University of Southern Denmark

On-board chargers (OBCs) with conventional two-stage architecture, consisting of an active front-end (AFE) converter and an isolated dc-dc stage, require bulky line filters and dc-link capacitors, resulting in low volumetric efficiency. Active third-harmonic injection and current unfolding methods offer significant improvement in terms of efficiency and power density in power factor correction (PFC) applications. However, existing unfolding-based topologies require two isolated dc-dc converters capable of handling the rated power for PFC and output voltage regulation. This article presents a three-phase ac-dc converter with a third-harmonic current injection circuit that processes a fraction of the total power and a single isolated dc-dc converter for galvanic isolation. Line frequency switching in the rectifier produces varying dc-link voltages, eliminating the requirement of bulky electrolytic capacitors. The article discusses detailed operation and design procedures along with an elaborate comparative analysis between the proposed topology and the conventional two-stage and Swiss rectifier-based isolated topologies. A 6.6 kW prototype is developed and tested for experimental validation of the system in both balanced and unbalanced grid conditions. The experimental results demonstrate unity power factor (upf) operation throughout the operating range, achieving a peak efficiency above 97%.

Perfluoroalkyl substances (PFAS) have been linked to immunotoxic effects in children, and the consequences of immune suppression could be particularly severe for children in low-income settings. We thus aimed to investigate associations between infant and maternal PFAS exposure and infant vaccine antibody concentrations in Burkina Faso. Infants (n = 200) were vaccinated against measles at baseline (age 4-7 months) and/or at 9 months. Associations between maternal and infant PFAS concentrations (quantified in serum collected at baseline) and infant measles antibody concentrations before and after vaccination were assessed in confounder-adjusted linear regression models. Influential observations were excluded in sensitivity analyses. Infant PFAS exposure was positively associated with pre-vaccination antibody concentrations, but associations were largely driven by a few influential observations. Maternal and infant PFAS concentrations were not consistently associated with infant measles antibody concentrations after one or two vaccinations. Thus, these results from a low-exposed population did not confirm findings from previous studies.

Intracranial calcifications are commonly found in adults and may represent either benign or pathological lesions. Conventional imaging modalities detect static macrocalcifications but do not capture molecular microcalcification. In this study, we used 18 F-sodium fluoride (NaF) PET/computed tomography (CT) to idetect intracranial molecular microcalcification. A total of 127 subjects underwent 18 F-NaF PET/CT 90 min following radiotracer injection. Artificial intelligence-based quantification was performed to obtain regions of interest for the brainstem, basal ganglia (caudate and lentiform nuclei), insula, thalamus, and ventricles. Linear regression models were used to correlate NaF mean standardized uptake value (SUV mean ) with various clinical factors. NaF SUV mean was highest in the insula (0.8 ± 0.4) and brainstem (0.8 ± 0.3), while uptake was lowest in the caudate nucleus (0.1 ± 0.1). No differences were found in NaF SUV mean between healthy volunteers and at-risk patients. On multivariate regression, NaF SUV mean directly correlated with age in the brainstem ( β = 0.01, P = 0.01), lentiform nucleus ( β < 0.01, P = 0.02), and ventricles ( β < 0.01, P < 0.01). Male sex inversely correlated with NaF SUV mean in the insula ( β = -0.30, P < 0.01). There was an association between NaF SUV mean and BMI in the brainstem, caudate nucleus, lentiform nucleus, thalamus, and ventricles ( β ≤ 0.01, P < 0.01 in all regions). Thalamic and ventricular NaF SUV mean directly correlated with hypertension on univariate but not multivariate analysis. NaF PET/CT detects intracranial molecular microcalcification that is not visible on conventional CT and may provide insight into pathology associated with this biological process.

People with schizophrenia experience markedly reduced health-related quality of life (QoL), partly driven by obesity and metabolic dysregulation. Glucagon-like peptide-1 receptor agonists such as semaglutide induce substantial weight loss in the general population and in patients receiving antipsychotic medication. However, the extent to which semaglutide-associated weight loss mediates changes in QoL and symptom severity in schizophrenia remains unclear. This secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity. Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30weeks. Outcomes were the SF-36v2 Physical and Mental Component Summary scores (PCS, MCS) and the Positive and Negative Syndrome Scale, 6-item version (PANSS-6). Causal mediation analyses estimated natural direct and indirect effects of semaglutide via weight loss at weeks 15 and 30. Semaglutide improved PCS at weeks 15 and 30, with effect sizes exceeding the minimally important difference. Indirect effects via weight loss were positive but not statistically significant, although at week 30 approximately half of the total PCS effect was estimated to be mediated through weight change. No total or mediated effects were found for MCS. For PANSS-6, no meaningful mediation was observed. Semaglutide improved physical QoL in patients with schizophrenia, and weight loss may partially contribute to this effect. Longer-term studies are needed to determine whether mental QoL or symptom effects emerge beyond 30weeks.

