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This paper describes a simulation-based project to help North Mersey Community National Health Service Trust to design and plan the operation of a NHS Walk-in Centre. The simulation model developed of this multi-service facility was used to facilitate managers and health professionals to recognize existing problems and potential future problems, and to investigate ideas for their 'solution'. In the fast-moving NHS where initiatives to improve access, such as walk-in centres, are a recent development and where no two centres are the same, ideas for best practice borrowed from elsewhere can be quickly tested for suitability in the local situation. Keywords: health; simulation; walk-in centres

Background Topical imiquimod is sometimes used for lentigo maligna ( LM) in situ melanoma instead of surgery, but frequency of cure is uncertain. Pathological complete regression ( pCR) is a logical surrogate marker for cure after imiquimod, although residual LM and atypical melanocytic hyperplasia may not be reliably distinguished. A trial comparing imiquimod vs. surgery might be justified by a high imiquimod pCR rate. Objectives Primary: to estimate the pCR rate for LM following imiquimod. Secondary: to assess the accuracy of prediction of pCR, using clinical complete regression ( cCR) plus negative post-treatment biopsies, tolerability, resource use, patients' preferences and induced melanoma immunity. Methods This was a single-arm phase II trial of 60 imiquimod applications over 12 weeks for LM then radical resection. A pCR rate ≥ 25 out of 33 would reliably discriminate between pCR rates < 60% and ≥ 85%. Clinical response was assessed and biopsies taken after imiquimod. Patients recorded adverse events in diaries. Patient preference was measured after surgery using a standard gamble tool. Results The pCR rate was 10 of 27 (37%, 95% confidence interval 19-58%). The rate of cCR plus negative biopsies was 12 of 28, of whom seven of 11 had pCR on subsequent surgery. The median dose intensity was 86·7%. Of the 16 surveyed patients, eight preferred primary imiquimod over surgery if the cure rate for imiquimod was 80%, and four of 16 if it was ≤ 40%. Conclusions The pCR rate was insufficient to justify phase III investigation of imiquimod vs. surgery. Clinical complete response and negative targeted biopsies left uncertainty regarding pathological clearance. Some patients would trade less aggressive treatment of LM against efficacy. [ABSTRACT FROM AUTHOR]

The presence of multiple independent sensing parameters in a single device is the key conceptual advantage of sensor devices based on an organic thin film transistor (OTFT) over simple organic chemiresistors. Practically, however, these multiple parameters must first be extracted from the electrical characteristics of the OTFTs and, thus, they are not immediately apparent. To exploit the advantage of OTFT sensors, we require a measurement technology to extract these parameters in real time. Here, we introduce an efficient, cost-effective system that is a faster and more compact alternative to the expensive and cumbersome laboratory-based instruments currently available. The characterisation system presented here records the electric behaviour of OTFTs in the form of its "saturated transfer characteristics" multiple times per second for virtually unlimited periods of time, with the option to multiplex up to 20 devices in parallel. By applying a bespoke algorithm to the measured transfer characteristics, the system then extracts, in real time, several underlying transistor parameters (on- and off-current, threshold voltage, and charge carrier mobility). Tests were conducted on the example of a poly(thieno[3,2-b]thiophene) (PBTTT) OTFT exposed to ethanol vapour. The system extracts the underlying OTFT parameters with very low noise without introducing apparent correlations between independent parameters as an artefact. [ABSTRACT FROM AUTHOR]

We experimentally demonstrate the creation of defects in monolayer WSe 2 via nanopillar imprinting and helium ion irradiation. Based on the first method, we realize atomically thin vertical tunneling light-emitting diodes based on WSe 2 monolayers hosting quantum emitters at deterministically specified locations. We characterize these emitters by investigating the evolution of their emission spectra in external electric and magnetic fields, as well as by inducing electroluminescence at low temperatures. We identify qualitatively different types of quantum emitters and classify them according to the dominant electron-hole recombination paths, determined by the mechanisms of intervalley mixing occurring in fundamental conduction and/or valence subbands., Competing Interests: Competing interests statement:The authors declare no competing interest.

