| 1. |
- Gonzalez-Ericsson, Paula, et al.
(författare)
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The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers into breast cancer clinical trials and daily practice
- 2020
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Ingår i: Journal of Pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 250:5, s. 667-684
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Forskningsöversikt (refereegranskat)abstract
- Immune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC.
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| 2. |
- Amgad, M, et al.
(författare)
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Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
- 2020
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.
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| 3. |
- Kolmert, Johan, et al.
(författare)
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Urinary Leukotriene E-4 and Prostaglandin D-2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation A Clinical Observational Study
- 2021
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - NEW YORK, USA : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 203:1, s. 37-53
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: New approaches are needed to guide personalized treatment of asthma. Objectives: To test if urinary eicosanoid metabolites can direct asthma phenotyping. Methods: Urinary metabolites of prostaglandins (PGs), cysteinyl leukotrienes (CysLTs), and isoprostanes were quantified in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy control participants. Validation was performed internally in 302 participants with SA followed up after 12-18 months and externally in 95 adolescents with asthma. Measurement and Main Results: Metabolite concentrations in healthy control participants were unrelated to age, body mass index, and sex, except for the PGE(2) pathway. Eicosanoid concentrations were generally greater in participants with MMA relative to healthy control participants, with further elevations in participants with SA. However, PGE(2) metabolite concentrations were either the same or lower in male nonsmokers with asthma than in healthy control participants. Metabolite concentrations were unchanged in those with asthma who adhered to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas those with SA treated with omalizumab had lower concentrations of LTE4 and the PGD(2) metabolite 2,3-dinor-11 beta-PGF(2 alpha). High concentrations of LTE4 and PGD(2) metabolites were associated with lower lung function and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum, and urine in U-BIOARED participants and in adolescents with asthma. These type 2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study and were found to be as sensitive to detect T2 inflammation as the established biomarkers. Conclusions: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new noninvasive approach for molecular phenotyping of adult and adolescent asthma.
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| 4. |
- Bauer, Fredric, et al.
(författare)
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Plastics and climate change breaking carbon lock-ins through three mitigation pathways
- 2022
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Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:4, s. 361-376
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Forskningsöversikt (refereegranskat)abstract
- The plastic industry is dependent on fossil fuels in various ways that result in strong “carbon lock-in” throughout the value chain and large and growing CO2 emissions. The industry must decarbonize to reach global net-zero pledges. Although a few initiatives have been launched, they primarily focus on plastic waste. Current research has investigated mitigation potential on different parts of the plastic value chain but remains in silos. Here, we review carbon lock-ins throughout the plastic value chain and identify possible mitigation pathways for each stage of the plastic life cycle. We show how lock-ins are stubbornly entrenched across the domains of production, markets, waste management, industry organization, and governance. Overcoming these carbon lock-ins and achieving zero-carbon targets for the sector by 2050 will require thorough systemic change to how plastics are produced, used, and recycled, including promotion of demand reduction strategies, bio-based feedstocks, and circular economy principles. Strict governance structures, enforceable regulation, and a new proactive and inclusive vision for the low-carbon transition are equally important.
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| 5. |
- Edberg, Anna-Karin, 1961-, et al.
(författare)
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Specialistsjuksköterskan inom vård av äldre gör skillnad
- 2013
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Ingår i: Ä : en tidning för Riksföreningen sjuksköterskan inom äldrevård : geriatriker, dietister inom geriatrik samt alla professioner runt den äldre patienten. - 2001-1164. ; :4, s. 33-36
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Edberg, Anna-Karin, et al.
(författare)
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Specialistsjuksköterskan inom vård av äldre gör skillnad
- 2013
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Ingår i: Ä : en tidning för Riksföreningen sjuksköterskan inom äldrevård : geriatriker, dietister inom geriatrik samt alla professioner runt den äldre patienten. - 2001-1164. ; :4, s. 33-36
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Eisler, Anna D, et al.
(författare)
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Risk judgments : A psychometric approach
- 2008
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Ingår i: Proceedings of the 24th Annual Meeting of the International Society for Psychophysics, Fechner Day. ; , s. 111-116
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Konferensbidrag (refereegranskat)abstract
- The present study examined perception of 54 global risk factors in a human ecological perspective, using a psychometric paradigm and psychophysical scaling. The results revealed significant gender differences. The female subjects estimated risks as more serious than the male did. Also significant age differences were obtained. Discussion focuses on the meaning of gender and age differences in risk perception as well on both theoretical and methodological implications.
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