Search

Abstract Background Partially driven by public concerns about modern food production practices, organic food has gained popularity among consumers. However, the impact of organic food consumption during pregnancy on offspring health is scarcely studied. We aimed to investigate the association between maternal intake of organic food during pregnancy and symptoms of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring at 8 years of age. Methods This study was based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). The total study sample included 40,707 mother–child pairs (children born 2002–2009). Organic food consumption during pregnancy was assessed by six questions from a food frequency questionnaire in mid-pregnancy (sum score 0–18). Symptoms of ADHD and ASD in the offspring aged 8 years were measured by ADHD (0–54) and ASD (0–39) symptom scores based on the Parent/Teacher Rating Scale for Disruptive Behaviour disorders and the Social Communication Questionnaire. Associations between maternal intake of organic food during pregnancy and symptoms of ADHD and ASD in the offspring were analyzed using regression models with adjustment for covariates such as maternal anxiety and depression, including sibling analysis. Results Mean ADHD and ASD symptom scores in the offspring differed only slightly by maternal intake of organic food. The covariate-adjusted unstandardized regression coefficient (adjusted(Adj)beta) with 95% confidence interval for the ADHD symptom score with one unit increase in organic food sum score was 0.03 (0.01, 0.05). Similarly, Adjbeta for autism symptom score was 0.07 (0.04, 0.10). For ADHD, the adjusted estimates weakened when adjusting for maternal symptoms of ADHD. The sibling analyses showed no significant results with Adjbeta − 0.07 (− 0.15, 0.01) and − 0.001 (− 0.12, 0.12) for ADHD and ASD outcomes, respectively. Conclusions We observed weak positive associations between frequent maternal organic food consumption during pregnancy and offspring ADHD and ASD symptom levels at 8 years of age. This trend weakened or disappeared after adjusting for maternal symptoms of ADHD, and in sibling analyses, suggesting that the associations mainly reflect genetic confounding. Our study indicates that consumption of organic food during pregnancy should neither be considered a risk factor nor protective against symptoms of ADHD and ASD in offspring.

Abstract Background Schistosomiasis remains a public health problem, particularly in sub-Saharan Africa. The disease is intimately connected to poverty and environmental factors. Our research was readily embedded into a multi-country schistosomiasis oversampling study. The aim of the study presented here was to determine the prevalence of Schistosoma mansoni and to investigate the role of water body characteristics and water-related human activities in disease transmission. Methods In August and September 2022, a cross-sectional study was conducted in the western part of Côte d’Ivoire. Stool and urine samples were collected from 1602 and 1729 children aged 5–14 years, respectively, in 65 villages in the health districts of Biankouma, Ouaninou and Touba. Additionally, data were collected from direct observation of water-related activities at water bodies and interviews conducted with community leaders and health workers. The prevalence and risk factors for Schistosoma infection were assessed using generalised estimating equation models. Results The prevalence ofS. mansoni and S. haematobium were 27.4% (95% confidence interval [CI] 21.5–34.3%) and 0.1% (95% CI 0.03–0.5%), respectively. Low prevalence of soil-transmitted helminths was observed with 2.4%, 0.4% and 0.2% for hookworm, Trichuris trichiura and Ascaris lumbricoides, respectively. At the health district level, we found S. mansoni prevalence of 34.4% (95% CI 25.0–45.3%), 34.3% (95% CI 24.0–46.2%) and 16.3% (95% CI 9.5–26.6%) for Biankouma, Ouaninou and Touba, respectively. Female and male participants were at a similar risk of infection (29.0% vs. 26.0%, odds ratio [OR]: 1.18, 95% CI 0.92–1.50). Children aged 9–14 years showed a higher prevalence than their younger counterparts aged 5–8 years (34.5% vs. 22.7%, OR: 1.80, 95% CI 1.42–2.27). High infection prevalence was observed in villages where children were washing clothes and dishes at open surface water sites and pursued recreational activities (e.g. swimming and playing in the water). The temperature, total dissolved solids and pH of water samples showed no significant association with S. mansoni infection at the village unit. Conclusions Human water-related activities such as washing clothes and playing in the water are risk factors for S. mansoni transmission. Hence, preventive chemotherapy should be combined with information, education and communication to avoid or reduce the frequency of water exposure in children as part of a comprehensive package of interventions towards elimination of schistosomiasis as a public health problem. Graphical Abstract

Abstract Background Respiratory syncytial virus (RSV) is the most common cause of hospitalisation in infants aged ≤ 6 months in Western countries. Nearly 1,500 infants under six months of age are hospitalised with RSV annually in Denmark. This nationwide study describes the healthcare resource utilisation and costs related to RSV hospitalisation in this vulnerable age group. Methods RSV cases were identified in the Danish National Patient Register. Infants were included if they at the age of 0–5 months had a (1) respiratory related hospital admission (duration > 12 h), (2) within 10 days of a positive RSV test, (3) between January 2013 and December 2022. Each case was matched with five individuals never diagnosed with RSV on age, sex, region of residence, birth (pre/full term), number of siblings

Fatigue behind the wheel has been addressed repeatedly for at least 15 years. Various research projects, studies, and systems have been developed to prove the effect of fatigue on the number of accidents and possibly to inform drivers that this situation has occurred. The article examines the influence of stimulants on the fatigue of young agricultural machinery drivers. Commonly available means for reducing driver fatigue were chosen as stimulants (coffee, tea, maté, guarana, energy drink, lemon extract with sugar). A special test station with automatic reaction time evaluation was developed to test drivers' reaction ability (responsiveness). Furthermore, the effects on the physical condition of the tested persons (systolic blood pressure, diastolic blood pressure, blood pressure amplitude and heart rate) were investigated. The conducted experiments confirmed a statistically significant effect of all tested stimulants, except for tea, for which no statistically significant changes in the monitored parameters were observed.

Temperature is a key parameter that influences the uptake and subsequent utilization of nitrogen by plants. Both suboptimal and supraoptimal temperatures can impair nutrient uptake. The close relatives of bread wheat provide a possible source for breeders to increase stress tolerance. The effect of the increasing temperature (5, 10, 15, 20 and 30 °C) on nitrate uptake and metabolism in five modern spring cultivars of bread wheat (Triticum aestivum L.) and two cultivars of emmer wheat (Triticum dicoccon Schrank), was monitored. Wheat plants were grown under controlled conditions in hydroponics. The parameters of Michaelis-Menten kinetics, maximum uptake rate (Vmax), the Michaelis constant (Km) and selected characteristics of nitrate metabolism, the activity of nitrate reductase (NR) and contents of nitrate in leaves were observed. The effect of temperature was significant for all studied traits except Km, while the cultivar factor was significant for Vmax, Km, NR and root/shoot ratio (R/S). Emmer wheat cultivar Rudico had significantly higher Vmax at 5, 15, 20 and 30 °C than all bread wheat cultivars, on average 7.07, in comparison with 4.09-4.43 μmol NO3-/g FW/h in bread wheat cultivars. Emmer wheat Rudico and Tapiruz had significantly higher Km (on average, 41.59 and 47.22 μM NO3-) than bread wheat cultivars (27.59-33.44 μM NO3-). Differences in the studied kinetic parameters of nitrate uptake offer the possibility of using T. dicoccon genotypes in breeding for better nitrogen use efficiency.

Abstract Accurate population data is crucial for assessing exposure in disaster risk assessments. In recent years, there has been a significant increase in the development of spatially gridded population datasets. Despite these datasets often using similar input data to derive population figures, notable differences arise when comparing them with direct ground-level observations. This study evaluates the precision and accuracy of flood exposure assessments using both known and generated gridded population datasets in Sweden. Specifically focusing on WorldPop and GHSPop, we compare these datasets against official national statistics at a 100 m grid cell resolution to assess their reliability in flood exposure analyses. Our objectives include quantifying the reliability of these datasets and examining the impact of data aggregation on estimated flood exposure across different administrative levels. The analysis reveals significant discrepancies in flood exposure estimates, underscoring the challenges associated with relying on generated gridded population data for precise flood risk assessments. Our findings emphasize the importance of careful dataset selection and highlight the potential for overestimation in flood risk analysis. This emphasises the critical need for validations against ground population data to ensure accurate flood risk management strategies.

