Publikationer från Uppsala Universitet
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Burials and grave goods in early Christian Sweden
No full textVikingatida gravar är kända för sina gravgåvor. Allt från enstaka mynt och verktyg i de flestagravarna till de stora skattkamrarna i Uppsalas gravhögar. Gravgåvorna försvinner däremotnär kristendomen anländer i norden. I den svenska medeltidens kyrkogårdar finns det intelängre några skatter och verktyg i jorden utan allt som hittas är skelett och rester från träkistor.Gravskick är dock ingenting som ändras på kort tid utan det finns alltid en övergångsperioddär den gamla traditionen lämnar plats till den nya seden. Denna uppsats undersöker vissa avde gravgåvor som hittats i gravar från denna övergångsperiod genom tolkning av tidigarepublicerad forskning i ämnet och en jämförelse av några av de artefakter som hittats för att fåen uppfattning om hur lång tid det tog för gravgåvorna att försvinna från gravskicket.During the Viking Age of Scandinavia, the people would bury their dead together with a suiteof gifts for use in the afterlife. This practice would later cease after the people of Scandinaviaconverted to Christianity. Though there is no consensus of exactly when this practice stoppedas there is some disagreement as to if some of the artefacts that have been found in earlyChristian graves can be considered as grave goods. This paper will take a look at some of theprior research that has been done on the topic of early Christian graves in order to try toanswer whether the tradition ended as soon as the people adopted the new religion or if itlived for at least a while longer. A comparison of the artefacts from different graves will bedone to see if the kind of objects changed together with the religion
Non-Uniform Sampling for Quantitative NOESY
No full textNon-uniform sampling (NUS) enables faster acquisition of NMR spectra. Concerns about spectral fidelity, particularly in high-dynamic-range experiments like NOESY, have limited its quantitative applications. In this study, we assessed whether optimised Poisson-gap sampling schemes can generate high-fidelity spectra suitable for quantitation and evaluated the effectiveness of NUS ranking tools, NUSscore and nus-tool, in identifying optimal sampling schemes. A total of 25,000 Poisson-gap sampling schemes were generated and ranked using NUSscore, with a subset of 11 of these spanning the score distribution, alongside 15 random-shuffle and the highest and lowest scoring Poisson-gap schemes determined using the signal apex-to-artefact ratio were used for comparison, all with 50% sampling coverage. Additionally, hybrid sampling schemes incorporating a long initial uniformly sampled section, termed US-NUS hybrid schemes, were evaluated. Spectral fidelity was evaluated on interproton distance accuracy, including the proportion of retained interproton distances and their deviation from uniformly sampled reference spectra. NUSscore showed a strong correlation with spectral fidelity. The peak-to-sidelobe ratio implemented in nus-tool showed no correlation, with the relative sensitivity metric showing a weak correlation. Signal-to-artefact apex ratio was also not predictive for identifying sampling schedules with maintained interproton distances. All Poisson-gap sampling schemes however outperformed random-shuffle. The US-NUS hybrids demonstrated improved interproton distance conservation than traditional Poisson-gap sampling schemes with a low seed dependence, making them a promising sampling schedule for quantitative NOESY analysis
Dual targeting of G9a and DNMTs induces antitumor effects in multiple myeloma
No full textMultiple myeloma (MM) is a hematological disease of the plasma cell that remains clinically challenging despite the development of novel therapies. Epigenetic alterations have been demonstrated to contribute to MM pathogenesis, yet comprehensive studies into the links between different epigenetic regulatory systems in myeloma progression and drug resistance, though clinically relevant, are largely lacking. G9a and the DNA methyltransferases (DNMTs) are epigenetic modifiers that exhibit increased activity in MM, correlating with poor prognosis. To investigate the partnership between G9a and DNMTs, we used a combinatorial treatment approach involving small-molecule inhibitors. In-depth molecular analysis of the histone H3 lysine dimethylation distribution, the DNA methylome and the transcriptome of MM revealed a silencing mechanism involving G9a and DNMTs that represses key tumor suppressor genes. Moreover, dual inhibition of G9a and DNMTs reduced cell viability in primary MM cells and induced apoptosis in MM cell