Modelling neurological diseases in large animals: criteria for model selection and clinical assessment

Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models

The Lore of Low Methane Livestock:Co-Producing Technology and Animals for Reduced Climate Change Impact

Methane emissions from sheep and cattle production have gained increasing profile in the context of climate change. Policy and scientific research communities have suggested a number of technological approaches to mitigate these emissions. This paper uses the concept of co-production as an analytical framework to understand farmers’ evaluation of a 'good animal’. It examines how technology and sheep and beef cattle are co-produced in the context of concerns about the climate change impact of methane. Drawing on 42 semi-structured interviews, this paper demonstrates that methane emissions are viewed as a natural and integral part of sheep and beef cattle by farmers, rather than as a pollutant. Sheep and beef cattle farmers in the UK are found to be an extremely heterogeneous group that need to be understood in their specific social, environmental and consumer contexts. Some are more amenable to appropriating methane reducing measures than others, but largely because animals are already co-constructed from the natural and the technical for reasons of increased production efficiency

Beam-target helicity asymmetry for γ→n→→π−p in the N*resonance region

We report the first beam-target double-polarization asymmetries in the γ þ nðpÞ → π− þ pðpÞ reaction spanning the nucleon resonance region from invariant mass W ¼ 1500 to 2300 MeV. Circularly polarized photons and longitudinally polarized deuterons in solid hydrogen deuteride (HD) have been used with the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The exclusive final state has been extracted using three very different analyses that show excellent agreement, and these have been used to deduce the E polarization observable for an effective neutron target. These results have been incorporated into new partial wave analyses and have led to significant revisions for several γnN* resonance photocouplings

What factors in rural and remote extended clinical placements may contribute to preparedness for practice, from the perspective of students and clinicians?

What factors in rural and remote extended clinical placements may contribute to preparedness for practice, from the perspective of students and clinicians? Michele Daly, David Perkins, Koshila Kumar, Chris Roberts and Malcolm Moore Background: Community based rural education opportunities have expanded in Australia, attracting more medical students to placements in rural and remote settings. Aim: To identify the factors in an integrated, community engaged rural placement that may contribute to preparedness for practice (P4P), from the perspective of students and clinicians Methods: Forty two semi-structured interviews with medical students, supervisors and clinicians analysed thematically. Results: Opportunities for clinical learning, personal and professional development and cultural awareness were reported by students and clinicians as key factors that contribute to preparedness for practice. Potential barriers in rural and remote settings included geographical and academic isolation, perceived educational risk and differing degrees of program engagement. Conclusions: A longitudinal clinical placement in a rural setting may enable development of enhanced competencies leading to P4P. A rural setting can help provide a unique experience through hands-on learning, enhanced personal and professional development opportunities and observation of the cultural and contextual impact on health

Nutrients cause grassland biomass to outpace herbivory

Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs ('consumer-controlled'). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food ('resource-controlled'). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk

Developing and evaluating packages to support implementation of quality indicators in general practice : the ASPIRE research programme, including two cluster RCTs

