Search

The study's purpose was to describe the competence in well-being at work of social and health care educators and the factors influencing it. Cross-sectional study. Data were collected using a questionnaire from social and health care educators (n=243) working at ten randomly selected educational organizations. K-means clustering was used to identify three distinct educator profiles. Educators belonging to profiles 1 and 2 exhibited low competence in managing work wellbeing. All profiles exhibited intermediate competence in promoting work wellbeing. Competence in appreciating the work of educators was either intermediate or high in all three profiles. Managers working in educational organizations need to ensure and support educators' well-being.

Chronic dysregulation of microglial phenotypic balance contributes to prolonged neuroinflammation and neurotoxicity, which is a hallmark of neurodegenerative diseases. Thus, targeting microglial inflammatory signaling represents a promising therapeutic strategy for neurodegenerative diseases. Regulator of G protein Signaling 10 (RGS10) is highly expressed in microglia, where it suppresses pro-inflammatory signaling. However, RGS10 is silenced following microglial activation, augmenting inflammatory responses. While modulating RGS10 expression is a promising strategy to suppress pro-inflammatory microglial activation, no chemical tools with this ability exist. We developed a phenotypic high-throughput assay to screen for compounds with the ability to reverse interferon-γ (IFNγ)-induced RGS10 silencing in BV-2 cells. Identified hits had no effect on RGS10 expression in the absence of stimulus or in response to lipopolysaccharide (LPS). Furthermore, the hits reversed some of the inflammatory gene expression induced by IFNγ. This is the first demonstration of the potential for small molecule intervention to modulate the RGS10 expression in microglia.

Abstract Bone mass and lean mass decrease with age and these changes are associated with increased fracture risk and sarcopenia. Previous studies demonstrated that a probiotic mixture of Lacticaseibacillus paracasei DSM13434, Lactiplantibacillus plantarum DSM 15312 and DSM 15313 (L. Mix) prevents bone loss in ovariectomized (ovx) female mice. The purpose of the present study is to test if the beneficial effect of L. Mix is modified by the diet. Female mice were fed either a high-fat (HFD, 60% kcal from fat) or a low-fat (LFD, 10% kcal from fat) diet and subjected to either sham or ovx surgery and treated with L. Mix for 12 weeks. L. Mix treatment increased total body bone mineral density (p ≤ 0.01), by increasing cortical bone area, and total body lean mass (p = 0.035) in mice on LFD but not in mice on HFD. Metagenome sequencing of cecal content showed that L. Mix treatment increased the relative abundance of Lacticaseibacillus paracasei and, Lactiplantibacillus plantarum, demonstrating successful treatment. In addition, the probiotic treatment affected the overall gut microbiota composition and functionality. These findings demonstrate that the L. Mix in combination with a healthy diet is beneficial for musculoskeletal health in female mice.

In this paper, we shed light on the mundane performance of market-logics in public educational settings by focusing on municipality websites in Skåne County, Sweden, that inform parents about local school choice policies and procedures. We build on existing knowledge about the importance of websites in school choice systems. The aim of the paper is to 1) identify different ways in which Swedish municipalities configure parents in local school choice settings and 2) relate these configurations of parents to different ideas about the purpose of education. We draw on theoretical insights from Science and Technology Studies (STS) on how technical systems shape their own (future) users as well as the theoretical conceptualisation of education as a private and public good. Our data derives from 27 municipalities in the Skåne County in southern Sweden. We identify two types of scripts in the data; one that expects parents to make a choice and one that does not expect such a choice from the parents. In conclusion, our study indicates that children and their families in Sweden might encounter different understandings of the aims and responsibilities related to education, depending on which municipality they live in.

