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Abstract Background Participatory research has gained traction as an approach to unlock perspectives when creating scientific knowledge and to facilitate societal changes. By conducting research with people, participatory research strives to engage individuals’ perspectives in designing, conducting, and disseminating the research. Nevertheless, few studies have unpacked how understandings of the studied phenomenon are shaped among diverse research partners and, concurrently, how different perspectives are combined. Nested within an overall participatory mixed methods study on aging with multiple sclerosis (MS), this qualitative study explores how understandings of aging with MS are shaped in encounters between university researchers, older adults with MS, and employees in a patient association. Methods The study was collaboratively conducted in Denmark by three research partners: a group of older adults with MS, employees in a patient association, and university researchers. Data on how different understandings of aging with MS were represented and shaped during the three-year research process was generated through field notes, meeting minutes, focus group interviews, and individual interviews. The collected data was analyzed through a thematic network analysis. Results The study demonstrates how different understandings of aging with MS were represented among the research partners when the research was initiated. These understandings were shaped prior to —and, therefore, outside—the research setting, drawing from the research participants’ lived experiences, professional backgrounds, and organizational cultures or situated in larger societal narratives. Through a process centered on reflexivity among the engaged research partners, the understandings of what it means to age with MS was shaped and re-shaped and eventually merged into a more dynamic understanding of later life with MS where different perspectives could co-exist. Conclusion The findings demonstrate that research partners, including older adults with MS and employees from a patient association, brought diverse understandings to the study. Reflexive practices enabled these perspectives to co-exist, enhancing engagement and transparency, and fostering a dynamic understanding of later life with MS. This highlights the value of reflexivity in evolving complex understandings within participatory research.

BackgroundThe digital shift toward remote consultations in general practice needs ongoing monitoring to understand its impact on general practice organizations and the wider health care system. ObjectiveThis study aimed to explore how remote consultations impact on contracted general practitioner (GP) practices and how GPs perceive the implications of this uptake for the overall health care system. MethodsIn total, 5 focus groups were conducted with a total of 18 GPs from all 4 health regions of Norway in 2022. The material was subjected to Braun and Clarke’s thematic analysis. ResultsThe analysis yielded six themes: (1) the design of novel effective clinical pathways: remote consultations empower GPs to tailor new effective clinical trajectories, blending modalities to address diverse needs across clinical episodes—from initial triage, through investigations to case closure; (2) increased workday flexibility: remote consultations introduce variability into daily work, allowing GPs to adjust patient contact intensity, and leading to a less stressful work-home balance; (3) erosion of organizational boundaries: easy remote access to GPs appears to reduce patients’ tolerance for minor illness and self-care, hindering effective gatekeeping and shifting GPs’ focus from proactive to more reactive work, increasing work-related stress; (4) degradation of clinical shrewdness: confronted with an increasing amount of unsorted and trivial remote inquiries, GPs observe challenges in detecting and prioritizing serious cases; (5) dilemmas related to responsibility, ethics, and legislation: remote consultations highlight a tension for contract GPs between legal responsibilities and ethical obligations, with implications for patients with limited health literacy; this may entail suboptimal evaluation or delayed treatment—potentially contributing to increased health care inequity; and (6) retaining clinical core values in a changing world. Overall, GPs affirm that remote consultations have come to stay and describe efforts to effectively manage the advantages and disadvantages inherent in such interactions to safeguard clinical effectiveness and organizational sustainability of primary health care. ConclusionsThe widespread adoption of remote consultations in the Norwegian contract GP scheme fundamentally reshapes the dynamics of GP work and the overall health care system. Awareness and proactive management of these changes are essential for maintaining sustainable, high-quality primary health care.

BackgroundIn recent years, text-based e-consultations have been widely implemented in general practice and are appreciated by patients for their convenience and efficiency. Policymakers aim to enhance patient access to clinical services with the general practitioner (GP) through text-based e-consultations. However, concerns are raised about their efficiency and security. We aimed to investigate users’ perceptions of potential improvements in the text-based e-consultation service provided by the national health portal in Norway.MethodWe conducted an online survey among users of text-based e-consultations with the GP on the national health portal Helsenorge. The survey was available from January-February 2023 and consisted of 20 questions. This study focused on the free-text answers to the question “Do you have any suggestions to improve the service?” The framework method was used for a thematic analysis of the answers.ResultsThe analysis of 2,954 free-text answers from users of the national e-consultation service resulted in six areas where suggestions for improvement were expressed. According to users, the service would benefit from: (1) a better set-up to facilitate the formulation of the patient's problem, (2) better value for money (in regards to both price and quality), (3) faster response time, (4) improved information and predictability about the status of the e-consultation (e.g., if it is received and when to expect an answer), (5) improvement in technical issues, and (6) improvement of access to dialogue-based services to replace or complement e-consultations.ConclusionThe analysis of users’ suggestions for improvements to the e-consultation service emphasised the need to customise the service to address individual patient needs. Users found a one-size-fits-all approach with mandatory questions, fixed pricing, and inflexible response times less appreciated. Some also felt forced to rely on e-consultations due to the perceived poor availability of other GP services. This highlights the importance of perceiving e-consultations not as a replacement for dialogue-enabled services, but rather as a potentially efficient addition, ensuring a well-tailored setup for appropriate patient use.

Abstract Background The shortage of pathologists in Germany, coupled with an aging workforce, requires innovative approaches to attract medical students to the field. Medical education must address different learning styles to ensure that all students are successful. Methods The pilot project “Practical Pathology” aims to enhance students' understanding of pathology by providing hands-on experience in macroscopic gross analysis through the use of tumor dummies built from scratch. Results An evaluation survey, completed by 63 participating students provided positive feedback on the course methodology, its relevance to understanding the pathology workflow, and its improvement over traditional teaching methods. The majority of students recognized the importance of hands-on training in medical education. Students with previous work experience rated the impact of the course on knowledge acquisition even more positively. Conclusion The course improved students' understanding of pathological processes and potential sources of clinical-pathological misunderstanding. An increase in motivation for a potential career in the field of pathology was observed in a minority of students, although this exceeded the percentage of pathologists in the total medical workforce.

Abstract Healthcare fraud, waste and abuse are costly problems that have huge impact on society. Traditional approaches to identify non-compliant claims rely on auditing strategies requiring trained professionals, or on machine learning methods requiring labelled data and possibly lacking interpretability. We present Clais, a collaborative artificial intelligence system for claims analysis. Clais automatically extracts human-interpretable rules from healthcare policy documents (0.72 F1-score), and it enables professionals to edit and validate the extracted rules through an intuitive user interface. Clais executes the rules on claim records to identify non-compliance: on this task Clais significantly outperforms two baseline machine learning models, and its median F1-score is 1.0 (IQR = 0.83 to 1.0) when executing the extracted rules, and 1.0 (IQR = 1.0 to 1.0) when executing the same rules after human curation. Professionals confirm through a user study the usefulness of Clais in making their workflow simpler and more effective.

