Publikationer från Uppsala Universitet
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Does the benefit of neoadjuvant chemotherapy at six months predict long-term outcomes in colon or rectal cancer? : A meta-analysis of randomised studies
No full textIntroduction The RAPIDO and PRODIGE-23 randomised trials of neoadjuvant versus adjuvant chemotherapy for rectal cancer showed that disease-free survival (DFS) curves diverged early, suggesting that much of the benefit from neoadjuvant chemotherapy occurred within six months. We aimed to determine whether the DFS benefit at six months in trials evaluating neoadjuvant chemotherapy can predict the benefit at 36 months, and to compare the timing of DFS benefit in trials of neoadjuvant versus in those of adjuvant chemotherapy. Material and methods A systematic review identified ten randomised trials comparing neoadjuvant with adjuvant chemotherapy and 37 randomised trials of adjuvant chemotherapy eligible for meta-analysis in rectal or colon cancer. Absolute differences in DFS between experimental and control groups at six and 36 months were extracted from Kaplan–Meier curves. The increment in the DFS benefit between the sixth and 36th months was calculated. Results In neoadjuvant chemotherapy trials, DFS benefit at six months (3.7 %, 95 % confidence interval [CI]: 1.9 to 5.4) did not differ significantly from that at 36 months (4.1 %, 95 % CI: 2.0 to 6.3), and the pooled absolute increment in DFS benefit between the sixth and 36th months was only 0.8 % (95 % CI: −1.6 to 3.2). The DFS benefit emerged earlier in neoadjuvant than in adjuvant chemotherapy trials. Conclusion In randomised trials comparing neoadjuvant with adjuvant chemotherapy, most of the DFS benefit from neoadjuvant chemotherapy manifests itself within the first six months. Therefore, assessing DFS at six months may potentially serve as an early indicator of long-term efficacy
Local US officials' views on the impacts and governance of AI : Evidence from 2022 and 2023 survey waves
No full textThis paper presents a survey of local US policymakers' views on the future impact and regulation of AI. Our survey provides insight into US policymakers' expectations regarding the effects of AI on local communities and the nation, as well as their attitudes towards specific regulatory policies. Conducted in two waves (2022 and 2023), the survey captures attitudinal changes within the six months following the public release of ChatGPT and the subsequent surge in public awareness of AI. Local policymakers express a mix of concern, optimism, and uncertainty about AI's impacts, anticipating significant societal risks such as increased surveillance, misinformation, and political polarization, alongside potential benefits in innovation and infrastructure. Many also report feeling underprepared and inadequately informed to make AI-related decisions. On regulation, a majority of policymakers support government oversight and favor specific policies addressing issues such as data privacy, AI-related unemployment, and AI safety and fairness. Democrats show stronger and more consistent support for regulation than Republicans, but the latter experienced a notable shift towards majority support between 2022 and 2023. Our study contributes to understanding the perspectives of local policymakers-key players in shaping state and federal AI legislation-by capturing evolving attitudes, partisan dynamics, and their implications for policy formation. The findings highlight the need for capacity-building initiatives and bi-partisan coordination to mitigate policy fragmentation and build a cohesive framework for AI governance in the US
Discovery of the pre-main-sequence eclipsing binary MML 48
No full textAims: We present the discovery of the eclipsing binary MML 48, which is a member of Upper Centaurus Lupus, has an associated age of 16 Myr, and is composed of two young, low-mass stars. Methods: We used space- and ground-based observations to characterize the system with both time-series photometry and spectroscopy. Given the extreme mass ratio between the stars, qEB = 0.209 ± 0.014, we modeled a single-lined spectroscopic and eclipsing binary system. Results: The orbital period, 2.0171068 ± 0.0000004 d, is measured from the highest precision light curves. We derive a primary mass of 1.2 ± 0.07 M⊙ using stellar models, and with radial velocities we measured a secondary mass of 0.2509 ± 0.0078 M⊙. The radii are large, as expected for pre-main-sequence stars, and are measured as 1.574 ± 0.026 ± 0.050 R⊙ and 0.587 ± 0.0095 ± 0.050 R⊙, for the primary and secondary stars, respectively. Conclusions: MML 48 joins the short list of known low-mass, pre-main-sequence eclipsing binaries (EBs), being one of only five systems with intermediate ages (15-25 Myr), and the system with the most extreme mass ratio. The primary star is currently at the "fusion bump", undergoing an over-production of energy in the core due to the build-up of 3He before reaching its equilibrium abundance set by the proton-proton (p-p) I chain. MML 48 A is the first young star in an eclipsing system that has been found during its fusion bump. MML 48 is thus an important benchmark for low-mass stellar evolution at a time when the stars are rapidly changing, which allows for a tight constraint on the corresponding isochrone given the uneven mass ratio
