Simplified modelling of air source heat pumps producing detailed results

Created by the Building Research Establishment (BRE), the Standard Assessment Procedure (SAP) is the UK Government‟s recommended method of assessing the energy ratings of dwellings. Modelling future complex dwellings, and their servicing systems, will require a more advanced calculation which is as simple as SAP to use but can produce more detailed results. This paper extends a novel advanced dynamic calculation method (IDEAS – Inverse Dynamics based Energy Analysis and Simulation) of assessing the controllability of a building and its servicing systems. IDEAS produces SAP compliant results and allows confident (i.e. calibrated in SAP) predictions to be made regarding the impact of novel heating and renewable energy systems. This paper describes the addition of an Air Source Heat Pump (ASHP) model to IDEAS. This allows for detailed analysis to be made of ASHPs in a SAP compliant framework. The benefits of using the IDEAS method is highlighted with capabilities outwith the scope of SAP also possible. For example, IDEAS can be used as sizing tool for a heating system in a building

A novel DSM philosophy for building integrated renewable systems

This paper presents an overview of a novel concept in IT network design and power control focused on matching building integrated renewable power generation with local demands. It describes how this is achieved through combination of energy demand reduction and dynamic utilisation of embedded energy storage in a robust, efficient and cost effective manner. A brief overview of the main features of the design is given in terms of its intended benefits as an integrated system. The load components and distribution topology are described for this experimental system within the limits set by the capacity, capabilities and desired function of the network. Power supply to the network is described as including a back-up source to the photovoltaic (PV) source to add functionality and stability with no requirements for undesirable exporting of excess PV generation. The necessary configuration of the renewable array integrating with the network is also highlighted with an example compatible solar module device. A trial of the technology and demand management control in a high profile office building is described. This trial in a live working environment is providing invaluable real world data to compare against modelling and network simulation results

A multimodal imaging study of recognition memory in very preterm born adults

Very preterm (<32 weeks of gestation) birth is associated with structural brain alterationsand memory impairments throughout childhood and adolescence. Here, we used functional MRI(fMRI) to study the neuroanatomy of recognition memory in 49 very preterm-born adults and 50 con-trols (mean age: 30 years) during completion of a task involving visual encoding and recognition ofabstract pictures. T1-weighted and diffusion-weighted images were also collected. Bilateral hippocam-pal volumes were calculated and tractography of the fornix and cingulum was performed and assessedin terms of volume and hindrance modulated orientational anisotropy (HMOA). Online recognitionmemory task performance, assessed with A scores, was poorer in the very preterm compared with thecontrol group. Analysis of fMRI data focused on differences in neural activity between the recognitionand encoding trials. Very preterm born adults showed decreased activation in the right middle frontalgyrus and posterior cingulate cortex/precuneus and increased activation in the left inferior frontalgyrus and bilateral lateral occipital cortex (LOC) compared with controls. Hippocampi, fornix and cin-gulum volume was significantly smaller and fornix HMOA was lower in very preterm adults. Amongall the structural and functional brain metrics that showed statistically significant group differences,LOC activation was the best predictor of online task performance (P 5 0.020). In terms of associationbetween brain function and structure, LOC activation was predicted by fornix HMOA in the pretermgroup only (P 5 0.020). These results suggest that neuroanatomical alterations in very preterm bornindividuals may be underlying their poorer recognition memory performance

Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment

Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.</p

The Developing Human Connectome Project Neonatal Data Release

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

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

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. FUNDING: British Heart Foundation