| 31. |
- Nyman, J., et al.
(författare)
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Dose Escalated Chemo-RT to 84 Gy in Stage III NSCLC Appears Excessively Toxic : Results from a Randomized Phase II Trial
- 2018
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Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 13:10, s. S373-S373
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease, however, with a rather high probability of locoregional and metastatic recurrence further treatment optimization is warranted. Based on previous one-armed trials with dose escalated radiotherapy, showing feasibility, the Swedish Lung Cancer Study Group aimed to investigate whether dose escalation based on individual normal tissue constraints could improve outcome in this randomized phase II trial.Method: NSCLC patients with stage III disease, good performance status (0-1), adequate lung function (FEV1 > 1.0 L and CO diff. > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. The radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to a total dose of 68 Gy (standard arm A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week while keeping the total treatment time constant at seven weeks with the same dose to involved nodes and primary tumor.Result: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in the dose escalated group compared to 28 and 45 months in the standard group. The 1-, 3- and 5-year survival rates were 56%, 33% and 17% in the escalated arm and 72%, 61% and 34% in the standard arm. There were four toxicity-related deaths due to esophageal perforations (one in arm A and three in arm B) and three deaths due to pneumonitis (one in arm A and two in arm B).Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 5-year survival of 34%. A possible step forward will be to improve systemic therapy, but future approaches with escalated radiotherapy may include boost techniques to remaining PET positive areas or different escalation schedules to the primary tumor and mediastinal nodes.
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| 32. |
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| 33. |
- Savage, C., et al.
(författare)
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Turning the tables : When the student teaches the professional - A case description of an innovative teaching approach as told by the students
- 2011
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Ingår i: Nurse Education Today. - : Elsevier BV. - 0260-6917 .- 1532-2793. ; 31:8, s. 803-808
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Tidskriftsartikel (refereegranskat)abstract
- Background: Is it possible to increase the value, meaningfulness, and relevance of a course experience by integrating it with the healthcare context? Students and teachers from a course on organization, learning and leadership sought to explore this possibility through a collaborative effort with nurses from an affiliated teaching hospital. Methods: Working as teachers, students created continuing nursing education (CNE) courses using the Adaptive Reflection process. The students and teachers then researched the experience in terms of: 1) content analysis of student self-reflections (discussion notes and logbooks) on the learning process, 2) a student self-assessed outcome achievement survey, and 3) perceived relevance of the CNE courses by the clinical nurse educators. Results: Thirteen nursing students created three CNE courses together with sixteen nurses. Each course consisted of multiple 20-minute long web-based modules with automatic formative feedback. In the process, students exceeded course outcome-levels, journeyed from chaos to confidence and experienced new ways of viewing the group and their own capabilities. Conclusions: The innovative design of the course moved the focus from student-centered learning to learning by contributing to health care. Working in a real world context, the content of the students' efforts and the skills they developed not only met course requirements, but were also aligned with the needs of the wards. This contribution was valued by the students and the RNs which enhanced students' feelings of self-confidence. Further research lies in testing the model in other contexts.
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| 34. |
- Sepponen, K., et al.
(författare)
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Steroidogenic factor 1 (NR5A1) induces multiple transcriptional changes during differentiation of human gonadal-like cells
- 2022
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Ingår i: Differentiation. - : Elsevier BV. - 0301-4681. ; 128:Nov-Dec, s. 83-100
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes steroidogenic factor 1 (SF1), a key regulatory factor that determines gonadal development and coordinates endocrine functions. Here, we have established a stem cell-based model of human gonadal development and applied it to evaluate the effects of NR5A1 during the transition from bipotential gonad to testicular cells. We combined directed differentiation of human induced pluripotent stem cells (46,XY) with activation of endogenous NR5A1 expression by conditionally-inducible CRISPR activation. The resulting male gonadal-like cells expressed several Sertoli cell transcripts, secreted anti-Müllerian hormone and responded to follicle-stimulating hormone by producing sex steroid intermediates. These characteristics were not induced without NR5A1 activation. A total of 2691 differentially expressed genetic elements, including both coding and non-coding RNAs, were detected immediately following activation of NR5A1 expression. Of those, we identified novel gonad-related putative NR5A1 targets, such as SCARA5, which we validated also by immunocytochemistry. In addition, NR5A1 activation was associated with dynamic expression of multiple gonad- and infertility-related differentially expressed genes. In conclusion, by combining targeted differentiation and endogenous activation of NR5A1 we have for the first time, been able to examine in detail the effects of NR5A1 in early human gonadal cells. The model and results obtained provide a useful resource for future investigations exploring the causative reasons for gonadal dysgenesis and infertility in humans. © 2022 The Authors
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| 35. |
- Stenler, S, et al.
(författare)
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Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses.
