Periodontal Ehlers–Danlos syndrome arising from heterozygous pathogenic mutation in C1R and/or C1S genes is an autosomal-dominant disorder characterized by early-onset periodontitis. Due to the difficulties in obtaining and culturing the patient-derived gingival fibroblasts, we established a model system by introducing a heterozygous C1RR301P/WT mutation into human TERT-immortalized gingival fibroblasts (hGFBs) to investigate its specific effects on collagen metabolism and inflammatory responses. A heterozygous C1RR301P/WT mutation was introduced into hGFBs using engineered prime editing. The functional consequences of this mutation were assessed at cellular, molecular, and enzymatic levels using a variety of techniques, including cell growth analysis, collagen deposition quantification, immunocytochemistry, enzyme-linked immunosorbent assay, and quantitative real-time reverse transcription polymerase chain reaction. The C1RR301P/WT-mutated hGFBs (mhGFBs) exhibited normal morphology and growth rate compared to wild-type hGFBs. However, mhGFBs displayed upregulated procollagen α1(V), MMP-1, and IL-6 mRNA expression while simultaneously downregulating collagen deposition and C1r protein levels. A modest accumulation of unfolded collagens was observed in mhGFBs. The mhGFBs exhibited a heightened inflammatory response, with a more pronounced increase in MMP-1 and IL-6 mRNA expression compared to TNF-α/IL-1β-stimulated hGFBs. Unlike cytokine-stimulated hGFBs, cytokine-stimulated mhGFB did not increase C1R, C1S, procollagen α1(III), and procollagen α1(V) mRNA expression. Our results suggest that the C1RR301P/WT mutation specifically disrupts collagen metabolism and inflammatory pathways in hGFBs, highlighting the mutation’s role in these processes. While other cellular functions appear largely unaffected, these findings underscore the potential of targeting collagen metabolism and inflammation for therapeutic interventions in pEDS.

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

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

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

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

Level of Evidence: Level V.

Large language models (LLMs) are artificial intelligence (AI) based computational models designed to understand and generate human like text. With billions of training parameters, LLMs excel in identifying intricate language patterns, enabling remarkable performance across a variety of natural language processing (NLP) tasks. After the introduction of transformer architectures, they are impacting the industry with their text generation capabilities. LLMs play an innovative role across various industries by automating NLP tasks. In healthcare, they assist in diagnosing diseases, personalizing treatment plans, and managing patient data. LLMs provide predictive maintenance in automotive industry. LLMs provide recommendation systems, and consumer behavior analyzers. LLMs facilitates researchers and offer personalized learning experiences in education. In finance and banking, LLMs are used for fraud detection, customer service automation, and risk management. LLMs are driving significant advancements across the industries by automating tasks, improving accuracy, and providing deeper insights. Despite these advancements, LLMs face challenges such as ethical concerns, biases in training data, and significant computational resource requirements, which must be addressed to ensure impartial and sustainable deployment. This study provides a comprehensive analysis of LLMs, their evolution, and their diverse applications across industries, offering researchers valuable insights into their transformative potential and the accompanying limitations.

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

Background

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

Methods

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

Results

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

Conclusions

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

Trial registration

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

The present study aims at discussing relevant aspects for a potential roll-out of Electric Road Systems (ERS) on transnational corridors, as well as generally for ERS introduction in Europe.

Feasibility criteria have thus been developed in order to assess the following topics for specific potential ERS corridor projects:

• Technical aspects: Which technical prerequisites exist for ERS corridors and to which extent can they expected to be met?
• Environmental aspects: Which effects can be expected on key environmental indicators?
• Economic aspects: Can an ERS corridor pose a business case? Could it contribute to the improvement of ERS economy in general?
• Political aspects: Would an ERS corridor implementation make sense from a political point of view?

The developed criteria may serve as a toolbox for scrutinizing future transnational ERS corridor projects. In order to illustrate their application, we used them to analyse a potential roll-out of an Electric Road System on a selected highway corridor (424 km) connecting Sweden and Germany, but mainly located on Danish territory. Based on traffic flows and patterns along the corridor route, it was found:

• A considerable part of the total truck mileage on the corridor is done by vehicles with a rather limited driving distance for pre- and post-haul, assuming the corridor is realized as a stand-alone project, and
• the CO₂ emissions (well-to-wheel) of truck traffic along the corridor route can be significantly reduced if electric trucks are powered by the national electricity mixes expected for the year 2030, and even more if it would be powered purely renewable.

