The Ottawa ankle rules for the use of diagnostic X-ray in after hours medical centres in New Zealand

Aims: The aims of this study were to measure baseline use of Ottawa ankle rules (OAR), validate the OAR and, if appropriate, explore the impact of implementing the Rules on X-ray rates in a primary care, after hours medical centre setting. Methods: General practitioners (GPs) were surveyed to find their awareness of ankle injury guidelines. Data concerning diagnosis and X-ray utilisation were collected prospectively for patients presenting with ankle injuries to two after hours medical centres. The OAR were applied retrospectively, and the sensitivity and specificity of the OAR were compared with GPs’ clinical judgement in ordering X-rays. The outcome measures were X-ray utilisation and diagnosis of fracture. Results: Awareness of the OAR was low. The sensitivity of the OAR for diagnosis of fractures was 100% (95% CI: 75.3 – 100) and the specificity was 47% (95% CI: 40.5 – 54.5). The sensitivity of GPs’ clinical judgement was 100% (95% CI: 75.3 – 100) and the specificity was 37% (95% CI: 30.2 – 44.2). Implementing the OAR would reduce X-ray utilisation by 16% (95% CI: approx 10.8 – 21.3). Conclusions: The OAR are valid in a New Zealand primary care setting. Further implementation of the rules would result in some reduction of X-rays ordered for ankle injuries, but less than the reduction found in previous studies.Accident Compensation Corporation of New ZealandOtago Universit

A review of probabilistic methods for defining reserve requirements

In this paper we examine potential improvements in how load and generation forecast uncertainty is captured when setting reserve levels in power systems with significant renewable generation penetration and discuss the merit of proposed new methods in this area. One important difference between methods is whether reserves are defined based on the marginal distribution of forecast errors, as calculated from historic data, or whether the conditional distribution, specific to the time at which reserves are being scheduled, is used. This paper is a review of published current practice in markets which are at the leading edge of this problem, summarizing their experiences, and aligning it with academic modeling work. We conclude that the ultimate goal for all markets expected to manage high levels of renewable generation should be a reserve setting mechanism which utilizes the best understanding of meteorological uncertainties combined with traditional models of uncertainty arising from forced outages

Manipulating Pesticide Use to Increase the Production of Wild Game Birds in Britain

We describe a management technique whereby the adverse effects of pesticides on game-bird chick production were alleviated following selective use or selective avoidance of pesticides on the edges of cereal crops. This technique (known as Conservation Headlands) provided increased amounts of food resources necessary for young gray partridge (Perdix perdix) and ring-necked pheasant (Phasianus colchicus) chicks. The use of Conservation Headlands has consistently increased average numbers of chicks per brood of both species via increases in the densities of arthropods and weed plants. These findings are discussed in the context of the other prerequisites of wild game-bird production in the UK and how these may be altered by recent Government policies to reduce cereal surpluses

Using event-related fMRI to examine sustained attention processes and effects of APOE ε4 in young adults

In this study we investigated effects of the APOE ε4 allele (which confers an enhanced risk of poorer cognitive ageing, and Alzheimer’s Disease) on sustained attention (vigilance) performance in young adults using the Rapid Visual Information Processing (RVIP) task and event-related fMRI. Previous fMRI work with this task has used block designs: this study is the first to image an extended (6-minute) RVIP task. Participants were 26 carriers of the APOE ε4 allele, and 26 non carriers (aged 18–28). Pupil diameter was measured throughout, as an index of cognitive effort. We compared activity to RVIP task hits to hits on a control task (with similar visual parameters and response requirements but no working memory load): this contrast showed activity in medial frontal, inferior and superior parietal, temporal and visual cortices, consistent with previous work, demonstrating that meaningful neural data can be extracted from the RVIP task over an extended interval and using an event-related design. Behavioural performance was not affected by genotype; however, a genotype by condition (experimental task/control task) interaction on pupil diameter suggested that ε4 carriers deployed more effort to the experimental compared to the control task. fMRI results showed a condition by genotype interaction in the right hippocampal formation: only ε4 carriers showed downregulation of this region to experimental task hits versus control task hits. Experimental task beta values were correlated against hit rate: parietal correlations were seen in ε4 carriers only, frontal correlations in non-carriers only. The data indicate that, in the absence of behavioural differences, young adult ε4 carriers already show a different linkage between functional brain activity and behaviour, as well as aberrant hippocampal recruitment patterns. This may have relevance for genotype differences in cognitive ageing trajectories