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer's disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

Abstract Patients with severe and sometimes moderate hemophilia B are prophylactically treated with factor IX concentrates to prevent bleeding. For some time now, various extended terminal half‐life (EHL) recombinant factor IX concentrates are available allowing less frequent administration during prophylaxis in comparison to standard half‐life recombinant FIX (rFIX). Especially, recombinant FIX‐Fc fusion protein (rFIXFc; Alprolix®) exhibits a rapid distribution phase, potentially due to binding to type IV collagen (Col4) in the extravascular space. Studies suggest that the presence of extravascular rFIXFc is protective against bleeding as without measurable FIX activity in plasma, and no extra bleeding seems to occur. The physiologically based pharmacokinetic (PBPK) model for rFIXFc which we describe in this study, is able to accurately predict the observed concentration‐time profiles of rFIXFc in plasma and is able to quantify the binding of rFIXFc to Col4 in the extravascular space after an intravenous dose of 50 IU/kg rFIXFc in a male population. Our model predicts that the total AUC of rFIXFc bound to Col4 in the extravascular space is approximately 19 times higher compared to the AUC of rFIXFc in plasma. This suggests that rFIXFc present in the extravascular compartment may play an important role in achieving hemostasis after rFIXFc administration. Further studies on extravascular distribution of rFIXFc and the distribution profile of other EHL‐FIX concentrates are needed to evaluate the predictions of our PBPK model and to investigate its clinical relevance.

Ruth Plummer,1 Alastair Greystoke,1 Gregory Naylor,2 Debashis Sarker,3,4 ANM Kaiser Anam,4 Hans Prenen,5 Laure-Anne Teuwen,5 Eric Van Cutsem,6 Jeroen Dekervel,6 Beate Haugk,1 Thomas Ness,1 Sujata Bhoi,7 Malene Jensen,7 Tom Morris,7 Pia Baumann,7 Niclas Sjögren,8 Karin Tunblad,7 Hans Wallberg,7 Fredrik Öberg,7 Thomas R Jeffry Evans2 1Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; 2Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK; 3School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK; 4Department of Medical Oncology, Guy’s Hospital, London, UK; 5Department of Oncology, Antwerp University Hospital, Edegem, Belgium; 6Department of Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium; 7Medivir AB, Huddinge, Sweden; 8SDS Life Science, Stockholm, SwedenCorrespondence: Pia Baumann, Medivir AB, Box 1086, SE-141 22, Huddinge, Sweden, Tel +46 739163897, Email pia.baumann@medivir.comPurpose: To evaluate safety, preliminary efficacy, pharmacokinetics, and pharmacodynamics, of fostroxacitabine bralpamide (fostrox, MIV-818), a novel oral troxacitabine nucleotide prodrug designed to direct exposure to the liver, while minimizing systemic toxicity.Patients and Methods: Fostrox monotherapy was administered in an open-label, single-arm, first-in-human, phase 1a/1b study, in patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, or solid tumor liver metastases. The first part (1a) consisted of intra/inter-patient escalating doses (3 mg to 70 mg) QD for up to 5 days, and the second part (1b), doses of 40 mg QD for 5 days, in 21-day cycles. Safety and tolerability were evaluated by the Safety Review Committee, and efficacy was assessed every 6 weeks with CT or MRI using RECIST 1.1 and mRECIST.Results: Nineteen patients were treated with fostrox. Most common adverse events (AEs) were hematological and increased AST. Grade 3 treatment related AEs (TRAE) were seen in 53% of the patients, with transient neutropenia and thrombocytopenia as the most common. No grade 5 AE was observed. Recommended Phase 2 dose of fostrox was 40 mg QD for 5 days in 21-day cycles. Preliminary efficacy showed a clinical benefit rate in the liver of 53% and stable disease (SD) as best response in 10 patients. Liver targeting with fostrox was confirmed with higher exposure of troxacitabine and its metabolites in liver compared to plasma. Systemic exposure of fostrox was generally low with troxacitabine as main analyte. Biopsies demonstrated tumor-selective, drug-induced DNA damage.Conclusion: The phase 1a/1b monotherapy study of fostrox, in patients with liver tumors, showed a tumor selective effect in the liver and that 40 mg QD for 5 days in 21-day cycles is safe and tolerable. Safety and preliminary efficacy in patients with advanced HCC supports clinical development of fostrox in combination with other modes of action in HCC.Keywords: phase 1, fostrox, hepatocellular carcinoma, nucleotide prodrug, pharmacokinetics, pharmacodynamics

