Lumbricus terrestris middens are biological and chemical hotspots in a minimum tillage arable ecosystem

The biological (macrofauna and mesofauna), physical (size) and chemical (nutrient availability) properties of Lumbricus terrestris middens were studied on a minimum tillage field trial amended with farmyard manure, compost or unamended treatments. Results showed that herbivorous-type interactions with wheat crop leaves were common. Midden microhabitats containing these fresh leaves were significantly enhanced by up to 2.8-fold in mesofauna (springtails, enchytraeidae, mites, millipedes) abundance. Midden microhabitats on plots amended with farmyard manure had significantly (p < 0.05) more endogeic earthworms than compost amended or control plots. Further, middens found on farmyard manure amended plots were significantly (p < 0.05) larger, being twice the size (20.6 ± 1.7 g dry weight) of middens found on compost or control plots, demonstrating that farmyard manure improves midden microhabitat size and quality. Middens were enriched in extractable plant nutrients including P, K, S and Mn

The Care Home Independent Pharmacist Prescriber Study (CHIPPS) : Development and implementation of an RCT to estimate safety, effectiveness and cost-effectiveness

This research was supported by the National Institute for Health and Care Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR YH PSTRC). The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This report is dedicated to Kate Massey, an active and enthusiastic member of the CHIPPS patient and public involvement team who sadly passed away during the delivery of this study.Peer reviewedPublisher PD

Assessing young people's political engagement: a critical and systematic literature review of the instruments used to measure political engagement

Over the past few decades, there has been an increasing interest in understanding youth political engagement. However, it has been argued that the instruments used to assess the concept often lack adequate validation, and this is important as this practice may result in biased statistical conclusions. Consequently, the main aim of the present study was to systematically review, summarize, and critique the extant research evidence on the development of psychometric instruments that assess young people’s political engagement. Following a systematic review of the literature, seven instruments were identified that were both valid and reliable, but none explicitly assessed young people’s political engagement. Instead, they considered broad concepts and/or dimensions related to political engagement. Emphasising the lack of statistically robust standardised measurement tools that empirically assess young people’s political engagement, the available evidence confirms the pressing need to adopt a robust psychometric approach to assess political engagement in youth

Evaluation of effectiveness and safety of pharmacist independent prescribers in care homes: cluster randomised controlled trial

Objective To estimate the effectiveness, cost effectiveness (to be reported elsewhere), and safety of pharmacy independent prescribers in care homes. Design Cluster randomised controlled trial, with clusters based on triads of a pharmacist independent prescriber, a general practice, and one to three associated care homes. Setting Care homes across England, Scotland, and Northern Ireland, their associated general practices, and pharmacy independent prescribers, formed into triads. Participants 49 triads and 882 residents were randomised. Participants were care home residents, aged ≥65 years, taking at least one prescribed drug, recruited to 20 residents/triad. Intervention Each pharmacy independent prescriber provided pharmaceutical care to approximately 20 residents across one to three care homes, with weekly visits over six months. Pharmacy independent prescribers developed a pharmaceutical care plan for each resident, did medicines reviews/reconciliation, trained staff, and supported with medicines related procedures, deprescribing, and authorisation of prescriptions. Participants in the control group received usual care. Main outcomes measures The primary outcome was fall rate/person at six months analysed by intention to treat, adjusted for prognostic variables. Secondary outcomes included quality of life (EQ-5D by proxy), Barthel score, Drug Burden Index, hospital admissions, and mortality. Assuming a 21% reduction in falls, 880 residents were needed, allowing for 20% attrition. Results The average age of participants at study entry was 85 years; 70% were female. 697 falls (1.55 per resident) were recorded in the intervention group and 538 falls (1.26 per resident) in the control group at six months. The fall rate risk ratio for the intervention group compared with the control group was not significant (0.91, 95% confidence interval 0.66 to 1.26) after adjustment for all model covariates. Secondary outcomes were not significantly different between groups, with exception of the Drug Burden Index, which significantly favoured the intervention. A third (185/566; 32.7%) of pharmacy independent prescriber interventions involved medicines associated with falls. No adverse events or safety concerns were identified. Conclusions Change in the primary outcome of falls was not significant. Limiting follow-up to six months combined with a small proportion of interventions predicted to affect falls may explain this. A significant reduction in the Drug Burden Index was realised and would be predicted to yield future clinical benefits for patients. This large trial of an intensive weekly pharmacist intervention with care home residents was also found to be safe and well received

Comparison of Marine Spatial Planning Methods in Madagascar Demonstrates Value of Alternative Approaches