Cognitive and neural signatures of the APOE E4 allele in mid-aged adults

The apolipoprotein E (APOE) e4 allele is strongly associated with increased risk of cognitive impairments in older adulthood. There is also a possible link to enhanced cognitive performance in younger adults, and the APOE e4 allele may constitute an example of antagonistic pleiotropy. The aim of this work was to investigate the cognitive and neural (functional) effects of the APOE e4 allele during mid-age (45-55 years), where a transition toward cognitive deficit might be expected. APOE e4 carriers (e4+) were compared with non-e4 carriers (e4-) on tasks of sustained and covert attention and prospective memory, and functional magnetic resonance imaging data acquired. Performance by e4+ was equivalent or better than e4- on all 3 tasks, although performance benefits were less pronounced than in youth. Neurally, e4+ showed less task-related recruitment of extrastriate and parietal areas. This became more evident when neural activation data were compared with that of young adults acquired in a parallel study. As expected, mid-age participants showed more diffuse neural activation. Notable was the fact that e4+ showed a relative inability to recruit parietal regions as they aged. This was coupled with a tendency to show greater recruitment of frontal regions, and underactivation of extrastriate visual regions. Thus, mid-age e4+ show a pattern of neural recruitment usually seen later in life, possibly reflecting the source of an accelerated aging profile that describes the e4 genotype

Mid age APOE ε4 carriers show memory-related functional differences and disrupted structure-function relationships in hippocampal regions

Carriers of the APOE e4 allele are at higher risk of age-related cognitive decline and Alzheimer's disease (AD). The underlying neural mechanisms are uncertain, but genotype differences in medial temporal lobe (MTL) functional activity and structure at mid-age might contribute. We tested 16 non-e4 and 16 e4 carriers (aged 45-55) on a subsequent memory task in conjunction with MRI to assess how hippocampal volume (from T1 structural) and microstructure (neurite orientation-dispersion, from NODDI) differs by genotype and in relation to memory encoding. No previous study has investigated APOE effects on hippocampal microstructure using NODDI. Recall performance did not differ by genotype. A genotype by condition interaction in left parahippocampus indicated that in e4 carriers activity did not differentiate subsequently remembered from forgotten words. Hippocampal volumes and microstructure also did not differ by genotype but hippocampal volumes correlated positively with recognition performance in non-e4 carriers only. Similarly, greater hippocampal neurite orientation-dispersion was linked to better recall but only in non-e4s. Thus, we suggest that mid-age e4 carriers show a breakdown of normal MTL activation and structure-performance relationships. This could reflect an inability to utilise compensatory mechanisms, and contribute to higher risk of cognitive decline and AD in later life

Discovery of Novel Adenosine Receptor Agonists That Exhibit Subtype Selectivity.

A series of N(6)-bicyclic and N(6)-(2-hydroxy)cyclopentyl derivatives of adenosine were synthesized as novel A1R agonists and their A1R/A2R selectivity assessed using a simple yeast screening platform. We observed that the most selective, high potency ligands were achieved through N(6)-adamantyl substitution in combination with 5'-N-ethylcarboxamido or 5'-hydroxymethyl groups. In addition, we determined that 5'-(2-fluoro)thiophenyl derivatives all failed to generate a signaling response despite showing an interaction with the A1R. Some selected compounds were also tested on A1R and A3R in mammalian cells revealing that four of them are entirely A1R-selective agonists. By using in silico homology modeling and ligand docking, we provide insight into their mechanisms of recognition and activation of the A1R. We believe that given the broad tissue distribution, but contrasting signaling profiles, of adenosine receptor subtypes, these compounds might have therapeutic potential.This study was supported by the Swiss National Science Foundation (SNSF professorship PP00P2_123536 and PP00P2_146321 to M.L.), the BBSRC (G.L., BB/G01227X/1 and BB/M00015X/1), an MRC Doctoral Training Partnership (I.W. MR/J003964/1), and the EPSRC (A.K., EP/G500045/1).This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/acs.jmedchem.5b0140