Abstract Background Modeling patient data, particularly electronic health records (EHR), is one of the major focuses of machine learning studies in healthcare, as these records provide clinicians with valuable information that can potentially assist them in disease diagnosis and decision-making. Methods In this study, we present a multi-level graph-based framework called MedMGF, which models both patient medical profiles extracted from EHR data and their relationship network of health profiles in a single architecture. The medical profiles consist of several layers of data embedding derived from interval records obtained during hospitalization, and the patient-patient network is created by measuring the similarities between these profiles. We also propose a modification to the Focal Loss (FL) function to improve classification performance in imbalanced datasets without the need to imputate the data. MedMGF’s performance was evaluated against several Graphical Convolutional Network (GCN) baseline models implemented with Binary Cross Entropy (BCE), FL, class balancing parameter $$\alpha$$ α , and Synthetic Minority Oversampling Technique (SMOTE). Results Our proposed framework achieved high classification performance (AUC: 0.8098, ACC: 0.7503, SEN: 0.8750, SPE: 0.7445, NPV: 0.9923, PPV: 0.1367) on an extreme imbalanced pediatric sepsis dataset (n=3,014, imbalance ratio of 0.047). It yielded a classification improvement of 3.81% for AUC, 15% for SEN compared to the baseline GCN+ $$\alpha$$ α FL (AUC: 0.7717, ACC: 0.8144, SEN: 0.7250, SPE: 0.8185, PPV: 0.1559, NPV: 0.9847), and an improvement of 5.88% in AUC and 22.5% compared to GCN+FL+SMOTE (AUC: 0.7510, ACC: 0.8431, SEN: 0.6500, SPE: 0.8520, PPV: 0.1688, NPV: 0.9814). It also showed a classification improvement of 3.86% for AUC, 15% for SEN compared to the baseline GCN+ $$\alpha$$ α BCE (AUC: 0.7712, ACC: 0.8133, SEN: 0.7250, SPE: 0.8173, PPV: 0.1551, NPV: 0.9847), and an improvement of 14.33% in AUC and 27.5% in comparison to GCN+BCE+SMOTE (AUC: 0.6665, ACC: 0.7271, SEN: 0.6000, SPE: 0.7329, PPV: 0.0941, NPV: 0.9754). Conclusion When compared to all baseline models, MedMGF achieved the highest SEN and AUC results, demonstrating the potential for several healthcare applications.

Abstract Pesticides applied to soil surface are subject to photodegradation if the parent molecule is sensitive to UV-light absorption. Photodegradation studies are therefore mandatory for the registration of plant protection products to provide data on the degradation rate and on the nature of photoproducts formed. In general, sunlight is simulated in these studies with xenon lamps, e.g., a Suntest® device. Surface application on very thin soil layers followed by direct irradiation is common practice, but the control of the boundary conditions, i.e. soil temperature and moisture, to maintain the structure and viability of the soil is challenging. A homogeneous and stable soil microclimate is crucial to compare the degradation data of the test item from the irradiated soil samples to the dark controls as well as to the results from the aerobic soil metabolism study. After trying different scale-up test systems with the UV-sensitive herbicide imazamox as comparative test item, a new soil photolysis test system was developed which is manageable in the laboratory and enables a more favorable management of the boundary conditions, especially with regard to the soil moisture and temperature. For this, the solar simulator SolarConstant® 1200, equipped with metal halide lamps Radium HRI-TS 1000W/D/S/PRO, was installed by Atlas Ametek (Germany) in a temperature controllable walk-in incubation chamber with aluminum racks and reflectors to minimize diffuse light and to maintain a homogenous temperature of 22(± 1)°C within the irradiated soil. Borosilicate glass vessels with an inner diameter of 10 cm and a maximum height of 9 cm, covered by quartz glass, were used for the incubation of the applied soil under light. Contrary to the imazamox degradation half-lives obtained with the Suntest® test system, where an unusual slower degradation was observed under light compared to the dark controls, the results from the new SolarConstant® study design showed the expected faster degradation under light. Hence, it can be concluded that the experimental boundary conditions of the new test system are more suitable to maintain the viablity of the irradiated soil. Since no adjustments of the soil water content were needed, compared to daily water adjustments for thin soil layers incubated under a Suntest®, drying–wetting cycles are eliminated and microbial-induced soil processes are maintained.

Abstract Background Adolescents with attention-deficit / hyperactivity disorder (ADHD) have an increased risk of self-harm. The risk of self-harm among adolescents who display an elevated level of ADHD symptoms, but without a formal diagnosis, is not well-studied and understood. Objective To investigate the relationship between self-reported symptoms of ADHD and self-harm in a population-based sample of adolescents. Methods Adolescents in the population-based youth@hordaland study were invited to complete the Adult ADHD Self-Report Scale (ASRS) and the Short Mood and Feelings Questionnaire (SMFQ). They were asked whether they ever deliberately have taken an overdose or tried to harm themselves on purpose, once or multiple times, defined according to the code used in the Child and Adolescent Self-harm in Europe (CASE) Study. Adolescents reporting severe problems on ≥ four of six selected items on the ASRS-v 1.1 screener were defined as ADHD-screen positive (ADHD-SC+), and the remaining sample as ADHD-screen negative (ADHD-SC-). SMFQ score ≥ 12 was used to define a high level of depressive symptoms. Results A total of 9692 adolescents (mean age 17.4 years, 53.1% females) participated in the study, of which 2390 (24.7%) screened positive on the ASRS. ADHD-SC+ adolescents engaged in self-harm more often than the ADHD-SC- group (14.6% vs. 5.4%, OR = 3.02, 95%CI [2.57–3.24]). This remained significant after adjustment for demographic variables, SMFQ score ≥ 12, symptoms of conduct disorder and familial history of self-harm and suicide attempts (OR = 1.58, 95%CI [1.31–1.89]). They were also more likely to report an overdose as their method of self-harm (OR = 1.52, 95%CI [1.05–2.23]). Within the ADHD-SC+ group female sex, high levels of inattention and hyperactivity/impulsivity symptoms, SMFQ score ≥ 12, symptoms indicating conduct disorder and familial history of self-harm and suicide attempts increased the likelihood of engaging in deliberate self-harm. Conclusion Adolescents who screened positive for ADHD had increased risk of engaging in self-harm. Clinicians should consider the increased risk of such engagement in adolescents who present with high level of ADHD symptoms, even in the absence of a clinical ADHD diagnosis.

Abstract Mitochondrial dysregulation plays a significant role in the carcinogenesis. On the other hand, its destabilization strongly represses the viability and metastatic potential of cancer cells. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities. Cyanine dyes, with strong mitochondrial selectivity, show significant potential in enhancing PDT and PTT. The potential and limitations of cyanine dyes for mitochondrial PDT and PTT are discussed, along with their applications in combination therapies, theranostic techniques, and optimal delivery systems. Additionally, novel approaches for sonodynamic therapy using photoactive cyanine dyes are presented, highlighting advances in cancer treatment.