Abstract Detailed knowledge regarding the associations between intake of different types of seafood and meat and the risk of type 2 diabetes (T2D), and insight into possible mechanisms are warranted. In this study we aimed to evaluate the associations between intake of different types of seafood and meat and the subsequent risk of T2D using the Norwegian Mother, Father, and Child Cohort Study (MoBa), and furthermore, by using a mouse model to gain further insight into possible molecular mechanisms contributing to the associated metabolic changes. Women in MoBa who were free of pharmacologically treated diabetes at baseline (n = 60,777) were prospectively evaluated for incident T2D, identified on the basis of medication usages > 90 days after delivery, ascertained by the Norwegian Prescription Database. Dietary intake was obtained with a validated 255-item food frequency questionnaire which assessed habitual diet during the first 4–5 months of pregnancy. Metabolic phenotypes and plasma metabolome were investigated in female mice fed isocaloric diets with different types of seafood and meat mimicking the dietary intake in the human cohort. During maximum 10-year and mean (SD) 7.2 (1.6) years follow-up time, 681 (1.1%) women developed pharmacologically treated T2D. All statistical models identified a higher risk of T2D with increased shellfish intake, whereas no associations were observed for total seafood, fatty fish, total meat and red meat in the adjusted models. In mice, the shellfish-based western diet induced reduced glucose tolerance and insulin secretion compared to the diet based on lean fish, and we identified a number of metabolites elevated in plasma from shellfish-fed mice that correlated with glucose intolerance. Mice fed a western diet based on meat also exhibited reduced glucose tolerance in comparison to lean fish fed mice, whereas mice fed fatty fish, total seafood or red meat did not differ from lean fish fed mice. We observed a diet-specific metabolic signature in plasma demonstrating five distinct metabolite profiles in mice fed shellfish, fatty fish, total seafood/lean fish, a mixed diet and meat. In conclusion, these findings demonstrate that different types of seafood have different outcome on T2D risk. In women, intake of shellfish was associated with higher risk of T2D. In female mice, a shellfish enriched diet reduced glucose tolerance and altered the abundance of several distinct plasma metabolites correlating with glucose tolerance.

Abstract The oral cavity harbors complex communities comprising bacteria, archaea, fungi, protozoa, and viruses. The oral microbiota is establish at birth and develops further during childhood, with early life factors such as birth mode, feeding practices, and oral hygiene, reported to influence this development and the susceptibility to caries. We here analyzed the oral bacterial composition in saliva of 260 Swedish children at two, three and five years of age using 16S rRNA gene profiling to examine its relation to environmental factors and caries development at five years of age. We were able to assign the salivary bacterial community in each child at each time point to one of seven distinct clusters. We observed an individual dynamic in the development of the oral microbiota related to early life factors, such as being first born, born by C-section, maternal perinatal antibiotics use, with a distinct transition between three and five years of age. Different bacterial signatures depending on age were related to increased caries risk, while Peptococcus consistently linked to reduced risk of caries development.

Abstract Background Interactions between the gut microbiota, diet, and host metabolism contribute to the development of cardiovascular disease, but a firm link between disease-specific gut microbiota alterations and circulating metabolites is lacking. Methods We performed shot-gun sequencing on 235 samples from 166 HF patients and 69 healthy control samples. Separate plasma samples from healthy controls (n = 53) were used for the comparison of imidazole propionate (ImP) levels. Taxonomy and functional pathways for shotgun sequencing data was assigned using MetaPhlAn3 and HUMAnN3 pipelines. Results Here, we show that heart failure (HF) is associated with a specific compositional and functional shift of the gut microbiota that is linked to circulating levels of the microbial histidine-derived metabolite ImP. Circulating ImP levels are elevated in chronic HF patients compared to controls and associated with HF-related gut microbiota alterations. Contrary to the microbiota composition, ImP levels provide insight into etiology and severity of HF and also associate with markers of intestinal permeability and systemic inflammation. Conclusions Our findings establish a connection between changes in the gut microbiota, the presence, etiology, and severity of HF, and the gut-microbially produced metabolite ImP. While ImP appears promising as a circulating biomarker reflecting gut dysbiosis related to HF, further studies are essential to demonstrate its causal or contributing role in HF pathogenesis. Trial registration NCT02637167, registered December 22, 2015.

Abstract The Illumina HiSeq platform has been a commonly used option for bacterial genome sequencing. Now the BGI DNA nanoball (DNB) nanoarrays platform may provide an alternative platform for sequencing of bacterial genomes. To explore the impact of sequencing platforms on bacterial genome assembly, quality assessment, sequence alignment, functional annotation, mutation detection, and metagenome mapping, we compared genome assemblies based on sequencing of cultured bacterial species using the HiSeq 2000 and BGISEQ-500 platforms. In addition, simulated reads were used to evaluate the impact of insert size on genome assembly. Genome assemblies based on BGISEQ-500 sequencing exhibited higher completeness and fewer N bases in high GC genomes, whereas HiSeq 2000 assemblies exhibited higher N50. The majority of assembly assessment parameters, sequences of 16S rRNA genes and genomes, numbers of single nucleotide variants (SNV), and mapping to metagenome data did not differ significantly between platforms. More insertions were detected in HiSeq 2000 genome assemblies, whereas more deletions were detected in BGISEQ-500 genome assemblies. Insert size had no significant impact on genome assembly. Taken together, our results suggest that DNBSEQ platforms would be a valid substitute for HiSeq 2000 for bacterial genome sequencing.

Abstract Climate change impact studies need climate projections for different scenarios and at scales relevant to planning and management, preferably for a variety of models and realizations to capture the uncertainty in these models. To address current gaps, we statistically downscaled (SD) 3–7 CMIP6 models for five key indicators of marine habitat conditions: temperature, salinity, pH, oxygen, and chlorophyll across European waters for three climate scenarios SSP1-2.6, SSP2-4.5, and SSP5-8.5. Results provide ensemble averages and uncertainty estimates that can serve as input data for projecting the potential success of a range of Nature-based Solutions, including the restoration of habitat-forming species such as seagrass in the Mediterranean and kelp in coastal areas of Portugal and Norway. Evaluation of the ensemble with observations from four European regions (North Sea, Baltic Sea, Bay of Biscay, and Mediterranean Sea) indicates that the SD projections realistically capture the climatological conditions of the historical period 1993–2020. Model skill (Liu-mean efficiency, Pearson correlation) clearly improves for both surface temperature and oxygen across all regions with respect to the original ESMs demonstrating a higher skill for temperature compared to oxygen. Warming is evident across all areas and large differences among scenarios fully emerge from the background uncertainties related to internal variability and model differences in the second half of the century. Scenario-specific differences in acidification significantly emerge from model uncertainty and internal variability leading to distinct trajectories in surface pH starting before mid-century (in some cases starting from present day). Deoxygenation is also present across all domains, but the climate signal was significantly weaker compared to the other two indicators when compared to model uncertainty and internal variability, and the impact of different greenhouse gas trajectories is less distinct. The substantial regional and local heterogeneity in these three abiotic indicators underscores the need for highly spatially resolved physical and biogeochemical projections to understand how climate change may impact marine ecosystems.

