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The adoption of the 1982 UN Convention on the Law of the Sea (UNCLOS) and the steady development of international environmental law in the twentieth century shaped the marine environment as an object of legal protection. However, the exponential growth of substantive obligations to protect the marine environment, conserve marine biodiversity, and prevent marine pollution, has been largely ineffective due to lack of enforcement. Unmanned aerial vehicles (UAVs) deployed for marine environmental protection are seen, in scholarship and policy, as a means to close the enforcement gap, thereby revolutionizing the field by significantly increasing states’ maritime awareness. In contrast, our tentative analysis shows that while UAVs can translate complex environmental concerns into data readily available for analysis and action, such datafication of marine environments comes with high risks. More specifically, datafication enables multiple uses of gathered data, including for surveillance, military, and commercial purposes. These concerns tend to fall outside current debates on the international regulation of the use of UAVs in marine environments. In our essay, we explore whether international law recognizes the possibilities and risks involved in deploying UAVs into the marine environment. We draw on doctrinal and posthuman feminist legal approaches to analyze how UAVs interact with the wider context of “marine ecosystem bodies” in terms of international law, as well as how those terms may need to be reconfigured to accommodate the complexity of the many actors, agents, and materials of marine ecosystems.

Spin defects in 2D hBN are promising for magnetic field sensing but suffer from short spin coherence times. Here the authors extend the coherence time for an ensemble of spins in hBN to 4 microseconds by using a continuous microwave drive and demonstrate qubit control in a protected spin space.

Compulsory schooling in Sweden was introduced in 1842. However, its meaning has changed over time, both in terms of who it applies to, how long it applies and how it can or should be implemented. During the 2000s, compulsory schooling has become synonymous with the obligation to be present in school and attend class. There are students who for medical, mental and social reasons can not go to school and fulfill their school obligation. In order to ensure that these students receive the education they are entitled to, a new chapter was introduced in 2020 in the Swedish Education Act, enabling distance learning. The purpose of the article is to learn more about how the educational policy framework of school attendance and everyone’s right to education can affect the meaning of compulsory schooling, and how this discursive change can have consequences for students, schools, and society. To achieve this, government policy texts on distance education and school attendance published in 2017-2021 are analyzed. The consequences that are perceived to follow from teaching beyond the school area are also discussed here. One consequence that is highlighted is that the school’s democracy mission ends up in danger. The analysis is inspired by Carol Lee Bacchi’s approach WPR (What’s the Problem Represented to be).

Abstract Background Histological feature representation is advantageous for computer aided diagnosis (CAD) and disease classification when using predictive techniques based on machine learning. Explicit feature representations in computer tissue models can assist explainability of machine learning predictions. Different approaches to feature representation within digital tissue images have been proposed. Cell-graphs have been demonstrated to provide precise and general constructs that can model both low- and high-level features. The basement membrane is high-level tissue architecture, and interactions across the basement membrane are involved in multiple disease processes. Thus, the basement membrane is an important histological feature to study from a cell-graph and machine learning perspective. Results We present a two stage machine learning pipeline for generating a cell-graph from a digital H &E stained tissue image. Using a combination of convolutional neural networks for visual analysis and graph neural networks exploiting node and edge labels for topological analysis, the pipeline is shown to predict both low- and high-level histological features in oral mucosal tissue with good accuracy. Conclusions Convolutional and graph neural networks are complementary technologies for learning, representing and predicting local and global histological features employing node and edge labels. Their combination is potentially widely applicable in histopathology image analysis and can enhance explainability in CAD tools for disease prediction.