Abstract Background Pediatric sepsis remains a leading cause of childhood morbidity and mortality worldwide. Despite advancements in modern medicine, it accounts for more than 3 million childhood deaths per year. Multiple studies have emphasized that sex and gender have an impact on the treatment and outcome of various diseases. Adult studies have revealed sex differences in pathophysiological responses to septic shock, as well as a possible protective effect of estrogens on critical illness. Sex-specific maturational and developmental differences in host immunology have been previously demonstrated for neonatal and pediatric age groups. At present, there are no studies assessing the impact of sex on outcomes of children with sepsis. Methods The goal of this study is to assess sex-specific differences in childhood sepsis survival outcomes. We will systematically assess associations of sex and gender with outcomes in pediatric sepsis in the literature by performing a systematic search of MEDLINE and Embase databases. We will include all English language randomized trials and cohort studies. The study population will include children > 37 weeks gestational age and

Abstract Introduction Sepsis is associated with neurocognitive impairment among preterm neonates but less is known about term neonates with sepsis. This systematic review and meta-analysis aims to provide an update of neurocognitive outcomes including cognitive delay, visual impairment, auditory impairment, and cerebral palsy, among neonates with sepsis. Methods We performed a systematic review of PubMed, Embase, CENTRAL and Web of Science for eligible studies published between January 2011 and March 2023. We included case–control, cohort studies and cross-sectional studies. Case reports and articles not in English language were excluded. Using the adjusted estimates, we performed random effects model meta-analysis to evaluate the risk of developing neurocognitive impairment among neonates with sepsis. Results Of 7,909 studies, 24 studies (n = 121,645) were included. Majority of studies were conducted in the United States (n = 7, 29.2%), and all studies were performed among neonates. 17 (70.8%) studies provided follow-up till 30 months. Sepsis was associated with increased risk of cognitive delay [adjusted odds ratio, aOR 1.14 (95% CI: 1.01—1.28)], visual impairment [aOR 2.57 (95%CI: 1.14- 5.82)], hearing impairment [aOR 1.70 (95% CI: 1.02–2.81)] and cerebral palsy [aOR 2.48 (95% CI: 1.03–5.99)]. Conclusion Neonates surviving sepsis are at a higher risk of poorer neurodevelopment. Current evidence is limited by significant heterogeneity across studies, lack of data related to long-term neurodevelopmental outcomes and term infants.

Abstract Nicotine intake is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in rodents and humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning. We conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n = 88). Our results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to enhanced physiological arousal to learned threats and overactivation of the ventral tegmental area. This study provides mechanistic evidence that single doses of nicotine impair neural substrates of adaptive aversive learning in line with the risk for the development of pathological anxiety.

Abstract Avoidance is an essential behaviour for ensuring safety in uncertain and dangerous environments. One way to learn what is dangerous and must be avoided is through observational threat learning. This online study explored the behavioural implications of observed threat learning, examining how participants avoided or approached a learned threat and how this affected their movement patterns. Participants (n = 89) completed an observational threat learning task, rating their fear, discomfort, and physical arousal in response to conditioned stimuli. The retrieval of learned threat was reassessed 24 h later, followed by a reminder of the observed threat associations. Participants subsequently completed a computerised avoidance task, in which they navigated from a starting point to an endpoint by selecting one of two doors, each associated with either safety or danger, relying on observed information. Opting for the safe door entailed increased effort to attain the goal. Results demonstrated that observational threat learning influenced avoidance behaviour and decision-making dependent on baseline effort level. Participants tended to exhibit thigmotaxis, staying close to walls and taking extra steps to reach their goal. This behaviour indirectly mediated the number of steps taken. This study provides valuable insights into avoidance behaviour following observational threat learning in healthy humans.

Abstract Background Pathological complete response (pCR) is a well-established prognostic factor in breast cancer treated with neoadjuvant systemic therapy (naST). The determining factors of pCR are known to be intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage as well as type of systemic therapy. The addition of neoadjuvant radiotherapy (naRT) to this paradigm might improve response, freedom from disease, toxicity and cosmetic outcome compared to adjuvant radiotherapy. The factors for pCR and primary tumor regression when neoadjuvant radiation therapy is added to chemotherapy have not been thoroughly described. Methods We performed a retrospective analysis of 341 patients (cT1-cT4/cN0-N+) treated with naRT and naST between 1990 and 2003. Patients underwent naRT to the breast and mostly to the supra-/infraclavicular lymph nodes combined with an electron or brachytherapy boost. NaST was given either sequentially or simultaneously to naRT using different regimens. We used the univariate and multivariate regression analysis to estimate the effect of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) as well as complete primary tumor response (ypT0/Tis; bpCR) in our cohort. Receiver operating characteristic (ROC) analysis was performed to evaluate the interval between radiotherapy (RT) and resection (Rx) as well as radiotherapy dose. Results Out of 341 patients, pCR and pbCR were achieved in 31% and 39%, respectively. pCR rate was influenced by resection type, breast cancer subtype, primary tumor stage and interval from radiation to surgery in the multivariate analysis. Univariate analysis of bpCR showed age, resection type, breast cancer subtype, clinical tumor stage and grading as significant factors. Resection type, subtype and clinical tumor stage remained significant in multivariate analysis. Radiation dose to the tumor and interval from radiation to surgery were not significant factors for pCR. However, when treatment factors were added to the model, a longer interval from radiotherapy to resection was a significant predictor for pCR. Conclusions The factors associated with pCR following naST and naRT are similar to known factors after naST alone. Longer interval to surgery might to be associated with higher pCR rates. Dose escalation beyond 60 Gy did not result in higher response rates.

Abstract Background Inequity in healthcare utilisation refers to differences between groups that remain after adjustment for need for health care. To our knowledge, no previous studies have aimed to assess social inequity in chiropractic utilisation in a general population. Therefore, the objective of this study was to evaluate social inequity in chiropractic utilisation in the general Danish population adjusted for health status as a proxy of need for chiropractic care. Methods A population-based repeated cross-sectional study design was used based on the Danish National Health Survey in 2010 and 2017. Overall, we included 288,099 individuals aged 30 years or older in 2010 or 2017. For each individual, information on chiropractic utilisation, socioeconomic status, and health status as a proxy of need for chiropractic care was retrieved from nationwide registers using the unique personal identification number. Measures of health status included demographics, poor self-rated physical health, activity limitations, musculoskeletal pain, number of musculoskeletal conditions, and number of chronic diseases. We investigated social inequity in chiropractic utilisation (yes, no) using logistic regression adjusted for health status, stratified by sex and year. Three characteristics of socioeconomic status (educational level, employment status and income) were investigated. To further quantify the degree of social inequity in chiropractic utilisation, we estimated the concentration index of inequity for each of the three characteristics of socioeconomic status. Results We found significantly higher odds of chiropractic utilisation among individuals with short or medium/long education compared with individuals with elementary education, and among employed individuals compared with individuals who were unemployed, receiving disability pension or retired. Furthermore, the odds of chiropractic utilisation increased with higher income. The concentration index indicated social inequity in chiropractic utilisation in favour of individuals with higher socioeconomic status, with income and employment status contributing more to inequity than educational level. Conclusion The study demonstrated social inequity in chiropractic utilisation in Denmark beyond differences in health status as a proxy of need for chiropractic care in the general population. The results suggest that new strategies are required if equal treatment for equal need is the goal.

Abstract The study aimed to investigate differences in hypertensive‐ and cardio‐preventive pharmacotherapy depending on if patients with hypertension received lifestyle counseling or not, including the difference between men and women. Data from the Region Stockholm VAL database was used to identify all patients with a hypertension diagnosis and had visited a primary health care center within the past five years. Data included registered diagnoses, pharmacotherapy, and codes for lifestyle counseling. Logistic regression adjusted for age and comorbidity (diabetes, stroke, coronary heart disease, atrial fibrillation, gout, obesity, heart failure) was used, presenting results as odds ratios (OR) with 99% confidence interval (CI). The study included 130,030 patients with hypertension; 63,402 men and 66,628 women. Patients receiving recommended lifestyle counseling were more frequently treated with three or more hypertensive drugs: women OR 1.38 (1.31, 1.45) and men = 1.36 (1.30, 1.43); certain drug classes: calcium antagonists: women 1.09 (1.04, 1.14) and men 1.11 (1.06, 1.16); thiazide diuretics: women 1.26 (1.20, 1.34) and men 1.25 (1.19, 1.32); and aldosterone antagonists: women 1.25 (1.12, 1.41) and men 1.49 (1.34, 1.65). Patients receiving recommended level of lifestyle counseling with concomitant coronary heart disease, atrial fibrillation, diabetes, or stroke were more frequently treated with statins than those who did not. Further, recommended lifestyle counseling was significantly associated with anticoagulant treatment in patients with atrial fibrillation. Lifestyle counseling according to recommendations in national guidelines was significantly associated with a more thorough pharmacological treatment of hypertension, statins, and antithrombotic drugs as well as anticoagulants, in both men and women.