Abstract Offshore wind power projects are currently booming around the North Sea. However, there are inherent correlation challenges between wind farms in this area, which has implications for the optimal composition of locations and the scale-up of installed capacities. This paper is aimed at addressing the correlation problem by minimizing the variance of total wind power accumulated around the North Sea. We show that this nonlinear convex optimization problem can be solved by applying the Augmented Lagrangian Algorithm (ALA). The premise of the study is that more interconnections between the EU countries will be prioritized in order to optimize and smooth out the wind power production patterns. A publicly available dataset with historical hour-by-hour data spanning over 20 years was used for the analysis. We explore two distinct scenarios for Norwegian offshore wind development. In the first scenario, we consider the ongoing activities on the European continental side of the North Sea and their implications for Norway. Here, we illustrate the advantages of focusing on expanding wind power capacity in the northern regions of Norway to enhance the overall value of the generated wind power. In contrast, the second reference scenario neglects these interconnections, resulting in a significantly greater concentration of offshore wind development in the southern parts of Norway, particularly in Sørlige Nordsjø II. Additionally, our work estimates the wind power correlation coefficient in the North Sea as a function of distance. Furthermore, we analyze deviations and intermittencies in North Sea wind power over various time intervals, emphasizing that the perceived integration challenges are highly dependent on the chosen time resolution in the analysis.

Abstract Systematic exercise training effectively improves exercise capacity in patients with coronary artery disease (CAD), but the magnitude of improvements is highly heterogeneous. We investigated whether this heterogeneity in exercise capacity gains is influenced by the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene. Patients with CAD (n = 169) were randomly assigned to 12 weeks of exercise training or standard care, and 142 patients completed the study. The ACE polymorphism was determined for 128 patients (82% males, 67 ± 9 years). Peak oxygen uptake was measured before and after the 12-week intervention. The ACE I/D polymorphism frequency was n = 48 for D/D homozygotes, n = 61 for I/D heterozygotes and n = 19 for I/I homozygotes. Baseline peak oxygen uptake was 23.3 ± 5.0 ml/kg/min in D/D homozygotes, 22.1 ± 5.3 ml/kg/min in I/D heterozygotes and 23.1 ± 6.0 ml/kg/min in I/I homozygotes, with no statistical differences between genotype groups (P = 0.50). The ACE I/D polymorphism frequency in the exercise group was n = 26 for D/D, n = 21 for I/D and n = 12 for I/I. After exercise training, peak oxygen uptake was increased (P

Abstract Background The majority of patients with recurrent or metastasized head and neck squamous cell carcinoma (HNSCC) do not benefit from immune checkpoint blockade (ICB) while several patients experience severe and persistent immune-mediated side effects. Therefore, predictive biomarkers are urgently needed to allow for a personalized treatment. In this study, we investigated DNA methylation of the immune checkpoint gene CTLA4 with regard to its predictive value. Methods We analyzed CTLA4 promoter methylation in tumors of HNSCC patients (N = 29) treated with ICB at the University Medical Center Bonn with regard to response to ICB and progression-free survival. We further analyzed a second cohort (N = 138) of patients that did not receive ICB with regard to CTLA4 promoter methylation, CTLA-4 protein expression, and immune cell infiltrates. Finally, we tested inducibility of CTLA-4 protein expression in HNSCC cells using the DNA methyltransferase inhibitor decitabine. Results Lower CTLA4 promoter methylation correlated with response to ICB and prolonged progression-free survival. We could show that not only tumor infiltrating immune cells, but also HNSCC cells harbor cytoplasmic and nuclear CTLA-4 expression. CTLA4 promoter methylation inversely correlated with infiltrates of CD3+, CD4+, CD8+, and CD45+ immune cells. CTLA4 methylation did not correlate with protein expression in tumors, however, decitabine treatment led to decreased CTLA4 methylation and an induction of CTLA4 mRNA and CTLA-4 protein expression in HNSCC cell lines. Conclusions Our results indicate that CTLA4 DNA hypomethylation is a predictive biomarker for response to ICB in HNSCC. Our study warrants further analyses of the predictive value of CTLA4 DNA methylation in clinical trials of anti-PD-1 and/or anti-CTLA-4 immunotherapy in HNSCC.

Objectives The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins.Methods This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel).Results Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p

Objectives There is a need for novel approaches to address the complexity of social inequality in health. Public–private partnerships (PPPs) have been proposed as a promising approach; however, knowledge on lessons learnt from such partnerships remain unclear. This study synthesises evidence on opportunities and challenges of PPPs focusing on social inequality in health in upper-middle-income and high-income countries.Design A systematic literature review and meta-synthesis was conducted using the Mixed Methods Appraisal Tool for quality appraisal.Data sources PubMed, PsychInfo, Embase, Sociological Abstracts and SocIndex were searched for studies published between January 2013 and January 2023.Eligibility criteria Studies were eligible if they applied a quantitative, qualitative, or mixed methods design and reported on lessons learnt from PPPs focusing on social inequality in health in upper-middle-income and high-income countries. Studies had to be published in either English, Danish, German, Norwegian or Swedish.Data extraction and synthesis Two independent reviewers extracted data and appraised the quality of the included studies. A meta-synthesis with a descriptive intent was conducted and data were grouped into opportunities and challenges.Results A total of 16 studies of varying methodological quality were included. Opportunities covered three themes: (1) creating synergies, (2) clear communication and coordination, and (3) trust to sustain partnerships. Challenges were identified as reflected in the following three themes: (1) scarce resources, (2) inadequate communication and coordination, and (3) concerns on distrust and conflicting interest.Conclusions Partnerships across public, private and academic institutions hold the potential to address social inequality in health. Nevertheless, a variety of important lessons learnt are identified in the scientific literature. For future PPPs to be successful, partners should be aware of the availability of resources, provide clear communication and coordination, and address concerns on distrust and conflicting interests among partners.PROSPERO registration number CRD42023384608.

Objectives To explore patients’ experiences with receiving sick leave certificates via remote consultations during the COVID-19 pandemic and investigate whether there were differences among the types of remote consultation (telephone, video or text).Design A nationwide online patient survey consisting of quantitative data supplemented by qualitative opinions conducted in Norway.Setting Primary care.Participants Patients who received a sick leave certificate via remote consultation in the period from 16 November to 15 December 2020.Results Of the 5429 respondents, 3233 (59.6%) received a sick leave certificate via telephone consultation, 657 (12.1%) via video consultation and 1539 (28.3%) via text-based e-consultation. Most respondents (76.8%) were satisfied. Only 10% of the respondents thought that the doctor would have obtained more information through an office appointment. The majority of the respondents (59.6%) found that they had as much time to explain the problem as at an office appointment. Some patients also thought that it was easier to formulate the problem via a remote consultation (18.2%) and agree with the doctor on the sick leave (10.3%).The users of text-based e-consultations were the most satisfied (79.3%, p

Abstract Myoglobin (MB) is expressed in different cancer types and may act as a tumor suppressor in breast cancer. The mechanisms by which basal MB expression level impacts murine mammary tumorigenesis are unclear. We investigated how MB expression in breast cancer influences proliferation, metastasis, tumor hypoxia, and chemotherapy treatment in vivo. We crossed PyMT and WapCreTrp53flox mammary cancer mouse models that differed in tumor grade/type and onset of mammary carcinoma with MB knockout mice. The loss of MB in WapCre;Trp53flox mice did not affect tumor development and progression. On the other hand, loss of MB decreased tumor growth and increased tissue hypoxia as well as the number of lung metastases in PyMT mice. Furthermore, Doxorubicin therapy prevented the stronger metastatic propensity of MB-deficient tumors in PyMT mice. This suggests that, although MB expression predicts improved prognosis in breast cancer patients, MB-deficient tumors may still respond well to first-line therapies. We propose that determining the expression level of MB in malignant breast cancer biopsies will improve tumor stratification, outcome prediction, and personalized therapy in cancer patients.