Many new drugs are poorly water-soluble requiring enabling formulations like amorphous solid dispersions or lipid-based formulations for oral administration. Phospholipid-based amorphous solid dispersions (PL-based ASDs) may combine the solubility advantages of ASDs and lipid-based formulations. Like lipid-based formulations, digestion may influence the biopharmaceutical performance of PL-based ASDs. Evaluating performance in the presence of solubilizing species as vesicles and micelles, forming during dissolution of PL-based ASDs, is difficult. To mitigate this, we used a novel biopharmaceutical approach based on microdialysis sampling to assess drug release from PL-based ASDs loaded with indomethacin under non-lipolytic and lipolytic conditions. Microdialysis sampling, unlike conventional sampling, can discern between molecularly dissolved drug and drug associated with colloidal species. The free drug is the main driving force for absorption. Therefore, we conducted dissolution/permeation experiments in non-lipolytic and lipolytic conditions for comparison. Microdialysis revealed that under lipolytic conditions the free drug concentration was increased as compared to non-lipolytic conditions for all PL-based ASDs agreeing with increased permeation under lipolytic conditions. PL-based ASDs with low to intermediate PL-to-drug ratios significantly improved biopharmaceutical performance. High phospholipid content impaired the performance due to colloidal entrapment. Correspondingly, the positive effect of lipolysis was most prominent at high phospholipid content. Microdialysis provided near real- time free drug concentrations and accurately ranked the formulations based on their ability to cross an absorptive barrier independent of lipolysis. Thereby, microdialysis resolves the limitations of coupled dissolution/permeation for PL-based ASDs. In conclusion, these findings provide a deeper understanding of the mechanisms of action of this formulation. The correlation between free drug concentration and permeability under simulated intestinal conditions may provide a framework for future design of PL-based ASDs presupposing that the observed correlation will be confirmed in an appropriate animal model.

Obstructive Sleep Apnoea (OSA) is a highly prevalent disease often treated with CPAP therapy, but long-term adherence remains a challenge. This study aimed to explore which phenotypes of OSA patients are more or less likely to achieve high adherence to CPAP therapy, based on pre-treatment characteristics. We analysed demographic, socioeconomic, and clinical characteristics across predefined CPAP adherence groups (high, low, and no adherence) in a multicentre cohort of newly diagnosed OSA patients. Multivariate logistic regression was used to assess predictive accuracy, and observed patterns were synthesised into rule-based clinical phenotypes. Among 2845 patients, 41% were highly adherent, 20% had low adherence, and 39% were non-adherent after one year. High adherence was associated with cohabitation, higher education, employment, and greater disease severity. Low or no adherence was linked to comorbidity burden and social vulnerability. The predictive model yielded an accuracy of 60%. Based on group-level differences and model outputs, three clinically reasoned phenotypes were identified: (1) Symptomatic severe OSA with social support, (2) Multimorbidity-dominated, and (3) Non-employed working-age adults. Distinct demographic, socioeconomic, and clinical profiles were associated with CPAP adherence. The identified phenotypes offer a practical framework for understanding adherence variation and may support more individualised approaches to treatment and follow-up.

Computed Tomography (CT) is central to modern imaging practice and accounts for over 60% of the collective radiation dose from medical imaging, underscoring the need for optimisation. Adjusting the scan range based on clinical indication is an evidence-based method for dose optimisation. However, the evidence remains dispersed across indications without a concise cross‑domain synthesis; this review consolidates evidence on indication-based scan range optimisation, evaluating its impact on radiation dose, diagnostic accuracy, and implications for missed findings across multiple CT applications. This scoping review followed Joanna Briggs Institute methodology and PRISMA-ScR guidelines. PubMed, Embase, and Scopus were searched for studies (2010-2025) on indication-driven CT scan range optimisation. Eligible studies evaluated reduced z‑axis coverage based on clinical indications and reported at least one outcome: scan length (mm), radiation dose metrics (mSv), or diagnostic accuracy (%). Data were synthesised narratively with descriptive reporting of key outcomes. Twenty-one studies across six clinical domains were included. Indication-driven protocols reduced radiation exposure proportionally to scan length, achieving reductions of 33-50% in scan length and 10-50% in dose. Organ-specific reductions reached 97% for breast and 81% for testes, with foetal dose reductions exceeding 80% in pregnancy-adapted protocols. Diagnostic sensitivity for the primary indication remained 98-100%. Aggressive truncation increased missed alternative diagnoses in up to 17% of patients, particularly in older or multimorbid cohorts. Clinical indication-driven optimisation of CT scan range achieves substantial radiation-dose reduction without compromising diagnostic accuracy. These findings support evidence-based adoption of landmark-based protocols for focused clinical questions, with selective application in patients with broader differential diagnoses. Future directions include AI-assisted landmark detection and automated planning tools to enhance reproducibility and workflow efficiency.

This study investigated the potential of developing long-acting injectable (LAI) formulations of the next-generation diarylquinoline antibacterial compounds TBAJ-587 and TBAJ-876, which have the potential to impact the tuberculosis (TB) treatment by providing an extended treatment option. The performance of these compounds, formulated as LAIs, were evaluated based on particle size stability, drug loading capacity, and in vivo pharmacokinetics in rats. The data showed that particularly high drug loadings could be obtained in aqueous suspensions using the salt forms of TBAJ-587 and TBAJ-876, with concentrations up to 750mg/mL TBAJ-587 fumarate and 650mg/mL TBAJ-876 tartrate, expressed as the equivalent concentration of free base. A long-term stability study of the TBAJ-876 tartrate formulation suggested that a relatively stable suspension was defined when stored at both ambient temperature and at 40°C. In contrast, the TBAJ-587 fumarate suspension formulation showed significant particle size growth as a function of time, indicating physical instability in the colloidal system. Analysis of both compounds by X-ray powder diffraction (XRPD) revealed no major changes in the crystal structure following milling or after 24weeks of storage at 40°C. The in vivo pharmacokinetic study in rats showed that the suspensions containing either TBAJ-587 fumarate or TBAJ-876 tartrate offered a promising LAI option for the prolonged treatment of TB, as all formulations achieved prolonged drug plasma exposure for at least three months following administration.