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Pragmatics refers to the ability to effectively use and interpret language in different contexts. Pragmatic abilities develop and refine through childhood, and they are essential for socialization, academic achievement and wellbeing. The scarcity of assessment tools in this field makes it challenging to provide a comprehensive assessment of pragmatic abilities. The Pragma test, originally developed for Finnish and also adapted into Italian, consists of a battery of tasks assessing children's pragmatic abilities. In this study, a first evaluation of the psychometric qualities of a Norwegian adaptation of this test is presented. In addition, we investigated pragmatic development between ages 5 and 7, and explored possible gender-based differences. Altogether 119 Norwegian-speaking children participated in the study. The children were tested with the Pragma test and parents completed the Children's Communication Checklist-2. The children were allocated into three groups: 5-year-olds, 6-year-olds and 7-year-olds. The psychometric qualities of this Norwegian adaptation supported its use as a tool for assessing pragmatics in children aged 5-7. Strong and significant growth in pragmatic competence was observed from age 5-6, subsequently flattening out between age 6 and 7, and gender differences in favour of girls were identified. These findings indicate that pragmatic ability, as measured by the Pragma test, shows similar age effects in a Norwegian setting as in Finnish and Italian contexts, paving the way for further cross-cultural and cross-linguistic studies.

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA-Cancer Moonshot and the EU-Mission on Cancer and Europes Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state-of-the-art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost-effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients needs and cost-effective healthcare.

Abstract Background Scaling up effective interventions to promote healthy eating habits in children in real-world settings is a pressing need. The success of implementation hinges crucially on engaging end-users and tailoring interventions to meet their specific needs. Building on our prior evaluation of a digital “healthy eating” resource for early childhood education and care (ECEC) staff; this qualitative study aims to pinpoint the barriers and facilitators that influence the successful implementation of such interventions. Methods We conducted twelve semi-structured interviews with ECEC teachers in a Norwegian municipality. Interview participants were later invited to participate in focus groups where two discussions were conducted with five of the participants to reflect on the initial interview findings. Thematic analysis, facilitated by NVivo software, was employed to analyse the data, aiming to identify and summarize teachers’ subjective experiences and perspectives. Results Teachers’ perceptions of barriers to the implementation of an upcoming digital “healthy eating” resource included: (1) No established tradition of using digital resources at work; (2) Uncertainty regarding the achievable outcomes of implementation; (3) Perception of the new “healthy eating” resource as cooking-focused and unnecessary; and (4) Hectic everyday life serving as a barrier to the long-term use of a digital resource. Facilitators for implementation included: (1) A user-friendly format; (2) Newsletters featuring seasonal tips inspire and serve as effective reminders; (3) Emphasis on research and legislation; and (4) Structuring the resource as a series and an idea bank. Conclusions The findings underscore the essential need for tailored strategies and comprehensive support structures to successfully implement a culturally appropriate digital “healthy eating” resource for ECEC staff, ensuring effectiveness and feasibility. Trial registration This study was not registered in a trial registry as it is not a clinical trial or intervention study but serves as a pilot for the Nutrition Now study, trial identifier ISRCTN10694967 ( https://doi.org/10.1186/ISRCTN10694967 ), registration date: 19/06/2022.

Abstract Background Mental health problems among adolescents is a global challenge. During the transition to adolescence, physiological, psychological, and social changes occur, leading to increased vulnerability. Thus, adolescent boys are less likely to seek help for mental health problems, which makes them an undetected group. The aim of this study was to gain a deeper understanding of adolescent boys’ experiences of mental health and school health service. Methods An inductive, qualitative design was chosen using three focus group interviews and three individual interviews. The study included 18 adolescent boys in 7th grade, in a school located in a medium-sized municipality in Norway. The interviews were analysed with qualitative content analysis. The consolidated criteria for reporting qualitative research (COREQ) were followed in this study. Results The overall theme “barriers towards seeking help”, and three categories— navigating stigma and privacy concerns; perceptions of self-responsibility; and lacking knowledge of mental health problems and help-seeking—described the adolescent boys experiences. The awareness and willingness to seek help were present, but there are barriers preventing the adolescent boys from acting on that willingness. Conclusions Lack of knowledge and a non-permissive culture for mental health problems among adolescents contributes to decreased help-seeking behaviour among adolescent boys. The school health service is the most related health service for adolescents and should focus on being available and strengthening empowerment and mental health literacy through the development and implementation of interventions to promote mental health.