Bandstructure engineering using alloying is widely utilized for achieving optimized performance in modern semiconductor devices. While alloying has been studied in monolayer transition metal dichalcogenides, its application in van der Waals heterostructures built from atomically thin layers is largely unexplored. Here, heterobilayers made from monolayers of WSe 2 (or MoSe 2 ) and Mo x W 1 - x Se 2 alloy are fabricated and nontrivial tuning of the resultant bandstructure is observed as a function of concentration x. This evolution is monitored by measuring the energy of photoluminescence (PL) of the interlayer exciton (IX) composed of an electron and hole residing in different monolayers. In Mo x W 1 - x Se 2 /WSe 2 , a strong IX energy shift of ≈100 meV is observed for x varied from 1 to 0.6. However, for x < 0.6 this shift saturates and the IX PL energy asymptotically approaches that of the indirect bandgap in bilayer WSe 2 . This observation is theoretically interpreted as the strong variation of the conduction band K valley for x > 0.6, with IX PL arising from the K - K transition, while for x < 0.6, the bandstructure hybridization becomes prevalent leading to the dominating momentum-indirect K - Q transition. This bandstructure hybridization is accompanied with strong modification of IX PL dynamics and nonlinear exciton properties. This work provides foundation for bandstructure engineering in van der Waals heterostructures highlighting the importance of hybridization effects and opening a way to devices with accurately tailored electronic properties., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Extensive efforts have been undertaken to combine superconductivity and the quantum Hall effect so that Cooper-pair transport between superconducting electrodes in Josephson junctions is mediated by one-dimensional edge states 1-6 . This interest has been motivated by prospects of finding new physics, including topologically protected quasiparticles 7-9 , but also extends into metrology and device applications 10-13 . So far it has proven challenging to achieve detectable supercurrents through quantum Hall conductors 2,3,6 . Here we show that domain walls in minimally twisted bilayer graphene 14-18 support exceptionally robust proximity superconductivity in the quantum Hall regime, allowing Josephson junctions to operate in fields close to the upper critical field of superconducting electrodes. The critical current is found to be non-oscillatory and practically unchanging over the entire range of quantizing fields, with its value being limited by the quantum conductance of ballistic, strictly one-dimensional, electronic channels residing within the domain walls. The system described is unique in its ability to support Andreev bound states at quantizing fields and offers many interesting directions for further exploration., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The availability of accessible fabrication methods based on deterministic transfer of atomically thin crystals has been essential for the rapid expansion of research into van der Waals heterostructures. An inherent issue of these techniques is the deformation of the polymer carrier film during the transfer, which can lead to highly nonuniform strain induced in the transferred two-dimensional material. Here, using a combination of optical spectroscopy, atomic force, and Kelvin probe force microscopy, we show that the presence of nanometer scale wrinkles formed due to transfer-induced stress relaxation can lead to strong changes in the optical properties of MoSe 2 /WSe 2 heterostructures and the emergence of linearly polarized interlayer exciton photoluminescence. We attribute these changes to local breaking of crystal symmetry in the nanowrinkles, which act as efficient accumulation centers for interlayer excitons due to the strain-induced interlayer band gap reduction. Surface potential images of the rippled heterobilayer samples acquired using Kelvin probe force microscopy reveal variations of the local work function consistent with strain-induced band gap modulation, while the potential offset observed at the ridges of the wrinkles shows a clear correlation with the value of the tensile strain estimated from the wrinkle geometry. Our findings highlight the important role of the residual strain in defining optical properties of van der Waals heterostructures and suggest effective approaches for interlayer exciton manipulation by local strain engineering.

We evaluate methods to calculate the economic value of protected areas derived from the improved mental health of visitors. A conservative global estimate using quality-adjusted life years, a standard measure in health economics, is US$6 trillion p.a. This is an order of magnitude greater than the global value of protected area tourism, and two to three orders greater than global aggregate protected area management agency budgets. Future research should: refine this estimate using more precise methods; consider interactions between health and conservation policies and budgets at national scales; and examine links between personalities and protected area experiences at individual scale.

