| 1. |
- Dillner, Joakim, et al.
(författare)
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Antibodies to SARS-CoV-2 and risk of past or future sick leave
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. We invited all employees (n=15,300) at work at the Karolinska University Hospital, Stockholm, Sweden to participate in a study examining SARS-Cov-2 antibodies in relation to registered sick leave. For consenting 12,928 healthy hospital employees antibodies to SARS-CoV-2 could be determined and compared to participant sick leave records. Subjects with viral serum antibodies were not at excess risk for future sick leave (adjusted odds ratio (OR) controlling for age and sex: 0.85 [95% confidence interval (CI) (0.85 (0.43-1.68)]. By contrast, subjects with antibodies had an excess risk for sick leave in the weeks prior to testing [adjusted OR in multivariate analysis: 3.34 (2.98-3.74)]. Thus, presence of viral antibodies marks past disease and protection against excess risk of future disease. Knowledge of whether exposed subjects have had disease in the past or are at risk for future disease is essential for planning of control measures.Trial registration: First registered on 02/06/20, ClinicalTrials.gov NCT04411576.
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| 2. |
- Earon, Robert, et al.
(författare)
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Insight into the influence of local streambed heterogeneity on hyporheic-zone flow characteristics
- 2020
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Ingår i: Hydrogeology Journal. - : Springer Science and Business Media Deutschland GmbH. - 1431-2174 .- 1435-0157. ; 28:8, s. 2697-2712
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Tidskriftsartikel (refereegranskat)abstract
- Interaction between surface water and groundwater plays a fundamental role in influencing aquatic chemistry, where hyporheic exchange processes, distribution of flow paths and residence times within the hyporheic zone will influence the transport of mass and energy in the surface-water/groundwater system. Geomorphological conditions greatly influence hyporheic exchange, and heterogeneities such as rocks and clay lenses will be a key factor for delineating the hyporheic zone. Electrical resistivity tomography (ERT) and ground-penetrating radar (GPR) were used to investigate the streambed along a 6.3-m-long reach in order to characterise geological layering and distinct features which may influence parameters such as hydraulic conductivity. Time-lapse ERT measurements taken during a tracer injection demonstrated that geological features at the meter-scale played a determining role for the hyporheic flow field. The penetration depth of the tracer into the streambed sediment displayed a variable spatial pattern in areas where the presence of highly resistive anomalies was detected. In areas with more homogeneous sediments, the penetration depth was much more uniformly distributed than observed in more heterogeneous sections, demonstrating that ERT can play a vital role in identifying critical hydraulic features that may influence hyporheic exchange processes. Reciprocal ERT measurements linked variability and thus uncertainty in the modelled resistivity to the spatial locations, which also demonstrated larger variability in the tracer penetration depth, likely due to local heterogeneity in the hydraulic conductivity field.
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| 3. |
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| 4. |
- Forsberg, Elin, et al.
(författare)
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Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary CAR-T cells are immune cells equipped with a claw that enable them to bind cancer cells. Usually, CAR-T cells are made using immune cells from blood. Here, we tested the hypothesis that also immune cells that reside in the tumor, so called tumor-infiltrating lymphocytes, can also be modified to carry the claw. This may mean that these cells, called CAR-TILs, will be able to attack cancer cells in two ways, using the claw or binding using its normal protein on the cell surface, the so-called T cell receptor. We show that CAR-TILs can be generated, and that they can kill melanoma cells in cell culture and in mice. Finally, to prepare for clinical trials, we also assess if CAR-TILs can be safe in a human cancer patient-like model, a companion dog suffering from cancer. Our data suggest that CAR-TILs may be a way to treat patients with melanoma but human clinical trials are needed. Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.
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| 5. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 6. |
- Karlsson, Joakim, et al.
(författare)
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Molecular profiling of driver events in metastatic uveal melanoma
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has ahigh mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genesassociated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
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| 7. |
- 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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| 8. |
- Ny, Lars, 1967, et al.
(författare)
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The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.
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| 9. |
- Olofsson, Hans, 1960-, et al.
