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    Anti-gene oligonucleotides targeting Friedreich's ataxia expanded GAAâ\u80¢TTC repeats increase Frataxin expression

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    Friedreich's ataxia is a progressive, autosomal recessive ataxia caused, in most cases, by homozygous expansion of GAA center dot TTC triplet-repeats in the first intron of the Frataxin gene. GAA center dot TTC repeat expansion results in the formation of a non-B-DNA intramolecular triplex as well as changes in the epigenetic landscape at the Frataxin locus. Expansion of intronic GAA center dot TTC repeats is associated with reduced levels of Frataxin mRNA and protein, resulting in disease development. In our previous study, we demonstrated that DNA-binding anti-gene oligonucleotides specifically targeting the GAA center dot TTC repeat expansion effectively disrupted the formation of intramolecular triplex structures. In this study, we extend these findings by showing that targeting repeat-expanded chromosomal DNA with anti-gene oligonucleotides leads to an increase in Frataxin mRNA and protein levels in cells derived from Friedreich's ataxia patients. We examined numerous anti-gene oligonucleotides and found that the design, length, and their locked nucleic acid composition have a high impact on the effectiveness of the treatment. Collectively, our results demonstrate the unique capability of specifically designed oligonucleotides targeting the GAA center dot TTC DNA repeats to upregulate Frataxin gene expression

    "We can't do everything ourselves."- Why Swedish municipalities deliberately promote intermediation in governing the mobility transition

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    Literature on intermediation in transitions has emphasised the importance of publicly promoting intermediation. To understand what drives authorities to financially promote intermediation, we conducted an exploratory study of 16 Swedish municipalities promoting an intermediary actor in the mobility transition, applying the framework of drivers of collaborative governance. The results highlight drivers common to most municipalities, including among others administrators' awareness of collaboration challenges, or their inability to conduct intermediary activities on their own. However, the results also reveal diversity and context dependency of the drivers, leading to municipalities voicing diverse and partly conflicting expectations towards the intermediary. These findings underline the importance of understanding the promotion of intermediation through municipalities as a transactional and personal relationship between administrators and intermediaries. They also underline the relevance of "affective work" to mitigating conflicts caused by the diversity of expectations facing intermediaries, and the importance of municipalities in shaping local ecologies of intermediation.Funding Agencies|Swedish energy agency through the project "Effective regional collaboration for a fossil-free society (VERSAM) [P2022-00149]</p

    Positive anticipated affective reactions increase pro-environmental behavior

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    With households accounting for 75% of global carbon emission, we need to find ways to motivate people to increase their climate change mitigating behaviors. Affective reactions have been linked to pro-environmental behaviors (PEBs), but it is unclear if positive (warm glow or hope) or negative (worry or hopelessness) is more impactful in motivating action. In this pre-registered study we used a unique longitudinal dataset from a Swedish sample to reveal that positive affect predicts more engagement in PEBs, and negative affect predicts less engagement in PEBs. A mediation model also suggests that anticipated (i.e., expected feelings of) positive affect is related to past pro-environmental engagement and could partly predict future PEBs. Hence, affective reactions may be one way to increase intrinsic motivation for a more sustainable lifestyle.Funding Agencies|Swedish Energy Agency (Energimyndigheten) [P2023-00210, P2024-00782]; Marianne and Marcus Wallenberg Foundation [KAW 2023.0289]</p

    The new industry playbook: digital service innovation in multi-platform ecosystems

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    PurposeThis study aims to explore the role of digital platforms in fostering digital service innovation (DSI) in business-to-business (B2B) settings. More specifically, it delineates how firms orchestrate and govern multi-platform ecosystems to pursue DSI, outlining key complementors and their interdependencies.Design/methodology/approachUsing 37 in-depth interviews with DSI decision-makers from leading transportation and healthcare firms, the study investigates how different types of digital platforms enable data-driven services.FindingsThe study extends B2B platform classification beyond traditional open vs closed architecture and transaction vs innovation platforms, revealing five distinct types of B2B digital platforms. These are manufacturer-led, provider-mediated, customer innovation, customer-moderated and data brokerage platforms. The study explores different actors-resources-activities constellations in these platforms for executing DSIs. It further elucidates how platform actors play different roles in DSI depending on their ecosystem positions. Finally, it underscores the importance of platform governance in facilitating interoperability and introduces the concept of customized technology adapters as tools for integrating external complementors and supporting DSI.Originality/valuePrior studies on digital platforms have predominantly concentrated on examining platform architecture and objectives to categorize platform types. Our investigation, which centers on platform-based DSI activities, identifies distinct platform types that revolve around idiosyncratic service business models implemented by B2B firms. Additionally, we distinguish emerging boundary resources employed by these firms to integrate complementors, which may play a crucial role in ensuring platform interoperability in subsequent developments.Funding Agencies|Excellence Center at Linkping-Lund in Information Technology (ELLIIT)</p

