Real-world evidence of epidemiology, patient characteristics, and mortality in people with drug-resistant epilepsy in the United Kingdom, 2011-2021.

BACKGROUND: A third of people with epilepsy are drug resistant. People with drug-resistant epilepsy (DRE) have a higher risk of mortality and physical injuries than those who respond to anti-seizure medication (ASM). This study describes patient characteristics, comorbidities, and mortality in people with DRE in the UK. METHODS: The Clinical Practice Research Datalink was utilised to select people with DRE prescribed a third ASM between 1 January 2011 and 31 March 2021. Annual incidence and prevalence of DRE, patient characteristics, comorbidities, and mortality rates were analysed. Subgroup analysis was performed by age, sex, presence of intellectual disabilities and time from epilepsy diagnosis to DRE. RESULTS: A total of 34,647 people with DRE were included (mean ± SD age 42.68 ± 23.59 years, 52.6% females). During the study period, annual DRE incidence ranged from 1.99% to 3.12%. As of 31 March 2021, DRE prevalence was 26.6% (95% confidence interval [CI] 26.3%-26.8%). A greater proportion of people with DRE resided in the most deprived regions, with 21.1% and 16.7% in the top two quintiles of the Index of Multiple Deprivation respectively, compared to < 15% in the three less deprived regions. All-cause mortality ranged from 3,687 to 4,802 per 100,000 persons with DRE, four times higher than that in the general population in the UK. Variations existed across subgroups. CONCLUSIONS: Considerable disease burden was observed in people with DRE in the UK. The findings emphasise the importance of early DRE diagnosis and appropriate disease management in people who develop DRE.

Monitoring of the Initial Stages of Diamond Growth on Aluminum Nitride Using In Situ Spectroscopic Ellipsometry.

The high thermal conductivity of polycrystalline diamond makes it ideally suited for thermal management solutions for gallium nitride (GaN) devices, with a diamond layer grown on an aluminum nitride (AlN) interlayer atop the GaN stack. However, this application is limited by the thermal barrier at the interface between diamond and substrate, which has been associated with the transition region formed in the initial phases of growth. In this work, in situ spectroscopic ellipsometry (SE) is employed to monitor early-stage microwave plasma-enhanced chemical vapor deposition diamond growth on AlN. An optical model was developed from ex situ spectra and applied to spectra taken in situ during growth. Coalescence of separate islands into a single film was marked by a reduction in bulk void fraction prior to a spike in sp2 fraction due to grain boundary formation. Parameters determined by the SE model were corroborated using Raman spectroscopy and atomic force microscopy.

Polycrystalline Diamond Micro-Hotplates.

Micro-hotplate structures are increasingly being investigated for use in a host of applications ranging from broadband infra-red sources within absorption-based gas sensors to in situ heater stages for ultra-high-resolution imaging. With devices usually fabricated from a conductive electrode placed on top of a freestanding radiator element, coefficient of thermal expansion (CTE) mismatches between layers and electro-migration within the heating element typically lead to failure upon exceeding temperatures of 1600 K. In an attempt to mitigate such issues, a series of hotplates of varying geometry have been fabricated from a single layer of mechanically robust, high thermal conductivity, and low CTE boron-doped polycrystalline diamond. Upon testing under high vacuum conditions and characterization of the emission spectra, the resulting devices are shown to exhibit a grey-body like emission response and reach temperatures vastly in excess of conventional geometries of up to 2731 K at applied powers of ⩽100 mW. Characterization of the thermalization time meanwhile demonstrates rapid millisecond response times, while Raman spectroscopy reveals the performance of the devices is dictated by cumulative graphitization at elevated temperatures. As such, both diamond and sp2 carbon are shown to be promising materials for the fabrication of next-generation micro-hotplates.

Levelling Up for health in towns? Development of a new deprivation index: the 'Stronger Towns Index' and its association with self-rated health and migration in England, between 2001 and 2011.

