36 research outputs found

    How fungi’s knack for networking boosts ecological recovery after bushfires

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    The unprecedented bushfires that struck the east coast of Australia this summer killed an estimated one billion animals across millions of hectares. Scorched landscapes and animal corpses brought into sharp relief what climate-driven changes to wildfire mean for Australia’s plants and animals. Yet the effects of fire go much deeper, quite literally, to a vast and complex underground world that we know stunningly little about, including organisms that might be just as vulnerable to fire, and vital to Australia’s ecological recovery: the fungi

    Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents

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    Proteins of the CLCA gene family including the human ClCa1 (hClCa1) have been suggested to constitute a new family of chloride channels mediating Ca2+-dependent Cl− currents. The present study examines the relationship between the hClCa1 protein and Ca2+-dependent Cl− currents using heterologous expression of hClCa1 in HEK293 and NCIH522 cell lines and whole cell recordings. By contrast to previous reports claiming the absence of Cl− currents in HEK293 cells, we find that HEK293 and NCIH522 cell lines express constitutive Ca2+-dependent Cl− currents and show that hClCa1 increases the amplitude of Ca2+-dependent Cl− currents in those cells. We further show that hClCa1 does not modify the permeability sequence but increases the Cl− conductance while decreasing the GSCN−/GCl− conductance ratio from ∼2–3 to ∼1. We use an Eyring rate theory (two barriers, one site channel) model and show that the effect of hClCa1 on the anionic channel can be simulated by its action on lowering the first and the second energy barriers. We conclude that hClCa1 does not form Ca2+-dependent Cl− channels per se or enhance the trafficking/insertion of constitutive channels in the HEK293 and NCIH522 expression systems. Rather, hClCa1 elevates the single channel conductance of endogenous Ca2+-dependent Cl− channels by lowering the energy barriers for ion translocation through the pore

    Relating therapy for voices (the R2V study): study protocol for a pilot randomized controlled trial

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    Background Evidence exists for the effectiveness of cognitive behaviour therapy for psychosis with moderate effect sizes, but the evidence for cognitive behaviour therapy specifically for distressing voices is less convincing. An alternative symptom-based approach may be warranted and a body of literature has explored distressing voices from an interpersonal perspective. This literature has informed the development of relating therapy and findings from a case series suggested that this intervention was acceptable to hearers and therapists. Methods/Design An external pilot randomized controlled trial (RCT) comparing outcomes for 15 patients receiving 16 hours (weekly sessions of one hour) of relating therapy and their usual treatment with 15 patients receiving only their usual treatment. Participants will be assessed using questionnaires at baseline, 16 weeks (post-intervention), and 36 weeks (follow-up). Discussion Expected outcomes will include a refined study protocol and an estimate of the effect size to inform the sample size of a definitive RCT. If evidence from a fully powered RCT suggests that relating therapy is effective, the therapy will extend the range of evidence-based psychological therapies available to people who hear distressing voices

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

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    Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

    Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

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    Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

    Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

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    Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

    The 13th Southern Hemisphere Conference on the Teaching and Learning of Undergraduate Mathematics and Statistics

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    Ngā mihi aroha ki ngā tangata katoa and warm greetings to you all. Welcome to Herenga Delta 2021, the Thirteenth Southern Hemisphere Conference on the Teaching and Learning of Undergraduate Mathematics and Statistics. It has been ten years since the Volcanic Delta Conference in Rotorua, and we are excited to have the Delta community return to Aotearoa New Zealand, if not in person, then by virtual means. Although the limits imposed by the pandemic mean that most of this year’s 2021 participants are unable to set foot in Tāmaki Makaurau Auckland, this has certainly not stopped interest in this event. Participants have been invited to draw on the concept of herenga, in Te Reo Māori usually a mooring place where people from afar come to share their knowledge and experiences. Although many of the participants are still some distance away, the submissions that have been sent in will continue to stimulate discussion on mathematics and statistics undergraduate education in the Delta tradition. The conference invited papers, abstracts and posters, working within the initial themes of Values and Variables. The range of submissions is diverse, and will provide participants with many opportunities to engage, discuss, and network with colleagues across the Delta community. The publications for this thirteenth Delta Conference include publications in the International Journal of Mathematical Education in Science and Technology, iJMEST, (available at https://www.tandfonline.com/journals/tmes20/collections/Herenga-Delta-2021), the Conference Proceedings, and the Programme (which has created some interesting challenges around time-zones), by the Local Organizing Committee. Papers in the iJMEST issue and the Proceedings were peer reviewed by at least two reviewers per paper. Of the ten submissions to the Proceedings, three were accepted. We are pleased to now be at the business end of the conference and hope that this event will carry on the special atmosphere of the many Deltas which have preceded this one. We hope that you will enjoy this conference, the virtual and social experiences that accompany it, and take the opportunity to contribute to further enhancing mathematics and statistics undergraduate education. Ngā manaakitanga, Phil Kane (The University of Auckland | Waipapa Taumata Rau) on behalf of the Local Organising Committ
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