Logo: to the web site of Uppsala University

Background and aim

Chronic pain is often accompanied by other symptoms such as fatigue and sleep disturbance, and these symptoms all correlate with neuroimmune activation. However, their relation to one another on a neuroimmune axis remains elusive. Based on a recent review, cytokines in the cerebrospinal fluid (CSF) seem to be generally upregulated in patients with chronic pain compared to controls, disregarding pain type. Some of these have the possilibity of altering blood–brain barrier (BBB) permeability. Therefore, cytokine levels in serum and CSF, as well as BBB permeability, were measured in a cohort of patients suffering from either degenerative disc disease (DDD), lumbar disc herniation (LDH) or osteoarthritis (OA). In this exploratory study, we were interested in whether cytokines in the serum or CSF are associated with sleep disturbance or fatigue, with special consideration of the effect of BBB permeability, and whether functional clusters can be found among these cytokines.

Method

One-hundred-twenty patients with DDD/LDH/OA, all awaiting surgery, were included. Blood and CSF were collected on the day of surgery. Pain was measured with a visual analog scale 0–100 mm, sleep disturbance was assessed using Pittsburgh Sleep Quality Index (PSQI), and fatigue was measured using the Multidimensional Fatigue Inventory (MFI). A 92-protein multiplex panel (OLINK, Sweden) was used to analyze cytokine expression in serum and CSF, respectively. CSF-serum albumin quotient was measured using ELISA. Non-parametric statistics were used for univariate analyses, and a false discovery rate (FDR) < 0.10 was considered statistically significant. Bonferroni correction was applied to all multivariable protein analyses to obtain conservative effect estimates.

Main results

There was an association between BBB permeability and serum-CSF dynamics: thirty-one cytokines showed significant CSF-serum correlation, and BBB permeability was significantly correlated to the quotients of 35 cytokines and to the CSF levels of 11 cytokines. Several cytokines were negatively correlated to both pain at rest and general fatigue. No correlations were found between sleep disturbance and cytokines. Network analyses of serum and CSF cytokines that were correlated with fatigue revealed functional clusters in both compartments. Anxiety, depression, and pain during rest were important regressors for sleep disturbance with an R² = 0.41. In addition to depression and pain during rest, CSF levels of CCL25 was a significant regressor regarding general fatigue, with an R² = 0.47.

Discussion and conclusion

In this exploratory study of immune profiles in chronic pain cohorts awaiting surgery, the importance of BBB dynamics on serum-CSF cytokine dynamics, and to a lesser extent on central levels of cytokines, is highlighted. Surprisingly, there were no associations between any cytokines in serum or CSF and sleep disturbance, despite a high prevalence of clinically significantly disturbed sleep. In contrast, several associations between general fatigue and cytokine levels in both serum and CSF were found. Cytokines of note are CXCL11 and CCL25 in the CSF, especially because of their direct functional association. CXCL11 has been found to exert neuroprotective effects in animal models, while CCL25 is known as a proinflammatory cytokine and is the only cytokine to fall out as a significant negative contributor to degree of fatigue. While causality cannot be addressed, the negative correlation between CCL25 and fatigue in both univariate and multivariate analyses implies that neuroimmune activity might have an ameliorating effect on the degree of fatigue.

This study further adds to existing evidence that centrally acting cytokines are associated with severity of symptomatology, and highlights that pain and fatigue seem to have slightly different cytokine profiles. Sleep disturbance needs to be further addressed, ideally using both subjective and objective assessment methods. CCL25 and CXCL11 are interesting biomarkers for future research on pain and associated symptoms.

How can robots learn and adapt to new tasks and situations with little data? Systematic exploration and simulation are crucial tools for efficient robot learning. We present a novel black-box policy search algorithm focused on data-efficient policy improvements. The algorithm learns directly on the robot and treats simulation as an additional information source to speed up the learning process. At the core of the algorithm, a probabilistic model learns the dependence between the policy parameters and the robot learning objective not only by performing experiments on the robot, but also by leveraging data from a simulator. This substantially reduces interaction time with the robot. Using the model, we can guarantee improvements with high probability for each policy update, thereby facilitating fast, goal-oriented learning. We evaluate our algorithm on simulated fine-tuning tasks and demonstrate the data-efficiency of the proposed dual-information source optimization algorithm. In a real robot learning experiment, we show fast and successful task learning on a robot manipulator with the aid of an imperfect simulator.

This study examines the long-term association between income and life expectancy in Sweden between 1960 and 2021. The study is based on register data that include all Swedish permanent residents aged 40 y and older. The results show that the gap in life expectancy between the top and bottom income percentiles widened substantially: For men, it increased from 3.5 yin the 1960s to 10.9 y by the 2010s, and for women, from 3.8 yin the 1970s to 8.6 y by the 2010s. Despite a reduction in income inequality and an expansion of social spending from the 1960s to the 1990s, health inequality continuously increased over the period under study. The changes of the relation between real income and life expectancy, the so-called Preston curve, reveal a much faster improvement in life expectancy in the upper half of the income distribution than suggested by the cross-sectional relation between income and life expectancy. Analysis of causes of death identified circulatory diseases as the main contributor to improved longevity, while cancer contributed more to the increased gap in life expectancy for women and equally for men. Finally, analysis of the change in the income gradient in avoidable causes of death showed the strongest contribution of preventable causes, both for men and women.

Background & aims

Malnutrition may be a hidden but relevant health condition in individuals with obesity and osteoarthritis. The Global Leadership Initiative on Malnutrition (GLIM) consensus includes muscle mass as one of the key phenotypic criteria, potentially enhancing its ability to detect malnutrition in individuals with obesity. We comprehensively profiled the nutritional status of individuals with obesity and advanced knee osteoarthritis and explored associations with health outcomes.

Methods

Data from the Prevention Of MusclE Loss in Osteoarthritis (POMELO) study was used, which included individuals with knee osteoarthritis and BMI≥35 kg/m². Nutritional status was evaluated using the GLIM and sarcopenic obesity (SO) criteria. Low muscle mass (dual-energy x-ray absorptiometry), inflammation (C-reactive protein [CRP]), low muscle strength (handgrip/BMI), objective physical function (chair-stand test, 6-min walk test), and self-reported measures (quality of life, arthritis symptoms, and self-efficacy) were evaluated. Linear regressions were performed between GLIM-malnutrition and health outcomes, adjusted by age.

Results

Forty-six individuals (73.9% female, age 64.2 ± 6.7 years, BMI 42.4 ± 4.7 kg/m²) were included. Regarding nutritional status, 26.1% were classified with malnutrition (i.e., defined by the combination of low muscle mass and elevated CRP concentration), 26.1% with SO, and 13% shared both conditions. Individuals with malnutrition presented with worse self-reported physical function (WOMAC function: 38.0 ± 6.6 vs. 32.0 ± 12.5, p = 0.04) and lower arthritis self-efficacy (‘other symptoms’ component: 5.1 ± 1.9 vs. 6.3 ± 1.7, p = 0.04) compared to those without malnutrition. A trend was identified for lower quality of life (visual analog scale 46.8 ± 12.3 vs. 58.3 ± 20.5, p = 0.06) in those with malnutrition. Poor lipid control (R² = 0.15, β = 0.76, 95% CI 0.08–1.44, p = 0.030), body fat (R² = 0.14, β = 5.56, 95% CI 1.01–10.11, p = 0.018), and poor arthritis self-efficacy (R² = 0.09, β = −1.23, 95% CI -2.39–0.06, p = 0.040) were also associated with malnutrition.

Conclusions

Participants presented with high malnutrition rates (1 out of 4), and half of them also had SO. Malnutrition was associated with abnormal metabolic parameters, lower arthritis self-efficacy, and worse self-reported physical function. An early nutritional assessment and intervention may be imperative for individuals with osteoarthritis and obesity to mitigate health consequences.

The study presents cellulose-based membranes derived from lignin-rich (unbleached high-kappa number softwood and hardwood) and lignin-free (fully bleached softwood) kraft pulps for the removal of cationic dyes from both simulated and real aqueous environmental systems. Characterization techniques revealed that the lignin-enriched cellulose-based membranes exhibited enhanced wet mechanical properties and a broader range of functional groups. The functional diversity inherent in lignin-containing membranes resulted in superior adsorption capacity for dyes such as Methylene Blue and Crystal Violet, compared to lignin-free counterparts.

Detailed adsorption performance metrics—including kinetics, equilibrium studies, and the effects of pH and ionic strength—were thoroughly investigated. The adsorption capacity was 99–102 μmol g⁻¹ for hardwood-derived membranes and 79–85 μmol g⁻¹ for softwood-derived membranes at 25 °C. The process followed the pseudo-first-order kinetic model, likely due to the membranes' low porosity and energy homogeneity, which facilitated rapid adsorption.