Based on arguments about the need for greater individual freedom, school choice was introduced in Sweden in the 1990s. Swedish municipalities now set up local school choice systems, whose organization varies between municipalities. This study is based on interviews with three politicians and two civil servants from two average-sized municipalities with different school choice system designs and different political majorities. The aim of this study is to analyze how representatives of Swedish municipalities conceptualize their role and responsibility in relation to the role of parents in school choice systems, with a focus on school choice from pre-school to first grade. The analysis is focused on those instances in which parents fail to act as the design intended in the school choice system. The analysis shows that parents trouble the local school choice systems by both being passive and active when they are encouraged to make a choice.

An educator's competence influences the implementation of evidence-based education and the overall quality of social and health care. This study aimed to identify distinct competence profiles from Finnish social, health and rehabilitative care educators, as well as describe which personal and professional characteristics influenced belonging to a certain profile. Data were collected from 28 educational organizations located throughout Finland using the Health and Social Care Educators' Competence instrument. The survey was answered by 422 educators. The performed K-means cluster analysis identified three distinct educator competence profiles, which differed in terms of self-assessed expertise in various competence areas and certain background characteristics. The results highlight that educational institutions should concentrate on refining the digital competence of educators, which requires networking, collaboration, and work-related pedagogical competence. The differences in evaluation identified for the three profiles demonstrates that more experienced educators should mentor their less experienced counterparts to ensure a high quality of education.

The overall objective of this study was to investigate the longitudinal association between diffusion of responsibility and pro-aggressive bystander behavior across three time points in upper elementary education. This three-wave longitudinal study included 1905 Swedish students who completed a questionnaire in at least one of the three waves: the fourth (M[subscript age] = 10.56), fifth (M[subscript age] = 11.55), and/or sixth grades (M[subscript age] = 12.58). Both traditional and random intercept cross-lagged panel models revealed a reciprocal relationship between pro-aggressive bystanding and diffusion of responsibility from the fourth to fifth grades, whereas the only significant cross-lagged path from the fifth to sixth grades was from pro-aggression to diffusion of responsibility in the traditional cross-lagged panel model. Thus, this study provides evidence for bidirectional longitudinal associations between diffusion of responsibility and pro-aggressive bystander behavior but did not support a full cross-lagged bidirectional model.

Teachers have a major impact on students' social cognition and behaviors, and previous research has found that students who have positive relationships with their teachers tend to be less bullied by their peers. However, this line of research is limited in that it has been (a) Dominated by cross-sectional studies and (b) Treated bullying victimization as a global construct without differentiating among its different forms (i.e., verbal, physical, and relational). The links might be reciprocal but further studies are needed to investigate the directionality. Therefore, this study aimed to examine the longitudinal associations between student-teacher relationship quality and two forms of bullying victimization, namely verbal and relational victimization. Three waves of data from 1885 Swedish fourth- through sixth-grade students were analyzed with cross-lagged panel models. The findings showed that the student-teacher relationship quality predicted and was predicted by verbal and relational victimization. Our findings thus underscore the importance of striving for caring, warm, supportive, and respectful student-teacher relationships as a component of schools' prevention efforts.

The aim of the current study was to examine whether students' perceptions of teacher support at an individual-level, teacher support and well-functioning class climate at classroom-level, and teacher support and well-functioning class climate at school-level were associated with peer victimization. Data were obtained from a Student School Survey administered by the selected Swedish municipality. Multilevel analyses were based on 5,646 students in 277 classes and 27 schools. At the individual-level, girls and students who perceived greater teacher support than their classmates were victimized less often by their peers. In addition, students in schools with classes characterized by greater cooperation, cohesion, working atmosphere and respect toward their teachers tended to score lower on peer victimization. Within schools, students belonging to classes with a more well-functioning class climate than what was average in the school, and students belonging to classes that scored their teacher as more caring, fair and respectful compared to other classes in the school, were less likely to be targets of peer victimization.