Abstract The prognosis of patients with advanced urothelial carcinoma (UC) remains poor and improving treatment continues to be a major medical need. CUB domain containing protein 1 (CDCP1) is a known oncogene in various types of solid cancers and its overexpression is associated with impaired prognosis. However, its role in UC remains undetermined. Here we assessed the clinical relevance of CDCP1 in two cohorts of UC at different stages of the disease. Immunohistochemistry showed that CDCP1 is highly expressed in advanced UC, which significantly correlates with shorter overall survival. Importantly, the basal/squamous UC subtype showed significantly enriched CDCP1 at the mRNA and protein levels. The functional role of CDCP1 overexpression was assessed taking advantage of ex vivo organoids derived from the CDCP1pcLSL/+ transgenic mouse model. Furthermore, CDCP1 knockout UC cell lines were generated using CRISPR/Cas9 technology. Interestingly, CDCP1 overexpression significantly induced the activation of MAPK/ERK pathways in ex vivo organoids and increased their proliferation. Similarly, CDCP1 knockout in UC cell lines reduced their proliferation and migration, concomitant with MAPK/ERK pathway activity reduction. Our results highlight the relevance of CDCP1 in advanced UC and demonstrate its oncogenic role, suggesting that targeting CDCP1 could be a rational therapeutic strategy for the treatment of advanced UC.

Abstract This paper introduces the annual energy density concept for electric power generation, which is proposed as an informative metric to capture the impacts on the environmental footprint. Our investigation covers a wide range of sources classified by rated power and compares different regions to establish typical spatial flows of energy and evaluate the corresponding scalability to meet future net-zero emission (NZE) goals. Our analysis is conducted based on publicly available information pertaining to different regions and remote satellite image data. The results of our systematic analysis indicate that the spatial extent of electric power generation toward 2050 will increase approximately sixfold, from approximately 0.5% to nearly 3.0% of the world’s land area, based on International Energy Agency (IEA) NZE 2050 targets. We investigate the worldwide energy density for ten types of power generation facilities, two involving nonrenewable sources (i.e., nuclear power and natural gas) and eight involving renewable sources (i.e., hydropower, concentrated solar power (CSP), solar photovoltaic (PV) power, onshore wind power, geothermal power, offshore wind power, tidal power, and wave power). In total, our study covers 870 electric power plants worldwide, where not only the energy density but also the resulting land or sea area requirements to power the world are estimated. Based on the provided meta-analysis results, this paper challenges the common notion that solar power is the most energy-dense renewable fuel source by demonstrating that hydropower supersedes solar power in terms of land use in certain regions of the world, depending on the topography.

Abstract Exercise training reduces cardiovascular mortality and improves quality of life in CAD patients. We investigated the feasibility and impact of 12 weeks of low-volume high-intensity interval training (HIIT) in CAD-patients. Patients with stable CAD were randomized 1:1 to supervised HIIT or standard care. HIIT sessions were completed three times weekly for 12 weeks on a rowing ergometer. Before and after the 12-week intervention, patients completed a physiological evaluation of cardiorespiratory performance and quality of life questionnaires. Mixed model analysis was used to evaluate differences between and within groups. A total of 142 patients (67 ± 9 years, nHIIT = 64, nStandard care = 78) completed the trial. Training adherence was 97% (range 86–100%). Six patients dropped out because of non-fatal adverse events. Weekly training duration was 54 min with an average power output of 138 W. HIIT increased peak oxygen uptake by 2.5 mL/kg/min (95% CI 2.1–3.0), whereas no change was observed in standard care (0.2 mL/kg/min, 95% CI − 0.2–0.6, P

Abstract The aim of this study is to characterize cell type-specific transcriptional signatures in non-alcoholic steatohepatitis (NASH) to improve our understanding of the disease. We performed single-cell RNA sequencing on liver biopsies from 10 patients with NASH. We applied weighted gene co-expression network analysis and validated our findings using a publicly available RNA sequencing data set derived from 160 patients with non-alcoholic fatty liver disease (NAFLD) and 24 controls with normal liver histology. Our study provides a comprehensive single-cell analysis of NASH pathology in humans, describing 19,627 single-cell transcriptomes from biopsy-proven NASH patients. Our data suggest that the previous notion of ”NASH-associated macrophages” can be explained by an up-regulation of normally existing subpopulations of liver macrophages. Similarly, we describe two distinct populations of activated hepatic stellate cells, associated with the level of fibrosis. Finally, we find that the expression of several circulating markers of NAFLD are co-regulated in hepatocytes together with predicted effector genes from NAFLD genome-wide association studies (GWAS), coupled to abnormalities in the complement system. In sum, our single-cell transcriptomic data set provides insights into novel cell type-specific and general biological processes associated with inflammation and fibrosis, emphasizing the importance of studying cell type-specific biological processes in human NASH.

Dippity Pig Syndrome (DPS) is a well-known but rare complex of clinical signs affecting minipigs, which has not been thoroughly investigated yet. Clinically affected animals show acute appearance of red, exudating lesions across the spine. The lesions are painful, evidenced by arching of the back (dipping), and the onset of clinical signs is generally sudden. In order to understand the pathogenesis, histological and virological investigations were performed in affected and unaffected Göttingen Minipigs (GöMPs). The following DNA viruses were screened for using PCR-based methods: Porcine cytomegalovirus (PCMV), which is a porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses (PLHV-1, PLHV-2, PLHV-3), porcine circoviruses (PCV1, PCV2, PCV3, PCV4), porcine parvovirus 1 (PPV1), and Torque Teno sus viruses (TTSuV1, TTSuV2). Screening was also performed for integrated porcine endogenous retroviruses (PERV-A, PERV-B, PERV-C) and recombinant PERV-A/C and their expression as well as for the RNA viruses hepatitis E virus (HEV) and SARS-CoV-2. Eight clinically affected and one unaffected GöMPs were analyzed. Additional unaffected minipigs had been analyzed in the past. The analyzed GöMPs contained PERV-A and PERV-B integrated in the genome, which are present in all pigs and PERV-C, which is present in most, but not all pigs. In one affected GöMPs recombinant PERV-A/C was detected in blood. In this animal a very high expression of PERV mRNA was observed. PCMV/PRV was found in three affected animals, PCV1 was found in three animals with DPS and in the unaffected minipig, and PCV3 was detected in two animals with DPS and in the unaffected minipig. Most importantly, in one animal only PLHV-3 was detected. It was found in the affected and unaffected skin, and in other organs. Unfortunately, PLHV-3 could not be studied in all other affected minipigs. None of the other viruses were detected and using electron microscopy, no virus particles were found in the affected skin. No porcine virus RNA with exception of PERV and astrovirus RNA were detected in the affected skin by next generation sequencing. This data identified some virus infections in GöMPs with DPS and assign a special role to PLHV-3. Since PCMV/PRV, PCV1, PCV3 and PLHV-3 were also found in unaffected animals, a multifactorial cause of DPS is suggested. However, elimination of the viruses from GöMPs may prevent DPS.