Background

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

Aim

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

Methods

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

Results

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

Conclusions

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

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

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

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

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

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

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

This research analyzes and compares two near-synonymous Russian discourse markers, čto ni govori (‘whatever you say’) and i pravda (‘truly’), both used to verify the truthfulness of statements within their contexts. Despite their crucial role in communication, their analysis remains incomplete. Using data from monolingual and parallel corpora in the Russian National Corpus (RNC) and Sketch Engine, we identified the unique features of these discourse markers, highlighting both their similarities and differences. Our findings reveal distinctions in their usage across various discourse modes (dialogue, questions, and monologues), the presuppositions they carry, their positioning within statements, and their combinatorial properties.

Background and objectives:

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

Design and methods:

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

Results:

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

Conclusion:

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

Long-term tactical infrastructure planning for a transportation network consists of deciding on renewals and major maintenance works. Such projects constitute large budget volumes and will impair the available traffic capacity during their execution, especially for railway systems. Quantitative methods that schedule and coordinate infrastructure projects together with traffic flow adaptations is however largely lacking today.

This paper addresses the joint planning of temporary capacity restrictions and traffic flow adaptions during track work closures, by proposing a bi-level optimization model which separates the problem into project scheduling (upper level) and traffic assignment (lower level). The latter model uses a novel traffic flow formulation for routing volumes of trains through the transportation network under the capacity restrictions given by the project scheduling. An aggregated network is used together with time discretized into uniform periods, which makes it possible to treat large national planning problems with a planning horizon of up to a year and a period length of a couple hours. The computational properties are evaluated, both for the individual models, and for their joint usage. Furthermore, results from applying the models on two case studies, concerning Northern and South-Western Sweden, are presented.

The main conclusion is that the model formulations are capable of solving realistic planning cases and to provide support for capacity planners at an infrastructure manager, even for a large national railway. The results show that a good overview over the collective traffic impact is obtained, but also that details of particular traffic relations or capacity usage over individual network links and their variation over time can be studied. One major deficiency has been identified in the flow-based traffic assignment model, which can lead to incoherent train flows over long traveling distances and many time periods.

Electric road systems (ERS) enable electric power transfer to moving vehicles by means of overhead lines, rails or wireless technology. ERS constitutes a new type of technological system (“permanent pick-up”) that is a paradigm shift compared to traditional refuelling at fuel stations. ERS offers the possibility to electrify long-distance heavy-duty road transport, as well as buses and passenger cars, without using large batteries. ERS has the potential to reduce fossil fuel dependency, emissions of greenhouse gases (GHG), air pollutants and noise in urban environments, while increasing energy efficiency in the transport sector. 

German and Swedish research organisations have conducted a joint study with the aim of (i) providing an assessment of different ERS concepts; (ii) assessing ERS markets, business models and financing strategies; (iii) researching requirements for international ERS interoperability; (iv) investigating the impact of ERS on the energy system and the environment; (v) recommending necessary policy actions to spur ERS introduction; and (vi) identifying a suitable ERS freight corridor between Sweden and Germany.

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

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

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

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

International migration creates a need for second language (L2) education in majority languages. The language programme Swedish for Immigrants (SFI) offers basic education in Swedish as an L2 to newly arrived adult migrants in Sweden. The aim of the study presented here is to explore the stability and dynamics of teachers’ beliefs about the education offered to students studying Literacy Education and Second Language Learning for Adults (LESLLA) during the COVID-19 pandemic. The study is part of an action research project that included teachers and students at four SFI schools. This sub-study builds on individual and focus group interviews with teachers from these schools, which are analysed though content analysis. The theoretical base for the study is the beliefs of teachers and the stability and dynamics thereof. For these teachers, the outbreak of the COVID-19 pandemic meant an abrupt switch from in-person instruction in the classroom to various combinations of digital education and in-person instruction in smaller groups. The beliefs of these teachers remained stable concerning their students’ needs, such as the importance of social interaction, varied exercises and frequent feedback. At the same time, they showed creativity in developing new forms of teaching. The situation was stressful for teachers and a higher level of stability could have allowed them to prioritise in other ways. In these politically and economically challenging times, LESLLA students are in even greater need of efficient and empowering education, not least access to digital tools and competence of high quality. We conclude that the possibilities for the schools of handling the crisis that the pandemic caused depended on the professional competence of individual teachers as well as their ability to act independently. 

