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Introduction

Chiari malformation type 1 (CM1) is a common congenital disorder affecting both children and adults. Although pediatric and adult CM1 patients share many characteristics, the differences between the groups are not fully described.

Method

A comparative analysis was made of two previously defined cohorts of adult and pediatric non-syndromic CM1, surgically treated at the study center. Clinical outcomes were assessed using the Chicago Chiari outcome scale (CCOS) and radiological outcomes were measured as change in cerebellar tonsil and syringomyelia status.

Results

A total of 209 patients (73 pediatric, 136 adults) were included, with median ages of 11 and 33 years, respectively. The proportion of female patients (62% vs 78%) was higher in the adult population (p = 0.012). Headache (p = 0.007), neck pain (p = 0.000), vertigo (p = 0.007), and sensory symptoms (p = 0.000) were more common in adults, while scoliosis (p = 0.000) and sleep apnea (p = 0.015) were more common in the pediatric population. Preoperative imaging findings did not differ significantly. After posterior fossa decompression, both groups scored a median CCOS of 15 at early follow-up (3 vs 4 months), though the pediatric population had a more favorable distribution of CCOS scores (p = 0.003). Postoperatively, syringomyelia status did not differ significantly between groups, but cerebellar tonsil status improved more frequently in adults (64% vs 88%, p = 0.000).

Conclusion

This study demonstrates that while headache is the most common presenting symptom in both pediatric and adult CM1 patients, pediatric patients are more likely to present with scoliosis and sleep apnea. In contrast adult patients more frequently experience headache, neck pain, vertigo, and sensory symptoms. There were no differences in other preoperative imaging variables and outcomes were favorable for most patients in both groups.

The Baltic Sea has undergone a regime-shift. Anthropogenic and abiotic factors have caused a shift to a system which is dominated by meso-predators instead of top-predator. This regime-shift has been seen in both the pelagic and the coastal ecosystem. In some coastal areas, there has been a decrease in predatory fishes, like pike (Esox lucius) and perch (Perca fluviatilis). Recruitment failure is one explanation, and habitat destruction is part of the problem. Sympatric populations of pike in the Baltic Sea have two different spawning strategies. One part of the population spawn in shallow, vegetated areas in the Baltic Sea. The other part is anadromous and migrate to freshwater wetlands to spawn. These areas warm up fast and have higher abundance of food. Many of these wetlands have been drained to increase area for agricultural land. Some of these wetlands have been restored to promote pike recruitment in the Baltic Sea. These restored wetlands are called “Pike factories”. In this project, two restored wetlands called Snäckstavik and Kyrksjön are studied with focus on pike larvae. Larvae production, habitat preferences, diet and morphology were investigated. A transect inventory using the “white-plate”-method was used to investigate the habitat preferences of pike larvae over time in different vegetation densities. To study the emigration larvae were caught for morphology and diet analyses. The water temperature and weather were noted each day to see what influenced emigration. The results from the study were that larvae preferred dense, rather than sparse and decayed vegetation. In dense vegetation, there is higher abundance of food and gives protection from predators. Emigration started when water temperature increased, and the pike were smaller than 2 cm. In Snäckstavik the emigration peaked with higher water temperature and higher light intensity, while in Kyrksjön the emigration peaked with decreasing water-level. The morphology of the pike depended on time of emigration and diet-choice. The findings of this study show that when restoring a wetland, dense vegetation is an important factor for recruitment success.

Background:

LGBTQ+ people have widely described harmful experiences in healthcare settings. To address this deficit in care, previous studies have focused on improving the education of nursing and allied health students to care for LGBTQ+ people, yet few evaluate faculty preparedness.

Aim:

This study aimed to assess faculty's LGBTQ+-related health knowledge, self-efficacy, and inclusion related to curriculum.

Methods:

A Qualtrics survey was developed to assess faculty's knowledge, self-efficacy, and inclusion of LGBTQ+ curriculum at a university in the United States between March 4 and April 13, 2022. Paired t-tests and correlation matrices were used to evaluate constructs. Results: Among 38 participants, LGB health content knowledge was greater than T+ knowledge. LGBTQ+ self-efficacy and inclusion were moderate, with no difference between subscales. LGBTQ+ health self-efficacy and inclusion were positively correlated.

Conclusions:

These findings highlight gaps in faculty knowledge and inclusion of health content, particularly related to T+ health. This study's findings form a foundation for continued efforts to improve nursing and other allied health faculty's preparedness to educate students to provide inclusive and affirming care to LGBTQ+ patients.

Gaze following in infancy allows triadic social interactions and a comprehension of other individuals and their surroundings. Despite its importance for early development, its ontology is debated, with theories suggesting that gaze following is either a universal core capacity or an experience-dependent learned behavior. A critical test of these theories among 809 nine-month-olds from Africa (Uganda and Zimbabwe), Europe (Sweden), and Asia (Bhutan) demonstrated that infants follow gaze to a similar degree regardless of environmental factors such as culture, maternal well-being (postpartum depression, well-being), or traumatic family events (related to war and/or climate change). These findings suggest that gaze following may be a universal, experience-expectant process that is resilient to adversity and similar across a wide range of human experiences-a core foundation for social development.

Introduction: The challenge of maintaining normoxemia in preterm infants undergoing respiratory support and oxygen therapy has led to the development of closed-loop automatic control systems for FiO₂. The aim of this study was to assess the effectiveness of these systems in maintaining SpO₂ within a target range (90% - 94%) in preterm neonates receiving supplemental oxygen.

Methods: We conducted a single-centre prospective study over a three-year period (2020 - 2023) including preterm infants with a gestational age < 33 weeks who received supplemental oxygen within the first 24 hours of life and either invasive or non-invasive respiratory support. The closed-loop automatic control of FiO₂ used was the Predictive Intelligent Control of Oxygenation feature on Fabian® ventilators. Two groups were randomized and compared, one receiving automatic plus manual control of FiO₂, and the other receiving routine manual control. Uni- and multivariable regression analyses (linear or Poisson) were used to evaluate the association between the use of closed-loop automatic control of FiO₂ and the parameters of manual adjustments, hypoxemia, hyperoxemia, and normoxemia.

Results: The study included 89 patients, of which 45 received automatic plus manual control of FiO₂ and 44 received routine manual control. The first group required fewer manual adjustments of FiO₂, experienced fewer episodes of hypoxemia and hyperoxemia (p < 0.002), and spent more time with SpO2 within the target range (p < 0.001), compared to the second group. After adjustment for confounding, the total time spent in normoxemia was higher when in automatic plus manual control of FiO₂ (β = 81.5; 95%CI: 47.9 - 115.2, p < 0.001).

Conclusion: The use of closed-loop automatic control of FiO₂ seems feasible and was associated with fewer episodes of hypoxia and hyperoxia, thereby maintaining SpO₂ within normal limits for longer periods. Additionally, it has been shown to be associated with a reduction in manual interventions.

CD93 is a receptor predominantly expressed on the surface of endothelial cells, where it plays a pivotal role in angiogenesis through its interaction with the extracellular matrix. In our previous studies, we identified the monoclonal antibody 4E1 as a potent inhibitor of angiogenesis by targeting the CD93-Multimerin-2 axis. Here, we report the development of 4E1 as a recombinant whole immunoglobulin and a single-chain variable fragment, designated sc-4E. Both formats retained the binding properties of the parental monoclonal antibody and exhibited comparable inhibitory effects on endothelial cell migration and differentiation. To elucidate the molecular basis of the 4E1-CD93 interaction, we initially employed machine learning-based modeling and docking analyses of the variable heavy and light domains of 4E1. Subsequent crystallographic analysis of sc-4E provided high-resolution structural insights, confirming and validating the predicted model. Further docking experiments and molecular dynamics simulations using the crystallographic structures of CD93 and sc-4E revealed that the interaction is primarily mediated by the CDR-H3 and CDR-L2 loops. Notably, these regions engage with the sushi-like domain of CD93, which is critical for its interaction with Multimerin-2. This comprehensive structural and functional characterization of 4E1 and sc-4E underscores their potential as anti-angiogenic agents. By effectively inhibiting endothelial cell migration and differentiation, 4E1 derivatives represent promising therapeutic candidates for the treatment of ocular vascular diseases driven by pathological angiogenesis.

Aim:

This study aimed to improve the efficacy of the CD44v6-targeting antibody UU-40 for molecular radiotherapy through affinity maturation and IgG subclass optimization.