    Bridging Technology and Mental Health : Challenges and Opportunities in Robot-assisted Perinatal Depression Screening

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    Perinatal depression (PND), affecting up to 20% of individuals during the perinatal period, presents serious risks to both maternal and child health. Despite the availability of effective interventions, many PND cases remain undiagnosed, highlighting the need for more accessible screening methods. This thesis explores the potential of machine learning, mobile health (mHealth), and socially assistive robots (SARs) to enhance PND screening and diagnosis. It focuses on three objectives: (1) to develop predictive machine learning models for PND prediction using app data; (2) to explore stakeholder perspectives on SARs in PND care; and (3) to design an SAR prototype for PND screening and diagnosis and evaluate user acceptance and ethical concerns. The first part of the research employed machine learning, which demonstrated that the occurrence of PND in the third trimester can be predicted using ecologically collected data. This highlights the potential of mHealth platforms for scalable early prediction of PND. The study also found that psychological health factors are the most predictive indicators for early PND. The second part of the research explored the integration of SARs into PND screening and diagnosis through qualitative interviews with psychiatrists, PND experts, gender scholars, and mothers. The findings revealed diverse perspectives on the efficiency, acceptability, and design of SARs. Ethical concerns, like data privacy and informed consent, were also raised. While participants generally welcomed the potential of SARs to support PND screening, they consistently emphasized the need for human oversight.  To translate high-level ethical guidelines into design practice, an exploratory case study developed SAR prototypes focusing on transparency and anthropomorphism. An online study examined how these traits influence the perception and efficacy of SARs. Results indicated that participants were more likely to agree with the transparent robot's recommendations. Findings from these studies, along with insights from subsequent participatory design sessions with mothers, informed the development of a real-world SAR prototype. User evaluations indicated that SARs are mostly welcomed in PND screening and can facilitate nonjudgmental interactions and emotional disclosure. This thesis shows how machine learning, mHealth, and SARs can complement clinical care, offering effective, scalable, ethical tools to address gaps in perinatal mental healthcare

    The science behind the lifesum app: an intervention design analysis

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    Wellness is an increasingly important part of public health and can prevent both disease and death. Diet and nutrition are important factors that contribute to wellness and predict health outcomes. Adhering to healthy diets is notoriously difficult for many, and some support is often required. Increasingly, that support may be found in the shape of an app in a smartphone. One such app is Lifesum, with some 65 million users worldwide. Lifesum adopts a more holistic approach to nutrition and well-being, and adopted an evidence-based approach to its development. The aim of this study was to describe the scientific, theoretical basis for the Lifesum app and contribute to advancing science in the field of wellness app development. This was an intervention design analysis, designed to describe the theoretical model and intervention theory used to create the Lifesum app in its current embodiment. A pragmatic theoretical model describing behaviour change in the context of healthy eating was devised based on findings in literature. Factors that drive unhealthy eating behaviours, but that were malleable and whose mechanisms of change were feasible to implement, were identified and used to form an intervention theory. The theoretical model and the intervention theory could then guide the implementation of the Lifesum app, illustrated by a logic model. The theoretical model emphasizes personal goal-attainment and motivation as keys to establishing and maintaining healthy eating behaviours, with proximal outcomes being nutrition knowledge, mindfulness about eating and macro-nutrient balance. Nutrition knowledge is achieved through the provision of nutrition information from a vast database on food items, easily available. Continuous feedback on food choices made will enhance this knowledge and a greater awareness of the impact of nutrition on health remains desirable. A more mindful disposition regarding foods is achieved through support in terms of tracking food intake continuously, as well as recommending meals or recipes. After collecting user preferences on health status, biometrics and goals, these meal plans and recipes can be made to offer the optimal macro-nutrient distribution for each individual user. A theoretical model for diet-related behavior change was developed and key dietary issues were identified, outlining mechanisms for positive impact. These insights informed a mechanistic description of the Lifesum app, providing a foundation for future research on intervention outcomes.Funding Agencies|Linkoping University</p

    Barnsjuksköterskans erfarenhet av att bemöta barn med autismspektrumtillstånd vid genomförande av vårdprocedurer.