Abstract Severe malnutrition accounts for half-a-million deaths annually in children under the age of five. Despite improved WHO guidelines, inpatient mortality remains high and is associated with metabolic dysfunction. Previous studies suggest a correlation between hepatic metabolic dysfunction and impaired autophagy. We aimed to determine the role of mTORC1 inhibition in a murine model of malnutrition-induced hepatic dysfunction. Wild type weanling C57/B6 mice were fed a 18 or 1% protein diet for two weeks. A third low-protein group received daily rapamycin injections, an mTORC1 inhibitor. Hepatic metabolic function was assessed by histology, immunofluorescence, gene expression, metabolomics and protein levels. Low protein-fed mice manifested characteristics of severe malnutrition, including weight loss, hypoalbuminemia, hypoglycemia, hepatic steatosis and cholestasis. Low protein-fed mice had fewer mitochondria and showed signs of impaired mitochondrial function. Rapamycin prevented hepatic steatosis, restored ATP levels and fasted plasma glucose levels compared to untreated mice. This correlated with increased content of LC3-II, and decreased content mitochondrial damage marker, PINK1. We demonstrate that hepatic steatosis and disturbed mitochondrial function in a murine model of severe malnutrition can be partially prevented through inhibition of mTORC1. These findings suggest that stimulation of autophagy could be a novel approach to improve metabolic function in severely malnourished children.

Abstract Precapillary pulmonary hypertension (PHprecap) is a condition with elevated pulmonary vascular pressure and resistance. Patients have a poor prognosis and understanding the underlying pathophysiological mechanisms is crucial to guide and improve treatment. Ventricular hemodynamic forces (HDF) are a potential early marker of cardiac dysfunction, which may improve evaluation of treatment effect. Therefore, we aimed to investigate if HDF differ in patients with PHprecap compared to healthy controls. Patients with PHprecap (n = 20) and age- and sex-matched healthy controls (n = 12) underwent cardiac magnetic resonance imaging including 4D flow. Biventricular HDF were computed in three spatial directions throughout the cardiac cycle using the Navier–Stokes equations. Biventricular HDF (N) indexed to stroke volume (l) were larger in patients than controls in all three directions. Data is presented as median N/l for patients vs controls. In the RV, systolic HDF diaphragm-outflow tract were 2.1 vs 1.4 (p = 0.003), and septum-free wall 0.64 vs 0.42 (p = 0.007). Diastolic RV HDF apex-base were 1.4 vs 0.87 (p

Summary: Background: The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection and mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact processes such as SIRT1- and mTORC1-mediated autophagy and mitochondrial homeostasis. Using a mouse and organoid model of SM, we studied the repercussions of these dysregulations on malnutrition enteropathy and the protective capacity of maintaining autophagy activity and mitochondrial health. Methods: SM was induced through feeding male weanling C57BL/6 mice a low protein diet (LPD) for 14-days. Mice were either treated with the NAD+-precursor, nicotinamide; an mTORC1-inhibitor, rapamycin; a SIRT1-activator, resveratrol; or SIRT1-inhibitor, EX-527. Malnutrition enteropathy was induced in enteric organoids through amino-acid deprivation. Features of and pathways to malnutrition enteropathy were examined, including paracellular permeability, nutrient absorption, and autophagic, mitochondrial, and reactive-oxygen-species (ROS) abnormalities. Findings: LPD-feeding and ensuing low-tryptophan availability led to villus atrophy, nutrient malabsorption, and intestinal barrier dysfunction. In LPD-fed mice, nicotinamide-supplementation was linked to SIRT1-mediated activation of mitophagy, which reduced damaged mitochondria, and improved intestinal barrier function. Inhibition of mTORC1 reduced intestinal barrier dysfunction and nutrient malabsorption. Findings were validated and extended using an organoid model, demonstrating that resolution of mitochondrial ROS resolved barrier dysfunction. Interpretation: Malnutrition enteropathy arises from a dysregulation of the SIRT1 and mTORC1 pathways, leading to disrupted autophagy, mitochondrial homeostasis, and ROS. Whether nicotinamide-supplementation in children with SM could ameliorate malnutrition enteropathy should be explored in clinical trials. Funding: This work was supported by the Bill and Melinda Gates Foundation, the Sickkids Research Institute, the Canadian Institutes of Health Research, and the University Medical Center Groningen.