Electrostatic interactions played a pivotal role in dye attraction, while pH and ionic strength studies emphasized the importance of hydrogen bonding between cationic dyes and lignocellulose-based membranes. This research highlights the significance of utilizing cellulose-based membranes with enhanced lignin content in water purification, demonstrating their effective adsorption capabilities in both controlled and real-world environments. The approbation tests of these membranes showcased their substantial potential for practical water purification applications, contributing to the development of sustainable and efficient water treatment solutions.

In this doctoral dissertation, I investigate the enactment of competition among upper secondary schools in the Swedish educational system. Following extensive market-inspired reforms in the late 1980s and early 1990s, the responsibility for schools was decentralized to municipalities and a voucher system was introduced aimed at increasing pedagogical diversity and improving school quality through competition. However, the transformation of schools from agents in a public education system to competitive actors has proven to be complex and challenging. The reform sought to stimulate pedagogical innovation and greater student involvement, yet many schools appear to have struggled with following through on this vision. Privately owned schools are increasingly questioned, and several schools struggle to provide pedagogically relevant offerings to students.

Two research questions guide this inquiry: (1) How does a school become a competing organization? and (2) How does a school create a competitive offering? To make sense of these questions, I draw on institutional organization theory and consumption scholarship. Emphasis is placed on the necessity of legitimacy in competition. Schools must not only have the legal authority to act autonomously to compete, but they must also be socially recognized and accepted as competitors, and their competitive offering must also be legitimate, yet distinct.

Previous research has largely examined the effects of competition on educational outcomes and schools’ competitive behaviors without investigating how schools become legitimate competing actors in the first place. In other words, legitimacy is assumed. The purpose of this dissertation is then to problematize how schools become competitors and enact competition. Through four empirical papers, I explore how schools navigate the challenges of competition, construct their offerings, and struggle with legitimacy as competitive actors. 

I find that schools enact competition by stumbling, fumbling, and rumbling. Trial and error seems to define the process of becoming a competitor. Furthermore, enacting competition appears to be much more intrusive than previously suggested as it affects the field of organizations, the very identities of these organizations, and the subjects in those organizations, including students and school leaders. This dissertation therefore contributes to a deeper understanding of the marketization of education and the social construction of competition.

Acute Respiratory Distress Syndrome (ARDS) is a leading cause of morbidity and mortality among critically ill patients, and mechanical ventilation (MV) plays a critical role in its management. One of the key parameters of MV is the level of positive end-expiratory pressure (PEEP), which helps to maintain an adequate lung functional volume. However, the optimal level of PEEP remains controversial. The classical approach in clinical trials for identifying the optimal PEEP has been to compare "high" and "low" levels in a dichotomous manner. High PEEP can improve lung compliance and significantly enhance oxygenation but has been inconclusive in hard clinical outcomes such as mortality and duration of MV. This discrepancy could be related to the fact that inappropriately high or low PEEP levels may adversely affect other organs, such as the heart, brain, and kidneys, which could counteract its potential beneficial effects on the lung. Patients with ARDS often develop acute kidney injury, which is an independent marker of mortality. Three primary mechanisms have been proposed to explain lung-kidney crosstalk during MV: gas exchange abnormalities, such as hypoxemia and hypercapnia; remote biotrauma; and hemodynamic changes, including reduced venous return and cardiac output. As PEEP levels increase, lung volume expands to a variable extent depending on mechanical response. This dynamic underlies two potential mechanisms that could impair venous return, potentially leading to splanchnic and renal congestion. First, increasing PEEP may enhance lung aeration, particularly in highly recruitable lungs, where previously collapsed alveoli reopen, increasing lung volume and pleural pressure, leading to vena cava compression, which can contribute to systemic venous congestion and abdominal organ impairment function. Second, in lungs with low recruitability, PEEP elevation may induce minimal changes in lung volume while increasing airway pressure, resulting in alveolar overdistension, vascular compression, and increased pulmonary vascular resistance. Therefore, we propose that high PEEP settings can contribute to renal congestion, potentially impairing renal function. This review underscores the need for further rigorous research to validate these perspectives and explore strategies for optimizing PEEP settings while minimizing adverse renal effects.

Mast cells are innate immune cells, which can be found in nearly all tissues of the human body. Activated by receptors for IgE or bacterial compounds, mast cells are complex effector cells which respond in many ways to bacterial infection. However, decades of research did not lead to a general model of how mast cells are activated by bacteria. Examples of pathogenic bacteria include the extracellular Streptococcus equi subspecies equi (S. equi) that colonizes the airways in horses by secretion of powerful toxins, and the invasive enterobacterium Salmonella enterica subspecies Typhimurium (S.Tm). The latter is taken up with contaminated food and invades the epithelium in the distal small and proximal large intestine to reach the deeper layers of the tissue. Mast cells are present as early responders towards both bacteria. In this thesis, I elucidated how pathogenic bacteria activate these versatile immune cells. In Paper I, I demonstrated which virulence factors of S. equi that activate mast cells, by utilizing bacterial knockout mutants of several virulence factors or a combination of those. While superantigens or the protective capsule did not lead to mast cell activation, removal of the pore-forming toxin streptolysin S led to complete ablation of the mast cell response to S. equi, establishing that sublytic pore formation leads to membrane stress, which results in inflammation. To compare our findings from extracellular bacteria with the invasive S.Tm, we explored in Paper II, if its type-three-secretion system induces a similar sublytic pore-mediated immune activation. We found however, that S.Tm triggers mast cell activation by a two-step activation process, involving 1) priming by toll-like receptor (TLR) 4 and 2) effector-induced immunity. While we mainly focused on classical mouse mast cells, we extended our findings further in Paper III. In this study, the use of connective tissue-type and mucosal-type mouse mast cells, as well as a human mast cell line broadened the validity of our two-step activation model. We discovered, moreover, that mucosal-like mast cells lack TLR2 and TLR4, making them only responsive to invasive bacteria. Overall, this thesis contributes to our understanding of the general mechanisms for how mast cells are activated by bacteria.

Background

Comorbid conditions and breathlessness are associated with poor outcomes in chronic obstructive pulmonary disease (COPD). We evaluated the associations of comorbid heart disease and depression/anxiety with breathlessness in daily life among people with COPD.

Methods

Cross-sectional analysis from the PRAXIS cohort in central Sweden. Data on patient characteristics and the modified Medical Research Council (mMRC) and Dyspnea-12 breathlessness instruments (D-12) were obtained from questionnaires in 2022. Lung function data were collected from record review. Outcome variables were clinically significant breathlessness defined as mMRC≥2 and D-12 total (>2.7), physical (>1.4) and affective (>1.2) scores above published minimal clinical important differences. Associations of heart disease and depression/anxiety with each outcome were analyzed using multivariable Poisson regression adjusted for relevant confounders.

Results

In 522 included patients, mMRC ≥2 was present in 59 % and increased D-12 total, physical and affective domain scores in 69 %, 74 %, and 50 %, respectively. Heart disease was independently associated with mMRC (relative risk ratio [95 % confidence interval] 1.34 [1.17–1.53]), D12 physical domain (1.12[1.02–1.24]) and D-12 affective domain (1.20[1.02–1.42]). Depression/anxiety was independently associated with increased D-12 affective domain (1.25[1.04–1.49]). In addition, previous exacerbations and GOLD stage 3–4 were associated with mMRC and D-12, respectively.

Conclusion

In COPD, comorbid heart disease is associated with both activity-related breathlessness and with physical and affective domains of breathlessness while depression/anxiety is associated with the affective domain of breathlessness. As the influence of different dimensions of breathlessness may differ according to comorbidity the D-12 instrument adds more information when assessing breathlessness in patients with COPD.

Background/Objectives: Polygenic risk scores (PRSs) have been extensively studied and are increasingly applied in healthcare. One of the most studied and developed areas is predictive medicine for breast cancer, but there is no wider consensus on the indications for the clinical use of PRSs for breast cancer. This current guidance endeavours to articulate the scientific evidence underpinning the clinical utility of PRSs in stratifying breast cancer risk, with a particular emphasis on clinical application.

Methods: This guidance has been prepared by a group of experts who have been active in breast cancer PRS research and development, combining a review of the evidence base with expert opinion for indications for clinical use.

Results: Based on data from various studies and existing breast cancer prevention and screening services, the indications for clinical use of breast cancer PRSs can be divided into the following scenarios: (1) Management of cancer-free women with a family history of cancer; (2) individual personalised breast cancer prevention and screening in healthcare services; and (3) breast cancer screening programs for more personalised screening.