Abstract Background Rupture of an intracranial aneurysm resulting in a subarachnoid hemorrhage (SAH) is a life-threatening situation. Obesity is an increasing health challenge associated with numerous comorbidities. However, recent studies have shown a surprising decreased risk of SAH with increasing body mass index (BMI). The aim was to explore associations between other anthropometric variables and the rupture risk of an intracranial aneurysm, which to our knowledge is lacking in present literature. Methods Using a bioelectrical impedance analysis device, we performed body composition analyses on 31 patients admitted with aneurysmal SAH (aSAH) and 28 patients with planned intervention on their unruptured aneurysm. We also collected information on comorbidities and relevant risk factors. Logistic regression was used to explore associations between anthropometric variables and patients with ruptured versus unruptured aneurysms. Results Unadjusted estimates showed a significant inverse relationship between body fat percent and aneurysmal rupture (OR [95% CI]: 0.92 [0.86, 0.97], P = 0.009), and between body fat mass and aneurysmal rupture (OR [95% CI]: 0.95 [0.90, 0.99], P = 0.047). These risk relationships remained significant in age- and sex-adjusted analyses for body fat percent (OR [95% CI]: 0.93, [0.87, 0.97], P = 0.028), and body fat mass (OR [95% CI]: 0.95 [0.90, 0.99], P = 0.041). Conclusions In recent studies showing a paradoxical relation between aSAH and obesity, BMI was the only parameter investigated. We further explored this “obesity paradox” and found lower body fat in aSAH patients compared to UIA. Future studies should investigate these relationships in larger samples. Clinical Trial Registration NCT04613427, November 3, 2020, retrospectively registered

Some parasites manipulate their hosts phenotype to enhance predation rates by the next host in the parasites life cycle. Our understanding of this parasite-increased trophic transmission is often stymied by study-design challenges. A recurring difficulty has been obtaining uninfected hosts with a coevolutionary history with the parasites, and conducting experimental infections that mimic natural processes. In 1996, Lafferty and Morris provided what has become a classic example of parasite-increased trophic transmission; they reported a positive association between the intensity of a brain-infecting trematode (Euhaplorchis californiensis) in naturally infected California killifish (Fundulus parvipinnis) and the frequency of conspicuous behaviors, which was thought to explain the documented 10-30× increase in predation by the final host birds. Here, we address the primary gap in that study by using experimental infections to assess the causality of E. californiensis infection for increased conspicuous behaviors in F. parvipinnis. We hatched and reared uninfected F. parvipinnis from a population co-occurring with E. californiensis, and infected them 1-2 times/week over half their life span with E. californiensis and a small cyathocotylid trematode (SMCY) that targets the hosts muscle tissue. At 3 time points throughout the hosts lives, we quantified several conspicuous behaviors: contorting, darting, scratching, surfacing, and vertical positioning relative to the waters surface. Euhaplorchis californiensis and SMCY infection caused 1.8- and 2.5-fold overall increases in conspicuous behaviors, respectively. Each parasite was also associated with increases in specific conspicuous behaviors, particularly 1.9- and 1.4-fold more darting. These experimental findings help solidify E. californiensis-F. parvipinnis as a classic example of behavioral manipulation. Yet our findings for E. californiensis infection-induced behavioral change were less consistent and strong than those previously documented. We discuss potential explanations for this discrepancy, particularly the idea that behavioral manipulation may be most apparent when fish are actively attacked by predators. Our findings concerning the other studied trematode species, SMCY, highlight that trophically transmitted parasites infecting various host tissues are known to be associated with conspicuous behaviors, reinforcing calls for research examining how communities of trophically transmitted parasites influence host behavior.

