Publikationer från Uppsala Universitet
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Comparing Supervised And Unsupervised Methods For Operationalizing Resilience Using Brain Age Gap
No full textBrain maintenance and cognitive reserve describe complementary resilience mechanisms supporting preserved cognition in aging. This study evaluates the Brain Age Gap (BAG) as a biomarker for these resilience mechanisms by comparing supervised and unsupervised grouping methods in 429 individuals with MRI (Magnetic Resonance Imaging), cortical thickness, and Mini-Mental State Examination (MMSE) data at ages 70 and 75. Supervised "theory-based" groups, defined from BAG and MMSE, are analyzed with Linear Mixed Effects models to assess trajectories of BAG and cortical thickness. Unsupervised "data-driven" groups are derived from K-means and Gaussian Mixture Model clustering applied to paired observations of the resilience variables BAG, MMSE, and cortical thickness. Theory-based analysis captures brain maintenance and cognitive reserve but not a distinct non-resilient group. Clustering partly aligns with these constructs but mainly reflects the cohort’s overall homogeneity. Results support the potential of BAG as a resilience biomarker, whilst highlighting the need for further refinement of the theory-based approach
Cryo-EM exposes diverse polymorphism in IAPP mutants to guide the rational design of peptide-based therapeutics
No full textIn the pursuit of potential therapeutic agents for type 2 diabetes, non-amyloidogenic forms of the human Islet Amyloid Polypeptide (hIAPP) containing site-specific mutations are of significant interest. In the present study, we dissect the three proline mutations present in the core region of the non-amyloidogenic rat IAPP into single-point mutations at A25P, S28P, and S29P sites. We apply high-resolution cryo-electron microscopy and solve the structures of 6 polymorphs formed by these mutants, revealing the peptide's self-assembly patterns and identifying critical interactions that reinforce these structures in the presence of the b-sheet breaker. A unique trimeric aggregate with C3 symmetry was identified in the A25P mutant, which we resolved with a 3.05 A resolution, while asymmetric trimeric assemblies were observed in the other mutants. Guided by the high-resolution structural models of A25P and S28P fibrils obtained in our study, we successfully designed novel non-amyloidogenic mutants of IAPP with potential therapeutic value. Our findings demonstrate the immense potential of structure-based approaches in developing effective therapeutics against amyloid diseases.
Enduring modulation of dorsal raphe nuclei regulates (R,S)-ketamine-mediated resilient stress-coping behavior
No full textKetamine may be a novel pharmacologic approach to enhance resilience and protect against stress-related disorders, but the molecular targets underlying this response remain to be fully characterized. The multifunctional protein p11 is crucial in the pathophysiology of depression and antidepressant responses. However, it is still unclear whether p11 plays a role in the pro-resilience effects induced by ketamine. Here, we demonstrated that prophylactic administration of ketamine buffers passive stress-induced maladaptive phenotypes induced by chronic stress exposure. Spatial neurotransmitter and metabolite analysis revealed that prophylactic ketamine was also effective in blunting stress-induced disturbances of tryptophan metabolism in dorsal raphe nuclei (DRN). Additionally, we demonstrated that ketamine prevented chronic restraint stress-induced p11 reduction in DRN, a highly p11-enriched region. Furthermore, we provide novel evidence indicating that p11 deficiency regulates susceptibility to stress-induced depression-related phenotypes, and these behavioral maladaptations are dependent, at least in part, on p11 function in serotonergic neurons. Spatial neurotransmitter and metabolite analysis also showed a reduction of tryptophan and dopamine metabolism in DRN of serotonergic p11-deficient mice. Viral-mediated downregulation of p11 within DRN induced a stress-susceptible phenotype. Finally, our results also unveiled that the ability of ketamine to elicit a pro-resilience response against stress-induced maladaptive phenotypes was occluded when p11 was selectively deleted in serotonergic neurons. Altogether, we showed a previously unexplored role of the DRN circuit in regulating stress susceptibility and resilience-enhancing actions of ketamine
Designing for Military Machine Learning: : A Echeloned Design Science Study on Developing an Automated Mission Summarisation System
No full textThis thesis explores the integration of automatic speech recognition (ASR) and large language models (LLMs) in the context of military communication, specifically focusing on the Swedish Armed Forces’ call-for-fire (CFF) procedures. The aim is to assess whether AI-based systems can support the transcription and structuring of spoken C2 (command and control) messages in operational environments. Using OpenAI’s Whisper model for ASR and a lightweight LLM for parsing, a prototype was developed to transcribe radio-style voice commands and generate structured, machine-readable reports. The system was evaluated using a domain-specific dataset, including native and non-native English commands recorded under noisy conditions, and refined through iterative feedback from defense stakeholders. Results show that while Whisper performs well out of the box, challenges remain in handling accented speech, numeric precision, and specialized jargon. The study applies a echeloned Design Science Research (eDSR) methodology and contributes both a functional prototype and a set of socio-technical design principles for AI integration in defense contexts. The findings demonstrate the feasibility of ASR-LLM pipelines in high-stakes domains and highlight considerations for future deployment in mission-critical military systems