High broad-band photoresponsivity of mechanically formed InSe-graphene van der Waals heterostructures is achieved by exploiting the broad-band transparency of graphene, the direct bandgap of InSe, and the favorable band line up of InSe with graphene. The photoresponsivity exceeds that for other van der Waals heterostructures and the spectral response extends from the near-infrared to the visible spectrum., (© 2015 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Clinical investigational studies were conducted to demonstrate the accuracy and reproducibility of the Illumina MiSeqDx CF System, a next-generation sequencing (NGS) in vitro diagnostic device for cystic fibrosis testing., Methods: Two NGS assays - a Clinical Sequencing Assay (Sequencing Assay) and a 139-Variant Assay (Variant Assay) - were evaluated in both an Accuracy Study and a Reproducibility Study, with comparison to bi-directional Sanger sequencing and PCR as reference methods. For each study, positive agreement (PA), negative agreement (NA), and overall agreement (OA) were evaluated., Results: In the Accuracy Study, the Sequencing Assay achieved PA of 99.7% including the polyTG/polyT region and PA of 100% excluding the region. The Variant Assay achieved PA of 100%. NA and OA were >99.99% for both Assays. In the Reproducibility Study, the Sequencing Assay achieved PA of 99.2%; NA and OA were both 99.7%. The Variant Assay achieved PA of 99.8%; NA and OA were both 99.9%. Sample pass rates were 99.7% in both studies for both assays., Conclusion: This is the first systematic evaluation of a NGS platform for broad clinical use as an in vitro diagnostic, including accuracy validation with multiple reference methods and reproducibility validation at multiple clinical sites. These NGS-based Assays had accurate and reproducible results which were comparable to or better than other methods currently in clinical use for clinical genetic testing of cystic fibrosis.

The use of the water-oil interface provides significant advantages in the synthesis of inorganic nanostructures. Employing the water-toluene interface, luminescent CdS nanocrystals have been obtained at a relatively modest temperature of 35 degrees C. The diameters of the particulates can be varied between 1.0 and 5.0 nm. In addition, we have devised a new method for transferring thin films at the water-toluene interface onto solid substrates. Using this method, thin films consisting of Au and Ag nanocrystals spread over very large areas (square centimetres) are obtained in a single step. These films are directly usable as ingredients of functional devices. We show this by constructing a working amine sensor based on films of Au nanocrystals. The materials obtained have been characterized by X-ray diffraction, scanning and transmission electron microscopy, absorption and emission spectroscopy and charge transport measurements.

Introduction: Idiopathic pulmonary arterial hypertension (IPAH) is associated with substantial morbidity and mortality. Treprostinil was compared to epoprostenol for the economic impact of treating IPAH patients who failed or were not candidates for bosentan., Methods: The model was a cost-minimization analysis, assuming clinical equivalence was achieved by proper dosing of both drugs, in terms of survival and surrogate measures. Two theoretical cohorts of 270 patients were treated with subcutaneous treprostinil and intravenous epoprostenol, and were evaluated over 3 years using a spreadsheet model. Annual survival rates were estimated for the cohorts so that at endpoint 114 (42%) patients survived in both groups. The model utilized resource valuation data for medication and supply costs from Medicare; hospital, consultation, surgical, and diagnostic procedural fees from North Carolina hospitals; and costs to treat adverse events from published sources. Costs were obtained from standard lists and were presented as 2003 US dollars, discounted at 3%. Sensitivity analyses were performed testing all model uncertainties., Results: In the base case analysis, treprostinil demonstrated savings of 22,701 US dollars and 37,433 US dollars per patient over 1- and 3-year time horizons, respectively. The greatest savings came from reduced or minimal hospitalizations attributed to the dose titration and treatment of adverse events, such as sepsis, associated with epoprostenol and its delivery system. Probabilistic sensitivity analyses resulted in average 3-year cost-savings of 41,051 US dollars (Standard Deviation = 13,902 US dollars) per patient., Conclusions: By initiating and continuing treatment with treprostinil over a 3-year period, the economic burden associated with IPAH may be reduced compared to treatment with epoprostenol. The greatest saving with treprostinil was attributed to decreased sepsis.