Bakgrunn: Atelektaser er den vanligste årsaken til hypoksemi hos pasienter i generell anestesi og kan føre til postoperative lungekomplikasjoner. Rekrutteringsmanøver (RM) og bruk av positivt endeekspiratorisk trykk (PEEP) er metoder for å forebygge og behandle atelektaser hos pasienter i narkose. Samtidig rapporteres det at manglende opplæring og prosedyrer fører til at anestesipersonell vegrer seg for å ta i bruk disse metodene. Hensikt: Å utarbeide en kunnskapsbasert fagprosedyre for bruk av RM og PEEP under generell anestesi. Prosedyren er avgrenset til pasienter over 18 år og ASA klasse 1–3. Metode: Vi brukte Helsebibliotekets metode og minstekrav for utarbeidelse av fagprosedyrer, basert på AGREE II-verktøyet. Systematiske søk ble gjort i seks medisinske databaser og fem databaser for kliniske retningslinjer. I tillegg ble det etablert en prosedyregruppe bestående av fire klinikere innen anestesiologi. Resultater: Resultatene viser at ved å gjøre rekrutteringsmanøver og optimalisere PEEP kan en oppnå en forbedret intraoperativ lungefunksjon. Det er likevel lav evidens for at effekten varer ut i den postoperative perioden. Derfor anbefales det kun å gjøre rekrutteringsmanøver på indikasjon. Konklusjon: RM er en trygg og effektiv metode for å oppheve atelektaser som medfører hypoksemi under generell anestesi. RM bør etterfølges av en justering av PEEP-verdi for å opprettholde effekten. Konsekvenser for klinisk praksis: Fagprosedyren er fremstilt som et praktisk flytskjema som kan tas i bruk som et beslutningsverktøy i klinisk praksis. Prosedyren gir også anbefalinger for monitorering av lungemekanikk som skal ligge til grunn for å utføre tiltak og evaluere effekt av tiltak. Implementering av fagprosedyren vil også gi økt fokus på lungemekanikk under generell anestesi. Systematisk undervisning og opplæring av anestesipersonell vil være nødvendig om fagprosedyren skal implementeres i klinisk praksis. ENGLISH ABSTRACT Recommendations for the Safe Use of the Recruitment Maneuver Under General Anaesthesia – A Clinical Practice Guideline Background: Atelectasis is the most common cause of hypoxemia in patients under general anesthesia, and can lead to postoperative pulmonary complications. Recruitment maneuver (RM) and the use of positive end-expiratory pressure (PEEP) are methods for preventing and treating atelectasis in patients under general anesthesia. It is reported that lack of training and procedures can lead to reluctance among anesthesia personnel to use these methods. Purpose: To develop an evidence-based, clinical procedure for the use of RM and PEEP during general anesthesia. The procedure is restricted to patients over 18 years of age and ASA classification 1–3. Method: We used the methods and criteria as lined out by The Norwegian Electronic Health Library, based on AGREE II. A systematic comprehensive search was made in six medical databases and five databases for clinical guidelines. In addition, a procedure group consisting of four clinicians in anesthesiology was established. Results: The results show that by performing a recruitment maneuver and optimizing PEEP, one can achieve an improved intraoperative lung function. However, there is little evidence that the effect lasts into the postoperative period. Therefore, it is recommended to only perform RM on indication. Conclusion: RM is a safe and effective method to reverse atelectasis causing hypoxemia under general anaesthesia. RM should be followed by an adjustment of PEEP value to maintain the effect. Implications for clinical practice: The clinical procedure is presented as a practical flow chart that can be used as a decision-making tool in clinical practice. The procedure gives recommendations for monitoring of lung mechanics, which will form the basis for carrying out the next step and evaluating the effect. It will also increase focus on lung mechanics during general anesthesia. Systematic instruction and training of anesthesia personnel is necessary if the procedure is going to be implemented in clinical practice.

This is an attempt to clarify certain concepts related to a debate on the interpretation of quantum mechanics, a debate between Khrennikov on the one hand and Stacey and Schack on the other hand. Central to this debate is the notion of quantum probabilities. I first take up the probability concept in the QBist school, as seen from my point of view, and then give my own arguments for the Born formula for calculating quantum probabilities. In that connection, I also sketch some consequences of my approach toward the foundation and interpretation of quantum theory. I discuss my general views on QBism as a possible alternative interpretation of quantum mechanics before I give some final remarks.