Conclusions: The integration of PRSs into clinical practice enables healthcare providers to deliver more accurate risk assessments, personalised prevention strategies, and optimised screening programmes, thereby improving patient outcomes and enhancing the effectiveness of breast cancer care. PRS testing represents a novel component in clinical breast cancer risk assessment, supporting a personalised, risk-based approach to breast cancer prevention and screening.

Purpose:

There is solid evidence that an early age at cochlear implantation, which reduces the period of auditory deprivation, positively impacts early spoken language development. However, there is an urgent need for more research to understand the long-term effects of early implantation on higher linguistic skills, such as metaphor comprehension. In this study, we explored metaphor comprehension in Swedish-speaking adolescents and young adults with cochlear implant (CI), compared to that of typically hearing peers, as well as its relationship with the age at first CI.

Method:

The participants consisted of 39 individuals who received CI before 30 months of age (M_age = 16.9 years, mean age at implant = 15.7 months) and a group of 27 individuals with typical hearing (M_age = 14.9 years). To assess metaphor comprehension, we developed a multiple-choice task that was administrated verbally. Standardized tests were used to evaluate vocabulary, reading skills, and nonverbal cognitive skills.

Results:

No significant differences were found in metaphor comprehension or other linguistic or cognitive skills between individuals with CI and the typically hearing peers. Further analysis indicated a moderate negative correlation between metaphor comprehension and age at implantation and other linguistic skills.

Conclusions:

Early-implanted children develop metaphor comprehension comparable to their typically hearing peers, with earlier age at implantation being associated with better metaphor comprehension in adolescence. However, age at implantation only partially explains the variation in metaphor comprehension abilities. Further research is needed to identify other factors that influence the development of metaphor comprehension in individuals with CI.

This study investigates the relationship between lithology and magnetic susceptibility in loessites from south-west England to examine if orbital forcing is a driving mechanism behind terrestrial climate change of interior Triassic hothouse Pangea. Using magnetic susceptibility and a simple colour analysis, a correlation could be established between lithology and changes in magnetic susceptibility. The magnetic susceptibility signal was analysed with a Fast Fourier Transformation and a Wavelet analysis to determine the cyclicity of change over time. Results showed strong coupling with precession, obliquity and eccentricity, though mostly when the long 400 kyr eccentricity cycle would peak in intensity.

Changes in lithology and magnetic susceptibility signal are caused by changes in environment from dry sub aerial desert basin to flooded desert basin under elevated ground water conditions, with lower magnetic susceptibility signals in the waterlogged sediments. These changes in water levels are thought to derive from increase in runoff coupled with a strong monsoonal precipitation. Orbital forcing is determined as a driving mechanism behind these changes, though mostly with high eccentricity within the 400 kyr cycle. It is hypothesised here that the mechanism behind the strong connection to the 400 kyr cycle is the very arid climate of interior Pangea, which makes it hard for the shorter orbital cycles to drive significant shifts in environment without the amplification under enhanced seasonality periods of the long eccentricity cycle.

Background: Idiopathic genu valgum beyond physiological limits may require treatment, which is based on age, growth remaining, and the magnitude of the deformity. There is no consensus on clinical, or radiologic evaluation, indications, and management of idiopathic genu valgum, which can range from observation to surgical treatment using various modalities. If available, such guidelines will help surgeons offer optimal treatment to their patients. The aim of our study was to establish an expert consensus on the evaluation and treatment of idiopathic genu valgum.

Methods: An international panel of 29 pediatric orthopaedic surgeons from 17 countries with clinical and research experience in the management of limb deformity participated in a modified Delphi survey. Surgeons were provided with patient and deformity characteristics and voted on 46 statements on history, clinical examination, radiographic evaluation, and treatment options for idiopathic genu valgum in round 1. Consensus was defined as when statements received >= 70% votes. Statements that were important but received <70% votes were reworded for clarity in round 2 (n=13).

Results: Consensus was achieved for 28/46 statements and included obtaining a full-length standing radiograph of the lower extremities and measuring joint orientation angles. Participants did not agree to offer surgical treatment based only on the intermalleolar distance. They recommended surgical treatment if the mechanical axis falls in zone 2 or beyond on the lateral side and using guided growth by tension-band plating when the growth remaining is at least 2 years. The panel agreed on performing common peroneal nerve decompression for specific indications such as acute, opening wedge osteotomy of >20 degrees, but not for gradual correction. Consensus was not reached for indications and methods of bone age assessment, treatment when growth remaining is <1 year, indications for implant removal after guided growth in younger children, and the type of osteotomy for acute deformity correction.

Conclusions: We have generated consensus statements to guide the management of idiopathic genu valgum. Statements that lack consensus are areas for future multicenter research.

Level of Evidence: Level V.

The genomic study of specimens dating to the Early and Middle Pleistocene (EP and MP), a period spanning from 2.6 million years ago (Ma) to 126 thousand years ago (ka), has the potential to elucidate the evolutionary processes that shaped present-day biodiversity. Obtaining genomic data from this period is challenging, but mitochondrial DNA, given its higher abundance compared to nuclear DNA, could play an important role to understand evolutionary processes at this time scale. In this study, we report 34 new mitogenomes, including two EP and nine MP mammoth (Mammuthus spp.) specimens from Siberia and North America and analyze them jointly with >200 publicly available mitogenomes to reconstruct a transect of mammoth mitogenome diversity throughout the last million years. We find that our EP mitogenomes fall outside the diversity of all Late Pleistocene (LP) mammoths, while those derived from MP mammoths are basal to LP mammoth Clades 2 and 3, supporting an ancient Siberian origin of these lineages. In contrast, the geographical origin of Clade 1 remains unresolved. With these new deep-time mitogenomes, we observe diversification events across all clades that appear consistent with previously hypothesized MP and LP demographic changes. Furthermore, we improve upon an existing methodology for molecular clock dating of specimens >50 ka, demonstrating that specimens need to be individually dated to avoid biases in their age estimates. Both the molecular and analytical improvements presented here highlight the importance of deep-time genomic data to discover long-lost genetic diversity, enabling better assessments of evolutionary histories.

Background

Knee pain is often an early sign of knee osteoarthritis (KOA). Physical activities (PA) constitute the recommended regime to those affected. However, knee-loading PA at work is linked to an increased risk for KOA. The primary aim of this study was to investigate associations between knee pain and accelerometer-measured knee-loading PA, at work and leisure respectively. The secondary aim was to investigate knee-related problems in relation to self-reported physical effort at work.

Methods

This cross-sectional study included 107 working participants (aged 30–67) with knee pain. Knee pain was evaluated using the Knee Injury and Osteoarthritis Outcome Scale (KOOS), subscale Pain. Knee-loading PA (including daily steps, time in upright position, stair walking), and sitting/lying were measured by accelerometer for one week. Each knee-loading PA was analysed separately for the measurement periods: (1) total period, (2) time at work, and (3) leisure on workdays. Knee-related problems were evaluated by the KOOS subscales Symptoms, Activities of Daily Living, Function in Sport and Recreation, and Quality of Life. Analyses were made with linear regression, and stratified by high or low self-reported physical effort at work.

Results

Participants with more knee pain walked on average fewer steps per day, and spent less time in an upright position during leisure on workdays, unstandardized coefficient (β) = 0.001, p = 0.044, β = 0.075, p = 0.001 respectively, i.e. spent less time in knee-loading PA. The associations were stronger for those reporting high physical effort at work, β = 0.116, p = 0.016. Participants with high physical effort at work rated their (knee-related) quality of life worse. There were no associations between knee pain and knee-loading PA during work hours.

Conclusions

Participants with more knee pain were less physically active during leisure, with stronger associations among those with higher physical effort at work. Those reporting high physical effort at work had worse (knee-related) quality of life compared to participants reporting low effort at work. This highlights the importance of taking knee-loading PA at work and leisure into account when recommending exercise regimes to individuals with knee pain.

Trial registration

ClinicalTrials.Gov (NCT04928170), Date of registration: 2017-12-20.

Background

Being a patient with multiple long-term conditions (MLTCs) often entails a need for complex medication treatment, which poses a challenge to medication self-management. Medication self-management during transition of care is often hindered by challenges such as inadequate communication, which increases the risk of medication errors and adverse outcomes.

Aim

Identify facilitators and barriers to medication self-management for patients with MLTCs transitioning from hospital to home.

Methods

Semi-structured interviews were conducted in patient's homes 1–2 weeks after hospital discharge. Interviews were transcribed and analysed by qualitative deductive content analysis using the Taxonomy of Every Day Self-management Strategies (TEDSS) framework. The data collection continued until enough information power and meaning saturation was reached.

