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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.

In strongly correlated systems, interactions give rise to critical fluctuations surrounding the quantum critical point (QCP) of a quantum phase transition. Quasicrystals allow the study of quantum critical phenomena in aperiodic systems with frustrated magnetic interactions. Here, we study the magnetic field and temperature scaling of the low-temperature specific heat for the quantum critical Yb-Au-Al quasicrystal. We devise a scaling function that encapsulates the limiting behaviors as well as the area where the system goes from a temperature-limited to a field-limited quantum critical region, where the magnetic field acts as a cutoff for critical fluctuations. The zero-field electronic specific heat is described by a power-law divergence, 𝐶el/𝑇∝𝑇^−0.54, aligning with previously observed ac-susceptibility and specific-heat measurements. The field dependence of the electronic specific heat at high magnetic fields shows a similar power law 𝐶el/𝑇∝𝐵^−0.50. In the zero-field and low-field region, we observe two small but distinct anomalies in the specific heat, located at 0.7 and 2.1 K.

Primitive nucleic acids and peptides likely collaborated in early biochemistry. What forces drove their interactions and how did these forces shape the properties of primitive complexes? We investigated how two model primordial polypeptides associate with DNA. When peptides were coupled to a ferromagnetic substrate, DNA binding depended on the substrate's magnetic moment orientation. Reversing the magnetic field nearly abolished binding despite complementary charges. Inverting the peptide chirality or just the cysteine residue reversed this effect. These results are attributed to the chiral-induced spin selectivity (CISS) effect, where molecular chirality and electron spin alter a protein's electric polarizability. The presence of CISS in simple protein-DNA complexes suggests that it played a significant role in ancient biomolecular interactions. A major consequence of CISS is enhancement of the kinetic stability of protein-nucleic acid complexes. These findings reveal how chirality and spin influence bioassociation, offering insights into primitive biochemical evolution and shaping contemporary protein functions.

TiO₂ nanopowders consisting of anatase and brookite, modified with all the rare earth (RE) group metals (except Pm), were successfully synthesized by a simple template-free one-step hydrothermal method using titanium butoxide as a precursor in water solutions. X-ray diffraction method showed that the addition of rare earth elements influenced the anatase-brookite (A-B) phase composition inconsistently: both an increase and a decrease in the brookite content were observed. XRD peak broadening analysis has been carried out by the Scherrer equation, modified Scherrer equation, the Williamson-Hall method, the Size-strain plot and the Halder-Wagner method. A decrease in the crystallite size due to the RE modification was confirmed in the novel RE/A-B materials. Porosity measurements revealed the mesoporous structure and developed surface area of the samples. UV-Vis diffuse reflectance spectra showed a blue shift compared to unmodified A-B, hereby indicating an increase in the band gap of the modified powders due to a phenomenon of quantum confinement or size quantization. The samples demonstrated high photocatalytic performance, particularly in the reaction of H₂ production, where the activity of RE (Gd, Tb, Tm)/A-B is approximately twice higher compared with A-B. This enhancement in photocatalytic activity is attributed to changes in the electronic structure, a reduction in crystallite size, increased porosity, and a larger surface area than A-B. These materials were also tested for the degradation of Rhodamine B in aqueous media, to prove the potential application in remediation processes.

Purpose Children living with respiratory support rely on medical technology, either fully or partially, throughout the day to meet their breathing requirements. Although children and young people living with respiratory support at home undergo long-term treatments and make extensive use of health and social care services, there is a notable absence of comprehensive outcome data on this group. The establishment of the first nationwide Course of DISease reported to the Swedish CPAP Oxygen and VEntilator RegistrY paediatrics cohort aims to investigate the disease trajectory, clinical and socioeconomic risk factors influencing incident illness, hospitalisation risk and mortality among children living with respiratory support.

Participants Data on patients aged 0–18 years reported to the Swedish National Registry for Respiratory Failure and Sleep Apnoea (Swedevox) 1 January 2015 to 29 July 2021 were merged with seven quality or governmental registries, the National Quality Registry for Intensive Care, the National Medical Birth Register, the Swedish Cause of Death Registry, the Registry for Interventions under the Act on Support and Service to Certain Disabled Persons, the Swedish National Patient Registry and with socioeconomic data from Total Population Registry and Longitudinal Integrated Database for health insurance and labour market studies.

Findings to date The cohort includes 716 children, 59% male, who began respiratory support at an average age of 6.4 years (SD 5.4). Among them, 28% use continuous positive airway pressure, 64% long-term mechanical ventilation (LTMV), 3% high-flow oxygen therapy (HFOT) and 5% other methods. Respiratory support is mostly used at night, but many LTMV (54%) and HFOT (81%) users need daytime aid. 77% of LTMV users rely on mask connection, differing from international data.

Future plans Future projects include exploring the impact of socioeconomic factors on hospitalisation rates and mortality. The dataset is due for an update in 2026.

We address reducing carbon footprint (CF) in the context of edge computing. The carbon intensity of electricity supply largely varies spatially as well as temporally. We consider optimal task scheduling and offloading, as well as battery charging to minimize the total CF. We formulate this optimization problem as a mixed integer linear programming model. However, we demonstrate that, via a graph-based reformulation, the problem can be cast as a minimum-cost flow problem, and global optimum can be admitted in polynomial time. Numerical results using real-world data show that optimization can reduce up to 83.3% of the total CF.