Purpose The Dynamics of Family Conflict (FamC) prospective cohort study was set up to investigate how and why interparental conflicts and family relations develop over time, and in which contexts which types of conflicts and relations are most negative for which children. FamC focuses on the family within a scope spanning macrolevel as well as microlevel processes.Participants Families were recruited from MoBa (pilot project) and family counselling offices across Norway when parents attended parental counselling, therapy or mandatory mediation in relation to parental relationship dissolution. All families were thus experiencing challenges and/or going through a family transition. Families were eligible for the study if parents had at least one joint child between 0 and 16 years. Both parents and up to five children from the same family could participate. A total of 2871 families were recruited (participation rate wave 1: 78%) and an estimated 55% of parents (based on wave 1 data) were divorced/separated. Additional data were obtained from therapists/mediators at the family counselling offices about the family, and childcare or schoolteachers provided data on the youngest (0–6 years) children.Findings to date Results show that interparental conflict patterns vary with family constellation. Interparental conflict severity is inversely related to the discrepancy between child-reported and parent-reported child reactions to interparental conflicts, and child-self-reported reactions are higher relative to parent-reported child reactions. Other findings show that family characteristics (eg, the number and age of children in the family and financial difficulties) are predictive of the type of residence arrangement that parents practice.Future plans The cohort is ideally suited for cross-cultural comparisons and further examination of family processes and dynamics including parent repartnering, step-parents and new family members, associations between different family constellations and child adjustment, and fathering, father–child relationship and child adjustment. There are plans for further follow-up data collection.

The gastrointestinal (GI) tract redox environment, influenced by commensal microbiota and bacterial-derived metabolites, is crucial in shaping T-cell responses. Specifically, metabolites from gut microbiota (GM) exhibit robust anti-inflammatory effects, fostering the differentiation and regulation of CD8+ tissue-resident memory (TRM) cells, mucosal-associated invariant T (MAIT) cells, and stabilizing gut-resident Treg cells. Nitric oxide (NO), a pivotal redox mediator, emerges as a central regulator of T-cell functions and gut inflammation. NO impacts the composition of the gut microbiome, driving the differentiation of pro-inflammatory Th17 cells and exacerbating intestinal inflammation, and supports Treg expansion, showcasing its dual role in immune homeostasis. This review delves into the complex interplay between GI redox balance and GM metabolites, elucidating their profound impact on T-cell regulation. Additionally, it comprehensively emphasizes the critical role of GI redox, particularly reactive oxygen species (ROS) and NO, in shaping T-cell phenotype and functions. These insights offer valuable perspectives on disease mechanisms and potential therapeutic strategies for conditions associated with oxidative stress. Understanding the complex cross-talk between GI redox, GM metabolites, and T-cell responses provides valuable insights into potential therapeutic avenues for immune-mediated diseases, underscoring the significance of maintaining GI redox balance for optimal immune health.

BackgroundRadiotherapy (RT) can be used to reduce symptoms and maintain open airways for patients with non-small cell lung cancer when systemic treatment is not sufficient. For some patients, tumor control is not achieved due to radioresistance. Concurrent inhibition of epidermal growth factor receptors has been proposed as a strategy to overcome radioresistance but may increase toxicity. We performed a randomized trial to assess the efficacy, tolerance, and quality of life of concurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer.MethodsPatients were randomized 1:1 to RT alone (arm A) or in combination with erlotinib (arm B). A computed tomography (CT) scan at baseline and one at 4–12 weeks after inclusion was used to evaluate treatment response. Adverse events were registered during treatment and the subsequent 30 days. Health-related quality-of-life questionnaires were completed by the patients at baseline, weeks 2, 6, and 20.ResultsA total of 114 patients were included. Of the 74 patients with CT scans available for evaluation of treatment effect, there were no significant differences in tumor size reduction between the two groups: median 14.5% reduction in the control arm A and 17.0% in the erlotinib arm B (p = 0.68). Overall survival was not significantly different between the two treatment arms: 7.0 and 7.8 months in arm A and arm B, respectively (log-rank p = 0.32). There was no significant increase in adverse events in the experimental arm, other than what is expected from erlotinib treatment alone. Overall, patients reported similar quality of life in both treatment arms.ConclusionConcurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer was well tolerated but did not improve the efficacy of the RT.Clinical trial registrationClinicalTrials.gov, identifier NCT02714530.

