemotherapy for gestational trophoblastic tumours. The records of 1532 patients treated for persistent gestational trophoblastic tumours at Charing Cross Hospital between 1969 and 1998 were reviewed. Patients were defined as receiving single agent or multi-agent treatment. Relapse rates and foetal outcome were reviewed in the 230 patients who became pregnant within 12 months of completing chemotherapy. In the single agent group 153 (22%) of 691 patients conceived early. Three subsequently relapsed. In the multi-agent group, 77 (10%) of 779 patients conceived early, two then relapsed. Relapse rates were 2% (3 out of 153) and 2.5% (2 out of 77) for each group compared to 5% and 5.6% in the comparative non-pregnant groups. Outcomes of 230 early pregnancies: 164 (71%) delivered at full term, 35 (15%) terminations, 26 (11%) spontaneous abortions, three (1.3%) new hydatidiform moles and two (1%) stillbirths. Early pregnancies were more common in the single agent group (P<0.001), but spontaneous miscarriages and terminations were more likely to occur in the multi-agent group (P=0.04 and 0.03, respectively). Of the full-term pregnancies, three (1.8%) babies were born with congenital abnormalities. Patients in either group who conceive within 12 months of completing chemotherapy are not at increased risk of relapse. Though, we still advise avoiding pregnancy within 12 months of completing chemotherapy, those that do conceive can be reassured of a likely favourable outcome

The acute effects of plyometric and sled towing stimuli with and without caffeine ingestion on vertical jump performance in professional soccer players

Abstract Background Post-activation potentiation (PAP) is the phenomenon by which muscular performance is enhanced in response to a conditioning stimulus. PAP has typically been evidenced via improved counter movement jump (CMJ) performance. This study examined the effects of PAP, with and without prior caffeine ingestion, on CMJ performance. Methods Twelve male professional soccer players (23 ± 5 years) performed two trials of plyometric exercises and sled towing 60 min after placebo or caffeine ingestion (5 mg.kg− 1) in a randomized, counterbalanced and double-blinded design. CMJ performance was assessed at baseline and 1, 3 and 5 min after the conditioning stimulus (T1, T3 and T5, respectively). Results Two way ANOVA main effects indicated a significant difference in jump height after the PAP protocol (F[3, 11] = 14.99, P  0.05) compared to placebo. Conclusions The results of this study suggest that acute plyometric and sled towing stimuli enhances jump performance and that this potentiation is augmented by caffeine ingestion in male soccer players

The Global Ambitions of Irish Universities: Internationalizing Practices and Emerging Stratification in the Irish Higher Education Sector

As higher education is increasingly harnessed to national economic goals and as funding shifts from public to private sources, Irish universities are under unprecedented pressure to “internationalize.” Yet the way they mediate national policy is constrained by funding and market forces as well as by their own organizational features and position in the field. Analysis of bilateral non-EU partnerships reveals competing logics of prestige, finances, and alignment with national ambitions in the global economy. Historical hierarchies between Irish third-level institutions are thus reinforced, while internally, status distinctions emerge between the various types of partnerships and student exchange programs. The shape taken by internationalization may reinforce various strands of inter-institutional and intra-institutional inequality, without guaranteeing that Irish universities succeed in their ambitions to achieve “world-class” status

Data-Driven Modelling of the Inositol Trisphosphate Receptor (IPR) and its Role in Calcium-Induced Calcium Release (CICR)

We review the current state of the art of data-driven modelling of the inositol trisphosphate receptor (IPR). After explaining that the IPR plays a crucial role as a central regulator in calcium dynamics, several sources of relevant experimental data are introduced. Single ion channels are best studied by recording single-channel currents under different ligand concentrations via the patch-clamp technique. The particular relevance of modal gating, the spontaneous switching between different levels of channel activity that occur even at constant ligand concentrations, is highlighted. In order to investigate the interactions of IPRs, calcium release from small clusters of channels, so-called calcium puffs, can be used. We then present the mathematical framework common to all models based on single-channel data, aggregated continuous-time Markov models, and give a short review of statistical approaches for parameterising these models with experimental data. The process of building a Markov model that integrates various sources of experimental data is illustrated using two recent examples, the model by Ullah et al. and the “Park–Drive” model by Siekmann et al. (Biophys. J. 2012), the only models that account for all sources of data currently available. Finally, it is demonstrated that the essential features of the Park–Drive model in different models of calcium dynamics are preserved after reducing it to a two-state model that only accounts for the switching between the inactive “park” and the active “drive” modes. This highlights the fact that modal gating is the most important mechanism of ligand regulation in the IPR. It also emphasises that data-driven models of ion channels do not necessarily have to lead to detailed models but can be constructed so that relevant data is selected to represent ion channels at the appropriate level of complexity for a given application