Publikationer från Uppsala Universitet
Not a member yet
127603 research outputs found
Sort by
Tumoral pSMAD2 as a prognostic biomarker in early-stage breast cancer : insights from the randomized SweBCG91RT trial
No full textBackground/Aim: The TGF-beta pathway can influence breast cancer progression and therapy efficacy, exhibiting both pro- and anti-tumoral effects. This study examined the impact of active TGF-beta signaling on recurrence and radiotherapy (RT) benefit in early-stage breast cancer, using nuclear phosphorylated Smad2 (pSMAD2) as a marker for pathway activation. Methods: Tissue-microarrays from 1178 stage I-IIA breast cancer patients in the SweBCG91RT trial (randomized to breast-conserving surgery with or without RT) were analyzed. pSMAD2 immunohistochemistry was scored as the mean percentage of tumor cells with nuclear staining. Recurrence risk and RT benefit were evaluated. Results: pSMAD2 scores were heavily skewed, with 45% of tumors demonstrating high staining (>= 80% tumor cells), 38% medium (21-79%), and 17% low (<= 20%). Low pSMAD2 tumors were associated with higher grade and larger size but not with subtype. Medium pSMAD2 tumors had a significantly increased ipsilateral breast tumor recurrence risk than high pSMAD2 tumors (HRadjusted = 1.82, p = 0.002), while no differences were observed for low pSMAD2 tumors. A similar result was obtained with all recurrences as endpoint. RT benefit was consistent across all pSMAD2 groups. In Luminal tumors, higher tumoral pSMAD2 levels were inversely correlated with tumor-infiltrating lymphocytes (TILs). Conclusion: Medium pSMAD2 levels were linked to an increased recurrence risk compared to high levels, suggesting a tumor-suppressive role of TGF-beta in early breast tumorigenesis. However, no significant differences were noted for low pSMAD2 levels. In Luminal tumors, TGF-beta signaling was negatively associated with TILs. These findings indicate that therapeutic targeting of TGF-beta warrants careful consideration of tumor stage and subtype.Axel Stenmark Tullberg, Viktoria Thurfjell, Per Karlsson and Carina Strell have contributed equally as first or last authors respectively.</p
Towards equitable partnerships in global health research : experiences from Ethiopia, Uganda, Lao PDR and Vietnam
No full textEquitable partnerships in global health research can counteract power imbalances in this field. Theoretical perspectives have been provided on equitable global health partnerships, but there are few reports from researchers actively engaged in such partnerships. This article departs from the experiences of four long-term global health research partnerships, two in Africa and two in Asia. It describes the challenges in enhancing an equitable research partnership and how these were addressed. The examples illustrate that funders can play a pivotal role in counteracting power imbalances by assigning leadership roles and directing primary funding to institutions where the research occurs. Such a transition requires adaptations and a new mindset on both sides. Embedded research capacity enhancement, part of all four partnership examples, is essential in correcting power imbalances. Capacity enhancement should preferably include enhancing the broader research ecosystem within the partner university, across academic institutions in the country or beyond. The development of mutual trust and respect takes time and requires long-term engagement, transparency in budgeting, project planning and all steps of the research process. Reciprocity in learning is important for all partners. It may include twinning of research students, joint degrees and efforts to bring research findings into policy and practice in all partner contexts. The partnership examples illustrate the achievements and challenges in bringing new research evidence into policy and practice, where early involvement and continuous buy-in by policymakers are crucial
Characterization of the solar wind context during the third Mercury flyby of BepiColombo
No full textContext: The interaction of the solar wind (SW) with the coupled magnetosphere-exosphere-surface of Mercury is complex. Charged particles released by the SW can precipitate along planetary magnetic field lines on specific areas of the surface of the planet. The processes responsible for the particle precipitation strongly depend on the orientation of the interplanetary magnetic field (IMF) upstream of Mercury. Aims: During the third Mercury flyby (MFB3) by BepiColombo, the properties of the SW inferred from BepiColombo observations of a highly compressed magnetosphere corresponded to those of a very dense plasma embedded in a slow SW. The Mercury Electron Analyzer (MEA) measured continuous high-energy electron fluxes in the nightside dawn sector of the compressed magnetosphere. In order to constrain further studies related to the origin of these populations, we aim to firmly confirm the initial inferences and detail the SW properties throughout MFB3. Methods: We took advantage of a close radial alignment between Parker Solar Probe (PSP) and Mercury. We monitored the activity of the Sun using SOHO coronagraphs and we used a potential field source surface model to estimate the location of the magnetic