Results

Twenty-one patients and three next of kin participated. Numerous facilitators and barriers to medication self-management were identified within all seven TEDSS domains, which varied extensively between individuals. Resource and process strategies were the most frequently discussed domains, while health behaviour and social interaction strategies were less frequently discussed. Key facilitators identified were access to resources that support medication self-management and knowing the medication's purpose. Key barriers included patients perceiving medications as burdensome or not recognising the importance of their medications.

Conclusions

This study highlights the complex and wide spectre of facilitators and barriers to medication self-management for patients with MLTCs transitioning from hospital to home. In clinical practice, patients' medication self-management could be supported through a holistic approach adapted to the individual patient's daily life, including improved care coordination and patient empowerment.

The northern shrimp Pandalus borealis (ice. Stóri kampalampi) is a North Atlantic crustacean of significant commercial interest which has been harvested consistently in Icelandic waters since 1936. In Icelandic waters, the length at which this protandrous species transitions from male to female differs between the inshore and offshore populations, suggesting a biologically meaningful stratification which may or may not be plastic. Using reduced representative genomes assembled from RADseq data, sampled from 96 individuals collected at two time points (2018 and 2021), we compare the level of genetic structure across a gradient extending out of Skjálfandi bay, north Iceland. These data are compared to samples from a far offshore site, some 65 km out from the bay, as well as another inshore fjord in Arnarfjörður, in northwestern Iceland. Since 1999, no harvesting of inshore populations of P. borealis in Skjálfandi has been allowed due to stock decline, but harvesting of offshore stocks has continued. Uncertainty surrounding the extent of structure between the in- and offshore aggregations has remained. Here we report distinct genetic structure defining the inshore and offshore populations of northern shrimp, but find significant admixture between the two. Most importantly, we see that genetically inshore populations of northern shrimp extend far outside the harvest boundaries of inshore shrimp, and offshore individuals may exhibit punctuated migration into the inshore areas.

This study investigates researcher variability in computational reproduction, an activity for which it is least expected. Eighty-five independent teams attempted numerical replication of results from an original study of policy preferences and immigration. Reproduction teams were randomly grouped into a 'transparent group' receiving original study and code or 'opaque group' receiving only a method and results description and no code. The transparent group mostly verified original results (95.7% same sign and p-value cutoff), while the opaque group had less success (89.3%). Second-decimal place exact numerical reproductions were less common (76.9 and 48.1%). Qualitative investigation of the workflows revealed many causes of error, including mistakes and procedural variations. When curating mistakes, we still find that only the transparent group was reliably successful. Our findings imply a need for transparency, but also more. Institutional checks and less subjective difficulty for researchers 'doing reproduction' would help, implying a need for better training. We also urge increased awareness of complexity in the research process and in 'push button' replications.

Objective Retinopathy of prematurity (ROP) registers enable population-based studies to monitor ROP screening programmes to improve their effectiveness. The aim of this study was to determine the frequency of ROP and the coverage of screening in a South African cohort using a prospective ROP South African (ROPSA) register.

Methods and analysis Infants born from 1 May 2022 to 31 January 2023 and screened prospectively for ROP at five neonatal intensive care units in Cape Town were included. The screening criteria were a gestational age (GA) <32 weeks or birth weight (BW) <1250 g. Data were extracted from the ROPSA register and analysed.

Results 696 of 1154 (60.3%) eligible infants were screened, almost half of whom (45.7%) did not complete screening. ROP was detected in 220 infants (31.6%, 95% CI 28.3% to 35.3%), 7 (1.0%) of whom required treatment. Infants with incomplete screening had a lower mean GA than those who completed screening; 28.7 (SD 1.6, range 25–33) and 29.1 (SD 1.7, range 24–36) weeks, respectively (p=0.004) and a lower mean BW; 1048 (SD 203, range 650–1690) g and 1108.5 (SD 227, range 640–1840) g, respectively (p<0.001).

Conclusions Data from the ROPSA register on the frequency of any ROP and treatment-requiring ROP may be biased due to low screening coverage and high incomplete screening. Reasons need to be explored and corrective interventions initiated. The ROPSA register will enable the impact of these interventions to be monitored. The findings of this study will contribute to the ongoing revision of South African national ROP screening guidelines.

Background and objectives:

The drop-out rate for inpatient treatment for substance use disorder continues to be a significant issue. To increase the knowledge about drop out in different settings, this study’s objective was to quantify the association for the previously identified risk factors of age, sex, and time in treatment at a private care institution offering substance use disorder treatment in Sweden.

Design and methods:

This retrospective cohort study of clinical record data included all 1334 adult clients who were discharged from substance use disorder treatment between 1 January 2014, to 30 June 2022, at one privately operated treatment institution. Drop out was defined as treatment terminated before the planned end. The association between three potential risk factors and drop out was analysed in a multivariable logistic regression model. Estimates were reported as marginal risk ratios (95% confidence intervals).

Results:

Of 1334 discharged clients, 34% dropped out, corresponding to 38% of females and 33% of males. Approximately 52% of clients dropped out within 30 days, 42% dropped out between 30 and 89 days, and around 15% from 90 days and onwards. In the multivariable model, both time in treatment (3.08 [2.34, 3.83] for 30 to 89 days vs 90 days and 3.55 [2.72, 4.39] for <30 days vs ⩾90 days) and age (1.19 [1.14, 1.23] for one decade) showed a strong inverse association with drop out. The results did not support an association between sex and drop out (1.05 [0.89, 1.22]).

Conclusion:

The risk for drop out is higher earlier in the treatment and for younger clients, so to reduce the drop out at private institutional care it is important to implement extensive interventions early in the treatment programme to increase the motivation for clients, particularly younger ones, to remain in treatment.

Intro: Seizure incidence in diffuse glioma ranges between 60% and 90%. This study aimed to investigate the association between seizures and diffuse glioma in subcortical and cortical brain regions, including white matter tracts.

Methods: Adult patients with diffuse glioma at Uppsala University Hospital from 2005 to 2021 were analysed retrospectively. The relationship between tumour location in specific brain voxels and preoperative seizures was examined concerning white matter tract involvement. Tumour volumes were segmented based on T2-weighted or FLAIR MRI after spatial normalisation to standard space (MNI) and combined to create a location-specific frequency map.

Results: Of the 93 patients meeting the inclusion criteria, 70 (75%) experienced seizures. A significant decreased risk was found in tumours present within the left fronto-mesial and dorsal voxel (A3C1S1). Increased seizure risk was found in tumours located in the left supramarginal and posterior insular voxel (A4C2S3). The voxels differed in terms of type and extent of white matter networks. Additionally, there was a difference in seizure risk and voxel associations between oligodendrogliomas and astrocytoma, with specific voxels associated with seizures identified in both groups.

Conclusion: The study provides new insights into the epileptogenic potential of diffuse gliomas in relation to their spatial distribution, highlighting the need to analyse both cortical and subcortical localisation of tumours. The observed differences in seizure risks across brain regions underscore the need for personalised post-surgery treatment strategies and further research to understand the pathophysiology of brain tumour-related epilepsy, BTRE.

Objectives:

This research aims to enhance the quality of hospital services by utilizing Quality Function Deployment (QFD) with a novel Multi-Dimensional House of Quality (MD-HOQ) approach. This method integrates Service Quality (SERVQUAL) analysis and considers resource constraints, such as financial and workforce limitations, to select and prioritize technical requirements effectively.

Methods:

The proposed MD-HOQ approach was applied to a private hospital in Tehran, Iran. Data were gathered from a sample of 8 experts and a sample of 386 patients, using 2 in-depth interviews and 4 questionnaires. The process included identifying hospital sections and determining their importance using the Analytic Hierarchy Process. Patients’ needs in each section were then identified and weighted through SERVQUAL analysis. Subsequently, technical requirements to meet these needs were listed and weighted using MD-HOQ. A mathematical model was employed to determine the optimal set of technical requirements under resource constraints.

Results:

Application of the MD-HOQ approach resulted in the identification of 50 patient needs across 5 hospital sections. Additionally, 40 technical requirements were identified. The highest implementation priorities were assigned to “training practitioners and nurses,” “improving the staff’s sense of responsibility,” and “using experienced specialists, physicians, and surgeons.”

Conclusions:

The integrated QFD approach, utilizing MD-HOQ and SERVQUAL analysis, provides a comprehensive framework for hospital managers to prioritize technical requirements effectively. By considering resource constraints and the gap between patient expectations and perceptions, this method ensures that resources are allocated to the most impactful technical requirements, leading to improved patient satisfaction and better overall hospital service quality. This approach not only enhances the quality of hospital services but also ensures efficient utilization of resources, ultimately benefiting patient satisfaction.

