Use of 3D visualisation tools for representing urban greenspace spatial planning.

The objective of this paper is to report on the development of prototype models for use in raising public awareness of changes in urban areas, focusing on green spaces, and testing responses to scenarios of change. Specifically, the focus is on the design of appropriate types of outdoor features for community planning and engagement. This modelling is fulfilled using the Autodesk Maya, Google SketchUp and ArcGIS software packages together in a novel combination of spatial and visualisation tools. The experiment results show evidence that different types of 3D iconic symbols with interactive communication will influence participation and decision making in land use planning

Application Of 1D And 2D Numerical Models For Assessing And Visualizing Effectiveness Of Natural Flood Management (NFM) Measures

Natural Flood Management (NFM) techniques that include alteration, restoration or use of landscape features, have emerged as a novel way of reducing flood risk in Scotland. NFM aims to reduce the peak flood downstreamincreasing the time available to prepare for flood. Water storage ponds are very effective for this purpose. The aim of the paper is to present findings of a modelling approach to floodinundation and risk assessment, and its application for assessing the effectiveness of wetland storage ponds as NFM measures. The study was undertaken in a rural catchment (Tarland Burn, area ~74 km2) located in Aberdeenshire, north-east Scotland. A one-dimensional numerical model – ISIS was used for assessing the effectiveness of storage ponds. It was developed using a Digital Elevation Model (DEM) based on channel cross-sections. The output was then used as inflow boundary to a two-dimensional hydrodynamic model – Tuflow to develop high resolution flood inundation maps. The model was developed by using a DEM derived from high-resolutionLiDAR. Modelling of an existing storage pond located in the middle of the catchment indicated that there was no significant flow attenuation as a result of the single pond. An additional storage capacity would be required to effectively attenuate the flow especially during the extreme flow events. Model output indicated that significant reduction in thedownstream flood peak is possible only if the pond area is increased -e.g.a five-fold increase in pond area would result in a 25 % decrease in peak flow.A range of flood water storage options in the headwater zone was assessed to minimise flood risks downstream. The flood inundation output products can be effectively visualised using Virtual Landscape Theatre (VLT), which is an interactive viewing environment that can be used for communicating flood risks to a wide variety of stakeholder groups

Net carbon dioxide emissions from an eroding Atlantic blanket bog

The net impact of greenhouse gas emissions from degraded peatland environments on national Inventories and subsequent mitigation of such emissions has only been seriously considered within the last decade. Data on greenhouse gas emissions from special cases of peatland degradation, such as eroding peatlands, are particularly scarce. Here, we report the first eddy covariance-based monitoring of carbon dioxide (CO2) emissions from an eroding Atlantic blanket bog. The CO2 budget across the period July 2018–November 2019 was 147 (± 9) g C m−2. For an annual budget that contained proportionally more of the extreme 2018 drought and heat wave, cumulative CO2 emissions were nearly double (191 g C m−2) of that of an annual period without drought (106 g C m−2), suggesting that direct CO2 emissions from eroded peatlands are at risk of increasing with projected changes in temperatures and precipitation due to global climate change. The results of this study are consistent with chamber-based and modelling studies that suggest degraded blanket bogs to be a net source of CO2 to the atmosphere, and provide baseline data against which to assess future peatland restoration efforts in this region

The potential for modelling peatland habitat condition in Scotland using long-term MODIS data

Funding: All James Hutton Institute authors are supported by the Scottish Government’s Rural and Environment Research and Analysis Directorate under the current Strategic Research Programme (2016-2021). Sally Johnson, Patricia Bruneau and Louise Ross did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors for this project. The peat spatial extent model was created in part within a UK Government – Department for Business, Energy and Industrial Strategy-funded project (TRN860/07/2014, Scoping the use of the methodology set out in Chapters 2 and 3 of the ‘2013 Supplement to the 2006 IPCC Guidelines for National Greenhouse Gas Inventories: Wetlands in the UK GHG Inventory: Land Use, Land Use Change and Forestry (LULUCF)), with further updates created within the Strategic Research Programme (2016-2021) funding.Peer reviewedPostprin

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Scoping a national peatland monitoring framework

Scotland is a peat-rich nation. Healthy peatlands deliver a wide range of ecosystem services, including carbon sequestration, carbon storage and a specialised biodiversity. Much of Scotland’s peat resource is damaged: eroding, drained or converted to other land uses. The Scottish Government has made a significant commitment to restore peatland areas that have been damaged. This paper explores how we can monitor success. Peatlands restored to a functioning ecosystem can better withstand a changing climate and also provide vital flood risk protection. It takes time for the benefits of restoration to take effect. Long-term monitoring is important to track this recovery and prompt intervention when necessary. Despite significant investment in peatland restoration we still have a lot to learn, particularly on the best techniques to use, and in understanding how long the process takes