Aims: Endotypes integrate individual clinical and molecular data and can be used to formulate molecular subclassifications of diseases. We previously derived four endotypes of subclinical carotid atherosclerosis in a large European cohort, c-IMT and c-IMT Progression as Predictors of Vascular Events in a High-Risk European Population (IMPROVE), identifying individuals with a specific cardiovascular (CV) risk, ranging from low (endotype 1) to very high (endotype 4). Here, we investigate the mechanisms underlying the differences in CV risk observed across these four endotypes.

Methods and results: We validated the four endotypes in SCAPIS (n = 5050) and UK Biobank (n = 50 396) using carotid plaque and carotid intima-media thickness (c-IMT) as subclinical atherosclerosis measures. Endotype 4 associated with a larger number of carotid plaques and increased c-IMT measures as compared to endotype 1. We performed a meta-analysis of individual genome wide association studies in IMPROVE (n = 3711), SCAPIS and UK Biobank, and identified 12 SNPs associated with endotypes. We investigated if they regulated gene expression and circulating protein levels. We found that rs2228145A/C at Interleukin-6 Receptor (IL6R), associated with endotype 4, regulated IL6R expression and circulating levels of OncoStatin M Receptor (OSMR), Complement Factor B (CFB) and Fibrinogen Chain A (FGA). We used rs2228145A/C as an instrument in two-sample Mendelian randomization analyses and showed that a decreasing IL6R expression, associated with increasing CFB, FGA, and OSMR circulating levels. Endotype 4, IL6R, CFB, FGA, and OSMR co-localized within 250 kb surrounding rs2228145A/C. However, only OSMR was up-regulated in advanced carotid atherosclerotic plaques in the presence of the A allele and in aortic region exposed to low wall shear stress. In the UK Biobank, we observed that each additional A allele at rs2228145 increased by 1.28-times the risk of myocardial infarction (MI) in endotype 4.

Conclusion: Rs2228145A/C associated with endotype 4 clinical and molecular characteristics and amplified the MI risk in individuals assigned to endotype 4. These effects appeared to be mediated by a crosstalk with OSMR.

Background and Aim: Coronary calcification has been described as a manifestation of subclinical atherosclerosis. However, its predictors are not well established. The aim of this study was to evaluate the relationship between coronary artery calcium score (CACs) evaluated by multi-detector computed tomography (MDCT) and atherosclerotic cardiovascular disease (CVD) risk factors in symptomatic patients in three European countries.

Method: We retrospectively analyzed 550 patients (age 62.7 +/- 12 year, 47.5% females) who presented with atypical chest pain in Germany, Denmark, and Sweden. The demographic indices, CVD risk factors, and CACs were analyzed. The CV risk factors were classified as low (no risk factors), intermediate (1-2 risk factors), and high (>= 3 risk factors). Patients were geographically classified into: Gr. I-German (n = 344), Gr. II-Danish (n = 84), and Gr. III-Swedish (n = 122) patients.

Results: In the cohort as a whole, the mean CACs was 270.3 +/- 72, and the intermediate risk was more prevalent than low and high-risk (p < 0.05 for all). Among the CVD risk profile, arterial hypertension (AH) was the most prevalent, followed by hypercholesterolemia, obesity, smoking, and diabetes (53, 38.2, 23.7, 17.6, and 10.5%; p < 0.05 for all). The German population was younger and had less CVD risk factors compared to the Danish and Swedish populations (p < 0.05, for all). CACSs adjusted to age and sex was lowest in Swedish patients, followed by German patients, and highest in Danish patients (p < 0.05). The CACs modestly correlated with age (r(pb) = 0.52, p < 0.001), sex (r(pb) = 0.48, p < 0.001), and extent of risk (r(pb) = 0.35, p = 0.001). On multivariate regression analysis, hypercholesterolemia beta = 185.1 (63.11 to 307.1), the extent of risk adjusted for age and sex beta 3.741 (2.566 to 4.916; p < 0.001), and AH, beta = 142.6 (11.25 to 274.1; p = 0.03) independently correlated with CACs. Furthermore, hypercholesterolemia was the only risk factor, consistently associated with CACs across all three countries.

Conclusions: In symptomatic European patients, hypercholesterolemia is the main player in coronary calcium formation

Sleep disturbances and inflammation are interconnected through shared regulatory mechanisms and are both implicated in age-related diseases. However, their connection at the level of brain-specific inflammation remains underexamined in humans. This study investigated whether specific dimensions of sleep are associated with microglial density, as measured by translocator protein (TSPO) levels, a biomarker of neuroinflammation. TSPO levels were measured using a single [¹¹C]PBR28 positron emission tomography (PET) scan in 39 healthy adults aged 50-81 years (M_age = 66.7, SD = 8.9; 19 females, 20 males). Sleep dimensions were assessed using the Karolinska Sleep Questionnaire on three occasions over five years, twice before and once around the time of PET imaging. Shorter sleep, more frequent napping, daytime fatigue, and sleep insufficiency were associated with higher TSPO levels in the middle frontal cortex (MFC). Conversely, longer sleep was associated with higher TSPO levels in the hippocampus and putamen. Exploratory factor analysis and bootstrapping confirmed a negative association between a factor representing shorter sleep and MFC TSPO levels. Additionally, a greater deviation from optimal sleep duration over the five years, in either direction from eight hours, was associated with higher current TSPO levels in all but one examined brain regions. Peripheral C-reactive protein levels did not significantly correlate with the sleep variables or TSPO levels in any of the brain regions. Analyses were adjusted for age and sex. These findings suggest that insufficient and prolonged sleep durations are associated with elevated microglial density in frontostriatal and limbic systems, respectively, among healthy middle-aged and older adults, without any associations with peripheral inflammation. Further longitudinal studies are needed to clarify directionality and whether changes in sleep duration over time may serve as early indicators of brain health.

Introduction: Type 1 diabetes is characterised by progressive loss of pancreatic beta cells. Studies have shown that interleukin (IL)-17 is likely a mediator for this destruction. Whether inhibition of IL-17 could preserve beta cell function in people with new-onset type 1 diabetes is unknown.

Methods and analysis: In this phase 2, randomised, multicentre, placebo-controlled, double-blind trial conducted at 17 study sites in Sweden, 127 adults aged 18-45 years old with newly diagnosed type 1 diabetes will be enrolled. Participants will be randomised to receive either subcutaneous IL-17 inhibitor or placebo for 52 weeks, in addition to their conventional therapy. The primary endpoint will be change in residual insulin secretion measured by the area under the curve for C-peptide in response to 2-hour mixed meal tolerance test between baseline and week 52. Additionally, masked continuous glucose monitoring will be performed during 14 days at the run-in period, week 13, week 26 and week 52. Secondary endpoints will be change in time in glucose range (3.9-10 mmol/L), time in hypoglycaemia (<3.9 mmol/L), HbA1c and mean insulin dosage per kilogram body weight. Patient-reported outcomes will be evaluated with questionnaires at baseline, week 26 and 52. Additionally, 1 and 3 years after the end of the treatment period, the participants will be examined during a visit regarding endogenous insulin production, glycaemic control, glucose metrics and insulin doses.

Background: There has been an increasing number of single-centre studies describing the long-term outcomes of patients with Hirschsprung disease. This study aimed to systematically review the literature on long-term bowel, urological, and sexual functional outcomes, fertility and quality of life in adults with Hirschsprung disease. Methods: A PROSPERO-registered systematic review of the English literature was conducted for studies published up to July 2025 that reported functional outcomes beyond childhood (>= 16 years) for patients who had undergone surgery for Hirschsprung disease. Centres were contacted individually for secondary analyses of patient-level data on bowel function score, Gastrointestinal Quality of Life Index, and Short Form 36 questionnaire. Data were analysed and compared with those from healthy controls in the studies retrieved and from a reference healthy population. Hirschsprung disease clinical and surgical variables were correlated with these outcomes of interest in a patient-level analysis. Results: Fifty-three manuscripts fulfilled the inclusion criteria of 4277 papers retrieved. Patients with Hirschsprung disease had a greater likelihood of constipation (odds ratio 9.27, 95% confidence interval (c.i.) 4.78 to 18.06) and soiling (odds ratio 2.76, 1.96 to 3.89) compared with healthy controls. They scored lower on the Gastrointestinal Quality of Life Index (mean difference -5.21, 95% c.i. -9.53 to -0.89; P = 0.020). There were no significant differences in Short Form 36 domain scores except for physical functioning (mean difference -6.30, -8.74 to -3.87; P < 0.001). At a patient level, longer-segment disease (P < 0.001) and redo pull-through surgery (P = 0.002) were associated with a poorer bowel function score. Short form 36 scores were lower in women across six of eight domains; similarly, Gastrointestinal Quality of Life Index scores were lower in women (P < 0.001) and in patients with longer-segment disease (P < 0.001). Conclusion: Among patients with Hirschsprung disease, women, those with longer-segment disease, and patients who underwent redo surgery may be at risk of poorer quality of life.

Inner speech, or covert speech, refers to the internal generation of language without overt articulation. Decoding inner speech has significant implications for brain-computer interfaces (BCIs), particularly for assistive communication in individuals with speech and motor impairments. To facilitate research in this area, we introduce a publicly available dataset comprising simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data during inner speech production.