Objectives:

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

Methods:

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

Results:

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

Conclusions:

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

The Swedish government has prioritized achieving a fossil fuel-independent vehicle fleet by 2030 which will require radical transformation of the transport industry. Electrifying the vehicle fleet forms an important part of this transformation. For light vehicles, electrification using batteries and charging during parking is already well advanced. For city buses, charging at bus stops and bus depots is being developed, but for heavy, long-distance road transport, batteries with enough capacity to provide sufficient range would be too cumbersome and too much time would have to be spent stationary for charging.

One solution might be the introduction of electric roads, supplying the moving vehicle with electricity both to power running and for charging. In the longer term, this approach could also be used for light vehicles and buses.

The objective of the Research and Innovation Platform for Electric Roads was to enhance Swedish and Nordic research and innovation in this field, this has been done by developing a joint knowledge base through collaboration with research institutions, universities, public authorities, regions, and industries.

The work of the Research and Innovation Platform was intended to create clarity concerning the socioeconomic conditions, benefits, and other effects associated with electric roads. We have investigated the benefits from the perspectives of various actors, implementation strategies, operation and maintenance standards, proposed regulatory systems, and factors conducive of the acceptance and development of international collaborative activities.

Traumatic head injuries represent a major global health burden, affecting up to 70 million people annually world-wide. To study head injury mechanisms and evaluate preventive measures, virtual, anatomically-detailed human surrogates, referred to as Human Body Models (HBMs), can be created using Finite Element (FE) modeling techniques. Such FE models can be used to computationally recreate real-world head traumas to study human response to impact and reveal injury mechanisms. However, since FE is an inherently heavy computational task, there are numerous modeling challenges associated with using FE analysis for this purpose: constitutive models need to be appointed to complex biological tissues, models need to be properly validated, the chosen approach should be feasible in terms of time, and so forth. This doctoral thesis aims to address a few of these difficulties.

This thesis is composed of four comprehensive studies, each related to the overall objective of developing new methodologies and models, and further developing existing ones, for in-depth FE reconstructions of real-world head trauma. To emphasize their applicability in head injury research, the four studies also feature in-depth reconstructions of real-world injurious events. In the first study, a male and female pedestrian HBM was developed based on an existing occupant HBM, along with an efficient framework for anthropometric personalization. In the second study, a framework for reconstructing head traumas of pedestrians and cyclists in real-world road traffic accidents was developed, validated and exemplified by reconstructing 20 real-world cases. In the third study, a material model for cranial bone was developed and validated, and used for predicting skull fractures in five fall accidents. Lastly, in the fourth study, the material model was applied to a subject-specific head model, used to conduct an in-depth reconstruction of a workplace fatality to assess the protective effect of construction helmets.

Together, these four studies highlight how in-depth FE reconstructions, involving geometrically personalized models of the human body, can provide head injury predictions with striking resemblance to real-world data. When conducted with care, such reconstructions can offer valuable insights into the complex dynamics of head trauma. They can be indispensable tools for evaluating injury prevention strategies, and can potentially be useful within the field of forensic medicine, as they may help open up for objectification of forensic evaluations.

Technology Readiness Levels (TRL) has become a standard approach to assessment of technological development projects. The origin of TRL is the US moon rocket programs. However, to develop and put intopractice advanced technology projects, also other aspects are important to evaluate in a systematic way.

This paper provides a tentative analytical model of four main perspectives to analyze readiness levels of technology projects; Technology Readiness Level (TRL), Political Readiness Level (PRL), Social and Societal Readiness Level (SRL), and Commercial Readiness Level (CRL). To be successful we need to explore and understand the process, interconnectivities between and the impact based on all those four aspects in an integrated way. 