Objectives Return to work is a key rehabilitation goal, however, people recovering from cardiovascular disease (CVD) often struggle with returning to work. The aim of this study was to conduct a systematic review and meta-synthesis of the existing qualitative evidence on barriers and facilitators to return to work experienced by people with CVD.Methods A systematic literature search was conducted in PubMed, Embase, Web of Science, PsycINFO, Scopus and CINAHL in August 2022. The reference lists of the included articles were searched. The Critical Appraisal Skills Programme was used for quality appraisal and a meta-synthesis was employed.Findings This review includes 15 studies of overall high methodological quality. Barriers covered four themes: physical limitations, psychological and relational factors, the working context and support within health and social care systems. Facilitators were related to five themes: return to normality, enhancing well-being, financial concerns, the working context and support within health and social care systems.Conclusion Our findings highlight that return to work following CVD is a complex process influenced by individual factors, as well as work-related factors, factors in the health and social care systems and social security policies and regulations. To improve return to work, this review illustrates a need for individualised, multidisciplinary and coordinated vocational rehabilitation programmes that accommodate potential barriers to re-employment. Similarly, this review highlights how vocational rehabilitation programmes should ensure individualised information and support early in the rehabilitation process, as well as the importance of engaging relevant stakeholders, such as employers, in making individualised return-to-work plans.

Close contacts of coronavirus disease (COVID-19) patients are at high risk for severe acute respiratory syndrome 2 (SARS-CoV-2) infection. We assessed the seroprevalence of SARS-CoV-2–specific antibodies among quarantined close contacts of COVID-19 patients in the Faroe Islands. We invited quarantined close contacts of COVID-19 index patients identified during March 3–April 22, 2020, to participate in this study; 584 (81%) contacts consented and underwent serologic testing. Among the 584 participants, 32 (5.5%) were seropositive for total antibody against SARS-CoV-2. Household and young or elderly contacts had higher risk for seropositivity than other contacts. We found a secondary attack rate of 19.2%. Seroprevalence among close contacts was almost 10-fold higher than among the general population of the Faroe Islands. Regularly testing household close contacts of COVID-19 patients might help track the transmission of SARS-CoV-2.

Abstract The intimate association between obesity and type II diabetes urges for a deeper understanding of adipocyte function. We and others have previously delineated a role for the tumor suppressor p53 in adipocyte biology. Here, we show that mice haploinsufficient for MDM2, a key regulator of p53, in their adipose stores suffer from overt obesity, glucose intolerance, and hepatic steatosis. These mice had decreased levels of circulating palmitoleic acid [non-esterified fatty acid (NEFA) 16:1] concomitant with impaired visceral adipose tissue expression of Scd1 and Ffar4. A similar decrease in Scd and Ffar4 expression was found in in vitro differentiated adipocytes with perturbed MDM2 expression. Lowered MDM2 levels led to nuclear exclusion of the transcriptional cofactors, MORC2 and LIPIN1, and thereby possibly hampered adipocyte function by antagonizing LIPIN1-mediated PPARγ coactivation. Collectively, these data argue for a hitherto unknown interplay between MDM2 and MORC2/LIPIN1 involved in balancing adipocyte function.

We conducted a second nationwide severe acute respiratory syndrome coronavirus 2 seroprevalence study in the Faroe Islands during November 2020. We found crude seroprevalence was 0.3% and prevalence was 0.4% after adjusting for test sensitivity and specificity. This low seroprevalence supports the prevention strategies used in the Faroe Islands.

This paper reviews dilemmas and implications of erroneous data for clinical implementation of AI. It is well-known that if erroneous and biased data are used to train AI, there is a risk of systematic error. However, even perfectly trained AI applications can produce faulty outputs if fed with erroneous inputs. To counter such problems, we suggest 3 steps: (1) AI should focus on data of the highest quality, in essence paraclinical data and digital images, (2) patients should be granted simple access to the input data that feed the AI, and granted a right to request changes to erroneous data, and (3) automated high-throughput methods for error-correction should be implemented in domains with faulty data when possible. Also, we conclude that erroneous data is a reality even for highly reputable Danish data sources, and thus, legal framework for the correction of errors is universally needed.

Abstract Objective The present study aimed to explore kindergarten staffs’ perceived usefulness of intervention components in association with changes in children’s vegetable intake and vegetables served in the kindergarten. Assessment of the perceived usefulness of intervention components consisted of a paper-based questionnaire for the kindergarten staff assessing usefulness of posters, supplementary material and 1-day inspirational course. Children’s vegetable intake in the kindergarten was assessed by direct observation, while vegetables served was assessed by a 5-day weighted vegetable diary. Results Seventy-three kindergartens in two counties in Norway participated (response rate 15%) and parental consent was obtained for 633 children 3–5 years of age at baseline (response rate 39%). Mixed effect models indicated a tendency that posters were associated with increased child vegetable intake (P = 0.062). Surprisingly, a low degree of perceived usefulness of supplementary material was associated with the largest increase in child vegetable intake (P = 0.020). No significant associations between perceived usefulness of intervention components and vegetables served in the kindergarten were found. This study indicated a tendency that posters were associated with increased child vegetable intake; however, this may also be due to synergies between multiple intervention components. Trial registration International Standard Randomized Controlled Trials ISRCTN51962956 ( http://www.isrctn.com/ISRCTN51962956 ). Registered 21 June 2016 (retrospectively registered).

Abstract Exploiting a pure culture strategy to investigate the composition of the human gut microbiota, two novel anaerobes, designated strains AF52-21T and CM04-06T, were isolated from faeces of two healthy Chinese donors and characterized using a polyphasic approach. The two strains were observed to be gram-negative, non-motile, and rod-shaped. Both strains grew optimally at 37 °C and pH 7.0. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the two strains clustered with species of the genus Faecalibacterium and were most closely related to Faecalibacterium prausnitzii ATCC 27768T with sequence similarity of 97.18% and 96.87%, respectively. The two isolates shared a 16S rRNA gene sequence identity of 98.69%. Draft genome sequencing was performed for strains AF52-21T and CM04-06T, generating genome sizes of 2.85 Mbp and 3.01 Mbp. The calculated average nucleotide identity values between the genomes of the strains AF52-21T and CM04-06T compared to Faecalibacterium prausnitzii ATCC 27768T were 83.20% and 82.54%, respectively, and 90.09% when comparing AF52-21T and CM04-06T. Both values were below the previously proposed species threshold (95–96%), supporting their recognition as novel species in the genus Faecalibacterium. The genomic DNA G + C contents of strains AF52-21T and CM04-06T calculated from genome sequences were 57.77 mol% and 57.51 mol%, respectively. Based on the phenotypic, chemotaxonomic and phylogenetic characteristics, we conclude that both strains represent two new Faecalibacterium species, for which the names Faecalibacterium butyricigenerans sp. nov. (type strain AF52-21T = CGMCC 1.5206T = DSM 103434T) and Faecalibacterium longum sp. nov. (type strain CM04-06T = CGMCC 1.5208T = DSM 103432T) are proposed.

The Faroe Islands was one of the first countries in the Western Hemisphere to eliminate coronavirus disease (COVID-19). During the first epidemic wave in the country, 187 cases were reported between March 3 and April 22, 2020. Large-scale testing and thorough contact tracing were implemented early on, along with lockdown measures. Transmission chains were mapped through patient history and knowledge of contact with prior cases. The most common reported COVID-19 symptoms were fever, headache, and cough, but 11.2% of cases were asymptomatic. Among 187 cases, 8 patients were admitted to hospitals but none were admitted to intensive care units and no deaths occurred. Superspreading was evident during the epidemic because most secondary cases were attributed to just 3 infectors. Even with the high incidence rate in early March, the Faroe Islands successfully eliminated the first wave of COVID-19 through the early use of contact tracing, quarantine, social distancing, and large-scale testing.