Data were collected from three healthy, right-handed participants performing an inner speech task. The task involved silent repetition of visually presented words belonging to either a social or numerical category. The experiment consisted of 40 trials per word, with eight unique words and starts with a fixation period of two seconds. Stimuli were displayed for two seconds at the beginning of each session, followed by a 12-second rest period to allow hemodynamic responses to return to baseline. Participants were instructed to remain still and avoid movements to minimize artifacts. EEG was recorded using a 64-channel MR-compatible cap (BrainCap MR, EasyCap GmbH) at a 5 kHz sampling rate. Electrocardiogram (ECG) signals were simultaneously acquired using an additional electrode placed on the trapezius muscle to facilitate cardioballistic artifact correction. Gradient and cardioballistic artifacts were corrected using BrainVision Analyzer software.

Functional MRI data were acquired using a 3T scanner with a 48-channel headcoil, and an echo-planar imaging (EPI) sequence optimized for whole-brain coverage. The repetition time (TR) was 2 s. High-resolution anatomical T1-weighted images were also acquired for structural reference. The dataset is publicly available in the OpenNeuro repository. The aim of this dataset is to provide a resource for studying inner speech processing, multimodal neuroimaging, EEG-fMRI fusion techniques, and BCI-driven speech prosthesis development.

Background: Heat events have detrimental effects on maternal and neonatal health, increasing the risk for maternal complications, preterm birth, and neonatal mortality. There is an urgent need to explore pregnant women’s heat risk perceptions and adaptive measures. This study uses the Health Belief Model (HBM) to investigate pregnant women’s perception of heat risks and related prevention and mitigation strategies and identifies barriers to the adoption of such behaviours.

Methods: Using a concurrent cohort design, a baseline assessment was conducted through semi-structured interviews with 745 pregnant women in a heat prone district in Nepal. The interviews collected socio-demographic information and assessed the five HBM constructs of heat event risk perception using a Likert scale. Heat maps were created to visualise perceptions, and Principal Component Analysis was undertaken to create a nominal scale score for each construct. Crude and adjusted linear regressions were performed to assess associations of socio-demographic characteristics and HBM constructs.

Results: Among the pregnant women, 68% perceived dehydration due to heat as a risk to their pregnancy, and 37% perceived sunburn as a risk to foetal health. In terms of perceived benefit, 34% agreed that staying in an air-conditioned environment could reduce their chances of suffering during a heat event. Adjusted linear regression showed that wealthier women perceived higher susceptibility (adj. β = 0.14, 95% CI: 0.07, 0.21; p < 0.001) and severity (adj.β = 0.16, 95% CI: 0.08, 0.23; p < 0.001), and reported more barriers (adj. β = 0.16, 95%CI: 0.08, 0.23; p < 0.001). Conversely, urban residents had significantly lower perceived susceptibility (adjusted β = -0.32, 95% CI: -0.41, -0.24; p < 0.001) and severity (adj. β = -0.34, 95%CI: -0.42, -0.25; p < 0.001), fewer barriers (adj. β = -0.34, 95%CI: -0.42,-0.25; p < 0.001) towards heat events, and perceived more benefits (adj. β = 0.31, 95%CI: 0.22, 0.39; p < 0.001) from heat stress prevention and mitigation strategies compared to their rural counterparts.

Conclusion: To promote adaptive behaviours in this vulnerable population and strengthen maternal and foetal resilience against the growing threat of heat, we recommend focusing on closing knowledge, availability, and accessibility gaps. Maternal health considerations should be integrated into national climate change adaptation strategies to ensure that pregnant women are prioritised in policies and interventions. Statistics: IBM SPSS statistic software for Windows version 26 and Stata/SE 18.0 were used for this study.

Objectives:

The International Classification of Functioning, Disability and Health (ICF) offers a standardised language to inform goal setting, support interventions and follow-up on personal functioning outcomes. There is a lack of knowledge about how ICF can be used in practice in residences providing special services for children with intellectual disabilities. This study explores programme theory when ICF categories were integrated into a support development programme to facilitate systematic follow-up on child-individual support interventions in residences with special services.

Methods:

The study employs a realist evaluation design, utilising data from individual child case studies, group interviews, and field notes.

Results:

The findings show that ICF-based follow-up can enable staff to connect personal out-come measures to goals, facilitate infrastructure for measurement and follow-up, create learning and can promote action to improve the children's support. Implementation challenges arose due to an unpredictable and demanding work environment, as well as difficulties in applying ICF categories across various aspects.

Conclusions:

The findings can inform future research regarding working methods as well as disability care organisations striving to develop evidence-based practices. Program design should respect staff workload and minimize elements that add unnecessary complexity to daily tasks.

A single, arterial-optimized 4D-flow MRI acquisition may enable fast assessment of both cerebral arterial and venous flow. However, arteries and veins require different velocity encoding (VENC) settings for optimal velocity-to-noise ratio (VNR). Consequently, venous measurements using arterial-optimized VENC settings are subject to reduced VNR and require further evaluation. This study compared cerebral venous flow and pulsatility assessments using a high-VENC (110 cm/s, adapted to the arterial system) and a low-VENC (40 cm/s, adapted to the venous system) 4D-flow MRI sequence at 3 Tesla. Flow and pulsatility index (PI) were calculated for cerebral veins, sinuses and internal jugular veins in 36 elderly volunteers (79 ± 5 years). The high-VENC acquisitions allowed visualization of nearly all venous structures. Mean flow differences were small and the correlation, strong, when comparing both acquisitions across sinuses (R = 0.90–0.99, difference = -8–7%) and cortical veins (R = 0.93, difference = − 6%). Inflow-outflow differences at the confluence of sinuses were similar between acquisitions. PI showed moderate to strong agreement except in the straight sinus. Both the vein of Galen and the jugular veins suffered from aliasing in the venous VENC acquisitions. In summary, this study demonstrated that a VENC setting adapted for the arterial cerebral circulation was feasible for studying cerebral venous flow and pulsatility.

Objectives: Antimicrobial resistance (AMR) poses a global challenge, especially in conflict-affected settings such as Syria, where health care infrastructure is compromised. This study assessed Syrian clinicians’ knowledge, attitudes, and practices regarding AMR and antimicrobial stewardship (AMS).

Methods: A two-phase online survey was conducted from June-July to October-November 2024 among physicians, pharmacists, dentists, and nurses across 11 Syrian governorates. Participants were recruited through professional networks, social media, and snowball sampling.

Results: Of 1179 respondents, 54% were male and 56% were residents (doctors in training); 32% had over 5 years’ experience. Most practiced medicine (78%), pharmacy (13%), or dentistry (8%). Awareness of AMR as a global (98%), national (93%), and local (67%) issue was high. Although 90% supported AMS, only 47% rated their hospital’s program as effective. Most desired more education (94%) and favored local guidelines (83%). Prescribing confidence was strong for routine cases (63%), but lower for complex ones (40-45%). Concerns included drug quality (80%), cost (52%), and ineffectiveness (47%). Notably, 39% struggled to withhold antibiotics in viral cases.

Conclusion: The survey reveals strong AMR awareness but significant gaps in AMS practice, microbiology access, and clinical guidance. Strengthening Syria’s national AMR strategy is urgently needed.

Murein lipoprotein (Lpp), also known as Braun's lipoprotein, stabilizes the cell wall of Escherichia coli by covalently tethering the outer membrane to the peptidoglycan (PG). Unlike E. coli , Salmonella enterica serovar Typhimurium encodes two murein lipoproteins, LppA and LppB, with LppB bearing an unusual C-terminal sequence, -RICKCOOH. Here, we investigated how LppA and LppB bind to the PG. Both lipoproteins were detected in pure PG material in a ∼ 400:1 LppA:LppB ratio with some LppB molecules forming a cysteine 78 (C78)-C78 intermolecular disulphide bridge. LppA and LppB anchor covalently to uncross-linked and cross-linked muropeptides. However, unlike LppA, which binds to 4,3- and 3,3-cross-linked muropeptides, LppB shows preferred binding to 4,3-cross-linked muropeptides. Mass spectrometry data revealed O -methylation at the terminal K79 residue in some PG-bound LppB molecules. The apparent selective anchoring of LppB to the PG and the K79 modification require the presence of the C78 residue. Anchoring of LppB to PG is mediated by the L,D-transpeptidase LdtB. A survey in more than 158,000 Salmonella genomes identified up to 31 murein Lpp variants differing in the C-terminal region that cluster in three phylogenetic groups. Most serovars of S. enterica subspecies enterica , responsible for infections in warm blooded animals, encode two or even three murein Lpp variants. Altogether, our data are consistent with subtle differences in the mode that LppB anchors to the PG and uncover an unprecedented diversity of murein lipoproteins within the Salmonella genus. The possibility that this variability evolved as strategy to evade host innate immunity, is also discussed.