Electric Road System (ERS) is a technology concept that has the potential to dramatically reduce the fossil fuel dependency in the transport system. ERS is defined by electric power transfer from the road to the vehicle while the vehicle is in motion, and could be achieved through different power transfer technologies from the road to the vehicle, such as rail, overhead line, and wireless solutions. The basic technologies for power transfer from the road to vehicles in motion have been developed through various international research projects. In recent years, ERS has moved from conceptual idea to real-world application in countries such as Sweden (2016 and 2018), the United States of America (California 2017), and Germany (2019). In addition, projects are being planned in Italy and China.

National and international freight transports in Europe are usually determined by national and EU strategies and regulations. The success of ERS implementation, especially when it comes to a transnational roll-out, depends on using regulatory frameworks to identify areas where adaptation is needed.

The work in the CollERS project has included a consideration of ERS in national and EU transport strategies. The present report relates to identification of areas where standards are missing or have to be adapted, as well a stakeholder dialogue (Germany, Sweden, Denmark and EU), e.g. by means of expert interviews at national and EU-level (industry, science, politics, and road administrations).

The aim of this report is to summarise, analyse and comment on the results from a collaborative workshop regarding standardisation of electric road systems that was organised by members of the CollERS project and hosted by FEHRL (the Forum of European National Highway Research Laboratories) at FIRM19 (the FEHRL Infrastructure Research Meeting 2019) in Brussels 28 March 2019.

This study is based on a collaborative project in which a lower secondary science teacher and researchers carried out formative interventions to explore epistemic emotions—particularly wonder—as a pedagogical tool in teaching evolutionary processes. Wonder is frequently highlighted as an emotion with strong potential to enhance students’ engagement in and understanding of science. However, few empirical studies have examined this phenomenon in authentic classroom settings. By using qualitative content analysis combined with multimodal interaction analysis of an audio- and video-recorded lesson designed for wonder, the study identified how students made meaning of and expressed emotions in relation to the subject matter. The results show that students engaged in more in-depth reasoning around the concepts of competition, variation, and adaptation—processes that also evoked emotional engagement. The study highlights the pedagogical potential of intentionally creating space for epistemic emotions in the teaching of complex scientific processes.

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

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

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

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

Poor data quality limits the advantageous power of Machine Learning (ML) and weakens high-performing ML software systems. Nowadays, data are more prone to the risk of poor quality due to their increasing volume and complexity. Therefore, tedious and time-consuming work goes into data preparation and improvement before moving further in the ML pipeline. To address this challenge, we propose an intelligent data-centric evaluation framework that can identify high-quality data and improve the performance of an ML system. The proposed framework combines the curation of quality measurements and unsupervised learning to distinguish high- and low-quality data. The framework is designed to integrate flexible and general-purpose methods so that it is deployed in various domains and applications. To validate the outcomes of the designed framework, we implemented it in a real-world use case from the field of analytical chemistry, where it is tested on three datasets of anti-sense oligonucleotides. A domain expert is consulted to identify the relevant quality measurements and evaluate the outcomes of the framework. The results show that the quality-centric data evaluation framework identifies the characteristics of high-quality data that guide the conduct of efficient laboratory experiments and consequently improve the performance of the ML system. 

In this longitudinal study, we examined the trajectories of sport and school burnout symptoms (exhaustion, cynicism, inadequacy) during the transition to lower secondary sport school among Norwegian student-athletes aged 13–14 years (n = 265; 58,5% males, 41,5% females). We also investigated how student-athletes’ gender and individual success expectations, and their parents’ reported levels of affection and success expectations, were associated with different burnout trajectories. Student-athletes completed associated questionnaires at the beginning and end of the first school year, while parents completed questionnaires at the end of the school year. Linear mixed models showed that sport and school burnout symptoms increased over the school year. Females reported higher baseline levels of sport burnout, and males lower baseline levels of school burnout. Low individual success expectations were associated with higher baseline levels of sport and school burnout, and increase in school burnout symptoms over time. High parental success expectations were associated with lower baseline levels of school-related exhaustion. Sport inadequacy increased for student-athletes whose parents reported either affection levels and success expectations that were either both high or both low. The results suggest that it is important that sport schools take the dual pressure student-athletes may experience into consideration, and provide them with adequate support during the transition to lower secondary education. In addition, interventions aimed at increasing parental knowledge of beneficial and harmful ways of involvement in student-athletes’ lives are needed to facilitate student-athlete wellbeing. 