Abstract While prolonged fasting induces significant metabolic changes in humans and mice, less is known about systems-wide metabolic changes in response to short-term feed deprivation, which is used in experimental animal studies prior to metabolic challenge tests. We here performed a systems biology-based investigation of connections between gut bacterial composition and function, inflammatory and metabolic parameters in the intestine, liver, visceral adipose tissue, blood and urine in high-fat fed, obese mice that were feed deprived up to 12 h. The systems-wide analysis revealed that feed deprivation linked to enhanced intestinal butyric acid production and expression of the gene encoding the pro-thermogenic uncoupling protein UCP1 in visceral adipose tissue of obese mice. Ucp1 expression was also positively associated with Il33 expression in ileum, colon and adipose tissue as well as with the abundance of colonic Porphyromonadaceae, the latter also correlating to cecal butyric acid levels. Collectively, the data highlighted presence of a multi-tiered system of inter-tissue communication involving intestinal, immune and metabolic functions which is affected by feed deprivation in obese mice, thus pointing to careful use of short-feed deprivation in metabolic studies using obese mice.

Objectives To assess the feasibility of using video recordings of neonatal resuscitation (NR) to evaluate the quality of care in a low-resource district hospital.Design Prospective observational feasibility study.Setting Chake-Chake Hospital, a district hospital in Pemba, Tanzania, in April and May 2019.Participants All delivering women and their newborns were eligible for participation.Main outcome measures Motion-triggered cameras were mounted on resuscitation tables and provided recordings that were analysed for quality of care indicators based on the national NR algorithm. Assessment of feasibility was conducted using Bowen’s 8-point framework for feasibility studies.Results 91% (126 of 139) of women and 96% (24 of 26) of health workers were comfortable or very comfortable with the video recordings. Of 139 newborns, 8 underwent resuscitation with bag and mask ventilation. In resuscitations, heat loss prevention measures were not performed in half of the cases (four of eight), clearing the airway was not performed correctly in five of eight cases, and all newborns were suctioned vigorously and repeatedly, even when not indicated. In a quarter (two of eight) of cases, the newborn’s head was not positioned correctly. Additionally, two of the eight newborns needing ventilation were not ventilated within the first minute of life. In none of the eight cases did ventilation appear to be performed effectively.Conclusions It proved feasible to use video recordings to assess quality of care during NR in a low-resource setting, and the method was considered acceptable for the delivering women and health workers. Recordings of eight resuscitations all demonstrated deviations from NR guidelines.

Abstract To investigate bone health and body composition in young women with long-duration type 1 diabetes (T1D) in relation to matched controls. Twenty-three Swedish women, age 19.2–27.9 years, with a T1D duration of 10 years or more were recruited from the Swedish National Diabetes Registry (NDR). An age-, gender- and geography-matched control group was recruited. Bone mass and body composition were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Data was retrieved from the NDR and SWEDIABKIDS registries. T1D individuals had a mean diabetes duration of 19 years. T1D individuals had reduced lean mass (40.0 ± 6.1 kg vs. 43.9 ± 4.9 kg) and were shorter (1.66 ± 0.06 m vs. 1.71 ± 0.06 m) although comparable BMI. Subjects with T1D had lower muscle area (P = 0.0045). No differences were observed for fractures; physical activity; total, lumbar spine or femur areal bone mineral density. The cortical bone strength strain index was lower for TD1 patients (1875 ± 399 mm3 vs. 2277 ± 332 mm3). In conclusion, young women with long-term diabetes duration showed reduced cortical bone strength, decreased periosteal circumference, endosteal circumference and altered body composition. These factors contribute to the health burden of TD1, which warrants further attention for advancing bone health in women with T1D.

Abstract Objective To report on long-term effects of a cluster randomized controlled kindergarten-based intervention trial, which aimed to increase vegetable intake among Norwegian preschool children (3–5 years at baseline). The effects of the intervention at follow-up 1 (immediately post-intervention) have previously been published. This paper presents the effects of the intervention from baseline to follow-up 2 (12 months post-intervention). Results Parental consents were obtained for 633 out of 1631 eligible children (response rate 38.8%). The effects of the intervention from baseline to follow-up 2 were assessed by mixed-model analyses taking the clustering effect of kindergartens into account. Children’s vegetable intake was reported by the parents at baseline (spring 2015), at follow-up 1 (spring 2016) and at follow-up 2 (spring 2017). No significant long-term effects in child vegetable intake were found. A mean difference of − 0.1 times per day (95% CI − 0.5, 0.2) (P = 0.44) was found for the daily frequency of vegetable intake. A mean difference of – 0.2 different kinds of vegetables eaten over a month (95% CI − 1.0, 0.7) (P = 0.70) was found and for daily amount of vegetables a mean difference of − 15.0 g vegetables (95% CI − 38.0, 8.0) (P = 0.19) was found. Trial registration International Standard Randomised Controlled Trials ISRCTN51962956 (http://www.isrctn.com/ISRCTN51962956). Registered 21 June 2016 (retrospectively registered)

Myoglobin (MB) is known to bind and deliver oxygen in striated muscles at high expression levels. MB is also expressed at much reduced levels in mammary epithelial cells, where the protein´s function is unclear. In this study, we aim to determine whether MB impacts fatty acid trafficking and facilitates aerobic fatty acid ß-oxidation in mammary epithelial cells. We utilized MB-wildtype versus MB-knockout mice and human breast cancer cells to examine the impact of MB and its oxygenation status on fatty acid metabolism in mouse milk and mammary epithelia. MB deficient cells were generated through CRISPR/Cas9 and TALEN approaches and exposed to various oxygen tensions. Fatty acid profiling of milk and cell extracts were performed along with cell labelling and immunocytochemistry. Our findings show that MB expression in mammary epithelial cells promoted fatty acid oxidation while reducing stearyl-CoA desaturase activity for lipogenesis. In cells and milk product, presence of oxygenated MB significantly elevated indices of limited fatty acid ß-oxidation, i.e., the organelle-bound removal of a C2 moiety from long-chain saturated or monounsaturated fatty acids, thus shifting the composition toward more saturated and shorter fatty acid species. Presence of the globin also increased cytoplasmic fatty acid solubility under normoxia and fatty acid deposition to lipid droplets under severe hypoxia. We conclude that MB can function in mammary epithelia as intracellular O2-dependent shuttle of oxidizable fatty acid substrates. MB’s impact on limited oxidation of fatty acids could generate inflammatory mediator lipokines, such as 7-hexadecenoate. Thus, the novel functions of MB in breast epithelia described herein range from controlling fatty acid turnover and homeostasis to influencing inflammatory signalling cascade. Future work is needed to analyse to what extent these novel roles of MB also apply to myocytic cell physiology and malignant cell behaviour, respectively.

