| 1. |
- Repapi, Emmanouela, et al.
(författare)
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Genome-wide association study identifies five loci associated with lung function.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:1, s. 36-44
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
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| 2. |
- Ahlstedt, Carina, 1969-
(författare)
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Registered nurses' work motivation and intention to stay at the workplace
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is currently a shortage of registered nurses (RNs) and high turnover of RNs, both nationally and internationally. Work motivation is an important part of a healthy work environment and something we need to know more about from an RN perspective.The overarching aim of this thesis was to enhance our understanding of the organisational and social workplace factors that contribute to an attractive environment for RNs, by exploring factors associated with work motivation. Four research questions were posed. (i) What factors create the conditions for motivation in RNs’ daily work? (ii) What role does social support in the workplace play in RNs’ work motivation? (iii) What role does the opportunity to work with relevant tasks play in RNs’ work motivation? (iv) Are there differences between healthcare settings regarding RNs’ social support, illegitimate tasks, and associations with work motivation? Four empirical studies were performed to answer these questions. Two were qualitative studies based on an ethnographic approach and two were quantitative cross-sectional studies based on a stratified national sample of RNs. The results of the qualitative studies indicate that crucial factors for RNs' work motivation include a friendly and permissive atmosphere in daily work. Visible progress and receiving feedback from the work itself also positively contributed to motivation. Additionally, RNs' opportunities to learn and support each other through ongoing communication during daily work tended to have a positive impact on work motivation. Effective collaboration between physicians and RNs with mutual respect, understanding of each other's competencies, and creating an environment where RNs could seek clarification were also central to work motivation. The quantitative studies revealed that the opportunity for social support from the immediate manager or co-workers was significant for dimensions related to RNs’ work motivation and the willingness to stay in the workplace. The associations differed in strength between healthcare settings. Furthermore, the results indicated that a factor in RNs' work motivation was the ability to work with tasks perceived as relevant, not illegitimate. However, the results highlighted that a significant portion of RNs performed illegitimate tasks, and that illegitimate tasks were more prevalent for RNs in home healthcare than those in primary care and hospitals. This is something to consider as more complex care is being conducted outside of hospitals. The thesis adds new knowledge that can be useful to the development of attractive workplaces, which could contribute to more RNs choosing to remain in their position for a longer period.
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| 3. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 4. |
- Bergström, Helena, et al.
(författare)
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Factors influencing the implementation of a school-based parental support programme to promote health-related behaviours--interviews with teachers and parents.
- 2015
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The 'Healthy School Start' programme was developed to promote healthy dietary habits and physical activity, targeting parents of 6-year-old children in pre-school class. Knowledge of barriers and facilitators of implementation is crucial before introducing this kind of programme on a larger scale. The aim of this study was to explore the views of teachers and parents regarding factors influencing the implementation of a school-based parental support programme to promote physical activity and healthy diet.METHODS: An inductive qualitative method was used to explore the experiences and views of teachers and parents involved in the programme. A group discussion was held with three teachers, and semi-structured interviews were conducted with 14 parents. Data were analysed using qualitative content analysis.RESULTS: Clear communication on roles and responsibilities was identified as an overarching theme, emphasising the importance of clear information and well-functioning cooperation between project management, schools and parents when implementing the programme in a school setting. Five categories at a manifest level described aspects influencing the implementation: 1) 'The programme' underlining the importance of flexibility and feed-back; 2) 'the school' referring to management and work routines; 3) 'family conditions', implying various life situations; 4) 'group dynamics' dealing with attitudes among children and parents; and 5) 'the surrounding community' including accessibility and attitudes within society.CONCLUSIONS: When implementing a parental support programme in a school setting it is important to facilitate communication and clearly define the division of responsibilities between project management, schools and parents. This emphasises the need for managerial support, and a professional prevention support system.
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| 5. |
- Bergström, Helena, et al.
(författare)
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Managing Implementation of a Parental Support Programme for Obesity Prevention in the School Context : The Importance of Creating Commitment in an Overburdened Work Situation, a Qualitative Study.
- 2020
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Ingår i: Journal of Primary Prevention. - : Springer. - 0278-095X .- 1573-6547. ; 41:3, s. 191-209
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Tidskriftsartikel (refereegranskat)abstract
- Health-related behaviours in children can be influenced by parental support programmes. The aim of this study was to explore barriers to and facilitators for the implementation of a parental support programme to promote physical activity and healthy dietary habits in a school context. We explored the views and experiences of 17 coordinating school nurses, non-coordinating school nurses, and school principals. We based the interview guide on the Consolidated Framework for Implementation Research. We held four focus group discussions with coordinating and non-coordinating school nurses, and conducted three individual interviews with school principals. We analysed data inductively using qualitative content analysis. We identified "Creating commitment in an overburdened work situation" as an overarching theme, emphasising the high workload in schools and the importance of creating commitment, by giving support to and including staff in the implementation process. We also identified barriers to and facilitators of implementation within four categories: (1) community and organisational factors, (2) a matter of priority, (3) implementation support, and (4) implementation process. When implementing a parental support programme to promote physical activity and healthy dietary habits for 5- to 7-year-old children in the school context, it is important to create commitment among school staff and school nurses. The implementation can be facilitated by political support and additional funding, external guidance, use of pre-existing resources, integration of the programme into school routines, a clearly structured manual, and appointment of a multidisciplinary team. The results of this study should provide useful guidance for the implementation of similar health promotion interventions in the school context.