lines. This was accompanied by increased expression of apoptosis-related genes and decreased protein levels of the MM-associated oncoproteins IRF4, XBP1, and MYC. To assess the translational relevance of our in vitro findings, we evaluated the combination therapy in an in vivo preclinical xenograft MM model. Specifically, we demonstrate that the G9a inhibitor A366 synergizes with the DNMTs inhibitor decitabine to promote a robust tumor regression in vivo. Together, these data provide new insights into the cooperative role of G9a and the DNMTs in regulating gene silencing in MM, and support dual epigenetic inhibition as a promising therapeutic strategy.De två första författarna delar förstaförfattarskapet</p
Integrated Physiologically-based Pharmacokinetic Model with a Quantitative Systems Pharmacology and Toxicology Model for Statins in Disease Population. Part 2 : MIDD and MIPD Applications
No full textThe conventional strategy of prescribing the same dosage to all patients can result in suboptimal efficacy and safety. This is particularly true when considering drug-gene interactions (DGIs), drug-drug interactions (DDIs), or in individuals with compromised organ function. Precision medicine, which aims to tailor drug regimens based on individual patient characteristics, offers a promising alternative by focusing on drug disposition, efficacy, and safety. However, clinical trials face ethical and practical challenges and cannot cover all real-world patient scenarios. Thus, physiological based pharmacokinetic (PBPK) modeling offers a unique framework for enhancing model-informed drug development (MIDD) and precision dosing (MIPD). Despite this, most PBPK applications primarily assess drug pharmacokinetics without evaluating efficacy or safety outcomes. This limits the full potential of mechanistic models. In this study we used integrated PBPK, Quantitative Systems Pharmacology (QSP), and toxicology models to predict risks in scenarios like DGIs, DDIs, and varied renal impairment by simultaneously assessing drug PK, pharmacological effect, and toxicity. The findings underscore the importance of considering pharmacological effects and myotoxicity risks, which differed from changes seen in plasma exposure. This study demonstrates the value of PBPK-QSP models in guiding dose adjustments to optimize the efficacy and safety balance in target patient populations, showcasing their strength in MIDD and MIPD strategies.Title in the list of papers of Luna Prieto Garcia's thesis: Integrated Physiologically-Based Pharmacokinetic Model with a Quantitative Systems Pharmacology and Toxicology Model for Statins in Disease PopulationThe manuscript included in the thesis was eventually published in two parts. See also part 1: https://doi.org/10.1208/s12248-025-01146-2</p
Contemporary randomized controlled trials in uncomplicated type B aortic dissection : a comparative methodological analysis
No full textThe management of uncomplicated type B aortic dissection (uTBAD) remains a subject of ongoing debate. While best medical therapy (BMT) has been the conventional approach, thoracic endovascular aortic repair (TEVAR) has been proposed as an alternative due to its potential to promote aortic remodeling and reduce long-term complications. However, conflicting evidence regarding its survival benefits, procedural risks, and long-term durability has limited its widespread adoption. Three contemporary randomized controlled trials, IMPROVE-AD, EARNEST, and SUNDAY, are currently evaluating the role of TEVAR in uTBAD management. IMPROVE-AD, conducted across NorthAmerica, aims to determine whether TEVAR reduces all-cause mortality and major aortic complications over six years in a cohort of 1,100 patients. The Scandinavian SUNDAY trial focuses on the subacute phase of uTBAD, investigating aortic remodeling, procedural safety, and long-term survival. EARNEST, based in the UK, integrates clinical, anatomical, and economic endpoints, assessing costeffectiveness alongside patient-reported quality-of-life outcomes. This article provides a comparative analysis of these trials, examining their study designs, inclusion criteria, intervention protocols, and outcome measures. By synthesizing their methodologies and expected findings, this review contextualizes the evolving role of TEVAR in uTBAD and highlights key considerations for future clinical practice. The results of these trials are expected to shape guideline recommendations, refine patient selection criteria, and clarify TEVAR's long-term benefits in uTBAD management
Climate Clash : A Multimodal Analysis of Movement–Countermovement Interactions in the Digital Sphere
