The PORTOLE Project: Supporting e-Learning

The PORTOLE (Providing Online Resources To Online Learning Environments) Project was a JISC-funded project which sought to produce a range of tools for tutors which could be used to enable them to discover information resources and to embed these into their course modules from within a University Virtual Learning Environment (VLE). The VLE in use at Universities of Leeds and Oxford is the Bodington system. A key deliverable of the Project was to produce tools that were designed with ease of incorporation into other VLE environments in mind. This paper discusses the background to the project and the key outcomes. Aworking service has been developed and is now being tested and evaluated with academic staff

Library project management in a collaborative web-based working environment

This paper discusses the emerging paradigm of project management performed in a web-based working environment. It highlights how project management and its associated features are strongly linked to fulfilling quality and value criteria for customers, and it examines how collaborative working environments can greatly reduce the administrative burden of managing large projects, especially and almost paradoxically, when resources are limited. Specifically, the paper examines the application of a project management methodology (PRINCE2) together with the use of a collaborative web-based working environment over a number of pilot projects at Leeds University Library. It describes the pilot phase of a library management decision to run a series of major Library projects using project management methodology, while continuing to run other projects through the existing locally developed planning mechanisms and describes the pitfalls of these latter alternatives, less sophisticated project management tools, and describes the main issues that this change in practice has brought to light. It draws preliminary conclusions about the effectiveness of this change in practice in one of the UK’s largest academic libraries

Demonstrating Value in Research Libraries: the Shared Service Standards Initiative

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Regulating own and teammates’ emotions prior to competition

We examined intra- and interpersonal emotion regulation in the hour prior to athletic competition. Specifically, we investigated the extent to which differences between experienced and desired emotions were related to emotion regulation processes. Participants (n = 114) from team/doubles sport rated their experienced and desired emotions before a recent competition, and listed strategies used to regulate emotions reporting frequency, effectiveness, and self-efficacy for each strategy used. They followed the same procedure in relation to perceived emotions in a teammate. Results show athletes who experienced emotions close to their desired states reported significantly higher regulatory emotional self- efficacy than those further from their desired states. Further, their emotion regulation strategies were used more frequently and were more effective. Qualitative results indicated that participants attempted to regulate similar emotions in themselves and others, but used different strategies to accomplish these tasks to different degrees of frequency. The findings highlight the role of self-efficacy in emotion regulation; an individual difference variable which merits attention in future emotion regulation interventions

The MELD-Plus: A generalizable prediction risk score in cirrhosis

Background and aims Accurate assessment of the risk of mortality following a cirrhosis-related admission can enable health-care providers to identify high-risk patients and modify treatment plans to decrease the risk of mortality. Methods: We developed a post-discharge mortality prediction model for patients with a cirrhosis-related admission using a population of 314,292 patients who received care either at Massachusetts General Hospital (MGH) or Brigham and Women’s Hospital (BWH) between 1992 and 2010. We extracted 68 variables from the electronic medical records (EMRs), including demographics, laboratory values, diagnosis codes, and medications. We then used a regularized logistic regression to select the most informative variables and created a risk score that comprises the selected variables. To evaluate the potential for generalizability of our score, we applied it on all cirrhosis-related admissions between 2010 and 2015 at an independent EMR data source of more than 18 million patients, pooled from different health-care systems with EMRs. We calculated the areas under the receiver operating characteristic curves (AUROCs) to assess prediction performance. Results: We identified 4,781 cirrhosis-related admissions at MGH/BWH hospitals, of which 778 resulted in death within 90 days of discharge. Nine variables were the most effective predictors for 90-day mortality, and these included all MELD-Na’s components, as well as albumin, total cholesterol, white blood cell count, age, and length of stay. Applying our nine-variable risk score (denoted as “MELD-Plus”) resulted in an improvement over MELD and MELD-Na scores in several prediction models. On the MGH/BWH 90-day model, MELD-Plus improved the performance of MELD-Na by 11.4% (0.78 [95% CI, 0.75–0.81] versus 0.70 [95% CI, 0.66–0.73]). In the MGH/BWH approximate 1-year model, MELD-Plus improved the performance of MELD-Na by 8.3% (0.78 [95% CI, 0.76–0.79] versus 0.72 [95% CI, 0.71–0.73]). Performance improvement was similar when the novel MELD-Plus risk score was applied to an independent database; when considering 24,042 cirrhosis-related admissions, MELD-Plus improved the performance of MELD-Na by 16.9% (0.69 [95% CI, 0.69–0.70] versus 0.59 [95% CI, 0.58–0.60]). Conclusions: We developed a new risk score, MELD-Plus that accurately stratifies the short-term mortality of patients with established cirrhosis, following a hospital admission. Our findings demonstrate that using a small set of easily accessible structured variables can help identify novel predictors of outcomes in cirrhosis patients and improve the performance of widely used traditional risk scores