Abstract Background After decades of praziquantel mass drug administration (MDA), several countries approach schistosomiasis elimination. Continuing MDA in largely uninfected populations no longer seems justified. Alternative interventions to maintain the gains or accelerate interruption of transmission are needed. We report results, strengths, and shortcomings of novel test-treat-track-test-treat (5T) interventions in low Schistosoma haematobium prevalence areas on Pemba, Tanzania. Methods School- and household-based surveys were conducted in 2021 and 2022 to monitor the S. haematobium and microhematuria prevalence and assess the impact of interventions. In 2021, 5T interventions were implemented in 15 low-prevalence areas and included: (i) testing schoolchildren in primary and Islamic schools for microhematuria as a proxy for S. haematobium, (ii) treating positive children, (iii) tracking them to their households and to water bodies they frequented, (iv) testing individuals at households and water bodies, and (v) treating positive individuals. Additionally, test-and-treat interventions were implemented in the 22 health facilities of the study area. Results The S. haematobium prevalence in the school-based survey in 15 low-prevalence implementation units was 0.5% (7/1560) in 2021 and 0.4% (6/1645) in 2022. In the household-based survey, 0.5% (14/2975) and 0.7% (19/2920) of participants were infected with S. haematobium in 2021 and 2022, respectively. The microhematuria prevalence, excluding trace results, in the school-based survey was 1.4% (21/1560) in 2021 and 1.5% (24/1645) in 2022. In the household-based survey, it was 3.3% (98/2975) in 2021 and 5.4% (159/2920) in 2022. During the 5T interventions, the microhaematuria prevalence was 3.8% (140/3700) and 5.8% (34/594) in children in primary and Islamic schools, respectively, 17.1% (44/258) in household members, and 16.7% (10/60) in people at water bodies. In health facilities, 19.8% (70/354) of patients tested microhematuria-positive. Conclusions The targeted 5T interventions maintained the very low S. haematobium prevalence and proved straightforward and feasible to identify and treat many of the few S. haematobium-infected individuals. Future research will show whether 5T interventions can maintain gains in the longer-term and expedite elimination. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493 .

Abstract SuperWIMPs are extremely weakly interacting massive particles that inherit their relic abundance from late decays of frozen-out parent particles. Within supersymmetric models, gravitinos and axinos represent two of the most well motivated superWIMPs. In this paper we revisit constraints on these scenarios from a variety of cosmological observations that probe their production mechanisms as well as the superWIMP kinematic properties in the early Universe. We consider in particular observables of Big Bang Nucleosynthesis and the Cosmic Microwave Background (spectral distortion and anisotropies), which limit the fractional energy injection from the late decays, as well as warm and mixed dark matter constraints derived from the Lyman- $$\alpha $$ α forest and other small-scale structure observables. We discuss complementary constraints from collider experiments, and argue that cosmological considerations rule out a significant part of the gravitino and the axino superWIMP parameter space.

The year 2024 marks 20 years since Poland joined the European Union. In this paper, the authors review the economic literature analysing the long-term economic effects of Poland’s membership in the EU. Their study is based on international and Polish literature referring mainly to partial and general equilibrium analyses. They show both the sectoral effects, as related to different EU policies, as well as the overall consequences of membership for the level of welfare of Polish society. The authors first discuss the trade effects in the context of the removal of barriers to the movement of goods within the Single European Market. Next, the consequences of the inflow of funds from the EU budget which finance the country’s structural funds and the Common Agricultural Policy, which are of particular importance to the Polish economy are discussed. A review of the consequences of the inflow of foreign direct investment from EU countries to Poland and the effects of labour migration within the EU is then conducted. A review of the related welfare consequences by aggregating the effects of individual policies and making an overall assessment based on a synthetic control method is then summarised. The authors then refer to their estimations showing that, thanks to EU accession, Poland’s GDP per capita 15 years after accession was higher by almost 55% compared to the counterfactual scenario of non-accession.

The process of procuring military equipment, technology, material, and associated services (VM) is frequently shrouded in concerns about cost-effectiveness and, in some instances, even becomes the focus of law enforcement investigations. This often leads to delays in strategic investments and exposes involved individuals to the risk of criminal charges. Additionally, there is a notable lack of capacity to impartially evaluate the overall investment's efficacy. Consequently, the "Znalec" (Expert Witness) project was initiated as a part of the defense research program. Its objective is to explore the feasibility of establishing an expert institute that could impartially assess the value of the military procurements, set a standard for evaluating these assets, and outline a training program for relevant experts. This paper specifically addresses the first objective of the project, proposing a legal framework for the expert institute based on an extensive systems analysis.

Abstract Background The inclusion of biomarkers could improve diagnostic accuracy of attention-deficit/hyperactivity disorder (ADHD). One potential biomarker is the ADHD polygenic score (PGS), a measure of genetic liability for ADHD. This study aimed to investigate if the ADHD PGS can provide additional information alongside ADHD rating scales and examination of family history of ADHD to distinguish between ADHD cases and controls. Methods Polygenic scores were calculated for 576 adults with ADHD and 530 ethnically matched controls. ADHD PGS was used alongside scores from the Wender-Utah Rating Scale (WURS) and the Adult ADHD Self-Report Scale (ASRS) as predictors of ADHD diagnosis in a set of nested logistic regression models. These models were compared by likelihood ratio (LR) tests, Akaike information criterion corrected for small samples (AICc), and Lee R². These analyses were repeated with family history of ADHD as a covariate in all models. Results The ADHD PGS increased the variance explained of the ASRS by 0.58% points (pp) (R2 ASRS = 61.11%, R2 ASRS + PGS=61.69%), the WURS by 0.61pp (R2 WURS = 77.33%, R2 WURS + PGS= 77.94%), of ASRS and WURS together by 0.57pp (R2 ASRS + WURS=80.84%, R2 ASRS + WURS+PGS=81.40%), and of self-reported family history by 1.40pp (R2 family = 28.06%, R2 family + PGS=29.46%). These increases were statistically significant, as measured by LR tests and AICc. Conclusion We found that the ADHD PGS contributed additional information to common diagnostic aids. However, the increase in variance explained was small, suggesting that the ADHD PGS is currently not a clinically useful diagnostic aid. Future studies should examine the utility of ADHD PGS in ADHD prediction alongside non-genetic risk factors, and the diagnostic utility of the ADHD PGS should be evaluated as more genetic data is accumulated and computational tools are further refined.

Abstract Background Schistosomiasis is a debilitating neglected tropical disease endemic in sub-Saharan Africa. The role of health facilities in the prevention, diagnosis, control, and elimination of schistosomiasis is poorly documented. In a setting targeted for schistosomiasis elimination in Zanzibar, we assessed the prevalence of Schistosoma haematobium among patients seeking care in a health facility and investigated schistosomiasis-related knowledge of staff, and health facilities’ capacities and needs for schistosomiasis diagnosis and management. Methods We conducted a health facility-based mixed-method study on Pemba Island from June to August 2023. Patients aged ≥ 4 years seeking care in four health facilities were screened for S. haematobium infection using urine filtration and reagent strips. Those patients aged ≥ 10 years were additionally interviewed about signs and symptoms. Staff from 23 health facilities responded to a questionnaire assessing knowledge and practices. Ten staff participated in a focus group discussion (FGD) about capacities and needs for schistosomiasis diagnosis and management. Results The prevalence of S. haematobium infection in patients attending the health facilities, as determined by the presence of eggs in urine, was 1.1% (8/712). Microhaematuria was detected in 13.3% (95/712) of the patients using reagent strips. Among patients responding to the questionnaire, pelvic pain, pain during sex, and painful urination were reported by 38.0% (237/623), 6.3% (39/623), and 3.2% (20/623), respectively. Among the health facility staff, 90.0% (44/49) and 87.8% (43/49) identified blood in urine and pelvic pain, respectively, as symptoms of urogenital schistosomiasis, 81.6% (40/49) and 93.9% (46/49) reported collecting a urine sample and pursuing a reagent strip test, respectively, for diagnosis, and 87.8% (43/49) administered praziquantel for treatment. The most reoccurring themes in the FGD were the need for more staff training about schistosomiasis, requests for diagnostic equipment, and the need to improve community response to schistosomiasis services in health facilities. Conclusions The prevalence of S. haematobium infection in patients seeking care in health facilities in Pemba is very low and similar to what has been reported from recent community-based cross-sectional surveys. The health facility staff had good schistosomiasis-related knowledge and practices. However, to integrate schistosomiasis patient management more durably into routine health facility activities, scalable screening pathways need to be identified and capacities need to be improved by regular staff training, and an unbroken supply of accurate point-of-care diagnostics and praziquantel for the treatment of cases. Graphical abstract