Passively cooled base stations (PCBSs) have emerged to deliver better cost and energy efficiency. However, passive cooling necessitates intelligent thermal control via traffic management, i.e., the instantaneous data traffic or throughput of a PCBS directly impacts its thermal performance. This is particularly challenging for outdoor deployment of PCBSs because the heat dissipation efficiency is uncertain and fluctuates over time. What is more, the PCBSs are interference-coupled in multi-cell scenarios. Thus, a higher-throughput PCBS leads to higher interference to the other PCBSs, which, in turn, would require more resource consumption to meet their respective throughput targets. In this paper, we address online decision-making for maximizing the total downlink throughput for a multi-PCBS system subject to constraints related on operating temperature. We demonstrate that a reinforcement learning (RL) approach, specifically soft actor-critic (SAC), can successfully perform throughput maximization while keeping the PCBSs cool, by adapting the throughput to time-varying heat dissipation conditions. Furthermore, we design a denial and reward mechanism that effectively mitigates the risk of overheating during the exploration phase of RL. Simulation results show that our approach achieves up to 88.6% of the global optimum. This is very promising, as our approach operates without prior knowledge of future heat dissipation efficiency, which is required by the global optimum.

Vikten av läsförståelse i dagens samhälle är betydande och läromedlen har en central plats i undervisningen. Syftet med denna kvalitativa textanalys är i förhållande till detta att bidra med kunskap om läsförståelseuppgifters utformning i svenskläromedel för årskurs 5. Studien ämnar behandla fyra frågeställningar: 1) Hur behandlar uppgifterna i svenskläromedel för årskurs 5 läsförståelse? 2) Vilka lässtrategier påvisas i uppgifterna? 3) På vilket sätt synliggörs lässtrategierna? 4) Hur främjar uppgifterna en djupare textförståelse? För att behandla dessa undersöks läsförståelseuppgifter i fyra läromedel i svenska. Uppgifterna undersöks genom två analysmodeller som behandlar lässtrategier och textrörlighet. Analysmodellen som berör lässtrategier är utformad av Roe och innefattar femton olika strategier. Den andra modellen, textrörlighet, definieras av Liberg m.fl. och delas in i tre olika rörlighetstyper. Resultatet analyseras i relation till de teoretiska utgångspunkterna Langers föreställningsvärldar samt Luke och Freebodys modell Four Resources Model. Den första teorin behandlar de faser en läsare intar i byggandet av föreställningsvärldar för djupare läsförståelse och den andra teorin belyser hur läsaren använder sig av fyra textpraktiker för effektiv läsförståelse. Analysen visar att undervisning om lässtrategier i läromedelsuppgifter är bristfällig och att frekvensen strategierna emellan är ojämn. Det ses även ett stort fokus på några få aspekter av läsförståelse och bortfall av andra vilket anses förhindra möjlighet till djupare förståelse. En tredje slutsats är att uppgifter ofta saknar textförankring då de fokuserar på isolerade språkövningar eller associationer utan avstamp i texten. En diskussion förs kring resultatet i relation till den rådande läroplanen samt tidigare forskning inom ämnet.

Extragalactic globular clusters (EGCs) are an abundant and powerful tracer of galaxy dynamics and formation, and their own formation and evolution is also a matter of extensive debate. The compact nature of globular clusters means that they are hard to spatially resolve and thus study outside the Local Group. In this work we have examined how well EGCs will be detectable in images from the Euclid telescope, using both simulated pre-launch images and the first early-release observations of the Fornax galaxy cluster. The Euclid Wide Survey will provide high-spatial resolution VIS imaging in the broad I-E band as well as near-infrared photometry (Y-E, J(E), and H-E). We estimate that the 24 719 known galaxies within 100 Mpc in the footprint of the Euclid survey host around 830 000 EGCs of which about 350 000 are within the survey's detection limits. For about half of these EGCs, three infrared colours will be available as well. For any galaxy within 50 Mpc the brighter half of its GC luminosity function will be detectable by the Euclid Wide Survey. The detectability of EGCs is mainly driven by the residual surface brightness of their host galaxy. We find that an automated machine-learning EGC-classification method based on real Euclid data of the Fornax galaxy cluster provides an efficient method to generate high purity and high completeness GC candidate catalogues. We confirm that EGCs are spatially resolved compared to pure point sources in VIS images of Fornax. Our analysis of both simulated and first on-sky data show that Euclid will increase the number of GCs accessible with high-resolution imaging substantially compared to previous surveys, and will permit the study of GCs in the outskirts of their hosts. Euclid is unique in enabling systematic studies of EGCs in a spatially unbiased and homogeneous manner and is primed to improve our understanding of many understudied aspects of GC astrophysics.

Background

Little is known regarding treatment with cangrelor during percutaneous coronary intervention (PCI) in patients with myocardial infarction complicated by cardiogenic shock or cardiac arrest.

Objectives

The aim of this study was to investigate the effects of such cangrelor treatment during PCI in patients with myocardial infarction complicated by cardiogenic shock or cardiac arrest.