M&M:

A panel of affinity-matured antibody candidates was generated and characterized as both human IgG4 and IgG1 with LALA mutations. Surface plasmon resonance and LigandTracer analyses identified several candidates with superior affinity and off-rates compared to the parental UU-40. Biodistribution studies in xenograft models using Lutetium-177 (177Lu)-labeled antibodies showed improved tumor retention for selected candidates, particularly UU-A-155. Species cross-reactivity assays confirmed binding to cynomolgus and rabbit v6-peptides, supporting future toxicity studies.

Results:

The IgG1 LALA format demonstrated reduced binding to Fc gamma receptors, potentially improving the safety profile. UU-A-155 emerged as the lead candidate for clinical translation, showing superior performance in both affinity and tumor retention. Our findings highlight the importance of comprehensive in vitro and in vivo assessments in antibody development, and provides valuable insights into optimizing antibody-based molecular radiotherapy.

Calprotectin, a calcium-binding protein complex of S100A8 and S100A9, is abundant in neutrophils and released upon their activation. It has emerged as a potential biomarker for several inflammatory conditions, including respiratory infections, sepsis, and rheumatoid arthritis. With increasing concerns about antibiotic resistance, there is a need to accurately differentiate between bacterial and viral infections for better treatment decisions.

This thesis investigates the diagnostic performance of calprotectin in respiratory tract infections, its activation kinetics following inflammatory stimuli, its role as a biomarker in rheumatoid arthritis, and to compare total calprotectin levels with its subunits in intensive care unit (ICU) patients with sepsis. The studies included patients with respiratory infections, post-operative inflammation, rheumatoid arthritis, and sepsis, measuring calprotectin levels in serum, plasma, and synovial fluid.

Results showed significantly higher calprotectin levels in bacterial infections compared to viral infections and healthy controls. It outperformed procalcitonin (PCT) and Heparin-binding protein (HBP) in distinguishing bacterial from viral respiratory infections, including mycoplasma. Calprotectin levels increased rapidly (within 2 hours) following inflammation, earlier than CRP and IL-6. In rheumatoid arthritis, serum calprotectin correlated strongly with inflammatory markers, particularly in anti-citrullinated protein antibodies (ACPA)-positive patients. In ICU patients, total calprotectin performed better than its subunits (S100A8 and S100A9) in differentiating sepsis from non-sepsis cases.

Calprotectin shows promise as a biomarker for early detection of bacterial infections and inflammation. Its rapid rise and superior ability to differentiate bacterial and viral infections highlight its potential to improve the management of respiratory infections and guide antibiotic use. However, further research is needed to standardise assays and fully understand its specificity in various clinical contexts.

Study Objectives

Evidence suggests that adolescents and adults with a later chronotype have poorer sleep habits and are more susceptible to unhealthy behaviors, but little is known about these associations in younger children. The objective of the study was to (1) identify and compare individual chronotype tendencies among preschool-aged children and (2) investigate associations of sleep dimensions and chronotype with diet.

Methods

Participants were 636 3–6 years old (mean ± SD age: 4.74 ± 0.89 years, 49% girls) preschoolers from the cross-sectional Increased Health and Well-Being in Preschoolers (DAGIS) study in Finland. Sleep duration, sleep variability (in duration and midpoint), social jetlag, and midsleep on weekends adjusted for sleep debt (MSWEadj) were measured with 7-day actigraphy. Morning, intermediate, and evening chronotype tendencies were defined based on the lowest and highest 10th percentile cutoffs of MSWEadj. Food, energy, and macronutrient intake were assessed from 3-day records. Associations between sleep dimensions and diet were assessed with regression models.

Results

MSWEadj was 1:13 ± 14 minutes for morning (n = 64), 2:25 ± 28 minutes for intermediate (n = 560), and 3:38 ± 15 minutes for evening (n = 64) chronotype tendency. Children with an evening chronotype tendency had greater social jetlag and sleep variability. Having an evening chronotype tendency was associated with higher added sugar, higher sugary food consumption, and lower vegetable consumption compared to intermediate tendency types. A later chronotype (MSWEadj) was associated with higher sugary food consumption, as well as lower vegetable and fiber intake. Sleep duration, social jetlag, and sleep variability were not associated with diet.

Conclusions

Several less healthy sleep and diet behaviors were observed among children with later chronotypes. Future public health interventions aimed towards children would benefit from taking into account chronotype.

Background:

Compared with other placements, thigh-worn accelerometers offer the advantage to accurately capture postures. However, the lack of standardized sensor placement on the thigh raises concerns about the comparability and harmonization of data across studies. This study aimed to investigate the impact of sensor placement on thigh-worn accelerometer measurements.

Methods:

Thirty-six participants wore two sensors simultaneously at center- and upper-thigh position on the same thigh during daily activities for several days. Metrics of vector magnitude (Euclidian Norm Minus One), postures, and activities generated by GGIR and ActiPASS were analyzed with Bland-Altman plots and linear regressions.

Results:

The findings revealed a significant dependence of vector magnitude on sensor placement: 1 cm higher distance between the center- and upper-thigh position was correlated with almost 1 mg higher difference in Euclidian Norm Minus One between the two positions (b = 0.94; 95% confidence interval [0.26, 1.62]). For time spent sedentary (b = 0.03; 95% confidence interval [-2.48, 2.55]) and intense physical activities (b = 0.22; 95% confidence interval [-0.10, 0.54]), the sensor position had no significant effect on the results. High concordance was also observed for other activities, such as walking, running, and sleeping.

Conclusions:

The analyses suggest that, despite variations in sensor placement, thigh-worn accelerometry data can be compared and harmonized for most postures and activities when analyzed by ActiPASS. The robust metrics by ActiPASS to accelerometer placements is likely because it utilizes multiple features in the acceleration signal (e.g., inclination, rotation) to classify activities and postures, rather than relying on a single feature (vector magnitude).

Objectives

To investigate current prescribing practices, knowledge levels and related disparities regarding menopausal hormone therapy (MHT) among physicians in Sweden.

Study design

A 45-item web-based MHT-focused survey conducted February–September 2023. Participants were specialists/residents in obstetrics and gynecology (gynaecologists) and general practitioners (GPs) in Sweden.

Main outcome measures

Experience with MHT prescription, prescription patterns and challenges and perceived knowledge of and adherence to national guidelines among gynaecologists and GPs, analyzed quantitatively, along with potential differences between the two groups.ResultsIn total, 542 physicians answered the survey (67.9 % gynaecologists and 32.1 % GPs). Over 90 % reported meeting women with menopausal symptoms in their clinical practice and among those 94.6 % prescribed systemic MHT. GPs prescribed MHT to a significantly lesser extent than gynaecologists. GPs reported a significantly higher level of difficulty in all but one of the examined aspects of MHT prescription. GPs demonstrated significantly lower awareness of current national guidelines than gynaecologists. Regarding self-perceived assessment of MHT-related education, 47.8 % of GPs, compared with 30.6 % of gynaecologists, reported inadequate theoretical education (p < 0.001). Physicians working in metropolitan areas were more experienced in prescribing micronized progesterone and dydrogesterone.

Conclusions

Differences were observed between responding gynaecologists and GPs in MHT-related practices and knowledge. While GPs reported lower awareness of guidelines and encountered more challenges in prescribing MHT, nearly one-third of gynaecologists also indicated inadequate education in MHT. This study underscores the need for improved guideline awareness and accessible education to support evidence-based menopause care for the expanding midlife female population.

This article analyses the tension between democratic and constitutional demands for controlover delegated mandates and contemporary trust-oriented management policies of theSwedish national executive. Competing management ideals are here analyzed in terms ofcontrol-oriented Principal-Agent (PA) models and trust-oriented Principal-Steward (PS)models. The case is studied from within three perspectives that constitute core dimensionsof the Swedish management regime: the constitutional preconditions for government-agency relations, the application of formal management instruments, and the role thatinformal instruments play in the management regime. We find that the Swedishmanagement regime is PA-oriented at its core – constitutionally and in terms of the choiceof management model for agencies – but featuring PS-oriented financial and policyautonomy for central government agencies. Informal steering is prohibited but the dominantinterpretation of the constitution is that it allows PS-oriented informal contacts that areequal, cooperative exchanges of information, including efforts to clarify formal steering.We question the validity of this conclusion as clarification of steering is too closely relatedto steering to be reliably something else. Thus, the role of informal contacts is formally andrhetorically reserved for PS-oriented use, that is, interaction on equal and cooperative terms,but in practice also entails PA-oriented top down control.