Abstract Generative models have demonstrated substantial promise in Natural Language Processing (NLP) and have found application in designing molecules, as seen in General Pretrained Transformer (GPT) models. In our efforts to develop such a tool for exploring the organic chemical space in search of potentially electro-active compounds, we present Llamol, a single novel generative transformer model based on the Llama 2 architecture, which was trained on a 12.5M superset of organic compounds drawn from diverse public sources. To allow for a maximum flexibility in usage and robustness in view of potentially incomplete data, we introduce Stochastic Context Learning (SCL) as a new training procedure. We demonstrate that the resulting model adeptly handles single- and multi-conditional organic molecule generation with up to four conditions, yet more are possible. The model generates valid molecular structures in SMILES notation while flexibly incorporating three numerical and/or one token sequence into the generative process, just as requested. The generated compounds are very satisfactory in all scenarios tested. In detail, we showcase the model’s capability to utilize token sequences for conditioning, either individually or in combination with numerical properties, making Llamol a potent tool for de novo molecule design, easily expandable with new properties. Scientific contribution We developed a novel generative transformer model, Llamol, based on the Llama 2 architecture that was trained on a diverse set of 12.5 M organic compounds. It introduces Stochastic Context Learning (SCL) as a new training procedure, allowing for flexible and robust generation of valid organic molecules with up to multiple conditions that can be combined in various ways, making it a potent tool for de novo molecular design.

Abstract Background Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an ultra-rare, autosomal-dominant small vessel disease caused by loss-of-function variants in the gene TREX1. Recently, elevated serum levels of von Willebrand Factor Antigen (vWF-Ag) pointed to an underlying endotheliopathy, and microvascular ischemia was suggested to contribute to the neurodegeneration in RVCL-S. Aim of this study was to further elucidate the endotheliopathy in RVCL-S. Methods vWF-Ag and ADAMTS-13 activity were repeatedly measured in two patients with genetically confirmed RVCL-S. Renal biopsy of both RVCL-S patients and autoptic brain, renal, hepatic, and pulmonary specimen of one patient with RVCL-S were examined immunohistochemically in comparison to matched controls. In addition, cerebral methylome analysis was performed in the autoptic brain specimen calculating differentially methylated positions compared to controls. Results While vWF-Ag and activity was strongly elevated, ADAMTS-13 activity was low in RVCL-S and further decreased over the course of the disease. Autoptic brain specimen showed signs of thromboinflammation in cerebral small vessels, and vWF-Ag staining was strongly positive in cerebral and renal small vessels in RVCL-S, while only a light to moderate vWF-Ag staining was found in controls. Cerebral methylome analysis yielded 115 differentially methylated CpGs (p

Abstract This review aims at providing an extensive discussion of modern constraints relevant for dense and hot strongly interacting matter. It includes theoretical first-principle results from lattice and perturbative QCD, as well as chiral effective field theory results. From the experimental side, it includes heavy-ion collision and low-energy nuclear physics results, as well as observations from neutron stars and their mergers. The validity of different constraints, concerning specific conditions and ranges of applicability, is also provided.

Summary: Difference-in-differences (DID) is a key tool for causal impact evaluation but faces challenges when applied to sensitive data restricted by privacy regulations. Obtaining consent can shrink sample sizes and reduce statistical power, limiting the analysis’s effectiveness. Federated learning addresses these issues by sharing aggregated statistics rather than individual data, though advanced federated DID software is limited. We developed a federated version of the Callaway and Sant’Anna difference-in-differences (CSDID), integrated into the DataSHIELD platform, adhering to stringent privacy protocols. Our approach reproduces key estimates and standard errors while preserving confidentiality. Using simulated and real-world data from a malaria intervention in Mozambique, we demonstrate that federated estimates increase sample sizes, reduce estimation uncertainty, and enable analyses when data owners cannot share treated or untreated group data. Our work contributes to facilitating the evaluation of policy interventions or treatments across centers and borders.

Introduction: The present study evaluated the consistency and reliability of five anatomical landmarks in the external auditory meatus using CBCT (cone beam computed tomography) scans. The goal was to determine if these landmarks could reliably replace the commonly used point Porion for superimposing CBCT scans in clinical practice. Consistent anatomical features in the external auditory meatus are essential for accurate cranial assessments in dentistry and medicine. Despite their importance, these features have been underexplored, making this study a valuable contribution to improving clinical evaluation accuracy. Materials and methods: 22 CBCT scans were analyzed using ITK-Snap software. The shape of the External Auditory Meatus had been rendered by segmentation. These segmentations were used as a basis to locate the landmarks. The spread in location of the suggested landmarks concerning a reference coordinate system was treated as a measure for consistency. For that purpose, the absolute mean distance from all registered landmarks to the center of the location cloud was calculated for each dataset. Results: The smallest spread in locations was measured for the so-called Epitympanic Notch, with 4.3 mm on average (SD 1.7). However, recognizing this landmark in the segmented images appeared to be relatively difficult. The landmark with the second smallest spread in locations (4.4 mm (SD 2.2)) and an easier recognition in the segmented image was the most superior point of the external auditory meatus. The most inferior point appeared to be the least reliable of all five landmarks. Conclusion: Based on the present study, a consistently reliable landmark in the External Auditory Meatus to replace point Porion could not be identified. The hypothesis that any landmark could suffice for superimposing CBCT scans was not confirmed.

Abstract Despite a substantial impact on various economic and cell technology factors, the influence of electrolyte quantities is rarely addressed in research. This study examines the impact of varying electrolyte quantities on cell performance and aging processes using three different electrolytes: LP57 (1 M LiPF6 in ethylene carbonate:ethyl methyl carbonate (EC:EMC 3:7 w/w), LP572 (LP57+2 wt.% vinylene carbonate (VC)) and LP57 + absVC (18.351 mg VC). Comprehensive analytical post mortem investigations revealed that continuous excessive electrolyte decomposition determines the performance of cells using LP57, leading to enhanced irreversible lithium‐ion loss and interphase thickening with increasing electrolyte volume. Impedance rise due to the growth of the interphase was also identified as the cause of degrading cell performance with rising amounts of LP572, attributed to an increasingly pronounced consumption of VC rather than electrolyte aging effects. By varying the electrolyte quantity while maintaining a constant amount VC within the cell system, the differences in cell performance were minimized, and observed deteriorating effects were suppressed. This study demonstrates the sensitive interdependence of electrolyte volume and additive concentration, practically affecting aging behavior. Comprehensively understanding the characteristics of each individual electrolyte component and tailoring the electrolytes to cell‐specific cell properties proves to be crucial to optimize cell performance.

