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In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and tumor pathology. We used National Comprehensive Cancer Network (NCCN) consensus guidelines, Food and Drug Administration (FDA) approvals, and provincially reimbursed treatments to define genomic biomarkers associated with approved targeted therapeutic options (TTOs). Tumor tissue/site of origin was reassessed for most cases using genomic analysis, including a machine learning algorithm (Supervised Cancer Origin Prediction Using Expression [SCOPE]) trained on The Cancer Genome Atlas data. WGTA was performed on 652 cases, including a range of primary tumor types/tumor sites and 15 malignant tumors of uncertain histogenesis (MTUH). At the time WGTA was performed, alterations associated with an approved TTO were identified in 39 (6%) cases; 3 of these were not identified through routine pathology workup. In seven (1%) cases, the pathology workup either failed, was not performed, or gave a different result from the WGTA. Approved TTOs identified by WGTA increased to 103 (16%) when applying 2021 guidelines. The histopathologic diagnosis was reviewed in 389 cases and agreed with the diagnostic consensus after WGTA in 94% of non‐MTUH cases (n = 374). The remainder included situations where the morphologic diagnosis was changed based on WGTA and clinical data (0.5%), or where the WGTA was non‐contributory (5%). The 15 MTUH were all diagnosed as specific tumor types by WGTA. Tumor board reviews including WGTA agreed with almost all initial predictive molecular profile and histopathologic diagnoses. WGTA was a powerful tool to assign site/tissue of origin in MTUH. Current efforts focus on improving therapeutic predictive power and decreasing cost to enhance use of WGTA data as a routine clinical test. [ABSTRACT FROM AUTHOR]

This paper describes a heat pump investigation for GreenSCIES (GS), a fifth Generation district heating and cooling (5DHC) network in Islington, London. The paper describes the GreenSCIES concept integrating Mobility, Power and Heat into a Smart Local Energy System (SLES). At the heart of the system is an ultra-low temperature ambient loop network, which permits bi-directional flow within the pipes to allow energy exchange between heating and cooling customers at different times and in different locations, depending on where demand is at any given time. An existing data centre provides the primary source of waste heat for the scheme. Heat pumps in distributed energy centres are utilised to amplify the temperature of the ambient loop to deliver heat in connected buildings. The energy centres integrate heat pumps with building-mounted solar photovoltaic (PV) systems and electric vehicle (EV) charging points. The paper provides an overview of the integrated SLES concept, focussing on the heat pump selection and the short and long-term thermal storage options designed for the scheme. The results show that even the smaller constructible 'New River' scheme will save 5,000 tons of CO2e annually. This will tend to 100% as the grid decarbonise further. Therefore, the GS SLES concept applied to urban areas could deliver significant carbon emission savings in the UK and elsewhere. Practical application: Project GreenSCIES, is a detailed design study to develop a Smart, Local Energy System (SLES) for a large community in the London Borough of Islington. Our consortium have developed an innovative SLES concept, centred around a fifth generation district heating and cooling network. The GS ambient loop systems have negligible losses and much greater efficiencies than traditional district heat networks. As recognised by the UK Government's Heat and Buildings Strategy, ambient loop systems should be considered where large-scale neighbourhood regeneration occurs. The proposed SLES concept applied to wider urban areas could deliver significant carbon emission savings in the UK. [ABSTRACT FROM AUTHOR]

This is the first report of a NACC2‐NTRK2 fusion in a histological glioblastoma. Oncogenomic analysis revealed this actionable fusion oncogene in a pediatric cerebellar glioblastoma, which would not have been identified through routine diagnostics, demonstrating the value of clinical genome profiling in cancer care. [ABSTRACT FROM AUTHOR]

Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain cancer with no effective therapy. Histological similarity of DIPG to supratentorial high-grade astrocytomas of adults has led to assumptions that these entities possess similar underlying molecular properties and therefore similar therapeutic responses to standard therapies. The failure of all clinical trials in the last 30years to improve DIPG patient outcome has suggested otherwise. Recent studies employing next-generation sequencing and microarray technologies have provided a breadth of evidence highlighting the unique molecular genetics and epigenetics of this cancer, distinguishing it from both adult and pediatric cerebral high-grade astrocytomas. This review describes the most common molecular genetic and epigenetic signatures of DIPG in the context of molecular subgroups and histopathological diagnosis, including this tumor entity's unique mutational landscape, copy number alterations, and structural variants, as well as epigenetic changes on the global DNA and histone levels. The increased knowledge of DIPG biology and histopathology has opened doors to new diagnostic and therapeutic avenues. [ABSTRACT FROM AUTHOR]