An injury-associated lobular microniche is associated with the classical tumor cell phenotype in pancreatic cancer
No full textPancreatic cancer is an aggressive disease with a dense fibrotic stroma and is often accompanied by chronic inflammation. Peritumoral inflammation is typically viewed as a reaction to nearby tumor growth. Here, we report that the inflamed pancreatic lobules are frequently invaded by tumor cells, forming a distinct, non-fibrotic tumor niche. Using a semi-supervised machine learning approach for annotations of clinical samples and multiplex protein profiling, we show that tumor cells at the invasion front are closely associated with acinar cells undergoing damage-induced changes, and with activated fibroblasts expressing markers of injury. The invaded lobules are linked to classical tumor phenotypes, in contrast to fibrotic areas where tumor cells display a more basal profile, highlighting microenvironment-dependent tumor subtype differences. In female mice, lobular invasion similarly aligns with the classical tumor phenotype. Together, our data reveal that pancreatic tumors colonize injured lobules, creating a unique niche that shapes tumor characteristics and contributes to disease biology
Barriers and Opportunities for Reducing Food Waste in Uppsala’s Public Meal Supply Chain
No full textFood waste contributes 8-10% of global greenhouse gas emissions, representing a critical sustainability challenge. Despite Sweden's commitment to achieving UN Sustainable Development Goal 12.3 and national targets for 20% food waste reduction by 2025, existing approaches have not addressed the systemic nature of the problem. This study examines systemic barriers and opportunities for reducing food waste within Uppsala's public meal supply chain from the perspective of stakeholders. Using a qualitative case study approach, semi-structured interviews were conducted with six key stakeholders, including representatives from Uppsala Municipality Meal Services, their meat supplier, and an academic expert specialized in meat losses. Data were analyzed using reflexive thematic analysis by Braun and Clarke, employed an inductive approach. Systems thinking and socio-technical transitions theory were subsequently applied as interpretive lenses to understand the patterns and relationships within the theme. Three primary thematic areas emerged: operational challenges, procurement and regulatory constraints and supplier dynamics. The findings reveal that food waste in Uppsala's public meal system stems from complex systemic barriers embedded within system rather than organizational inefficiencies. Current prevention strategies, while well-intentioned, target shallow leverage points with limited transformative potential. Key barriers include institutional lock-ins that prioritize risk avoidance over resource efficiency, technical-material lock-ins related to information asymmetries and infrastructure design, and regulatory frameworks that create tensions between food safety and waste reduction objectives. However, opportunities exist for transformation through flexible procurement frameworks allowing conditional exceptions for surplus food utilization, improved stakeholder transparency and information sharing. The study concludes that effective food waste reduction requires coordinated interventions addressing multiple system components simultaneously rather than isolated operational improvements. These findings contribute to understanding food waste as a systemic phenomenon in public institutional contexts and provide practical insights for policy development and stakeholder collaboration in sustainable food systems
Too Expensive to Protect Children? – When a Child’s Safety Costs More Than the State Is Willing to Pay : An Analysis of How Legal Aid and Legal Expenses Insurance Affect Parents’ Ability to Safeguard Their Children’s Rights in Custody and Contact Proceedings
