73 research outputs found

    GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson's disease

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    In Parkinson's disease (PD), elevated beta (15-35Hz) power in subcortical motor networks is widely believed to promote aspects of PD symptomatology, moreover, a reduction in beta power and coherence accompanies symptomatic improvement following effective treatment with l-DOPA. Previous studies have reported symptomatic improvements that correlate with changes in cortical network activity following GABAA receptor modulation. In this study we have used whole-head magnetoencephalography to characterize neuronal network activity, at rest and during visually cued finger abductions, in unilaterally symptomatic PD and age-matched control participants. Recordings were then repeated following administration of sub-sedative doses of the hypnotic drug zolpidem (0.05mg/kg), which binds to the benzodiazepine site of the GABAA receptor. A beamforming based 'virtual electrode' approach was used to reconstruct oscillatory power in the primary motor cortex (M1), contralateral and ipsilateral to symptom presentation in PD patients or dominant hand in control participants. In PD patients, contralateral M1 showed significantly greater beta power than ipsilateral M1. Following zolpidem administration contralateral beta power was significantly reduced while ipsilateral beta power was significantly increased resulting in a hemispheric power ratio that approached parity. Furthermore, there was highly significant correlation between hemispheric beta power ratio and Unified Parkinson's Disease Rating Scale (UPDRS). The changes in contralateral and ipsilateral beta power were reflected in pre-movement beta desynchronization and the late post-movement beta rebound. However, the absolute level of movement-related beta desynchronization was not altered. These results show that low-dose zolpidem not only reduces contralateral beta but also increases ipsilateral beta, while rebalancing the dynamic range of M1 network oscillations between the two hemispheres. These changes appear to underlie the symptomatic improvements afforded by low-dose zolpidem

    The importance of long‐term experiments in agriculture: their management to ensure continued crop production and soil fertility; the Rothamsted experience

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    Summary Long‐term field experiments that test a range of treatments and are intended to assess the sustainability of crop production, and thus food security, must be managed actively to identify any treatment that is failing to maintain or increase yields. Once identified, carefully considered changes can be made to the treatment or management, and if they are successful yields will change. If suitable changes cannot be made to an experiment to ensure its continued relevance to sustainable crop production, then it should be stopped. Long‐term experiments have many other uses. They provide a field resource and samples for research on plant and soil processes and properties, especially those properties where change occurs slowly and affects soil fertility. Archived samples of all inputs and outputs are an invaluable source of material for future research, and data from current and archived samples can be used to develop models to describe soil and plant processes. Such changes and uses in the Rothamsted experiments are described, and demonstrate that with the appropriate crop, soil and management, acceptable yields can be maintained for many years, with either organic manure or inorganic fertilizers. Highlights Long‐term experiments demonstrate sustainability and increases in crop yield when managed to optimize soil fertility. Shifting individual response curves into coincidence increases understanding of the factors involved. Changes in inorganic and organic pollutants in archived crop and soil samples are related to inputs over time. Models describing soil processes are developed from current and archived soil data

    Advances in diffusion MRI acquisition and processing in the Human Connectome Project

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    The Human Connectome Project (HCP) is a collaborative 5-year effort to map human brain connections and their variability in healthy adults. A consortium of HCP investigators will study a population of 1200 healthy adults using multiple imaging modalities, along with extensive behavioral and genetic data. In this overview, we focus on diffusion MRI (dMRI) and the structural connectivity aspect of the project. We present recent advances in acquisition and processing that allow us to obtain very high-quality in-vivo MRI data, whilst enabling scanning of a very large number of subjects. These advances result from 2 years of intensive efforts in optimising many aspects of data acquisition and processing during the piloting phase of the project. The data quality and methods described here are representative of the datasets and processing pipelines that will be made freely available to the community at quarterly intervals, beginning in 2013

    Novel genetic loci associated with hippocampal volume

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    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

    Prevalence of Frailty in European Emergency Departments (FEED): an international flash mob study

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    Introduction Current emergency care systems are not optimized to respond to multiple and complex problems associated with frailty. Services may require reconfiguration to effectively deliver comprehensive frailty care, yet its prevalence and variation are poorly understood. This study primarily determined the prevalence of frailty among older people attending emergency care. Methods This cross-sectional study used a flash mob approach to collect observational European emergency care data over a 24-h period (04 July 2023). Sites were identified through the European Task Force for Geriatric Emergency Medicine collaboration and social media. Data were collected for all individuals aged 65 + who attended emergency care, and for all adults aged 18 + at a subset of sites. Variables included demographics, Clinical Frailty Scale (CFS), vital signs, and disposition. European and national frailty prevalence was determined with proportions with each CFS level and with dichotomized CFS 5 + (mild or more severe frailty). Results Sixty-two sites in fourteen European countries recruited five thousand seven hundred eighty-five individuals. 40% of 3479 older people had at least mild frailty, with countries ranging from 26 to 51%. They had median age 77 (IQR, 13) years and 53% were female. Across 22 sites observing all adult attenders, older people living with frailty comprised 14%. Conclusion 40% of older people using European emergency care had CFS 5 + . Frailty prevalence varied widely among European care systems. These differences likely reflected entrance selection and provide windows of opportunity for system configuration and workforce planning

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
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