Peer victimization in schools most often occurs in the presence of bystanders. When bystanders intervene on behalf of the victims, they are often successful in stopping the victimization. Defender self-efficacy (i.e., the belief in one's ability to successfully defend victims) has consistently been associated with greater defending and less passive bystanding in peer victimization. However, the lack of longitudinal research designs has resulted in a limited understanding of how these relationships develop over time. This five-wave longitudinal study involving 2507 Swedish students addressed this gap by examining longitudinal associations of defender self-efficacy with defending and passive bystanding. Participating students answered a self-report questionnaire once a year, from fourth to eighth grade. Our findings provide partial evidence for reciprocal associations among the variables. Moreover, there were more significant associations in the traditional than in the random intercept model, thus favoring between-person interpretations of the longitudinal associations. The findings highlight the importance of understanding the link between defender self-efficacy and bystander behavior of peer victimization, and that schools in their efforts in preventing school violence and bullying support students in increasing their defender self-efficacy and capacity in defending.

IntroductionParticipation is one of the core elements of health promotion, which means that approaches and methods should focus on involvement. The process of involving women with a migration background in health promotion needs to be further explored. Thus, the aim of this study was to explore the development process of a type 2 diabetes health-promotive community-based participatory research intervention among Middle Eastern women with a migration background, living in Sweden.Materials and methodsThis study was performed within the context of a community-based participatory research program in Sweden. The design of this study followed the development process of a community-based participatory research conceptual model, including three of the original four dimensions, that is, the context, the partnership process, and the intervention and research dimension. Appropriate methods for data collection were used in the various dimensions. Participants from the community, active in the program, conducted dialogue cafés, together with the core partners of the program, to inventory existing needs as well as what actions were needed for promoting health and thereby prevent type 2 diabetes.ResultsThe two dialogue cafes resulted in one long term and three short term goals. The third short-term goal—create health circles around food and nutrition was decided to be in focus for this study together with cooperation with the local health care center. The partnership process made it possible to involve relevant collaborators, which resulted in a jointly developed nurse-led educational intervention. Participants and stakeholders were also involved in the process of modifying and elaborating evaluation tools appropriate for the intervention.Discussion/conclusionsThe community-based participatory research approach enables the acknowledgement and use of the various kinds of knowledge of all stakeholders, including the community members. In this study, the community members’ knowledge was obtained through participation and dialogue, aimed at balancing power between stakeholders. This approach, that is, developing a community-based participatory research intervention, offers a possibility for the primary health care to engage with the community members and for other stakeholders to work in a health-promotive way.

Rationale Preterm infants diagnosed with bronchopulmonary dysplasia (BPD) are thought to have fewer and larger alveoli than their term peers, but it is unclear to what degree this persists later in life.Objectives To investigate to what degree the distal airspaces are enlarged in adolescents born preterm and to evaluate the new Airspace Dimension Assessment (AiDA) method in investigating this group.Methods We investigated 41 adolescents between 15 and 17 years of age, of whom 25 were born very preterm (a gestational age

Multiple Sclerosis (MS) is a neurological disease affecting particularly the working age population. The prevalence of MS in Finland is one of the highest in the world. Finnish social, health care and rehabilitation services providers need to solve many complex challenges, for example, how to increase the cost-effectiveness of the services, simultaneously meeting the essential needs of rehabilitees. Physiotherapy is one of the most common rehabilitation modalities for rehabilitees with MS. Telerehabilitation as a novel mode of physiotherapy has been recognized in Finland, but its applicability for successful physiotherapy remains unclear. This study is part of an interdisciplinary project conducted at the University of Jyväskylä, Finland. The goal of the project has been to develop a tentative prototype application of telerehabilitation for early stage MS rehabilitees. Information search was conducted to proof of concept of the telerehabilitation applications. Professional’s consultations were conducted to understand the applicability and usability of our application. In addition, the application development principles for our development purposes were discussed. In this study we report the idea of the developed telerehabilitation application as a product of a multi-professional development process. Findings of this study highlights the importance of critical and open reflection at every stage of any application development work to support interdisciplinary product development, cocreation process, as well as research, development and innovation (RDI) activities at various organizations.