Background Polypharmacy, defined as the concurrent use of ≥5 medications, increases the risk of drug-drug and drug-disease interactions as well as non-adherence to drug therapy. This may have negative health consequences particularly among older adults due to age-related pharmacokinetic and pharmacodynamic changes. This study aims to uncover the occurrence of polypharmacy among older adults in Denmark and investigate how polypharmacy relates to mortality. Method This nationwide register-based study included 1,338,058 adults aged 65+ years between January 2013 and December 2017 in Denmark. Polypharmacy prevalence was measured at time of inclusion while incidence and the association between polypharmacy and mortality were measured over the five-year follow-up using Cox regression. In an attempt to adjust for confounding by indication, propensity scores with overlap weighting were introduced to the regression model. Results At time of inclusion, polypharmacy prevalence was 29% and over the five years follow-up, 47% of the remaining adults transitioned into polypharmacy. Identified risk factors included multimorbidity (2+ morbidities: HR = 3.51; 95% CI = 3.48–3.53), age (95+ years: HR = 2.85; 95% CI = 2.74–2.96), socioeconomic factors (Highest income quartile: HR = 0.81; 95% CI = 0.80–0.81), region of birth region (Non-western migrants: HR = 0.77; 95% CI = 0.75–0.79), marital status (Divorced: HR = 1.10; 95% CI = 1.10–1.12) and year of inclusion (2017: HR = 1.19; 95% CI = 1.19–1.22). Further analyses showed that polypharmacy involves many different drug cocktails with medication for the cardiovascular system (95%), blood and blood-forming organs (69%), alimentary tract and metabolism (61%) and nervous system (54%) contributing the most. After adjustment for propensity scores with OW, both polypharmacy (HR = 3.48, CI95% = 3.41–3.54) and excessive polypharmacy (HR = 3.48, CI95% = 3.43–3.53) increased the risk of death substantially. Conclusion A considerable proportion of older adults in Denmark were exposed to polypharmacy dependent on health status, socio-economic status, and societal factors. The associated three- to four-fold mortality risk indicate a need for further exploration of the appropriateness of polypharmacy among older adults.

Primary sclerosing cholangitis is an important reason for liver transplantation. Hepatic alveolar echinococcosis (AE) is caused by Echinococcus multilocularis and presents characteristic calcified conglomerates detected by ultrasound or computed tomography scan of the liver. Symptoms of AE only occur after a long period of infection when cholestasis or cholangitis becomes apparent. Here, we report on a patient with presumed autoimmune hepatitis and primary sclerosing cholangitis. After liver transplantation, alveolar echinococcosis was diagnosed in the liver explant.

Introduction Person-centred care based on systematic and comprehensive patient-engagement is gaining momentum across healthcare systems. Providing care that is responsive to the needs, values and priorities of each patient is important for patients, relatives and providers alike, not least for the growing population of older patients living with multi-morbidity and associated complex care trajectories.Objectives The aim of this systematic review is to investigate the effects of patient engagement interventions for older patients with multimorbidity.Methods Systematic review conducted in August 2021. Two reviewers independently screened the international databases Embase and PubMed. Reviewers carried out duplicate and independent data extraction and assessment of study quality. Grading of Recommendations Assessment, Development and Evaluation was used to assess the quality of the evidence for each study.Results We included twelve studies from primary care setting and hospitals. The included studies were heterogeneous in terms of characteristics of populations, types of interventions to enhance patient-engagement, outcome measures and length of follow-up. Nine of the 12 included studies found significant improvements in health and patient-reported outcomes such as higher quality-adjusted life-years, fewer hospital visits and disease specific symptoms. Quality of the included studies was of low to moderate.Conclusion This review identifies potential beneficial effects of interventions to enhance patient-engagement in older adults with multimorbidity. Nevertheless, the limited and very diverse evidence-based calls for more robust studies into efficient approaches to engaging older adults with multimorbidity in care trajectories.

We aimed to identify how additional information about benefits and harms of cervical cancer (CC) screening impacted intention to participate in screening, what type of information on harms women preferred receiving, from whom, and whether it differed between two national healthcare settings. We conducted a survey that randomized screen-eligible women in the United States (n = 1084) and Norway (n = 1060) into four groups according to the timing of introducing additional information. We found that additional information did not significantly impact stated intentions-to-participate in screening or follow-up testing in either country; however, the proportion of Norwegian women stating uncertainty about seeking precancer treatment increased from 7.9% to 14.3% (p = 0.012). Women reported strong system-specific preferences for sources of information: Norwegians (59%) preferred it come from a national public health agency while Americans (59%) preferred it come from a specialist care provider. Regression models revealed having a prior Pap-test was the most important predictor of intentions-to-participate in both countries, while having lower income reduced the probabilities of intentions-to-follow-up and seek precancer treatment among U.S. women. These results suggest that additional information on harms is unlikely to reduce participation in CC screening but could increase decision uncertainty to seek treatment. Providing unbiased information would improve on the ethical principle of respect for autonomy and self-determination. However, the clinical impact of additional information on women’s understanding of the trade-offs involved with CC screening should be investigated. Future studies should also consider country-specific socioeconomic barriers to screening if communication re-design initiatives aim to improve CC screening participation.

Objectives The objective of this study was to investigate the use of, and predictors for, pharmaceutical anticancer treatment (PACT) towards the end of a patient’s life in a country with a public healthcare system.Design Retrospective registry study.Setting Secondary care in Norway.Participants All Norwegian patients with cancer (International Classification of Diseases tenth revision (ICD-10) codes C00–99, D00–09, D37–48) in contact with a somatic hospital in Norway between 2009 and 2017 (N=420 655). Analyses were performed on a subsample of decedents with follow-back time of more than 1 year (2013–2017, N=52 496).Interventions N/A.Primary and secondary outcome measures Proportion of patients receiving PACT during the last year and month of life. We calculated CIs with block bootstrapping, while predictors of PACT were estimated with logistic regression.Results 24.0% (95% CI 23.4% to 24.6%) of the patients received PACT during the last year of life and 3.2% (95% CI 3.0% to 3.5%) during their final month. The proportion during the last month was highest for multiple myeloma (12.7%) and breast cancer (6.5%) and lowest for urinary tract (1.1%) and prostate and kidney cancer (1.4%). Patients living in northern (OR 0.80, 95% CI 0.68 to 0.94) and western (OR 0.85, 95% CI 0.75 to 0.96) Norway had lower odds of PACT during the last month, while patients with myeloma (OR 3.0, 95% CI 2.5 to 3.7) and breast (OR 1.4, 95% CI 1.1 to 1.6) had higher odds. Kidney cancer (OR 0.25, 95% CI 0.2. to 0.4), urinary tract (OR 0.38, 95% CI 0.3 to 0.5) and prostate cancer (OR 0.4, 95% CI 0.3 to 0.5) were associated with lower probability of receiving PACT within the last month.Conclusions The proportion of patients receiving PACT in Norway is lower than in several other industrialised countries. Age, type of cancer and area of living are significant determinants of variation in PACT.

Abstract We describe two clinical prenatal cases with rare de novo RIT1 variants, which showed more severe clinical manifestations than other Noonan Syndrome genotypes, resulting in fetal death. Extra attention is recommended when these variants are detected.

We conducted a nationwide study of the prevalence of severe acute respiratory syndrome coronavirus 2 infection in the Faroe Islands. Of 1,075 randomly selected participants, 6 (0.6%) tested seropositive for antibodies to the virus. Adjustment for test sensitivity and specificity yielded a 0.7% prevalence. Our findings will help us evaluate our public health response.