Genome integrity is constantly challenged by the incorporation of ribonucleotides ribonucleoside monophosphates (rNMPs) during DNA synthesis. Covalently linked single and several consecutive rNMPs occur in the genome of a number of organisms. They are mainly introduced by DNA polymerases during DNA replication and repair. In general, cells evolved ribonucleases H (RNases H) specialized in the removal of rNMPs from DNA to avoid any detrimental consequences on genome stability. Here, we describe the involvement of types 1 and/or 2 RNases H in processing embedded rNMPs in the genome of two archaeal species Haloferax volcanii and Thermococcus barophilus. Genome-wide, nucleotide-resolution maps of embedded rNMPs reveal oriC-centered strand-switching profiles in H. volcanii ΔrnhB, indicating origin firing in native cells, while their absence in T. barophilus reflects low origin usage. The data also define archaeal sequence-context rules for rNMP embedment, confirm the predominant role of RNase HII in rNMP removal with evidence of compensatory repair pathways, and link incorporation patterns to measured rNTP/dNTP pools. Together, these findings uncover archaeal-specific mechanisms of rNMP incorporation and repair with implications for replication and genome stability.

 Denna forskningsrapport redovisar en metod för kapacitetsanalys och dimensionering av trafikflöden över en järnvägsstation under olika driftsförhållanden. 

En optimeringsmodell har utvecklats, vilken maximerar mängden tåg som körs över en uppsättning med trafikrelationer, var och en med olika ruttningsalternativ. Modellen hanterar begränsad spårkapacitet på anslutande spår, plattformar och eventuella uppställningsspår, samt använder en probabilistisk kapacitetsmodell för växlingsområden. Den senare hanterar samtidiga tågrörelser över de olika växlingsområdena på en driftplats, där beräkningsformlerna generaliserats från existerande forskningslitteratur. Tågvägarna kan ha olika beläggningstid, baserat på tågens körtider inklusive tider för tågvägsläggning och frisläppning i signalsystemet. Dessutom hanteras stopp- och uppställningstider vid plattformar och bangårdsspår. Framför allt beräknas alla tågvägar och deras inbördes konflikter automatiskt från driftplatsens spårlayout. 

Beräkningsmodellen har implementerats och testats på olika testinstanser och i en fallstudie för Gävle driftplatsområde. Resultaten visar att modellen kan användas för realistiska problem och för att snabbt skapa kapacitetsanpassade trafiklösningar under olika avstängningsalternativ. En stor fördel är att en generaliserad trafikbeskrivning används, samt att tågvägarna beräknas automatiskt. Detta gör modellen lättare att använda och att den också passar för strategiska analyser av olika driftplatsutformningar. 

Den föreslagna modellen skulle kunna bli ett viktigt verktyg för kapacitetsanalyser, dimensionering av tågtrafik, och utformning av såväl arbetsområden på existerande driftplatser, som framtida spårlayouter eller ombyggnader. Därmed skulle ett viktigt analysbehov för långsiktig kapacitetsplanering på större driftsplatser kunna erbjudas och på sikt ge ett sammanhållet stöd för kapacitetskoordinering av hela järnvägsnätet och dess trafikering. 

Arbetet har utförts i forskningsprojektet ProPå (Probabilistisk metod för trafioch kapacitetspåverkan på driftplatser), finansierat av Trafikverket (FoI-portfölj Vidmakthålla, ärende-ID 8139, diarienummer TRV2024/111657) via branschprogrammet KAJT, Kapacitet i järnvägstrafiken (www.kajt.org). 

The two murine double minute (MDM) family members, MDM2 and MDMX, are a well-established negative regulator of p53 activity. Under DNA damage conditions, MDM2 and MDMX are phosphorylated near their RING domains (serine 395 at MDM2 and serine 403 at MDMX) and switch to act as p53 positive regulators. MDMX binds to TP53 mRNA and acts as a chaperone for RNA structure, enabling MDM2 to bind. This interaction enhances TP53 mRNA translation, leading to increased p53 protein production. While the biological significance of this interaction has been described, the specific features of the MDMX-RNA interaction remain poorly understood. We used various MDMX protein constructs to characterize binding to TP53 mRNA and identified that the interaction mediated by the RING domain is modulated by the presence of other domains. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) and binding assays in high salt conditions and various pH demonstrate that the whole protein participates in RNA interaction, with the C-terminal domain likely providing the contact with RNA by electrostatic forces. We show that protein structural changes induced by the chelating agent EDTA or the reducing agent TCEP enhance RNA binding by promoting partial structural destabilization of the protein. Our findings suggest that the MDMX/TP53 mRNA interaction is complex, with the RING domain binding to RNA and being supported by the entire protein, which acts as a scaffold for the RNA interaction. These results contribute to a better understanding of MDMX's role in TP53 mRNA binding and provide valuable insights for future investigation of the MDM2-MDMX-TP53 mRNA complex, which is crucial for p53 stabilization and activation under DNA-damaging conditions.

Subthalamic nucleus deep brain stimulation (STN-DBS) is a safe and effective therapy for Parkinson’s disease (PD) in selected patients. However, various side effects such as paraesthesia, diplopia, ataxia, worsened akinesia, emotional changes, dysarthria, and muscle contractions can occur due to the current spread to the adjacent structures during the STN-DBS programming sessions. Muscle contractions result from the corticospinal and corticobulbar side effects, which can manifest due to the current spread to the pyramidal tract during DBS programming. Here, we report a case of tongue-twisting movement as a unique corticobulbar side effect of the STN-DBS programming in a patient with PD.

Introduction: Medication-related problems (MRPs) are common among older adults. The global population is ageing and there are health-related challenges linked to ageing in rural areas. Home-living rural older adults often face barriers to access healthcare, like long distances to healthcare services and poor continuity of care. Telepharmacy is the remote provision of pharmaceutical care, and telepharmacy could be of particular importance for rural older adults to improve their access to clinical pharmacy services and reduce the incidence of MRPs. The objective of this study is to develop and evaluate a novel telepharmacy service in primary care for home-living older adults in Northern Sweden’s rural areas. The primary objective is to evaluate the effect of the telepharmacy service regarding the identification, classification and resolution of MRPs.

Methods and analysis: This study will be conducted as a single-arm interventional study. A total of 100 people ≥65 years will receive the telepharmacy service for 12 weeks. The key principles of the telepharmacy service are to perform medication interviews and follow-up meetings with study participants, to conduct structured medication reviews, to conduct regular electronic medical record reviews and to have interprofessional collaboration with primary care physicians. All meetings will be conducted through video conferencing via a secure virtual care platform. Identified MRPs will be classified, and the acceptance rate of the pharmacists’ recommendations will be evaluated. The results will be presented with descriptive statistics. As secondary objectives, intra-individual changes in participants’ medication adherence, health-related quality of life and beliefs about medicines will be assessed through self-report questionnaires. Statistical analysis will be conducted using two-sided McNemar’s tests. Semi-structured interviews will also be conducted to explore participants’ and healthcare professionals’ experiences and attitudes towards this telepharmacy service.

Ethics and dissemination: This study has been granted ethical approval by the Swedish Ethical Review Authority (registration number 2022-03819-01 and 2024-08441-02). Participant informed consent is required. The results will be published in peer-reviewed journals and presented at scientific conferences.

En ny förbindelse under Fehmarn Bält förväntas stå färdig runt år 2030 och kommer att öka kapaciteten och förkorta transporttiderna. Detta får betydande konsekvenser för både väg- och järnvägstrafiken till och från Sverige. Den nya förbindelsen har varit känd sedan länge och är en förutsättning i Trafikverkets basprognos och som planeringsunderlag. Det finns dock fortfarande anledning att analysera eventuella osäkerheter i prognosen och identifiera aspekter som kan behöva belysas ytterligare.

Syftet med rapporten är att säkerställa och tydliggöra effekterna av en ny förbindelse under Fehmarn Bält med hjälp av Trafikverkets prognosmodeller. Detta görs för att kunna verifiera åtgärdsförslag och effektanalyser som har tagits fram. Vidare syftar utredningen till att ge underlag för att anpassa transportmodellen för godstrafik, så att den bättre återspeglar godstågens egenskaper i relationen Sverige - Tyskland.

Background: Abdominal aortic aneurysm (AAA) is a multifactorial vascular disease with limited therapeutic options, as no pharmacological treatments currently exist to mitigate the progression of small AAAs. Quality of life (QoL) has emerged as a valuable supplementary metric for assessing the efficacy of pharmacological interventions. This study evaluated QoL scores of MetAAA trial patients on metformin therapy compared to those with placebo intake.

Methods: Overall, 54 patients with AAA were included in the MetAAA trial (ClinicalTrials.gov-Identifier:NCT03507413) and randomized to either metformin or placebo treatment. All participants were asked to complete three established and validated (in total 659 longitudinally collected) QoL questionnaires: (1) the 36-Item Short Form Health Survey (SF-36), (2) the Aneurysm Symptom Rating Questionnaire (ASRQ), and (3) the Aneurysm-Dependent Quality of Life questionnaire (ADQoL).

Results: A superior health-related QoL was found in metformin-treated AAA patients compared to enrolled AAA patients receiving a placebo. In detail, AAA patients undergoing metformin treatment showed a superior overall current QoL score (p = 0.038), general health perception (p = 0.013), improved physical functioning (p = 0.004), and increased energy/lower fatigue scores (p = 0.008). Furthermore, fewer limitations due to cognitive distress (p = 0.001) and lower limb function (p = 0.021) were detected. Other QoL subscales did not show statistical significance. Inflammatory blood parameters suggest that while systemic inflammation may have some impact on perceived QoL, the relationship is largely limited.