BackgroundWell-targeted balance, walking, and weight-shift training can improve balance capabilities in the chronic phase of stroke. There is an urgent need for a long-term approach to rehabilitation that extends beyond the acute and subacute phases, supporting participation without increasing the demand for health care staff. ObjectiveThis study aims to evaluate the effectiveness of therapeutic exercise interventions with virtual reality (VR) training on balance and walking at the activity and participation levels in individuals with chronic stroke, compared with control groups receiving no treatment, conventional physical therapy, specific training, similar treatment, or identical treatment without VR. MethodsStudies were searched across 6 databases. The inclusion criteria were as follows: Adults aged 18 years or older with a stroke diagnosis for at least 6 months (population). Therapeutic exercises within a VR environment, using VR glasses or interactive games (intervention). Control groups without the use of VR (including no treatment, conventional physical therapy, specific training, similar treatment without VR, or identical treatment without the additional use of VR; comparison). We evaluated the Berg Balance Scale score, Functional Reach Test performance, Activities-specific Balance Confidence Scale score, Six-minute Walk Test, Two-minute Walk Test, 10-meter Walk Test results, and cadence (outcome measures). We investigated randomized controlled trials (study design). A meta-analysis and a meta-regression analysis were conducted to evaluate whether the content of VR interventions or control groups, as well as the level of VR immersion used, was related to balance or walking outcomes. ResultsA total of 43 randomized controlled trials involving 1136 participants were included in this review. The use of VR training in therapeutic exercise interventions had a large effect on balance (standardized mean difference 0.51, 95% CI 0.29-0.72; P

Well maintained cycleways will encourage more people to cycle, as the condition of cycleways is important for the safety, accessibility and riding comfort of cyclists. Despite that, only a few models used to describe the quality of service for cyclists take the surface condition into account. Objective measuring methods are needed to enable reliable and effective assessment of surface conditions, and measurable performance criteria related to the needs of cyclists should be developed. The purpose of this study has been to test the reliability and validity of using accelerometers in smartphones to assess the riding comfort on cycleways. A smartphone application converting three-dimensional accelerometer measurements into a single indicator for cycleways has been used to assess road surfaces in two field studies, in Sweden and Norway, respectively. Both studies assessed test sections of varying quality. To relate the measurements to subjective riding comfort assessments by cyclists, recruited cyclists collected quantitative data using the app, whilst also rating their perceived riding comfort by completing a survey. Measurements were also related to standard road surface condition indicators, generated from a road surface tester equipped with 19 laser sensors: international roughness index (IRI), mega- and macrotexture. The results show that it is possible to describe the unevenness of a cycleway using the technology present in smartphones. A software application can be used to collect and analyse data from the acceleration sensors in the phone, which can then be used to describe the riding comfort of cyclists. It is mainly the unevenness in the 50–1000 mm size-range that create the greatest discomfort for cyclists, and intermittent vibrations are perceived as more uncomfortable than more evenly distributed vibrations. Therefore, IRI is not a relevant measurement for describing the riding comfort of cyclists.