Aim: To develop the 'Stronger Towns Index': a deprivation index that took into account characteristics of areas encompassing towns that may be eligible for redevelopment funding and explore how this index was associated with self-rated health and migration within England between 2001 and 2011. Subject and methods: All members of the ONS Longitudinal Study in England aged 16 and over in 2001 whose records included a self-rated health response and a valid local authority code.Local authorities in England were ranked using a composite index developed using the five metrics set out in the Stronger Towns Funding: productivity, income, skills, deprivation measures, and the proportion of people living in towns.The index was split into deciles, and logistic regression carried out on the association between decile and self-rated health in 2001 in the main sample (n = 407,878) and decile change and self-rated health in 2011 in a subsample also present in 2011, with migration information (n = 299,008). Results: There were areas in the lowest deciles of Town Strength who did not receive funding. After multiple adjustment, LS members living in areas with higher deciles were significantly more likely (7% to 38%) to report good health than those in the lowest decile in 2001. Remaining in the same decile between 2001 and 2011 was associated with 7% lower odds of good self-rated health in 2011. Conclusion: It is important to consider health in towns when allocating funding. Areas in the Midlands may have missed out on funding which might help mitigate poor health.

Implementation research for promoting access and rational use of antibiotics for children: lessons learnt from Tanzania.

Implementation research (IR) has proved to be a potential catalyst in facilitating the uptake of evidence-based innovations into routine practices and thereby maximizing public health outcomes. IR not only focuses on the effectiveness of the innovations but also identifies and addresses the barriers and facilitators to maximize their uptake into routine practices. This article describes the processes undertaken to implement a research project aimed at promoting access and rational use of antibiotics for children (PARAC). It also provides an overview of the lessons learnt during its implementation in Tanzanian hospital and community settings.

Practical and General Alcohol Deoxygenation Protocol.

Herein, we describe a practical protocol for the removal of alcohol functional groups through reductive cleavage of their benzoate ester analogs. This transformation requires a strong single electron transfer (SET) reductant and a means to accelerate slow fragmentation following substrate reduction. To accomplish this, we developed a photocatalytic system that generates a potent reductant from formate salts alongside Brønsted or Lewis acids that promote fragmentation of the reduced intermediate. This deoxygenation procedure is effective across structurally and electronically diverse alcohols and enables a variety of difficult net transformations. This protocol requires no precautions to exclude air or moisture and remains efficient on multigram scale. Finally, the system can be adapted to a one-pot benzoylation-deoxygenation sequence to enable direct alcohol deletion. Mechanistic studies validate that the role of acidic additives is to promote the key C(sp3 )-O bond fragmentation step.

SAW Resonators and Filters Based on Sc0.43Al0.57N on Single Crystal and Polycrystalline Diamond.

The massive data transfer rates of nowadays mobile communication technologies demand devices not only with outstanding electric performances but with example stability in a wide range of conditions. Surface acoustic wave (SAW) devices provide a high Q-factor and properties inherent to the employed materials: thermal and chemical stability or low propagation losses. SAW resonators and filters based on Sc0.43Al0.57N synthetized by reactive magnetron sputtering on single crystal and polycrystalline diamond substrates were fabricated and evaluated. Our SAW resonators showed high electromechanical coupling coefficients for Rayleigh and Sezawa modes, propagating at 1.2 GHz and 2.3 GHz, respectively. Finally, SAW filters were fabricated on Sc0.43Al0.57N/diamond heterostructures, with working frequencies above 4.7 GHz and ~200 MHz bandwidths, confirming that these devices are promising candidates in developing 5G technology.

Non-Markovian temporal networks with auto- and cross-correlated link dynamics.