footpoints of PSP and BepiColombo on the photosphere of the Sun. We propagated the plasma parameters and the IMF measured by PSP at BepiColombo, to check if the plasma impacted Mercury. Results: We show that during MFB3, PSP and BepiColombo connected magnetically to the same region at the solar surface. The slow SW perturbation first measured at PSP propagated to Mercury and BepiColombo, as was confirmed by similarly elevated plasma densities measured at PSP and BepiColombo. The IMF orientation stayed southward during the whole MFB3. Conclusions: Our results provide strong constraints for future studies of the magnetospheric structure and dynamics during MFB3, including tail reconnection, electron and ion energization, and subsequent plasma precipitation onto the surface of Mercury
Observation of the decay Ψ\u88(3686) → Σ0Σ<over-bar>0ω
No full textUsing a dataset of (27.12 ± 0.14) x 108 ψ(3686) events collected by the BESIII detector operating at the BEPCII collider, we report the first observation of the decay ψ(3686) → Σ0Σ<over bar>0ω. with a statistical significance of 8.9σ. The measured branching fraction is (1.24 ± 0.16stat ± 0.11sys) x 10-5, where the first uncertainty is statistical and the second is systematic. Additionally, we investigate potential intermediate states in the invariant mass distributions of Σ0ω, Σ<over bar>0ω. and Σ0Σ<over bar>0ω. A hint of a resonance is observed in the invariant mass distribution of MΣ0(Σ<over bar>0)ω, located around 2.06 GeV/c2, with a significance of 2.5σ.For complete list of authors see http://dx.doi.org/10.1103/PhysRevD.111.092007</p
Engagement and attrition in digital mental health : current challenges and potential solutions
No full textIn digital mental health engagement rates are consistently low, which may limit its effects. Using an international multidisciplinary consensus method, including lived experience expertise and a systematic review, we identified three key challenges: (i) lack of agreed metrics for engagement; (ii) lack of evidence on how better engagement improves outcomes; (iii) lack of standards for user involvement. Three potential solutions encompassed: (i) standardisation of frameworks for reporting engagement metrics and optimal doses of digital tools, (ii) measuring engagement with more precise reporting of outcomes, including potential harms; (iii) defining standards of user involvement (including appropriate diversity, and clinician as well as user input). Digital interventions have real potential in meeting the shortfall in service provision for mental health, but this will require focus on high quality research studies of the underlying mechanisms of engagement and optimal outcomes. Our findings identify and highlight the next best steps in this process
Statistical Analysis of the Warm Plasma Cloak in the Dayside Magnetosphere : 9 Years of MMS Observations
No full textThe warm plasma cloak (WPC) is a plasma population located in the outer magnetosphere. It is composed primarily of electrons and H+ ions with energies of tens to hundreds electronvolts and can contain significant amounts of O+. We conduct a statistical survey of the WPC using 9 years of observations in the dayside magnetosphere from the Magnetospheric Multiscale mission. WPC is found in 51% of the observations and it is 1.6 times more abundant in the dawn than in the dusk sector. O+-rich WPC is detected in 7.5% of the observations, being 3 times more probable in the dawn sector. We find that after a peak of strong geomagnetic activity, it takes approximately 9 hr to detect the WPC in the dayside magnetosphere
AI-supported versus manual microscopy of Kato-Katz smears for diagnosis of soil-transmitted helminth infections in a primary healthcare setting
No full textSoil-transmitted helminths primarily comprise Ascaris lumbricoides, Trichuris trichiura, and hookworms, infecting more than 600 million people globally, particularly in underserved communities. Manual microscopy of Kato-Katz thick smears is a widely used diagnostic method in monitoring and control programs, but is time-consuming, requires on-site experts and has low sensitivity, especially for light intensity infections. In this study, portable whole-slide scanners and deep learning-based artificial intelligence (AI) were deployed in a primary healthcare setting in Kenya. Stool samples (n = 965) were collected from school children and Kato-Katz thick smears were digitized for AI-based detection. Light-intensity infections accounted for 96.7% of cases. Three diagnostic methods - manual microscopy, autonomous AI and human expert-verified AI - were compared to a composite reference standard, which combined expert-verified helminth eggs in physical and digital smears. Sensitivity for A. lumbricoides, T. trichiura and hookworms was 50.0%, 31.2%, and 77.8% for manual microscopy; 50.0%, 84.4%, and 87.4% for the autonomous AI; and 100%, 93.8%, and 92.2% for expert-verified AI in smears suitable for analysis (n = 704). Specificity exceeded 97% across all methods. The expert-verified AI had higher sensitivity than the other methods while maintaining high specificity for the detection of soil-transmitted helminths in Kato-Katz thick smears, especially in light-intensity infections