Abstract Statins are used to reduce liver cholesterol levels but also carry a dose‐related risk of skeletal muscle toxicity. Concentrations of statins in plasma are often used to assess efficacy and safety, but because statins are substrates of membrane transporters that are present in diverse tissues, local differences in intracellular tissue concentrations cannot be ruled out. Thus, plasma concentration may not be an adequate indicator of efficacy and toxicity. To bridge this gap, we used physiologically based pharmacokinetic (PBPK) modeling to predict intracellular concentrations of statins. Quantitative data on transporter clearance were scaled from in vitro to in vivo conditions by integrating targeted proteomics and transporter kinetics data. The developed PBPK models, informed by proteomics, suggested that organic anion–transporting polypeptide 2B1 (OATP2B1) and multidrug resistance–associated protein 1 (MRP1) play a pivotal role in the distribution of statins in muscle. Using these PBPK models, we were able to predict the impact of alterations in transporter function due to genotype or drug–drug interactions on statin systemic concentrations and exposure in liver and muscle. These results underscore the potential of proteomics‐guided PBPK modeling to scale transporter clearance from in vitro data to real‐world implications. It is important to evaluate the role of drug transporters when predicting tissue exposure associated with on‐ and off‐target effects.

Neurotrophic factor 3 (NTF3) is a cysteine knot protein and a member of the nerve growth factor (NGF) family of cytokines. NTF3 engages the Trk family of receptor tyrosine kinases, playing a pivotal role in the development and function of both the central and peripheral nervous systems. Its involvement in neuronal survival, differentiation, and growth links NTF3 to a spectrum of neurodegenerative diseases. Consequently, targeting NTF3 with antibodies holds promise as a first in class therapeutic opportunity for a wide range of conditions.Specific and neutralizing antibodies against NTF3 were successfully isolated using phage display. Initial phage display selections revealed a preference of hits for a longer than average complementarity-determining region 3 (CDR3) in the heavy chain variable domain (VH). To investigate this further we developed a long loop length VH CDR3 antibody library that demonstrated increased hit rates versus a standard antibody library and allowed the isolation of IgG that demonstrated inhibition of functional activity, coupled with a favourable kinetic profile.Structural analysis of the Fab/NTF3 interaction, via X-ray crystallography, unveiled an unconventional interaction wherein regions beyond the longer CDR loops of the Fab induced ordering in a flexible loop on NTF3, which remained disordered in its free antigenic state. This comprehensive approach not only sheds light on the therapeutic potential of NTF3-specific antibodies but also provides critical structural details that enhance our understanding of the complex NTF3-Fab interaction thus offering valuable insights for future antibody design and therapeutic development.

Samtida svensk finansiering av utbildningsforskning tenderar att i allt högre utsträckning främja tillämpad och praktiknära forskning, där forskningsfrågor initieras genom samarbeten mellan praktiker och forskare. Även om det finns ett värde i sådan forskning, hävdar författaren till denna essä att tillämpad forskning framför allt kan bidra med kunskap som inte utmanar den nuvarande ordningen. Författaren hävdar vidare att kritisk forskning däremot har potential att bidra till oförutsägbara resultat och värden som inte kan definieras eller fastställas innan forskningen genomförts. På så sätt har kritisk forskning potential att bidra med nytta som går utöver det som på förhand tas för givet, vilket kan öppna för kunskap om underliggande, överraskande och undantryckta aspekter av olika sociala praktiker. Syftet med denna text är att argumentera för den kritiska utbildningsforskningens existensberättigande och nytta genom att introducera och förespråka begreppet oförutsägbar forskningsnytta, som ställs i kontrast till begreppet förutbestämd forskningsnytta. English abstract On the Value of Critical Research and Unforeseeable Research Utility in Educational Science Contemporary educational research funding in Sweden tends to promote applied research, where research questions are initiated through collaborations between practitioners and researchers. Although there is value in such research, the author of this essay argues that applied research contributes foremost with knowledge where the current order of things remains unchallenged. Furthermore, the author argues that critical research might contribute to unpredictable outcomes and values that cannot be defined or established before the research is conducted. In this way, critical research has a potential to contribute with utility that goes beyond the taken for granted, which might open for acknowledging the underlying, surprising, morbid, and abject aspects of social practices. The purpose of this text is thus to defend the raison d’être and utility of critical educational research by introducing and advocating the concept of unpredictable research utility, which is contrasted with the concept predetermined research utility.