Conclusions: In patients with small AAA, metformin led to a limited improvement in health-related QoL compared to a placebo.

BACKGROUND: It is suggested that late initiation of toilet training contributes to functional gastrointestinal disorders in children. This study aims to evaluate if assisted infant toilet training can reduce the prevalence of functional gastrointestinal disorders during the first 9 months of life.

METHODS: The ongoing Bowel And Bladder function in Infant Toilet Training (BABITT) study is a randomised, controlled trial that recruited infants aged 0-2 months at six Child Health Centres in Sweden. Infants were randomly assigned (1:1) to either start parent-assisted infant toilet training at the age of 0-2 months (intervention) or as controls. The intervention group was encouraged to practise at a moderate frequency of 1-3 times/day, 5-7 days/week. A validated web questionnaire was answered at ages 2, 3, 6 and 9 months.

RESULTS: 271 infants (145 males, 54%) were randomly assigned at median age of 34 days (136 intervention; 135 controls). The intention-to-treat analysis with complete cases (127 intervention; 132 controls) showed no difference in the total period prevalence of functional gastrointestinal disorders (infant colic, infant dyschezia and/or functional constipation, defined by Rome IV criteria) between the intervention group and controls (52.0% vs 49.6%, difference 2.4% (95% CI -9.8 to 14.7); p=0.6956) up to the age of 9 months. Parent-reported intervention adherence ranged between 53% and 63%.

CONCLUSIONS: This study does not support that assisted infant toilet training, practised at a moderate frequency, reduces the prevalence of gastrointestinal disorders during infancy. Long-term effects are being evaluated in the ongoing BABITT study up to the age of 4 years.

TRIAL REGISTRATION NUMBER: NCT04082689.

Syftet med omvärldsanalysen har varit att identifiera drivkrafter, tekniska lösningar och hållbara affärsmodeller som är relevanta för etablering och utveckling av Eko-Industriella Parker (EIP), både i Sverige och internationellt. Särskilt fokus har lagts på vattenresurser och hantering, med målet att uppdatera kunskapsläget kring framgångsfaktorer och utmaningar inom området.

Det huvudsakliga målet har varit att stödja Umeå Eko-Industrial Park (UEIP) i att formulera en strategisk inriktning för industriell symbios, baserad på lärdomar från etablerade exempel och anpassad till de specifika förutsättningarna i norra Sverige, såsom kallt klimat, god tillgång till förnybar energi, långa logistikkedjor och behovet av resilient infrastruktur. Den strategiska inriktningen tar även hänsyn till ambitionen att attrahera nya aktörer till industriklustret på UEIP, särskilt företag verksamma inom bioekonomi, cirkulära materialflöden och teknologier för grön omställning, vilka kan bidra till ett integrerat och hållbart industriellt ekosystem. Omvärldsanalysen omfattade ett flertal nationella och internationella exempel på industriell symbios och hållbar utveckling. Med utgångspunkt i dessa fallstudier, samt projektgruppens samlade erfarenheter, utvecklades ett koncept för en modern EIP med särskilt fokus på hållbar och cirkulär vattenhantering. Konceptet bygger på synergier mellan olika aktörer som etableras inom området, där resursdelning och samverkan kring vattenflöden utgör centrala komponenter i parkens symbiosstrategi.

Implementering av framtaget koncept på UEIP kommer att kräva olika förändringar och utvecklas genom både stegvis och radikal innovation. För att vattensymbiosen ska kunna realiseras på UEIP behöver en detaljerad kartläggning av varje aktörs vattenbehov och vattenflöden genomföras. Detta bör integreras som en naturlig del av etableringsprocessen inom EIP. Information om exempelvis vattenkvalitet, kvantitet och temperatur måste tydliggöras, både för inkommande och utgående vatten, för att det ska vara möjligt att identifiera matchningar och synergier mellan olika aktörer. Framtida insatser bör ta ett helhetsgrepp där teknik, affärsmodeller, reglering och aktörssamverkan utvecklas parallellt för att skapa ett hållbart och framtidssäkrat vattenhanteringssystem.

High resolution air quality dispersion modelling was applied to assess the health risks of long-term exposure to ultrafine particles (UFP) emitted from the transport sector and to evaluate the health benefits of different local interventions in Stockholm. Health impacts, based on associations between exposure, premature mortality and various diseases, were quantified as quality adjusted life years (QALYs) and monetized as health-related costsIrrespective of local mitigation measures in the city, fleet renewal driven byvehicle emission regulations is projected to reduce UFP exposure by 86 % between 2021 and 2030, saving almost 1700 QALYs corresponding to approximately €500 M in health-related costs. The renewal of the fleet affects mainly diesel passenger cars and heavy goods diesel vehicles equipped with particle filters, whichefficiently remove most exhaust particles, including UFPs. Among the local mitigation policies, the introduction of a low emission zone (LEZ) in 2030 covering 16 km2 of the inner city is estimated to save around 40 QALYs. In contrast, a much smaller LEZ (0.2 km2) approved by the city council would yield minimal health benefits, saving only 0.1 QALYs. Electrification of road vehicles under the business as usual (BAU) scenario is projected to save around 70 QALYs in 2030, exceeding the gains of any local policy scenario. Comparisons using PM2.5 and NO2 as predictors of health-related emissions, shows that gains in adverse health impacts of local mitigation actions may be severely underestimated if only health impacts of UFP exposure is considered.

Dissolved organic matter (DOM) is a major source of macronutrients to freshwaters, yet it has variable and poorly understood bioavailability. Because intrinsic variation in bioavailability is caused by chemical structures of organic nutrients, DOM composition data should improve predictions of bioavailable resource pool sizes. We hypothesized that bioavailable organic carbon (C) and nitrogen (N) fractions are made up of freshly produced humic- and protein-like DOM, respectively, whereas bioavailable phosphorus (P) is linked to microbially-derived DOM with potential organophosphate content and/or to humic-like structures associated with DOM-Fe-phosphate complexes. These hypotheses were tested from surface waters collected at eight, unproductive and organic matter-rich stream and lake sites, from which we performed C, N and P microbial bioassays with flow cytometry in combination with analyses of DOM composition using fluorescence excitation-emission matrix (EEM) analysis. Bioavailable C followed the predicted patterns, with strong links to fluorescent features indicating recently produced DOM. Surprisingly, bioavailable N was relatively poorly related to DOM composition, including protein-like fluorescence, and was instead driven mainly by the amount of inorganic N. The bioavailable P showed patterns in support of the hypothesized link to microbially-derived organic components, whereas its relationships to free or complex-bound forms of inorganic phosphate were inconclusive. Thus, the strength of the hypothesized patterns varied. Nonetheless, in addition to the variability in bioavailable nutrient concentrations explained by standard bulk nutrient variables, we show that DOM composition variables made significant and unique contributions to explaining the variance in bioavailable C (19%), N (13%) and P (18%). Therefore, improved regression models for bioavailable nutrient concentrations could be achieved by including DOM composition among the explanatory variables. Overall, DOM composition analysis is a promising tool to improve prediction and develop our understanding of bioavailable macronutrients in organic matter-rich freshwaters.

BACKGROUND: In Sweden, almost 60% of patients seeking care at primary healthcare centers do so due to musculoskeletal disorders. These patients constitute a strain on the healthcare system. Manual therapists are experts in diagnosing patients with these conditions but are usually not part of healthcare centers in Sweden. Further, there is a significant societal problem with overuse of medications, injections, medical imaging, and unnecessary surgeries, so-called low-value care, for back and neck pain. We aimed to explore the current management of patients with back and neck pain in primary healthcare centers, staff's perceptions regarding the need for improvement, and incentives and concerns about having licensed chiropractors and naprapaths (manual therapists) triage these patients as part of the primary healthcare center team.

METHODS: In this qualitative study, we conducted semi-structured focus group interviews with 20 participants employed at three primary healthcare centers in the Stockholm region, chosen based on location, organization, and exposure to manual therapists. Participants were purposefully selected from different professions. Data were analyzed using inductive qualitative manifest and latent content analysis.

RESULTS: The current management of patients with back and neck pain was described in terms of long waiting times and patients' expectations of seeing a medical doctor and receiving imaging. Thus, there was room for improvement by reducing low-value care. Participants had limited knowledge about the competence of chiropractors and naprapaths and were concerned about the boundaries of professional identity. Decreased physician workload and more choices for patients were mentioned as incentives for manual therapists to take on a triaging role.

CONCLUSIONS: Staff at three primary healthcare centers in the Stockholm area described the current management of patients with back and neck pain as navigating the expectations of patients and their overreliance on seeing their physician, not other caregivers, resulting in long waiting times. Alongside patients expecting imaging, these were incentives for chiropractors and naprapaths triaging these patients as an opportunity to improve care. A lack of knowledge about the competence of manual therapists was a concern, and assigning manual therapists to the primary healthcare team would necessitate a reconfiguration of the care process, potentially challenging the boundaries of professional identity.