Objectives This study aims to investigate the cost-effectiveness of individually tailored self-management support, delivered via the artificial intelligence-based selfBACK app, as an add-on to usual care for people with low back pain (LBP).Design Secondary health-economic analysis of the selfBACK randomised controlled trial (RCT) with a 9-month follow-up conducted from a Danish national healthcare perspective (primary scenario) and a societal perspective limited to long-term productivity in the form of long-term absenteeism (secondary scenario).Setting Primary care and an outpatient spine clinic in Denmark.Participants A subset of Danish participants in the selfBACK RCT, including 297 adults with LBP randomised to the intervention (n=148) or the control group (n=149).Interventions App-delivered evidence-based, individually tailored self-management support as an add-on to usual care compared with usual care alone among people with LBP.Outcome measures Costs of healthcare usage and productivity loss, quality-adjusted life-years (QALYs) based on the EuroQol-5L Dimension Questionnaire, meaningful changes in LBP-related disability measured by the Roland-Morris Disability Questionnaire (RMDQ) and the Pain Self-Efficacy Questionnaire (PSEQ), costs (healthcare and productivity loss measured in Euro) and incremental cost-effectiveness ratios (ICERs).Results The incremental costs were higher for the selfBACK intervention (mean difference €230 (95% CI −136 to 595)), where ICERs showed an increase in costs of €7336 per QALY gained in the intervention group, and €1302 and €1634 for an additional person with minimal important change on the PSEQ and RMDQ score, respectively. At a cost-effectiveness threshold value of €23250, the selfBACK intervention has a 98% probability of being cost-effective. Analysis of productivity loss was very sensitive, which creates uncertainty about the results from a societal perspective limited to long-term productivity.Conclusions From a healthcare perspective, the selfBACK intervention is likely to represent a cost-effective treatment for people with LBP. However, including productivity loss introduces uncertainty to the results.Trial registration number NCT03798288.

Abstract Datasets consist of measurement data and metadata. Metadata provides context, essential for understanding and (re-)using data. Various metadata standards exist for different methods, systems and contexts. However, relevant information resides at differing stages across the data-lifecycle. Often, this information is defined and standardized only at publication stage, which can lead to data loss and workload increase. In this study, we developed Metadatasheet, a metadata standard based on interviews with members of two biomedical consortia and systematic screening of data repositories. It aligns with the data-lifecycle allowing synchronous metadata recording within Microsoft Excel, a widespread data recording software. Additionally, we provide an implementation, the Metadata Workbook, that offers user-friendly features like automation, dynamic adaption, metadata integrity checks, and export options for various metadata standards. By design and due to its extensive documentation, the proposed metadata standard simplifies recording and structuring of metadata for biomedical scientists, promoting practicality and convenience in data management. This framework can accelerate scientific progress by enhancing collaboration and knowledge transfer throughout the intermediate steps of data creation.

Abstract Background Research waste is defined as research outcomes with no or minimal societal benefits. It is a widespread problem in the healthcare field. Four primary sources of research waste have been defined: (1) irrelevant or low priority research questions, (2) poor design or methodology, (3) lack of publication, and (4) biased or inadequate reporting. This commentary, which was developed by a multidisciplinary group of researchers with spinal manipulative therapy (SMT) research expertise, discusses waste in SMT research and provides suggestions to improve future research. Main text This commentary examines common sources of waste in SMT research, focusing on design and methodological issues, by drawing on prior research and examples from clinical and mechanistic SMT studies. Clinical research is dominated by small studies and studies with a high risk of bias. This problem is compounded by systematic reviews that pool heterogenous data from varying populations, settings, and application of SMT. Research focusing on the mechanisms of SMT often fails to address the clinical relevance of mechanisms, relies on very short follow-up periods, and has inadequate control for contextual factors. Conclusions This call to action is directed to researchers in the field of SMT. It is critical that the SMT research community act to improve the way research is designed, conducted, and disseminated. We present specific key action points and resources, which should enhance the quality and usefulness of future SMT research.

Gastroenterologists are exposed daily to musculoskeletal (MSK) stress during upper and lower gastrointestinal endoscopy, both during routine endoscopies and during long, demanding therapeutic procedures. There is evidence that endoscopy-related MSK injuries are becoming more common, particularly in the back, neck, shoulders, elbows, and hands. The aims of this study were to identify the most stressed muscle groups during endoscopy; to measure their activity using surface electromyographical (EMG) sensors; to detect areas of muscle overload; and to identify the number of microbreaks taken in specific muscles. Furthermore, we measured differences in the loading of these muscle groups with and without the use of special support systems such as a belt-like holder. Measurements were performed on 15 subjects (7 experienced endoscopists and 8 non-endoscopists). Due to this small sample size, inside each group, we achieved inconclusive results regarding statistically significant differences in different muscle groups. We increased the sample size by comparing all participants with and without the belt support system, disregarding their endoscopic background. There was a statistically significant difference (p < 0.05) in muscle tension and in levels of microbreaks in the muscles of the left forearm, biceps, and trapezius muscles. No statistically significant difference was observed in the muscle tension and level of microbreaks in the left deltoid muscle (p > 0.05). We hypothesize that the increased level of muscle loading and decreased level of microbreaks in the deltoid muscle are due to different muscle activity and different shoulder movements. Additionally, the deltoid muscle is not connected to the kinetic chain of body posture and stabilization. It is our belief that MSK injuries in gastrointestinal (GI) endoscopy can be prevented with the use of a belt-like support system.

Abstract Background Individual goal setting is a fundamental element in self-management supportive interventions, serving to guide actions and enhance motivation for engagement. Despite this, little is known about the goals people with back pain have and to what extent these differ across genders, age groups and geographical location. This study aimed to elucidate this by first describing individual goals set by Danish and Canadian participants in a self-management intervention for people with back pain using the ICF framework; then, determining what proportion of these goals met criteria for being specific, measurable, acceptable, and time bound, and finally, by investigating differences between countries, sexes, and age groups. Methods In a cross-sectional study conducted August 2018 to June 2020, 394 Danish and 133 Canadian (Alberta Province) participants defined their individual goals of participating in a self-management programme involving patient education and supervised exercises. The goals were linked to the ICF framework. Distribution of goals was compared between countries, sexes, and age groups. Results Goals most often related to the ICF component of ‘Activity and Participation’. The most prevalent goals were “Walking” (DK: 20%; CA: 15%) and “Maintaining a body position” (DK: 17%; CA: 22%). Only few goals differed between populations, age and sex. All elements of SMART goal setting were recorded for 88% of Danish and 94% of Alberta participants. Conclusions People with low back pain attending a self-management programme established goals according to the SMART criteria and focused primarily on activity. Goals were similar across countries and showed few differences across sex and age groups. The high number of different goals points to the need for individualised person-centred care.

Abstract Under-reporting of COVID-19 and the limited information about circulating SARS-CoV-2 variants remain major challenges for many African countries. We analyzed SARS-CoV-2 infection dynamics in Addis Ababa and Jimma, Ethiopia, focusing on reinfection, immunity, and vaccination effects. We conducted an antibody serology study spanning August 2020 to July 2022 with five rounds of data collection across a population of 4723, sequenced PCR-test positive samples, used available test positivity rates, and constructed two mathematical models integrating this data. A multivariant model explores variant dynamics identifying wildtype, alpha, delta, and omicron BA.4/5 as key variants in the study population, and cross-immunity between variants, revealing risk reductions between 24% and 69%. An antibody-level model predicts slow decay leading to sustained high antibody levels. Retrospectively, increased early vaccination might have substantially reduced infections during the delta and omicron waves in the considered group of individuals, though further vaccination now seems less impactful.

Abstract Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson’s disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.

