University of York

Timely discharge of patients who are clinically ready to be discharged from hospitals to the next point of care is a common health system challenge. Ensuring safe and effective discharge holds new urgency, given the backlogs and increased waiting times for inpatient services in many countries after the COVID-19 pandemic. The study aimed to identify policy options for addressing delayed discharges in six European countries (Denmark, France, Germany, the Netherlands, Norway, and Sweden), and to summarise available evidence on their effectiveness. Experts from the Health Systems and Policy Monitor (HSPM) network of the European Observatory on Health Systems and Policies and additional country experts identified relevant policies and initiatives up to November 2023. When evaluations were available, the experts also provided information on their findings. The data collection was followed by a qualitative, cross-country comparative analysis. A total of 17 policies or initiatives were identified in the study countries. Hospital-based initiatives included discharge planning and transitional care. Community and home care initiatives included municipal emergency beds, intensive home rehabilitation, and assisted discharge. Cross-sectoral initiatives ranged from coordination efforts at the regional and municipal levels to decision support systems and financial incentives. Several common factors or principles underpin many of the identified policies and initiatives. These include clarity of responsibility, effective planning and communication, resourcing of community-based capacity, possible unintended consequences of financial penalties, and the need to adopt a systemic approach.

Linear long-chain hydrocarbons are common constituents of the outer cuticle of most insects. These cuticular hydrocarbons form the first barrier to the environment, preventing desiccation, but also play important roles in communication among many insects, transporting, for example, information on species, sex, or physiological state. Eueides is a genus of heliconiine butterflies, a group known for their complex mimicry systems. We report here the identification and synthesis of large macrocyclic lactones from the cuticles of five Eueides species, which largely replace the hydrocarbons. These lactones have chain lengths of 23-34 and ring sizes of 17-29. They occur in Eueides but not in other closely related genera such as Heliconius, Dryas, Dryadula, Agraulis, or Dione. Each species has a specific mixture of macrocyclic lactones. These unique bouquets may be used in species recognition, as visual cues may be unreliable in mimicry rings. We identified 43 different compounds using GC/MS, GC/IR, and enantioselective synthesis via ring-closing metathesis and Jacobsen hydrolytic kinetic resolution. The absolute configuration could not be determined because these lactones were not separable by gas chromatography on chiral phases.

l-Tryptophan (Trp) is an essential amino acid catabolised through the kynurenine pathway, which is mediated by the enzymes indoleamine-2,3-dioxygenase 1 (IDO1), IDO2, or Trp-2,3-deoxygenase. In cancer, IDO1 acts as an immune checkpoint, suppressing effector T cell function. Yet, direct inhibition of IDO1 has had limited success in clinical trials. Therefore, alternative approaches to Trp metabolism therapeutic targeting are needed. We screened a library of 597 natural products (NPs) or NP derivatives for their effect on kynurenine production in triple-negative breast cancer cells. This revealed 24 candidate inhibitors of kynurenine production. Among them, artemether, a member of the artemisinin family of anti-malarial drugs, suppressed kynurenine production, likely via an endoperoxide bridge-dependent mechanism. The Euphorbia factor L9 (EFL9) inhibited kynurenine production, likely via a C7-benzoylation-dependent mechanism. Neither artemether nor EFL9 affected JAK/STAT signalling or IDO1 levels. Targeted metabolomics and molecular docking analyses demonstrated that artemether suppressed kynurenine production through heme sequestration and potential interactions with the IDO1 heme-binding pocket A. EFL9 affected Trp metabolism through heme-independent mechanisms and resulted in changes in purine and amino acid metabolism and the cellular redox balance. Notably, ouabain, a regulator of IDO1 levels, and linrodostat, a clinically approved IDO1 inhibitor, revealed distinct metabolic profiles, with ouabain and EFL9 showing the largest overlap. Importantly, the kynurenine-suppressing activities of artemether and EFL9 were observed in non-transformed primary mammary epithelial cells and also lung cancer cells. Overall, our findings set the foundation for future studies exploring the use of artemether or EFL9 as novel Trp metabolism-targeting therapeutics.