INTRODUCTION: Academic literacy in higher education has been widely studied, but less attention has been given to literacy practices within professional programmes such as nursing education. This study aimed to analyze one Swedish undergraduate nursing programme regarding the presence of academic and professional literacy, and secondarily to explore students' note-taking as a component of literacy practices.

METHODS: The study employed a descriptive and exploratory design, analyzing curriculum documents and surveying nursing students. An analysis of the intended curriculum (course syllabi) of a three-year undergraduate nursing programme at Karolinska Institutet was conducted to identify explicit and implicit literacy components. A digital questionnaire focusing on note-taking practices was distributed to second-semester students (n = 67; response rate 40%). Closed questions were analyzed using descriptive statistics, while open-ended responses underwent qualitative content analysis.

RESULTS: The curriculum analysis demonstrated that academic literacy was primarily addressed through scientific writing, group projects, and thesis work, particularly in the first two and final two semesters. Professional literacy was integrated across all semesters and included communication with patients, families, and interprofessional teams, documentation, and interpretation of professional texts. Surveyed students reported frequent note-taking, primarily during lectures and prior to examinations, using both pen and paper and digital devices, with a preference for pen and paper. Qualitative data indicated that students use note-taking mainly to support memorization, understanding, and exam preparation, with limited focus on professional literacy needs.

CONCLUSION: The nursing curriculum integrates both academic and professional literacy practices, although with different emphases across the study period. Students' current note-taking practices are predominantly academically oriented. These findings highlight the need for more explicit integration and scaffolding of both academic and professional literacy throughout nursing education to better prepare students for their future professional roles, i.e., for clinical communication, documentation, and interprofessional collaboration essential to safe and effective patient care.

OBJECTIVES: To examine injury prevention strategies and potentially modifiable risk factors (MRFs) for upper extremity (UE) injuries in female, woman and/or girl athletes (female/woman/girl).

DESIGN: Systematic review with meta-analysis, semiquantitative analyses and Grading of Recommendations Assessment, Development and Evaluation in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

DATA SOURCES: MEDLINE (Medical Literature Analysis and Retrieval System Online), CINAHL (Cumulative Index to Nursing and Allied Health Literature), APA PsycINFO (American Psychological Association Psychological Information Database), SPORTDiscus (Sports Discus Database), EMBASE (Excerpta Medica Database), and ERIC (Education Resources Information Center) (30 October 2023) and Cochrane Systematic Review Database and the Cochrane Central Register of Controlled Trials (CENTRAL) (25 November 2023).

ELIGIBILITY: Primary data studies with comparison group(s) assessing the association of prevention strategies and/or MRFs for sport-related UE injury, with ≥1 female/woman/girl in each study group.

RESULTS: 55 studies (n=20 intervention, n=35 MRF) were included with 33 228 athletes (8642 female/woman/girl; 26%). Of these, 17 (31%) reported female/woman/girl-specific estimates and included five injury locations (n=3 general UE, n=12 shoulder, n=3 elbow, n=3 wrist/hand). One prevention strategy (n=5 shoulder-specific exercise programmes) and seven MRFs were identified, including less range of motion (n=6), less shoulder muscle strength (n=8), high training load (n=1), presence of scapular dyskinesis (n=3), high sport specialisation (n=2), equipment differences (n=1) and less sport-specific conditioning (n=1). Pooled data from three studies suggest that shoulder exercise programmes consisting of strength, stability/control and sport-specific exercises reduce shoulder injury rates by 51% (95% CI 0.30 to 079; I² 0.0%; very-low certainty evidence) across paediatric (≤18 years) and adult handball and volleyball players.

CONCLUSIONS: Our understanding of female/woman/girl UE injury prevention is limited by heterogeneity across injury outcomes, interventions, MRFs and limited female/woman/girl athlete-specific data. Shoulder-specific strengthening and stability exercise programmes may be beneficial to reduce shoulder injury rates in female/woman/girl handball and volleyball players. Future research should prioritise female/woman/girl athletes to reduce the burden of UE injuries.

PROSPERO REGISTRATION NUMBER: PROSPERO CRD42024494967.

This study investigates how academic writing practices at university are represented and introduced through instructional models in Swedish and English teaching materials. The scaffolding power of such models is often assumed without scrutinizing how these models can provide entrance points to writing practices for students dealing with specific writing tasks. Grounded in an interest in learning, the study analyses selected models in frequently-used teaching materials for academic writing in Sweden. Findings are: the same model is used to present writing as a matter of language or as academic work; the introduction of the models positions students as responders to assignment tasks in the Swedish materials or as actors on the global research market in the English materials. How writing can become relevant for learning by connecting students’ prior knowledge – gained from writing in different contexts and in different languages – with engaging in current writing tasks remains tacit.

Incorrect human behavior is a significant contributor to maritime accidents. Navigation skills therefore represent a critical factor for safety at sea. Integration, digitalization, and intelligent navigation technologies impact Maritime Education and Training (MET). The study aims at understanding how maritime experts and maritime trainees allocate their visual attention to avoid collision during intense maritime traffic in a full-mission bridge simulator. A sample of two experienced active navigators and seven maritime students were fitted with a wearable eye-tracker and placed in different navigational watchkeeping simulation contexts. Individual visual attention was quantified through the analysis of areas of interest (AOIs) and gaze shifts between these AOIs. Experts and novices differ in their gaze patterns. The most prominent difference is that experts make less use of instruments and look out more for information gathering. As ships are complex socio-technical systems, the results of this study may provide Integrated Bridge Systems (IBS) designers and MET professionals with useful insights on the interaction between humans and navigation instruments.

Objectives: The aim of this study was to investigate whether any feature of carotid artery calcification (CAC) detected on panoramic radiographs (PRs) is associated with more severe signs of cardiovascular disease (CVD), as assessed by carotid ultrasound (CUS) including multi-view assessment of carotid intima media thickness (cIMT).

Methods: The present investigation was a retrospective sub-study of the randomized controlled trial visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA), which included 60-, 50-, and 40-year-old inhabitants of V & auml;sterbotten County, each of whom underwent CUS. The present sub-study included 135 participants who had undergone PR for odontological indications within 18 months before or after CUS examination. Findings of CAC on PR were compared with CUS findings of cIMT and carotid plaque. CAC features were categorized into 4 types: single, scattered, vessel width-defining, or vessel-outlining.

Results: Compared to participants without CAC on PR, those with any CAC type on PR exhibited significantly more carotid plaque (80.9% vs 43.2%, P < .001) and a higher average cIMT score (0.83 vs 0.77 mm, P = .013) on CUS. The vessel-outlining CAC group exhibited the most pronounced cIMT and carotid plaque occurrence (P = .011).

Conclusions: All CAC types detected on PR were associated with CVD on CUS, and vessel-outlining CAC indicated more severe CVD. By detecting CAC on PR, especially vessel-outlining CACs, dentists could contribute to the early identification of patients with asymptomatic CVD, and recommend that these patients seek medical attention for preventive treatment.

Advances in knowledge: All types of CAC detected on PR-particularly the vessel-outlining type-are associated with carotid ultrasound findings, including carotid intima media thickness, indicating CVD and increased risk of stroke and myocardial infarction. Thus, dentists can identify patients at increased risk of cardiovascular events by detecting CAC on PR, with higher diagnostic reliability in cases with vessel-outlining calcification.

Improving the social environment conducive to learning in schools is a critical challenge globally and within the Swedish context, as education systems face persistent issues like a lack of classroom safety and a concurrent crisis in teacher well-being and professional leadership. Therefore, various intervention frameworks are implemented to address the issue. This study investigated how two Swedish compulsory schools implemented the Positive Behaviour Supports (PBS) framework. By combining classroom observations and teacher interviews, the research addresses a gap in existing research that often provides an incomplete view of actual practices. The results, based on observations and interviews with 14 staff members, confirmed that PBS successfully creates a calm and predictable school climate. Teachers consistently maintained a calm demeanour and used clear lesson structures, along with positive feedback. However, the study also revealed a significant gap between the intended proactive nature of PBS and the observed reactive behaviours of teachers. While the framework fostered a shared, collaborative approach among staff, it was inconsistently applied when it came to proactive strategies, such as explicitly teaching social and life skills. The results suggest that future professional development should focus on helping teachers shift from a reactive to a more consistently proactive and positive model of behavioural support.

Den här rapporten handlar om förebyggande socialt arbete med familjer som har migrerat till Sverige och lever i långvarig väntan på livsavgörande beslut om exempelvis uppehållstillstånd, var de ska bo, hur de ska försörja sig och kanske återförening med familjemedlemmar. Syftet är att synliggöra och ge en fördjupad förståelse för föräldraskapets villkor och familjecentralernas arbetssätt i relation till familjernas behov. [. . .]

We consider the computation of dynamic arrival routes (DARs): arrival routes from all entry points of a terminal maneuvering area that merge traffic arriving in a given time interval towards the runway for which we can guarantee separation for all arriving aircraft and enable all aircraft to follow optimal descent profiles. We exploit our recent mathematical results to bring the concept of DARs closer to practical applicability by demonstrating how we can integrate both the impact of atmospheric conditions on the aircraft’s descent profiles and the interaction with departing traffic into our DARs framework. With experimental results for Stockholm Arlanda airport, we give a proof of concept of this integration—showing that we can quickly obtain optimal solutions—and highlight the importance of these aircraft-specific and traffic-situation-dependent factors.