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| 6. |
- Bjersand, Kathrine, et al.
(författare)
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Ex vivo assessment of cancer drug sensitivity in epithelial ovarian cancer and its association with histopathological type, treatment history and clinical outcome
- 2022
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 61:4
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial ovarian cancer (EOC) is divided into type I and type II based on histopathological features. Type I is clinically more indolent, but also less sensitive to chemotherapy, compared with type II. The basis for this difference is not fully clarified. The present study investigated the pattern of drug activity in type I and type II EOC for standard cytotoxic drugs and recently introduced tyrosine kinase inhibitors (TKIs), and assessed the association with treatment history and clinical outcome. Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short-term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross-resistance and association with progression-free survival (PFS). Out of 128 EOC samples, 120 samples, including 21 type I and 99 type II, were successfully analyzed using FMCA. Patients with EOC type I had a significantly longer PFS time than patients with EOC type II (P=0.01). In line with clinical experience, EOC type I samples were generally more resistant than type II samples to both standard cytotoxic drugs and the TKIs, reaching statistical significance for cisplatin (P=0.03) and dasatinib (P=0.002). A similar pattern was noted in samples from patients treated with chemotherapy prior to surgery compared with treatment-naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross-resistance between drugs was in most cases statistically significant yet moderate in degree (r<0.5). The clinically observed relative drug resistance of EOC type I, as well as in patients previously treated, is at least partly due to mechanisms in the tumor cells. These mechanisms seemingly also encompass kinase inhibitors. Ex vivo assessment of drug activity is suggested to have a role in the optimization of drug therapy in EOC.
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| 7. |
- Bobjer, Johannes, et al.
(författare)
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Location of retroperitoneal lymph node metastases in upper tract urothelial carcinoma : results from a prospective lymph node mapping study
- 2023
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 57, s. 37-44
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC).Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND).Design, setting, and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node–positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates.Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used.Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates.Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited.Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.
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| 8. |
- Brändstedt, Johan, et al.
(författare)
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Urosymphyseal fistula after pelvic radiotherapy in a tertial referral centre : a rare entity with significant comorbidity requiring multidisciplinary management
- 2023
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 58, s. 4-10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To report population-based clinical presentation and outcomes in patients with urosymphyseal fistula (USF) after pelvic radiotherapy (RT).Patients and methods: A retrospective chart review was performed in 33 consecutive patients diagnosed with suspicion of USF in a tertial referral center from 2014–2022 to ascertain information about diagnostic delay, clinical presentation, precipitating causes, treatments received and outcomes during the median 22 months follow-up. Out of 33 consecutive patients with suspicion of USF, one female with vesicovaginal fistula, one patient developing RT-associated bladder angiosarcoma, four patients with short follow-up (<3 months), and three patients that during chart review not were considered to have a USF were excluded.Results: In all, 24 males with a median age of 77 years were diagnosed with USF. Local pain was the predominating symptom in 17/24 (71%) patients. Endourologic manipulations preceded the diagnosis of USF in 16 patients. Five patients had a diagnostic delay of more than 3 months. At diagnosis, 20/24 patients had radiological signs of osteomyelitis, and five had a concomitant rectourethral fistula. Due to comorbidity, five patients were not amenable to any other interventions than urinary catheter or suprapubic tube in conjunction with long-term antibiotics, of which three died from infections related to the USF. Out of the remaining 19 patients receiving some form of urinary diversion, five had recurrent osteomyelitis, of which four did not undergo cystectomy in conjunction with surgery for the USF.Conclusions: Urethral endourologic interventions in patients previously subjected to pelvic RT should be performed cautiously.
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| 9. |
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| 10. |
- Dahgam, Santosh, et al.
(författare)
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Haplotypes of the inducible nitric oxide synthase gene are strongly associated with exhaled nitric oxide levels in adults: a population-based study
- 2014
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 51:7, s. 449-454
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous genetic association studies have reported evidence for association of single-nucleotide polymorphisms (SNPs) in the NOS2 gene, encoding inducible nitric oxide synthase (iNOS), to variation in levels of fractional exhaled nitric oxide (FENO) in children and adults. In this study, we evaluated 10 SNPs in the region of chromosome 17 from 26.07Mb to 26.13Mb to further understand the contribution of NOS2 to variation in levels of FENO. Methods In a cohort of 5912 adults 25-75years of age, we investigated the relationship between NOS2 haplotypes and FENO, and effect modification by asthma. Results Seven common (frequency 5%) haplotypes (H1-H7) were inferred from all possible haplotype combinations. One haplotype (H3) was significantly associated with lower levels of FENO: -5.8% (95% CI -9.8 to -1.7; p=0.006) compared with the most common baseline haplotype H1. Two haplotypes (H5 and H6) were significantly associated with higher levels of FENO: +10.7% (95% CI 5.0 to 16.7; p=0.0002) and +14.9% (95% CI 10.6 to 19.3; p=7.8x10(-13)), respectively. The effect of haplotype H3 was mainly seen in subjects with asthma (-21.6% (95% CI -33.5 to -5.9)) and was not significant in subjects without asthma (-4.2% (95% CI -8.4 to 0.2)). The p value for interaction between H3 and asthma status was 0.004. Conclusions Our findings suggest that several common haplotypes in the NOS2 gene contribute to variation in FENO in adults. We also saw some evidence of effect modification by asthma status on haplotype H3.
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