Many of the biological, social and man-made networks around us are inherently dynamic, with their links switching on and off over time. The evolution of these networks is often observed to be non-Markovian, and the dynamics of their links are often correlated. Hence, to accurately model these networks, predict their evolution, and understand how information and other relevant quantities propagate over them, the inclusion of both memory and dynamical dependencies between links is key. In this article we introduce a general class of models of temporal networks based on discrete autoregressive processes for link dynamics. As a concrete and useful case study, we then concentrate on a specific model within this class, which allows to generate temporal networks with a specified underlying structural backbone, and with precise control over the dynamical dependencies between links and the strength and length of their memories. In this network model the presence of each link is influenced not only by its past activity, but also by the past activities of other links, as specified by a coupling matrix, which directly controls the causal relations, and hence the correlations, among links. We propose a maximum likelihood method for estimating the model's parameters from data, showing how the model allows a more realistic description of real-world temporal networks and also to predict their evolution. Due to the flexibility of maximum likelihood inference, we illustrate how to deal with heterogeneity and time-varying patterns, possibly including also nonstationary network dynamics. We then use our network model to investigate the role that, both the features of memory and the type of correlations in the dynamics of links have on the properties of processes occurring over a temporal network. Namely, we study the speed of a spreading process, as measured by the time it takes for diffusion to reach equilibrium. Through both numerical simulations and analytical results, we are able to separate the roles of autocorrelations and neighborhood correlations in link dynamics, showing that not only is the speed of diffusion nonmonotonically dependent on the memory length, but also that correlations among neighboring links help to speed up the spreading process, while autocorrelations slow it back down. Our results have implications in the study of opinion formation, the modeling of social networks, and the spreading of epidemics through mobile populations.

The shape of memory in temporal networks.

How to best define, detect and characterize network memory, i.e. the dependence of a network's structure on its past, is currently a matter of debate. Here we show that the memory of a temporal network is inherently multidimensional, and we introduce a mathematical framework for defining and efficiently estimating the microscopic shape of memory, which characterises how the activity of each link intertwines with the activities of all other links. We validate our methodology on a range of synthetic models, and we then study the memory shape of real-world temporal networks spanning social, technological and biological systems, finding that these networks display heterogeneous memory shapes. In particular, online and offline social networks are markedly different, with the latter showing richer memory and memory scales. Our theory also elucidates the phenomenon of emergent virtual loops and provides a novel methodology for exploring the dynamically rich structure of complex systems.

Trace gas analysis with laser dispersion spectroscopy.

Trace gas analysis provides a wide range of insights into environmental processes, particularly with regards to global warming and air quality. With the urgent need to identify sources and accurately measure the harmful emissions negatively impacting our planet, Laser Dispersion Spectroscopy (LDS) offers a unique approach. LDS technology measures optical molecular dispersion via a differential phase measurement of light and, operating in the mid-infrared, provides highly sensitive and robust measurements. This enables highly precise, real-time gas measurements even in adverse environmental conditions such as rain, fog, snow or dust. The technology can be used in both extractive and open-path formats, with real-world applications including emissions monitoring on oil and gas sites, measuring the impact of agricultural activities and monitoring carbon capture storage facilities.

Non-innocent Radical Ion Intermediates in Photoredox Catalysis: Parallel Reduction Modes Enable Coupling of Diverse Aryl Chlorides.

We describe a photocatalytic system that elicits potent photoreductant activity from conventional photocatalysts by leveraging radical anion intermediates generated in situ. The combination of an isophthalonitrile photocatalyst and sodium formate promotes diverse aryl radical coupling reactions from abundant but difficult to reduce aryl chloride substrates. Mechanistic studies reveal two parallel pathways for substrate reduction both enabled by a key terminal reductant byproduct, carbon dioxide radical anion.

Electropositive Nanodiamond-Coated Quartz Microfiber Membranes for Virus and Dye Filtration.