This paper introduces a project called GreenSCIES; an InnovateUK funded detailed design project to develop a Smart Local Energy System (SLES) delivering a significant carbon saving for local residents, schools and businesses. The SLES is centred around a 5th Generation District Heating and Cooling (5DHC) network in the London Borough of Islington. The local energy system will deliver low carbon heating, cooling, power and e-mobility charging powered by renewable energy and waste heat, sourced from the local area. The proposed SLES will manage and balance the supply, storage (both thermal and electrical) and use of local energy across mobility, power and heat vectors. It will do so using smart control technologies, bringing significant energy efficiency and security as well as social, environmental and economic benefits to Islington. The paper introduces the holistic SLES design approach developed by the GreenSCIES consortium, building upon an initial feasibility study previously published by the authors. The design methodology described takes technical and commercial aspects of a SLES design into account, whilst also explaining the importance of effective stakeholder engagement and co-design with local communities. The paper also provides a technical overview around the intended operation of ambient loop and heat pumps alongside long and short term thermal energy storage. A technical approach selected for integrating electric vehicles (EVs) and solar photovoltaic (PV) is also discussed in detail, alongside the control system architecture developed for the integrated SLES. The paper subsequently moves into demonstrating the benefits of the integrated SLES through a focused scheme design called New River, demonstrating integrated SLES performance compared to conventional systems in a real setting, through a comprehensive energy model. The results presented from a techno-economic analysis demonstrate that significant carbon savings and an attractive internal rate of return of (10%) can be achieved. The results presented show that even the smaller constructible "New River" scheme will save more 5000 tons of CO 2 e annually. This is a reduction in carbon emissions by 80% over conventional systems and, therefore a major decarbonisation solution in large cities across the world. The GreenSCIES approach presented in this paper is replicable worldwide and could become a central part of delivering nations' net zero carbon strategy. • Ambient loops integrated with EV and PV could help decarbonise urban areas. • Aquifer Thermal Energy Storage provides a novel way of balancing the system. • The Behind the Meter electrical connection approach is cost-effective. • Significant carbon savings and an attractive internal rate of return. • The holistic SLES design approach is replicable and it can be used as a guide. [ABSTRACT FROM AUTHOR]

Nine subjects with late onset unipolar depression were studied, before and after treatment, using I-123 iodoamphetamine SPECT. In all nine subjects clinical improvement was associated with a significant increase (p<0.01) in cerebral/cerebellar activity ratios that correlated well with the decline in Hamilton depression scores. [ABSTRACT FROM AUTHOR]

Integrated smartly controlled energy networks have the potential to deliver significant reductions in carbon emissions, improve air quality and reduce energy costs for end-users across the world. This paper introduces a novel methodology for the development of integrated thermal, power and mobility 5th generation (5G) smart energy networks. The proposed 5G concept builds on state of the art by connecting flexible electricity demands such as heat pumps, and electric vehicles to intermittent, renewable and secondary energy sources and storage using artificial intelligence to facilitate optimal control and to maximise revenue and carbon savings. The proposed innovative method is being applied in central London through the development of two independent 5G smart energy schemes. The proposed schemes will incorporate a range of different renewables and secondary energy sources, for example, waste heat from local data centres and the London Underground that will supply a large proportion of the energy demand of the overall district network capacity. Both networks will operate at close to ambient temperature, approximately 15–25 °C as a so-called 'ambient loop' system, with individual heat pumps for each end-user or building connected to the network. The system also integrates thermal and electrical storage to create additional flexibility for the network and smart control for demand-side management. A smart management system flexibly controls individual assets such as heat pumps and electric vehicles in response to price signals reflecting the intermittency of renewable energy sources on the electricity grid. The ambient district thermal loop will distribute low carbon energy to a range of end users. Results presented in this paper provide an understanding of capital costs associated with integrated smart energy systems and the relative performance of individual technologies in a complex system using a techno-economic modelling approach. Overall, this paper demonstrates that the implementation of the 5G concept results in lower energy costs to consumers while at the same time transforming a large existing urban area to a near zero-carbon energy system in terms of heating, cooling, electricity and transport. [ABSTRACT FROM AUTHOR]