The effects of recycling pharmaceutical formulations in laser powder bed fusion 3D printing - the influence of physical phenomena on printing performance
No full textLaser powder bed fusion is an attractive technology for 3D printing objects in a powder bed and has been explored for printing pharmaceutical dosage forms, such as tablets. Recycling of non-sintered residual powder is not well understood, but is critical to prevent economic losses and improve the sustainability of this technique. We investigated the recyclability of three pharmaceutical formulations in the context of laser powder bed fusion of tablets. Three formulations consisting of common pharmaceutical polymers and the model drug indomethacin have been investigated up to ten print cycles. For each print cycle, powder and tablet samples were collected and analyzed for ageing phenomena. Results showed that polyvinyl alcohol and methacrylic acid-ethyl acrylate copolymer-based formulations were recyclable without changes in critical quality attributes of printed dosage forms for 5 and 9 cycles, respectively. A copovidone-based formulation showed a gradual increase in particle size over 10 cycles, resulting in a gradual decrease in tablet weight. This formulation was considered non-recyclable under the conditions evaluated in this work. The observed ageing phenomena were mainly related to changes in particle size, powder cohesion, and glass transition temperature. It is shown that considering powder ageing during formulation development is critical for optimal print performance and further development of laser powder bed fusion for pharmaceutical applications
Variation in emergency department visits among residents of Swedish nursing homes between 2019 and 2020 : a population-based cohort study
No full textBackground Nursing homes have limited capacity to provide medical care to clinically frail residents and therefore rely on transferring residents to hospital-based emergency departments when acute medical needs arise. The utilization of emergency department care varies between nursing homes but the extent of this variation is unexplored. Further, the effect of organizational characteristics of nursing homes on emergency department utilization is unknown. This study aims to characterize the variation in emergency department visit rates between nursing homes, and to identify contextual and organizational characteristics that contribute to this variation. Study design Population-based cohort study of individuals living in nursing homes during 2019 and 2020 in Sweden. Methods National registry data on nursing home residents were linked to nursing homes based on civil- and business registration addresses. Emergency department visits were identified for each resident in the national patient registry and measured as incidence rates per nursing home. Multi-level analysis was performed to investigate the association between emergency department visit rates, and contextual and organizational characteristics of nursing homes. Results The median incidence rate of emergency department visits from nursing homes was 5.2 per 100 person-months in 2019 (IQR = 3.7–6.9) and 4.4 per 100 person-months in 2020 (IQR = 3.0–5.7). Individuals living in nursing homes in the most rural locations had lower odds of emergency department visits (OR 0.51, 95% CI 0.41–0.61 versus the most urban locations). Moreover, individuals in nursing homes specialized in dementia care had lower odds of emergency department visits (OR 0.90, 95% CI 0.87–0.94 versus somatic care). Conclusion The results suggest that the location and organizational characteristics of nursing homes may have an impact on the utilization of medical services by the nursing home resident population. Further research is warranted to investigate any ensuing health inequities
Att bemöta desinformation : En kvalitativ studie om kommunernas och Socialtjänstens förebyggande arbete efter desinformationen och LVU kampanjerna
No full textUnder 2021 startades en LVU-kampanj i samband med en misstro mot svenska myndigheter. LVU-kampanjen började i en Facebookgrupp där medborgare delade med sig av sina erfarenheter kring Socialtjänstens bemötande och hantering av ärenden. Framdeles uppstod det ett missnöje som synliggjorde bristande tillit och förtroende mellan medborgarna och Socialtjänsten (Socionomen publicerad 28 april 2023). Då följde fler och fler skildringar av sina erfarenheter. Oro och rädsla för myndigheter som exempelvis mot Socialtjänsten ökade bland medborgarna i Facebookgruppen (Socialstyrelsen 2024, s 15). Detta visade på en stor besvikelse och missnöje hos en liten del av samhällets medborgare och kritiken riktades därför mot Socialtjänsten för sitt agerande gällande omhändertaganden av barn och unga enligt tvångsvårdslagstiftningen LVU, Lag (1990:52) med särskilda bestämmelser om vård av unga (SVT 6 mars 2024). Syftet med denna studie har varit att undersöka hur Socialtjänsten i svenska kommuners arbetssätt har påverkats i samband med LVU-kampanjen. Hur det förebyggande arbetet visats i praktiken. Denna kvalitativa studie utfördes genom en enkät med tre frågor som mejlades ut till 290 kommuner. Uppsatsen har utgått från kritisk praktikteori och Rothstein’s teori om social tillit, legitimitet, input och output. Studiens tre frågeställningar har besvarats genom enkätfrågor. Metoden som använts är innehållsanalys och abduktiv ansats i analysen av insamlade materialet för att kunna identifiera olika mönster och teorier. Studien visade att fler kommuner arbetat förebyggande efter LVU kampanjen genom bland annat dialoger, skapande av olika projekt, anställt medarbetare för olika uppdrag och förnyat informationsmaterial. Slutsatsen av studien är att det förebyggande arbetet sker på olika sätt och till olika målgrupper. Flera kommuner har uttryckt att det påverkats av LVU-kampanjen och börjat tänka om i organisationen och andra kommuner har uttryckt att de inte påverkats alls. In 2021, an