| 1. |
- Dutta, Nikita, et al.
(författare)
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Combinatory analysis of immune cell subsets and tumor-specific genetic variants predict clinical response to PD-1 blockade in patients with non-small cell lung cancer
- 2023
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Immunotherapy by blocking programmed death protein-1 (PD-1) or programmed death protein-ligand1 (PD-L1) with antibodies (PD-1 blockade) has revolutionized treatment options for patients with non-small cell lung cancer (NSCLC). However, the benefit of immunotherapy is limited to a subset of patients. This study aimed to investigate the value of combining immune and genetic variables analyzed within 3-4 weeks after the start of PD-1 blockade therapy to predict long-term clinical response.Blood collected from patients with NSCLC were analyzed for changes in the frequency and concentration of immune cells using a clinical flow cytometry assay. Next-generation sequencing (NGS) was performed on DNA extracted from archival tumor biopsies of the same patients. Patients were categorized as clinical responders or non-responders based on the 9 months' assessment after the start of therapy.We report a significant increase in the post-treatment frequency of activated effector memory CD4+ and CD8+ T-cells compared with pre-treatment levels in the blood. Baseline frequencies of B cells but not NK cells, T cells, or regulatory T cells were associated with the clinical response to PD-1 blockade. NGS of tumor tissues identified pathogenic or likely pathogenic mutations in tumor protein P53, Kirsten rat sarcoma virus, Kelch-like ECH-associated protein 1, neurogenic locus notch homolog protein 1, and serine/threonine kinase 11, primarily in the responder group. Finally, multivariate analysis of combined immune and genetic factors but neither alone, could discriminate between responders and non-responders.Combined analyses of select immune cell subsets and genetic mutations could predict early clinical responses to immunotherapy in patients with NSCLC and after validation, can guide clinical precision medicine efforts.
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| 2. |
- Harbst, Katja, et al.
(författare)
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Molecular profiling reveals low- and high-grade forms of primary melanoma.
- 2012
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
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Tidskriftsartikel (refereegranskat)abstract
- For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
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| 3. |
- Dimenäs, Sandra L., 1989, et al.
(författare)
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Adolescents' self-reported experiences following a person-centred, theory-based educational intervention versus conventional education for improved oral hygiene: Analysis of secondary outcomes of a randomized field study
- 2023
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Ingår i: JOURNAL OF CLINICAL PERIODONTOLOGY. - 0303-6979. ; 51:1, s. 63-73
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To analyse adolescents' self-reported experiences and behavioural outcomes of a person-centred, theory-based intervention in comparison with conventional information/instruction for improved oral hygiene.Materials and Methods: Data were derived from a prospective, multi-centred, two-arm, quasi-randomized field study focusing on the effectiveness of educational interventions for improved oral hygiene. Dental hygienists working within the Public Dental Service, Vastra Gotaland, Sweden, provided treatments, and adolescents with poor oral hygiene conditions were eligible for participation. The person-centred test intervention was based on social cognitive constructs, and motivational interviewing was used as an approach in communication. The control intervention included conventional information/instructions. Clinical examinations were performed, and questionnaires were distributed at baseline and at 6 months. Three-hundred and twelve patients were enrolled, and data from 276 patients, following treatment per protocol, were analysed.Results: The test group was more satisfied with the education about gingivitis (very good: 61% vs. 37%) and communication during therapy (very good: 69% vs. 50%) and reported to a larger extent that they were much more careful regarding their oral hygiene after the treatment (30% vs. 15%) and had higher confidence about keeping up healthy gingival conditions, in comparison with the control group (all p < .01).Conclusions: The person-centred, theory-based intervention was superior in terms of adolescents' experiences of education and communication during therapy and self-reported oral hygiene behavioural outcomes at 6 months, in comparison with conventional information/instruction.
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| 4. |
- Johansen, Karin, 1990-, et al.