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     Bakgrund: Barn med autismspektrumtillstånd (AST) har rätt till individanpassad vård utifrån sina behov, enligt både Barnkonventionen och LSS. Barnsjuksköterskor har ett ansvar att inkludera barnet, ge trygghet och respektera barnets autonomi. Tidig diagnostik och anpassade vårdmiljöer är avgörande för att minska stress och förbättra kommunikationen. Familjesamverkan och ökad kunskap är centrala faktorer för att skapa en trygg och effektiv vårdsituation. Motiv: Barn med AST är en sårbar grupp som ofta upplever oro vid vårdprocedurer, vilket kräver individanpassad vård. Tidigare forskning visar brister i resurser och kunskap hos vårdpersonal.Syfte: Syftet med studien är att undersöka barnsjuksköterskans erfarenhet av att bemöta barn med autismspektrumtillstånd vid genomförande av vårdprocedurer. Metod: Studien har en kvalitativ design med semistrukturerade intervjuer. Åtta barnsjuksköterskor deltog i studien. Datamaterialet analyserades med hjälp av kvalitativ innehållsanalys. Resultat: Huvudfynden mynnade ut i tre kategorier med totalt åtta underkategorier. Kategorin “Att anpassa vårdprocedurer utifrån barnets behov innehöll underkategorierna: “Individanpassade förberedelser som trygghetsskapande strategier”, “Föräldrars roll i att vägleda till trygghet” och “Fysiska vårdmiljön som stöd vid vårdprocedurer.” Kategorin “Att bemästra svåra situationer” innehöll underkategorierna “Barns reaktioner på vårdprocedurer” och “Barnsjuksköterskans känslomässiga påverkan vid vårdprocedur”. Kategorin “Att stärka kunskap och kompetens innehöll underkategorierna “Önskan om mer utbildning i AST”, “Kollegiala erfarenhetsutbyten och handledning” och “Förbättringsområden för tryggare vård av barn med AST”. Konklusion: Individanpassad och strukturerad vård, i kombination med ökad kunskap om barn med AST hos barnsjuksköterskorna är avgörande, för att skapa trygga vårdsituationer för barn med AST och förbättra kvaliteten i vården. Föräldrar har en viktig roll som stöd och vägledare i vårdprocessen. Genom att stärka sjuksköterskans kompetens och implementera anpassade arbetssätt kan vården bli mer inkluderande, förutsägbar och trygg för både barn och personal

    Reports of Concern - Child Health Nurses' Experiences

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    Orosanmälningar - BHV-sjuksköterskors erfarenheter  Bakgrund: Barn definieras i Sverige som individer under 18 år med egna rättigheter. En trygg uppväxtmiljö är avgörande för deras framtida hälsa. Barn som far illa är ett omfattande globalt problem. Trots lagstiftning och ökad medvetenhet utsätts många barn fortfarande för våld i hemmet. Sjuksköterskor har en central roll i att identifiera och anmäla misstanke om att barn far illa, men brister i kunskap, stöd och struktur kan påverka anmälningsbenägenheten negativt.  Motiv: Barnhälsovårdssjuksköterskor har särskilda möjligheter att upptäcka omsorgssvikt genom sin kontinuerliga kontakt med familjer, men möter också stora utmaningar i processen.  Syfte: Att undersöka barnhälsovårdsjuksköterskors erfarenheter av att göra orosanmälningar.  Metod: Studien hade en kvalitativ design med induktiv ansats och baserades på åtta semistrukturerade intervjuer. Analysen utfördes enligt Graneheim &amp; Lundmans innehållsanalys.  Resultat: Studien identifierade fyra kategorier: samverkan med familjen, att agera på sin oro, behov av stöd och samverkan med socialtjänsten. Kommunikation och relation med föräldrar var avgörande, men också utmanande. Osäkerhet vid diffusa tecken, brist på återkoppling från socialtjänsten och känslomässig påfrestning var återkommande teman. Stöd från kollegor, handledning och tydliga riktlinjer upplevdes som avgörande för trygghet i anmälningsprocessen.  Konklusion: Studien visar att barnhälsovårdssjuksköterskor slits mellan att balansera barnets bästa och relationen till föräldrarna. Besluten är känslomässigt tunga och det finns ett stort behov av tydliga riktlinjer, kollegialt stöd och bättre samverkan med socialtjänsten. Slutsatsen är att dessa faktorer är avgörande för att säkerställa ett effektivt skydd för barn Reports of Concern - Child Health Nurses' Experiences  Background: In Sweden, individuals under the age of 18 are defined as children with their own rights. A safe upbringing is crucial for their future health. Children at risk is a widespread global issue. Despite legislation and increased awareness, many children are still exposed to domestic violence. Nurses play a key role in identifying and reporting suspected child maltreatment, but a lack of knowledge, support, and structure may negatively affect their willingness to report.  Motive: Specialist nurses in child health services have unique opportunities to detect neglect through continuous contact with families but face significant challenges in the reporting process.  Aim: The aim of this study was to explore child health nurses' experiences of making reports of concern.  Methods: This qualitative study, using an inductive approach, was based on eight semi-structured interviews. The analysis followed Graneheim &amp; Lundman’s qualitative content analysis.  Result: The study identified four categories: collaboration with families, acting on concern, need for support and collaboration with social services. Communication and relationships with parents were crucial but challenging. Uncertainty related to vague signs, lack of feedback from social services, and emotional strain were frequently upcoming themes. Support from colleagues, guidance, and clear guidelines were considered essential for confidence in the reporting process.  Conclusion: The study shows that child health nurses struggle to balance the best interests of the child with their relationship with the parents. The decisions are emotionally heavy, and there is a great need for clear guidelines, collegial support, and better collaboration with social services. The conclusion is that these factors are crucial to ensuring effective protection for children.