Electropositive membranes demonstrating high flux at low pressure differentials show great promise as universal separation platforms for viruses and other charged entities when centralized systems of water and power are scarce. However, the fabrication of a suitably stable membrane with optimal electrostatic characteristics remains a challenge. Here, hydrogenated detonation nanodiamond was loaded onto a quartz microfiber support membrane and coupled to the membrane surface under a high vacuum annealing process. The fabricated membranes display a zeta potential of +45 mV at pH 7 and an isoelectric point around pH 11. We show that the nanodiamond coating is robust to prolonged periods of pressurized water flow by performing extensive zeta potential measurements over time, and water filtration tests demonstrated excellent membrane retention for the electronegative dye molecule acid black 2, and at least a 6.2 log10 reduction in MS2 bacteriophage from feed waters (>99.9999%).

Unveiling Potent Photooxidation Behavior of Catalytic Photoreductants.

We describe a photocatalytic system that reveals latent photooxidant behavior from one of the most reducing conventional photoredox catalysts, N-phenylphenothiazine (PTH). This aerobic photochemical reaction engages difficult to oxidize feedstocks, such as benzene, in C(sp2)-N coupling reactions through direct oxidation. Mechanistic studies are consistent with activation of PTH via photooxidation and with Lewis acid cocatalysts scavenging inhibitors inextricably formed in this process.

Is studying medicine good for your health? Long-term health outcomes of a cohort of clinical medicine graduates in England and Wales in the ONS Longitudinal Study.

OBJECTIVE: To quantify the potential protective effect on health associated with study of a clinical medicine degree. DESIGN: Prospective population-based cohort data collected at census and linked over time: cohort born before 1976 and survived to 2011. Subgroup analysis on those who reported having a degree at 1991 census. SETTING: England and Wales population-based, including institutions. PARTICIPANTS: 159 116 men and 174 062 women; 13 390 men with degrees and 8143 women with degrees. MAIN OUTCOME MEASURE: Self-reported general health in 2011 based on logistic regression analysis. RESULTS: Male graduates had 92% higher odds of having good or very good health than male non-graduates after adjustment for age and socioeconomic position (CI 1.82 to 2.03). Female graduates had 85% higher odds of having good or very good health than female non-graduates after adjustment for age and socioeconomic position (CI 1.73 to 1.98). Male clinical medicine graduates had 45% higher odds of having good or very good health than male humanities graduates after adjustment for age and socioeconomic position (CI 1.09 to 1.92). Male physical sciences graduates also had higher odds of having good or very good health than male humanities graduates after adjustment for age and socioeconomic position, but life sciences and social science graduates did not. There were no significant differences by degree subject for women. CONCLUSIONS: Male graduates in clinical medicine have higher odds of good self-reported health. Knowledge of medicine may confer a health advantage for men above that of other degrees.

Crystalline Interlayers for Reducing the Effective Thermal Boundary Resistance in GaN-on-Diamond.

Integrating diamond with GaN high electron mobility transistors (HEMTs) improves thermal management, ultimately increasing the reliability and performance of high-power high-frequency radio frequency amplifiers. Conventionally, an amorphous interlayer is used before growing polycrystalline diamond onto GaN in these devices. This layer contributes significantly to the effective thermal boundary resistance (TBReff) between the GaN HEMT and the diamond, reducing the benefit of the diamond heat spreader. Replacing the amorphous interlayer with a higher thermal conductivity crystalline material would reduce TBReff and help to enable the full potential of GaN-on-diamond devices. In this work, a crystalline Al0.32Ga0.68N interlayer has been integrated into a GaN/AlGaN HEMT device epitaxy. Two samples were studied, one with diamond grown directly on the AlGaN interlayer and another incorporating a thin crystalline SiC layer between AlGaN and diamond. The TBReff, measured using transient thermoreflectance, was improved for the sample with SiC (30 ± 5 m2 K GW-1) compared to the sample without (107 ± 44 m2 K GW-1). The reduced TBReff is thought to arise from improved adhesion between SiC and the diamond compared to the diamond directly on AlGaN because of an increased propensity for carbide bond formation between SiC and the diamond. The stronger carbide bonds aid transmission of phonons across the interface, improving heat transport.