Magmatic dikes form an integral part of volcanic systems and transport magma from depth towards the surface. Dike propagation through the Earth’s crust is affected by the mechanical properties of the crust, which is important to better understand potential effects on volcanic activity. This thesis investigates the influence of crustal heterogeneity on magmatic dikes, focusing specifically on the interaction between magma and pre-existing weaknesses and on the influence of tectonic stress. Basaltic dikes exposed in moderately fractured hyaloclastite in the extinct Dyrfjöll volcanic system, NE Iceland, showed that dikes can follow existing fractures, change strike when intersecting them without propagating into a fracture or be arrested in front of a fracture. Laboratory models of intrusions into pre-faulted crust demonstrate that the host rock cohesion and the strength contrast between intact and faulted host rock strongly control if and how faults affect intrusions. Faults additionally affect the amplitude and pattern of intrusion-associated surface deformation. Finite Element models simulated dike opening in a tectonic stress field. Comparison of these to surface deformation associated with the 2021 February-March Fagradalsfjall dike, SW Iceland, show that tectonic stress can be a sufficient driving mechanism for dike opening. The relative amount of predicted opening and shearing of the dike plane is consistent with expectations based on geological models and the area’s obliquely-spreading tectonic setting. This thesis demonstrates the complexity of dikes interacting with heterogeneous crust and the potential of considering multidisciplinary research as a key to advance understanding of such interactions. 

Background

The role of Helicobacter pylori ( H. pylori ) screening and eradication on reducing upper gastrointestinal bleeding (UGIB) complications after acute myocardial infarction (MI) is uncertain. The HELicobacter pylori screening to prevent gastrointestinal bleeding in patients with acute MI (HELP-MI SWEDEHEART) trial aims to determine whether systematic H. pylori screening compared to usual care reduces UGIB, mortality, and cardiovascular outcomes after MI.

Methods

A cluster randomized, crossover, registry-based clinical trial using SWEDEHEART as trial platform for study population definition and source for data collection in combination with nationwide Swedish health data registries. Thirty-five Swedish hospitals, organized into 18 clusters based on percutaneous coronary intervention networks, were randomized to either routine H. pylori screening for adults with acute type-1 MI or usual care. After 1 year, a 2-month blanking period was followed by a crossover to the alternate allocation for 1 year. The trial enrolment was concluded after one additional year of registry-based follow-up. The primary endpoint is UGIB. Secondary endpoints include all-cause death, cardiovascular death, readmission for MI, stroke, or heart failure. Endpoints will be reported combined (Net Adverse Clinical Events; Major Adverse Cardiac or Cerebrovascular Events) and separately. The primary analysis will include all available follow-up time corresponding to a maximum follow-up time of 3 years and 2 months.

Conclusion

HELP-MI SWEDEHEART aims to determine the utility of routine H. pylori screening to reduce UGIB and improve cardiovascular outcomes after MI. By integrating national registry follow-up data with a pragmatic trial design, it has the potential to provide evidence for the effect of the implementation of routine H. pylori screening as part of acute MI care.

Trial Registration

ClinicalTrials.gov, NCT05024864.

Background

The European Code Against Cancer (ECAC) aims to increase the awareness of modifiable cancer risk factors among the general public. A goal set by the European Commission was that 80% of European citizens should be aware of this code by 2025. This study aims to examine the awareness and attitudes towards the ECAC among the general public in Sweden.

Methods

A randomly selected sample of 1520 Swedes (18–84 years old) were recruited from a survey panel and invited to respond to an online study-specific questionnaire. The questionnaire included general questions regarding cancer prevention, as well as awareness and attitudes specific to the ECAC. Data were analysed univariately and with adjusted logistic regression, using post-stratification weights based on gender, age, education, and expressed political party orientation.

Results

In total, 3.7% of the respondents had heard about the ECAC before taking this survey. Respondents with a college/university education were more likely to have heard about the ECAC (odds ratio [OR] 2.23; 95% confidence interval [CI] 1.23–4.06). Males (OR 0.56; 95% CI 0.32–0.99), and those living alone (OR 0.47; 95% CI 0.23–0.95) were less likely to have heard about the ECAC. In total, 60.6% of the respondents agreed with the ECAC recommendations, while 27.4% reported that their motivation to improve their lifestyle increased after reading the ECAC.

Conclusions

Awareness of the ECAC among the general public in Sweden is very low. Still, a majority seem to agree with its recommendations. The results also indicate that the ECAC motivates some, but far from all, to improve their lifestyle habits to reduce their cancer risk. Consequently, further research is warranted on how the ECAC best could and should be used in order to improve cancer prevention awareness and motivation.

One of the most recent crop species to be domesticated is sugar beet (Beta vulgaris L. ssp. vulgaris Doell.), which was bred for high sucrose content within the last few centuries in Europe. Crop domestication can also lead to the evolution of novel pathogens, which may spread across large geographical distances with their crop host. In this study, we addressed the recent evolution of the fungal pathogen causing the disease Cercospora leaf spot, Cercospora beticola. This pathogen has become increasingly important in sugar beet and table beet production worldwide. We used genome sequences of 326 C. beticola isolates collected from 4 continents from 4 closely related Beta subspecies (3 domesticated and 1 wild). We applied population genomic analyses to identify signatures of population differentiation and host specialization in C. beticola populations derived from the cultivated and wild hosts. We found evidence that C. beticola populations in agro-ecosystems likely originate from sea beet-infecting isolates. Intriguingly, host jumps from wild to cultivated beet occurred in at least 2 independent events as evidenced by our population data of C. beticola from wild beet collected in the Mediterranean and the UK. We explore the occurrence of genetic variants associated with fungicide resistance and virulence and show that standing genetic variation in C. beticola populations from both wild and domesticated plants may serve as a reservoir of functionally important alleles. Overall, our results highlight the ability of C. beticola to invade the agro-ecosystem and establish new populations, demonstrating the rapid adaptation potential of the species.

Porifera is a highly diverse phylum that can be found all over our planet, being particularly important in the deep-sea. Deep-sea sponges serve a great purpose for the welfare of many other organisms, providing ecosystem services such as habitat, nutrient recycling, and food sources. They are also exposed to several anthropogenic disturbances such as trawling and climate change which increases the conservation interests regarding this group. Despite this, there is a huge knowledge gap regarding the diversity of deep-sea sponges, their abundance, as well as their distribution. One location where this is the case is in the Denmark Strait and around Iceland. The deep-sea in these regions has a unique oceanographic setting with cold Arctic waters and warm Atlantic saline waters, which allows for a great diversity of benthic communities. By examining the spicule content as well as sequencing the COI marker of specimens from the Icelandic AS11-2016 cruise, the diversity of boreo-arctic deep-sea sponges could be investigated. With the help of spicules, the classes Hexactinellida and Demospongiae were identified, as well as nine different demosponge orders. Demospongiae was the largest part of this collection, and the most abundant order was Tetractinellida. Amongst these nine orders, 52 different species were identified. With COI barcoding, a subset of specimens could be determined either to species level or identified further than with morphology. This study sheds light on the diversity of Porifera that exists in the deep-sea of the Denmark Strait and around Iceland. The diversity and rarity of some species that were found highlight the conservation value for this area, making this study particularly important regarding the distribution and diversity of deep-sea sponges.

Canine pyometra is a suppurative uterine infection associated with immune dysregulation. This study investigated the role of regulatory T cells (Tregs) and associated factors in the pus accumulation within the canine uterus. Sixteen client-owned intact bitches, eight diagnosed with pyometra and the other eight healthy animals undergoing elective ovariohysterectomy, were enrolled. Blood samples were collected into ethylenediaminetetraacetic acid (EDTA)-coated tubes for flow cytometry. Tissue samples were obtained after ovariohysterectomy and used to examine localization of interleukin (IL)-2 and IL-2Rα as key regulators of Treg functions. Gene expression was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results of flow cytometry analysis revealed a significant increase in the population of Tregs in the uterine tissue and their corresponding decrease in the peripheral blood. This shift is likely reflective of the recruitment of Tregs from the peripheral blood to the decidua in pyometra. There was a marked upregulation in the expression of IL-2 in the uterine tissue. There was dysregulation in the expression of anti-inflammatory cytokines produced by Tregs (such as IL-10) and pro-inflammatory factors secreted by effector T cells (such as RORγt and IL-17A), which gave a deeper insight into the mechanism underlying the immune dysfunction in canine pyometra. Taken together, these observations elucidate the dynamic changes in Tregs and related factors during canine uterine pyometra, thus providing a new perspective on the equilibrium of the uterine immune microenvironment.