Abstract Background During the last two decades, Caesarean section rates (C-sections), overweight and obesity rates increased in rural Peru. We examined the association between pre-pregnancy body mass index (BMI) and C-section in the province of San Marcos, Northern Andes-Peru. Methods This is a prospective cohort study. Participants were women receiving antenatal care in public health establishments from February 2020 to January 2022, who were recruited and interviewed during pregnancy or shortly after childbirth. They answered a questionnaire, underwent a physical examination and gave access to their antenatal care card information. BMI was calculated using maternal height, measured by the study team and self-reported pre-pregnancy weight measured at the first antenatal care visit. For 348/965 (36%) women, weight information was completed using self-reported data collected during the cohort baseline. Information about birth was obtained from the health centre’s pregnancy surveillance system. Regression models were used to assess associations between C-section and BMI. Covariates that changed BMI estimates by at least 5% were included in the multivariable model. Results This study found that 121/965 (12.5%) women gave birth by C-section. Out of 495 women with pre-pregnancy normal weight, 46 (9.3%) had C-sections. Among the 335 women with pre-pregnancy overweight, 53 (15.5%) underwent C-sections, while 23 (18.5%) of the 124 with pre-pregnancy obesity had C-sections. After adjusting for age, parity, altitude, food and participation in a cash transfer programme pre-pregnancy overweight and obesity increased the odds of C-section by more than 80% (aOR 1.82; 95% CI 1.16–2.87 and aOR 1.85; 95% CI 1.02–3.38) compared to women with a normal BMI. Conclusions High pre-pregnancy BMI is associated with an increased odds of having a C-section. Furthermore, our results suggest that high BMI is a major risk factor for C-section in this population. The effect of obesity on C-section was partially mediated by the development of preeclampsia, suggesting that C-sections are being performed due to medical reasons.

Jan von der Velde kjøpte i 1741 offentlige rettigheter i Sunnfjord av den dansk-norske kongen, som retten til å utnevne dommer på det tidligere Svanøygodset og tienden av korn og fisk. Samlingen av rettigheter ble kalt Svanøy birks herligheter. Artikkelens første hovedtema er omfanget av dem. De gikk over til etterkommerne i et sameie i 1755. Dette bestod til den siste rettigheten ble innløst ved lov i 1903. Det andre hovedtemaet er om sameiet var et fideikommiss.

Abstract Aims In patients with recently diagnosed non‐ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short‐term follow‐up. The aim of our study was to assess the long‐term clinical course and stability of LVRR in these patients. Methods and results We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting

AbstractBackground Steatotic liver disease (SLD) prevalence is rising worldwide, linked to insulin resistance and obesity. SLD prevalence can surpass 10% even among those with normal weight. In Lao People’s Democratic Republic (Lao PDR), where Opisthorchis viverrini (OV) trematode infection and type 2 diabetes mellitus (T2DM) are common, infection related liver morbidity such as cholangiocarcinoma (CCA) is high, but data on SLD prevalence is lacking. The objective of this study was to estimate the prevalence and explore determinants of SLD in rural southern Lao PDR for lean and non-lean populations.Method A cross-sectional community-based study assessed SLD prevalence using abdominal ultrasonography (US). Factors investigated for association with SLD were identified by interview, serological tests (Hepatitis B surface antigen (HBsAg); lipids and HbA1c), anthropometrical measurements, and parasitological assessments (OV infection). Uni- and multivariable logistic regression analyses with SLD as endpoint were conducted separately for lean (body mass index (BMI)

The Sauersack/Rolava POW camp from World War II is the first archaeologically investigated site of its kind in Bohemia, and thanks to its highly authentic state of preservation it can be considered one of the best archaeologically known internment facilities in Europe. Nevertheless, new findings continue to emerge, including information from illegal treasure hunters. In 2022, the main settlement waste dump was identified and due to the threat to the site from illegal excavations, pre-emptive archaeological testing was immediately undertaken. The research has resulted in the documentation of a remarkable structure suited to waste disposal and the recovery of an assemblage of artefacts and ecofacts that complement and extend our knowledge of the communities that inhabited the POW camp.

Abstract Brucellosis, a zoonotic disease impacting public health and economies, is prevalent in several countries, particularly low- and middle-income regions. This study centers on Armenia, where the Veterinary Department of the Food Safety Inspection Body employs a test-and-slaughter strategy to control the disease. A dynamic deterministic compartmental model was constructed using seropositive reported data from humans and livestock (cattle and sheep) from 2019 to 2021. The model simulates the effects of enhanced test-and-slaughter strategies from 2022 to 2031 on brucellosis transmission among sheep, cattle, and humans. The results suggest that an increase in testing and slaughter rates leads to a decrease in infected populations among both humans and livestock. Approximately 65% of the human brucellosis cases are a result of sheep-to-human transmissions. This reduction in infected populations is expected to subsequently lower the overall transmission rates in livestock and humans. However, even with the highest coverage levels (75% for sheep and 90% for cattle), infections in humans and livestock are projected to persist. The study highlights the need for a One Health approach that integrates mathematical modeling with public health intervention strategies. While the upgraded test-and-slaughter strategy could prove effective, an economic analysis of the predicted cumulative incidence in humans and livestock prevalence could guide decision making processes. Compensation for culled animals is a critical factor. The success of the intervention relies on collaboration between veterinary and public health sectors, community engagement, and awareness campaigns. One Health impact statement This study applied a mathematical model to investigate brucellosis transmission within the livestock population and from animals to humans. It assessed the impact of different test-and-slaughter coverage levels from 2022 to 2031 on disease burden and livestock populations. Although the research did not encompass the entire One Health spectrum, it shed light on the potential benefits of integrating human and animal health interventions. Local institutions (such as the Food Safety and Inspectorate Body and the National Centre for Disease Control in Armenia) and international collaboration among scientists contributed to a better understanding and controlling zoonotic diseases. The findings offer valuable insights for decision making, aiding Armenian policy makers in effectively managing brucellosis and enhancing public health, food safety, and monetary savings. Furthermore, the research provides a basis for further exploration in this field.

Dieser Beitrag diskutiert schwerpunktmäßig aus einer sozialwissenschaftsfachdidaktischen Perspektive den Umgang von Lehrkräften mit fachdidaktischem Wissen im Unterrichtsfach Gesellschaftslehre an Gesamtschulen in Nordrhein-Westfalen. Dazu werden auf der Grundlage qualitativer Interviews Strategien im Umgang mit fachdidaktischem Wissen rekonstruiert. Mit der Gesellschaftslehre geht es dabei um ein Unterrichtsfach, das sich durch Bezüge zu den universitären Studienfächern Geschichte, Sozialwissenschaften und Geografie auszeichnet – eine Kombination, die kaum eine Lehrkraft qua Studium aufweist. Vor diesem Hintergrund geht es um die Frage, welche Anforderungen sich für Lehrkräfte in Bezug auf das fachdidaktische Wissen in einem solchen Integrationsfach stellen. Ausgehend von den Ergebnissen schlägt der Beitrag Schritte hin zu einer fachdidaktisch-reflexiven Integrationskompetenz (F-R-I-K) vor. From a Social Science didactic perspective, this article focuses on how teachers deal with subject-specific didactic knowledge in the subject of Social Studies at comprehensive schools in North Rhine-Westphalia. Social Studies is a subject that is characterized by its links to the university subjects of History, Social Sciences and Geography – a combination that hardly any teachers have as part of their studies. Against this background, the question arises which requirements do teachers have in terms of didactic knowledge in such an integrated subject? Based on the results, the article proposes steps towards a subject-didactic-reflective integration competence (F-R-I-K).

Background: Many individuals with hypertension remain undiagnosed. We aimed to develop a predictive model for hypertension using diagnostic codes from prevailing electronic medical records in Swedish primary care. Methods: This sex- and age-matched case-control (1:5) study included patients aged 30–65 years living in the Stockholm Region, Sweden, with a newly recorded diagnosis of hypertension during 2010–19 (cases) and individuals without a recorded hypertension diagnosis during 2010–19 (controls), in total 507,618 individuals. Patients with diagnoses of cardiovascular diseases or diabetes were excluded. A stochastic gradient boosting machine learning model was constructed using the 1,309 most registered ICD-10 codes from primary care for three years prior the hypertension diagnosis. Results: The model showed an area under the curve (95 % confidence interval) of 0.748 (0.742–0.753) for females and 0.745 (0.740–0.751) for males for predicting diagnosis of hypertension within three years. The sensitivity was 63 % and 68 %, and the specificity 76 % and 73 %, for females and males, respectively. The 25 diagnoses that contributed the most to the model for females and males all exhibited a normalized relative influence >1 %. The codes contributing most to the model, all with an odds ratio of marginal effects >1 for both sexes, were dyslipidaemia, obesity, and encountering health services in other circumstances. Conclusions: This machine learning model, using prevailing recorded diagnoses within primary health care, may contribute to the identification of patients at risk of unrecognized hypertension. The added value of this predictive model beyond information of blood pressure warrants further study.