Simply by existing, we are continuously exposed to potentially harmful chemicals present in our environment. The presence of endocrine-disrupting chemicals poses a risk, as they have the potential to interfere with systems that regulate human development and function, even at low concentrations. Triphenyl phosphate (TPHP) is a suggested developmental neurotoxicant, prevalent in house dust and plastics. Its presence in human milk and placenta raises concern about potential risks to the developing fetus. In a step to evaluate TPHP’s potential for endocrine induced developmental neurotoxicity, C17.2 cells were exposed to concentrations between 50 μM - 0.005 nM in order to cover human exposure levels. The exposure occurred for 10 days of differentiation and the cell viability, neuronal morphology (neurite outgrowth and branching) and neuronal differentiation was assessed. The treatment did not significantly affect cell viability or neuronal differentiation and morphology. However, an insignificant increase in neurite outgrowth and branching was observed, suggested to be a sign for retinoic acid receptor antagonism. Our findings indicate that TPHP is not manifesting developmental neurotoxicity by affecting the tested endpoints under the described conditions. To uncover the mechanism a broader range of endpoints should be assessed.

 Sökandet efter en fungerande behandling mot Amyotrofisk lateralskleros (ALS) har pågått sedan första gången sjukdomen beskrevs på mitten av 1800-talet. Sjukdomen karaktäriseras av en successiv degeneration av motorneuroner, men i dagsläget är verkningsmekanismerna bakom detta fortfarande okända. Kunskapsluckorna kring de bakomliggande genetiska orsakerna är stora, trots konstant pågående forskning och nya fynd. Att få förståelse för den kliniska bilden av sjukdomen utgör grunden för att framställa en behandling som angriper de rätta molekylära processerna. I denna text sammanfattas de huvudsakliga patogena mekanismerna bakom de fyra generna med starkast association till ALS; SOD1, C9orf72, TARDBP samt FUS. Där forskningen är idag har man funnit att genernas respektive grundläggande funktioner är relativt åtskilda, men att det finns somliga gemensamma patogena mekanismer. Fellokalisering och aggregatbildning är ett återkommande tema hos alla fyra generna, där störningar i bildningen av stressgranuler är gemensamt för bland annat C9orf72 och FUS.  Den sammanställda kunskapen pekar på att patogeniciteten främst härstammar från en gain-of-function (GOF)-mekanism, där toxiska ansamlingar av genprodukterna samt andra ALS-förknippade proteiner tenderar att bildas i cytoplasman av motorneuroner. Utifrån den sammanställda informationen bör framtida ALS-forskning lägga vikt vid toxiciteten hos de sjukdomsrelaterade proteinerna. Vidare bör man ha i åtanke att toxiska GOF-orsaker kan gå hand i hand med loss-of-function (LOF), då den ena inte nödvändigtvis utesluter den andra. 

Crayfish use their native immune system to avoid infections. They produce new stem cells and blood cells (hemocytes) continuously throughout their lifetimes. The hemocytes are produced by stem cells in the hematopoietic tissue and released into the circulation. The release occurs when the cytokine astakine 1 inhibits the crosslinking between TGase in the extracellular matrix in the hematopoietic lobules. The stem cells can differentiate into different types of cells. They mainly differentiate into different types of immune cells, but also a minor population that gets transported to the brain. One of these are neuronal precursor cells that gets transported to the brain. There are several cell-type specific markers that can be used to identify the types of cells produced from the hematopoietic tissue. By injecting astakine, different methods can be used to investigate how this protein is affecting the immune response in the crayfish. In this study, RT-qPCR and RNA-FISH are used to detect different types of cells after an injection of astakine, compared to a crayfish saline injection. Samples are gathered at different time-points after the injection to investigate the effects over time. RT-qPCR measured the total mRNA expression of several cell-type specific markers. This was furthered studied with RNA-FISH to investigate the cause of the change in mRNA expression. In conclusion this study shows some results using only a few replicates, but further studies with more replicates and RNA-FISH as the main method is necessary. 

The ongoing transition to a net-zero emissions energy system is driven by what can be called a fourth wave of electrification, where fossil fuel-dependent processes are increasingly replaced by electric-powered appliances. At the same time, a substantial rise in electricity production is coming from renewable energy sources. Both developments are critical for a successful energy transition over the coming decades. A key aspect of this transition is understanding the load demand of electricity users.

The aim of this thesis is to analyze and assess the impact of different electricity users on the local grid, focusing on their consumption behavior. Conducted in collaboration with Uppsala Municipality, the research emphasizes a public perspective, user-friendliness, and a technologically-agnostic presentation of results. Three research objectives have been pursued throughout the thesis: (1) analyzing the impact of a single user's behavior in detail on the grid, incorporating peak shaving and distributed energy resources, in addition to a broader analysis to assess multiple users through a peak load correlation analysis; (2) proposing a framework to generate typical load profiles for various users, using time series clustering and a qualitative clustering step to model their demand patterns throughout the year; and (3) designing an index to quantify and compare the flexibility potential of electricity users, based on a rankable index developed using limited information.        

The results reveal considerable variation among users in both peak load contributions and flexibility potential. The peak load analysis and the flexibility index both identify users that could benefit from behavioral changes or offer potentially valuable flexibility to support grid stability. To test the framework of generating typical load profiles, a case study of elementary schools in Uppsala Municipality was conducted that showed that these institutions exhibited similar load patterns. The most typical load profile was rescaled to represent load variability based on the heated indoor area of an arbitrary school, showing a reasonable accuracy. These profiles can inform the selection of distributed energy resources, such as photovoltaic systems, or facilitate the co-location of users with complementary consumption patterns to minimize grid impacts.

The methods, tools, and frameworks presented in this thesis are versatile and can serve as valuable inputs for strategic decision-making by municipalities, businesses, and other stakeholders. By providing insights into user behavior, these tools can guide focused interventions to support the continued evolution of the energy transition.

Flooding impairs plant growth through oxygen deprivation, which activates plant survival and acclimation responses. Transcriptional responses to low oxygen are generally associated with the activation of group VII ETHYLENE-RESPONSE FACTOR (ERFVII) transcription factors. However, the exact mechanisms and molecular components by which ERFVII factors initiate gene expression are not fully elucidated. Here, we show that the ERFVII factors RELATED TO APETALA 2.2 (RAP2.2) and RAP2.12 cooperate with the Mediator complex subunit AtMED25 to coordinate gene expression under hypoxia in Arabidopsis thaliana. Respective med25 knock-out mutants display reduced low-oxygen stress tolerance. AtMED25 physically associates with a distinct set of hypoxia core genes and its loss partially impairs transcription under hypoxia due to decreased RNA polymerase II recruitment. Association of AtMED25 with target genes requires the presence of ERFVII transcription factors. Next to ERFVII protein stabilisation, also the composition of the Mediator complex including AtMED25 is potentially affected by hypoxia stress as shown by protein-complex pulldown assays. The dynamic response of the Mediator complex to hypoxia is furthermore supported by the fact that two subunits, AtMED8 and AtMED16, are not involved in the establishment of hypoxia tolerance, whilst both act in coordination with AtMED25 under other environmental conditions. We furthermore show that AtMED25 function under hypoxia is independent of ethylene signalling. Finally, functional conservation at the molecular level was found for the MED25-ERFVII module between A. thaliana and the monocot species Oryza sativa, pointing to a potentially universal role of MED25 in coordinating ERFVII-dependent transcript responses to hypoxia in plants.

In this article, I investigate the interaction between the rural environment and disability to explore how place can be a resource in processes of participation and belonging. The aim is to explain how individuals experiencing disability make use of, give meaning to, evaluate, and negotiate their surroundings. The embodied experiences of individuals living in rural places are at the centre of the study that this work is based on. The empirical material includes in-depth interviews with 15 men and women experiencing either a physical or a neuropsychiatric impairment. The analysis focuses upon the environmental-social interface. The article argues that the concept of spatial competence offers a relatively open entrance for studying enabling spaces and identifying factors contributing to the well-being of individuals and places. Spatial competence is understood as a process that emphasises agency and the ability to navigate social and material environments. Departing from the participants' elaborations and reflexivity with regard to their local places, I argue that the physical environment, social networks and local welfare structures constitute pillars in the development of spatial competence. Welfare structures are explicitly addressed, for example regarding social support in everyday life or material support in the case of remodelling a home. These structures are also implicitly present in narratives on excursions, outdoor activities or social contexts initiated or supported by the public sector or civil society. A conclusion is that the development of spatial competence intersects with a functioning welfare society.