No full textThis article investigates the intensity and character of interaction between the climate movement and countermovement in the online sphere. Theoretically, we contribute by proposing a novel categorization of movement–countermovement interaction that considers whether the action directly or indirectly targets the adversary, their argument, or their actions. While in physical interaction, the activists clash on the streets, in social media, rival actors can address each other via direct responses (e.g., retweets, mentions) or indirect discursive actions that aim to delegitimize opposing actors, their arguments or actions via text or images. We adopt a multimodal approach to illustrate these patterns. More specifically, we have extracted climate change-specific posts from Twitter (now X) using several hashtags typical of the climate movement and its counterpart (e.g., #climateaction; #climatehoax) during the weeks of Global Climate Action in September and the COP25 meeting in December 2019. The movement and countermovement accounts were identified interactively by examining network diagrams and structural network properties and manually inspecting samples of the tweets posted inside each group. The results of the multimodal analysis indicate that the level of direct and indirect interaction between climate activists and their adversaries is small, asymmetrical, varies based on language, and is unexpectedly similar during the weeks of strike and COP. The countermovement targets climate activists, their arguments, and actions much more than vice versa. The presented discursive and visual struggle demonstrates movement–countermovement interaction on social media
Carbapenem-resistant Enterobacterales (CRE) acquisition and molecular characterization following colistin monotherapy and colistin-meropenem combination therapy : findings from the AIDA randomized trial
No full textBackground: Colistin-carbapenem combination therapy is frequently used for carbapenem-resistant Gram-negative infections, but its impact on subsequent acquisition of carbapenem-resistant Enterobacterales (CRE) requires further investigation. We evaluated the incidence of CRE acquisition and performed molecular characterization of recovered isolates following treatment with colistin-meropenem versus colistin monotherapy. Methods: This analysis addressed a pre-specified secondary aim of the AIDA multicenter randomized controlled trial, which compared colistin monotherapy to colistin-meropenem combination therapy for carbapenem-resistant Gram-negative infections at six hospitals in Israel, Greece, and Italy. Rectal swabs were obtained at enrollment and weekly until day 28 or discharge. Swabs were processed centrally by plating onto MacConkey agar supplemented with imipenem to selectively isolate CRE. Recovered colonies were identified using MALDI-TOF mass spectrometry, and meropenem minimum inhibitory concentrations (MICs) were determined by broth microdilution. Clinical cultures were obtained as indicated and processed locally, and CRE isolates were sent to the central laboratory for confirmation and characterization. Whole-genome sequencing was used to determine sequence types and resistance genes. Patients were excluded if they had CRE detected at baseline, either by rectal culture or as the index clinical isolate, or if no follow-up rectal cultures were available. Results: Among 197 eligible patients (99 colistin; 98 colistin-meropenem), CRE acquisition occurred in 6 (3.0%): 1/99 (1.0%, 95% CI 0.03-5.5%) in the monotherapy arm and 5/98 (5.1%, 95% CI 1.7-11.5%) in the combination arm (p = 0.12). Two patients in the combination arm developed clinical infections caused by CRE (bacteremia and pneumonia); none occurred in the monotherapy arm. Carbapenemase genes were detected in four of the six acquired CRE isolates: one in the monotherapy arm (blaVIM) and three in the combination arm (all blaKPC). Identified species included Klebsiella pneumoniae and Escherichia coli belonging to established and emerging high-risk, multidrug-resistant clones. Conclusions: Patients treated with colistin-meropenem had a higher, though not statistically significant, rate of CRE acquisition. Early detection of high-risk CRE clones highlights the need to weigh potential unintended consequences when selecting combination regimens for multidrug-resistant infections.Trial RegistrationAIDA trial was registered with ClinicalTrials.gov, number NCT01732250 (submitted 19-11-2012)
Reformation of science publishing : the Stockholm Declaration