LVU campaign was launched in connection with a distrust of Swedish authorities. The LVU campaign began in a Facebook group where citizens shared their experiences with the Social Services' response and handling of cases. From then on, there was dissatisfaction that highlighted a lack of april confidence between citizens and the Social Services (Socionomen published april 28, 2023). This was followed by more and more descriptions of their experiences. Concern and fear of authorities, such as the Social Services, increased among citizens in the Facebook group (National Board of Health and Welfare 2024, p. 15). This showed great disappointment and dissatisfaction among a small part of society's citizens and criticism was therefore directed at the Social Services for their actions regarding the care of children and young people, according to the compulsory care legislation LVU, Act (1990:52) with special provisions on the care of young people (SVT March 6, 2024). The purpose of this study was to investigate how the Social Services in Swedish municipalities have been affected in connection with the LVU campaign. How the preventive work has been demonstrated in practice. This qualitative study was carried out through a survey with three questions that were emailed to 290 municipalities. The paper is based on critical practice theory and Rothstein's theory of social trust, legitimacy, input and output. The study's three questions have been answered through survey questions. The method used is content analysis and an abductive approach in the analysis of the collected material in order to identify different patterns and theories. The study showed that more municipalities have worked preventively after the LVU campaign through, among other things, dialogues, the creation of different projects, hiring employees for different assignments and renewed information material. The conclusion of the study is that the preventive work is carried out in different ways and for different target groups. Several municipalities have expressed that they have been affected by the LVU campaign and have started to rethink their organization, and other municipalities have expressed that they have not been affected at all
Future climate impact of all-solid-state batteries
No full textAll-solid-state batteries (ASSBs) are considered a next-generation technology with the potential to enhance the safety and extend driving range in electric vehicles. This study assesses the climate impact of two ASSB chemistries in 2025, 2030, 2040, and 2050, using a prospective life cycle assessment. The study accounts for changes in energy-intensive processes, secondary material use, and advances in battery design. A battery dimensioning model is developed to quantify material demand and the corresponding specific energies. The findings indicate that ASSB NMC811 with LLZO electrolyte likely has a higher climate impact than LIBs, while ASSB LFP with a polymer electrolyte has the potential to be achieve impacts comparable to LIB LFP. Minimizing non-cathode materials significantly lowers the climate impact of ASSBs, making them comparable to LIBs. Key contributors to the climate impact of both ASSBs are the electrolyte and cathode active materials, with the anode and current collector also important in polymer-based ASSBs. The analysis also shows the availability of lanthanum may pose constraint on scaling LLZO based ASSBs
Unraveling the Crop Yield response under shading conditions through the deployment of a drought index : A meta-analysis
No full textExtensive meta-analyses have examined the effects of shading on vegetation growth and Crop Yields (CY) in Agrivoltaic (AV) systems. These studies have demonstrated a strong relationship between shading and crop performance. Certain varieties, such as Berries and Leafy Vegetables, thrive under shaded conditions, while Forage Crops remain largely unaffected. Conversely, other crops, including C3 Cereals, Grain Legumes, Fruits, and Root Crops, experience reduced yields when exposed to shade. Previous meta-analyses often neglected environmental factors such as temperature, evapotranspiration, and precipitation when evaluating the effects of shading on CY, making it difficult to fully understand how shading influences crop performance. This study seeks to address this research gap by integrating a drought index, the Standardized Precipitation Evapotranspiration Index (SPEI), for an improved meta-analysis on shading and CY across various crops. SPEI, encompassing information on potential evapotranspiration and precipitation is an effective indicator of moisture availability and accessible worldwide at a reasonable temporal and spatial resolution. Multiple Linear Regression (MLR) techniques are used to analyze various crop categories. From a policy perspective, the MLR models developed in this study can help policymakers make more accurate assessments of the impact of AV systems deployment on CY at both national and regional levels. The results of the MLR models, both with and without the inclusion of the SPEI, were compared to evaluate the impact of shading on determining CY under different environmental conditions. Incorporating SPEI into the MLR models improved performance metrics across all crop categories with adequate sample sizes. The least improvement was observed for Fruits, with a marginal 0.01 gain in coeffiecient of determination (R2), while the most substantial improvement was seen in Berries, with a 0.32 increase. The analysis was reinforced by uncertainty quantification, which demonstrated that the predictability of CY improves when SPEI was included, as supported by a 95 % confidence level. In all crop categories, the MLR model exhibited increased certainty when SPEI was considered, compared to using shading alone as a determinant for CY in the uncertainty analysis. A minor improvement of 13 % was observed in Forage Crops, while a significant increase of 47 % was noted in Root Crops