During embryogenesis, endothelial cells (ECs) are generally described to arise from a common pool of progenitors termed angioblasts, which diversify through iterative steps of differentiation to form functionally distinct subtypes of ECs. A key example is the formation of lymphatic ECs (LECs), which are thought to arise largely through transdifferentiation from venous endothelium. Opposing this model, here we show that the initial expansion of mammalian LECs is primarily driven by the in situ differentiation of mesenchymal progenitors and does not require transition through an intermediate venous state. Single-cell genomics and lineage-tracing experiments revealed a population of paraxial mesoderm-derived Etv2⁺Prox1⁺ progenitors that directly give rise to LECs. Morphometric analyses of early LEC proliferation and migration, and mutants that disrupt lymphatic development supported these findings. Collectively, this work establishes a cellular blueprint for LEC specification and indicates that discrete pools of mesenchymal progenitors can give rise to specialized subtypes of ECs.

Efficient long-term cultivation of chicken primordial germ cells (cPGCs) is essential for various avian research and biotechnology applications. Our study aimed to address the challenge of inconsistent culture success by investigating strain-specific variations and optimizing culture conditions using two distinct media: Ovotransferrin-enriched medium (OTM) and chicken serum-supplemented medium (CSM). We demonstrated that each chicken strain has unique nutritional requirements, with Hubbard cPGCs thriving in OTM and Bovans cPGCs favoring CSM. This strain-specific variation was effective in derivation and proliferation rates and the expression of stem cell-specific markers such as POU5F3/OCT4 and NANOG. Furthermore, our study confirmed the sustained germ cell identity of long-term cultured cPGCs through the expression of DAZL, DDX4, and EMA1 germ cell markers. We also showed that cultured cPGCs retained their migratory abilities and transfectability, successfully generating G0 germline chimeras and G1 transgenic Bovans chickens. These findings highlight the importance of optimized culture conditions depending on the genotype to enhance the viability and genetic stability of cPGCs, paving the way for more effective genetic modifications and conservation strategies in avian species.

Lichen are a symbiosis between a mycobiont and a photobiont. Sanger sequencing is a popular method to identify the photobiont species, though it has recently been suggested that it tends to only amplify the most common genotype. Using next generation sequencing (NGS) has revealed that the lichen thalli often include more than one photobiont. The majority of discoveries in lichen biology, including both the photo- and mycobiont, are made using the internal transcribed spacer (ITS). It is a good tool for distinguishing between species but makes sequence alignment difficult. This study proposes that using the whole rDNA operon, including both the conserved 18- and 28S as well as the ITS, will resolve this issue. Therefore, this study examines whether metagenomic data sequenced at 30X can be used to retrieve the rDNA operon of photo- and mycobionts in Thamnolia lichen, as well as if it is able to identify more than one photobiont. It also examines which photobionts associate with Thamnolia lichens and if there is a correlation between them as well as between them and the temperature in which they grew. Further, if the identified photobionts are found in other mycobiont species beyond Thamnolia. To establish this, 150 Thamnolia samples from all continents of the world except Africa were collected between 1994-2023, their DNA was extracted and sequenced. The rDNA operon of both the photo- and mycobiont of 39 of the samples, including the 18S, ITS and 28S, were retrieved through metagenomic assembly using metaSPAdes. With the obtained data, phylogenies, maps, one-way ANOVAs and Fisher’s Exact test were made. With this method, six Thamnolia mycobiont lineages were discovered: A, B, C1, C2, C3 and C4, through their distribution it could be established that they had different regions of origin and were impacted by the average temperature in which they grew. Five Trebouxia photobiont lineages were discovered: ‘pink’, ‘red’, ‘yellow’, ‘green’ and ‘blue’, from their distribution the same conclusions regarding origins and temperature could be established, as for the mycobionts. Fisher’s Exact test also showed that the lineages have specific associations with each other. The results indicate that the Thamnolia and Trebouxia lineages have spatial and thermal patterns, meaning that their distribution differs depending on origin and temperature, as well as certain associations with each other and that this is worth investigating further to establish the true depiction of reality. 

Bakgrund: Prehospital vård är en central del av akutsjukvården och bidrar till trygghet isamhället. Ambulanssjuksköterskan möter patienter i akuta och ofta stressfyllda situationerdär tillit spelar en avgörande roll för vårdrelationen. För att skapa tillit krävs både medicinskkompetens och en förmåga att kommunicera lugnt och empatiskt. Tidigare forskning om tillitär begränsad och utrycker ett behov av att närmare studera patientens upplevelse av tillit. Syfte: Syftet med studien är att beskriva vuxna patienters och deras anhörigas upplevelser avtillit till ambulanspersonalen i det prehospitala vårdmötet. Metod: Kvalitativ litteraturstudiemed systematisk ansats med 19 inkluderade artiklar som analyserats med en latentinnehållsanalys. Resultat: Patienters tillit till ambulanspersonalen kan börja redan vidlarmcentralens besked om att hjälp är på väg och stärks av snabb ankomst och professionelltbemötande. Ambulanspersonalens medicinska kompetens är avgörande för tryggheten,medan bristande kunskap kan leda till misstro. Ett empatiskt och tydligt bemötande stärkerrelationen och ökar tilliten, medan dålig kommunikation och ifrågasättande kan minskaförtroendet. Slutsats: Tilliten till ambulanspersonalen är avgörande för patientens upplevelseav trygghet och vårdkvalitet i det prehospitala mötet. Studien visar att faktorer somprofessionellt bemötande, medicinsk kompetens, tydlig kommunikation och en respektfullvårdrelation bidrar till att stärka denna tillit. När patienter och anhöriga känner sig lyssnadepå, informerade och bekräftade skapas en vårdmiljö där tilliten kan utvecklas, vilket i sin turunderlättar samverkan mellan patient och ambulanspersonal. Vidare forskning bör undersökahur olika utbildningsnivåer hos ambulanspersonalen påverkar patientens upplevelse av tillitsamt om specifika utbildningsinsatser kan stärka patientens upplevelse av tillit.

Background: Postoperative pain is a common issue that can affect the patient's physical and psychological well-being and prolong recovery time. Despite the availability of both pharmacological and non-pharmacological pain relief methods, the under-treatment of postoperative pain remains a widespread problem. Music therapy has been highlighted as a potential non-pharmacological method to complement standard pain management and enhance patient well-being. 

Aim: The aim of this literature review was to examine the effect of music therapy as a non-pharmacological complement to pain relief in postoperative pain management. 

Method: A systematic literature review was conducted using PubMed and CINAHL with specific inclusion criteria, such as peer-reviewed quantitative studies in English. A total of 20 articles were included and assessed based on quality criteria för relevance and reliability. A narrative synthesis was used to analyze and categorize the result. 

Results: Music therapy demonstrated positive effects by reducing pain intensity, lowering anxiety levels, and improving sleep quality. Patients who listened to music postoperatively often had lower heart rates and blood pressure, as well as a reduced need for analgesic medication. Personalized music therapy also improved the patient's experience of care. Challenges in implementering music therapy were identified, such as a lack of knowledge and guidelines within healthcare settings.

Conclusion: Music therapy is an effective and side-effect-free method to complement pharmacological pain management postoperatively. Integrating music into healthcare can reduce pain perception, lower anxiety level, and enhance recovery. Despite its positive effects further research is needed to evaluate long-term outcomes and develop clear guidelines for implementation in clinical practice. 

We present hardware/software techniques to intelligently regulate supply voltage and clock frequency of intermittently computing devices. These devices rely on ambient energy harvesting to power their operation and small capacitors as energy buffers. Statically setting their clock frequency fails to capture the unique relations these devices expose between capacitor voltage, energy efficiency at a given operating frequency, and the corresponding operating range. Existing dynamic voltage and frequency scaling techniques are also largely inapplicable due to extreme energy scarcity and peculiar hardware features. We introduce two hardware/software co-designs that accommodate the distinct hardware features and function within a constrained energy envelope, offering varied tradeoffs and functionalities. Our experimental evaluation combines tests on custom-manufactured hardware and detailed emulation experiments. The data gathered indicate that our approaches result in up to 3.75x reduced energy consumption and 12x swifter execution times compared to the considered baselines, all while utilizing smaller capacitors to accomplish identical workloads.