The Government of Madagascar plans to increase marine protected area coverage by over one million hectares. To assist this process, we compare four methods for marine spatial planning of Madagascar's west coast. Input data for each method was drawn from the same variables: fishing pressure, exposure to climate change, and biodiversity (habitats, species distributions, biological richness, and biodiversity value). The first method compares visual color classifications of primary variables, the second uses binary combinations of these variables to produce a categorical classification of management actions, the third is a target-based optimization using Marxan, and the fourth is conservation ranking with Zonation. We present results from each method, and compare the latter three approaches for spatial coverage, biodiversity representation, fishing cost and persistence probability. All results included large areas in the north, central, and southern parts of western Madagascar. Achieving 30% representation targets with Marxan required twice the fish catch loss than the categorical method. The categorical classification and Zonation do not consider targets for conservation features. However, when we reduced Marxan targets to 16.3%, matching the representation level of the “strict protection” class of the categorical result, the methods show similar catch losses. The management category portfolio has complete coverage, and presents several management recommendations including strict protection. Zonation produces rapid conservation rankings across large, diverse datasets. Marxan is useful for identifying strict protected areas that meet representation targets, and minimize exposure probabilities for conservation features at low economic cost. We show that methods based on Zonation and a simple combination of variables can produce results comparable to Marxan for species representation and catch losses, demonstrating the value of comparing alternative approaches during initial stages of the planning process. Choosing an appropriate approach ultimately depends on scientific and political factors including representation targets, likelihood of adoption, and persistence goals

Evaluation of effectiveness and safety of pharmacist independent prescribers in care homes: cluster randomised controlled trial

Objective: To estimate the effectiveness, cost effectiveness (to be reported elsewhere), and safety of pharmacy independent prescribers in care homes. Design: Cluster randomised controlled trial, with clusters based on triads of a pharmacist independent prescriber, a general practice, and one to three associated care homes. Setting: Care homes across England, Scotland, and Northern Ireland, their associated general practices, and pharmacy independent prescribers, formed into triads. Participants: 49 triads and 882 residents were randomised. Participants were care home residents, aged ≥65 years, taking at least one prescribed drug, recruited to 20 residents/triad. Intervention: Each pharmacy independent prescriber provided pharmaceutical care to approximately 20 residents across one to three care homes, with weekly visits over six months. Pharmacy independent prescribers developed a pharmaceutical care plan for each resident, did medicines reviews/reconciliation, trained staff, and supported with medicines related procedures, deprescribing, and authorisation of prescriptions. Participants in the control group received usual care. Main outcomes measures: The primary outcome was fall rate/person at six months analysed by intention to treat, adjusted for prognostic variables. Secondary outcomes included quality of life (EQ-5D by proxy), Barthel score, Drug Burden Index, hospital admissions, and mortality. Assuming a 21% reduction in falls, 880 residents were needed, allowing for 20% attrition. Results: The average age of participants at study entry was 85 years; 70% were female. 697 falls (1.55 per resident) were recorded in the intervention group and 538 falls (1.26 per resident) in the control group at six months. The fall rate risk ratio for the intervention group compared with the control group was not significant (0.91, 95% confidence interval 0.66 to 1.26) after adjustment for all model covariates. Secondary outcomes were not significantly different between groups, with exception of the Drug Burden Index, which significantly favoured the intervention. A third (185/566; 32.7%) of pharmacy independent prescriber interventions involved medicines associated with falls. No adverse events or safety concerns were identified. Conclusions: Change in the primary outcome of falls was not significant. Limiting follow-up to six months combined with a small proportion of interventions predicted to affect falls may explain this. A significant reduction in the Drug Burden Index was realised and would be predicted to yield future clinical benefits for patients. This large trial of an intensive weekly pharmacist intervention with care home residents was also found to be safe and well received

Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s) underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI) methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition.</p> <p>Methods</p> <p>To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis.</p> <p>Results</p> <p>Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99) between the total number of hypermethylated CGIs and GI₅₀values (<it>i.e</it>., increased drug resistance) following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells.</p> <p>Conclusion</p> <p>Selective epigenetic disruption of distinct biological pathways was observed during development of platinum resistance in ovarian cancer. Integrated analysis of DNA methylation and gene expression may allow for the identification of new therapeutic targets and/or biomarkers prognostic of disease response. Finally, our results suggest that epigenetic therapies may facilitate the prevention or reversal of transcriptional repression responsible for chemoresistance and the restoration of sensitivity to platinum-based chemotherapeutics.</p