Air pollution exposure has been increasingly linked to adverse pregnancy outcomes. This study aimed to investigate the effects of PM_2.5 exposure throughout pregnancy on preterm birth, low birth weight (LBW), and small for gestational age (SGA). We analyzed a cohort of 16,965 pregnant women living in northern Thailand between 2016 and 2022. PM_2.5 concentration data were collected from two air quality monitoring stations operated by the Pollution Control Department (PCD) of Thailand. Logistic regression models were used to assess the association between daily PM_2.5 exposure and pregnancy outcomes. PM_2.5 exposure at levels exceeding 37.5 μg/m³ throughout pregnancy significantly increased the risk of preterm birth (aOR = 2.19, p < 0.001) and LBW (aOR = 1.99, p < 0.001) compared to the reference group (15.1–37.5 μg/m³). However, exposure at levels ≤15.0 μg/m³ also increased the risk for both outcomes compared to the same reference group. Subgroup analysis of high-risk pregnant women, including women aged > 35 years, with pre-pregnancy BMI (<18.5), pregnancy-induced hypertension, and nulliparous women, showed that the range of the critical PM_2.5 exposure threshold was 32.3–38.4 μg/m³ for preterm birth and 31.2–38.2 μg/m³ for LBW. This study highlights the significant association between PM_2.5 exposure and adverse pregnancy outcomes and suggests the need for targeted interventions to mitigate its effects on maternal and child health.

Jellyfish blooms are dynamic events driven by environmental and anthropogenic factors. This study reports the first documented bloom of the cannonball jellyfish (Stomolophus sp.) in Venezuelan waters, observed between March and April 2024 along approximately 120 km of coastline. Reports from anglers and divers confirmed high jellyfish abundances (~3 ind. m⁻³) across multiple sites. Environmental analyses suggest that fluctuations in sea surface temperature, increased chlorophyll a concentrations, and high precipitation in the preceding months may have triggered strobilation and subsequent bloom formation. However, the polyps have not yet been observed in the field, and advective movement from other locations cannot be ruled out. Given the commercial importance of Stomolophus spp. in neighboring regions, this record underscores the need for continued monitoring to assess potential range expansions and their ecological and socio-economic impacts. Additionally, the emergence of this bloom raises questions about the species’ distribution patterns, potential establishment in Venezuelan waters, and possible implications for local fisheries. Our findings contribute to the broader understanding of gelatinous zooplankton dynamics in the Caribbean Sea and provide baseline information for future ecological assessments and fisheries management strategies. Further studies, including genetic analyses, are needed to confirm species identity and investigate the drivers behind this unprecedented bloom.

The Cambrian Series 2–Miaolingian boundary interval in Australia—equivalent to the local Ordian and Templetonian stages—has long been a source of controversy, with a practical and consistent subdivision of this interval proving elusive. Recent ratification of the Miaolingian Series and Wuliuan Stage Global Boundary Stratotype Section and Point (GSSP) in South China, based primarily on the first appearance of the trilobite Oryctocephalus indicus and the coincident Redlichiine–Olenelline Extinction Carbon isotope Excursion (ROECE), highlights the importance of resolving this interval in Australia. In this contribution, we present an updated synthesis of Cambrian Series 2, upper Stage 4–Miaolingian, Wuliuan (Ordian–Templetonian) intervals across Australia, focusing on the reported ranges of small shelly fossils (SSF) and δ¹³C/δ¹⁸O isotope chemostratigraphy, in addition to trilobite and agnostid arthropod occurrences. Results show an underappreciated sequential series of taxon lowest occurrences across this interval. Based on these, we define two new organophosphatic brachiopod biozones: an upper Stage 4 (Ordian) Schizopholis napuru Zone, and an uppermost Stage 4–Wuliuan (upper Ordian–Templetonian) Micromitra nerranubawu Zone. Taxon ranges across these zones are consistent with the Cambrian Series 2–Miaolingian boundary at the Miaolingian/Wuliuan GSSP, allowing direct correlation with South China. Preliminary work in the Australian Stansbury and Georgina basins has revealed the promise of high-resolution SSF biostratigraphy coupled with δ¹³C/δ¹⁸O chemostratigraphy in addressing the ongoing issues associated with this interval. It is clear that such multi-proxy studies can assist in locating boundaries and correlating intervals across different Cambrian terranes with a high degree of precision, even when lacking index fossils such as O. indicus. Future work should focus on a systematic program of such studies within this interval, which will greatly assist in resolving correlations both within Australia and globally.

Growing awareness of the environmental cost of mining operations has led to increased research on monitoring and restoring legacy mine sites. Hyperspectral imaging (HSI) has emerged as a valuable tool in the mining life cycle, including post-mining environment. By detecting variations in crystal structure and physicochemical attributes on the surface of materials, HSI provides insights into site environmental and ecological conditions. Here, we explore the capabilities of drone-based HSI for mapping surface patterns related to contamination dispersal in a legacy uranium-rare earth element mine site. Hyperspectral data across the visible to near-infrared (VNIR) and short-wave infrared (SWIR) wavelength ranges (400-2500 nm) were collected over selected areas of the former Mary Kathleen mine site in Queensland, Australia. Analyses were performed using data-driven (Spectral Angle Mapper-SAM) and knowledge-based (Band Ratios-BRs) spectral processing techniques. SAM identifies contamination patterns and differentiates mineral compositions within visually similar areas. However, its accuracy is limited when mapping specific minerals, as most endmembers represent mineral groups or mixtures. BR highlights reactive surfaces and clay mixtures, reinforcing key patterns identified by SAM. The results indicate that drone-based HSI can capture and distinguish complex surface trends, demonstrating the technology's potential to enhance the assessment and monitoring of environmental conditions at a mine site.

Reports have indicated an increase in anti-Jewish hostility and antisemitic incidents following the Hamas terrorist attack in Israel on October 7, 2023, and the subsequent war in Gaza. In two studies (NStudy1 = 354 and NStudy2 = 490), we experimentally investigated the impact of priming with material referring to the war in Gaza on hostility toward Jews, and on antisemitism as well as other various ethnic groups (to determine whether this exposure specifically affected attitudes toward Jews or had a broader impact on ethnic attitudes in general). We also examined the indirect relationship between political orientation and anti-Jewish hostility and antisemitism, through sociopolitical factors such as global identification, out-group identity fusion, social dominance orientation, and misanthropy. Our results showed an experimental effect of increased negative attitudes toward Jews, as well as toward Britons and Scandinavians, but did not reveal an increase in antisemitism. This effect was not replicated in Study 2, possibly due to reduced media attention. The indirect effects suggested that political orientation (left vs. right-wing) was positively associated with anti-Jewish hostility and antisemitism through social dominance orientation. In contrast, conservative political orientation was negatively associated with antisemitism through out-group identity fusion with the Palestinian people. Our findings imply two distinct political pathways to antisemitism: one linked with classical political right-wing orientation and the other to a complex identity-based conflation of attitudes toward Israel with prejudice toward the Jewish ethnic group.

Purpose

The aim of this study was to translate the health-related quality-of-life questionnaire EORTC QLQ-LMC21 into Swedish and to test its clinical and psychometric reliability and validity in patients with liver metastases from colorectal cancer (CRC) undergoing surgical treatment.

Methods

The Swedish versions of the EORTC QLQ-C30 and EORTC QLQ-LMC21 were administered to 250 patients with liver metastases from CRC in four Swedish hospitals before and 3 months after surgical treatment. Psychometric validation of the questionnaire´s structure, reliability, and convergent and divergent validity was performed.

Results

Data from 242 (97%) patients were suitable for analysis. The QLQ-LMC21 was found to be sensitive to changes over time. Cronbach´s alpha coefficient indicated good internal consistency, ranging from 0.84 to 0.89. Test–retest reliability was evaluated in 120 patients (49%), and the intraclass correlation coefficient (ICC) indicated good reproducibility, ranging from 0.67 to 0.93. Convergent and discriminant validity were demonstrated adequately in the multitrait scaling analysis. There were weak correlations between the QLQ-C30 and QLQ-LMC21, which confirms that the health problems addressed by the QLQ-LMC21 are different from those addressed by the QLQ-C30.

Conclusions

The Swedish version of the EORTC QLQ-LMC21 proved to be a valid and reliable questionnaire to use in conjunction with the EORTC QLQ-C30.

The rapid datafication of society has impacted every aspect of our daily lives. However, the literature and discussions thus far on data are largely techno-centric. The agency and effect of individuals in data ecosystems are either reduced to a mere facilitative role or backgrounded in the data discourses. In this dissertation, data-related activities such as those found in data management and analytics processes were problematised as digital phenomena that await critical examination through the lens of Routine Dynamics theory.