Background: Vaccinia immune globulin (VIG) administered via the intramuscular route has historically been used for the treatment of complications of smallpox vaccination. Intravenous formulations of VIG are required to improve tolerability and pharmacokinetic profile., Methods: We conducted 2 separate studies to evaluate the feasibility of administration of an intravenous formulation of antivaccinia immune globulin (VIGIV). The first study assessed the pharmacokinetics and safety of a newly manufactured lyophilized VIG product for intravenous administration (VIGIV-lyo). Seventy-eight healthy volunteers received an intravenous infusion of VIGIV-lyo at doses of 100 mg/kg, 200 mg/kg, or 500 mg/kg. In the second study, we evaluated the safety of a liquid product of VIGIV (VIGIV-liq) in 33 healthy volunteers receiving an intravenous infusion of 100 mg/kg VIGIV-liq., Results: The geometric mean titer of VIG at the target dose (100 mg/kg) after intravenous administration is 2.5 times higher than the predicted geometric mean titer after intramuscular injection (P<.001). The pharmacokinetics of VIGIV-lyo are linear for doses from 100 mg/kg through 500 mg/kg. Administration of the 200-mg/kg and 500-mg/kg doses of VIGIV-lyo does not result in markedly higher adverse event rates. The adverse event rates observed with the liquid product are comparable to those seen with the lyophilized product., Conclusions: These 2 studies suggest that intravenous administration of VIG is well tolerated and results in a more favorable pharmacokinetic profile than does VIG administered intramuscularly.

In Experiment 1, golden hamsters were injected with either 0.9% saline or the nausea-inducing agent, lithium chloride (LiCL), immediately after consuming a flavored diet that was either novel or familiar. The LiCl-induced aversion was strong in hamsters for which the flavored diet was novel, but no significant aversion was observed in hamsters that were familiar with the flavored diet. In Experiment 2, the strength of the LiCl-induced aversion was related inversely to the amount of conditioned-stimulus (CS) preexposure and directly to the duration of the preexposure-conditioning interval. Thus, although some previous researchers have suggested that hamsters may not demonstrate the CS-preexposure effect in a conditioned taste-aversion paradigm, they clearly did so under the conditions of the present experiments, and moreover, the characteristics of the CS-preexposure effect in hamsters were generally similar to those observed in rats.

Background: The study was conducted to compare lung transplantation outcomes between ABO-identical (AI) and ABO-compatible (AC) recipients., Methods: Charts of lung allograft recipients transplanted between February, 1990 and October, 1995 were reviewed. Standard triple-drug immunosuppression and general antimicrobial prophylaxis were provided. Surveillance spirometry was administered every three months. Flexible bronchoscopy (FB) with transbronchial biopsies (TBBs) were undertaken for clinical indications. Time to event analysis on acute (AR) and chronic (CR) rejection and actuarial survival were determined by Kaplan-Meier analysis. Cumulative curves were compared with a log rank test. Comparisons of age, maximum forced expiratory volume in one second (FEV1) in the single (SLT) and double (DLT) lung recipients, duration of intensive care unit and hospital stay were carried out using the Wilcoxon Rank Sum test. Gender, race, underlying diagnoses, cytomegalovirus (CMV) status and pulmonary reimplantation response (PRR) were compared by Chi-square or Fisher's exact test where appropriate., Results: Of the 100 lung recipients (age = 42.5 +/- 13.4 years; M:F = 50:50), 64 were AI and 36 AC. Median follow-up was 22 (range = 0-78) months. Outcome did not differ significantly between the 2 groups in terms of intensive care unit and hospital stay, PRR incidence and grade, incidence and frequencies of AR, median time and grade of first AR, maximum FEV1 for SLT and DLT recipients, incidence of CR and survival at 12 months., Conclusions: As the donor supply remains limited, this could considerably simplify the logistics of future transplantation.