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

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

Since the launch of the Sustainable Development Goals (SDGs) in 2015, there has been a growing interest in localizing SDGs through co-designed and participatory approaches. However, the implementation of SDGs in Arctic towns and cities has been the subject of limited research. The unique environmental, economic, and social conditions of these cities raise questions about the suitability of applying generalized approaches and indicators. To shed light on the unique challenges faced by Arctic cities and to gain insight into local urban development professionals’ perspectives and priorities regarding sustainable urban development, we employed a multidisciplinary approach based on Q-methodology. We focus on towns and cities in the Nordic plus Greenland Arctic. The results reveal seven distinct factors representing both shared perspectives and areas of disagreement on sustainable development. The findings indicate that tailored approaches are necessary for the successful implementation of the SDGs in Arctic cities.

This article analyses the #HerYürüyüşümüzOnurYürüyüşü (Every Parade of Ours is a Pride Parade) hashtag campaign for 2019 Pride month in Turkey, expressing the collective frustration of the LGBTI+ community against long-lasting bans for LGBTI+ events and public assembly. Drawing on a digital ethnography from Twitter, the article explores networked resistances within the complexity of online and offline entanglements of activism during Istanbul Pride 2019. The multimodal discourse analysis conducted in this article focuses on the interactions of digital affordances and embodied street actions in rearticulating queer political places. The study emphasizes the important role of hashtag activism in the (re)making of place as a trans-located experience, as well as affording emergent LGBTI+ resistances.

The below-ground growing season often extends beyond the above-ground growing season in tundra ecosystems and as the climate warms, shifts in growing seasons are expected. However, we do not yet know to what extent, when and where asynchrony in above- and below-ground phenology occurs and whether variation is driven by local vegetation communities or spatial variation in microclimate. Here, we combined above- and below-ground plant phenology metrics to compare the relative timings and magnitudes of leaf and fine-root growth and senescence across microclimates and plant communities at five sites across the Arctic and alpine tundra biome. We observed asynchronous growth between above- and below-ground plant tissue, with the below-ground season extending up to 74% (~56 days) beyond the onset of above-ground leaf senescence. Plant community type, rather than microclimate, was a key factor controlling the timing, productivity, and growth rates of fine roots, with graminoid roots exhibiting a distinct ‘pulse’ of growth later into the growing season than shrub roots. Our findings indicate the potential of vegetation change to influence below-ground carbon storage as the climate warms and roots remain active in unfrozen soils for longer. Taken together, our findings of increased root growth in soils that remain thawed later into the growing season, in combination with ongoing tundra vegetation change including increased shrub and graminoid abundance, indicate increased below-ground productivity and altered carbon cycling in the tundra biome.

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

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

Background: Omentectomy has traditionally been performed in gastric cancer surgery, but omental preservation has become increasingly common. It is unclear whether omentectomy leads to additional survival benefit compared with omental preservation. This nationwide population-based cohort study aimed to assess survival and surgical outcomes comparing omental preservation to omentectomy in curative-intent gastrectomy.

Methods: Patients were identified from the Swedish National Registry for Oesophageal and Gastric Cancer with inclusion between 2006 and 2022. The primary endpoint was overall survival assessed by a multivariable Cox proportional hazards model, adjusted for age, sex, American Society of Anesthesiologists physical status score, clinical T and N stage, type of gastrectomy, surgical approach, extent of lymphadenectomy, neoadjuvant chemotherapy, surgery year and regional cancer centre. Secondary endpoints were surgical outcomes including tumour-free resection margins, lymph node yield and postoperative complications.

Results: A total of 1615 patients were included, 517 (32.0%) underwent gastrectomy with omental preservation, and 1098 (68.0%) underwent gastrectomy with omentectomy. Overall survival after omental preservation was similar compared with omentectomy in the multivariable Cox model (HR 1.00, 95% c.i. 0.83 to 1.20; P = 0.967). Omental preservation also had similar surgical outcomes including lymph node yield and postoperative morbidity rate, compared with omentectomy.

Conclusions: Omental preservation was similar to omentectomy in terms of overall survival and surgical outcomes. The results suggest that omentectomy can safely be omitted in curative-intent gastrectomy for gastric cancer.

