Charge injection instability in perfect insulators

We show that in a macroscopic perfect insulator, charge injection at a field-enhancing defect is associated with an instability of the insulating state or with bistability of the insulating and the charged state. The effect of a nonlinear carrier mobility is emphasized. The formation of the charged state is governed by two different processes with clearly separated time scales. First, due to a fast growth of a charge-injection mode, a localized charge cloud forms near the injecting defect (or contact). Charge injection stops when the field enhancement is screened below criticality. Secondly, the charge slowly redistributes in the bulk. The linear instability mechanism and the final charged steady state are discussed for a simple model and for cylindrical and spherical geometries. The theory explains an experimentally observed increase of the critical electric field with decreasing size of the injecting contact. Numerical results are presented for dc and ac biased insulators.Comment: Revtex, 7pages, 4 ps figure

Sustainable Treatment of Acidic and Alkaline Leachates from Mining and Industrial Activities: Current Practice and Future Perspectives

Water resources are under continued pressure from anthropogenic sources, including acidic waste from abandoned mine sites and alkaline waste from a variety of industrial activities. Large quantities of mine and industrial wastes are typically stored in tailings facilities which can generate significant quantities of leachates due to weathering. If released untreated to the aquatic environment these have the potential to contaminate surface and ground waters. In addition, generation of leachates from abandoned or closed sites presents a major long-term environmental challenge where the generation of leachates is expected to continue for decades if not centuries post closure. An overview of leachate production and associated treatment technologies are described, with an emphasis on passive and potentially sustainable technologies. Measures to prevent the formation of acidic leachates and the potential for resource recovery from acidic and alkaline wastes and leachates are also discussed. Finally, technologies that require further development for long term and sustainable treatment are highlighted

A multi-energy system optimisation software for advance process control using hypernetworks and a micro-service architecture

This paper describes a multi-energy system optimisation software, “Sustainable Energy Management System” (SEMS), developed as part of a Siemens, Greater London Authority and Royal Borough of Greenwich partnership in collaboration with the University of Nottingham, Nottingham Trent University and Imperial College London. The software was developed for application at a social housing estate in Greenwich, London, as part of the Borough’s efforts to retrofit the energy systems and building fabric of its housing stock. Its purpose is to balance energy across vectors and networks through day-ahead forecasting and optimisations that can be interpreted as control outputs for energy plant such as a water source heat pump, district heating pumps and values, power switchgear, gas boilers, a thermal store, electric vehicle chargers and a photovoltaic array. The optimisation objectives are to minimise greenhouse gas emissions and operational cost. The tool uses Hypernetwork Theory based orchestration coupled with a microservice architecture. The distributed nature of the design ensures flexibility and scalability. Currently, microservices have been programmed to forecast domestic heating demand, domestic electricity demand, electric vehicle demand, solar photovoltaic generation, ground temperature, and to run a day-ahead energy balance optimisation. This paper presents the results from both domestic heat and electricity demand forecasting, as well as the overall design and integration of the software with a physical system. The works build on that of O’Dwyer, et al. (2020) who developed a preliminary energy management software and digital twin. Their work acts as a foundation for this real-world commercialisation-ready program that integrates with physical assets

Consistency, completeness and external validity of ethnicity recording in NHS primary care records: a cohort study in 25 million patients’ records at source using OpenSAFELY

Background: Ethnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients’ ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however, the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data. Methods: We describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in > 25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census. Results: 78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%). Conclusions: Primary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data

Association between tissue hypoxia and elevated non-protein sulphydryl concentrations in human cervical carcinoma xenografts

A double staining technique was developed for the simultaneous measurement of tissue hypoxia and the concentration of non-protein sulphydryls (NPSH), based on the fluorinated nitroimidazole EF5 and the fluorescent histochemical NPSH stain 1-(4-chloromercuriphenoylazo)-naphthol-2 (mercury orange). Cryostat sections of tumour tissue were examined by fluorescence image analysis, using a computer-controlled microscope stage to generate large tiled field images of the cut tumour surface. This method was applied to the human cervical squamous cell carcinoma lines ME180 and SiHa, grown as xenografts in severe combined immunodeficient (SCID) mice, in order to determine if there is a systematic relationship between tissue hypoxia and NPSH levels. Hypoxic regions of the tumours, defined by EF5 labelling, were found to show greater NPSH concentrations relative to better oxygenated regions. This is probably due to increases in glutathione, since the ME180 and SiHa xenografts contained low levels of cysteine and metallothionein; the other major cellular thiols that can bind to mercury orange. Because the effects of glutathione on radiation and chemotherapy resistance are likely to be greater under hypoxic conditions, these results have potentially important implications for the study of resistance mechanisms in solid tumours. © 1999 Cancer Research Campaig