Implementing the Green Energy Transition in a UNESCO World Heritage City : A Case Study of Visby, Sweden
No full textOver 300 cities are inscribed on the World Heritage List. While each site has its unique challenges and opportunities, in each of them a balance must be achieved in protecting heritage values and meeting demands of modern life, including the demand for energy efficiency and the reduction of greenhouse gas emissions. This article uses Visby (Sweden) as a case study to examine how conservation laws implementing the World Heritage Convention in light of international commitments to mitigate climate change can influence the balance between cultural heritage preservation and energy measures in historic sites. International laws must be implemented by states. But these national laws must be applied locally, in each heritage site. It is therefore important to examine how regional and local decision makers, including individual property owners, navigate and understand their obligations stemming from international laws in order to understand the impact and challenges in meeting sustainability goals in heritage sites. We find that while Visby’s World Heritage status promotes a high level of cultural heritage protection, restrictive laws alone fall short in achieving sustainability. Supportive factors such as funding, planning tools, knowledge support and dissemination, and community engagement help bridge these gaps. We recommend further support for financial incentives, place-based technological solutions, and collaboration amongst experts and others to help officials and property owners make choices that are sustainable from both energy and heritage perspectives
The Mediating Role of Psychological Flexibility and Inflexibility Between Impulsivity and Opioid Misuse in People With Chronic Noncancer Pain
No full textBackground: The prescription of opioid medication is a frequent therapeutic approach in chronic noncancer pain, as is misuse of prescribed opioids. There is previous evidence for associations between personal variables such as impulsivity and opioid misuse. Psychological flexibility and inflexibility have also been associated with pain-related outcomes and opioid misuse. The aim of this cross-sectional study was to examine the combined role of a dispositional variable (impulsivity) along with psychological factors (Psychological Flexibility and Inflexibility) in pain outcomes and opioid misuse. Methods: The sample comprised 155 people with chronic noncancer pain. A hypothetical model was tested using correlation and structural equation modelling analyses. Results: The results show significant associations between impulsivity and Psychological Flexibility, Psychological Inflexibility and opioid misuse. Psychological Flexibility and Inflexibility were related to pain intensity, interference and opioid misuse. Structural equation modelling showed significant associations between impulsivity, Psychological Inflexibility and pain interference, and opioid misuse. Associations between Psychological Flexibility and pain interference and opioid misuse were nonsignificant. These results support the hypothesis that impulsivity and Psychological Inflexibility are factors that contribute to pain interference and opioid misuse, but do not support the hypothesis that Psychological Flexibility reduces opioid misuse. Conclusions: It is recommended to assess these psychological aspects prior to the prescription of opioid medication, and, if necessary, offering Acceptance and Commitment and Mindfulness Based Therapies could be desirable. Significance: The results of this study provide further evidence of the role of trait impulsivity as a transdiagnostic antecedent variable in opioid misuse, both by a direct association and through psychological inflexibility. It can be drawn from these results that psychological transdiagnostic variables, rather than pain outcomes alone, would be key factors influencing opioid misuse. These findings underscore the need for comprehensive psychological assessments prior to the prescription of opioids
Optimising the Next-Generation Borrow Checker for Rust
No full textRust is a modern systems programming language that has been praised for its remarkable safety and speed. It stands out by using rules of borrowing and ownership to ensure memory safety at compile time, avoiding the need for a garbage collector. Polonius is a more flexible version of the Rust compiler’s borrow checker, designed to apply these rules with greater precision. However, Polonius has been blocked from adoption into stable Rust for nearly seven years due to significant performance issues. In this thesis, we explore how to optimise Polonius using a graded approach to borrow checking, where the complex, location-sensitive analysis is invoked lazily and only when needed. Our implementation yields promising results: compilation speed improves by 0.15--0.5\,\% on average. However, some outliers exhibit regressions in compilation time and memory usage. Certain design issues related to the complex location-sensitive analysis also remain unresolved. Nevertheless, our work brings Polonius much closer to adoption and paves the way for a more flexible and precise borrow checker for Rust