Sweden's fauna and flora are constantly changing. Humans have not only deliberately promoted and introduced new species in horticulture, agriculture and forestry, they have also acted as a vector for the introduction of alien species through, for example, transportation and food. When these species spread rapidly and affect biodiversity, they are deemed ‘invasive alien species’. This artistic research project explores and articulates how humans, as part of a system where nature and culture meet, affect complex functioning ecosystems through the movement of species. The starting point is the iconic elm tree and how its cultural and natural ecosystems have been wiped out in large parts of Europe by the invasive fungus Ophistoma novo ulmi. With the extinction of the elm come ecological and cultural losses. Those losses are examined and interpreted in this work, in a dialogue with nature and with people. At the same time, another species is explored, the Canadian goldenrod, which, unlike the elm, is expanding rapidly. With these explorations, life stories about the elm will be created not only for our collective memory, but also for speculation about what happens when a new and invasive alien species, such as the Canadian goldenrod, spreads. The form of my narrative is based in materials, crafts and objects. It is primarily the objects and the process that are the carriers of the stories. As a ceramicist, I use clay as a sketching material, binder and a tool for documentation. These species, the elm and the goldenrod, constitute the materiality that are part of the exploration and creation.

IntroductionThe suitability of whole-genome sequencing (WGS) as the sole method to detect clinically relevant genomic aberrations in B-cell acute lymphoblastic leukemia (ALL) was investigated with the aim of replacing current diagnostic methods.MethodsFor this purpose, we assessed the analytical performance of 150 bp paired-end WGS (90x leukemia/30x germline). A set of 88 retrospective B-cell ALL samples were selected to represent established ALL subgroups as well as ALL lacking stratifying markers by standard-of-care (SoC), so-called B-other ALL.ResultsBoth the analysis of paired leukemia/germline (L/N)(n=64) as well as leukemia-only (L-only)(n=88) detected all types of aberrations mandatory in the current ALLTogether trial protocol, i.e., aneuploidies, structural variants, and focal copy-number aberrations. Moreover, comparison to SoC revealed 100% concordance and that all patients had been assigned to the correct genetic subgroup using both approaches. Notably, WGS could allocate 35 out of 39 B-other ALL samples to one of the emerging genetic subgroups considered in the most recent classifications of ALL. We further investigated the impact of high (90x; n=58) vs low (30x; n=30) coverage on the diagnostic yield and observed an equally perfect concordance with SoC; low coverage detected all relevant lesions.DiscussionThe filtration of the WGS findings with a short list of genes recurrently rearranged in ALL was instrumental to extract the clinically relevant information efficiently. Nonetheless, the detection of DUX4 rearrangements required an additional customized analysis, due to multiple copies of this gene embedded in the highly repetitive D4Z4 region. We conclude that the diagnostic performance of WGS as the standalone method was remarkable and allowed detection of all clinically relevant genomic events in the diagnostic setting of B-cell ALL.

The accurate estimation of energy expenditure from simple objective accelerometry measurements provides a valuable method for investigating the effect of physical activity (PA) interventions or population surveillance. Methods have been evaluated previously, but none utilize the temporal aspects of the accelerometry data. In this study, we investigated the energy expenditure prediction from acceleration measured at the subjects’ hip, wrist, thigh, and back using recurrent neural networks utilizing temporal elements of the data. The acceleration was measured in children (N = 33) performing a standardized activity protocol in their natural environment. The energy expenditure was modelled using Multiple Linear Regression (MLR), stacked long short-term memory (LSTM) networks, and combined convolutional neural networks (CNN) and LSTM. The correlation and mean absolute percentage error (MAPE) were 0.76 and 19.9% for the MLR, 0.882 and 0.879 and 14.22% for the LSTM, and, with the combined LSTM-CNN, the best performance of 0.883 and 13.9% was achieved. The prediction error for vigorous intensities was significantly different (p < 0.01) from those of the other intensity domains: sedentary, light, and moderate. Utilizing the temporal elements of movement significantly improves energy expenditure prediction accuracy compared to other conventional approaches, but the prediction error for vigorous intensities requires further investigation.

This study investigates whether the quantity and quality of contact with migrants and perceiving that cultural diversity is accepted at school (as a dimension of the perceived school climate) are associated with perpetrating bullying toward migrant classmates. Quantity and quality of contact are also examined as moderators of the association between perceived cultural acceptance at school and bullying toward migrant students. One hundred and sixty-six adolescents (M[subscript age] = 16.26; SD = 1.53) belonging to the societal majority group answered a battery of self-report measures. Bullying migrant peers was associated with more negative quality of the contact. Bullying migrants was also associated with lower perceived acceptance of cultural diversity at school for the adolescents reporting higher levels of contact with migrants at school. The role of contact in explaining bullying toward migrant peers is also discussed in light of possible interventions.

