| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 3. |
- Welen, Karin, et al.
(författare)
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COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
- 2021
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial.The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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| 4. |
- Berghammer, Malin, et al.
(författare)
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The impact of anxiety in relation to COVID-19 on the life-situation of young people in Sweden
- 2021
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Ingår i: Quality of Life Research. - : SPRINGER. - 0962-9343 .- 1573-2649. ; 30:SUPPL 1, s. S4-S4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aims: In general, COVID-19 symptoms are milder in children than inadults, but the experience of the pandemic could increase anxiety andsignificantly affect the life situation of children and adolescents. Itcould also lead to a long-term negative effect on their health. To studyhow the corona pandemic affected the life situation of children andadolescents in Sweden. Methods: A self-reported online survey wasperformed July–November 2020. Cross-sectional data were collectedusing non-probability and convenience sampling methods. The sample consisted of children 6–14 years and their guardians, and adolescents 15–19 years. The questionnaire covered items regarding the life situation including demographics, school situation, social isolation, and an open-ended question to provide a subjective expression of the living situation. A standardized measurement of anxiety was collected using the Children’s Anxiety Questionnaire (CAQ) (scores range 4–12) and the Numeric Rating Scale (NRS)(scores range 0–10). Data were analyzed by descriptive statistics andwith qualitative manifest content analysis. Results: In total, 1487 participants, 768 children with guardians and 719 adolescents participated. Most of the participants, 754 children (97.2%) and 634 adolescents (89.2%) attended school where a mixture of physical attendance and distance learning was reported by 79 children (10.2%)and 261 adolescents (36.7%). Two children (0.3%) and 298 adolescents (41.9%) reported only having distance learning. A larger proportion of children (n = 339, 43.9%) and adolescents (n = 420,59.2%) reported abstaining from leisure activities, while a minority ofchildren (n = 103, 13%) and adolescent (n = 135, 19%) reportedexperiencing a feeling of ‘social isolation’. These experiences ofchanges in daily routine were prominent in the qualitative result. Social restrictions and loss of contact with older relatives led to fear and anxiety. However, for young children, their lives continued torevolve around the everyday things in life rather than the coronapandemic, for the adolescents; however, their life situation was negatively affected by isolation from peer groups and the loss ofschool routine. Conclusion: The experiences by children due toCOVID-19 in Sweden highlight the importance that children continue living their lives as unchanged as possible and that particularly adolescents need receiving greater support with the maintenance of an educational routine.
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| 5. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 6. |
- Martin, Myriam, et al.
(författare)
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Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDysregulated complement activation, increased protein citrullination, and production of autoantibodies against citrullinated proteins are hallmarks of rheumatoid arthritis (RA). Citrullination is induced by immune cell-derived peptidyl-Arg deiminases (PADs), which are overactivated in the inflamed synovium. We characterized the effect of PAD2- and PAD4-induced citrullination on the ability of the plasma-derived serpin C1-inhibitor (C1-INH) to inhibit complement and contact system activation. MethodsCitrullination of the C1-INH was confirmed by ELISA and Western blotting using a biotinylated phenylglyoxal probe. C1-INH-mediated inhibition of complement activation was analyzed by C1-esterase activity assay. Downstream inhibition of complement was studied by C4b deposition on heat-aggregated IgGs by ELISA, using pooled normal human serum as a complement source. Inhibition of the contact system was investigated by chromogenic activity assays for factor XIIa, plasma kallikrein, and factor XIa. In addition, autoantibody reactivity to native and citrullinated C1-INH was measured by ELISA in 101 RA patient samples. ResultsC1-INH was efficiently citrullinated by PAD2 and PAD4. Citrullinated C1-INH was not able to bind the serine protease C1s and inhibit its activity. Citrullination of the C1-INH abrogated its ability to dissociate the C1-complex and thus inhibit complement activation. Consequently, citrullinated C1-INH had a decreased capacity to inhibit C4b deposition via the classical and lectin pathways. The inhibitory effect of C1-INH on the contact system components factor XIIa, plasma kallikrein, and factor XIa was also strongly reduced by citrullination. In RA patient samples, autoantibody binding to PAD2- and PAD4-citrullinated C1-INH was detected. Significantly more binding was observed in anti-citrullinated protein antibody (ACPA)-positive than in ACPA-negative samples. ConclusionCitrullination of the C1-INH by recombinant human PAD2 and PAD4 enzymes impaired its ability to inhibit the complement and contact systems in vitro. Citrullination seems to render C1-INH more immunogenic, and citrullinated C1-INH might thus be an additional target of the autoantibody response observed in RA patients.
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| 7. |
- Martinsson, Ulla, et al.
(författare)
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Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008-2019
- 2023
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Ingår i: ACTA ONCOLOGICA. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:10, s. 1348-1356
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019.Material and Methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position.Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each).Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.
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| 8. |
- Nilsson Hammar, Anna, et al.