Evolution and development of the arthropod head are heavily debated topics often referred to as "The arthropod head problem" (AHP) or the "Endless dispute". One aspect of the AHP concerns the evolutionary origin and homology of the most anterior head segments, the pre-gnathal segments (PGS), that are associated with the tripartite brain of arthropods. It has been suggested that the PGS could have evolved independently from the segments that build the rest of the arthropod body. One argument supporting this hypothesis is that the PGS are patterned by an initial transverse stripe of hedgehog (hh)-expression that splits once or twice, giving (in the case of double splitting) raise to the three PGS in distantly related arthropods such as the fly Drosophila melanogaster and the spider Parasteatoda tepidariorum. It has been implied that this splitting-event may recapitulate evolution of these segments, i.e. the splitting of an initial anterior body unit into three, or at least that the single splitting may represent a remnant of this process. In this paper, I show that two-fold splitting of an initial anterior hh-stripe is not conserved in chelicerates or even spiders. Instead, I find that a single splitting event correlated to the development of the most anterior two segments, the protocerebral and the deuterocerebral segment, is conserved among arthropods as a whole. There are, however, deviations from this pattern including a third or even fourth consecutive head segment, or even hh-splitting in more posterior segments.

Transmission spectroscopy is a prime method to study the atmospheres of extrasolar planets. We obtained a high-resolution spectral transit time series of the hot Jupiter WASP-121 b with CRIRES+ to study its atmosphere via transmission spectroscopy of the He I λ10833 triplet lines. Our analysis shows a prominent He I λ10833 absorption feature moving along with the planetary orbital motion, which shows an observed, transit-averaged equivalent width of approximately 30 mÅ, a slight redshift, and a depth of about 2%, which can only be explained by an atmosphere overflowing its Roche lobe. We carried out 3D hydrodynamic modeling to reproduce the observations, which favors asymmetric mass loss with a more pronounced leading tidal tail, possibly also explaining observational evidence for additional absorption stationary in the stellar rest frame. A trailing tail is not detectable. From our modeling, we derived estimates of ≥2 × 10¹³ g s⁻¹ for the stellar and 5.4 × 10¹² g s⁻¹ for the planetary mass loss rate, which is consistent with X-ray and extreme-ultraviolet (XUV) driven mass loss in WASP-121 b.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes. Frequent loss of heterozygosity in FGFR3 and 17p (affecting TP53) was found in tumors with mutations in FGFR3 and TP53, respectively. Whole-genome doubling (WGD) was observed in 15% of the tumors and was associated with worse outcomes. Tumors with WGD were genomically unstable, with alterations in cell-cycle-related genes and an altered immune composition. Finally, integrative clustering of multi-omics data highlighted the important role of genomic instability and immune cell exhaustion in disease aggressiveness. These findings advance our understanding of genomic differences associated with disease aggressiveness in NMIBC and may ultimately improve patient stratification.

Background:

Acceptance and Commitment Therapy (ACT) has been found to be beneficial for individuals dealing with chronic pain. The theoretical mechanisms of change proposed by ACT are based on the Hexaflex model. To comprehensively reflect this model, the Multidimensional Psychological Flexibility Inventory (MPFI) and Psy-Flex have been developed. The study aimed to adapt the MPFI-24 and the Psy-Flex for Spanish-speaking populations with chronic pain and to examine their dimensionality, internal consistency, convergent validity and incremental validity.

Methods:

This cross-sectional study involved 309 Spanish-speaking adults with chronic pain who completed an online survey. The majority of the participants were women (88.3%). The ages ranged from 18 to 79 years.

Results:

Factor analysis showed that the Spanish version of the MPFI-24 has 12 factors, consisting of six flexibility and six inflexibility factors, similar to the original version, but lacking second-order general factors. The Psy-Flex demonstrated a single-factor structure, maintaining the general factor of psychological flexibility seen in the original version. The MPFI-24 showed good internal consistency and adequate convergent validity, with the exception of the Acceptance and Experiential Avoidance subscales. The Psy-Flex showed good internal consistency and convergent validity. Notably, both the MPFI-24 and Psy-Flex scores significantly explained additional variance in psychological distress beyond other ACT-related measures of Hexaflex processes; however, only the Psy-Flex explained pain interference.

Conclusions:

The Spanish adaptations of the MPFI-24 and Psy-Flex are valid and reliable instruments for assessing the Hexaflex model processes in Spanish-speaking adults with chronic pain.

Significance Statement:

Practitioners and researchers in chronic pain will find the Spanish versions of the MPFI-24 and the Psy-Flex here, along with recommendations for their use and scoring based on a robust psychometric rationale. It should be noted that these measures surpass the Chronic Pain Acceptance Questionnaire (CPAQ) and the Psychological Inflexibility in Pain Scale (PIPS), which are considered gold standards in chronic pain assessment.

Background. National epidemiological investigations of microbial infections greatly benefit from the increased information gained by whole- genome sequencing (WGS) in combination with standardized approaches for data sharing and analysis.

Aim. To evaluate the quality and accuracy of WGS data generated by different laboratories but analysed by joint pipelines to reach a national surveillance approach.

Methods. A national methicillin- resistant Staphylococcus aureus (MRSA) collection of 20 strains was distributed to nine participating laboratories that performed in- house procedures for WGS. Raw data were shared and analysed by three pipelines: 1928 Diagnostics, JASEN (GMS pipeline) and CLC- Genomics Workbench. The outcomes were compared according to quality, correct strain identification and genetic distances.

Results. One isolate contained intraspecies contamination and was excluded from further analysis. The mean sequencing depth varied between sites and technologies. However, all analysis methods identified 12 strains that belonged to one of five outbreak clusters. The cut- off definition was set to <10 allele differences for core genome multilocus sequence typing (cgMLST) and <20 genetic differences for SNP analysis in a pairwise comparison.

Conclusions. MRSA isolates, which are whole genome sequenced by different laboratories and analysed using the same bioinformatic pipelines, yielded comparable results for outbreak clustering for both cgMLST and SNP, using the 1928 analysis pipeline. In this study, JASEN was best suited to analyse Illumina data and CLC to analyse within respective technology. In the future, real- time sharing of data and harmonized analysis within the Genomic Medicine Sweden consortium will further facilitate investigations of outbreaks and transmission routes.

We describe features of the X-ray: Generate and Analyse (XGA) open-source software package that have been developed tofacilitate automated hydrostatic mass (Mhydro ) measurements from XMM X-ray observations of clusters of galaxies. This includesdescribing how XGA measures global, and radial, X-ray properties of galaxy clusters. We then demonstrate the reliability ofXGA by comparing simple X-ray properties, namely the X-ray temperature and gas mass, with published values presented bythe XMM Cluster Survey (XCS), the Ultimate XMM eXtragaLactic survey project (XXL), and the Local Cluster SubstructureSurvey (LoCuSS). XGA measured values for temperature are, on average, within 1 per cent of the values reported in the literaturefor each sample. XGA gas masses for XXL clusters are shown to be ∼10 per cent lower than previous measurements (though thedifference is only significant at the ∼ 1.8σ level), LoCuSS R2500 and R500 gas mass re-measurements are 3 per cent and 7 per centlower, respectively (representing 1.5σ and 3.5σ differences). Like-for-like comparisons of hydrostatic mass are made to LoCuSSresults, which show that our measurements are 10±3 per cent (19±7 per cent) higher for R2500 (R500 ). The comparison betweenR500 masses shows significant scatter. Finally, we present new Mhydro measurements for 104 clusters from the Sloan DigitalSky Survey (SDSS) DR8 redMaPPer XCS sample (SDSSRM-XCS). Our SDSSRM-XCS hydrostatic mass measurements are ingood agreement with multiple literature estimates, and represent one of the largest samples of consistently measured hydrostaticmasses. We have demonstrated that XGA is a powerful tool for X-ray analysis of clusters; it will render complex-to-measureX-ray properties accessible to non-specialists.

Essay I: This paper examines the career/family trade-off at labor market entry using unique data on job preferences among Swedish law graduates. Using ranked job applications, I document gender differences in employment and location preferences: women are less geographically mobile and less likely to pursue private-sector career paths. I focus in particular on cohabitation status at labor market entry to investigate how early family ties may constrain preferences. Cohabiting applicants—regardless of gender—are less mobile, reflecting short-run career constraints. However, cohabitation at labor market entry does not predict long-run gender differences in earnings. Instead, career trajectories begin to diverge with the timing of parenthood, underscoring the unequal career costs of family formation.    

Essay II (with Seema Jayachandran, Lea Nassal, Matthew J. Notowidigdo, Marie Paul and Heather Sarsons): Many couples face a trade-off between advancing one spouse’s career or the other’s. We study this trade-off using administrative data from Germany and Sweden and find that when couples move across commuting zones, men’s earnings increase more than women’s. To distinguish between men's greater earnings potential and a gender norm that prioritizes men’s careers, we examine how the patterns differ depending on whether the man or the woman has higher potential earnings. We then estimate a household decision-making model in which households can—and empirically do—place more weight on the man’s income. 