Transition to low emission transportation and cleaner cities requires a broad introduction of low- and zero-carbon alternatives to conventional petrol- and diesel-powered vehicles. New-generation gas buses are a cost-effective way to reduce local air pollutants from urban transportation. Moreover, major greenhouse gas (GHG) savings may be achieved using biogas as the power source. The main objective of this research was to investigate CH4 and other gaseous emissions of a biogas-fueled urban bus equipped with a three-way catalyst (TWC) in real-world conditions. The study focused on emissions from a six-year-old gas-powered city bus, supplementing emission data from aging bus fleets. Impaired CH4 oxidation and NOx reduction were observed in the catalyst after its service life of 375,000 km–400,000 km. The main reason for low CH4 and NOx conversion over the TWC was concluded to be the partial deactivation of the catalyst. Another critical issue was the fluctuating air-to-fuel ratio. The results show that the efficiency of exhaust after-treatment systems should be closely monitored over time, as they are exposed to various aging processes under transient driving conditions, leading to increased real-world emissions. However, the well-to-wheels (WTW) analysis showed that an 80% GHG emission benefit could be achieved by switching from diesel to biomethane, giving a strong environmental argument for biogas use.

Abstract Pulmonary arterial hypertension (PAH) is a rare vasculopathy, with high morbidity and mortality. The sensitivity of the current european society of cardiology/european respiratory society (ESC/ERS) risk assessment strategy may be improved by the addition of biomarkers related to PAH pathophysiology. Such plasma‐borne biomarkers may also reduce time to diagnosis, if used as diagnostic tools in patients with unclear dyspnea, and in guiding treatment decisions. Plasma levels of proteins related to tumor necrosis factor (TNF), inflammation, and immunomodulation were analyzed with proximity extension assays in patients with PAH (n = 48), chronic thromboembolic pulmonary hypertension (PH; CTEPH, n = 20), PH due to left heart failure (HF) with preserved (HFpEF‐PH, n = 33), or reduced (HFrEF‐PH, n = 36) ejection fraction, HF without PH (n = 15), and healthy controls (n = 20). TNF‐related apoptosis‐inducing ligand (TRAIL) were lower in PAH versus the other disease groups and controls (p

Summary: Progressive multiple sclerosis (PMS) is currently diagnosed retrospectively. Here, we work toward a set of biomarkers that could assist in early diagnosis of PMS. A selection of cerebrospinal fluid metabolites (n = 15) was shown to differentiate between PMS and its preceding phenotype in an independent cohort (AUC = 0.93). Complementing the classifier with conformal prediction showed that highly confident predictions could be made, and that three out of eight patients developing PMS within three years of sample collection were predicted as PMS at that time point. Finally, this methodology was applied to PMS patients as part of a clinical trial for intrathecal treatment with rituximab. The methodology showed that 68% of the patients decreased their similarity to the PMS phenotype one year after treatment. In conclusion, the inclusion of confidence predictors contributes with more information compared to traditional machine learning, and this information is relevant for disease monitoring.

BackgroundClimate change has effects on multiple aspects of human life, such as access to food and water, expansion of endemic diseases as well as an increase of natural disasters and related diseases. The objective of this review is to summarize the current knowledge on climate change effects on military occupational health, military healthcare in a deployed setting, and defense medical logistics.MethodsOnline databases and registers were searched on August 22nd, 2022 and 348 papers retrieved, published between 2000 and 2022, from which we selected 8 publications that described climate effects on military health. Papers were clustered according to a modified theoretical framework for climate change effects on health, and relevant items from each paper were summarized.ResultsDuring the last decades a growing body of climate change related publications was identified, which report that climate change has a significant impact on human physiology, mental health, water- and vector borne infectious diseases, as well as air pollution. However, regarding the specific climate effects on military health the level of evidence is low. The effects on defense medical logistics include vulnerabilities in the cold supply chain, in medical devices functioning, in need for air conditioning, and in fresh water supply.ConclusionsClimate change may transform both the theoretical framework and practical implementations in military medicine and military healthcare systems. There are significant knowledge gaps on climate change effects on the health of military personnel in operations of both combat and non-combat nature, alerting the need for prevention and mitigation of climate-related health issues. Further research within the fields of disaster and military medicine is needed to explore this novel field. As climate effects on humans and the medical supply chain may degrade military capability, significant investments in military medical research and development are needed.