(författare)
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Laparoscopic distal pancreatectomy is more cost-effective than open resection: results from a Swedish randomized controlled trial
- 2023
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Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 25:8, s. 972-979
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLaparoscopic distal pancreatectomy is being implemented worldwide. The aim of this study was to perform a cost-effectiveness analysis from a health care perspective.MethodsThis cost-effectiveness analysis was based on the randomized controlled trial LAPOP, where 60 patients were randomized to open or laparoscopic distal pancreatectomy. For the follow-up of two years, resource use from a health care perspective was recorded, and health-related quality of life was assessed using the EQ-5D-5L. The per-patient mean cost and quality-adjusted life years (QALYs) were compared using nonparametric bootstrapping.ResultsFifty-six patients were included in the analysis. The mean health care costs were lower, €3863 (95% CI: -€8020 to €385), for the laparoscopic group. Postoperative quality of life improved with laparoscopic resection and resulted in a gain in QALYs of 0.08 (95% CI: −0.09 to 0.25). The laparoscopic group had lower costs and improved QALYs in 79% of bootstrap samples. With a cost-per-QALY threshold of €50 000, 95.4% of the bootstrap samples were in favour of laparoscopic resection.ConclusionLaparoscopic distal pancreatectomy is associated with numerically lower health care costs and improvements in QALYs compared with the open approach. The results support the ongoing transition from open to laparoscopic distal pancreatectomies.
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| 5. |
- Lundgren, Anna, 1974, et al.
(författare)
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Safety and immunogenicity of an improved oral inactivated multivalent enterotoxigenic Escherichia coli (ETEC) vaccine administered alone and together with dmLT adjuvant in a double-blind, randomized, placebo-controlled Phase I study
- 2014
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 32:52, s. 7077-7084
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have developed a new oral vaccine against enterotoxigenic Escherichia coli (ETEC), which is the most common cause of bacterial diarrhea in children in developing countries and in travelers. Methods: The vaccine was tested for safety and immunogenicity alone and together with double-mutant heat-labile toxin (dmLT) adjuvant in a double-blind, placebo-controlled Phase I study in 129 Swedish adults. The vaccine consists of four inactivated recombinant E. coli strains overexpressing the major ETEC colonization factors (CFs) CFA/I, CS3, CS5, and CS6 mixed with an LT B-subunit related toxoid, LCTBA. Volunteers received two oral doses of vaccine alone, vaccine plus 10 mu g or 25 mu g dmLT or placebo. Secretory IgA antibody responses in fecal samples and IgA responses in secretions from circulating intestine-derived antibody secreting cells were assessed as primary measures of vaccine immunogenicity. Results: The vaccine was safe and well tolerated; adverse events were few and generally mild with no significant differences between subjects receiving placebo or vaccine with or without adjuvant. As many as 74% of subjects receiving vaccine alone and 83% receiving vaccine plus 10 mu g dmLT showed significant mucosal IgA responses to all five primary vaccine antigens and about 90% of all vaccinees responded to at least four of the antigens. Subjects receiving vaccine plus 10 mu g dmLT responded with significantly increased intestine-derived anti-CS6 responses compared to subjects receiving vaccine alone. Conclusions: The vaccine was safe and broadly immunogenic. dmLT further enhanced mucosal immune responses to CF antigens present in low amounts in the vaccine. Based on these encouraging results, the vaccine will be tested for safety and immunogenicity in different age groups including infants in Bangladesh and for protective efficacy in travelers. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.
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| 6. |
- Lundgren, Lina, 1982-, et al.