Benchmarking atomic data for astrophysics: a first look at the soft X-ray lines

A collection of the best solar and laboratory spectra in the soft X-rays is used here to perform a preliminary benchmark in this wavelength region, by comparing observed vs. predicted wavelengths and calibrated solar irradiances. The benchmark focuses on the Fe IX - Fe XIV ions,for which we have recently calculated the relevant atomic data, however a few other ions have also been benchmarked. The iron ions are dominating the soft X-rays, however a large fraction of the strongest soft X-ray lines due to n=4 -> n=3 transitions were previously unidentified. The strongest transitions are all identified here, in particular the decays from the core-excited levels (3s 3p^l 4s, l=$ 5,4,3,2,1 for Fe X, Fe XI, Fe XII, Fe XIII, and Fe XIV respectively) which are the strongest soft X-ray transitions from these ions. Many new identifications are proposed, some only tentatively. Good agreement in terms of solar irradiances between the soft X-ray and EUV (n=3 -> n=3) transitions is found, confirming the reliability of the new large-scale calculations. Some of the new atomic data and identifications are particularly important for the Solar Dynamic Observatory (SDO) Atmospheric Imaging Assembly (AIA) 94 A band.Comment: Accepted for publication in A&A (under revision

Molecular therapy for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Conventional cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. Recently, a number of new drugs targeting molecular mechanisms involved in liver cell transformation have entered into clinical trials and led to encouraging results. In this review we summarise this data and point to a number of new compounds, which are currently being tested and can potentially broaden our therapeutic arsenal even further

Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma

Background:Hepatocellular carcinoma (HCC) is a highly vascularised and poor-prognosis tumour. NGR-hTNF is a vascular-targeting agent consisting of human tumour necrosis factor-alpha fused to the tumour-homing peptide NGR, which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels.Methods:Twenty-seven patients with advanced-stage disease resistant to either locoregional (59%; range, 1-3), systemic treatments (52%; range, 1-3) or both (33%) received NGR-hTNF 0.8 gm-2 once every 3 weeks. The primary aim of the study was progression-free survival (PFS).Results:No grade 3-4 treatment-related toxicities were noted. Common toxicity included mild-to-moderate, short-lived chills (63%). Median PFS was 2.3 months (95% CI: 1.7-2.9). A complete response ongoing after 20 months was observed in a sorafenib-refractory patient and a partial response in a Child-Pugh class-B patient, yielding a response rate of 7%. Six patients (22%) experienced stable disease. The disease control rate (DCR) was 30% and was maintained for a median PFS time of 4.3 months. Median survival was 8.9 months (95% CI: 7.5-10.2). In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months.Conclusion:NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest

Sexual Dimorphism in Healthy Aging and Mild Cognitive Impairment: A DTI Study

Previous PET and MRI studies have indicated that the degree to which pathology translates into clinical symptoms is strongly dependent on sex with women more likely to express pathology as a diagnosis of AD, whereas men are more resistant to clinical symptoms in the face of the same degree of pathology. Here we use DTI to investigate the difference between male and female white matter tracts in healthy older participants (24 women, 16 men) and participants with mild cognitive impairment (21 women, 12 men). Differences between control and MCI participants were found in fractional anisotropy (FA), radial diffusion (DR), axial diffusion (DA) and mean diffusion (MD). A significant main effect of sex was also reported for FA, MD and DR indices, with male control and male MCI participants having significantly more microstructural damage than their female counterparts. There was no sex by diagnosis interaction. Male MCIs also had significantly less normalised grey matter (GM) volume than female MCIs. However, in terms of absolute brain volume, male controls had significantly more brain volume than female controls. Normalised GM and WM volumes were found to decrease significantly with age with no age by sex interaction. Overall, these data suggest that the same degree of cognitive impairment is associated with greater structural damage in men compared with women