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Introduction The prevalence of sleep disorders and use of sleep medication, particularly melatonin, are rising among adolescents and young adults (13–24 years). In Denmark, melatonin is approved for use in children with autism and ADHD up to 18 years of age, with other prescriptions being off-label in these age groups. The perspectives of medical practitioners on prescribing sleep medications to this age group remain largely unexplored.Aim This study aims to investigate the considerations of general practitioners (GPs) and child and adolescent psychiatrists (psychiatrists) when prescribing and deprescribing sleep medications for 13–24-year-olds.Methods We conducted qualitative semi-structured interviews with 10 GPs and six psychiatrists. Data were analyzed using an inductive approach.Results Psychiatrists typically prescribed melatonin with the expectation that deprescription would occur in general practice. Despite the universal goal of deprescription, it was hindered by various challenges. GPs identified patient motivation and a clear focus on deprescription as facilitative factors and expressed a need for enhanced emphasis on these aspects in general practice.Discussion and implications The findings align with existing prescription trends and literature on factors that promote and inhibit deprescription. The study underscores the complexities of deprescribing sleep medications for adolescents and young adults, suggesting the need for expanded guidelines and enhanced continuing education for GPs.Conclusions The research highlights significant discrepancies among medical practitioners regarding the deprescription process of sleep medications for young individuals, complicated by multiple factors. This underscores the need for better guidelines and further studies.

Introduction Patients with complex multimorbidity face a high treatment burden and frequently have low quality of life. General practice is the key organisational setting in terms of offering people with complex multimorbidity integrated, longitudinal, patient-centred care. This protocol describes a pragmatic cluster randomised controlled trial to evaluate the effectiveness of an adaptive, multifaceted intervention in general practice for patients with complex multimorbidity.Methods and analysis In this study, 250 recruited general practices will be randomly assigned 1:1 to either the intervention or control group. The eligible population are adult patients with two or more chronic conditions, at least one contact with secondary care within the last year, taking at least five repeat prescription drugs, living independently, who experience significant problems with their life and health due to their multimorbidity. During 2023 and 2024, intervention practices are financially incentivised to provide an extended consultation based on a patient-centred framework to eligible patients. Control practices continue care as usual. The primary outcome is need-based quality of life. Outcomes will be evaluated using linear and logistic regression models, with clustering considered. The analysis will be performed as intention to treat. In addition, a process evaluation will be carried out and reported elsewhere.Ethics and dissemination The trial will be conducted in compliance with the protocol, the Helsinki Declaration in its most recent form and good clinical practice recommendations, as well as the regulation for informed consent. The study was submitted to the Danish Capital Region Ethical Committee (ref: H-22041229). As defined by Section 2 of the Danish Act on Research Ethics in Research Projects, this project does not constitute a health research project but is considered a quality improvement project that does not require formal ethical approval. All results from the study (whether positive, negative or inconclusive) will be published in peer-reviewed journals.Trial registration number NCT05676541.

This paper investigates the competition between two charge point operators at the same site for future battery electric long-haul trucks. The charge point operators are located along one of the busiest highways in Sweden. The investigation is carried out using an agent-based model where trucks select charge point operators based on charging prices and the length of any queues, while charge point operators adjust their prices and number of chargers to improve their profitability. The study aims to predict conditions for trucks and charge point operators in a future public fast-charging market. Our findings indicate the potential for a well-functioning future public fast-charging market with small queuing problems, high utilisation, and reasonable prices for public fast charging. Assuming a price for electricity of EUR 0.08/kWh and a minimum profit margin of EUR 0.001/kWh for charge point operators, the findings indicate that the price level outside rush hours will be low, approximately EUR 0.1/kWh. The prices during rush hours will likely be much higher, but it is harder to predict the value due to uncertainties of how charge point operators will act in the future market. Still, from the model result, the price during rush hours is suggested to be just above EUR 0.5/kWh, with an average charging price of around EUR 0.15/kWh. It also seems likely that it is profitable for charge point operators to build enough chargers so that charging queues are short.