Essay III (with Dana Scott): We investigate whether the expansion of remote work following the COVID-19 pandemic helped mitigate child penalties in Sweden. A household labor supply model predicts that work-from-home opportunities reduce the child penalty only when primarily accessible to mothers, with little effect if both parents have equal access. Consistent with this, our empirical results show that remote work has had limited impact on mothers’ relative earnings, employment, hours, and wages. 

Essay IV (with Daniel Avdic, Arizo Karimi and Anna Sjögren): This paper studies how parental time investments affect children's human capital development. We exploit Sweden’s 1995 parental leave reform in an RD-DD framework and find that, while average GPA effects are limited, the reform reduced school-leaving grades for sons of non-college educated fathers and increased intergenerational skill correlations. We find no support for mental health, fertility, or role model channels. Instead, the results suggest that increased separation risk in disadvantaged families may have reduced paternal time investments. 

The dual-mode elpasolite scintillation material CLLBC (Cs2LiLaBr4.8Cl1.2:Ce) is capable of measuring both𝛾-rays and neutrons. The neutron detection capability spans from thermal energies up to about 10 MeV,making these detectors attractive options for studying prompt fission neutron spectra (PFNS). In this work, acomprehensive characterization of CLLBC detectors is performed. Three CLLBC detectors were characterized,in addition to three LaBr3:Ce and two LaBr3:Ce,Sr for comparison. For the best-performing CLLBC detector,the results indicate an energy resolution of 3.7% at 𝐸𝛾 = 662 keV and an intrinsic timing resolution of1.2 ns (FWHM) above 𝐸𝛾 = 1 MeV using 60Co. A 𝛾-neutron separation figure-of-merit of 2.7 is obtainedby means of pulse-shape discrimination. Tagged neutron time-of-flight measurements were conducted usinga 241Am9Be neutron source, by coincident detection of the 4.44 MeV 𝛾-ray and the neutron, to determinethe intrinsic neutron detection efficiency between 2–6 MeV. Neutron detection efficiencies of about 0.2% forthe 6Li(n,t)4He reaction and 1% for three types of (n,n′) reactions were obtained. Two of three investigatedCLLBC detectors exhibit an energy peak asymmetry, resulting in worse performance, indicating scintillatorquality issues and motivating further investigation. Future studies are anticipated using the 252Cf(sf) promptfission neutron spectrum to determine neutron efficiencies for a wider range of neutron energies. Althoughobserved in a previous study, neutron detection via 35Cl(n,p)35S was not identified in this work but is plannedto be determined using quasi-monoenergetic neutrons generated at the JRC MONNET facility.

Barns och ungas livsvillkor påverkas av hur våra städer och byggda miljöer utformas. När barnkonventionen inkorporerades 2020 lyftes därför bland annat vikten av att beakta barns rättigheter och intressen i planläggning av mark- och vattenanvändning. I samband med inkorporeringen betonades därtill att det även efter att barnkonventionen blivit lag fanns ett behov av fortsatt vägledning och ett systematiskt transformeringsarbete av konventionens artiklar i svensk lagstiftning. Trots detta har några initiativ till att införa bestämmelser om barns rättigheter i den svenska plan- och bygglagstiftningen inte tagits. Till skillnad från den svenska lagstiftningen innehåller den norska plan- och bygglagstiftningen krav på beaktande av barns rättigheter och intressen. Mot denna bakgrund undersöks och jämförs i artikeln hur barns rättigheter reglerats i svensk respektive norsk plan- och bygglagstiftning. Därtill diskuteras om den svenska regleringen bör influeras av den norska regleringen. I artikeln visas att det råder oklarheter kring om och hur barns rättigheter ska beaktas vid planering i Sverige medan den norska lagstiftaren tydligt tagit ställning till att barns och ungas rättigheter och intressen ska beaktas vid planering i Norge. Den norska lagstiftningen, som består av allmänt hållna bestämmelser, kompletteras med nationella riktlinjer och vägledningar, vilket innebär att förväntningarna på den kommunala planeringen är betydligt tydligare i Norge än i Sverige. För att tydliggöra intentionerna med hur barnkonventionen ska förstås vid planläggning bör därför den svenska lagstiftaren överväga att införa bestämmelser om barns och ungas rättigheter och intressen i plan- och bygglagstiftningen. Den norska lagstiftningen kan med fördel fungera som inspiration.

Artificial superlattices exhibit exceptional electronic, magnetic, optical, and mechanical properties which make them unique candidates for applications in a broad range of technologies. A common key feature of superlattices is the need for atomically abrupt interfaces. However, superlattices comprised of materials with different properties, such as melting points and diffusivities, pose large challenges for achieving high crystal quality of both constituents with abrupt interfaces. By employing ion-assisted magnetron sputter epitaxy, we present an innovative solution to this problem with utilizing a unique combination of thermal radiation and kinetic energy that enable sufficient adatom mobility for epitaxial growth of both materials. The research was implemented for the case of CrB₂/TiB₂ heteroepitaxial superlattices, as neutron interference mirrors, wherein the constituents’ melting points differ by 1100 K. Ion-induced intermixing was avoided by commencing growth of each TiB₂ and CrB₂ layer by up to 3 unit cells (uc) without ion assistance, forming a buffer to protect the interface during the ion-assisted growth of the remainder of each layer. Heteroepitaxial superlattice growth with interface widths σ_CrB2 ∼1 uc and σ_TiB2 ∼2 uc was confirmed for different modulation periods. More than 3000 uc (∼1 µm) thick superlattices with abrupt interfaces were demonstrated for neutron mirror applications.

According to the UN Convention on the Rights of the Child, children have the right to a stan-dard of living adequate for their development. The responsibility to realise this lies primarily with parents, but states have a duty to support parents and an ultimate responsibility to protect child-ren from harm. Yet, studies show that children in Sweden are affected by economic vulnerability, and that the right to financial support is conditional, leading to a risk that children’s needs are not being met. This article looks at how the social services in Sweden should deal with child poverty. From a legal perspective, it examines what applies in situations where children do not have their basic needs met and where parents are not granted financial support. An important question is whether there are legal prerequisites to take children into care in such situations. It is shown that there are no explicit legal provisions legitimising taking children into care solely on the basis of poverty. Further, case law of the European Court of Human Rights, and statements from the UN Committee on the Rights of the Child, indicate that taking children into care because of poverty is a disproportionate restriction of children’s rights. However, the national legal framework is unclear. Children are to be protected from harm, but parents who do not meet the conditions set out by the social services are denied financial support. Overall, this means that there is a risk that children will be taken into care as a result of poverty, even though the needs could be met through financial support. The article discusses the need for legal clarifications and reforms in order to better protect children’s needs and rights.

Tick-borne encephalitis (TBE) is caused by the tick-borne encephalitis virus (TBEV) and is mainly transmitted to humans through bites from infected Ixodes ticks. TBE is a growing public health challenge in Europe, including Sweden, and is a reportable disease in at least 37 European countries.

TBEV can infect the central nervous system, causing symptoms from mild illness to severe disease or death. It may lead to lasting sequelae and reduced quality of life, although asymptomatic cases are likely common.

TBEV is traditionally classified into three subtypes: European, Siberian, and Far Eastern. It belongs to the Flaviviridae family and the Orthoflavivirus genus and is the only endemic vector-borne flavivirus in Sweden.

TBE vaccines are generally effective, though vaccine failures occur. Sweden lacks a national TBE vaccine register and seroprevalence studies are limited.

TBEV-specific antibody detection in serum or cerebrospinal fluid is the most common diagnostic method. Antibody detection is generally reliable but occasionally limited by cross-reactivity and false positives. Diagnosing TBE in vaccinated individuals is even more challenging. Traditional serological methods cannot distinguish infection-induced from vaccine-induced antibodies. Viral RNA detection has low clinical sensitivity.

This thesis aimed to improve TBE diagnostics by developing and evaluating new methods and to expand knowledge of TBEV, including vaccination data, through a seroprevalence study in Sweden.

In Paper I, we developed and validated a method to differentiate between antibodies caused by infection and those from vaccination. Antibody patterns in TBE-infected patients were compared with those in vaccinated individuals to demonstrate the concept. In Paper II, we applied the method to samples from suspected vaccine failure cases. In Paper III, we evaluated the performance of a commercial TBEV test in a European multi-laboratory study. In Paper IV, we investigated TBEV seroprevalence and vaccination coverage in collaboration with eight Swedish regions. Our findings include vaccination and infection rates, estimated totals, and evidence that over 90% of TBEV infections go undiagnosed.

In conclusion, this thesis presents improvements in TBEV diagnostics and new data on the seroprevalence of TBEV in Sweden, including vaccination data and information of the ratio between TBEV infections and reported TBE cases.