16 research outputs found

    Disruption of Rolandic Gamma-Band Functional Connectivity by Seizures is Associated with Motor Impairments in Children with Epilepsy

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    Although children with epilepsy exhibit numerous neurological and cognitive deficits, the mechanisms underlying these impairments remain unclear. Synchronization of oscillatory neural activity in the gamma frequency range (>30 Hz) is purported to be a mechanism mediating functional integration within neuronal networks supporting cognition, perception and action. Here, we tested the hypothesis that seizure-induced alterations in gamma synchronization are associated with functional deficits. By calculating synchrony among electrodes and performing graph theoretical analysis, we assessed functional connectivity and local network structure of the hand motor area of children with focal epilepsy from intracranial electroencephalographic recordings. A local decrease in inter-electrode phase synchrony in the gamma bands during ictal periods, relative to interictal periods, within the motor cortex was strongly associated with clinical motor weakness. Gamma-band ictal desychronization was a stronger predictor of deficits than the presence of the seizure-onset zone or lesion within the motor cortex. There was a positive correlation between the magnitude of ictal desychronization and impairment of motor dexterity in the contralateral, but not ipsilateral hand. There was no association between ictal desynchronization within the hand motor area and non-motor deficits. This study uniquely demonstrates that seizure-induced disturbances in cortical functional connectivity are associated with network-specific neurological deficits

    Stroke genetics informs drug discovery and risk prediction across ancestries

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    Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

    The role of policy in supporting alternative marine farming methods: A case study of seafloor ranching in Australia

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    Recent attention to the ecosystem service-generating potential of marine aquaculture (mariculture) indicates that there is substantial opportunity for marine farming to optimise practices that benefit both production and nature. One strategy for augmenting sustainability within the mariculture industry is to develop more diverse farming practices and culture species that can operate within existing ocean space constraints, contribute to ecological and conservation objectives, and assuage negative public sentiment towards mariculture. While this strategy has the potential to expand mariculture's sustainability, the implementation of these alternative culture approaches will likely depend on whether the management frameworks that regulate the industry have the authority and the capacity to enable farming innovations and encourage investment in diverse mariculture systems. Using Australia and seafloor ranching of molluscs as a case study, we explore the suitability of existing policy and legislation to support novel farming methods. We find that the policy frameworks differ across States in terms of their applicability (both implicit and explicit) to seafloor ranching activities, with substantial gaps regarding the siting and building of farming infrastructure. In the context of these results, we discuss potential strategies for leveraging existing policy and management frameworks to meet the needs of seafloor ranching and identify operational stages where new, targeted policy could be particularly impactful. Our case study offers practical insights to policymakers in Australia and other countries and regions seeking to support innovations in culture methods with a greater potential for sustainability

    Microfiber Masses Recovered from Conventional Machine Washing of New or Aged Garments

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    Synthetic textiles can shed numerous microfibers during conventional washing, but evaluating environmental consequences as well as source-control strategies requires understanding mass releases. Polyester apparel accounts for a large proportion of the polyester market, and synthetic jackets represent the broadest range in apparel construction, allowing for potential changes in manufacturing as a mitigation measure to reduce microfiber release during laundering. Here, detergent-free washing experiments were conducted and replicated in both front- and top-load conventional home machines for five new and mechanically aged jackets or sweaters: four from one name-brand clothing manufacturer (three majority polyester fleece, and one nylon shell with nonwoven polyester insulation) and one off-brand (100% polyester fleece). Wash water was filtered to recover two size fractions (>333 μm and between 20 and 333 μm); filters were then imaged, and microfiber masses were calculated. Across all treatments, the recovered microfiber mass per garment ranged from approximately 0 to 2 g, or exceeding 0.3% of the unwashed garment mass. Microfiber masses from top-load machines were approximately 7 times those from front-load machines; garments mechanically aged via a 24 h continuous wash had increased mass release under the same wash protocol as new garments. When published wastewater treatment plant influent characterization and microfiber removal studies are considered, washing synthetic jackets or sweaters as per this study would account for most microfibers entering the environment
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