Four studies are presented in this dissertation that investigate how people and technologies enact intricate routines for interoperating data in digital infrastructures;  how organisations manage the interplay of humans and technologies for structuring systems and data to implement the single source of truth concept; and how knowledge management models can unpack the intersection of in-house data analytics systems and cloud services in small- and medium-sized organisations to transform raw data into actionable knowledge. The insights from applying Routine Dynamics theory in those first three studies culminated in developing a conceptual model of routines.

The theory-informed problematisation of various data-driven activities in an empirical setting less represented in the scientific literature, such as in the nascent data ecosystem of Bhutan, advances the relevant body of knowledge with fresh perspectives on data management and analytics processes. Similarly, the rich account of data that factors in the role of humans will allow individuals and organisations to reframe narratives on data and enrich their data management and analytics practices in complex data ecosystems.

Background:

Genetic diversity in closed populations, such as pedigree dogs, is of concern for maintaining the health and vitality of the population in the face of evolving challenges. Measures of genetic diversity rely upon estimates of homozygosity without consideration of whether the homozygosity is desirable or undesirable or if heterozygosity has a functional impact. Pedigree coefficients of inbreeding have been the classical approach yet they are inadequate unless based upon the entire population.

Methods:

Homozygosity measures based upon pedigree analyses (n = 11,898), SNP array data (n = 244), and whole genome sequencing (n = 23) were compared in the Bearded Collie, as well as a comparison of SNP array data to a pedigree cohort (n = 5042) and a mixed-breed cohort (n = 1171).

Results:

Molecular measures based upon DNA are more informative on an individual's homozygosity levels than pedigree analyses, although SNP coefficients of inbreeding overestimate the level of inbreeding based on the nature of SNP array methodology. Whole genome sequence (WGS) analyses revealed that the heterozygosity observed is generally in variants having neutral or low impact, which would indicate that the variability may not contribute substantially to functional diversity in the population. The majority of high-impact variants were observed in the shortest runs of homozygosity (ROH) reflecting ancestral breeding and domestication practices. As expected, mixed-breed dogs displayed higher measures of genomic diversity than either Bearded Collies or other pedigree dogs as a whole using the current paradigm algorithm models to calculate homozygosity.

Conclusions:

Using typical DNA-based measures reflect only a single individual and not the population thereby failing to account for regions of homozygosity that reflect ancestral breeding, domestication history, breed-defining regions, or regions positively selected for health traits. Incorporating measures of genetic diversity into dog breeding schemes is meritorious. However, until measures of diversity can distinguish between breed-defining homozygosity and homozygosity associated with positive health alleles, the measures to use as selection tools need refinement before their widespread implementation.

Background

Higher meat intake has been associated with adverse health outcomes, including cardiovascular disease (CVD). This study investigated plasma metabolites associated with meat intake and their relation with cardiometabolic biomarkers, subclinical CVD markers, and incident CVD.

Methods

Associations between self-reported meat intake and 1272 plasma metabolites were investigated in the SCAPIS cohort (n = 8,819; ages 50–64). Meat-associated metabolites were further examined for relation with subclinical CVD markers in the POEM cohort (n = 502; age 50) and incident CVD in the EpiHealth cohort (n = 2,278; ages 45–75; 107 incident cases over 9.6 years follow-up). Meat intake was categorized into white, unprocessed red, and processed red meat. Linear regression analyzed associations between meat intake, metabolites and cardiometabolic biomarkers, and subclinical CVD markers, while Cox models evaluated association between meat-associated metabolites and incident CVD.

Results

After correction for multiple testing, 458, 368, and 403 metabolites were associated with white, unprocessed red, and processed red meat, respectively. Processed red meat-associated metabolites were associated with higher levels of fasting insulin, hemoglobin A1c, and lipoprotein(a), and were inversely associated with maximal oxygen consumption. Two metabolites, 1-palmitoyl-2-linoleoyl-GPE (16:0/18:2) (hazard ratios (HR: 1.32; 95 % CI: 1.08, 1.62)) and glutamine degradant (HR: 1.35; 95 % CI: 1.07, 1.72), that were inversely associated with intake of all meat types, were also associated with a higher risk of incident CVD.

Conclusions

This study provides comprehensive analysis of self-reported meat intake and plasma metabolites. The findings may enhance our understanding of the relationship between meat intake and CVD, and provide insights into underlying mechanisms.

Polar lows (PLs) are intense, high-latitude mesoscale weather systems that develop over oceanic areas near the polar regions during the cold season. Due to their association with severe weather conditions, they can significantly impact human life and socioeconomic activities. However, their small size, short lifespan, and limited observational data make forecasting PLs particularly challenging. Moreover, the complex physical mechanisms underlying their formation and intensification remain insufficiently understood, highlighting the need for further investigation.

The ocean plays a critical role in PL development, making an accurate representation of air-sea heat fluxes essential for enhancing forecasts and improving numerical simulations. Intense PLs are often accompanied by localized gale-force winds (>30 m/s), which can extract substantial heat (>1000 W/m²) from the ocean, sufficient to leave pronounced effects on the underlying ocean. Given the strong interactions between PLs and the ocean, this thesis aims to address key knowledge gaps in this field.

Sea spray, generated by wave breaking under high wind conditions, significantly influences turbulent heat fluxes at the air-sea interface. The first part of this thesis investigates the impact of spray-mediated heat fluxes on PLs through an atmosphere-wave coupled model. Results indicate that spray-enhanced sensible heat fluxes play a crucial role in PL development, whereas spray-enhanced latent heat fluxes have a relatively minor effect. Beyond sea spray, the ocean surface contains mesoscale structures such as eddies and fronts, which create mesoscale sea surface temperature anomalies. These anomalies can also influence air-sea turbulent heat and momentum fluxes, thereby favoring the intensification of PLs, as explored in the second part of this thesis. The third part of this thesis examines the impact of PLs on the global ocean. The findings indicate that the oceanic response to PLs exhibits strong regional variability. The Atlantic Ocean emerges as the most sensitive region.

In the context of global warming, PL activity is expected to shift poleward as the sea ice edge retreats to higher latitudes, resulting in a reduced frequency of occurrence. However, the response of individual PL development to a warming climate remains uncertain. The final part of this thesis addresses this uncertainty by applying a pseudo-global warming approach to investigate how individual PLs respond to climate change. The results reveal a general weakening of PL intensity under warmer conditions, reflected in lower maximum surface wind speeds and higher minimum sea level pressure. Nevertheless, PL-associated precipitation is projected to intensify, primarily due to increased latent heat release in a warmer atmosphere.

This article presents evidence on how students’ risk of dropping out or becoming inactive (NEET) are affected by pursuing a general (academic) versus vocational upper secondary education. We use a regression discontinuity design exploiting the grade-based admission process in Sweden. The results suggest that, among those students who apply to both types of education, starting a general program is associated with a higher likelihood of not graduating on time and spending more time without employment and outside studies during early adulthood. Furthermore, students on general programs perform worse in tests for courses mandatory for graduation, compared to students on vocational programs. We also find an increased dropout risk among students starting general programs when running family fixed effects models on the population of upper secondary students.

A measurement of the CP -violating parameters in B⁰_s → D∓s K± decays is reported, based on the analysis of proton-proton collision data collected by the LHCb experiment corresponding to an integrated luminosity of 6 fb⁻¹ at a centre-of-mass energy of13 TeV . The measured parameters are obtained with a decay-time dependent analysis yielding C_f = 0.791 ± 0.061 ± 0.022, ^A∆Γ_f = −0.051 ± 0.134 ± 0.058, A^∆Γ¯_f = −0.303 ± 0.125 ± 0.055,S_f = −0.571 ± 0.084 ± 0.023 and S_f = −0.503 ± 0.084 ± 0.025, where the first uncertainty is statistical and the second systematic. This corresponds to CP violation in the interference between mixing and decay of about 8.6 σ. Together with the value of the B_s⁰ mixing phase−2β_s, these parameters are used to obtain a measurement of the CKM angle γ equal to (74 ± 12)^◦ modulo 180^◦, where the uncertainty contains both statistical and systematic contributions. This result is combined with the previous LHCb measurement in this channelusing 3 fb⁻¹ resulting in a determination of γ = (81⁺¹²₋₁1)^◦.

