Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors.

Paclitaxel is a common chemotherapy drug associated with the development of chronic paclitaxel-induced peripheral neuropathy (PIPN). PIPN is associated with neuroinflammatory mechanisms in pre-clinical studies. Here, we evaluated for differential gene expression (DGE) in peripheral blood between breast cancer survivors with and without PIPN and for neuroinflammatory (NI) related signaling pathways and whole-transcriptome profiles from other experiments. Pathway impact analysis identified 8 perturbed NI related pathways. Expression profile analysis found 15 experiments having similar whole-transcriptome profiles of DGE related to neuroinflammation and PIPN. These findings suggest that perturbations in pathways associated with neuroinflammation are found in cancer survivors with PIPN

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT):Study protocol for a randomised controlled feasibility trial

Background: A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The ‘Prostate Cancer: Evidence of Exercise and Nutrition Trial’ investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. Methods/design: The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). Discussion: The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.10 page(s

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Cancer survivors and neurotoxic chemotherapy: hearing loss and tinnitus

ObjectivesLittle is known about hearing loss and tinnitus associated with neurotoxic chemotherapy. Study evaluated for differences in occurrence rates and effects of hearing loss and tinnitus in survivors who received a platinum alone, a taxane alone or a platinum and taxane containing regimen.MethodsTotal of 273 survivors with breast, gastrointestinal, gynaecological or lung cancer completed self-report measures of hearing loss and tinnitus and had an audiometric assessment that obtained pure tone air conduction thresholds bilaterally at frequencies of between 0.25 kHz to 16.0 kHz. To adjust for age-related and gender-related changes in hearing, each survivor's audiogram was evaluated using the National Health and Nutrition Examination Survey-modified Occupational Safety and Health Administration standards. Survivor was classified as having hearing loss if at any frequency they scored poorer than the 50th percentile for their age and gender. Survivors were categorised as having tinnitus if they reported that for >10% of their time awake, they were consciously aware of their tinnitus. Differences among the chemotherapy groups were evaluated using parametric and non-parametric tests.ResultsFor most of the demographic and clinical characteristics, no differences were found among the three chemotherapy groups. Occurrence rates for audiogram-confirmed hearing loss ranged from 52.3% to 71.4%. Occurrence rates for tinnitus ranged from 37.1% to 40.0%. No differences were found among the three chemotherapy groups in the occurrence rates or effects of hearing loss and tinnitus.ConclusionThese findings suggest that regardless of the chemotherapy regimen common mechanistic pathway(s) may underlie these two neurotoxicities

Postdigital Videogames Literacies: Thinking With, Through, and Beyond James Gee’s Learning Principles

This article is a collective response to the 2003 iteration of James Paul Gee’s What Video Games Have to Teach Us About Learning and Literacy. Gee’s book, a foundational text for those working in game studies, literacy studies, and education, identified 36 principles of ‘good learning’ which he argued were built into the design of good games, and which have since been used to unsettle the landscape of formal education. This article brings together 21 short theoretical and empirical contributions which centre postdigital perspectives to re-engage with, and extend, the arguments first raised by Gee regarding the relationship between videogames and learning. Organised into five groups, these contributions suggest that concepts and attitudes associated with the postdigital offer new thinking tools for challenging grand narrative claims about the educative potential of technologies while also providing rich analytical frames for revisiting Gee’s claims in terms of postdigital videogame literacies

Be prepared: communism and the politics of scouting in 1950s Britain

This article examines the exposure, and in some cases dismissal, of Boy Scouts who belonged or sympathised with the Young Communist League in Britain during the early 1950s. A focus on the rationale and repercussions of the organisation's approach and attitudes towards ‘Red Scouts’ found within their ‘ranks’ extends our understanding of youth movements and their often complex and conflicting ideological foundations. In particular, the post-World War Two period presented significant challenges to these spaces of youth work in terms of broader social and political change in Britain. An analysis of the politics of scouting in relation to Red Scouts questions not only the assertion that British McCarthyism was ‘silent’, but also brings young people firmly into focus as part of a more everyday politics of communism in British society

The Demise of Islet Allotransplantation in the US: A Call for an Urgent Regulatory Update The ISLETS FOR US Collaborative