This work provides an investigation of the influence of low temperature heat treatments on the fatigue behavior of a PBF-LB AlSi10Mg alloy. Fatigue specimens are produced in form of round bars on a build platform preheated at 200 °C. The specimens have been tested in three different conditions: as-built, and after heat treatments at 265 °C for 1 h and 300 °C for 2 h. Prior to the fatigue testing, the defect distribution is analyzed by means of micro computed tomography. Subsequently, the peak over threshold method is successfully applied to provide a prediction of the size of killer defect. The defect population was of gas porosity type. No clear improvement of the fatigue performance is observed after the heat treatments. The fatigue strength predicted using fracture mechanics-based approaches is in good agreement with the experimental data. Among the studied approaches, short crack models provided the most conservative predictions.

The growth pattern of oropharyngeal squamous cell carcinomas (OPSCC) varies from compact tumor cell aggregates to diffusely infiltrating tumor cell-clusters. The influence of the growth pattern on local tumor control and survival has been studied mainly for surgically treated oral cavity carcinomas on a visual basis. In this study, we used multiplex immunofluorescence staining (mIF) to examine the antigens pan-cytokeratin, p16INK4a, Ki67, CD271, PD-L1, and CD8 in pretherapeutic biopsies from 86 OPSCC. We introduce Tumor-stroma contact ratio (TSC), a novel parameter, to quantify the relationship between tumor cells in contact with the stromal surface and the total number of epithelial tumor cells. mIF tumor cores were analyzed at the single-cell level, and tumor-stromal contact area was quantified using the R package ''Spatstat''. TSC was correlated with the visually assessed invasion pattern by two independent investigators. Furthermore, TSC was analyzed in relation to clinical parameters and patient survival data to evaluate its potential prognostic significance.Higher TSC correlated with poor response to (chemo-)radiotherapy (r = 0.3, p < 0.01), and shorter overall (OS) and progression-free (PFS) survival (median OS: 13 vs 136 months, p < 0.0001; median PFS: 5 vs 85 months, p < 0.0001). Visual categorization of growth pattern according to established criteria of tumor aggressiveness showed interobserver variability increasing with more nuanced categories (2 categories: k = 0.7, 95 %-CI: 0.55 - 0.85; 4 categories k = 0.48, 95 %-CI: 0.35 - 0.61).In conclusion, TSC is an objective and reproducible computer-based parameter to quantify tumor-stroma contact area. We demonstrate its relevance for the response of oropharyngeal carcinomas to primary (chemo-)radiotherapy.

OBJECTIVES:. In critically ill children with severe sepsis, septic cardiomyopathy (SCM) denotes the subset of patients who have myocardial dysfunction with poor response to fluid and inotropic support, and higher mortality risk. The objective of this review was to evaluate the role of speckle-tracking echocardiography (STE) in the diagnosis and prognosis of pediatric SCM in the PICU setting. DATA SOURCES:. We performed detailed searches using PubMed, Scopus, Web of Science, and Google Scholar. Reference lists of all included studies were also examined for further identification of potentially relevant studies. STUDY SELECTION:. Studies with the following medical subject headings and keywords were selected: speckle-tracking echocardiography, strain imaging, global longitudinal strain, echocardiography, sepsis, severe sepsis, septic shock, septic cardiomyopathy, and myocardial dysfunction. DATA EXTRACTION:. The following data were extracted from all included studies: demographics, diagnoses, echocardiographic parameters, severity of illness, PICU management, and outcomes. DATA SYNTHESIS:. STE is a relatively new echocardiographic technique that directly quantifies myocardial contractility. It has high sensitivity in diagnosing SCM, correlates well with illness severity, and has good prognosticating value as compared with conventional echocardiographic parameters. Further studies are required to establish its role in evaluating biventricular systolic and diastolic dysfunction, and to investigate whether it has a role in individualizing treatment and improving treatment outcomes in this group of patients. CONCLUSIONS:. STE is a useful adjunct to conventional measures of cardiac function on 2D-echocardiography in the assessment of pediatric SCM in the PICU.

Background: The PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06; NCT05871021) is designed to determine whether a dose escalation with 75.0 Gy in 30 fractions can enhance the median overall survival (OS) in patients with methylguanine methyltransferase (MGMT) promotor unmethylated glioblastoma compared to historical median OS rates, while being isotoxic to historical cohorts through the addition of concurrent bevacizumab (BEV). To ensure protocol-compliant irradiation planning with all study centers, a dummy run was planned and the plan quality was evaluated. Methods: A suitable patient case was selected and the computed tomography (CT), magnetic resonance imaging (MRI) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) contours were made available. Participants at the various intended study sites performed radiation planning according to the PRIDE clinical trial protocol. The treatment plans and dose grids were uploaded as Digital Imaging and Communications in Medicine (DICOM) files to a cloud-based platform. Plan quality and protocol adherence were analyzed using a standardized checklist, scorecards and indices such as Dice Score (DSC) and Hausdorff Distance (HD). Results: Median DSC was 0.89, 0.90, 0.88 for PTV60, PTV60ex (planning target volume receiving 60.0 Gy for the standard and the experimental plan, respectively) and PTV75 (PTV receiving 75.0 Gy in the experimental plan), respectively. Median HD values were 17.0 mm, 13.9 mm and 12.1 mm, respectively. These differences were also evident in the volumes: The PTV60 had a volume range of 219.1–391.3 cc (median: 261.9 cc) for the standard plans, while the PTV75 volumes for the experimental plans ranged from 71.5–142.7 cc (median: 92.3 cc). The structures with the largest deviations in Dice score were the pituitary gland (median 0.37, range 0.00–0.69) and the right lacrimal gland (median 0.59, range 0.42–0.78). Conclusions: The deviations revealed the necessity of systematic trainings with appropriate feedback before the start of clinical trials in radiation oncology and the constant monitoring of protocol compliance throw-out the study. Trial registration: NCT05871021

Background Retinal imaging, including fundus autofluorescence (FAF), strongly depends on the clearness of the optical media. Lens status is crucial since the ageing lens has both light-blocking and autofluorescence (AF) properties that distort image analysis. Here, we report both lens opacification and AF metrics and the effect on automated image quality assessment.Methods 227 subjects (range: 19–89 years old) received quantitative AF of the lens (LQAF), Scheimpflug, anterior chamber optical coherence tomography as well as blue/green FAF (BAF/GAF), and infrared (IR) imaging. LQAF values, the Pentacam Nucleus Staging score and the relative lens reflectivity were extracted to estimate lens opacification. Mean opinion scores of FAF and IR image quality were compiled by medical readers. A regression model for predicting image quality was developed using a convolutional neural network (CNN). Correlation analysis was conducted to assess the association of lens scores, with retinal image quality derived from human or CNN annotations.Results Retinal image quality was generally high across all imaging modalities (IR (8.25±1.99) >GAF >BAF (6.6±3.13)). CNN image quality prediction was excellent (average mean absolute error (MAE) 0.9). Predictions were comparable to human grading. Overall, LQAF showed the highest correlation with image quality grading criteria for all imaging modalities (eg, Pearson correlation±CI −0.35 (−0.50 to 0.18) for BAF/LQAF). BAF image quality was most vulnerable to an increase in lenticular metrics, while IR (−0.19 (−0.38 to 0.01)) demonstrated the highest resilience.Conclusion The use of CNN-based retinal image quality assessment achieved excellent results. The study highlights the vulnerability of BAF to lenticular remodelling. These results can aid in the development of cut-off values for clinical studies, ensuring reliable data collection for the monitoring of retinal diseases.