This study investigates the effects of incorporating ¹¹B₄C interlayers into Fe/Si multilayers, with a focus on interface quality, reflectivity, polarization, and magnetic properties for polarizing neutron optics. It is found that the introduction of 1–2 Å ¹¹B₄C interlayers significantly improves the interface sharpness, reducing interface width and preventing excessive Si diffusion into the Fe layers. X-ray reflectivity and polarized neutron reflectivity measurements show enhanced reflectivity and polarization, with a notable increase in polarization for 30 Å period multilayers. The inclusion of interlayers also helps prevent the formation of iron-silicides, improving both the magnetic properties and neutron optical performance. However, the impact of interlayers is less pronounced in thicker-period multilayers (100 Å), primarily due to the ratio between layer and interface widths. These results suggest that ¹¹B₄C interlayers offer a promising route for optimizing Fe/Si multilayer performance in polarizing neutron mirrors.

In this study, we developed and characterized a fully biodegradable composite bone cement reinforced with short, randomly oriented amorphous magnesium fibers. Fibers of composition Mg₆₀Zn₃₅Ca₅ (in at.%) with 50 μm diameter and 2 mm length were produced by wire spinning and then mixed with a magnesium calcium phosphate cement using fiber volume fractions between 10 and 20 %. The interface strength between the fibers and cement was improved by treating the fibers with diammonium hydrogen phosphate. Compared to the reference cement without fibers, flexural strength was increased by 18 % for the composites with 13 and 18 vol% fibers, and the work of fracture was increased by over 1000× in all cases (p < 0.05, n = 6). Immersion in simulated body fluid for two and four weeks showed that the cement's struvite phase degrades first, and overall, the composite degrades slower. The degradation rate can be tailored to the application by changing the fiber percentage or the cement/fiber composition. Murine pre-osteoblastic cells (MC3T3) cultured in extracts of reference and composite cements had significantly higher cell viability, and composites with 13 vol% fibers also had a significantly higher number of cells compared to the control, indicating that the fibers can enhance and promote pre-osteoblastic cell growth. The results demonstrate that amorphous magnesium fibers enhance both the mechanical and biological properties of ceramic bone cement, expanding their prospects for clinical application.

Harmful effects of mechanical ventilation with large tidal volumes, volutrauma, may contribute much to diffuse acute lung injury. Extracellular vesicles have been noted in the context of vital organ injury. We hypothesized that extracellular vesicles from acutely injured lung can be found in both lung and blood. In a two-hit experimental porcine model, we tested if extracellular vesicles could be detected in bronchoalveolar lavage fluid and in plasma over a six-hour period of large tidal volume ventilation after surfactant depletion. After 2 hours of volutrauma, bronchoalveolar lavage fluid showed increased levels of extracellular vesicles containing nucleic acids (stained by SYTO 13) and those positive for both SYTO 13 and HMGB1. No such increase was detected in plasma at any timepoint during the six-hour experiments. This shows that nucleic acid-containing extracellular vesicles appear to be involved in progression of lung injury, possibly indicating cellular damage, but their potential to serve as diagnostic biomarkers of acute lung injury progression, based on plasma sampling, and in the very early phase, is not confirmed by these findings.

Lakes are important in global carbon cycling and play a crucial role in the exchange of CO2 between the atmosphere and a Lake. Where lakes act mainly as a source of CO2 and sometimes as a sink, this study highlights the key dynamics of CO2 by exploring the seasonal and interannual variation of CO2 with a special focus on the surface layer of water in Lake Erken. I have worked on the data collected by high-frequency automated sensors placed at different depths for 2020 and 2021. This study focuses on the surface water layer because it has had direct contact with the atmosphere for two years, excluding the winter period from both years. I considered the daily average of all study parameters for performing statistical analysis. This study showed how the partial pressure of CO2 (pCO2)is influenced by other key variables by exploring the impact of both biological (photosynthesis and respiration) and physical processes (i.e., water temperature and windspeed). Statistical analysis showed that both years have clear seasonal patterns where pCO2 is lower in the spring, possibly due to photosynthesis, and higher in the summer and autumn due to respiration and decomposition processes. Nevertheless, there were no significant variations between the years. Univariate analysis showed a strong linear relationship between O2 and pCO2, while O2 explained 95% of the variation in pCO2.Nevertheless, other parameters such as wind speed, chlorophyll, water temperature, and Schmidt stability were found to have a lesser influence. However, multiple regressions found oxygen, chlorophyll, and wind speed to be the most significant parameters. These parameters played a significant role in photosynthetic activity, which ultimately impacted pCO2 variations. R2 stated that 98% of the variation was only due to O2 and wind speed. These results highlight the importance of biological cycling and physical conditions on pCO2.Therefore, O2 was found to be a powerful predictor of CO2 dynamics because it combines biological and physical processes. After O2, the results also illustrate that windspeed has a significant contribution to pCO2 cycling. These findings contribute to our understanding of pCO2 dynamics in lakes and advance the prediction of CO2 emissions from lakes to the atmosphere.

Ineffective medication is a major healthcare problem causing significant patient suffering and economic costs. This issue stems from the complex nature of diseases, which involve altered interactions among thousands of genes across multiple cell types and organs. Disease progression can vary between patients and over time, influenced by genetic and environmental factors. To address this challenge, digital twins have emerged as a promising approach, which have led to international initiatives aiming at clinical implementations. Digital twins are virtual representations of health and disease processes that can integrate real-time data and simulations to predict, prevent, and personalize treatments. Early clinical applications of DTs have shown potential in areas like artificial organs, cancer, cardiology, and hospital workflow optimization. However, widespread implementation faces several challenges: (1) characterizing dynamic molecular changes across multiple biological scales; (2) developing computational methods to integrate data into DTs; (3) prioritizing disease mechanisms and therapeutic targets; (4) creating interoperable DT systems that can learn from each other; (5) designing user-friendly interfaces for patients and clinicians; (6) scaling DT technology globally for equitable healthcare access; (7) addressing ethical, regulatory, and financial considerations. Overcoming these hurdles could pave the way for more predictive, preventive, and personalized medicine, potentially transforming healthcare delivery and improving patient outcomes.

Background: Apps have the potential to support psychological treatments by providing psychoeducation, increasing homework compliance, and generalizing therapeutic skills outside of sessions. However, there are few apps developed to support specific evidence-based treatment for PTSD for adolescents.

Objective: This paper shares experiences developing an app to complement Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). It also describes adolescents’ and therapists’ perceived usefulness and the potential effect of the app ‘My everyday life’ on posttraumatic stress symptoms (PTSS).

Methods: We did a needs assessment with adolescents, therapists, and TF-CBT trainers, followed by programming and beta-testing. We carried out a mixed methods study of 59 adolescent patients (aged 13–18 years) and their therapists. Using a triangulation design, we combined quantitative data on app use and changes in PTSS with qualitative data from interviews with 10 adolescents and 10 therapists who described their experiences with the app.

Results: The app includes psychoeducation, mental health self-monitoring, coping tools, and goal-setting functionality. The most used features were psychoeducation and breathing exercises. Few therapists actively used the monitoring progress feature. Both adolescents and therapists found the app beneficial for everyday use, though some therapists were unsure about how to integrate it with TF-CBT. Adolescents reported significant PTSS improvement during TF-CBT with the app as a complement. Adolescents with post-treatment data (n = 13) did not report significantly different PTSD improvement compared to adolescents without access to app, but the study lacked power to draw strong conclusions.

Conclusions: The app ‘My everyday life’ can be useful for adolescents receiving TF-CBT. The therapists may benefit from clearer guidelines on how to integrate apps with evidence-based treatments. Digital tools are a promising avenue for supporting the implementation of evidence-based treatment.

In many cancers, the tumor microenvironment is enriched with cholesterol due to increased biosynthesis and uptake by cancer cells, resulting in the accumulation of cholesterol, cholesterol esters, oxysterols and other metabolites with various functions. These molecules serve as structural components, energy sources and intracellular signaling mediators, while their toxic by-products are secreted to suppress anti-tumor immune activity and prevent lipid peroxidation that could induce cancer cell apoptosis. Immune cells in the tumor microenvironment also contribute to cholesterol dynamics. Tumor-associated macrophages (TAMs) release cholesterol to support tumor cell metabolism, while myeloid-derived suppressor cells (MDSCs) also release cholesterol and consume essential metabolites such as L-arginine, which impairs T-cell proliferation and activation. Elevated cholesterol in dendritic cells impairs migration and tumor antigen presentation and, in lymphocytes, favors the development of a regulatory T cells (Treg) phenotype and inhibits the release of antitumor cytokines, further weakening the immune response. These findings suggest that targeting cholesterol metabolism is a promising strategy for cancer treatment, improving the efficacy of immune checkpoint blockade (ICB) therapies. In this manuscript, the molecular mechanisms underlying the effects of cholesterol on the tumor immune landscape are reviewed and the potential of cholesterol-lowering drugs to enhance antitumor immune responses is explored.