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

Temperature influences the transmission of mosquito-borne pathogens with significant implications for disease risk under climate change. Mathematical models of mosquito-borne infections rely on functions that capture mosquito-pathogen interactions in response to temperature to accurately estimate transmission dynamics. For deriving these functions, experimental studies provide valuable data on the temperature sensitivity of mosquito life-history traits and pathogen transmission. However, the scarcity of experimental data and inconsistencies in methodologies for analysing temperature responses across mosquito species, pathogens, and experiments present major challenges. Here, we introduce a new approach to address these challenges. We apply this framework to study the thermal biology of West Nile virus (WNV). We reviewed existing experimental studies, obtaining temperature responses for eight mosquito-pathogen traits across 15 mosquito species. Using these data, we employed Bayesian hierarchical models to estimate temperature response functions for each trait and their variation between species and experiments. We incorporated the resulting functions into mathematical models to estimate the temperature sensitivity of WNV transmission, focusing on six mosquito species of the genus Culex. Our study finds a general optimal transmission temperature around 24°C among Culex species with only small species-specific deviations. We demonstrate that differing mechanistic assumptions underlying published mosquito population models result in temperature optima estimates that differ by up to 3°C. Additionally, we find substantial variability between trait temperature responses across experiments on the same species, possibly indicating significant intra-species variation in trait performance. We identify mosquito biting rate, lifespan, and egg viability as priorities for future experiments, as they strongly influence estimates of temperature limits, optima, and overall uncertainty in transmission suitability. Experimental studies on vector competence traits are also essential, because limited data on these currently require model simplifications. These data would enhance the accuracy of our estimates, critical for anticipating future shifts in WNV risk under climate change

Small and medium-sized enterprises (SMEs) in Sweden’s Northern expanse, Norrland, operate in remote locations and challenging conditions. AI has been adopted by many organizations, providing a valuable addition to the digital toolkit. However, SMEs lack resources and capacity compared to larger organizations. the AI systems adopted are often limited and can leave them vulnerable. A qualitative exploratory study was undertaken with rural SMEs and associated stakeholders in Norrland to understand how AI was impacting the digital divide. The findings show that Norrland SMEs are leveraging AI to their benefit. However, there are emerging concerns regarding wider implications including cost and potential nefarious uses.

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

The present article examines the transition of regular lexical and syntactic structures to discourse markers. The concept of pragmaticalization and its positioning within linguistic theory continue to be subjects of ongoing debate. The analysis focuses two near-synonymous constructions – kak by to/tam ni bylo ‘however that may be’ and čto by to/tam ni bylo 'whatever it is’. Using this example, the investigation aims to show the principles underlying the pragmaticalization of constructions. The study uses data from the Russian National Corpus (RNC) and from Sketch Engine. Both constructions are based on the general concessive patterns kak by ni Р and čto by ni Р. The construction kak by to/tam ni bylo has completed the lexicalization and pragmaticalization process, but čto by to/tam ni bylo has not yet. The function of the discourse markers analyzed in the article is to accentuate the proposition within their scope as true despite potential doubts or contradicting circumstances.

Sedan 1992 har forskare Centrum för civilsamhällesforskning vid Marie Cederschiöld högskola genomfört befolkningsundersökningar för att följa utvecklingen av ideellt arbete och andra former av engagemang. Denna rapport presenterar resultaten från den sjunde undersökningen som genomfördes 2024 vilken är central del av vår forskning om det svenska civilsamhället. Resultaten erbjuder en unik inblick i civilsamhällets mest värdefulla resurs – de ideella krafterna.

Denna första delrapport från den sjunde undersökningen fokuserar på ideellt arbete. Här analyseras omfattningen av och förändringarna i ideellt arbete sedan tidigt 1990-tal och undersöker faktorer som kan förklara varför medborgare engagerar sig ideellt. Rapporten belyser även skillnader i hur ideellt arbete utövas i städer jämfört med på landsbygden.

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

Since 2018, the City of Gothenburg has implemented mobility and parking guidelines that allow developers to reduce the number of parking spaces in new housing projects in exchange for various mobility measures. These measures – such as car and bike sharing, free public transport period tickets, and information efforts – aim to reduce the need for private car use and car ownership. The process is voluntary, and property developers can decide for themselves which measures and what level of parking reduction they want to achieve, and in this way tailor the process to the individual project. The GotPark project has evaluated the effects of implemented mobility agreements. In the project, we have analyzed relevant documents such as detailed plans, building permits and the agreements themselves.