Alcohol addiction is a psychiatric disorder characterized by a chronic relapsing trajectory and continued drinking despite negative consequences, also referred to as compulsive drinking. Craving for alcohol, a hallmark of addiction, is a predictor of relapse, and can be triggered by social stress. The mechanisms of alcohol addiction are complex, and involve environmental and genetic susceptibility factors. Social marginalization, commonly experienced by people with alcohol addiction, can promote a vicious circle of drinking and further social rejection that exacerbates the addictive state. Several studies implicate the endogenous opioid system as a link between these behaviors.

The endogenous opioid system acting through mu-opioid receptors (MORs), plays a key role in the modulation of pain and reward, but has also been proposed as a neural substrate of social attachment. Functional genetic variation in the gene encoding the MOR, OPRM1 A118G, has been reported to moderate rejection sensitivity in both primates and humans, but previous studies have been criticized due to small sample sizes. Therefore, the aim of Paper I was to test if OPRM1 A118G influenced dispositional sensitivity to rejection in an online game setting, with a sample large enough to detect small effects. However, we did not find support for this hypothesis.

The anterior cingulate cortex (ACC) and the insula are neural structures typically activated during somatic pain, but have also been reported to become activated during experimental social rejection.  This has led to the hypothesis that physical and social pain share a common alarm system, a notion consistent with high concentrations of MORs in these shared areas. However, the evidence for a social pain construct has primarily relied on fMRI studies showing task-based activations, or correlations with MOR-ligand displacement during positron emission tomography (PET) scans. These studies are merely correlational, and Paper II therefore aimed to test if MOR activation using exogenous opioids would alleviate rejection related distress in a randomized controlled trial (RCT). We found that the experimental social exclusion was associated with negative affect and the expected neural activity in the insula and the orbitofrontal cortex (OFC). However, contrary to our hypothesis, we found no influence of the prototypical MOR agonist morphine on self-reported distress or neural activity. 

Childhood maltreatment, a form of severe social stress, is a risk factor for developing addiction, but clinical assessments commonly rely on retrospective self-reports that are subject to bias. In Paper III, we examined the performance of the Childhood Trauma Questionnaire (CTQ) to detect prospectively documented childhood maltreatment in a unique cohort, that allowed us to test how Substance Use Disorder (SUD) influenced the retrospective reports. We found that the CTQ had an excellent ability to identify childhood maltreatment in individuals without SUD, but performed only slightly better than chance in people with SUD.

The insula has also been proposed to play an important role in processing alcohol craving. The insular cortex has only recently become accessible for non-invasive neuromodulation, and treatment using deep repetitive transcranial magnetic stimulation (rTMS) was reported to reduce both cigarette craving and smoking. Paper IV aimed to test if deep rTMS would be efficacious against alcohol craving and drinking. We found imaging-based evidence of neuromodulation of insula function, but despite this, we found no significant treatment effects of deep rTMS targeting this structure on alcohol craving or use.

Recent advances in brain imaging have shown that emotional and motivational states, including craving, recruit networks across the whole brain rather than being represented in isolated brain areas. The newly developed Neurobiological Craving Signature (NCS) has been shown to correlate with self-reported drug craving, an established predictor of relapse. This prompted the question whether the NCS could also predict clinical outcomes in alcohol addiction. This was evaluated in Paper V in the same patient cohort as in Paper IV. Here, we showed that the NCS was strongly correlated with self-reported craving. Most importantly, it predicted relapse and alcohol use during the three month follow-up phase.

This report concerns the design of speed-reducing measures in rural areas. More specifically, an experiment was conducted in a driving simulator to study how vehicle speed through the measure is affected when the length and width (lateral shift) of the measure are increased or decreased. The experiment was based on two existing locations where various geometric modifications were made in the digital environment. One of the locations is situated on a 70 km/h road entering a small village with a 40 km/h limit, while the other location is on a 100 km/h 2 plus 1 road, situated just before an intersection with a 70 km/h limit. A total of 19 people participated in the experiment, resulting in 197 driving sessions across 12 different scenarios (6 per location). The results of the experiment show how vehicle speed at different points through the measure is influenced by the length and lateral shift of the measures. In general, the results indicate that increasing the lateral shift by 1 meter reduces speed by 2–5 km/h, and decreasing the length of the measure by 1 meter reduces speed by 0.3–0.6 km/h. The experiment also shows that the smallest turning radius of the vehicles’ driving paths is generally 1.5 times the minimum radius of the implemented measures.

BACKGROUND: Low lung function has been consistently associated with increased cardiovascular disease (CVD) risk, with emerging evidence suggesting a potential causal relationship. However, underlying biological mechanisms remain unclear. AIM: To investigate relationships between CVD-associated plasma proteins and lung function.

METHODS: We analysed plasma protein profiles in two Swedish population-based cohorts: the Swedish CArdioPulmonary bioImage Study (SCAPIS) (n = 4,982, mean age 57.6 years) as the discovery cohort and the SCAPIS pilot study (n = 1,054, mean age 57.7 years) for replication. Multiple linear regression models were used to assess associations between 92 CVD-associated proteins and z-scores of FEV1, FVC, and FEV1/FVC, adjusting for known confounders. P-values were corrected using the Benjamini-Hochberg method (5% FDR). Significantly associated proteins were validated in the replication cohort. R

ESULTS: A total of 69 proteins were associated with FEV1, 57 with FVC, and 9 with FEV1/FVC. Several inflammatory proteins and adipokines, including leptin, interleukin-6, fatty acid-binding protein (adipocyte), were consistently linked to lower lung function. Leptin had the strongest negative association (FEV1: β = -0.50, 95 % CI: [-0.69, -0.31], p < 0.001; FVC: β = -0.52, 95 % CI: [-0.68, -0.35], p < 0.001 per-SD increase).

CONCLUSIONS: Multiple CVD-associated proteins, mainly reflecting inflammatory and metabolic processes, were associated with reduced FEV1 and FVC, supporting a link between systemic inflammation, adipokine metabolism and impaired lung function. Leptin had the strongest association, suggesting that its effects on lung function may extend beyond adiposity. Further research is needed to clarify the mechanisms driving these associations and to assess whether these proteins could serve as early biomarkers or intervention targets.

Aim: To evaluate the use of patient-controlled sedation with propofol in outpatients with anxiety and fear of gynaecological procedures, considering patient satisfaction, feasibility and costs.

Design: This quantitative study used a descriptive retrospective design.

Review Methods: This study evaluated patient satisfaction, procedure feasibility and direct costs for PCS with propofol for outpatients with anxiety and fear of gynaecological outpatient procedures. Data including patient age and evaluation of the procedure, as well as procedure-related information describing the type of procedure, duration of the procedure, drugs used, vital signs, interventions and evaluations by staff was extracted from medical records.

Data Sources: Data was collected from the medical records of all outpatients who completed a gynaecological procedure using PCS with propofol during the period February 2021 until July 2023 at the GC, Vrinnevi Hospital (Sweden).

Results: A total of 128 gynaecological procedures with patient-controlled sedation were performed successfully. Few transient cardiopulmonary events occurred (n = 13), and only one needed use of a jaw thrust to resolve desaturation. The feasibility of the procedure and sedation were assessed to ‘Easy’ (84%, 96%) and no sedation-related cancellations of the procedure were reported. Patients' overall satisfaction was high and they were reported to be ‘Very satisfied’ in 86% of the procedures. The mean cost per patient was 85% lower when the procedure was completed at a gynaecological outpatient clinic instead of a daycare surgical unit.

Conclusion: Patient-controlled sedation outpatients with anxiety and fear for gynaecological procedures has been shown to be a well-tolerated method of sedation that gives high patient satisfaction, allows procedures to be completed in a high-quality way and has the potential reduce direct costs.

Implications for the Profession and/or Patient Care: Patient-controlled sedation with propofol in outpatients with anxiety and fear of gynaecological procedures may improve patient satisfaction and procedure with the potential to reduce direct costs.

Impact: The findings of this study contribute to the growing body of knowledge on patient-controlled sedation (PCS) in gynaecological procedures. By demonstrating that PCS with propofol is feasible, safe and associated with high patient satisfaction, this study highlights its potential to reduce patient anxiety and improve the sense of control during procedures. In addition, PCS may decrease the need for premedication with oral benzodiazepines and reduce referrals to day-surgery units, thereby saving healthcare resources and increasing accessibility for patients. Taken together, the results suggest that PCS can be an important tool in enhancing both the quality and efficiency of gynaecological care.

Reporting Method: Reporting followed the STROBE checklist for cross-sectional studies.

Patient or Public Contribution: No patient or public contribution. 

Purpose: This study evaluated interfractional bladder volume variations and the resulting dosimetric changes during short-course radiotherapy (SCRT) 5 × 5 Gy (relative biological effectiveness) in patients with locally advanced rectal cancer.

Materials and Methods: Twenty patients received either protons or photons with daily cone-beam computed tomography (CBCT). All patients received the same drinking instructions prior to the planning computed tomography (CT) and each fraction. For each patient, volumetric modulated arc therapy (VMAT) and proton beam therapy (PBT) plans were generated. The bladder was delineated on each CBCT which were registered to the planning CT in the treatment planning system. The baseline bowel bag structure was adjusted accordingly for each bladder volume. Volumetric and dosimetric data for the bladder and bowel bag were then analyzed.