Recent work by the ICGC-PCAWG consortium identified recurrent focal deletions in the BRD4 gene, decreasing expression despite increased copy number. We show that these focal deletions occur in the context of cyclin E1 amplification in breast, ovarian, and endometrial cancers, and serve to disrupt BRD4 regulatory regions and gene expression across isoforms. We analyze open reading frame screen data and find that overexpression of BRD4 long (BRD4-L) and short isoform BRD4-S(a) impairs cell growth across cell lines. We confirm these results in OVSAHO ovarian cancer cells, where the overexpression of BRD4 isoforms significantly reduces tumor growth. Next, we mimic BRD4 focal deletions using CRISPR-Cas9 technology and show that these focal deletions rescue ovarian cancer cells from toxicity associated with BRD4 overexpression, suggesting that BRD4 levels must be fine-tuned for cancer cell proliferation. Our study provides experimental evidence for the first recurrent deletion reducing toxicity in cancer, expanding the landscape of cancer progression mechanisms.

Extreme temperature events can cause severe disruptions to society, from negative health consequences to infrastructure damage. Heat action plans, including early warning systems, are a key element in the mitigation of such impacts. Here we investigate the predictability of temperature extremes and their associated health impacts in Europe, in the context of our changing climate. We first investigate the predictability of temperature extremes from a theoretical standpoint, leveraging techniques from dynamical systems theory to quantitatively assess atmospheric persistence. Our results show a regionally and tropospheric-level dependent relationship between warm temperature extremes and atmospheric persistence. We then assess the practical predictability of hot and cold temperature extremes utilising sub-seasonal reforecast data, and the aforementioned measure of persistence. We demonstrate atmospheric persistence informing on practical predictability, measured here by forecast skill, in some cases, again with marked seasonal variation. Furthermore, local processes appear to play an important role in the endgenderment of, and forecast skill for, temperature extremes. Next, we apply methods from epidemiology to temperature forecasts, to produce heat-related mortality forecasts for 2022 and 2023. We find that heat-related mortality can, on average, be forecasted skilfully up to approximately one week. However, we emphasise the increased forecast skill in Iberia associated with the record-breaking temperatures experienced in 2022. Finally, we assess the role of changes in atmospheric circulation patterns for heat-related mortality. We note that changes in the dynamics of the atmosphere can play a reinforcing role to that of the thermodynamic warming trend, such as during the European summer of 2003. These findings could help inform the development of fit-for-purpose heat warning systems. Collectively, this thesis highlights the value in combining theoretical, and impact-focused approaches, for predicting extreme temperatures and their associated health impacts. This is imperative for society’s broader effort to adapt to a warmer climate.

I det här självständiga arbetet har vi bidragit med kunskap om hur pedagoger förhåller sig till val av barnlitteratur och metoder för att integrera ett genusperspektiv i högläsning och litteratursamtal. Det genomfördes sju stycken semistrukturerade intervjuer under två veckor med både förskollärare och barnskötare i tre olika svenska kommuner. Med teorin om didaktiska val som utgångspunkt analyserades intervjusvaren tematiskt. Detta resulterade i fem teman. De olika teman fokuserade på olika överväganden pedagoger gör vid valet av litteratur med fokus på genus, som att böckerna skulle anpassas efter barnens ålder och passa det aktuella projektet avdelningen arbetar med. Andra pedagoger hade ett specifikt mål med litteraturen och valde bok efter vad de ville uppnå med läsningen av normkritisk litteratur. Sedan undersöktes även hur pedagoger jobbar med denna litteratur ute i verksamheten. Här gavs många varierande svar mellan hur pedagogerna specifikt jobbar med barnen när hen läser boken där hen fokuserar på samtal och diskussioner om bokens innehåll, men även hur de jobbar allmänt med normkritisk litteratur på hela förskolan. Under intervjuerna gavs även förslag på böcker som pedagogerna skulle kunna jobba utifrån med fokus på genus. Dessa böcker har analyserats, tematiseras och kopplats till de svar som pedagogerna själva gav kring hur de jobbar med boken. Denna analys baserades på socialkonstruktivismens syn på genus och gav fyra teman som visar att pedagoger uppmärksammar olika egenskaper hos böcker som gör att de väljer att de läser dem för barnen. Vissa teman visades starkare som att pedagogerna ville ha mångfald och representation, medan vissa ville att barnen skulle känna igen sig i karaktärerna i böckerna. Resultatet kopplas sedan till tidigare forskning och relevant didaktisk teori. Slutligen diskuteras även studiens brister och förslag på vidare forskning. 

Syftet med studien är att undersöka verbaliserade erfarenheter av estetiska uttrycksformer i förskolan, samt hur de uppfattar att dessa arbetssätt påverkar barns lärande och utveckling. Studien består av två delstudier: den första omfattar intervjuer med fem förskollärare och den andra med fem specialpedagoger. Genom att samla in båda yrkesgruppernas uppfattningar skapas en bredare förståelse för hur estetiska uttrycksformer upplevs och kommuniceras i förskolans kontext. Studien har en kvalitativ ansats och utgår teoretiskt från didaktik i förskolan med en läroplansteoretisk grund med stöd av de didaktiska frågorna vad, hur och varför. Analysen genomfördes med hjälp av tematisk analys. Resultatet från delstudie 1 visar att förskollärare uppfattar estetiska uttrycksformer som centrala för att stödja barns kommunikation, känslomässiga uttryck och delaktighet. De används för att skapa kreativa och inkluderande lärmiljöer. Hinder som brist på tid, resurser och kompetens lyfts fram som utmaningar. Resultatet från delstudie 2 lyfter specialpedagogerna fram sina erfarenheter om de estetiska uttrycksformerna och hur detta påverkar barns lärande och utveckling. De framhåller både möjligheter till fortsatt utveckling och utmaningar, såsom begränsade ekonomiska resurser. Studien betonar även vikten av barns rättigheter samt anpassning för att möta individuella behov.

In myelodysplastic syndromes (MDS), cytogenetic characteristics of the malignant bone marrow cells influence the clinical course. The aim of this study was to evaluate whether cytogenetics is useful to predict outcome and response in patients with del(5q) under azacitidine (AZA) +/- lenalidomide (LEN) therapy. We therefore performed comprehensive cytogenetic analyses in MDS patients with del(5q) treated within the randomized phase II trial NMDSG10B. Seventy-two patients were enrolled in the study and 46 patients (64%) had sufficient cytogenetics at inclusion and response evaluation. Karyotyping was significantly more sensitive during follow-up to detect del(5q) compared to FISH, 34 patients (97%) versus 27 patients (77%) (p = 0.027). The overall response rate (ORR) did not differ between the 11 patients with < 3 aberrations (median 1 aberration) and the 59 patients with >= 3 aberrations (median 7 aberrations, range 3-16), while >= 3 aberrations were associated with shorter overall survival (OS), 9.9 months versus 25.2 months (p = 0.004). OS was significantly shorter in patients with unbalanced translocation of 5q than patients with del (5)(q14q34), 8.4 months versus 21.1 months (p = 0.004). Both complex karyotype and multi-hit TP53 alterations were more frequent in patients with unbalanced translocations of 5q versus del (5)(q14q34), 98% and 88% versus 67% and 47% (each p = < 0.001). Most patients with cytogenetic progression had multi-hit TP53 alterations at inclusion. Cytogenetic progression occurred at a similar frequency in the AZA arm and in the AZA + LEN arm. In summary, this study in homogenously treated MDS patients with different abnormalities of 5q demonstrates the influence of cytogenetics on treatment results. Trial Registration: EudraCT number: 2011-001639-21; identifier: NCT01556477.

Using (27.12 +/- 0.14) x 10(8) psi(2S) events collected by the BESIII detector operating at BEPCII, we search for the decay eta(c) (2S) -> p (p) over bar via the process psi(2S) -> gamma eta(c)(2S) and only find a signal with a significance of 1.7 sigma. The upper limit of the product branching fraction at the 90% confidence level is determined to be B(psi(2S) -> gamma eta(c)(2S)) B(eta(c) (2S) -> p (p) over bar)< 2.4 x 10(-7). The branching fractions of chi(cJ) -> p<(p)over bar> (J = 0, 1, 2) are also measured to be B(chi(c0) -> p (p) over bar) = (2.51 +/- 0.02 +/- 0.08) x 10(-4), B(chi(c1) -> p (p) over bar) = (8.16 +/- 0.09 +/- 0.25) x 10(-4), and B(chi(c2) -> p (p) over bar) = (8.33 +/- 0.09 +/- 0.22) x 10(-4), where the first uncertainty is statistical and the second systematic.