High-throughput nitrogen-vacancy center imaging for nanodiamond photophysical characterization and pH nanosensing.

The fluorescent nitrogen-vacancy (NV) defect in diamond has remarkable photophysical properties, including high photostability which allows stable fluorescence emission for hours; as a result, there has been much interest in using nanodiamonds (NDs) for applications in quantum optics and biological imaging. Such applications have been limited by the heterogeneity of NDs and our limited understanding of NV photophysics in NDs, which is partially due to the lack of sensitive and high-throughput methods for photophysical analysis of NDs. Here, we report a systematic analysis of NDs using two-color wide-field epifluorescence imaging coupled to high-throughput single-particle detection of single NVs in NDs with sizes down to 5-10 nm. By using fluorescence intensity ratios, we observe directly the charge conversion of single NV center (NV- or NV0) and measure the lifetimes of different NV charge states in NDs. We also show that we can use changes in pH to control the main NV charge states in a direct and reversible fashion, a discovery that paves the way for performing pH nanosensing with a non-photobleachable probe.

Suppression of Deflecting Forces in Planar-Symmetric Dielectric Wakefield Accelerating Structures with Elliptical Bunches.

Wakefield based accelerators capable of accelerating gradients 2 orders of magnitude higher than present accelerators offer a path to compact high energy physics instruments and light sources. However, for high gradient accelerators, beam instabilities driven by commensurately high transverse wakefields limit beam quality. Previously, it has been theoretically shown that transverse wakefields can be reduced by elliptically shaping the transverse sizes of beams in dielectric structures with planar symmetry. Here, we report experimental measurements that demonstrate reduced transverse wakefields for elliptical beams in planar symmetric structures which are consistent with theoretical models. These results may enable the design of gigavolt-per-meter gradient wakefield based accelerators that produce and stably accelerate high quality beams.

Potent Reductants via Electron-Primed Photoredox Catalysis: Unlocking Aryl Chlorides for Radical Coupling.

We describe a new catalytic strategy to transcend the energetic limitations of visible light by electrochemically priming a photocatalyst prior to excitation. This new catalytic system is able to productively engage aryl chlorides with reduction potentials hundreds of millivolts beyond the potential of Na0 in productive radical coupling reactions. The aryl radicals produced via this strategy can be leveraged for both carbon-carbon and carbon-heteroatom bond-forming reactions. Through direct comparison, we illustrate the reactivity and selectivity advantages of this approach relative to electrolysis and photoredox catalysis.

Facile Amine Termination of Nanodiamond Particles and Their Surface Reaction Dynamics.

Nanodiamond synthesized by the detonation method is a composite of sp3/sp2 carbon structures; amorphous and disordered-sp2 carbons populate the surface of a sp3 diamond core lattice. Because of the production process, various elemental impurities such as N, O, H, and so forth are inherent in interstitial sites or the surface carbon (sp2/amorphous) network. Herein, the reaction dynamics on the surface of ultradisperse diamond (UDD) due to the surface transformation or reconstruction during annealing in vacuum with temperatures ranging from ambient to 800 °C is described. In situ measurement of Fourier transform infrared spectroscopic analysis shows that low-temperature (<500 °C) annealing of UDD in vacuum results in isonitrile/isocyanide (-N=C:) and nitrile functionalization (-C≡N) on the surface. At temperatures ∼500 °C, the surface hydrogenation of UDD is initiated. During annealing at 780-800 °C, the nitrile group (-C≡N) is reduced to the primary amine (NH2), and isonitrile (-N=C:) turns it to be in the saturated () structure. On exposure to air, the obtained isonitrile is transformed to an N-formyl derivative (Aryl/R-NH-CHO) structure via hydrolysis. This study provides a fundamental insight into the surface reactive profile of UDD which could lead to facile surface functionalization properties and their applications in various fields such as biomedical, biosensing, drug delivery, epoxy materials process, tribology, and possibly in cyano (-C≡N/-N=C:) chemistry.