Background and aimsCirrhosis entails high risk of serious infections and abated efficiency of vaccination, but the underlying mechanisms are only partially understood. This study aimed at characterizing innate and adaptive immune functions, including antigen-specific T cell responses to COVID-19 vaccination, in patients with compensated and decompensated cirrhosis.MethodsImmune phenotype and function in peripheral blood from 42 cirrhotic patients and 44 age-matched healthy controls were analysed after two doses of the mRNA-based COVID-19 vaccines [BNT162b2 (Pfizer BioNTech) or mRNA-1273 (Moderna)].ResultsCirrhotic patients showed significantly reduced blood counts of antigen-presenting dendritic cells (DC) and high counts of monocytic myeloid-derived suppressor cells (M-MDSC) as compared to healthy controls. In addition, monocytic cells recovered from cirrhotic patients showed impaired expression of the antigen-presenting molecule HLA-DR and the co-stimulatory molecule CD86 upon Toll-like receptor (TLR) stimulation. These features were more prominent in patients with decompensated cirrhosis (Child-Pugh classes B & C). Interestingly, while patients with compensated cirrhosis (Child-Pugh class A) showed an inflammatory profile with myeloid cells producing the proinflammatory cytokines IL-6 and TNF, decompensated patients produced reduced levels of these cytokines. Cirrhotic patients, in particular those with more advanced end-stage liver disease, mounted reduced antigen-specific T cell reactivity to COVID-19 vaccination. Vaccine efficiency inversely correlated with levels of M-MDSC.ConclusionThese results implicate MDSC as mediators of immunosuppression, with ensuing deficiency of vaccine-specific T cell responses, in cirrhosis.

Type 1 conventional dendritic cells (cDC1) efficiently cross-present antigens that prime cytotoxic CD8+ T cells. cDC1 therefore constitute conceivable targets in cancer vaccine development. We generated recombinant fusion cancer vaccines that aimed to concomitantly deliver tumor antigen and adjuvant to CD103+ migratory cDC1, following intranasal administration. The fusion vaccine constructs comprised a cDC1-targeting anti-CD103 single chain antibody (aCD103) and a cholera toxin A1 (CTA1) subunit adjuvant, fused with MHC class I and II- or class II-restricted tumor cell antigens to generate a CTA1-I/II-aCD103 vaccine and a CTA1-II-aCD103 vaccine. The immunostimulatory and anti-tumor efficacy of these vaccines was evaluated in murine B16F1-ovalbumin (OVA) melanoma models in C57BL/6 J mice. The CTA1-I/II-aCD103 vaccine was most efficacious and triggered robust tumor antigen-specific CD8+ T cell responses along with a Th17-polarized CD4+ T cell response. This vaccine construct reduced the local growth of implanted B16F1-OVA melanomas and efficiently prevented hematogenous lung metastasis after prophylactic and therapeutic vaccination. Anti-tumor effects of the CTA1-I/II-aCD103 vaccine were antigen-specific and long-lasting. These results imply that adjuvant-containing recombinant fusion vaccines that target and activate cDC1 trigger effective anti-tumor immunity to control tumor growth and metastasis.

This paper investigates the charging needs and charger utilisation of a system of battery electric trucks and their public fast chargers, along the highway between the Swedish cities of Helsingborg and Stockholm, in a possible future scenario in which all trucks are battery electric. The system is investigated via an agent-based model which simulates a typical day with current levels of truck traffic on the road. The traffic flow is based on hourly truck flow data during a day and the annual flow of trucks. The findings indicate major potential for a well-functioning system of public chargers for trucks, with high utilisation, few queuing problems at charging stations, cheap public fast charging and a robust response to queues caused by peaks or increases in the traffic flow. The number of 900 kW chargers along the road needed to achieve this has been estimated at 140, and the utilisation factor for the chargers is predicted to be 30%.

Background & Aims: Cirrhosis entails elevated risk of COVID-19-associated mortality. This study determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 patients with cirrhosis and 39 healthy controls after mRNA COVID-19 vaccination. Methods: SARS-CoV-2-specific T-cell reactivity was measured by induced level of T cell-derived interferon-γ (IFN-γ) in blood cells stimulated ex vivo with multimeric peptides spanning the N-terminal portion of S1. S1-induced IFN-γ was quantified before and after the 1st and 2nd vaccination (BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) alongside serum IgG against the receptor-binding domain (RBD) within S1 (anti-RBD-S1 IgG). Results: T-cell reactivity against S1 was reduced in patients with cirrhosis after the 1st (p

This paper investigates the economic consequences of a haulage company replacing its line-haul diesel trucks with battery-electric ones. It also examines how large truck batteries should be, whether the haulage companies should use public fast chargers to complement their own, and whether public fast chargers have the potential to be profitable. The potential extra cost of losing payload capacity is estimated and there is an investigation of whether a charge-point operator should meet the peak demand for charging. The case under analysis is designed to represent a typical line-haul service between terminals in a major logistics system, with the finding that, in this case, a transition to battery-electric trucks seems cost effective for the company. Moreover, it is advisable for the company to use public fast chargers and these will likely become profitable given that the utilisation factor of the investigated public fast chargers may realistically exceed 20%.