(författare)
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Comfort aspects important for the performance and safety of kitesurfing
- 2012
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Ingår i: Work. - Amsterdam : IOS Press. - 1051-9815 .- 1875-9270. ; 41:Supplement: 1, s. 1221-1225
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Tidskriftsartikel (refereegranskat)abstract
- Equipment used in sports is of great importance, especially when the equipment is in direct contact with the athlete or is important for safety. In the sport kitesurfing environmental factors and the equipment design are crucial for the comfort and safety. The participants' choice and opinion of equipment can show which factors are considered most important for the performance and to reduce risk for injury. This study has evaluated self-reported information from the participants about what equipment they use, comfort of the equipment and if the equipment has contributed to any injuries. The methods used were questionnaires (n-206) and interviews (n-17), which in combination allows to assess the problem both quantitatively and qualitatively. The results showed that supported leading edge kites are most frequently used, with a waist harness and foot straps to attach the feet. The choice of kite type was mainly based on the discipline of riding for the respondent. Some issues concerning comfort of riding and injury risk the respondents did relate to the design of harness and foot straps. The information from this study can be used for development strategies for industry manufacturers and for further studies in the area of equipment design and biomechanics.
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| 7. |
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| 8. |
- Lundgren, Lina, 1982-, et al.
(författare)
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Implementation of usability analysis to detect problems in the management of kitesurfing equipment
- 2011
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Ingår i: Procedia Engineering. - Amsterdam : Elsevier. - 1877-7058 .- 1877-7058. ; 13, s. 525-530
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Tidskriftsartikel (refereegranskat)abstract
- Equipment used for high-risk sports, such as kitesurfing, needs to be efficient for the intended use and the user, and thus meet the mechanical demands and provide sufficient safety. Accidents related to kitesurfing occur, and the consequences are sometimes catastrophic. One important factor is the equipment design, which can influence the type and number of injuries due to insufficient safety systems. The aim of this study was to investigate how the design of kitesurfing equipment can affect safety issues from a usability perspective in relation to the task of preparation. A focus group of 6 subjects analyzed the task of preparing kitesurfing equipment for riding, using the evaluation methods Enhanced Cognitive Walkthrough (ECW) and Predictive Use Error Analysis (PUEA). From the evaluation, a list of plausible usability problems was identified together with proposed design guidelines. The results showed that usability problems occur during preparation. In total 35 usability problems were found, of which 11 (4 from ECW and 7 from PUEA) have a great impact on safety. These 11 problems were hard to detect for the user and could result in serious consequences for the kitesurfers during rideing. The analysis resulted in some general guidelines that are possible to implement on different types of kites. To conclude, education and improved design of the equipment are essential to increase the safety of the sport.
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| 9. |
- Lundgren, Lina, 1982, et al.
(författare)
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Injuries related to injuries
- 2011
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Ingår i: ICSMSS: VII. International Conference on Sport Medicine and Sport Science.
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Konferensbidrag (refereegranskat)
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| 10. |
- Lundgren, Lina, 1982-, et al.
(författare)
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Injuries related to kitesurfing
- 2011
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Ingår i: World Academy of Science, Engineering and Technology. - Istanbul, Turkey : World Academy of Science, Engineering and Technology, WASET. - 2010-3778 .- 2010-376X. ; :77, s. 1132-1136
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Tidskriftsartikel (refereegranskat)abstract
- Participation in sporting activities can lead to injury. Sport injuries have been widely studied in many sports including the more extreme categories of aquatic board sports. Kitesurfing is a relatively new water surface action sport, and has not yet been widely studied in terms of injuries and stress on the body. The aim of this study was to get information about which injuries that are most common among kitesurfing practitioners, where they occur, and their causes. Injuries were studied using an international open web questionnaire (n=206). The results showed that many respondents reported injuries, in total 251 injuries to knee (24%), ankle (17%), trunk (16%) and shoulders (10%), often sustained while doing jumps and tricks (40%). Among the reported injuries were joint injuries (n=101), muscle/tendon damages (n=47), wounds and cuts (n=36) and bone fractures (n=28). Also environmental factors and equipment can influence the risk of injury, or the extent of injury in a hazardous situation. Conclusively, the information from this retrospective study supports earlier studies in terms of prevalence and site of injuries. Suggestively, this information should be used for to build a foundation of knowledge about the sport for development of applications for physical training and product development.
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