Abstract Background Physical inactivity is a main cause of childhood obesity which tracks into adulthood obesity, making it important to address early in life. Physical activity on prescription (PAP) is an evidence-based intervention that has shown good effect on physical activity levels in adults, but has not been evaluated in children with obesity. This project aims to evaluate the prerequisites, determinants, and feasibility of implementing PAP adapted to children with obesity and to explore children’s, parents’, and healthcare providers’ experiences of PAP. Methods In the first phase of the project, healthcare providers and managers from 26 paediatric clinics in Region Västra Götaland, Sweden, will be invited to participate in a web-based survey and a subset of this sample for a focus group study. Findings from these two data collections will form the basis for adaptation of PAP to the target group and context. In a second phase, this adapted PAP intervention will be evaluated in a clinical study in a sample of approximately 60 children with obesity (ISO-BMI > 30) between 6 and 12 years of age and one of their parents/legal guardians. Implementation process and clinical outcomes will be assessed pre- and post-intervention and at 8 and 12 months’ follow-up. Implementation outcomes are the four core constructs of the Normalization Process Theory; coherence, cognitive participation, collective action, and reflexive monitoring; and appropriateness, acceptability, and feasibility of the PAP intervention. Additional implementation process outcomes are recruitment and attrition rates, intervention fidelity, dose, and adherence. Clinical outcomes are physical activity pattern, BMI, metabolic risk factors, health-related quality of life, sleep, and self-efficacy and motivation for physical activity. Lastly, we will explore the perspectives of children and parents in semi-structured interviews. Design and analysis of the included studies are guided by the Normalization Process Theory. Discussion This project will provide new knowledge regarding the feasibility of PAP for children with obesity and about whether and how an evidence-based intervention can be fitted and adapted to new contexts and populations. The results may inform a larger scale trial and future implementation and may enhance the role of PAP in the management of obesity in paediatric health care in Sweden. Trial registration ClinicalTrials.gov Identifier: NCT04847271 , registered 14 April 2021.

Abstract Background Dental caries is a multifactorial disease that is highly dependent on diet, where a lower consumption and intake frequency of sugar would be favorable. The aims were (i) to examine dietary intake and meal patterns, more specifically sugar intake and foods high in sugar, among young adults with high caries activity, and (ii) to investigate the association between dietary and meal patterns consumption, and level of caries activity. Methods This study presents baseline data from an ongoing randomized controlled trial. A total of 50 young adults (aged 23.0 ± 3.0 years) with ≥ 2 decayed tooth surfaces were included. Dietary intake was captured with a 59-item food frequency questionnaire (FFQ) and a three-day food diary. Adherence to dietary guidelines was analyzed by comparing the dietary intake to the Nordic Nutritional Recommendations (NNR) 2012 and by using the Healthy Dietary Adherence score (HDAS). Participants were categorized into two groups: (i) the Caries group with 2–4 decayed surfaces, and (ii) the High caries group with ≥ 5 decayed surfaces. Results The High caries group reported a statistically significantly higher snack and total meal intake compared to the Caries group, as well as a sugar intake exceeding the Nordic nutritional recommendations. The majority of the participants reported a high intake frequency (> 2.5/day) of sweet foods and drinks and less than one intake of fruit and vegetables, respectively, per day. Similar results were found when analyzing adherence by using the HDAS, where the lowest adherence according to dietary guidelines was shown for the food groups of sugar, whole meal products, and fruit and vegetables. Conclusion The results indicated a high intake of sugar and low intake of fruit, vegetables, and fiber in high caries-active individuals.