No full textI detta examensarbete undersöks föräldrars faktiska möjligheter att tillvarata sina barns rättigheter, med fokus på tillgång till ekonomiskt stöd för juridiskt biträde i ärenden och mål om vårdnad och umgänge. Med rättsdogmatisk metod analyseras förälderns ansvar gentemot barnet, barnets rättigheter samt de förutsättningar som måste vara uppfyllda för att rättsskydd respektive rättshjälp ska kunna utnyttjas. Underlaget för analysen av rättsskyddet utgörs av försäkringsvillkoren i hem- och villaförsäkringar som erbjuds av Sveriges fyra största försäkringsbolag: If Skadeförsäkringar, Folksam, Trygg-Hansa och Länsförsäkringar, medan studiet av rättshjälpen utgår från rättshjälpslagen (1996:1619). Resultaten visar att dessa finansieringssystem uppställer praktiska och i synnerhet ekonomiska hinder som begränsar föräldrars tillgång till rättslig hjälp, vilket i sin tur påverkar deras möjligheter att säkerställa sina barns rättigheter. Hindren drabbar i första hand redan socialt och ekonomiskt utsatta föräldrar, vilka i högre utsträckning än andra återfinns i vårdnadsrelaterade tvister och därmed kan anses ha ett särskilt behov av rättsligt bistånd.This thesis examines parents’ actual ability to safeguard their children’s rights, focusing on access to financial support for legal representation in custody and contact proceedings. Using a legal dogmatic method, the thesis outlines parental responsibilities, the child’s rights, and the conditions that must be fulfilled for legal aid and legal expenses insurance to be utilized. The analysis of legal expenses insurance is based on the policy terms of home and homeowner insurance offered by the four largest insurance providers in Sweden: If Skadeförsäkringar, Folksam, Trygg-Hansa, and Länsförsäkringar, while the examination of legal aid primarily draws on the Legal Aid Act (1996:1619). The findings indicate that the current financing systems impose practical and, in particular, economic barriers that limit parents’ access to legal assistance, which in turn affects their ability to ensure the protection of their children’s rights. These barriers primarily affect parents who are already socially and economically disadvantaged, and who are also overrepresented in custody-related disputes and therefore could be said to have a particular need for legal assistance
A proposed classification of incisional hernias after kidney transplantation
No full textObjectives Incisional hernia (IH) following kidney transplantation is underdiagnosed, with reported incidence rates of 1–7%. This study aimed to evaluate IH prevalence using computed tomography (CT), propose a novel classification system correlated with symptomatology, and evaluate its effect on interobserver IH detection rates. Materials and methods A retrospective review of adults undergoing kidney-alone transplantation (2010–2017) at two Swedish centres was conducted. Patients with previous ipsilateral transplantation or poor-quality CT were excluded. Abdominal CT scans obtained ≥ 30 days postoperatively were reviewed by a multidisciplinary team (radiologist, transplant surgeon, and hernia specialist, all with > 20 years of experience), blinded to clinical data. Four subtypes of IHs after kidney transplantation were identified: 1A (normal contour, incomplete hernia), 1B (normal contour, complete hernia), 2A (abnormal contour, incomplete hernia), and 2B (abnormal contour, complete hernia). Symptomatology was assessed via medical records. Four external radiologists evaluated the classification’s impact on detection rates. Results Of 673 participants, 361 (54%) had evaluable CT scans. IHs were detected in 243 (68%), of which 36% were symptomatic. The proposed classification improved detection rates from 54% to 76% (p = 0.03) after an educational intervention. Symptom prevalence increased with hernia severity: 11% in type 1A, 13% in type 1B, 36% in type 2A, and 86% in type 2B (p < 0.01). Only 55% of symptomatic participants referred for IH mapping were correctly diagnosed prior to study reassessment. Conclusion IHs are prevalent and underdiagnosed after kidney transplantation. The proposed classification improves diagnostic accuracy, correlates with symptomatology, and facilitates clinical management and research
Risk Assessment Models and Event‐Free Survival in Pulmonary Arterial Hypertension