    MATLAB software for recursive identification of Wiener Systems : Revision 3

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    This report is intended as a users manual for a package of MATLAB scripts and functions, developed for recursive identification of discrete time nonlinear Wiener systems and nonlinear static systems. Wiener systems consist of linear dynamics in cascade with a static nonlinearity. The core of the package is an implementation of 9 recursive SISO output error identification algorithms. Three main cases are treated. The first set of 5 algorithms identify the FIR or IIR linear dynamics in cases where the static nonlinearity is known. It is stressed that the nonlinearity is allowed to be non-invertible. The second set of 2 algorithms simultaneously identifies the linear dynamics and the static non-linearity. The nonlinearity is parameterized as a piecewise linear or a piecewise quadratic nonlinear function. The last set of two algorithms exploits the above parameterization of the static nonlinearity for estimation of static nonlinear systems. Colored, additive measurement noise is handled by all algorithms. The software can only be run off-line, i.e. no true real time operation is possible. The algorithms are however implemented so that true on-line operation can be obtained by extraction of the main algorithmic loops. The user must then provide the real time environment. The software package contains scripts and functions that allow the user to either input live measurements or to generate test data by simulation. The functionality for display of results include scripts for plotting of data, parameters and prediction errors. Model validation is supported by several methods apart from the display functionality. First, calculation of the RPEM loss function can be performed, using parameters obtained at the end of an identification run. Pole-zero plots can be used to investigate possible overparameterization in the linear dynamic part of the Wiener model. Finally, the static accuracy as a function of the output signal amplitude can be assessed by mean residual analysis

    Structural Insights Into centSIRT6 : Bioinformatic Analysis of N308K and A313S Substitution Effects

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    Sirtuin 6 (SIRT6), a member of the class III histone deacetylase (HDAC) family, is crucial for the maintenance of general health and is associated with increased life expectancy and resistance to age-related diseases such as cancer and metabolic disorders. A comparative analysis of the SIRT6 gene in Ashkenazi Jewish (AJ) centenarians and noncentenarian controls found a distinct allele, centSIRT6, enriched in the centenarian group. This allele features 2 linked substitutions, N308K and A313S, and exhibits enhanced functions, including more efficient suppression of LINE1 retrotransposons, improved repair of DNA double-strand breaks, and increased efficiency in cancer cell killing. Notably, centSIRT6 shows lower deacetylase activity but higher mono-adenosine diphosphate (ADP) ribosyl transferase activity compared with the wild-type enzyme. This study used several bioinformatics tools to explore the structural changes caused by the N308K and A313S substitutions in centSIRT6 and to elucidate how these alterations contribute to changes in the enzymatic activities of SIRT6. The results indicate that these mutations reduce the structural flexibility of centSIRT6, thus weakening its interactions with acetyl-lysine but strengthening its interactions with ADP-ribose. This research provides useful information for future experimental studies to further investigate the molecular mechanisms of centSIRT6

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