Methods

The study population included patients undergoing PCI (2016-2022) for myocardial infarction with cardiogenic shock or cardiac arrest from SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Propensity score (PS)–matched groups were compared regarding major adverse cardiovascular events (MACE) within 30 days, in-hospital major bleeding, and all-cause mortality within 30 days.

Results

A total of 3,014 patients with cardiogenic shock or cardiac arrest were included, 1,011 receiving and 2,003 not receiving cangrelor. In the PS-matched analysis regarding patients with cardiogenic shock (n = 994), the risk ratio (with vs without cangrelor) was 0.82 (95% CI: 0.71-0.94) for MACE, with an absolute risk reduction of 8.9 percentage points (95% CI: 2.7-15 percentage points) (number needed to treat = 12); 1.60 (95% CI: 0.93-2.76) for major bleeding; and 0.81 (95% CI: 0.70-0.94) for mortality, with an absolute risk reduction of 8.9 percentage points (95% CI: 2.7-15 percentage points) (number needed to treat = 12). In the PS-matched analysis regarding patients with cardiac arrest (n = 1,138), the risk ratio was 1.01 (95% CI: 0.87-1.18) for MACE; 2.26 (95% CI: 1.25-4.11) for major bleeding, with an absolute risk increase of 3.5 percentage points (95% CI: 1.0-5.7 percentage points); and 0.97 (95% CI: 0.83-1.13) for all-cause mortality.

Conclusions

For patients with cardiogenic shock, administration of cangrelor during PCI was associated with a lower risk for both MACE and all-cause mortality. For patients with cardiac arrest, no such benefit was observed, and a higher risk for major bleeding was found.

This study provides a comprehensive guide to robotic-assisted microsurgery. Following more than 900 clinical cases in 13 centers, this joint project was initiated to summarize and consent to the user experience. Two robotic systems specifically designed for the needs of open microsurgery received the first certification for clinical application (CE mark) in 2019 and 2020. Since their introduction into clinical application, several European microsurgical centers have implemented these systems, generating user experiences in multiple microsurgical subspecialties. All institutions using the MUSA-2 microsurgical robot (Microsure B.V., Eindhoven, Netherlands) or Symani Surgical System (Medical Microinstruments, Inc., Wilmington, Delaware, US) were invited to join the multicenter project. A modified nominal group technique was applied to answer five major questions regarding current and future indications and developments in open robotic-assisted microsurgery. Steep preclinical and clinical learning curves were characterized. General considerations concerning the two different systems are presented. Specifics for each microsurgical subspecialty are reported. Following two voting rounds, a consensus was reached in three of the five major questions with "lymphatics" being the top indication, "higher precision" being the top benefit, and "automation" being the top long-term goal of robotic-assisted microsurgery. This joint project of all Symani and MUSA-2 users presents clinical cases and the subsequent initial knowledge and experience. Lymphatics as a top indicator and a higher precision as the top benefit point toward the capabilities of robotic-assisted microsurgery in manipulation of smallest structures. Automation may further enhance and simplify robotic procedures in future. This project also provides a comprehensive guide to any institution aiming to introduce such a system for open robotic-assisted microsurgery in future.

Fear and avoidance remain important concepts for understanding chronic pain. The objective of our research was to develop and evaluate a Polish version of a measure to assess these concepts: the 20-item Pain Anxiety Symptoms Scale (PASS-20). The goal also included establishing a cutoff score to differentiate between individuals with a high level of pain-related disability and those with lower levels. The scale underwent back-translation into Polish, and two studies were conducted among individuals reporting chronic pain: in a large online sample (N = 418; 60% women, 40% men; age: 19–86, M = 49), and in a hospital-recruited sample (N = 148; 77% women, 22% men; age: 18–85; M = 57). We assessed validity, internal consistency, and test–retest reliability. Confirmatory factor analyses supported both a model with four correlated factors—cognitive anxiety, physiological responses, avoidance, and fearful thinking—and a hierarchical model with four lower order factors and a higher order factor representing general pain anxiety. There was no evidence of ceiling or floor effects. Cronbach’s αs exceeded .82 and .76 for the online and hospital-recruited samples, respectively, indicating robust internal consistency. The translated PASS-20 scores showed moderate test–retest reliability and positively correlated with pain catastrophizing, depression, stress, anxiety, and pain intensity. Women and individuals with disabilities reported higher scores. Receiver operating characteristic analysis determined an optimal cutoff score of 52 or above to distinguish highly disabled individuals with 82.35% sensitivity and 58.86% specificity. A minimal detectable change of 26.81 for the PASS-20 total score was identified. The Polish PASS-20 provides valid and reliable scores for measuring pain-related anxiety.

Introduction: The Russian invasion of Ukraine displaced over 14 million people. By 2024, around 6 million Ukrainian refugees settled in Europe under the EU Temporary Protection Directive, providing permit of residence, work and health care. This influx strained European healthcare systems, particularly in addressing acute injuries. As the stay of refugees in EU countries prolongs, the management of chronic conditions becomes increasingly important. However, there is limited information available about Ukrainian refugees' access to various healthcare services.

Aim: The aim of this study was to evaluate perceived accessibility of healthcare services in Europe for Ukrainian war refugees and to identify barriers to healthcare access, in order to inform improvements in healthcare provision.

Methods: A cross-sectional online survey was conducted across Europe from July 2023 to April 2024, targeting adult Ukrainian war refugees. Survey explored areas defined as key health care needs. Descriptive, parametric and non-parametric statistical analysis methods were employed in data analysis.

Results: Of 659 respondents, 550 (83.4%) were included in the final analysis due to having reported need to use healthcare services in the past year. The most prevalent needs included dental care (82.9%), prescription medication (81.6%), care for acute (78.4%), and chronic conditions (64.0%). Perceived access to care varied across services, with vaccinations rated highest, while chronic condition care rated lowest. Around ¼ of respondents reported that they had to temporarily return to Ukraine for services not available in the countries where they stayed, these being mostly dental and gynaecologic care. The most prevalent barriers reported were long waiting times (64.2%), information barriers (55.5%), and high service costs (49.1%).

Discussion: The survey identified several barriers in the access to healthcare system for Ukrainians, particularly for chronic conditions care. Some barriers may be subjective, relating to limited access to information. However, others point to potential shortcomings within national healthcare systems, suggesting areas that require further review and improvement.

Conclusions: Addressing language barriers, improving information dissemination, and enhancing chronic condition management were identified as crucial for improving healthcare access for Ukrainian war refugees. Coordinated strategies are needed to support refugees and ensure the sustainability of host healthcare systems.

Background: Guidelines recommend neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). Current recommendations do not consider genomic profiles, although the Basal/Squamous (Ba/Sq) subtype is less likely to respond to NAC compared to Urothelial-like (Uro) and Genomically Unstable (GU) subtypes. The aim of this study is to perform cost-effectiveness analyses of a de-escalated use of NAC in patients with Ba/Sq tumors and MIBC.

Methods: A cost-effectiveness analysis was performed using a decision analytic Markov model using a healthcare provider perspective. Treatment and prognosis probabilities originated from the Bladder Cancer Data Base, Sweden (BladderBaSe) 2.0. Information on molecular subtype and outcomes was retrieved from published studies, and quality-adjusted life year (QALY) data were obtained from the iROC trial. Costs were collected from the regional healthcare registers in Sweden, utility values were obtained from the literature, and outcomes are presented as incremental cost-effectiveness ratio (ICER). Scenario analyses, along with several one-way and probabilistic sensitivity analyses were performed to capture uncertainties.

Results: At a 5-year time horizon, the model predicts that molecular subtype-based treatment has an ICER of 4,964 Euro/QALY (66,766 Swedish Krona/QALY), which is deemed cost-effective in the Swedish setting. At €7,427 (100,000 SEK) willingness-to-pay threshold, the molecular subtype-based treatment has a 65% probability of being cost-effective. The results were not sensitive to uncertainty analyses.

Conclusion: Molecular subtype-based treatment of MIBC, i.e., refraining from administering NAC to patients with Ba/Sq tumors, is cost-effective compared to the current treatment practices in Sweden.

AbstractIntroduction: Family members play a central role in end-of-life care for their loved ones,both at home and in hospital settings. Palliative care for cancer affects not only the patient butalso the lives, emotions, and health of their relatives.Aim: The aim was to describe family members’ experiences of palliative cancer care.Method: A literature review with a qualitative, descriptive design. The databases PubMed andCINAHL were used for the literature search. Ten articles were selected and reviewed usingthe quality assessment tool from the Swedish Agency for Health Technology Assessment andAssessment of Social Services. The results were analyzed using a method described byFriberg.Results: The findings are presented in four themes: Psychological burden, Need for supportand relief, Communication and information are crucial, and Preparations for death.Conclusion: The study shows that when family members are involved in the care of a lovedone, they often experience psychosocial stress. When support was provided by healthcareprofessionals and other relatives, the caregiving burden was eased. It is crucial that nurseswork in an ethically sound and person-centered manner, using clear and direct communicationand providing information to reduce the suffering of relatives.Keywords: family member, patients with cancer, family, experiences, palliative care

When charged particles interact with laser fields, they are usually thought to be pushed out from the regions of higher laser intensity via the mechanism known as the ponderomotive force (PMF). In contrast to the existing theories, we show that there exist several regimes in which charged particles are drawn into the regions of strongly focused laser fields. We derive a simple, covariant, and relativistically correct expression for the ponderomotive laser force that holds for arbitrary strength of field focusing and for all particle velocities. We predict three new, to the best of our knowledge, physical effects: (1) focusing-dependent reversal of PMF, (2) non-relativistic reversal of PMF, and (3) non-reciprocity of PMF for weakly relativistic particle velocities. Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

This thesis connects ethnic and socioeconomic spatial sorting and its neighbourhood effects to the spatial dimension of well-being. The work investigates how well-being is spatially sorted, particularly where and why. Three papers explore these questions through measures of well-being either as a good life through the performance in seven or eight well-being-related life course domains (known as external well-being) obtained from the population registers or satisfaction with life (known as internal well-being) obtained from the 2020 Neighbourhood Survey. 

Paper 1 explores the spatial distribution of external well-being over various bespoke scales finding the most variation at the most-detailed scales. The neighbourhood level well-being is correlated with levels of education and concentration of ethnic minorities. K-means cluster analysis finds that 24% of the labour force live in neighbourhoods of homogenised well-being over all scales. 10% of the labour force live in areas of spatially homogenous low well-being. Paper 2 explores the variation in internal well-being between sociodemographic neighbourhood types in relation to attitudes towards the neighbourhood. Linear regression shows that migrant-dense, socioeconomically deprived neighbourhoods are associated with lower well-being. This association disappears when attitudes towards the neighbourhoods are included. Paper 3 explores the development of external well-being around the time of moving among various types of movers. Fixed effect growth curve models find that ethnic minorities and long-distance relocators have a long-term decrease in well-being after moving. Ethnic minorities already have a decline in well-being before moving, which might suggest a tendency for forced relocations.

It is concluded that well-being is spatially sorted at the neighbourhood level: a geography and demography of low well-being can be observed to answer the ‘where’ well-being is spatially sorted. The geography of low well-being refers mainly to migrant-dense areas built during the Million Homes programme at the edge of cities. The demography of low well-being refers to non-European migrants consistently having lower well-being. Regarding ‘why’ well-being is spatially sorted indications are found for both sorting effects, through the differences in well-being around moving, and neighbourhood effects, through the difference in neighbourhood appraisal. 

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Its progressively expanding, fluid-filled renal cysts eventually lead to end-stage renal disease. Despite the relatively high prevalence, treatment options are currently limited to a single drug approved by the FDA and EMA. Here, we investigated human ADPKD patient-derived three-dimensional cyst cultures (3DCC) as an in vitro model for ADPKD and drug repurposing research. First, we analyzed the proteomes of 3DCC derived from healthy and diseased tissues. We then compared the protein expression profiles with those of reference tissues, mainly from the same patients. We quantified 290 proteins affecting drug disposition and proposed target proteins for drug treatment. Lastly, we investigated the functional response of the quantified target proteins after exposure to repurposing candidates in the 3DCC. Proteomic profiling of human 3DCC reflected previously reported pathophysiological alterations, including aberrant protein expression in inflammation and metabolic reprogramming. While the 3DCCs largely recapitulated the disease phenotype in vitro, drug transporter expression was reduced compared to in vivo conditions. Target proteins for proposed repurposing candidates showed similar expression in vitro and in tissues. Exposure to these repurposing candidates inhibited cyst swelling in vitro, supporting the suitability of the 3DCC for ADPKD drug screening. In summary, our results provide new insights into the ADPKD proteome and offer a starting point for further research to improve treatment options for affected individuals.

Syftet med studien var att undersöka hur förskollärare och rektorer definierade begreppet resurser samt hur de upplevde tillgången och funktionaliteten av dessa resurser och särskilt stöd i förskolan ur ett fenomenologiskt perspektiv. I studien utgick vi från en kvalitativ metod med semistrukturerade intervjuer och en urvalsgrupp bestående av 6 förskollärare och 6 rektorer från olika svenska förskolor. De centrala teoretiska begrepp som användes i den fenomenologiska analysen var livsvärld, fenomen, common sense-värld och intersubjektivitet. 

Resultatet indikerade huvudsakligen att informanterna hade åtskilda upplevelser av vad begreppet “resurser” betydde. Några exempel som framgick i studiens resultat var ekonomi, miljö, hjälpmedel, kompetens och extra personal. Resultatet visade även att majoriteten av yrkesgrupperna upplevde att tillgången till särskilt stöd och resurser var för litet, samt att orsaken till detta främst baserades på de ekonomiska förutsättningarna för förskolans verksamhet. Vidare beskrevs funktionen av resurser som dels kompetenshöjande genom handledning av en specialpedagog eller en ökning av bemanningen för att kunna tillgodose barn som har behov av särskilt stöd.

Background: A virtually complete and articulated plesiosaur skeleton (MH 7) is described from the Lower Jurassic (Toarcian) Posidonienschiefer Formation near Holzmaden in southern Germany. Plesiosaur remains are rare in this rock unit compared to those of other marine reptiles, such as ichthyosaurs and thalattosuchian crocodylomorphs. The new specimen offers an opportunity to assess the biodiversity of Early Jurassic plesiosaurs documented from what is now Central Europe.

Methods: The osteology of MH 7 is described and compared with other Early Jurassic plesiosaurs based on first-hand observations. Phylogenetic analyses using both equal weighting and weighted parsimony determined phylogenetic placement within Plesiosauria.

Results: Plesiopterys wildi is an early-diverging plesiosauroid and a sister taxon to Franconiasaurus brevispinus and Cryptoclidia. MH 7 represents a subadult individual, providing an updated character state diagnosis of Plesiopterys wildi, which has hitherto only been known from the osteologically immature holotype SMNS 16812. The presence of multiple regionally distinct plesiosaur genera and species within the European epicontinental marine basins suggests possible paleobiogeographical segregation during the Toarcian.

Aim: To describe nursing home care staff's experiences of encounters and communication with colleagues, residents and residents' family members as well as their experiences during the Covid-19 pandemic while working in a multicultural environment.

Design: A qualitative descriptive study.

Methods: Interviews with 17 care staff from nursing homes in Sweden were analysed using qualitative content analysis.

Results: Care staff reported different working experiences related to their possibility to prepare themselves, and some felt more supported than others by their managers. Feelings of pride were experienced when Covid-19 infections were prevented. Overall, they received information about Covid-19, but not initially. Acceptance of colleagues with limited Swedish language skills was reported, but frustration and impaired communication were common. Negative mental health effects from working with critically ill residents and taking care of the deceased were reported.

Conclusion: Employers did not provide care staff with sufficient information and support, and strategies are needed to maintain communication with and between care workers. Further support is needed to maintain care workers' mental health and well-being during critical working conditions.

Implications for the Profession and/or Patient Care: Nursing home management needs to implement clear structured tools for communicating essential information. These tools should take language skills into consideration. During pandemics, care workers must receive the support they need to maintain their mental health and well-being.

Patient or Public Contribution: No patient or public contribution.

This article explores the phenomenon of juridification in education with a focus on Swedish education law. Two key legislative areas are analysed: regulations on the discrimination and degrading treatment of students (DDT) and the incorporation of the United Nations Convention on the Rights of the Child (CRC) into Swedish law. Using Blichner and Molander’s (2008) framework for the dimensions of juridification with an additional dimension by Rosén, Arneback, and Bergh (2021), the article examines how the laws manifest different forms of juridification within the educational system. The findings reveal distinct patterns, with DDT representing an accountability-oriented juridification characterised by detailed legal obligations and enforcement mechanisms, while CRC exemplifies an elusive juridification with a symbolic legal status and uncertainty regarding how the law should be enacted and implemented. The study highlights the complexities of the juridification of and in education and the implications for legal and pedagogical practices, contributing to a nuanced understanding of how law reshapes educational contexts.

In this study, laser-material interactions during laser-powder bed fusion of WE43 magnesium alloy were characterized through numerical and experimental analyses. Various melting modes (i.e., conduction, transition, and keyhole) were induced through deposition of laser tracks at powers ranging from 80 to 130 W, and used as input parameters for a thermo-fluid model. Results of microscopy demonstrated good agreement between numerical and experimental measurements of melt pool depth, as well as a strong correlation between melt pool microstructure and the thermo-fluid conditions predicted by the model. Specifically, for conduction mode at 80 W, a predominance of cellular subgrains within the melt pool was consistent with the predicted steep thermal gradients, while for keyhole mode at 130 W, low thermal gradients correlated with high presence of equiaxed dendrites. Moreover, convection currents attributed to high recoil pressure in keyhole melt pools, were in agreement with locations of numerous subgrain boundaries having non-uniform morphologies, while under conduction, outward Marangoni flow led to a unique alignment of cellular subgrains and fewer subgrain boundaries. This study demonstrates the interplay among processing, thermal history, fluid flow and microstructure in WE43, and provides a basis for future design of microstructures for improved material properties.

WallGo is an open-source software designed to compute the bubble wall velocity in first-order cosmological phase transitions. Additionally, it evaluates the energy budget available for generating gravitational waves. The main part of WallGo, built in Python, determines the wall velocity by solving the scalar-field(s) equation of motion, the Boltzmann equations and energy-momentum conservation for the fluid velocity and temperature. WallGo also includes two auxiliary modules: WallGoMatrix, which computes matrix elements for out-of-equilibrium particles, and WallGoCollision, which performs higher-dimensional integrals for Boltzmann collision terms. Users can implement custom models by defining an effective potential and specifying a list of out-of-equilibrium particles and their interactions.

As the first public software to compute the wall velocity including out-of-equilibrium contributions, WallGo improves the precision of the computation compared to common assumptions in earlier computations. It utilises a spectral method for the deviation from equilibrium and collision terms that provides exponential convergence in basis polynomials, and supports multiple out-of-equilibrium particles, allowing for Boltzmann mixing terms. WallGo is tailored for non-runaway wall scenarios where leading-order coupling effects dominate friction.

While this work introduces the software and the underlying theory, a more detailed documentation can be found in https://wallgo.readthedocs.io.

Background

Patients with inflammatory bowel disease have an increased risk of colorectal cancer. There is a scarcity of large studies with a focus on rectal cancer in patients with inflammatory bowel disease. This study aimed to compare survival in resected patients with rectal cancer with and without inflammatory bowel disease.

Methods

This national population-based study used the Colorectal Cancer Data Base. All Swedish patients ≥18 years of age with a diagnosis of stage I–III rectal cancer between 1997 and 2021, surgically treated with curative intent, were included and followed up until 2022. The outcome of interest was recurrence-free survival. Flexible parametric survival models adjusted for time since surgery, year of diagnosis, sex, age at diagnosis, and Charlson Co-morbidity Index were used to estimate proportional and time-dependent hazard ratios of recurrence-free survival with 95% confidence intervals.

Results

Overall, 22 082 patients with rectal cancer were included, among whom 323 (1.5%) had inflammatory bowel disease. Neoadjuvant radiotherapy/chemoradiotherapy was given to 55% and 63% of patients with and without inflammatory bowel disease respectively. The median follow-up time was 5.2 years (interquartile range (i.q.r.) 2.3–10) in patients with inflammatory bowel disease and 5.9 years (i.q.r. 2.9–10) in patients without inflammatory bowel disease. Based on the adjusted proportional hazards model, no overall difference in recurrence-free survival was found (HR 1.05, 95% c.i. 0.87 to 1.26). In the time-dependent adjusted model, patients with rectal cancer with inflammatory bowel disease experienced a lower recurrence-free survival during the first year after surgery (1 year HR 1.36, 95% c.i. 1.06 to 1.73), after which there was no difference in comparison with patients without inflammatory bowel disease (5 years HR 0.77, 95% c.i. 0.56 to 1.06).

Conclusion

Despite lower recurrence-free survival during the first year among those with inflammatory bowel disease, there were no long-term differences between patients with or without inflammatory bowel disease.

Lymphatic vessels within different organs have diverse developmental origins, depend on different growth factor signaling pathways for their development and maintenance, and display notable tissue-specific adaptations that contribute to their roles in normal physiology and in various diseases. Functional studies on the lymphatic vasculature rely extensively on the use of mouse models that allow selective gene targeting of lymphatic endothelial cells (LECs). Here, we discuss LEC diversity and provide an overview of some of the commonly used LEC-specific inducible Cre lines and induction protocols, outlining essential experimental parameters and their implications. We describe optimized treatment regimens for embryonic, postnatal and adult LECs, efficientlytargeting organs that are commonly studied in lymphatic vascular research, such as the mesentery and skin. We further highlight the anticipated outcomes and limitations associated with each induction scheme and mouse line. The proposed protocols serve as recommendations for laboratories initiating studies involving targeting of the lymphatic vasculature, and aim to promote uniformity in lineage tracing and functional studies within the lymphatic vascular field.

Understanding the complex behavior of fractured rock systems is critical for applications in energy development, geological sequestration, and tunnel construction. Microscale fracture surface morphology influences flow and mechanical behaviors, while upscaling frameworks. Despite progress in hydro-mechanical and thermo-hydro-mechanical coupling models, two-way mechanical-chemical interactions remain underexplored. Discrete fracture networks offer a robust statistical framework for modeling subsurface fracture systems. Advances in machine learning have accelerated the simulation and optimization of fractured geothermal systems, addressing the computational limitations of high-fidelity models. These methods support multi-objective design, enhance life cycle assessments, and provide insights into optimal geothermal management strategies. Fractured rocks serve as preferential pathways for fluid flow and heat transport, significantly influencing permeability and mechanical stability. However, the inherent complexity of coupled thermo-hydromechanical-chemical processes in these systems presents major challenges. Nonlinear fracture mechanics, stress perturbations, and chemical interactions drive dynamic changes in fracture connectivity and permeability, further complicated by recursive feedback mechanisms. By integrating numerical tools, machine learning techniques, and advanced discrete fracture network models, the fractured rock system could be optimized and clearly analyzed.

OBJECTIVES

This study evaluated the long-term risk of permanent pacemaker implantation following Cox-maze IV (CMIV) and concurrent mitral valve surgery.

METHODS

A retrospective, nationwide, registry-based analysis was conducted on postoperative permanent pacemaker implantation in 397 patients with symptomatic mitral valve insufficiency and atrial fibrillation who underwent CMIV and mitral valve surgery in Sweden between 2009 and 2017. They were compared to a registry group of 346 patients with atrial fibrillation who underwent mitral valve surgery without surgical ablation during 2014–2017. The follow-up ended on 30 September 2022.

RESULTS

CMIV patients were on average 4 years younger and had lower surgical risk than registry patients. More CMIV patients underwent early (<30 days) pacemaker implantation (13.3% vs. 5.5%, P = 0.002). CMIV patients had a doubled adjusted risk of requiring a pacemaker compared to registry patients after 8 years [HR 1.96, 95% CI 1.27–3.04]. In the CMIV group, 22% (95% CI 18–26%) had a pacemaker by 5 years, increasing to 27% (95% CI 22–31%) by 8 years, compared to 13% (95% CI 10–17%) at both time intervals in the registry group. Atrioventricular block II/III accounted for >60% of early pacemaker indications in both groups, and sinus node dysfunction was the indication for late pacemaker implantation in 48% in the CMIV group.

CONCLUSIONS

Patients undergoing CMIV concomitant with mitral valve surgery have a higher rate of postoperative pacemaker implantation compared to patients with atrial fibrillation undergoing mitral valve surgery alone. Sinus node dysfunction was the main indication for late pacemaker among CMIV patients.

Aim

There is very limited data regarding the impact of centralization of care of patients with congenital diaphragmatic hernia (CDH). The National Board of Health and Welfare in Sweden decided to centralize the care of CDH from July 2018.

The aim of this study was to assess the short-term impact of centralization in patient outcomes.