No full textEvidence on the predictive ability of risk assessment models for event-free survival (EFS) in patients with pulmonary arterial hypertension is scarce. We aimed to investigate the relationship between risk status at 6 months after diagnosis (6 M) and EFS, by three risk models: Multicomponent Improvement (MCI), ESC/ERS 4-Strata Risk (4SR), and noninvasive French PH Registry Score (FRS). Data collected in the Swedish PAH Registry 2008–2021 were used. The study population was risk-stratified at 6 M according to each model. Information on PAH-related hospitalization (HOSP) was collected from the National Patient Register. EFS was defined as survival without occurrence of: (1) HOSP; (2) initiation of parenteral prostacyclin therapy or dose increase ≥ 10%; (3) lung transplantation. The association between risk and EFS was evaluated by Kaplan–Meier estimates and Cox proportional models. The analysis included 411 incident patients, median age 66 y [50, 73]. Median survival time was 3.5 y [1.7; 5.4], and cumulative EFS was 55%. In a Cox proportional regression adjusted for age, eGFR, obesity, atrial fibrillation, and systemic hypertension, EFS was higher in patients who: (1) achieved two or three MCI criteria compared to one or no MCI criterion (HR 0.58; CI 0.39–0.84, p = 0.005); (2) were assessed as low, intermediate–low, or intermediate–high compared to high risk (HR 0.16; CI 0.09–0.28, p < 0.001); or (3) fulfilled one, two, or three low-risk FRS criteria, compared to no low-risk criterion (HR 0.29; CI 0.19–0.43, p < 0.001). Performing a risk assessment 6 months after diagnosis effectively predicts the likelihood of EFS in the studied population, highlighting its prognostic value
Polythieno[3,4-b]pyrazine : pathways to metallic charge transport
No full textFor the first time, an alkyl-chain free variant of polythieno[3,4-b]pyrazine (PTP) was created in a conductive state via oxidative chemical vapour deposition (oCVD). The charge transport properties of this new PTP are superior to those of the state-of-the-art ones by ten-fold with a conductivity of 0.5 S cm(-1) and the material is found in the metallic regime of the metal-insulator-transition as the conductivity is vastly independent on temperature. Herein, we investigate the chemical and physical composition of the material in order to explain this improvement and discuss the results in light of the polythiophenes produced using the same method. Using GIWAXS, we discover large crystalline features combined with smaller, highly organized assemblies and gain insight into the chain length. The chemical composition of the material is determined via XPS and FTIR and further supplemented by computational methods. We employ DFT calculations (omega B97X-V/def2-QZVP) to understand the differences between unsubstituted and alkylated PTP. The former shows stronger proclivity to form planar structures, and the conjugation is broken upon distortion. Alternatively, in the latter case, such disorder does not considerably affect the conjugation. Furthermore, we simulate the effects of doping based on XPS results and reveal the possibility of protonation, despite the low pK(a) of the materials. Furthermore, this protonation allows the materials to achieve a cis conformer despite the typical expectation suggesting the prevalence of the trans form. Molecular dynamics simulations (NPT MD) of 24 dodecamers confirm the prevalence of a trans conformer. However, at multiple occasions, trimers of the cis motif form. The simulations predict stronger charge transport in the trans conformer. However, the cis isomer exhibits relevant levels and an extremely low HOMO-LUMO difference (<0.1 eV). This indicates the possibility of high conductivities and explains the hallmarks of metallic charge transport we observe experimentally
Hjälper det att hjälpa? : En kvantitativ analys av prosocialt beteende och psykiskt välbefinnande bland unga
No full textSyftet med denna studie var att kvantitativt undersöka sambandet mellan prosocialt beteende och psykiskt välbefinnande hos ungdomar samt att utreda om detta samband modereras av kön och förändrats i samband med Covid-19-pandemin. Studien bygger på data från Uppsala läns omfattande enkätundersökning ”Liv och hälsa ung”, där data från insamlingsår 2023 varit i fokus men kompletterats med data från 2019 och 2021, vilket totalt omfattar cirka 23000 observationer. Efter bortfall kvarstod 17480 observationer. Genom en kombination av korrelationsanalys och linjära regressionsmodeller, med kontrollvariabler såsom kön och årskurs, undersöktes om en högre grad av prosocialt beteende är kopplat till ett bättre psykiskt välbefinnande. Resultaten visar att det finns ett signifikant positivt samband mellan prosocialitet och psykiskt välbefinnande, vilket innebär att ungdomar som rapporterar högre nivåer av hjälpfulla handlingar också tenderar att uppleva bättre psykiskt välbefinnande. Vid kontroll för kön och årskurs stärktes effekten av prosocialt beteende, medan deskriptiva skillnader visade att flickor i genomsnitt skattar sig själva med lägre psykiskt välbefinnande än pojkar; dock visade ingen interaktionsanalys att könstillhörighet påverkar relationens styrka. Ytterligare analyser över tid indikerar att sambandet mellan prosocialt beteende och psykiskt välbefinnande är ihållande positivt, men att effekten försvagats i övergången mellan perioden under och efter Covid-19-pandemin