Results: Baseline bladder volumes were on average 71 cm3 larger than the average volume during treatment (95% confidence interval, 15 to 126). No significant difference was detected during treatment. Mean bladder doses decreased significantly from baseline to during treatment for both VMAT and PBT treatment plans (p = 0.021 and p = 0.002, paired two-sided t-test). Compared to baseline, the dose to the bowel bag adjusted for daily bladder volume increased by 3.8% for VMAT (t = –2.56, p = 0.019, two-tailed) and 18.7% for PBT (t= –2.415, p = 0.026, two-tailed).

Conclusion: We report consistently smaller bladder volumes during SCRT compared to baseline. This resulted in lower-than-expected mean bladder doses during the treatment course and consequently an increase in dose to bowel bag. Variations in bladder volume resulted in larger changes in delivered dose to bladder and bowel bag in PBT compared to VMAT.

The p-i-n junction structure that develops dynamically under an applied bias via electrochemical doping (ECD) is of key importance for the performance of light-emitting electrochemical cells (LECs). While the complex electronic and ionic processes that govern its transient formation have been extensively studied by both experiments and drift-diffusion modeling, less attention has been given to the steady-state junction as a function of voltage. Here we study the formed p-i-n structure of a polymer LEC at the steady state by measuring and analyzing its most distinctive feature: the current density-voltage-luminance characteristics. Unexpectedly, we find that the effective conductance of the p-i-n structure exhibits a positive correlation with the applied bias, a behavior not predicted by existing LEC drift-diffusion models. We attribute this discrepancy to the assumption in these models of a constant density of mobile ions. Hence, we present a modified model in which the ECD level - represented by the number of ions with which the organic semiconductor is doped - scales with the applied voltage, implying a voltage-dependent doping efficiency. We validate this hypothesis using electron spin resonance spectroscopy and drift-diffusion modeling, while additionally establishing that only a small fraction of the available ions in our system, which increases from 1% to 3% with increasing bias, contributes to the ECD and is necessary for efficient LEC operation. These findings not only provide fundamental insights into the operational mechanism of LECs but also have direct implications for the broader organic mixed ionic and electronic conductor community.

This research investigates the needs and preferences of low-income angioplasty patients and their caregivers in India during post-angioplasty recovery. Through in-depth interviews and contextual inquiries, the study uncovers critical informational, physical, and emotional needs. Patients often lack access to reliable health information, leading to misconceptions about care and medication adherence. Pain management and emotional support are significant concerns for both patients and caregivers. The study proposes the integration of digital health solutions to address these challenges, providing a platform for reliable information, communication, and support. This research emphasizes the need for context-sensitive interventions to improve patient outcomes and enhance the quality of life for vulnerable populations in developing countries.

The Swedish MASiP project presents a multidisciplinary evaluation of the Mobile Automated Spiral Intelligent Pipe (MASiP), a novel technology for hydrogen transport. The study assesses its feasibility for deployment in Sweden through a case study of the planned 170 km Letsi-Luleå hydrogen pipeline, part of Nordion Energy’s Nordic Hydrogen Route. The assessment combines technical, economic, environmental, regulatory, and risk analyses to guide the implementation of MASiP under Swedish conditions. Close communication and information shared by the technology provider Sustainable Pipeline Systems made it possible to understand the technology a perform the assessment. Hydrogen transport infrastructure is key to Sweden’s 2045 net-zero goal.

MASiP replaces conventional welded steel pipelines with an on-site manufactured composite pipe combining a polymer liner, steel layers, coatings, and integrated fibre-optic monitoring. The techno-economic evaluation of the case study found that MASiP could reduce investment costs by around 29% and achieve a 25% lower levelized cost of transport (0.4 EUR/tH₂-km) compared with conventional pipelines. Lower pressure drop due to the smoother HDPE surface may also reduce compressor requirements. The environmental assessment of the case study indicates that there could be potential benefits, with greenhouse gas emissions during construction being up to 57% lower than conventional pipelines when fossil steel is used and up to 79% lower with green steel. The reduction is primarily due to on-site manufacturing, less steel usage, and minimized transport. Overall emissions from the MASiP system were estimated at 18.3 kg CO₂e per tonne of transported hydrogen, 40–55% lower than conventional systems. An implementation plan outlines the steps to bring MASiP from Technology Readiness Level (TRL) 7 to 9.

The plan identifies key technical, market, and regulatory risks and proposes mitigation through pilot testing under Swedish conditions, stakeholder collaboration, and early regulatory engagement. In conclusion, the MASiP technology demonstrates possible advantages in cost, safety, and environmental performance and could play a central role in Sweden’s emerging hydrogen network. However, further full-scale validation, regulatory adaptation, and strategic partnerships are required to achieve commercial deployment.

Background/Objectives: Undergoing intensive cancer treatment, such as allogeneic haematopoietic stem cell transplantation, challenges the entire life situation of patients and their family caregivers. A prerequisite for effective care is that interventions are tailored to the unique circumstances of each individual. The aim of this study was to examine the feasibility of a developed person-centred nursing model in this context.

Methods: The nursing model involves systematic use of conversation tools with subsequent conversations to assess and address the needs of patients (two tools) and their family caregivers (one tool). Patients, family caregivers and registered nurses from two Swedish stem cell transplantation centres testing the model were included. Data to measure practicality were gathered from the tools and documented conversations, while acceptability was assessed from the interviews.

Results: 36 patients, 32 family caregivers and 16 registered nurses participated. 67-94% of the patients and 94% of the family caregivers completed the tools. 78-97% of the subsequent conversations were conducted as planned. 78% of the patients and registered nurses were positive about one of the patient tools, while 41% were positive about the other patient tool. 95% of the family caregivers and registered nurses were positive about the family caregiver tool. Most participants considered that the systematic use of tools helped to structure a holistic needs assessment.

Conclusions: This feasibility study indicates that most components of our nursing model are practical, acceptable and support registered nurses when conducting person-centred nursing. With further development, the model has the potential to enhance the quality of care and support within the cancer context.

How can societies escape the conflict trap of violence and distrust between social outgroups? Existing research offers a plethora of tools for reducing conflict through peacemaking, peacebuilding, and reconstruction efforts. Peacemaking tools are often international efforts aimed at reducing violence in the short term by changing the immediate behavior of organized actors. Once violence has been stymied, additional peacebuilding efforts are necessary to foster intergroup trust, tolerance, and a shared national identity, thereby reducing incentives for violence and building resilience against future “shocks” to tolerance in the long term. Such efforts typically occur at the grassroots level, seeking to change the attitudes of individuals in post-conflict societies. We provide an overview of the evidence base on peacemaking and peacebuilding—identifying promising policies and programs, limitations, and shared mechanisms driving positive effects. We integrate these literatures into a framework tracing the path from immediate violence reduction to durable peace, pinpointing critical empirical and theoretical gaps in our knowledge of how to break the conflict trap.

BACKGROUND: Digital interventions offering behaviour change support are warranted to prevent and treat non-communicable diseases, and have been evaluated rigorously in controlled settings. Effectivenss, factors influencing the uptake of scaled-up interventions-such as reach, received dose, usability and acceptability- and predictors and mediators of efficiency are rarely explored in research. The study described herein aims to evaluate the effectiveness of a personally tailored digital intervention (the app EviBody®), intended to support healthy and sustained lifestyle behaviours among the adult population, on well-being and behaviour change. Further aims are to explore context and uptake factors, predictors and mediators for behaviour change over 24 months.

METHODS: This is a real-world study, employing a quasi-experimental design and a process evaluation. EviBody® will be marketed and managed by its owner. A four-armed design will allow for comparison between three levels of intervention (basic, standard and premium) and a control group. Adults who sign up for the app will be invited to the research study including sharing app data and answering questionnaires at 0, 1, 3, 6, 12, 18, and 24 months. Study start is Autumn 2025. Controls (n = 200 to evaluate the primary endpoint well-being at 6 months) will be recruited through advertisements on social media and asked to answer the same questionnaires at 0 and 6 months provided by email. For predicting and mediating analyses the intention is to recruit 1500 app users. Well-being (measured with the WHO-5 Well-Being Index), goal achievement, physical activity, eating habits, mental health, mediators (motivation, self-efficacy, and perceived barriers), and demographics will be self-reported. Uptake will be collected using analytics and ratings of usability and acceptability, and described by demographics. Mixed models for repeated measures and structural equation modelling will be employed for data analysis.

DISCUSSION: Besides evaluating the effectivenss of a digital intervention, this study also applies a theory-based evaluation to understand which mediators are effective, for whom they are effective, and the specific conditions under which they are most beneficial.

TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT05973383 on 8 July 2023.

BACKGROUND: Understanding the subjective experiences of patients living with chronic, acute, and cancer pain can significantly enhance the selection of treatment approaches, care, and support, ultimately improving their quality of life. This qualitative systematic review aimed to analyze if the patients' subjective experiences of living with pain differ between acute, chronic, and cancer pain states.