Abstract To describe glucose metabolism in the late, weight stable phase after Roux-en-Y Gastric Bypass (RYGB) in patients with and without preoperative type 2 diabetes we invited 55 RYGB-operated persons from two existing cohorts to participate in a late follow-up study. 44 (24 with normal glucose tolerance (NGT)/20 with type 2 diabetes (T2D) before surgery) accepted the invitation (median follow-up 2.7 [Range 2.2–5.0 years]). Subjects were examined during an oral glucose stimulus and results compared to preoperative and 1-year (1 y) post RYGB results. Glucose tolerance, insulin resistance, beta-cell function and incretin hormone secretion were evaluated. 1 y weight loss was maintained late after surgery. Glycemic control, insulin resistance, beta-cell function and GLP-1 remained improved late after surgery in both groups. In NGT subjects, nadir glucose decreased 1 y after RYGB, but did not change further. In T2D patients, relative change in weight from 1 y to late after RYGB correlated with relative change in fasting glucose and HbA1c, whereas relative changes in glucose-stimulated insulin release correlated inversely with relative changes in postprandial glucose excursions. In NGT subjects, relative changes in postprandial nadir glucose correlated with changes in beta-cell glucose sensitivity. Thus, effects of RYGB on weight and glucose metabolism are maintained late after surgery in patients with and without preoperative T2D. Weight loss and improved beta-cell function both contribute to maintenance of long-term glycemic control in patients with type 2 diabetes, and increased glucose stimulated insulin secretion may contribute to postprandial hypoglycemia in NGT subjects.

Background: The immune checkpoint, indoleamine 2,3-dioxygenase 1, is under investigation as target of novel immunotherapies for cancers, including head and neck squamous cell carcinomas (HNSCC). The aim of our study was to analyze DNA methylation of the encoding gene (IDO1) in HNSCC. Methods: Methylation of three CpG sites within the promoter, promoter flank, and gene body was investigated and correlated with mRNA expression, immune cell infiltration, mutational burden, human papillomavirus (HPV)-status, and overall survival in a cohort of N = 528 HNSCC patients obtained from The Cancer Genome Atlas. In addition, IDO1 immunohistochemistry and DNA methylation analysis was performed in an independent cohort of N = 138 HNSCC samples. Findings: Significant inverse correlations of IDO1 methylation and IDO1 mRNA expression were found in the promoter and promoter flank region (Spearman's ρ = −0.163 and ρ = −0.377, respectively) while a positive correlation was present in the gene body (ρ = 0.502; all P

Background: The gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development. Method: We used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naïve type 2 diabetic (TN-T2D, n = 77), pre-diabetic (Pre-DM, n = 80), and normal glucose tolerant (NGT, n = 97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naïve T2D individuals to elucidate possible host-microbial interplays characterizing different disease stages. Findings: We observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups. Interpretation: Our findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and point to the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host. Fund: The study was supported by the National Natural Science Foundation of China (No. 31601073), the National Key Research and Development Program of China (No. 2017YFC0909703) and the Shenzhen Municipal Government of China (No. JCYJ20170817145809215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Keywords: Metagenomics, Metaproteomics, Prediabetes, Treatment-naïve type 2 diabetes

Up to half of all women do not receive follow-up as recommended after cervical cytology testing and are thus at increased risk of dysplasia progression. Women from lower social positions are at increased risk of not receiving follow-up. Sample takers, often general practitioners, convey results to women, but communication problems constitute a challenge. We aimed to investigate the effect of direct notification of cervical cytology results on follow-up rates.In a 1:1 cluster-randomised controlled trial, we assessed if having the pathology department convey cervical cytology results directly to the investigated women improved timely follow-up, compared with conveying the results via the general practitioner as usual. All women with a cervical cytology performed in a general practice in the Central Denmark Region (2013–2014) and receiving follow-up recommendation were included (n = 11,833).The proportion of women without timely follow-up was lower in the group with direct notifications than in the control group of women receiving usual care, regardless of age, educational status, cohabitation status and ethnicity. Among the women with the most severe cervical cytology diagnoses who are recommended gynaecological follow-up within 3 months, the percentage without timely follow-up was 15.1% in the intervention group and 19.5% in the control group (prevalence difference: −0.04 (95%CI: −0.07; −0.02)). Improved timely follow-up was also observed for women with a recommendation to have follow-up performed at 3 and 12 months.Cervical cytology results conveyed directly by letter to women increased the proportion of women with timely follow-up without raising inequality in follow-up measured by social position.Trial registration: ClinicalTrials.gov (TRN: NCT02002468) 29 November 2013. Keywords: General practice, Uterine cervical dysplasia, Mass screening, Early detection of cancer, Socioeconomic factors, Quality of health care

Background: Murine studies demonstrate that maternal prenatal gut microbiota influences brain development and behaviour of offspring. No human study has related maternal gut microbiota to behavioural outcomes during early life. This study aimed to evaluate relationships between the prenatal faecal microbiota, prenatal diet and childhood behaviour. Methods: A sub-cohort of 213 mothers and 215 children were selected from a longitudinal pre-birth cohort. Maternal prenatal exposure measures collected during the third trimester included the faecal microbiota (generated using 16S rRNA amplicon sequencing), and dietary intake. The behavioural outcome used the Childhood Behaviour Checklist at age two. Models were adjusted for prenatal diet, smoking, perceived stress, maternal age and sample batch. Findings: We found evidence that the alpha diversity of the maternal faecal microbiota during the third trimester of pregnancy predicts child internalising behaviour at two years of age (−2·74, (−4·71, −0·78), p = 0·01 (Wald test), R2=0·07). Taxa from butyrate-producing families, Lachnospiraceae and Ruminococcaceae, were more abundant in mothers of children with normative behaviour. A healthy prenatal diet indirectly related to decreased child internalising behaviours via higher alpha diversity of maternal faecal microbiota. Interpretation: These findings support animal studies showing that the composition of maternal prenatal gut microbiota is related to offspring brain development and behaviour. Our findings highlight the need to evaluate potential impacts of the prenatal gut microbiota on early life brain development. Funding: This study was funded by the National Health and Medical Research Council of Australia (1082307, 1147980), Murdoch Children's Research Institute, Barwon Health and Deakin University.

Introduction Traumatic injuries constitute a major cause of mortality and morbidity. Still, the public health burden of trauma in Norway has not been characterised using nationwide registry data. More knowledge is warranted on trauma risk factors and the long-term outcomes following trauma. The Injury Prevention and long-term Outcomes following Trauma project will establish a comprehensive research database. The Norwegian National Trauma Registry (NTR) will be merged with several data sources to pursue the following three main research topics: (1) the public health burden of trauma to society (eg, excess mortality and disability-adjusted life-years (DALYs)), (2) trauma aetiology (eg, socioeconomic factors, comorbidity and drug use) and (3) trauma survivorship (eg, survival, drug use, use of welfare benefits, work ability, education and income).Methods and analysis The NTR (n≈27 000 trauma patients, 2015–2018) will be coupled with the data from Statistics Norway, the Norwegian Patient Registry, the Cause of Death Registry, the Registry of Primary Health Care and the Norwegian Prescription Database. To quantify the public health burden, DALYs will be calculated from the NTR. To address trauma aetiology, we will conduct nested case–control studies with 10 trauma-free controls (drawn from the National Population Register) matched to each trauma case on birth year, sex and index date. Conditional logistic regression models will be used to estimate trauma risk according to relevant exposures. To address trauma survivorship, we will use cohort and matched cohort designs and time-to-event analyses to examine various post-trauma outcomes.Ethics and dissemination The project is approved by the Regional Committee for Medical Research Ethics. The project’s data protection impact assessment is approved by the data protection officer. Results will be disseminated to patients, in peer-reviewed journals, at conferences and in the media.