- 2017
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Ingår i: Human Vaccines & Immunotherapeutics. - : Taylor & Francis. - 2164-5515 .- 2164-554X. ; 13:12, s. 2849-2858
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid. In addition, three conventional plasmids that express the envelope of HIV-1 subtypes A, B and C and contain T20 in their gp41 sequences were also tested.RESULTS: All combinations induced HIV-specific antibodies and cellular responses. The addition of T20 as a peptide and as an expression cassette in the three DNA vectors enhanced antibody responses. The highest anti-HIV-1 Env titers were obtained by the replicon T20 construct. This demonstrates that besides its known antiviral activity, T20 promotes immune responses. We also confirm that the combination of slightly divergent antigens improves immune responses.CONCLUSIONS: The antiretroviral T20 HIV-1 sequence can be used as an immunogen to elicit binding and neutralizing antibodies against HIV-1. These, or similarly modified gp41 genes/peptides, can be used as priming or boosting components for induction of broadly neutralizing anti-HIV antibodies. Future comparative studies will reveal the optimal mode of T20 administration.
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| 36. |
- Walsh, Roddy, et al.
(författare)
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Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
- 2021
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Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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| 37. |
- Wirfält, Elisabet, et al.
(författare)
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Food sources of carbohydrates in a European cohort of adults.
- 2002
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Ingår i: Public Health Nutrition. - 1475-2727. ; 5:6B, s. 1197-1215
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the average consumption of carbohydrate-providing food groups among study centres of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Of the 27 redefined EPIC study centres, 19 contributed subjects of both genders and eight centres female participants only (men, n=13 031; women, n=22 924, after exclusion of subjects under 35 and over 74 years of age from the original 36 900 total). Dietary data were obtained using the 24-hour recall methodology using the EPIC-SOFT software. The major sources of dietary carbohydrate were identified, and 16 food groups were examined. Results: The 10 food groups contributing most carbohydrate were bread; fruit; milk and milk products; sweet buns, cakes and pies; potato; sugar and jam; pasta and rice; vegetables and legumes; crispbread; and fruit and vegetable juices. Consumption of fruits as well as vegetables and legumes was higher in southern compared with northern centres, while soft drinks consumption was higher in the north. Italian centres had high pasta and rice consumption, but breakfast cereal, potato, and sweet buns, cakes and pies were higher in northern centres. In Sweden, lower bread consumption was balanced with a higher consumption of crispbread, and with sweet buns, cakes and pies. Overall, men consumed higher amounts of vegetables and legumes, bread, soft drinks, potatoes, pasta and rice, breakfast cereal and sugar and jam than women, but fruit consumption appeared more frequent in women. Conclusion: The study supports the established idea that carbohydrate-rich foods chosen in northern Europe are different from those in the Mediterranean region. When comparing and interpreting diet-disease relationships across populations, researchers need to consider all types of foods.
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| 38. |
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| 39. |
- Bratt, E., et al.
(författare)
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The STEPSTONES transition program for adolescents with congenital heart disease is effective in improving patient empowerment : a randomized controlled trial
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:Suppl. 2, s. 2745-2745
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Congenital heart disease (CHD) is the most common birth defect, with a global birth prevalence of 8.2 per 1000 new-borns. Improvements in the diagnosis and treatment of children with CHD have resulted in increasing life prospects, with more than 90% surviving into adulthood today. To ensure expert lifetime care, patients need to transfer from paediatric-oriented care to adult-oriented care. At the same time, they need to transition from a dependent child with CHD to an independent adult who can manage living with CHD. Thus, during adolescence, patients with CHD need to acquire knowledge and skills to independently manage their health, while simultaneously experiencing a series of physical, cognitive and social changes. To facilitate this phase, transitional care is needed. However, high-level empirical evidence on the effectiveness of transitional care is scarce.Purpose: To investigate the empowering effect (primary outcome) of a structured person-centred transition programme for adolescents with CHD, and to study the effectiveness on transition readiness, patient-reported health, quality of life, health behaviours, disease-related knowledge, parental uncertainty, and parental perception of transition readiness (secondary outcomes).Methods: The STEPSTONES-CHD trial comprised a hybrid experimental design, in which a randomized controlled trial (RCT) was embedded in a longitudinal, observational study. The trial was conducted in seven CHD centres in Sweden. Two centres were allocated to the RCT-arm, randomising participants to intervention (IG) or control group (CG). The other five centres were intervention-naïve centres and served as contamination check control group (CCCG). Outcomes were measured at the age of 16 y (T0; baseline), 17y (T1) and 18.5y (T2).Results: The change in empowerment from T0 to T2 differed significantly between the IG and CG (mean difference=3.44; 95% CI: 0.27–6.65; p=0.036) in favour for IG. For the secondary outcomes, significant differences in change over time were found in parental involvement (p=0.008), CHD-specific knowledge (p=0.0002), and satisfaction with physical appearance (p=0.039). No differences in primary or secondary outcomes were detected between CG and CCCG, indicating that there was no contamination in the CG.Conclusion: The STEPSTONES-CHD trial demonstrated the effectiveness of a person-centred transition programme in empowering adolescents with CHD. Furthermore, parental involvement, satisfaction with physical appearance and CHD-related knowledge were positively influenced. This trial provides empirical underpinnings for the implementation of transition programmes for afflicted adolescents.
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| 40. |
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