This is the final version. Available from the NIHR Journals Library via the DOI in this recordData-sharing statement: All data requests should be submitted to the corresponding author for consideration. Access to anonymised data may be granted following review.Background Dissemination of clinical guidelines is necessary but seldom sufficient by itself to ensure the reliable uptake of evidence-based practice. There are further challenges in implementing multiple clinical guidelines and clinical practice recommendations in the pressurised environment of general practice. Objectives We aimed to develop and evaluate an implementation package that could be adapted to support the uptake of a range of clinical guideline recommendations and be sustainably integrated within general practice systems and resources. Over five linked work packages, we developed ‘high-impact’ quality indicators to show where a measurable change in clinical practice can improve patient outcomes (work package 1), analysed adherence to selected indicators (work package 2), developed an adaptable implementation package (work package 3), evaluated the effects and cost-effectiveness of adapted implementation packages targeting four indicators (work package 4) and examined intervention fidelity and mechanisms of action (work package 5). Setting and participants Health-care professionals and patients from general practices in West Yorkshire, UK. Design We reviewed recommendations from existing National Institute for Health and Care Excellence clinical guidance and used a multistage consensus process, including 11 professionals and patients, to derive a set of ‘high-impact’ evidence-based indicators that could be measured using routinely collected data (work package 1). In 89 general practices that shared data, we found marked variations and scope for improvement in adherence to several indicators (work package 2). Interviews with 60 general practitioners, practice nurses and practice managers explored perceived determinants of adherence to selected indicators and suggested the feasibility of adapting an implementation package to target different indicators (work package 3). We worked with professional and patient panels to develop four adapted implementation packages. These targeted risky prescribing involving non-steroidal anti-inflammatory and antiplatelet drugs, type 2 diabetes control, blood pressure control and anticoagulation for atrial fibrillation. The implementation packages embedded behaviour change techniques within audit and feedback, educational outreach and (for risky prescribing) computerised prompts. We randomised 178 practices to implementation packages targeting either diabetes control or risky prescribing (trial 1), or blood pressure control or anticoagulation (trial 2), or to a further control (non-intervention) group, and undertook economic modelling (work package 4). In trials 1 and 2, practices randomised to the implementation package for one indicator acted as control practices for the other package, and vice versa. A parallel process evaluation included a further eight practices (work package 5). Main outcome measures Trial primary end points at 11 months comprised achievement of all recommended levels of glycated haemoglobin, blood pressure and cholesterol; risky prescribing levels; achievement of recommended blood pressure; and anticoagulation prescribing. Results We recruited 178 (73%) out of 243 eligible general practices. We randomised 80 practices to trial 1 (40 per arm) and 64 to trial 2 (32 per arm), with 34 non-intervention controls. The risky prescribing implementation package reduced risky prescribing (odds ratio 0.82, 97.5% confidence interval 0.67 to 0.99; p = 0.017) with an incremental cost-effectiveness ratio of £2337 per quality-adjusted life-year. The other three packages had no effect on primary end points. The process evaluation suggested that trial outcomes were influenced by losses in fidelity throughout intervention delivery and enactment, and by the nature of the targeted clinical and patient behaviours. Limitations Our programme was conducted in one geographical area; however, practice and patient population characteristics are otherwise likely to be sufficiently diverse and typical to enhance generalisability to the UK. We used an ‘opt-out’ approach to recruit general practices to the randomised trials. Subsequently, our trial practices may have engaged with the implementation package less than if they had actively volunteered. However, this approach increases confidence in the wider applicability of trial findings as it replicates guideline implementation activities under standard conditions. Conclusions This pragmatic, rigorous evaluation indicates the value of an implementation package targeting risky prescribing. In broad terms, an adapted ‘one-size-fits-all’ approach did not consistently work, with no improvement for other targeted indicators. Future work There are challenges in designing ‘one-size-fits-all’ implementation strategies that are sufficiently robust to bring about change in the face of difficult clinical contexts and fidelity losses. We recommend maximising feasibility and ‘stress testing’ prior to rolling out interventions within a definitive evaluation. Our programme has led on to other work, adapting audit and feedback for other priorities and evaluating different ways of delivering feedback to improve patient care.National Institute for Health Research (NIHR

Renal magnesium handling: New insights in understanding old problems

Many sharp-eyed readers have pointed out to us that in the photo next to the article about yams in Ghana (Spore 87, June 2000, page 8), the woman had put all her cassava in one basket, and not the yams she planned to use. Point taken. Whatever you want to point out, point to or point at, your letters, faxes and emails are always welcome at the Spore address in the box on the right. Write now.MailboxMany sharp-eyed readers have pointed out to us that in the photo next to the article about yams in Ghana (Spore 87, June 2000, page 8), the woman had put all her cassava in one basket, and not the yams she planned to use. Point taken...

The role of soil community biodiversity in insect biodiversity

1. This study demonstrates that feedback loops between plants and insects contribute to both plant and insect diversity. Synthesis of several studies reveals that both bottom-up and top-down forces are important for plant and insect communities.2. Feedback loops between plants and soil organisms contribute to plant and soil diversity. An analysis of multiple systems reveals that pathogens, mutualists, and a wide variety of soil fauna directly influence, and are influenced by, plant diversity.3. The connection of plant–insect and soil–plant feedback loops leads to the maintenance of all three groups, and the maintenance of these feedback loops crucially affects insect diversity. Examples of the influence of soil community diversity on insect diversity, and the influence of insect diversity on soil community diversity, as well as feedbacks through all three trophic levels are provided.4. Finally, means of conserving and restoring soil communities to influence the conservation and restoration of insect communities are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78730/1/j.1752-4598.2010.00086.x.pd

Direct costs of dementia in nursing homes

Dementia represents an economical burden to societies nowadays. Total dementia expenses are calculated by the sum of direct and indirect costs. Through the stages of the diseases, as the patients may require institutionalization or a formal caregiver, the direct costs tend to increase. This study aims to analyze the direct costs of dementia in Portuguese nursing homes in 2012, compare the spending between seniors with and without dementia, and propose a predictive costs model. The expenses analysis was based on (1) the use of emergency rooms and doctor’s appointments, either in public or private institutions; (2) days of hospitalization; (3) medication; (4) social services use; (5) the need for technical support; and (6) the utilization of rehabilitation services. The sample was composed of 72 people, half with dementia and half without. The average annual expense of a patient with dementia was e15,287 thousand, while the cost of a patient without dementia was about e12,289 thousand. The variables “ability to make yourself understood,” “self-performance: getting dressed” and “thyroid disorders” were found to be statistically significant in predicting the expenses’ increase. In nursing homes, in 2012, the costs per patient with dementia were 1, 2 times higher than per patient without dementia