(författare)
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Introduction
- 2022
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Ingår i: Gender, materiality, and Politics : Essays on the making of power - Essays on the making of power. - 9789189361379 ; , s. 7-21
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Norrhem, Svante, et al.
(författare)
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The capacity to act
- 2023
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Ingår i: Knowledge Actors : Revisiting Agency in the History of Knowledge - Revisiting Agency in the History of Knowledge. - 9789189361652 ; , s. 139-158
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Bokkapitel (refereegranskat)
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| 10. |
- Poulikidou, Sofia, 1984, et al.
(författare)
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Impacts on fuel producers and customers of conflicting rules for life cycle assessment
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The use of life cycle assessment (LCA) as a tool for estimating the environmental performance of a product or service in a holistic and systematic manner is increasing. Fuel producers may need to apply different methodological frameworks to be used in different contexts; internally for product development activities as well as externally for communication with customers or authorities. Different LCA frameworks may vary in scope, system boundaries (i.e. life cycle stages to be considered) or modelling requirements (such as data demands but also more detailed methodological features). They may also vary in terms of information they can provide in relation to the environmental performance of the product. Those variations could lead to conflicting outcomes and conclusions and may also increase complexity for the LCA practitioner leading to high competence and resource requirements. Within the research project: Impacts on fuel producers and customers of conflicting rules for LCA , the requirements of different LCA frameworks and their implications to fuel producers are investigated. Focus has been given on three specific frameworks that are identified as relevant or potentially relevant for fuel producers, namely: the recast of the EU Renewable Energy Directive (referred to here as RED II), the EU framework for Product Environmental Footprint (PEF), and the framework of Environmental Product Declaration (EPD). The aim of the project is to increase understanding on the different LCA frameworks available and identify whether the multitude of such frameworks gives conflicting recommendations for environmental improvements and fuel choices. The three LCA frameworks listed above were applied in case studies. To illustrate the potential differences that the different frameworks may lead to, a variation of production pathways and feedstocks were selected including first generation as well as advanced biofuels. Based on the results obtained it can be concluded that applying all three frameworks is not a straightforward task. The methods contain fundamental differences and are at different levels of development, maturity, and adoption. In certain situations, they can lead to diverging conclusions as a result of different quantitative outcomes for a specific production pathway, thus influencing decision making processes in different directions. Understanding those differences and underlying assumptions is important for understanding the variations in outcome. The result for a specific fuel could differ substantially depending on the framework applied and the assumptions and interpretations made when applying this framework. Certain methodological parameters were identified to have a greater impact on the results than others: • The three frameworks diverge in the methods applied for modelling waste management, which can be very important for the results when the biofuel is produced from waste. • The frameworks diverge in what approaches are allowed for modelling processes with multiple products. This can be very important for the results when the fuel is co-produced with other products. • The frameworks also diverge in how the electricity supply is modelled. This is not very important for the results in most of our case studies, because the production of these biofuels does not require a lot of electricity. The study confirms that applying a framework like EPD or PEF in addition to RED II would require significant supplementary efforts. Not only because of different rules which were often contradicting or difficult to interpret but also because of additional data and reporting requirements. The need for expertise and resources is increasing for fuel producers to be able to provide EPD and PEF compliant assessments. To enhance the development and harmonization of LCA approaches this project stresses the need for product specific rules (in the form of Product Environmental Category Rules (PEFCR) and Product Category Rules (PCR)) for renewable fuels. Future versions of all three studied frameworks should be clearer on how specific methodological choices are to be applied (e.g., when it comes to allocation and multifunctional processes) as well as when it comes to model electricity supply. RED for example shall be clearer on how to define the electricity region while EPD guidelines on how to define the electricity market. Although it is not realistic to aim for a single unified LCA framework, the biofuel PCR and PEFCR can be developed with RED in mind. Some aspects of the PEF methodology can perhaps also be integrated into RED III that is currently under development. This would enhance the broader adoption of the frameworks among fuel producers. Finally, the involvement and engagement of the industry, and fuel producers themselves is very important. Industry initiatives are essential for the development of biofuel PCR and PEFCR while the general development of the three frameworks can also be influenced. In this study, we also investigated the relationship between the LCA frameworks and schemes for chain of custody certification (CoCC), in particular schemes for mass balance certifications (MBC) to investigate to what extent these schemes complement or overlap with LCA. The purpose of MBC schemes and LCA are different, in the sense that the first aim at verifying the sources and sustainability of total amounts of raw materials used by tracking them throughout the value chain, while the second at quantifying specific environmental impact. The system boundaries are similar, since both cover the entire value chain, but may be applied differently depending on the detailed frameworks applied and choices made in applying the MBC schemes. By identifying and clearly illustrating the variations among the studied frameworks the study enhances application, development, and harmonization of LCA, in a broader perspective, informs LCA practitioners but also decision makers and provides insights on how the identified challenges can be addressed.
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