We have interviewed developers about their views on and experiences of the mobility agreements and associated measures. We have also conducted a survey among residents to investigate the effects on their transport and travel habits as well as attitudes towards the measures as such. The project shows that mobility agreements contribute to more sustainable mobility in Gothenburg. In properties with mobility agreements, there are approximately 25% fewer parking spaces than in comparable properties without agreements. Both car ownership and car use are lower and public transport is used more than in comparable properties without agreements. Residents have a generally positive view of the measures, while several of the measures are used very sparingly. Property developers have a generally positive view of mobility agreements and see many advantages in creating fewer parking spaces. The reasons are primarily economic, while the climate and urban planning arguments are less prominent. They also point to possible improvements in the agreement process, in the selection of appropriate measures and in the issue of follow-up and evaluation.

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

Background:

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

Methods:

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

Results:

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

Conclusions:

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

Significance Statement:

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

Background: Accurate assessments of current and future fertility—including overall trends and changing population age structures across countries and regions—are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios. Methods: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10–54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values—a metric assessing gain in forecasting accuracy—by comparing predicted versus observed ASFRs from the past 15 years (2007–21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline. Findings: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63–5·06) to 2·23 (2·09–2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137–147), declining to 129 million (121–138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1—canonically considered replacement-level fertility—in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7–29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59–2·08) in 2050 and 1·59 (1·25–1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6–43·1) in 2050 and 54·3% (47·1–59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions—decreasing, for example, in south Asia from 24·8% (23·7–25·8) in 2021 to 16·7% (14·3–19·1) in 2050 and 7·1% (4·4–10·1) in 2100—but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40–1·92) in 2050 and 1·62 (1·35–1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction. Interpretation: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world. Funding: Bill & Melinda Gates Foundation. © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

At the early maturity stage, the curing temperature has a significant impact on the mechanical properties of concrete. Concrete cubes are cured in water baths at different temperatures—5 °C, 20 °C, 35 °C, and 50 °C—in order to measure their compressive strength. This method is predicated on the knowledge that the pace of cement hydration is strongly influenced by the curing temperature. Then, the realistic curing temperature regime was imposed where the temperature of the curing water was modified based on the temperature patterns obtained from semi-adiabatic testing of concrete mixes to simulate curing conditions in the core of massive concrete structures. Ordinary Concrete: Compared to specimens cured at an isothermal curing at 20 °C, those cured in water baths at realistic curing showed an increase in compressive strength of 48% at seven days and 18.5% at 28 days. Fly Ash 18% Replacement: Compared to specimens cured at at 20 °C, the compressive strength of those cured at realistic curing increased by 45% at seven days, with a modest rise of 0.2% by the 28th day. Slag 18% Replacement: Compared to specimens cured at 20 °C, the compressive strength of those cured at realistic curing increased significantly by 121% at seven days and by 21.7% at 28 days. 

Background: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Funding: Bill & Melinda Gates Foundation. © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

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

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

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

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

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

Topology optimization methods employing binary (also known as discrete) design variables currently lack mathematical formulations to ensure length scale control in their solutions. This paper proposes and applies a morphology-mimicking filtering scheme to provide a minimum size control (often also referred to as minimum length scale control) in this class of binary designs. The Topology Optimization of Binary Structures (TOBS) method was chosen as the foundational framework for this length scale control study. Thermal and structural compliance scenarios were explored under this approach. Numerical results show that the proposed filter efficiently imposes the desired minimum length scale. The optimized designs were also less dependent on the filtering parameters when compared to designs optimized using standard techniques that employ continuous design variables. 

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

Continued improvement of heat control in mesoscopic conductors brings novel tools for probing strongly correlated electron phenomena. Motivated by these advances, we comprehensively study transport due to a temperature bias in a quantum point contact device in the fractional quantum Hall regime. We compute the charge-current noise (so-called delta-T noise), heat-current noise, and mixed noise and elucidate how these observables can be used to infer strongly correlated properties of the device. Our main focus is the extraction of so-called scaling dimensions of the tunneling anyonic quasiparticles, of critical importance to correctly infer their anyonic exchange statistics.