Abstract Background Dental caries diagnosis requires the manual inspection of diagnostic bitewing images of the patient, followed by a visual inspection and probing of the identified dental pieces with potential lesions. Yet the use of artificial intelligence, and in particular deep-learning, has the potential to aid in the diagnosis by providing a quick and informative analysis of the bitewing images. Methods A dataset of 13,887 bitewings from the HUNT4 Oral Health Study were annotated individually by six different experts, and used to train three different object detection deep-learning architectures: RetinaNet (ResNet50), YOLOv5 (M size), and EfficientDet (D0 and D1 sizes). A consensus dataset of 197 images, annotated jointly by the same six dental clinicians, was used for evaluation. A five-fold cross validation scheme was used to evaluate the performance of the AI models. Results The trained models show an increase in average precision and F1-score, and decrease of false negative rate, with respect to the dental clinicians. When compared against the dental clinicians, the YOLOv5 model shows the largest improvement, reporting 0.647 mean average precision, 0.548 mean F1-score, and 0.149 mean false negative rate. Whereas the best annotators on each of these metrics reported 0.299, 0.495, and 0.164 respectively. Conclusion Deep-learning models have shown the potential to assist dental professionals in the diagnosis of caries. Yet, the task remains challenging due to the artifacts natural to the bitewing images.

Abstract Background The main focus on the characteristics of malignant lung tumours has been the size, position within the lobe, and infiltration into neighbouring structures. The aim of this study was to investigate the distribution and characteristics of malignant tumours between the lung lobes and whether the diagnosis, treatment, and outcome differed based on location. Methods This study is based on 10,849 lung cancer patients diagnosed in 2018–2022 with complete data on the location and characteristics of the tumours. The proportions of tumours in each lobe divided by its volume were termed the relative proportion. Results The right upper lobe comprised 31.2% of the tumours and 17.6% of the lung volume. The relative proportion of 1.77 was higher than in the other lobes (p

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA‐Cancer Moonshot and the EU‐Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state‐of‐the‐art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost‐effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost‐effective healthcare.

This study explores whether and to what extent the background information supplied by 10,155 immigrants who took an official language test in Norwegian affected their chances of passing one, two, or all three parts of the test. The background information included in the analysis was prior education, region (location of their home country), language (first language [L1] background, knowledge of English), second language (hours of second language [L2] instruction, L2 use), L1 community (years of residence, contact with L1 speakers), age, and gender. An ordered logistic regression analysis revealed that eight of the hypothesised explanatory variables significantly impacted the dependent variable (test result). Several of the significant variables relate to pre-immigration conditions, such as educational opportunities earlier in life. The findings have implications for language testing and also, to some extent, for the understanding of variation in learning outcomes.

Background: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. Patients and methods: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. Results: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. Conclusion: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.

Background and purpose: In Norway, comprehensive molecular tumour profiling is implemented as part of the public healthcare system. A substantial number of tumours harbour potentially targetable molecular alterations. Therapy outcomes may improve if targeted treatments are matched with actionable genomic alterations. In the IMPRESS-Norway trial (NCT04817956), patients are treated with drugs outside the labelled indication based on their tumours molecular profile. Patients and methods: IMPRESS-Norway is a national, prospective, non-randomised, precision cancer medicine trial, offering treatment to patients with advanced-stage disease, progressing on standard treatment. Comprehensive next-generation sequencing, TruSight Oncology 500, is used for screening. Patients with tumours harbouring molecular alterations with matched targeted therapies available in IMPRESS-Norway, are offered treatment. Currently, 24 drugs are available in the study. Primary study endpoints are percentage of patients offered treatment in the trial, and disease control rate (DCR) defined as complete or partial response or stable disease in evaluable patients at 16 weeks (W16) of treatment. Secondary endpoint presented is DCR in all treated patients. Results: Between April 2021 and October 2023, 1,167 patients were screened, and an actionable mutation with matching drug was identified for 358 patients. By the data cut off 186 patients have initiated treatment, 170 had a minimum follow-up time of 16 weeks, and 145 also had evaluable disease. In patients with evaluable disease, the DCR was 40% (58/145). Secondary endpoint analysis of DCR in all treated patients, showed DCR of 34% (58/170). Interpretation: Precision cancer medicine demonstrates encouraging clinical effect in a subset of patients included in the IMPRESS-Norway trial.