METHODS: After registration in PROSPERO (CRD42023491745), an electronic search was conducted in the databases Medline (Ovid), Embase (embase.com), Cochrane (Wiley), Web of Science (Clarivate Analytics), and CINAHL (EBSCO) from their inception to 19 April 2024. Out of 8443 articles, 62 articles were included. The inclusion criteria that were applied were as follows: (1) participants aged 18 or older; and (2) participants' subjective experiences of chronic, acute, or cancer pain. The exclusion criteria were as follows: (a) studies presented in other languages than English, Spanish, Portuguese, Greek, and Scandinavian languages; (b) editorials, letters, legal cases, case series, and case-control studies; (c) studies and articles based on duplicated data; (d) study population with ages below 18 years. Forty-four articles regarding chronic pain, thirteen regarding cancer pain, and five regarding acute pain were included. Methodological limitations were assessed using the CASP tool for quality appraisal in qualitative evidence synthesis. Certainty of evidence was assessed with GRADE-CERQual. All included studies showed moderate (n = 18) to high (n = 44) confidence.

RESULTS: Based on the qualitative synthesis in GRADE-CERQual, four main themes were identified: (1) impact of pain on social life, work life, and family life; (2) challenges in healthcare access; (3) psychological impact and emotional struggles from pain; and (4) barriers to effective pain management.

CONCLUSIONS: Taken together, patients with chronic, acute, or cancer pain face challenges in social, work, and personal lives. They often lack recognition and support from healthcare providers, relying on self-managed methods and facing barriers to effective management. Therefore, future research examining how the different pain types affect the lives of the patients and at the same time exploring personalized and collaborative treatment approaches is warranted. In conclusion, patients' experiences of living with pain remain unexplored in clinical practice. Understanding the impact of various pain types on mental health, self-esteem, daily life, and relationships is crucial. Also, how personalized treatments, collaborative healthcare access, and long-term management strategies can improve quality of life for patients living with pain.

SYSTEMIC REVIEW REGISTRATION: PROSPERO CRD42023491745.

Background: Safe Environment for Every Kid (SEEK) is one of few evidence-based approaches to identify psychosocial problems and facilitate support to families within pediatric primary care. The Swedish version of SEEK, called BarnSäkert (“Child Safe”), is being evaluated as a complex intervention in the Swedish child health services (CHS) for children aged 0–6 years.

Objective: Assessment of parents’ views of the acceptability and efficacy of the BarnSäkert/SEEK model within the CHS in Sweden. Participants and setting: Mothers and fathers (n = 353) whose children were enrolled in the CHS.

Methods: An anonymous web-based survey posed questions regarding how parents perceived BarnSäkert/SEEK and whether services had been offered, accessed or planned as a result. Efficacy was measured as parents’ reports of an improved life situation or having been helped by the model.

Results: Among parents who discussed their situation with the nurse, 80 % reported that it had helped, 24 % had received help that they otherwise would not have and 20 % that their situation had improved. Appropriateness of the model was scored at 91/100 by mothers and 86/100 by fathers. Logistic regression showed significantly higher odds ratios for efficacy measures and service uptake for parents who were younger, born outside of Sweden or had lower levels of education.

Conclusions: Parents reported that the model was highly acceptable and efficacious in meeting their psychosocial needs. The findings lend support for application of the BarnSäkert/SEEK model in the Swedish CHS as an equitable approach to address psychosocial problems in families with young children. 

AIM: To explore aspects of interpersonal relationships in palliative care nursing, focusing on confidential conversations between patients and registered nurses (RN).

DESIGN: A qualitative study employing focused ethnography.

METHODS: Data were collected through unstructured participant observations, field notes and interviews with patients and RN in specialist palliative care. Data were analysed using reflective thematic analysis.

FINDINGS: Confidential conversations in palliative care are founded on trust that is fragile and develops dynamically through consistent interactions. Small talk, presence and silence are essential for initiating and maintaining trust and the interpersonal relationship. The environment, patient condition and RN emotional presence and competence shape these conversations. As the relationship evolves, conversations adapt to the patient's changing needs. Missed signals or interruptions can disrupt flow, but the potential for repair remains, allowing for restoration and strengthening of trust and connection.

CONCLUSION: Confidential conversations in palliative care are grounded in fragile, dynamic trust, necessitating ongoing presence, sensitivity and adaptability from RN. To support these interactions, healthcare environments must prioritise privacy, relational continuity and communication training. Future research should investigate how organisational structures and clinical settings influence confidential conversations.

IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Healthcare environments should facilitate confidential conversations by ensuring relational continuity and minimising distractions. Communication training that emphasises presence and management of silence can strengthen nurse-patient relationships, enhancing patient care and emotional support.

IMPACT: This study explores key aspects of confidential conversations in palliative care, emphasising trust and emotional sensitivity. It addresses a research gap in palliative care using rare observational methods to deepen understanding of nursing relational aspects. The findings offer practical guidance for enhancing communication and relational skills, informing training and policy development and ultimately, improving emotional support and care.

REPORTING METHOD: Findings are reported in accordance with the Consolidated Criteria for Reporting Qualitative Research guidelines.

PATIENT OR PUBLIC CONTRIBUTION: This study did not involve patient or public participation in its design, conduct or reporting.

We consider nonlinear trident, e− → e−e−e+, in various electric background fields. This process has so far been studied for plane-wave backgrounds, using Volkov solutions. Here we first use WKB for trident in time-dependent electric fields, and then for fields which vary slowly in space. Then we show how to use worldline instantons for more general fields which depend on both time and space. For time-dependent fields the WKB approach is at least as simple to use as the worldline approach, but already the relatively modest step of including a slow spatial dependence makes the worldline approach much more efficient.

Diving beetles (Dytiscidae) are important generalist predators in freshwater ecosystems that have been around since the Jurassic. Previous phylogenetic studies have identified a largely stable set of monophyletic named groups (subfamilies, tribes and subtribes); however, backbone relationships among these have remained elusive. Here we use whole genome sequencing to reconstruct the phylogeny of Dytiscidae. We mine de novo assemblies and combine them with others available from transcriptome studies of Adephaga to compile a dataset of 149 taxa and 5364 orthologous genes. Species tree and concatenated maximum likelihood methods provide largely congruent results, resolving in agreement all but two inter-subfamily nodes. All 11 subfamilies are monophyletic, supporting previous results; possibly also all tribes, but Hydroporini is recovered as paraphyletic with weak support and monophyly of Dytiscini is method dependent. One large clade includes eight of 11 subfamilies (excluding Laccophilinae, Lancetinae and Coptotominae). Matinae is sister to Hydrodytinae + Hydroporinae, in contrast with previous studies that have hypothesized Matinae as sister to the remaining Dytiscidae. Copelatinae belong in a clade with Cybistrinae, Dytiscinae, Agabinae and Colymbetinae. Strongly confirmed sister group relationships of subfamilies include Cybistrinae + Dytiscinae, Agabinae + Colymbetinae, Lancetinae + Coptotominae and Hydrodytinae + Hydroporinae. Remaining problems include resolving with confidence the basal ingroup trichotomy and relationships between tribes in Hydroporinae. Resolution of tribes in Dytiscinae is affected by methodological inconsistencies. Platynectini, new tribe, is described and Hydrotrupini redefined within subfamily Agabinae. This study is a step forward towards completely resolving the backbone phylogeny of Dytiscidae, which we hope will stimulate further work on remaining challenges.

Autonomous vehicles (AVs) depend critically on vision-based perception systems, with traffic sign classification (TSC) playing a crucial role in interpreting regulatory and warning signs for safe navigation. However, these systems are highly vulnerable to adversarial attacks, subtle input perturbations that deceive deep learning models while appearing benign to human drivers. While detection has been the primary focus of defense, recovery of adversarial perturbed signs remains significantly underexplored, despite its importance for maintaining real-time decision-making and operational safety. To bridge this gap, we present the first comprehensive benchmarking of state-of-the-art image classification recovery methods adapted to the traffic sign domain. We address three domain-specific challenges for autonomous driving: (1) robustness to real-world conditions (e.g., weather, occlusion), (2) latency compatible with real-time pipelines (100 ms), and (3) preservation of geometric/structural integrity. Our adaptations combine weather-resilient preprocessing, shape-preserving restoration, and latency-aware implementation. Under unified white-box attacks, we evaluate across TSRD, BTSC, and GTSRB using recovery rate (RR), structural similarity (SSIM), and recovery time (RT). To connect latency to function, we introduce the recovery-induced distance (RID), which maps recovery time (RT) to added travel distance. PuVAE, VAE, c-GAN, and CD-GAN achieve subfewmillisecond RT with (Formula presented.) of the nominal braking distance; DIR remains within (Formula presented.) 0.3% at (Formula presented.), CSC is (Formula presented.) 1.9%–3.3%, and DiffPure incurs 150–165 ms latency, yielding (Formula presented.) 8%–10% at (Formula presented.) (multi-meter delay), thus violating real-time constraints ((Formula presented.))). Cross-dataset transfer on shared classes shows that VAE-based method generalizes better than GAN-based while maintaining timing safety. Overall, PuVAE offers the best accuracy–latency trade-off. These findings provide practical guidance for deploying recovery as a real-time, safety-aligned complement to detection in AV perception.