Smokers quitting successfully with the help of e-cigarettes often continue vaping. It is not known whether this promotes or prevents relapse back to smoking. This study aimed to determine whether use of e-cigarettes after successful smoking cessation affects the probability of relapse later on. Secondary analysis of a randomised controlled trial where participants received combination nicotine replacement therapy (NRT) or e-cigarettes to compare relapse rates in the two study arms and in abstainers who did and did not use e-cigarettes. Four stop-smoking services in the United Kingdom. 886 smokers (median age 41, smoking on average 15 cigarettes per day, 48% female) seeking help with stopping smoking. Main outcome was relapse to smoking by 12 months in participants who were abstinent at 4 weeks or at 6months. Relapse was defined as abstinence at 4weeks but not at one year or abstinence at 6months but not at one year. Abstinence from smoking was defined as no smoking over the past 7days. E-cigarette use was defined as using e-cigarettes at the time of abstinence on at least one day per week. Abstainers in the e-cigarette arm were less likely to relapse than abstainers in the NRT arm [relative risk (RR) =0.78, 95% confidence interval (CI) = 0.64-0.96 for relapse between 4weeks and 1year; RR =0.71, 95% CI = 0.55-0.93 for relapse between 6months and 1year). Relapse rates over both time periods were also lower in abstainers who used e-cigarettes compared with abstainers who did not use e-cigarettes (RR =0.79, 95% CI = 0.65-0.97 and RR =0.75, 95% CI = 0.57-0.98, respectively). Use of e-cigarettes after stopping smoking is associated with a reduced risk of relapse.

• Ownership shifts are linked to mining temporalities. • The decarbonisation agenda has promoted shifts in coal investors in Mozambique. • The ownership shift has shaped people's displacement and resettlement experiences. • Temporal disruptions have increased insecurities among local residents.

Alcohol use is driven not only by environmental cues but also by individual differences in motivational style. Recent work has demonstrated how memory cues can reduce subsequent desire for alcohol, yet it remains unclear how personality traits shape this effect. To address this, we recruited male and female participants ( N = 169) who completed the behavioural inhibition/approach system (BIS/BAS) scales and were then cued to recall either a previous alcohol drinking episode and estimate the number of alcohol calories consumed (Alcohol Cue, AC) or a control (Neutral Cue, NC). They then rated their desire for alcohol (DAQ). Findings revealed lower desire for those in the AC compared to NC group and separately, a positive association between alcohol desire and BAS and particularly BAS-Drive. We further found that a measure of residual BAS (BAS less BIS) was positively related to desire but did not moderate the effect of memory cue. These findings suggest that being reminded of a previous drinking episode can exert a modest but consistent influence on alcohol desire. • Memory of a recent drinking episode reduced alcohol desire in males and females. • Increases in Behavioural Approach System (BAS) increased alcohol desire. • BAS did not moderate the effect of the alcohol memory cue. • Memory cues could offer a simple method of reducing alcohol desire.

There is extensive literature on automated test generation using reactive design models, where control is determined by events. In contrast, the (idealised) simulation paradigm defines control through cycles dictated by the passage of time. Within each cycle, inputs are read and processed, and outputs are provided, all instantaneously, and afterwards time progresses. To exercise a simulation using tests generated from a reactive design model requires changes to the tests to take into account this paradigm shift. This paper focuses on automation of the necessary changes and of the use of the resulting tests in a simulation campaign. Based on a notion of conformance that establishes whether a simulation is correct with respect to a reactive design, we (1) identify the reactive tests that are meaningful; (2) define a process to convert those tests; (3) provide an algorithm to execute those tests; and (4) prove soundness and completeness of our approach. Our work is described in the context of the RoboStar framework for model-based development of control software for robotics applications, and its process algebraic semantics. The testing approach we propose here represents a significant advancement in the current testing practices within the field of robotics, where simulations are widely used.