(författare)
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Nationella prov i historia för åk 6 : Några erfarenheter
- 2021. - 1
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Ingår i: Att bedöma i historieämnet. - Uddevalla : Historielärarnas förening. - 9789151976105 ; , s. 113-142
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Vilka utmaningar finns kring bedömning i historia? Under de senaste åren har förutsättningarna för historieundervisning förändrats som en följd av en dramatiskt förändrad bedömningspraktik. Kapitlen i denna bok diskuterar olika aspekter av bedömning i historieämnet. Sammantaget ger de en fördjupad insikt om bedömningspraktiken i det moderna historieämnet, men därutöver får läsaren indirekt bred kunskap om de villkor som gäller för historieundervisning i svensk skola under tidigt 2020-tal.
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| 10. |
- Petersson, Jöran, Docent, et al.
(författare)
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Nya kursplanen : Enhetsanalys för attundervisa omhärledda enheter
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Härledda enheter ligger i området proportionalitet, vilket matematikdidaktisk forskning betraktar som både svårt att undervisa och svårt att lära sig. I ett regionalt skolutvecklingsprojekt omformade vi högskolematematikens enhetsanalys (dimensionsanalys) till att passa åk 7-gy då grundidén är att betrakta en storhets enhet, exempelvis kr/kg, och dra slutsatser om hur storheten (kvot eller produkt) ska beräknas. I projektet utvecklade vi både övningsproblem och undervisningsmetoder för detta.
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| 11. |
- Sah, Vasu R., et al.
(författare)
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Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
- 2023
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Ingår i: Cancer Research Communications. - : American Association For Cancer Research (AACR). - 2767-9764. ; 3:5, s. 884-895
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tu-mor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.Results: Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of respond-ing patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling ter -tiar y lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.Significance: The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble and tumor markers can inform on predictive biomark-ers needing validation and become hypothesis generating for experimental research.
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| 12. |
- Saini, Puneet Kumar
(författare)
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Solar integrated heating systems: Applications in buildings and industries
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- “Heat is half” of the global final energy consumption, and the decarbonization of the heating sector is critical to achieving climate goals. This thesis employs a system modelling approach to evaluate renewable heating systems. The overarching goal is to reduce fossil fuel reliance by integrating renewable energy technologies, such as solar thermal, photovoltaics, photovoltaic thermal, heat pump, and thermal energy storage in different system concepts. Two primary sectors are addressed: buildings, with a focus on utilizing solar collectors and heat pumps for heating systems in multifamily houses by recovery of waste heat; and industries, utilizing solar collectors for steam generation below 200 °C. The work is centred around five primary research questions, addressing the technical and economic feasibility of the mentioned technologies and their roles in decarbonization.Two system arrangements were simulated to address the heating demands of buildings: a) Centralized heat pump that utilizes ventilation air as a heat source, serving three multifamily buildings, and b) A fifth generation district heating system that utilizes industrial waste heat as its source. The techno-economic performance of these systems was evaluated. The results suggest that the economic viability of such arrangements largely depends on critical factors that include the costs of heat pump sub-stations, prevailing electricity prices, and the cost of waste heat. Incorporating solar air heating collectors and optimizing flow controls enhance both component and system energy efficiency. Moreover, integrating photovoltaic systems, up to a specific capacity, is advantageous as it offers reductions in heating costs.For industrial steam generation, the importance of the solar fraction in technological comparisons is highlighted. Parabolic trough collector and heat pump for steam generation are compared for 34 locations in the European Union, using solar fraction as an indicator. The results highlight the economic competitiveness of both technologies for a wide range of boundary conditions. However, heating costs from solar thermal collectors increase at higher solar fractions, primarily due to the storage costs. This trend sets an economic limit on the maximum feasible solar fraction. As a result, hybrid systems combining solar thermal collectors with steam heat pumps offer a promising combination to achieve a high renewable fraction for industrial applications.Concerns about CO2 emissions from the electricity grid, and its reliability in many countries, necessitate the exploration of alternative system concepts to meet a higher fraction of heating demand. One such novel energy system combines a parabolic trough collector, photovoltaic, and thermal energy storage (using water and sand as storage media) to reach a combined solar fraction of 90 %, while remaining cost-competitive with fossil fuels. The techno-economic performance of solar thermal collectors is system dependent, largely influenced by their integration within industrial systems. Two novel indicators are introduced to quantify the integration incompatibilities, offering insights into the dynamics for specific integration point. Using this method for a case study resulted in an optimized configuration, improving the overall system performance.Collectively, the results are expected to be leveraged by relevant stakeholders to advance the cause of heating decarbonization in buildings and industries.
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