Based on 7.33 fb(-1) of e(+)e(-) collision data collected by the BESIII detector operating at the BEPCII collider at center-of-mass energies from 4.128 to 4.226 GeV, a search for the Majorana neutrino nu(m) is conducted in the lepton-number-violating decays of D-s(+) -> h(-)h(0)e(+)e(+). Here, h(-) represents a K- or pi(-), and h(0) represents a pi(0), K-S(0) or phi. No significant signal is observed, and the upper limits of their branching fractions at the 90% confidence level are determined to be B(D-s(+) -> phi pi(-)e(+)e(+)) < 6.9 x 10(-5), B(D-s(+) -> phi K(-)e(+)e(+)) < 9.9 x 10(-5), B(D-s(+)-> K-S(0)pi(-)e(+)e(+)) < 1.3 x 10(-5), B(D-s(+) -> K(S)(0)K(-)e(+)e(+)) < 2.9 x 10(-5), B(D-s(+) -> pi(-)pi(0)e(+)e(+)) < 2.9 x 10(-5) and B(D-s(+) -> K-pi(0)e(+)e(+)) < 3.4 x 10(-5). The Majorana neutrino is searched for with different mass assumptions within the range [0.20, 0.80] GeV/c(2) in the decay of D-s(+) -> phi e(+)nu(m) with nu(m) -> pi(-)e(+), and the upper limits of the branching fractions at the 90% confidence level are at the level of 10(-5)-10(-2), depending on the mass of the Majorana neutrino.

In this paper we present the framework for measuring angular power spectra in the Euclid mission. The observables in galaxy surveys, such as galaxy clustering and cosmic shear, are not continuous fields, but discrete sets of data, obtained only at the positions of galaxies. We show how to compute the angular power spectra of such discrete data sets, without treating observations as maps of an underlying continuous field that is overlaid with a noise component. This formalism allows us to compute the exact theoretical expectations for our measured spectra, under a number of assumptions that we track explicitly. In particular, we obtain exact expressions for the additive biases ('shot noise') in angular galaxy clustering and cosmic shear. For efficient practical computations, we introduce a spin-weighted spherical convolution with a well-defined convolution theorem, which allows us to apply exact theoretical predictions to finite-resolution maps, including HEALPix. When validating our methodology, we find that our measurements are biased by less than 1% of their statistical uncertainty in simulations of Euclid's first data release.

The Euclid mission of the European Space Agency will provide weak gravitational lensing and galaxy clustering surveys that can be used to constrain the standard cosmological model and its extensions, with an opportunity to test the properties of dark matter beyond the minimal cold dark matter paradigm. We present forecasts from the combination of the Euclid weak lensing and photometric galaxy clustering data on the parameters describing four interesting and representative non-minimal dark matter models: a mixture of cold and warm dark matter relics; unstable dark matter decaying either into massless or massive relics; and dark matter undergoing feeble interactions with relativistic relics. We modelled these scenarios at the level of the non-linear matter power spectrum using emulators trained on dedicated N-body simulations. We used a mock Euclid likelihood and Monte Carlo Markov chains to fit mock data and infer error bars on dark matter parameters marginalised over other parameters. We find that the Euclid photometric probe (alone or in combination with cosmic microwave background data from the Planck satellite) will be sensitive to the effect of each of the four dark matter models considered here. The improvement will be particularly spectacular for decaying and interacting dark matter models. With Euclid, the bounds on some dark matter parameters can improve by up to two orders of magnitude compared to current limits. We discuss the dependence of predicted uncertainties on different assumptions: the inclusion of photometric galaxy clustering data, the minimum angular scale taken into account, and modelling of baryonic feedback effects. We conclude that the Euclid mission will be able to measure quantities related to the dark sector of particle physics with unprecedented sensitivity. This will provide important information for model building in high-energy physics. Any hint of a deviation from the minimal cold dark matter paradigm would have profound implications for cosmology and particle physics.

Essay I:First-Degree Price Discrimination achieves efficiency in monopoly settings by having the producer appropriate the total surplus, while uniform pricing leads to higher consumer surplus but is inefficient. The market for multi-indication drugs – those that have multiple uses – has two features that distinguish it from a static monopoly model. Firstly, the monopoly is time-bound and is followed by a competitive market. Secondly, manufacturers have private information about which groups of patients their drug could be useful for and must incur a cost to reveal each one. I extend Bergemann et. al (2015) to this setting to develop a mechanism which maximises consumer surplus and achieves weakly higher efficiency than First-Degree Price Discrimination (which can be inefficient as the monopolist does not internalise the long-term benefit). By conditioning market segmentation on the manufacturer's revealed information, a regulator can incentivise it to conduct costly trials for the most socially beneficial uses of their drugs and maximise achievable total and consumer surplus. Ex-post, First-Degree Price Discrimination may appear as a specific case as a result of the segmentation - as such, I reveal conditions under which First-Degree Price Discrimination may be efficient. I also provide solutions for achieving market segmentation that minimizes variance in prices or individual consumer surplus while still achieving the primary aims of maximising achievable surplus. In doing so I make the case for regulators to use market segmentation as a tool to provide incentives for manufacturers. 

Essay II: Advanced Therapy Medicinal Products (ATMPs) are novel, expensive, one-time treatments that have the potential to cure certain medical conditions, but their long-term effectiveness carries inherent risk. Risk-sharing agreements (RSAs) have been proposed as a means to mitigate the negative impacts of this uncertainty. However, traditional models of RSAs often fail to account for the irreversibility of ATMPs and their long-term implications for payers’ budgets and future decision-making, as well as the fact that payers and manufacturer interact repeatedly. 

In this paper, I develop a model in which a payer and a manufacturer engage in an infinitely repeated stochastic game. Patients arrive following an overlapping-generations framework, and the price of treatment is negotiated based on the state of the budget and population health. Effective ATMPs free up resources in the budget for future incoming patients and increase demand. The outcomes of this game are analysed under two distinct payment structures: one where payments are made upfront for each patient and another where payments are contingent on the continued effectiveness of the ATMP. Results show that when the health benefits of the ATMP are comparable to those of an outside option, the RSA improves efficiency. However, when the health benefits of the ATMP are significantly higher, the efficiency of upfront payment can improve.

Essay III: (with Erik Grönqvist, Per Johansson and August Wadell Leimdörfer)How should limited resources for health care be prioritized? Health economic evaluation can inform decision makers if new medical treatments are good value for money. The standard cost-effectiveness framework maximizes QALY gains without considering the distribution of these gains across individuals or groups. However, the way health is produced matters for most people. With general preferences for equity in society, also disease severity would matter for welfare when prioritizing. With public preferences over both disease severity and cost-effectiveness, and policymakers need to balance equity with efficiency. We provide evidence for how the public trades disease severity for cost-effectiveness from a novel striped-down discrete choice experiment, and we also provide a method for adjusting the ICER threshold to account for disease severity.

Studiens syfte är att undersöka lärares upplevelser kring tillgången till konkret material på sex olika skolor i Uppsala län, samt i vilken utsträckning och på vilket sätt deras elever får tillgång till konkret material i årskurs 1. Vidare syftar studien till att analysera hur lärare interagerar med och använder det konkreta materialet som ett medierande redskap i undervisningspraktiken. Med särskilt fokus på dess betydelse för elevers lärande och förståelse av matematiska områden. För att besvara dessa frågor genomförs semistrukturerade intervjuer med sex behöriga lärare. I intervjuerna undersöker vi hur de arbetar med konkret material i klassrummet, hur tillgången ser ut på skolnivå samt vilka elever som får tillgången till att använda konkret material. Det insamlade materialet analyseras genom tematisk analys med utgångspunkt i sociokulturella perspektivet. Resultatet vi fick fram i studien var att alla elever hade tillgång till att använda allt konkret material i början av årskurs 1. Dock framkom det att det var framförallt elever med matematiksvårigheter som regelbundet fick tillgång till materialet under hela läsåret. Tillgången till materialet på skolorna var generellt bra och majoriteten av de undersökta skolorna hade en bra uppsättning av konkret material. I diskussionen belyser vi bland annat hur konkret material fungerar som ett medierande redskap i undervisningen, samt den positiva påverkan konkret material har på lärandet för att det aktiverar flera sinnen.