This paper investigates the competition between two charge point operators at the same site for future battery electric long-haul trucks. The charge point operators are located along one of the busiest highways in Sweden. The investigation is carried out using an agent-based model where trucks select charge point operators based on charging prices and the length of any queues, while charge point operators adjust their prices and number of chargers to improve their profitability. The study aims to predict conditions for trucks and charge point operators in a future public fast-charging market. Our findings indicate the potential for a well-functioning future public fast-charging market with small queuing problems, high utilisation, and reasonable prices for public fast charging. Assuming a price for electricity of EUR 0.08/kWh and a minimum profit margin of EUR 0.001/kWh for charge point operators, the findings indicate that the price level outside rush hours will be low, approximately EUR 0.1/kWh. The prices during rush hours will likely be much higher, but it is harder to predict the value due to uncertainties of how charge point operators will act in the future market. Still, from the model result, the price during rush hours is suggested to be just above EUR 0.5/kWh, with an average charging price of around EUR 0.15/kWh. It also seems likely that it is profitable for charge point operators to build enough chargers so that charging queues are short. [ABSTRACT FROM AUTHOR]

One possible step for reducing humans’ use of fossil fuel due to transport tasks is to replace diesel trucks with battery electric ones. This paper introduces the energy distribution diagram, which makes it easy to visualise the trucks’ daily energy consumption over their full service life. The energy distribution is used to investigate which driving patterns are suitable for cost-effective battery electric trucks when compared to commercial diesel trucks. It is shown that the battery capacity that results in the lowest cost per kilowatt-hour propulsion energy depends on the driving pattern, and an algorithm for selecting the most cost-effective capacity is presented. In many instances, it was found that battery electric trucks competed favourably with diesel trucks, especially when the trucks had low variations in daily energy consumption. It is beneficial to determine the circumstances under which they may be cheaper, as this will facilitate the transition to battery electric trucks in segments with a reduced overall cost of ownership.

Transport of ore and overburden in open-pit mines is often performed with large haul trucks. Battery-electric operation of haul trucks can significantly reduce the CO2 emissions and the fossil fuel dependence of open-pit mining. This simulation study investigates the feasibility and economy of operating large haul trucks battery-electrically, charging from an electric road system in the form of overhead trolley lines. The used simulation model is verified against measurements on diesel-electric haul trucks in normal operation. The simulation model is then tested with five drive cycles representing typical operations in the Aitik copper mine in northern Sweden. This simulation study shows that battery-electric operation with an electric road is feasible. It is shown that battery-electric operation is much cheaper than diesel-electric operation under reasonable assumptions. It is also much cheaper than diesel-electric operation assisted by an electric road.

Background: Waning of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates the diagnosis of past infection. The durability of T-cell memory against SARS-CoV-2 remains unclear, and most current T-cell protocols are unsuited for large-scale automation.Methods: Whole-blood samples from 31 patients with verified past coronavirus disease 2019 (COVID-19) and 46 controls, of whom 40 received COVID-19 vaccine, were stimulated with peptides spanning the nucleocapsid (NC) or spike 1 (S1) regions of SARS-CoV-2 and analyzed for interferon γ in supernatant plasma. Diagnostic accuracy of these assays was evaluated against serum anti-NC and anti-receptor-binding domain S1-IgG.Results: Induction of interferon γ in whole blood by NC or S1 peptides diagnosed past COVID-19 with high accuracy (area under the receiver operating characteristic curve, 0.93 and 0.95, respectively). In accordance with previous studies, NC-IgG levels rapidly waned with only 5 of 17 patients (29%) remaining seropositive >180 days after infection. By contrast, NC peptide-induced T-cell memory responses remained in 13 of 17 study participants (76%) >180 days after infection (P = .01 for comparison with NC-IgG; McNemar test). After 2 vaccine doses, all 18 donors exhibited S1-specific T-cell memory.Conclusions: Cytokine release assays for the monitoring of T-cell memory in whole blood may be useful for evaluating complications following unverified past COVID-19 and for long-term assessment of vaccine-induced T-cell immunity.Clinical Trials Registration: EudraCT 2021-000349-42. [ABSTRACT FROM AUTHOR]