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and more than minimally manipulated human cell and tissue products (HCT/Ps). Across the world, human islets are appropriately defined as minimally manipulated tissue which has led to islet transplantation becoming a standard-of-care procedure for patients with type 1 diabetes mellitus and problematic hypoglycemia. As a result of the outdated US regulations, only eleven patients underwent allo-ITx in the US between 2011-2016 and all in the setting of a clinical trial. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both, better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States

The Tri-Trophic Interactions Hypothesis: Interactive Effects of Host Plant Quality, Diet Breadth and Natural Enemies on Herbivores

Several influential hypotheses in plant-herbivore and herbivore-predator interactions consider the interactive effects of plant quality, herbivore diet breadth, and predation on herbivore performance. Yet individually and collectively, these hypotheses fail to address the simultaneous influence of all three factors. Here we review existing hypotheses, and propose the tri-trophic interactions (TTI) hypothesis to consolidate and integrate their predictions. The TTI hypothesis predicts that dietary specialist herbivores (as compared to generalists) should escape predators and be competitively dominant due to faster growth rates, and that such differences should be greater on low quality (as compared to high quality) host plants. To provide a preliminary test of these predictions, we conducted an empirical study comparing the effects of plant (Baccharis salicifolia) quality and predators between a specialist (Uroleucon macolai) and a generalist (Aphis gossypii) aphid herbivore. Consistent with predictions, these three factors interactively determine herbivore performance in ways not addressed by existing hypotheses. Compared to the specialist, the generalist was less fecund, competitively inferior, and more sensitive to low plant quality. Correspondingly, predator effects were contingent upon plant quality only for the generalist. Contrary to predictions, predator effects were weaker for the generalist and on low-quality plants, likely due to density-dependent benefits provided to the generalist by mutualist ants. Because the TTI hypothesis predicts the superior performance of specialists, mutualist ants may be critical to A. gossypii persistence under competition from U. macolai. In summary, the integrative nature of the TTI hypothesis offers novel insight into the determinants of plant-herbivore and herbivore-predator interactions and the coexistence of specialist and generalist herbivores

Phase II randomised control feasibility trial of a nutrition and physical activity intervention after radical prostatectomy for prostate cancer

Objective Dietary factors and physical activity may alter prostate cancer progression. We explored the feasibility of lifestyle interventions following radical prostatectomy for localised prostate cancer.Design Patients were recruited into a presurgical observational cohort; following radical prostatectomy, they were offered randomisation into a 2×3 factorial randomised controlled trial (RCT).Setting A single National Health Service trust in the South West of England, UK.Participants Those with localised prostate cancer and listed for radical prostatectomy were invited to participate.Randomisation Random allocation was performed by the Bristol Randomised Trial Collaboration via an online system.Interventions Men were randomised into both a modified nutrition group (either increased vegetable and fruit, and reduced dairy milk; or lycopene supplementation; or control) and a physical activity group (brisk walking or control) for 6 months.Blinding Only the trial statistician was blind to allocations.Primary outcome measures Primary outcomes were measures of feasibility: randomisation rates and intervention adherence at 6 months. Collected at trial baseline, three and six months, with daily adherence reported throughout. Our intended adherence rate was 75% or above, the threshold for acceptable adherence was 90%.Results 108 men entered the presurgical cohort, and 81 were randomised into the postsurgical RCT (randomisation rate: 93.1%) and 75 completed the trial. Of 25 men in the nutrition intervention, 10 (40.0%; 95% CI 23.4% to 59.3%) adhered to the fruit and vegetable recommendations and 18 (72.0%; 95% CI 52.4% to 85.7%) to reduced dairy intake. Adherence to lycopene (n=28), was 78.6% (95% CI 60.5% to 89.8%), while 21/39 adhered to the walking intervention (53.8%; 95% CI 38.6% to 68.4%). Most men were followed up at 6 months (75/81; 92.6%). Three ‘possibly related’ adverse events were indigestion, abdominal bloating and knee pain.Conclusions Interventions were deemed feasible, with high randomisation rates and generally good adherence. A definitive RCT is proposed.Trial registration number ISRCTN 99048944

The Multiple Sclerosis Risk Sharing Scheme Monitoring Study – early results and lessons for the future

Background: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis (MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. Results: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. Conclusion: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed