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Coastal communities are situated in dynamic socio-ecological contexts at risk from the impacts of climate change and other hazards. Meaningful strategies to maintain and/or improve community wellbeing are more important than ever; and so too is understanding the impact of chosen strategies. Past research has highlighted divergence in the how problems impacting the coast are framed in policies that direct management action; hampering the ability to holistically improve wellbeing (across social, economic and environmental grounds). Yet calls to better understand whether perceptions of those responding to change also diverge, and implications for improving wellbeing in coastal areas, remain unanswered. To address this gap, we interviewed key stakeholders that respond to change (coastal managers) and seek to improve wellbeing (community service providers) in Australia's fastest growing coastal areas and used Maslow's Hierarchy of Needs theory to examine divergence and convergence in perceptions of needs attainment as indicative of progress towards improved wellbeing. All stakeholders identified inequity in the ability of community members to meet their needs, but the impact of coastal hazards on community needs were perceived differently. Coastal managers perceived greater impacts on higher order needs (self-esteem and self-actualisation) while community service providers perceived greater impacts on lower order needs (physiological). These differences shape the prioritisation of responses and highlight the need for improved multisectoral understanding and collaborative strategies to improve wellbeing in coastal areas.

As in other parts of Southeast Asia, efforts to achieve or sustain malaria elimination in Indonesia have been threatened by the emergence of human infection with the primate species P. knowlesi. To understand the transmission dynamics of this species, investigation of P. knowlesi genetic diversity and population structure is needed. A molecular surveillance study was conducted in two phases between June 2014 and September 2018 at five primary health facilities in Aceh Province, Indonesia, an area nearing malaria elimination. Dried blood spot samples were collected from patients presenting with suspected malaria and testing positive for malaria by microscopy. PCR was performed for molecular confirmation and species identification. Forty-six samples were confirmed to be P. knowlesi, of which 41 were amplified with genotyping targeting ten known P. knowlesi microsatellite markers. For samples within a site, nearly all (9 of 10 loci) or all loci were polymorphic. Across sites, multiple identical haplotypes were observed, though linkage distribution in the population was low (index of association (I_A^S) = 0.008). The parasite population was indicative of low diversity (expected heterozygosity [HE] =  0.63) and low complexity demonstrated by 92.7% monoclonal infections, a mean multiplicity of infection of 1.06, and a mean within-host infection fixation index (F_ST) of 0.05. Principal coordinate and neighbour-joining tree analyses indicated that P. knowlesi strains from Aceh were distinct from those reported in Malaysia. In a near-elimination setting in Indonesia, we demonstrate the first evidence that P. knowlesi strains were minimally diverse and were genetically distinct from Malaysian strains, suggesting highly localized transmission and limited connectivity to Malaysia. Ongoing genetic surveillance of P. knowlesi in Indonesia can inform tracking and planning of malaria control and elimination efforts.

Tracing fast nanopore-translocating analytes requires a high-frequency measurement system that warrants a temporal resolution better than 1 mu s. This constraint may practically shift the challenge from increasing the sampling bandwidth to dealing with the rapidly growing noise with frequencies typically above 10 kHz, potentially making it still uncertain if all translocation events are unambiguously captured. Here, a numerical simulation model is presented as an alternative to discern translocation events with different experimental settings including pore dimension, bias voltage, the charge state of the analyte, salt concentration, and electrolyte viscosity. The model allows for simultaneous analysis of forces exerting on a large analyte cohort along their individual trajectories; these forces are responsible for the analyte movement leading eventually to the nanopore translocation. Through tracing the analyte trajectories, the Brownian force is found to dominate the analyte movement in electrolytes until the last moment at which the electroosmotic force determines the final translocation act. The mean dwell time of analytes mimicking streptavidin decreases from approximate to 6 to approximate to 1 mu s with increasing the bias voltage from +/- 100 to +/- 500 mV. The simulated translocation events qualitatively agree with the experimental data with streptavidin. The simulation model is also helpful for the design of new solid-state nanopore sensors. The study investigates the translocation dynamics based on COMSOL Multiphysics mimicking the actual experiment configurations. A key development of the model is the consideration of Brownian motion in addition to the already established electroosmotic and electrophoretic forces. The results are expected to be useful not only for the analysis of experimental results but also for the design of new solid-state nanopore sensors. image

Background: Chronic heart failure has high morbidity and mortality, with approximately half of the patients dying within 5 years of diagnosis. Recent additions to the armamentarium of anti–heart failure therapies include angiotensin receptor-neprilysin inhibitors (ARNIs) and sodium/glucose cotransporter 2 inhibitors (SGLT2is). Both classes have demonstrated mortality and morbidity benefits. Although these new therapies have morbidity and mortality benefits, it is not known whether rapid initiation is beneficial when compared with the conventional, slower-stepped approach. Many clinicians have been taught that starting with low-dose therapies and gradually increasing the dose is a safe way of intensifying treatment regimens. Pharmacologically, it is rational to use a combination of drugs that target multiple pathological mechanisms, as there is potential synergism and better therapeutic outcomes. Theoretically, the quicker the right combinations are used, the more likely the beneficial effects will be experienced. However, rapid up-titration must be balanced with patient safety and tolerability.

Objective: This study aims to determine if early addition of ARNIs, SGLT2is, β-blockers, and mineralocorticoid receptor antagonists (within 4 weeks), when compared with the same therapies initiated slower (within 6 months), will reduce all-cause mortality and hospitalizations for heart failure in patients with stable heart failure with reduced ejection fraction.

Methods: This is a single-center, randomized controlled, double-arm, assessor-blinded, active control, and pragmatic clinical trial. Adults with stable heart failure with reduced ejection fraction and idiopathic dilated cardiomyopathy will be randomized to conventional sequencing (the control arm; over 6 months) of anti–heart failure therapies, and a second arm will receive rapid sequencing (over 4 weeks). Study participants will be followed for 5 years to assess the safety, efficacy, and tolerability of the 2 types of sequencing. Posttrial access and care will be provided to all study participants throughout their lifespan.

Results: We are currently in the process of obtaining ethical clearance and funding.

Conclusions: We envisage that this study will help support evidence-based medicine and inform clinical practice guidelines on the optimal rate of sequencing of anti–heart failure therapies. A third placebo arm was considered, but costs would be too much and not providing study participants with therapies with known morbidity and mortality benefits may be unethical, in our opinion. Given the post–COVID-19 economic downturn and posttrial access to interventions, a major challenge will be acquiring funding for this study.

Invasiva arter blir ett allt större problem. Impatiens glandulifera (Jättebalsamin) räknas som en av de mest invasiva arterna i Europa och kan skapa problem för inhemska arter i habitaten den invaderar. I. glandulifera växer främst i strandzonen längs med vattendrag, men kan även förekomma i andra habitat. I naturen sprids arten främst genom att frön förflyttas långa avstånd via vattendragen samt översvämningar. I. glandulifera är väldigt konkurrenskraftig eftersom den kan växa i många olika förhållanden och snabbt etablera sig och konkurrera ut inhemsk flora. I och med dess konkurrenskraft påverkas de ekosystemen den invaderar. Allelokemikalier, vilka I. glandulifera producerar, kan användas för att påverka tillväxten hos konkurrerande växter. Allelokemikalien kan också läcka ut i vattendrag och påverka primärproducenter och primärkonsumenter. Detta gör att dessa populationer minskar vilket kan påverka hela näringskedjan. I. glandulifera kan också påverka biodiversiteten, dock finns det motsägelser inom forskningen kring detta. Vissa menar att I. glandulifera minskar biodiversiteten i habitaten den invaderar medan andra menar att biodiversiteten inte påverkas. Arten är även associerad med högre erosion hos strandbankar. Även pollinerare påverkas av I. glandulifera eftersom arten producerar mer socker än någon inhemsk europeisk art. Den drar därför till sig pollinerare vilket gör att inhemska arter inte pollineras lika effektivt. Evertebratsamhällens sammansättning kan också påverkas av invasioner och andelen mykorrhiza svampar minskar i närvaro av I. glandulifera. Det är viktigt att försöka minska spridningen av I. glandulifera så mycket som möjligt. För att göra detta kan man till exempel använda sig av bete eller översvämningar under specifika tider på året. 

This paper uses a neo-institutional perspective to examine possibilities and obstacles for participation in coordinated individual planning (CIP) for people with intellectual disabilities. CIP is a tool for interprofessional and interorganizational coordination with the objective of creating a joint plan for a person needing cohesive care. Participation by the service-user is considered important for effective coordination but involving someone with an intellectual disability may require special adaptations. A thematic analysis of interviews with 17 professionals from different organizations in Sweden reveals that service user participation is considered an important goal by professionals, but also that it is difficult to put into practice. The results indicate that CIP is characterized by tensions and policy-practice decoupling that limit the service-users' possibilities for participation. Different organisations and professionals sometimes give support to one individual. They need to coordinate this support.It is necessary for service-users to be involved in coordinated planning of the support and care they need.The study analyses how professionals experience participation in coordinated planning when the service-user has an intellectual disability.The study found that coordinated planning can be difficult to adapt for service-user participation.The study found a gap between ideals and practice caused by the organizations' rules, norms, and structures.The findings reveal a risk of focusing on changing the service-user's behaviour or situation rather than addressing problems within the organizations.

Iron porphyrins are molecular catalysts recognized for their ability to electrochemically and photochemically reduce carbon dioxide (CO2). The main reduction product is carbon monoxide (CO). CO holds significant industrial importance as it serves as a precursor for various valuable chemical products containing either a single carbon atom (C1), like methanol or methane, or multiple carbon atoms (Cn), such as ethanol or ethylene. Despite the long-established efficiency of these catalysts, optimizing their catalytic activity and stability and comprehending the intricate reaction mechanisms remain a significant challenge. This article presents a comprehensive investigation of the mechanistic aspects of the selective electroreduction of CO2 to CO using an iron porphyrin substituted with four trimethylammonium groups in the para position [(pTMA)Fe-III-Cl](4+). By employing infrared and UV/Visible spectroelectrochemistry, changes in the electronic structure and coordination environment of the iron center can be observed in real-time as the electrochemical potential is adjusted, offering new insights into the reaction mechanisms. Catalytic species were identified, and evidence of a secondary reaction pathway was uncovered, potentially prompting a re-evaluation of the nature of the catalytically active species.

Parenthood can be defined by the contradiction that it is one of the most satisfying yet stressful experiences in life. Many parents experience stress during parenthood, and some to the extent that they display symptoms of parental burnout. Nevertheless, research on parental burnout is scant and many studies have only examined the condition in Western settings. The aim of this study was to examine parental burnout among Somali mothers in Mogadishu, Somalia, and its association with certain psychological, psychosocial, and sociodemographic factors. In this cross-sectional study, questionnaire data were collected through the measurements Parental Burnout Assessment and Patient Health Questionnaire 9, as well as through social and demographic questions. A total of 882 Somali mothers in Mogadishu participated. The analysis methods used were univariate, bivariate, and multiple linear regression analysis. The results revealed that the mean parental burnout score was low in the sample. Additionally, a significant association was found between higher levels of parental burnout and higher levels of depression, perceived lack of social support, being unmarried, having a low monthly household income, and when the youngest child was of school-age.

Background Acute appendicitis is one of the most common causes of acute abdominal pain. Differences in the management of this large group of patients has important consequences for the patients and the healthcare system. Controversies regarding the understanding of the natural course of the disease, the utility of new diagnostic methods, and alternative treatments have lead to large variations in practice patterns between centres. These national guidelines present evidence-based recommendations aiming at a uniform, safe and cost-efficient management of this large group of patients.Method A working group of six experts with broad clinical and research experience was formed. Additional expertise from outside was consulted during the process. A national survey revealed significant variations in the management of patients with suspicion of appendicitis. The evidence provided in published guidelines and reviews were extracted and systematically graded, according to the GRADE methodology. This was supplemented by additional more recent and more directed search of the literature. Patients treated for appendicitis were involved through interviews. The guidelines were reviewed by external experts before the final version was determined.Results The guidelines cover an extensive number of issues: pathology, epidemiology, aetiology, natural history, clinical and laboratory diagnosis, diagnostic scoring systems, diagnostic imaging, treatment, nursing care, follow-up, quality registers and quality indicators, among others. Special considerations related to children and pregnant women are covered.Conclusion These national guidelines present an extensive and thorough review of the current knowledge base related to appendicitis, and provide up-to-date evidence-based recommendations for the management of this large group of patients.

Purpose of Review To summarize articles describing how to personalize care for heart failure (HF) informal caregivers on the basis of the literature review results. We also describe informal caregivers' preferences and wishes regarding personalized care.Recent FindingsRecent interventions to support informal caregivers were delivered face-to-face or online in group or individual sessions. The sessions embraced various elements, including coaching on setting personalized goals and developing problem-solving strategies. The interventions improved a range of variables, such as caregiver burden, quality of life, depression, stress and anxiety. Informal caregivers described personalized care as being in a partnership, clear communication and coordination of care.SummarySeveral intervention studies reported positive caregiver effects; however, they were small, and sometimes, the interventions were only briefly described. A deeper and more comprehensive understanding of the experiences and needs of informal caregivers is essential before new tailored interventions can be developed.

Recently formed allopolyploid species offer unprecedented insights into the early stages of polyploid evolution. This review examines seven well-studied neopolyploids (we use 'neopolyploid' to refer to very recently formed polyploids, i.e. during the past 300years), spanning different angiosperm families, exploring commonalities and differences in their evolutionary trajectories. Each neopolyploid provides a unique case study, demonstrating both shared patterns, such as rapid genomic and phenotypic changes, and unique responses to hybridization and genome doubling. While previous studies of these neopolyploids have improved our understanding of polyploidy, significant knowledge gaps remain, highlighting the need for further research into the varied impacts of whole-genome duplication on gene expression, epigenetic modifications, and ecological interactions. Notably, all of these neopolyploids have spontaneously arisen due to human activity in natural environments, underscoring the profound consequences of polyploidization in a rapidly changing world. Understanding the immediate effects of polyploidy is crucial not only for evolutionary biology but also for applied practices, as polyploidy can lead to novel traits, as well as stress tolerance and increased crop yields. Future research directions include investigating the genetic and epigenetic mechanisms underlying polyploid evolution, as well as exploring the potential of neopolyploids for crop improvement and environmental adaptation.

Differential measurements of Higgs boson production in the τ-lepton-pair decay channel are presented in the gluon fusion, vector-boson fusion (VBF), VH and t¯tH associated production modes, with particular focus on the VBF production mode. The data used to perform the measurements correspond to 140 fb⁻¹ of proton-proton collisions collected by the ATLAS experiment at the LHC. Two methods are used to perform the measurements: the Simplified Template Cross-Section (STXS) approach and an Unfolded Fiducial Differential measurement considering only the VBF phase space. For the STXS measurement, events are categorized by their production mode and kinematic properties such as the Higgs boson’s transverse momentum (p^H_T), the number of jets produced in association with the Higgs boson, or the invariant mass of the two leading jets (m_jj). For the VBF production mode, the ratio of the measured cross-section to the Standard Model prediction for m_jj > 1.5 TeV and p^H_T > 200 GeV (p^H_T < 200 GeV) is 1.29^+0.39_−0.34 (0.12^+0.34_−0.33). This is the first VBF measurement for the higher-pHT criteria, and the most precise for the lower-p^H_T criteria. The fiducial cross-section measurements, which only consider the kinematic properties of the event, are performed as functions of variables characterizing the VBF topology, such as the signed ∆ϕ_jj between the two leading jets. The measurements have a precision of 30%–50% and agree well with the Standard Model predictions. These results are interpreted in the SMEFT framework, and place the strongest constraints to date on the CP-odd Wilson coefficient c_H∼W.

Åldrandet är en komplex process som utmanar vår förståelse av biologiska system. Från en evolutionär synvinkel kan det verka paradoxalt att organismer åldras, och forskningen kring cellulär senescens - den gradvisa förlusten av cellers förmåga att förnya sig - utforskar just detta fenomen. Även de minsta encelliga organismer och våra egna kroppsceller åldras, vilket har betydande konsekvenser för vår hälsa och samhället i stort, särskilt med tanke på den ökande andelen äldre i befolkningspyramiden. Forskningen om cellulär senescens och dess roll i åldrandet har identifierat biomarkörer och mekanismer som kan användas för att mäta och manipulera denna process. Exempelvis har senolyter, molekyler som kan döda senescenta celler, visat lovande resultat i laboratoriestudier. Dessa inkluderar metformin, rapamycin, fisetin, dasatinib och quercetin där de alla visade på senolytisk förmåga. Studier på djur och människor har visat att dessa substanser kan minska antalet senescenta celler och bidra till förlängd livslängd och förbättrad hälsa. Rapamycin har visat sig förlänga livslängden till viss del hos olika organismer, medan kombinationen av dasatinib och quercetin har visat viss evidens på positiva effekter hos djur och människor. Metformin verkar även agera som förstärkare för rapamycin, och verkar inte ha någon senolytisk förmåga på egen hand.

Även om forskningen på senolyter är lovande, finns det fortfarande många frågor och utmaningar att lösa. Bland annat krävs det mer forskning för att förstå hur dessa substanser fungerar i olika vävnader och sjukdomsmodeller samt för att säkerställa deras säkerhet och effektivitet hos människor. Dessutom kan behovet av kombinationer av flera senolyter för att täcka ett brett spektrum av sjukdomar och vävnader kräva ytterligare forskning och utveckling. Forskningen om cellulär senescens och senolyter har potentialen att revolutionera vår förståelse och behandling av åldersrelaterade sjukdomar. Genom att angripa roten till många av åldrandets problem kan dessa upptäckter öppna dörren för nya behandlingar som kan förlänga människors livslängd. Fortsatt forskning på detta område förväntas vara avgörande för att förverkliga denna potential och adressera de utmaningar som åldrandet för med sig.

Virus kan orsaka förödande konsekvenser för samhället. I denna artikel studeras hur SARS-CoV-2 sprider sig mellan individer via luften och hur nuvarande vaccinationer mot viruset funkar. Studien visar även olika metoder för att påverka spridningen i lokaler och i olika transportmedel; detta kan utföras genom att förbättra ventilationssystemen eller införa filter som kan döda viruset. Transmissionen av viruset kan även påverkas av vaccination utav individer då spridningen minskar mellan personer när de är vaccinerade. Genom att studera olika vetenskapliga artiklar är slutsatsen att virusets spridning påverkas av ventilation i lokaler och fordon samt att filter som RM3 utvecklade till att ta bort virus minskar spridningen. Även olika typer av vaccin har visat på minskad infektionsrisk för personer och därmed leder vaccinering till en minskad spridning av viruset i samhället. Genom god ventilation och vaccinering av individer kan spridningen av virus reduceras i samhället och därmed rädda liv.

Introduction: Hypoglycemia in type 1 diabetes (T1D) ranges from mild to life-threatening events, yet most studies of hypoglycemia frequency rely on self-reported or aggregated data. Residual endogenous insulin production is associated to fewer severe hypoglycemic events, highlighting the potential benefit of preserving or restoring insulin production. For this purpose, gamma-aminobutyric acid (GABA) has emerged from experimental studies as a potential therapeutic drug candidate.

Aim: This thesis aimed to investigate the real-world frequency of hypoglycemia in children and adolescents with T1D, and to evaluate GABA’s therapeutic potential in a clinical trial.

Methods: Five studies were included. Endogenous GABA, C-peptide, counter-regulatory hormones and cytokine levels were analyzed in plasma. A controlled-release oral formulation of GABA (Remygen®) was assessed in a randomized controlled Phase I/II clinical trial in individuals with long-standing T1D (n=35) for safety, effect on endogenous insulin production and hypoglycemic counter-regulation.

The real-world frequency of hypoglycemia and its relationship to overall metabolic control and age was evaluated using retrospective continuous glucose monitoring (CGM)-data and clinical records. More than 50,000 hypoglycemic events were analyzed. Additionally, a single-metric scoring model for CGM-data evaluation was developed based on n=82,114 days of CGM-data by assessing three dimensions of glucose control. The models validity was evaluated against clinical treatment targets and interpretations of a clinical expert board (CEB). 

Results: GABA levels did not differ between individuals with T1D and healthy controls, but correlated with anti-GAD and cytokines. GABA treatment showed no improvements in endogenous insulin production or hypoglycemic counter-regulation, but side-effects were commonly observed. In the retrospective studies on CGM-data, mild hypoglycemic events (<3.9 mmol/L) were common. On average occurring on a near daily basis, regardless of age or metabolic control. However, no increased risk of severe- or serious (<3.0 mmol/L) hypoglycemia was observed in children achieving HbA1c ≤48 mmol/mol. The developed CGM scoring model correlated well with CGM-metrics and CEB interpretations.

Conclusions: Despite technological advancements, hypoglycemia remains a persistent challenge in T1D. GABA failed to regain beta-cell function, underscoring the need for alternative therapies in this aspect. Meanwhile, models for enhanced CGM analyses may aid in optimizing glucose management.

Human DNA constantly faces endogenous and exogenous damage, with DNA double-strand breaks (DSBs) posing the greatest threat to genome integrity. However, DSBs can be leveraged to kill cancer cells, as many treatments act as DSB inducers. The dominant repair pathway, non-homologous end-joining (NHEJ), resolves the majority of DSBs. This thesis explores strategies to sensitize resistant cancer cells through combination therapy and investigates NHEJ’s response to varying DSB complexities.

Paper I addresses cisplatin resistance in ovarian cancer. We found that combining cisplatin with the HSP90 inhibitor onalespib enhances sensitivity by increasing DSB levels, inducing apoptosis, and causing G2/M arrest, making it a promising strategy. Paper II focuses on glioblastoma (GBM), an aggressive brain tumor with limited treatment options. We demonstrated that onalespib enhances radiosensitivity in 2D and 3D GBM models by increasing DSB levels, promoting apoptosis, and altering protein expression, suggesting that HSP90 inhibition could improve radiotherapy outcomes. Paper III investigates the alpha emitter Ra-223, used in bone-metastatic prostate cancer. Our findings revealed that Ra-223 generates clustered DSBs, triggering NHEJ activation, growth inhibition, and apoptosis in prostate cancer cells, with no detectable cellular uptake. Paper IV explores pharmacological ascorbate (Asc) effect on NHEJ pathway. We found that Asc induces delayed DSBs, extensive pan-nuclear γH2AX formation, necrosis, and G2/M arrest in colorectal cancer cells, with stronger effects in XRCC4 KO cells. We concluded that Asc does not generate prompt DSBs, and the delayed DSBs are linked to necrotic nuclear degradation, with sensitivity influenced by cell cycle regulation rather than NHEJ deficiency. Paper V examines NHEJ’s role in repairing DSBs of varying complexity in colorectal cancer cells. Wild-type cells exhibited both fast and slow repair kinetics, while NHEJ-deficient cells showed only a fast repair phase, followed by repair failure. Non-DSB clusters increased as the DSB:SSB ratio decreased (from calicheamicin to X-rays, bleomycin, etoposide, and temozolomide). These clusters were rapidly removed, independent of NHEJ, highlighting the impact of DSB type/complexity on repair efficiency.

In conclusion, this thesis presents strategies to overcome cisplatin resistance, enhance radiosensitivity in GBM, and elucidate Ra-223 toxicity mechanisms in prostate cancer. It also examines Asc’s effects on DSB induction and repair and reveals NHEJ’s role in processing complex DSBs. Our findings provide new insights into optimizing DSB repair and therapeutic strategies in cancer treatment.

Geografi är ett tvärvetenskapligt ämne som förenar naturvetenskap och samhällsvetenskap för att hjälpa elever att förstå de komplexa relationerna mellan människor och miljö. I en värld som står inför globala utmaningar som klimatförändringar, migration och hållbar utveckling är det avgörande att geografiundervisningen inte bara förmedlar faktakunskaper utan också ger verktyg för att analysera och agera i en sammanlänkad värld. Denna studie undersöker hur geografilärare i högstadiet planerar och genomför sin undervisning för att främja elevernas förståelse av geografi som ett tvärvetenskapligt ämne. Studien belyser hur lärare balanserar teoretiska och praktiska metoder, särskilt behavioristiska och pragmatiska ansatser i sina klassrum. Genom att undersöka hur lärare använder olika strategier, som fältstudier och interaktiva undervisningsmetoder, framträder hur geografiundervisningen kan skapa meningsfulla lärandeupplevelser som både stärker grundläggande färdigheter och kritiskt tänkande. Resultaten visar att både behavioristiska och pragmatiska undervisningsmetoder är viktiga, men att faktorer som begränsade resurser och tidsbrist ofta påverkar hur dessa metoder tillämpas i praktiken.

Nuclear power is a key electricity source, with light water reactors being the most common type. Their fuel typically consists of uranium dioxide pellets stacked in zirconium alloy cladding tubes. The purpose of the fuel is to produce heat and act as a barrier against releasing radioactive material. During operation, heat and radiation cause thermomechanical changes that can lead to fuel failure if not controlled. Thus, the nuclear industry needs efficient fuel performance codes with well-quantified uncertainties to predict fuel rod behavior. This thesis focuses on improving inverse uncertainty quantification and surrogate modeling for efficient fuel performance predictions.

Inverse uncertainty quantification is essential because fuel performance codes require calibrated model parameters to ensure that predictions match measurements. However, standard calibration methods often underestimate uncertainties due to unaccounted-for uncertainty sources, such as model inadequacy. Therefore, this thesis presents how unknown sources of uncertainty can be accounted for in calibration using Markov Chain Monte Carlo (MCMC) by assuming a variability in the calibration parameters. Two methods are presented, and both are based on MCMC, requiring numerous samples to converge. Hence, Gaussian Process (GP) surrogate modeling is used in place of the code to provide the calibration methods with inexpensive estimates of code responses. The first method is derivative-based, relying on differentiated GPs. While it effectively calibrates cladding oxidation, it struggles with fission gas release. Consequently, a more accurate method based on MH-within-Gibbs sampling is presented that successfully calibrates fission gas release.

The presented calibration methods use GP surrogate models to efficiently calibrate model parameters with inexpensive scalar estimates of code predictions. Beyond calibration, surrogate modeling is also essential when time-dependent predictions are needed for numerous fuel rod irradiations simultaneously. For example, if time-dependent predictions of fuel rod behavior are required in core optimization or core monitoring, calculation time can become a limiting factor. Therefore, this work also investigates neural network architectures for temporal data based on Temporal Convolutional Neural Networks (TCNs) and Fourier Neural Operators (FNOs) designed to model numerous fuel rods with varying irradiation histories. These networks accurately predict the behavior of thousands of fuel rods within seconds, significantly improving computational efficiency.

Understanding fishing practices through the zooarchaeological record offers crucial insights into past human-environment interactions, subsistence strategies, and the development of the modern fishery practices. Past fishing practices varied widely depending on geographical location, environmental factors, and cultural contexts. In this thesis, I explore fish and fisheries in the Baltic Sea from different time frames. Evidence from archaeological fishbones and teeth provides a direct link to fishing practices in the past. Species diversity and anatomical distribution patterns are used to explore fishing methods. Isotope analysis on fish teeth offers further refinement of ecological patterns, including fish migration and mobility. Using zooarchaeological materials from Gotland and Åland, this thesis identifies and discusses patterns in relation to climate change and cultural shifts from the Mesolithic until the Early Modern Period. By applying the theoretical framework of negative space and values the formation of past assemblages and the remains excavated in the present are evaluated. Using strontium isotope analysis, the likely origin, fresh or brackish water, of euryhaline fish on Gotland is explored. The results indicate that fluctuations in aquatic habitat utilisation are tied to environmental shifts and influenced by cultural preferences and values.  To understand how fish are transformed from living creatures to products for human consumption, Medieval zooarchaeological material from Åland was used to investigate shifting patterns in the transportation of cod from a local fishery.  A possible difference in fish products was identified related to the Gotlandic sources. This has implications on how the written record might be interpreted. The aspects above are discussed in a diachronic way and modern concepts such as fishing down the food web are used to examine the sustainability of past fisheries. The findings contribute to broader discussion on past aquatic resource utilisation and fish's value and identities at different time frames in the Baltic Sea context. Highlighting the significance of fishbone analyses and the potential to incorporate archaeological data in contemporary sustainability discourse. 

Drug development is the process of advancing novel therapeutics to market to improve patient outcomes. However, in hard-to-treat diseases like neurodegenerative disorders there is a high failure rate in late-stage trials, creating significant unmet needs. This highlights the need for more sensitive endpoints, improved trial designs, or analytical methods to optimize data utilization.  In many diseases, clinical outcome assessments (COAs) serve as clinical endpoints and are often reported as a composite score, potentially losing important information present at the item level. Alternatively, item response theory (IRT) leverages item-level data to describe the relationship between a subject’s response on an item and their underlying ability, through item characteristic functions (ICFs), offering a more informed analysis of COAs. This thesis evaluates the robustness of IRT, estimation strategies and its applicability to model rating-scale-based COAs to facilitate model-informed drug development (MIDD). 

For single time point analysis, our findings suggest at least 100 subjects and 20 items are generally sufficient. Comparison of Laplace and Gaussian-hermite quadrature (GHQ-EM) for the estimation of item parameters, indicated similar accuracy and precision with slight improvement in accuracy for GHQ-EM.   IRT models in reduced assessments were relatively stable up to ~40-60% information remaining. However, removing items shifts the measured disease construct, which can affect the accurate assessment of disease progression and drug effect. The trade-offs in information lost or gained should be considered when shortening assessments. Comparison of two common estimation strategies for determining ICFs indicated similar performance, each providing different advantages. IRT was also effective in classifying disease (Parkinson’s vs SWEDDs), showing comparable performance to artificial neural networks. Additionally, IRT demonstrated superior power for detecting symptomatic treatment effect in a short duration trial compared to traditional approaches, highlighting IRT’s potential not only for endpoint analyses but as a strategic tool to optimize trial design. Greater public disclosure of applied IRT in real-time drug development, such as inclusion in trial protocols or in regulatory milestones could foster broader acceptance and wider adoption beyond ad-hoc analyses. In conclusion, this thesis presents a methodological foundation for successful implementation of IRT in a pharmacometric framework to facilitate MIDD and inform clinical decision-making.

Denna studie undersöker sambandet mellan ESG-poäng (Environmental, Social och Governance) och riskjusterad avkastning för bolag noterade på Stockholmsbörsen under perioden 2016–2023. Forskning kring ESG och finansiell prestation har visat på varierande resultat, vilket motiverar ytterligare studier. Syftet är att undersöka hur ESG-poäng påverkar den riskjusterade avkastningen och om ESG kan betraktas som en självständig värdeskapande faktor när bolagsstorlek beaktas. Studien använder kalenderportföljmetoden och fyrap ortföljer har konstruerats baserade på börsvärde och ESG-poäng. Data om aktiekurser, börsvärde och ESG-poäng har hämtats från LSEG Eikon. Resultaten visar att portföljer med lägre ESG-poäng tenderar att generera högre riskjusterad avkastning. Hedgeportföljer som konstruerats för att isolera ESG-effekten, uppvisade negativa alfa-värden. Studien drar slutsatsen att ESG-poäng inte bör betraktas som en isolerad indikator för överavkastning på Stockholmsbörsen under den studerade perioden och att ESG-faktorer snarare bör integreras i en bredare investeringsanalys.

As the Russian war in Ukraine expanded in 2022, it was made clear that the targeted sanctions directed at the power structure supporting Vladimir Putin had failed. This opened up for the question this paper attempts to answer, would more economically hurtful sanctions be more effective at stopping the Russian aggression? It is hypothesized that a resultsoriented study of the matter that eschews the formulaic restraints of the targeted vs. comprehensive sanctions debate could get to the bottom of this. Specifically, introducing GDP growth reduction as a metric for economic harm allowed for a quantitative study examining the variable’s relationship with the effectiveness of sanctions. Logistic regression returned a weak but existing relationship at the bivariate level, but as control variables were introduced to the regression this relationship softened beyond statistical significance. These findings suggest that although harsher sanctions on Russia could be a component of a strategy to dissuade continued aggression in Ukraine, as they have no demonstrated negative impact on the effectiveness of sanctions, such a strategy will need to be expanded beyond the targeting of GDP growth. 

Dyslexia affects around 5-8% of children, causing significant challenges with word decoding and spelling. It´s often a comorbidity with other conditions, such as language disorders. It can also be linked to more subtle language difficulties that don’t necessarily lead to a formal diagnosis but still impact functionality. The aim of this study is to examine the occurrence of language difficulties in children with dyslexia without a diagnosed language disorder in comparison to typically developing children. Data was gathered from 65 children, aged 9-13, with 30 diagnosed with dyslexia and 30 typically developing children. The children were part of the research project "Reading, Memory, and Brain" (REMEMBR), which explores the relationship between language, memory functions, and reading development. To measure language difficulties, the 5–15 Parent Assessment Form was used, where parents reported their children's challenges in areas such as comprehension, expressive language, and communication. The 5–15 Parent Assessment Form is designed to identify symptoms of language difficulties and conditions like ADHD. The results revealed a group difference in language difficulties between children with dyslexia and children without dyslexia. Children with dyslexia showed clear difficulties in both receptive and expressive language abilities, even though their performance on standardized tests did not differ from typically developing children. The parental assessment tool 5–15 appears to be a useful tool to identifying language challenges, but more research is needed to ensure more reliable results.

This thesis explores the impact of governance practices by extremist groups - Specifically ISIS in Syria (2014-2017) and the Taliban in Afghanistan (post-2021) - on women's reproductive rights in politically fragile contexts. Using a qualitative research approach and Mill's Method of Difference, the study highlights how both groups enforce strict interpretations of religious law that deeply restrict women's autonomy and access to reproductive healthcare. The findings show that while both groups impose severe limitations on women's reproductive rights, the nature and scope of these restrictions vary according to their governance strategies and socio-political contexts. This research emphasizes the urgent need for targeted interventions to address the unique challenges faced by women under extremist rule and contributes to the broader discussion on gender equality and governance in conflict-affected regions. By examining how radical ideologies shape women's rights, the thesis advocates for stronger efforts to protect reproductive rights as essential to women's health, dignity, and societal participation in areas of instability and conflict. 

This thesis will seek to test whether a causal relationship can be established between export dependencies on cash crops and state repression. A theory will be developed based on previous research on the topic of natural resources and state repression. Furthermore, this paper will examine whether a causal relationship exists between a dependence on the export of cash crops and state repression, while developing a hypothesis to test this relationship. Furthermore, this paper will also look closely into the legacy of colonialism and cash crops, which will serve as a basis for the theoretical arguments. However, much of the previous research has mainly focused on natural resources like oil and minerals. A research gap can therefore be observed when it comes to cash crops and state repression. Furthermore, state repression has previously been explained by the level of democracy and the presence of a potential civil war. This paper aims to take a different approach in order to test whether this new theory is applicable or not. The research question for this paper will be: “How does a country’s dependence on cash crop exports affect its willingness to engage in state repression?” The research of this paper will be conducted using qualitative methods in combination with Mill’s method of agreement. The findings of this paper indicate that support for the hypothesis could not be established.

Clays and clay-rich rocks play often an important role in nuclear waste disposal due to their low permeability and high sorption capacity, acting as natural barriers to fluid movement and contaminant migration. Understanding the transport and sorption behaviours of hazardous elements in clay-rich environments is therefore essential for long-term simulations with validated models of experimental data. This study investigates the reactive transport of 17 ionic compounds in the Woodford claystone using both experimental and modelling approaches. The experiment was conducted by injecting a multi-tracer solution into a column filled with crushed claystone, employing a flow-interruption method for examining kinetic behaviour during diffusion-dominated mass transfer. TOUGHREACT V4.0 OMP reactive transport code was applied to replicate the tests, using an advective-diffusive single porosity flow model that considers mineral dissolution/precipitation and cation exchange. The modelling results demonstrated that cation exchange and diffusion, along with advection, were the primary processes influencing ionic concentrations in the experiment. The primary mineral dissolution reactions were pyrite oxidation and silicate weathering, releasing Si, Al, and Fe that reprecipitated or contributed to cation exchange. The findings indicated that the claystone sample effectively sorbs Cs, Pb, and Eu through cation exchange. While the model showed good agreement with the experimental data, an excessive diffusion effect was simulated using the single-porosity model, which would likely be less if employing a dual-porosity model and accounting for immobile water.

Estimating the distribution and abundance of species is an important part of biodiversity conservation. Automatic camera traps have emerged as one of the most promising methods for making such estimates. Despite many advantages of these cameras, there are also disadvantages, such as problems of getting animals to stay in front of the camera long enough to get identifiable images. One method to reduce this problem is to apply odor-based bait in front of the cameras. Although previous studies have shown that baits can improve detection rates for some species, there is a limited knowledge of how baits influence detection rates of many other species. The aim of this study is to evaluate how the odor of rotted fish affects the effectiveness of camera traps, and whether a possible effect differs among mammal species. The study was conducted in the province of Cantabria, northern Spain in five regions with varying habitat types. The experiment consisted of 20 camera traps; 10 with bait and 10 without bait. The mammals included in the analysis had at least 10 observations: badger, red deer, marten, roe deer, fox and wild boar. The use of bait did not increase the number of observations, but the effect of baiting may vary between species. Badgers were observed more frequently at cameras without bait than at cameras with bait. Limitations of the study such as the time of data collection may have affected the results, and therefore a longer data collection period would have been of interest in future studies. Different kinds of bait could also have been included. More studies are needed to gain a better understanding of how baiting can be used to optimize data collection with camera traps in ecology and conservation biology.

This thesis explores the potential of using Received Signal Strength Indicators (RSSIs) as a Shared Secret Source for generating secret keys between two small IoT (Internet of Things) devices, notably for wearables and implantable medical devices. The main goal is to create an efficient algorithm, decreasing the computational cost required for key generation without compromising security. The algorithm consists of three main parts: preparing the data, quantizing the data into bits for key generation, and reconciling errors. The results suggest a promising potential for the use of RSSI as a shared source for secret key generation, with efficiency at a peak bit generation rate of 1.27 valid key bits per RSSI value for 64-bit keys with 8-bin quantization while blocking 97.6% of intrusion attempts. Future work for improving the results further includes exploring a narrower requirement for what values are to be used at the quantization stage as well as implementing a more sophisticated error reconciliation algorithm.

In the Russian history, the relationship between the Russian Orthodox Church and the Russian government has fluctuated, from being a beneficial relationship for both parties in the era before Peter the Great, to almost being eradicated under the Soviet Union. Research focusing on the contemporary Russian state-church relationship have pointed to signs that the church has become a central actor in shaping the Russian identity, legitimizing the state and its policies as well as influencing government policies, but at same time research has also shown that there are more than a few critical voices expressing discontent on state policy. The purpose of this qualitative study is to investigate how representatives of the Russian state publicly describe its relationship with the Russian Orthodox Church by applying a framing typology, that previously have been used on Orthodox online media, on statements given by Russian government representatives between January 2012 and March 2024. This thesis concludes that there is a discrepancy in how representatives from the two government branches under investigation, the Presidential Administration and the Foreign Ministry, describe the relationship with the Russian Orthodox Church. While the Presidential Administration describes the relationship through positive commentary and the Foreign Ministry more through cooperation, the overall description should be seen somewhere between cooperation and support. 

Obesity is associated with an increased risk of morbidity and mortality. Achieving a healthy body composition, which involves maintaining a balance between fat and muscle mass, is important for metabolic health and preventing chronic diseases. Computed tomography (CT) imaging offers detailed insights into the body’s internal structure, aiding in understanding body composition and its related factors. In this feasibility study, we utilized CT image data from 2,724 subjects from the large metabolic health cohort studies SCAPIS and IGT. We train and evaluate an uncertainty-aware deep regression based ResNet-50 network, which outputs its prediction as mean and variance, for quantification of cross-sectional areas of liver, visceral adipose tissue (VAT), and thigh muscle. This was done using collages of three single-slice CT images from the liver, abdomen, and thigh regions. The model demonstrated promising results with the evaluation metrics – including R-squared (R²) and mean absolute error (MAE) for predictions. Additionally, for interpretability, the model was evaluated with saliency analysis based on Grad-CAM (Gradient-weighted Class Activation Mapping) at stages 2, 3, and 4 of the network. Deformable image registration to a template subject further enabled cohort saliency analysis that provide group-wise visualization of image regions of importance for associations to biomarkers of interest. We found that the networks focus on relevant regions for each target, according to prior knowledge.

Studien syftar till att öka kunskapen om hur statens förmåga att styra mot transportpolitiska mål kan förändras i olika framtider med smart mobilitet. Smart mobilitet kan förstås som ett paraplybegrepp som samlar ett antal olika trender inom transportsektorn och som alla har det gemensamt att de knyter an till digitalisering. Generellt handlar omställningen mot smart mobilitet om två parallella processer: dels en utveckling i riktning mot självkörande och uppkopplade fordon, dels en utveckling i riktning mot nya former av delad mobilitet.

Analysen har baserats på det svenska transportsystemet men vi bedömer det som troligt att analyserna på en aggregerad nivå kommer vara giltig även i andra länder med liknande transportsystem. Vi konstaterar att staten idag förfogar över en stor mängd styrmedel, och sannolikt kommer många av dagens styrmedel vara aktuella även i en framtid med smart mobilitet. Vissa styrmedel påverkas direkt av smart mobilitet. Primärt styrmedel som drar nytta av uppkopplade fordon. Statens möjligheter är avhängigt deras tillgång till data och syn på sin egen roll att styra transportsystemet. Smart mobilitet kan även mer indirekt påverka styrningskapaciteten för olika styrmedel. Det beror på olika antaganden om trafikens utveckling, exempelvis ökad biltrafik eller mer delad mobilitet. Frågor om samhällets organisation har också stor betydelse. Smart mobilitet aktualiserar t.ex. att staten behöver ha en annan kompetens för att effektivt kunna verka i framtiden.

Smart mobilitet tillskrivs ofta en nyckelroll i den omställning som transportsektorn måste genomgå för att säkerställa ett hållbart transportsystem. Likt den gröna omställningen i stort så ställs många förhoppningar på att yngre generationer ska anamma de hållbarhetslösningar som nu presenteras. Samtidigt har smart mobilitet som koncept mottagit kritik för att inte i tillräckligt hög utsträckning ha tagit hänsyn till rättvisefrågor och jämställdhet i transportsystemet utan istället utformats som ett ”one-size-fits-all”-koncept. Unga som grupp har särskilda behov och förutsättningar. I denna rapport frågar vi oss hur väl dessa förutsättningar och behov har uppmärksammats och bemötts. Vidare ställer vi frågor om hur unga själva resonerar kring smart mobilitet, vilken potential den smarta mobiliteten har att förenkla deras dagliga resande och slutligen hur den skulle kunna utformas för att bättre svara upp mot deras behov. Undersökningen baseras dels på en litteraturöversikt i vilken vi fokuserat på vad tidigare forskning säger som ungas föreställningar och relation till smart mobilitet, hur den smarta mobiliteten hitintills använts av unga och vilka möjliga förbättringar som kan göras. Därtill har vi genomfört intervjuer med unga i mindre tätorter och landsbygd kring deras livssituationer i relation till mobilitet och transport och vilken roll de tänker sig att smart mobilitet skulle kunna spela i deras dagliga resande. Valet av unga på landsbygden grundar sig i att de ofta drabbats hårdare av transportrelaterad utsatthet än motsvarande grupper i storstadsområden. De saknar ofta tillfredsställande tillgång till kollektiva transportmedel vilket kombinerat med de ofta ganska långa avstånden till skola, arbete och fritidsaktiviteter skapar ett beroende av vuxna med bil som kan skjutsa. Den naturliga lösningen på denna beroendeställning blir därför ofta att skaffa körkort och bil i tidig ålder. Unga i mindre orter och på landsbygd utgör därför en nyckelgrupp både i termer av bristande valmöjligheter och autonomi och det bilberoende som denna brist ofta leder till.

Various services based on sharing have recently emerged in cities across the globe. They entail promises of a more sustainable mode of transportation. Through an in-depth case study, this paper follows the undertakings within a recent demonstration project aimed at implementing a residential bike-sharing service. The involved actors succeeded in presenting a functional service but failed to make the service commercially viable. Consequently, the configuration did not spread beyond the niche level. Based on this finding, the paper identifies a risk in enforcing progressive solutions to becoming commercialised, and urges public actors to play a greater role in steering the transition towards a more sustainable future transport system. By shedding light on the process of failing, the paper contributes important lessons concerning the setup of future bike-sharing systems that can challenge the automobility regime. © 2020 The Authors

Nanostructured silicon oxides (SiOx) are close-to-market anode materials for increasing the energy density of next-generation lithium-ion batteries (LIBs), offering a balance between high capacity and enhanced cycling stability. However, achieving precise control over SiOx composition while maintaining structural integrity remains a challenge. In this study, we pioneer the use of nanostructured diatom-SiO2 frustules from industrially cultured Nitzschia sp. microalgae as a sustainable and tunable precursor for high-performance SiOx anodes via scalable magnesiothermic reduction reaction (MgTR). By optimizing the Mg-to-diatom-SiO2 molar ratio, we demonstrate controlled partial reduction of SiO2, yielding Si nanocrystals embedded within an SiO2 matrix. Notably, we reveal that the preservation of diatom-SiOx nanoporosity is highly sensitive to reaction exothermic conditions and is effectively stabilized by introducing NaCl as a heat scavenger. Tailoring the reactant composition (SiO2:Mg:NaCl = 1:1:2.5) resulted in anodes with superior electrochemical performance, delivering high capacity retention over 200 cycles. Through a comprehensive suite of characterization techniques, we establish the structure-property-performance relationships governing SiOx anode behavior. These findings mark a major advancement in sustainable SiOx anode design, providing a scalable strategy for integrating biologically templated nanostructures into high-performance LIBs.

The Weberian apparatus is a novel hearing adaptation that facilitates increased hearing sensitivity in otophysan fishes. The apparatus is a complex system composed of modifications to anterior vertebral elements, the inner ear, and the swim bladder. A critical piece of the system that often receives minor attention are the various ligaments that bridge these three regions. The most famous of the ligaments is the interossicular ligament, which connects the Weberian ossicle chain (scaphium-intercalarium-tripus). Several other ligaments are present, including the suspensor (tripus to parapophysis 4) and the triple ligament (tripus-os suspensorium-tunica externa). Here, by combining diffusible iodine-based contrast enhancement (DICE) and propagation phase-contrast synchrotron radiation micro-computed tomography (PPC-SR mu CT) with classic histological methods, we shine new light on the first intercostal ligament (ICL1) and discuss its potential function in relation to the Weberian apparatus. ICL1 is nearly absent from the cypriniform literature, typically only mentioned in a general discussion together with other intercostal ligaments. This study examines the development and structure of ICL1 comparatively with the other definitive Weberian ligaments in the zebrafish (Danio rerio). We provide a comprehensive view of three-dimensional shape, development, and composition to generate hypotheses regarding potential functions of ICL1 within the greater Weberian apparatus. Given new detail presented herein regarding the structure of ICL1, modifications to rib 5 and parapophysis 4 for ICL1 attachment, and the alignment of ICL1 with the os suspensorium, we propose a supportive (anchoring) role of ICL1 to aid in minimizing non-optimal movement of the structures of the fourth vertebra. This addition would focus vibrations anteriorly through the ossicle chain with minimal signal loss in zebrafish and other species with similar Weberian apparatus morphologies. We conclude that ICL1 should be included in future analyses of Weberian apparatus function where ligaments are addressed.

Zinc oxide (ZnO) is a semiconductor with a wide range of applications, and often the properties are modified by metal-ion doping. The distribution of dopant atoms within the ZnO crystal strongly affects the optical and magnetic properties, making it crucial to comprehend the structure down to the atomic level. Our study reveals the dopant structure and its contents in Eu-doped ZnO nanosponges with up to 20% Eu-O clusters. Eu was distributed over the ZnO:Eu crystals, with an additional amorphous intercrystalline phase observed, especially in the 20% Eu sample. The electron pair distribution function revealed the presence of nonperiodic Eu3+-oxide clusters and proved highly effective for analyzing the coordination environment of Eu-O, ranging from 2.0 to 2.8 & Aring;. It uncovered three-, four-, and five-coordinate Eu-O configurations in the 20% Eu sample, and there were significant changes in Eu coordination between the samples, which is ascribed due to the intercrystalline phase. The proposed method offers a potential characterization routine for a detailed investigation of complex doped materials.

Aristotle grants perceptible qualities the power to generate sense perception in animals. But it is unclear whether, for him, these qualities can produce any effect other than perception. In this paper, I address this issue through a novel approach. To show that they can produce non-perceptual effects, I explore contexts in his extant works where qualities appear to do causal work in nature without leading to perception in animals. This inquiry aims to demonstrate that Aristotle's realism about qualities survives a potential threat posed by views that dispute the qualities' causal efficacy outside perception.

In June 2022, an innovative seismic survey was conducted in Bl & ouml;tberget, central Sweden, to evaluate the effectiveness of employing both a broadband seismic source and broadband receivers for mineral exploration in a challenging hardrock setting. The Bl & ouml;tberget mine hosts high-quality iron oxides, predominantly magnetite and hematite, sometimes enriched with apatite. These deposits comprise 10-50 m thick sheet-like horizons with a moderate eastward dip (similar to$\sim$45 degrees) along an NNE-trending zone. The survey employed a combination of co-located micro-electromechanical sensors, three-component recorders, surface and borehole distributed acoustic sensing, along with a 77-kN broadband seismic vibrator operating with 2-200 Hz linear sweeps. A tailored processing workflow was applied to preserve the broadband nature of the recorded data, and a one-dimensional velocity model was derived from the borehole distributed acoustic sensing data for migration and time-to-depth conversion purposes. Compared to the previous seismic surveys, the resulting seismic cross section reveals several well-defined reflections with improved resolution. Notably, a reflection intersecting the main deposits at a depth of approximately 1200 m exhibits a distinct polarity reversal relative to the reflection from the mineralization, providing further evidence for its interpretation as originating from a fault zone. Shallow reflections align with geological boundaries and partially coincide with weak magnetic anomalies. Additional reflections were revealed underneath the known mineralization on both sides of the fault zone and may suggest the presence of potential additional resources. The delineation of these reflections and the fault zone is critical for future mine planning and development in the region. This case study underscores the potential of broadband data in achieving high-resolution subsurface imaging in hardrock environment and its pivotal role in mineral resource assessment processes.

We have studied polarized Au(100) and Au(111) electrodes immersed in electrolyte solution by implementing finite-field methods in density functional theory-based molecular dynamics simulations. This allows us to directly compute the Helmholtz capacitance of electric double layer by including both electronic and ionic degrees of freedom, and the results turn out to be in excellent agreement with experiments. It is found that the electronic response of Au electrode makes a crucial contribution to the high Helmholtz capacitance and the instantaneous adsorption of Cl can lead to a charge inversion on the anodic polarized Au(100) surface. These findings point out ways to improve popular semi-classical models for simulating electrified solid-liquid interfaces and to identify the nature of surface charges therein which are difficult to access in experiments.

Disordered regions are an important functional feature of many multidomain proteins. A prime example is proteins in membraneless organelles, which contain folded domains that engage in specific interactions and disordered low-complexity (LC) domains that mediate liquid-liquid phase separation. Studying these complex architectures remains challenging due to their conformational variability. Native mass spectrometry (nMS) is routinely employed to analyze conformations and interactions of folded or disordered proteins; however, its ability to analyze proteins with disordered LC domains has not been investigated. Here, we analyze the ionization and conformational states of designed model proteins that recapitulate key features of proteins found in membraneless organelles. Our results show that charge state distributions (CSDs) in nMS reflect partial disorder regardless of the protein sequence, providing insights into their conformational plasticity and interactions. By applying the same CSD analysis to a spider silk protein fragment, we find that interactions between folded domains that trigger silk assembly simultaneously induce conformational changes in the LC domains. Lastly, using intact nucleosomes, we demonstrate that CSDs are a good predictor for the disorder content of complex native assemblies. We conclude that nMS reliably informs about the conformational landscape of proteins with LC domains, which is crucial for understanding protein condensates in cellular environments.

BackgroundNonalcoholic fatty liver disease (NAFLD) comprises multiple heterogeneous pathophysiological conditions commonly evaluated by suboptimal liver biopsies. This study aimed to elucidate the role of 13 diverse histological liver scores in assessing NAFLD disease activity using an in silico pharmacometric model-based approach. We further sought to investigate various noninvasive patient characteristics for their ability to reflect all 13 histological scores and the NAFLD activity score (NAS).MethodsA histological liver score model was built upon 13 biopsy-based pathological features (binary and categorical scores) from the extensive NASH-CRN (Nonalcoholic Steatohepatitis-Clinical Research Network) observational NAFLD Database study (n = 914 adults) using the concept of item response theory. The impact of 69 noninvasive biomarkers potentially reflecting NAFLD activity was quantitatively described across the entire spectrum of all 13 histological scores.ResultsThe model suggested that four different disease facets underlie the cardinal NAFLD features (steatosis, inflammation, hepatocellular ballooning (= NAS); fibrosis; highest correlations: corrballooning-fibrosis = 0.69/corrinflammation-ballooning = 0.62/corrsteatosis-inflammation = 0.60). The 13 histological liver scores were best described by contrasting noninvasive biomarkers: Age and platelets best reflected the fibrosis score, while alanine and aspartate aminotransferase best described the NAS, with diverging contributions of the three individual NAS components to the results of the overall NAS.ConclusionsAn in silico histological liver score model allowed to simultaneously quantitatively analyze 13 features beyond NAS and fibrosis, characterizing different disease facets underlying NAFLD and revealing the contrasting ability of 69 noninvasive biomarkers to reflect the diverse histological (sub-)scores.

Why are so few women given public assistance to relocate away from violence? This article will try to answer this question using findings from a study co-created by women with lived experiences and academic researchers. Public assistance for this group is, in Sweden, a right granted by the national Social Services Act, but a significant proportion of women in need of it do not receive it. A survey of local social services reveals a pattern of chance, low priorities, and lack of awareness of this group within the public administration. The pattern is the same for women with children, in spite of their additional legal protection.

In this work, we present the synthesis, solid-state characterization, and in silico studies of two pyrazole derivatives: 5-(2-methylphenoxy)-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (I) and 5-(4-methylphenoxy)-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (II). The molecular crystal properties, in terms of intermolecular hydrogen bonds and other weak interactions, are analyzed using single crystal X-ray diffraction. The Hirshfeld surfaces computational method is used to quantify the intermolecular interactions, density functional theory for theoretical structural optimization, and its comparison with the experimental structure and in-silico studies using docking and molecular dynamics studies of I and II with CDC7-kinase. In addition, the quantum theory of atoms in molecules (QTAIM) approach is applied to calculate the topological properties of electron density and the Laplacian of electron density of the chemical bonds of both molecules. Compounds I and II crystallize in a monoclinic crystal system, and molecules are connected via C-H<middle dot><middle dot><middle dot>O intermolecular hydrogen bonds. Hirshfeld surfaces analysis revealed that the H<middle dot><middle dot><middle dot>H type intercontact contributes more toward the crystal packing. DFT-optimized structures show a perfect overlay with the experimental structures. The in silico results show that both I (-41.50 kcal/mol) and II (-44.53 kcal/mol) exhibit strong binding free energies as ligands binding to the active sites of the CDC7-kinase. The most significant contributions for ligand and protein binding in both compounds are dominated by van der Waals interactions.

Methods for detecting gene flow between populations often rely on asymmetry in the average length of particular genealogical branches, with the ABBA-BABA test being a well-known example. Currently, asymmetry-based methods cannot be applied to a pair of populations and such analyses are instead performed using model-based methods. Here we investigate genealogical asymmetry under a two-population Isolation with Migration model. We focus on genealogies where the first coalescence event is between lineages sampled from different populations, as the external branches of these genealogies have equal expected length as long as there is no post-divergence gene flow. We show that unidirectional gene flow breaks this symmetry and results in the recipient population having longer external branches. We derive expectations for the probability of this genealogical asymmetry and propose a simple statistic (Am) to detect it from genome sequence data. Am provides a two-taxon test for gene flow that only requires a single unphased diploid genome from each population, with no outgroup information. We use analytic expectations and simulations to explore how recombination, unequal effective population sizes, bidirectional gene flow and background selection influence Am and find that the statistic provides unambiguous evidence for gene flow under a continent-island history. We estimate Am for genome sequence data from Heliconius butterflies and Odocoileus deer, generating results consistent with previous model-based analyses. Our work highlights a signal of gene flow overlooked to date and provides a method that complements existing approaches for investigating the demographic history of recently diverged populations.

Background and Objectives: Peritoneal metastasis from colorectal cancer carries a high risk for relapse after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). A novel alpha-emitting radiopharmaceutical (Radspherin) has been designed to deliver short-range radiation to micrometastases and free-floating tumor cells. Methods: A Phase 1/2a study evaluated the safety, tolerability, and signal of efficacy of escalating doses of Radspherin injected intraperitoneally after CRS-HIPEC. Results: Eleven patients received 1-4 MBq (Group 1) whereas 12 patients received 7 MBq; nine patients single dose/three patients split-dose (Group 2). Median age was 66.5 and 61.5 years, and median peritoneal cancer index 6 and 7, respectively. One hundred and seventy-eight adverse events were reported, only seven were deemed related to Radspherin. Thirteen serious adverse events (SAEs) were reported in eight patients and no SAEs were related to Radspherin. At 18-months, none of the 12 patients receiving 7 MBq experienced peritoneal recurrences, however four had non-peritoneal recurrences. Across both groups (n = 22), 41% had recurrent disease, only 14% of them in the peritoneum. Conclusions: Radspherin was well tolerated. At 18 months, median disease-free survival has not been reached, and none of the patients receiving the recommended dose (7 MBq) had peritoneal recurrences. The results are encouraging and warrant further clinical evaluation.