No full textScience relies on integrity and trustworthiness. But scientists under career pressure are lured to purchase fake publications from 'paper mills' that use AI-generated data, text and image fabrication. The number of low-quality or fraudulent publications is rising to hundreds of thousands per year, which-if unchecked-will damage the scientific and economic progress of our societies. The result is editor and reviewer fatigue, irreproducible experiments, misguided experiments, disinformation and escalating costs that devour funding from taxpayers intended for research. It is high time to reevaluate current publishing models and outline a global plan to stop this unhealthy development. A conference was therefore organized by the Royal Swedish Academy of Sciences to draft an action plan with specific recommendations, as follows. (i) Academia should resume control of publishing using non-profit publishing models (e.g. diamond open-access). (ii) Adjust incentive systems to merit quality, not quantity, in a reputation economy where the gaming of publication numbers and citation metrics distorts the perception of academic excellence. (iii) Implement mechanisms to prevent and detect fake publications and fraud which are independent of publishers. (iv) Draft and implement legislations, regulations and policies to increase publishing quality and integrity. This is a call to action for universities, academies, science organizations and funders to unite and join this effort
Towards realizing life cycle net-zero energy/emissions (LCNZE) buildings : A systematic literature review
No full textIn recent decades, the growing recognition of embodied energy and associated emissions in buildings has increased interest in life cycle assessment of buildings. The concept of net-zero operational energy buildings is now evolving into the more holistic idea of life cycle net-zero energy/emissions (LCNZE) buildings, where on-site renewable energy offsets not only operational demands but also the embodied impacts throughout the building's life cycle. This study aims to systematically review research published over the past twelve years, along with relevant policies in developed countries, to identify key advancements and knowledge gaps in the pursuit of LCNZE buildings. Given the limited availability of systematic literature reviews in this area, the novelty of this research lies in its comprehensive and structured synthesis of current knowledge and gaps, providing stakeholders, policymakers, and researchers with an improved understanding of the practices, actions, and research needed to support the transition toward a decarbonised building sector. The findings indicate that, despite a recent increase in research on LCNZE buildings, a substantial gap remains concerning how buildings can achieve a net-zero energy/ emissions balance from a life cycle perspective, as well as which passive, active, and renewable measures are necessary to ensure this outcome. Future studies should comprehensively analyse the feasibility of achieving LCNZE buildings by addressing all life cycle stages (including end-oflife), considering the impact of building lifespan and its extension, climate dynamics, and employing dynamic life cycle assessments that account for variations and future improvements in material production and energy supply. Additionally, research should explore the potential of artificial intelligence, either independently or in combination with other data-driven approaches (e.g., BIM, optimisation), to support and facilitate the realisation of LCNZE buildings. From a policy perspective, while some European countries have recently introduced mandatory requirements and limit values to reduce life cycle CO2 emissions, particularly for new buildings, it is essential to expand these requirements to include the retrofitting of existing buildings; moreover, greater harmonisation across national policies is necessary to ensure comparability and coherence
Cancer Patients' Sharing of Electronic Health Records with Informal Caregivers
No full textPatients' online record access (ORA) enables patients with complex diagnoses like cancer to involve their informal caregivers in care management by sharing health information, either through proxy access functionality or informally. The extent to which cancer patients use electronic health records (EHRs) for information sharing is unknown. Using the NORDeHEALTH 2022 Patient Survey, we compared cancer and other patients' reasons for using the EHR in Sweden. We found that although the majority of respondents did not access their records with the purpose of sharing with family or friends, cancer patients were more likely to state this as a reason than other patients, or those with no recent treatment experience. This indicates an increased need for proxy access functionality in patient portals among cancer patients