Methods

This was a retrospective observational study including all centers in Sweden managing CDH before and after centralization. Outcomes for patients born with CDH who were managed from 1st of July 2013 to 30th of June 2018 (before centralization) were compared with patients managed 1st of July 2018 to 30th of June 2023 (after centralization). Fisher’s exact test and non-parametric tests were used to compare differences between the two time periods and a p < 0.05 was considered statistically significant. The study was approved by the Swedish Ethical Review Authority (2023-02650-01).

Main results

A total of 243 patients with CDH were managed nationally during the study period, 111 before and 132 after centralization. The rates of prenatal diagnosis, side of the defect, need of patch, or mortality did not differ significantly between the study periods. The need for ECMO decreased significantly after centralization 18 % vs. 7 %, p < 0.01).

Conclusions

After centralization, we observed a decreased rate of need for ECMO support. Although the time from centralization push through is short, it underscores the importance of an ongoing evaluation, optimization and strategic planning in order to find, describe and maximize the possible benefits of a centralization of CDH in our settings.

Type of Study

Retrospective cohort study, nationwide.

Level of Evidence

II.

Hypothermia remains a leading contributing factor to neonatal mortality. This study reports testing of a thermoregulatory device-'Thermal Jacket' that includes a reusable chemical warming pad (CWP) and an insulating jacket designed for hypothermia management. The laboratory experiments were conducted in two distinct phases between February'21 and June'22. In phase 1, a ternary composite of Sodium-Acetate-Trihydrate, Glycerol, Paraffin, and water contained in a high-density polyethylene-pouch named 'CWP' was finalised, and an insulating jacket was designed for targeted heat retention. In phase 2, the device's efficacy was evaluated using a mannequin in a controlled setting. The sample size was 81 events. Welch's t-test, ANOVA, and GEE were used to assess any significant differences between successful and failed events. Among 81 events, approximately 93% events of CWP and 98% events of insulating jacket successfully maintained temperature within 36-38 degrees C for 120 minutes. Moreover, ambient temperature, reuse of CWPs, humidity did not have any significant effect on the success rate of the CWP and insulating jacket. Thermal Jacket had achieved and sustained the temperature range of 36-38 degrees C for 2 hours. While this study used mannequin, clinical trial with preterm or low birthweight neonates is imperative to assess its effectiveness for thermal care management.

We prove the existence of piecewise smooth MHD equilibria in three-dimensional toroidal domains of R3 where the pressure is constant on the boundary but not in the interior. The pressure is piecewise constant and the plasma current exhibits an arbitrary number of current sheets. We also establish the existence of free boundary steady states surrounded by vacuum with an external surface current. The toroidal domains where these equilibria are shown to exist need not be small perturbations of an axisymmetric domain, and in fact they can have any knotted topology. The building blocks we use in our construction are analytic toroidal domains satisfying a certain nondegeneracy condition, which roughly states that there exists a force-free field that is ergodic on the surface of the domain. The proof involves three main ingredients: a gluing construction of piecewise smooth MHD equilibria, a Hamilton-Jacobi equation on the two-dimensional torus that can be understood as a nonlinear deformation of the cohomological equation (so the nondegeneracy assumption plays a major role in the corresponding analysis), and a new KAM theorem tailored for the study of divergence-free fields in three dimensions whose Poincar & eacute; map cannot be computed explicitly.

Tuberculosis (TB) remains a significant global health threat as one of the leading causes of death from an infectious agent. Despite decades of global efforts, an estimated 25000-32000 children develop multidrug-resistant (MDR) TB each year, yet only about 3000 children are diagnosed and treated. Critical gaps remain in paediatric TB research to generate evidence for dosing optimisation, ensuring timely access for children to effective and safe treatment. The overall aim of this thesis was to use pharmacometric tools to support paediatric clinical study design and establish robust evidence bases for paediatric dosing with paediatric-friendly options in MDR-TB treatment.  

A population pharmacokinetic model was developed for pretomanid with its newly developed child-friendly dispersible tablet formulation based on healthy adult data. The absorption properties of this new formulation were compared with the marketed formulations to assess its dosing implications in children or patients with swallowing difficulty. For delamanid, the bioavailability of the crushed and dispersed adult tablets was compared with the reference whole tablets in healthy adults through population pharmacokinetic modelling. This was to evaluate the feasibility of crushing delamanid adult tablets for use in children before the paediatric formulations become widely available. 

The population pharmacokinetics of new child-friendly formulations of moxifloxacin and clofazimine were characterised in children with TB from a multisite trial. Both drugs demonstrated absorption properties comparable to routinely used adult formulations. For moxifloxacin, the currently available dosing table was evaluated and optimised dosing was proposed based on the developed model. 

An approach was proposed for evaluating paediatric pharmacokinetic study design, focusing on a directly clinically relevant criterion, accuracy of dose selection, as an alternative to parameter precision, a commonly used criterion. The new approach evaluated the ability of a given design to accurately select doses that achieved closest-to-target exposures. This approach could support paediatric clinical trial development by balancing the study objectives and efficiency, potentially reducing costs and recruitment challenges. 

In summary, this thesis has, through pharmacometric applications, provided evidence to support the improvement of MDR-TB treatment in children, including the pharmacokinetics of child-friendly formulations for priority anti-TB drugs, optimized paediatric dosing, and paediatric pharmacokinetic clinical trial designs.