Rituximab-induced HMGB1 release is associated with inhibition of STAT3 activity in human diffuse large B-cell lymphoma

Treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has greatly improved clinical outcomes in patients with diffuse large B-cell lymphoma (DLBCL) compared with CHOP. The mechanism of rituximab-induced cell death is poorly understood. We found that rituximab does not enhance the directly killing efficacy of CHOP, as tested on a panel of DLBCL cell lines. Rituximab induced a rapid release of HMGB1 (High mobility group protein B 1). This release is independent of cell death but significantly correlated with an inhibition on STAT3 activity. In the resting state, HMGB1 co-localizes and interacts with STAT3 in the nucleus of DLBCL cells. Treatment with rituximab breaks this binding and triggers HMGB1 release. Treatment with R-CHOP but not CHOP significantly increased plasma HMGB1 and decreased IL-10 concentrations in DLBCL patients compared with controls. The conditioned medium from rituximab-treated DLBCL cells is able to trigger dendritic cell maturation, phagocytosis, and IFN-g secretion by cytotoxic T cells. In conclusion, our results demonstrate that rituximab induces an inhibition on STAT3 activity, leading to increased HMGB1 release and decreased IL-10 secretion, which elicits immune responses, suggesting that indirect effects on the immune system rather than direct killing contribute to elimination of DLBCL

Effects of mindfulness and distraction on pain depend on individual differences in pain catastrophizing: an experimental study

BackgroundThe aim of this study was to investigate whether the perception of experimental pain was different during a mindfulness manipulation than during a distraction manipulation. Furthermore, it was examined if effects were moderated by dispositional pain catastrophizing. MethodsUndergraduate students (n=51) completed self-report measures of pain catastrophizing and mindfulness. Subsequently, they were administered a series of mildly painful heat stimuli, which they had to rate. During pain induction, participants listened to either a pre-recorded mindfulness instruction (mindfulness group) or a pre-recorded story (distraction group). ResultsAfter controlling for baseline experimental pain ratings, we found no overall group effect, indicating that there was no difference in experienced pain between the mindfulness group and the distraction group. However, a significant moderation effect was found. When dispositional pain catastrophizing was high, pain was less pronounced in the mindfulness group than in the distraction group, whereas the opposite effect was found when the level of pain catastrophizing was low. ConclusionsThe findings suggest that in persons with a high level of catastrophic thinking about pain, mindfulness-based coping may be a better approach than distraction

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Insect Neuropeptide Bursicon Homodimers Induce Innate Immune and Stress Genes during Molting by Activating the NF-κB Transcription Factor Relish

BACKGROUND: Bursicon is a heterodimer neuropeptide composed of two cystine knot proteins, bursicon α (burs α) and bursicon β (burs β), that elicits cuticle tanning (melanization and sclerotization) through the Drosophila leucine-rich repeats-containing G protein-coupled receptor 2 (DLGR2). Recent studies show that both bursicon subunits also form homodimers. However, biological functions of the homodimers have remained unknown until now. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we show in Drosophila melanogaster that both bursicon homodimers induced expression of genes encoding antimicrobial peptides (AMPs) in neck-ligated adults following recombinant homodimer injection and in larvae fat body after incubation with recombinant homodimers. These AMP genes were also up-regulated in 24 h old unligated flies (when the endogenous bursicon level is low) after injection of recombinant homodimers. Up-regulation of AMP genes by the homodimers was accompanied by reduced bacterial populations in fly assay preparations. The induction of AMP expression is via activation of the NF-κB transcription factor Relish in the immune deficiency (Imd) pathway. The influence of bursicon homodimers on immune function does not appear to act through the heterodimer receptor DLGR2, i.e. novel receptors exist for the homodimers. CONCLUSIONS/SIGNIFICANCE: Our results reveal a mechanism of CNS-regulated prophylactic innate immunity during molting via induced expression of genes encoding AMPs and genes of the Turandot family. Turandot genes are also up-regulated by a broader range of extreme insults. From these data we infer that CNS-generated bursicon homodimers mediate innate prophylactic immunity to both stress and infection during the vulnerable molting cycle