| 1. |
- Aust, Birgit, et al.
(författare)
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The Danish national return-to-work program - aims, content, and design of the process and effect evaluation
- 2012
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 38:2, s. 120-133
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Tidskriftsartikel (refereegranskat)abstract
- The Danish national return-to-work (RTW) program aims to improve the management of municipal sickness benefit in Denmark. A study is currently ongoing to evaluate the RTW program. The purpose of this article is to describe the study protocol. The program includes 21 municipalities encompassing approximately 19 500 working-age adults on long-term sickness absence, regardless of reason for sickness absence or employment status. It consists of three core elements: (i) establishment of multidisciplinary RTW teams, (ii) introduction of standardized workability assessments and sickness absence management procedures, and (iii) a comprehensive training course for the RTW teams. The effect evaluation is based on a parallel group randomized trial and a stratified cluster-controlled trial and focuses on register-based primary outcomes-duration of sickness absence and RTW and questionnaire-based secondary outcomes such as health and workability. The process evaluation utilizes questionnaires, interviews, and municipal data. The effect evaluation tests whether participants in the intervention have a (i) shorter duration of full-time sickness absence, (ii) longer time until recurrent long-term sickness absence, (iii) faster full RTW, (iv) more positive development in health, workability, pain, and sleep; it also tests whether the program is (v) cost-effective. The process evaluation investigates: (i) whether the expected target population is reached; (ii) if the program is implemented as intended; (iii) how the beneficiaries, the RTW teams, and the external stakeholders experience the program; and (iv) whether contextual factors influenced the implementation. The program has the potential to contribute markedly to lowering human and economic costs and increasing labor force supply. First results will be available in 2013. The trial registrations are ISRCTN43004323, and ISRCTN51445682.
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| 2. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 3. |
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| 4. |
- Nielsen, Karina, et al.
(författare)
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Workplace resources to improve both employee well-being and performance : A systematic review and meta-analysis
- 2017
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Ingår i: Work & Stress. - : Informa UK Limited. - 0267-8373 .- 1464-5335. ; 31:2, s. 101-120
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Forskningsöversikt (refereegranskat)abstract
- Organisations are becoming increasingly aware of the importance of employees in gaining and maintaining competitive advantage. The happy worker-productive worker thesis suggests that workers who experience high levels of well-being also perform well and vice versa; however, organisations need to know how to ensure such happy and productive workers. The present review and meta-analysis identifies workplace resources at the individual, the group, the leader, and the organisational levels that are related to both employee well-being and organisational performance. We examine which types of resources are most important in predicting both employee well-being and performance. We identified 84 quantitative studies published in print and online from 2003 to November 2015. Resources at either of the four levels were related to both employee well-being and performance. We found no significant differences in employee well-being and organisational performance between the four levels of workplace resources, suggesting that interventions may focus on any of these levels. Cross-sectional studies showed stronger relationships with well-being and performance than longitudinal studies. Studies using objective performance ratings provided weaker relationships between resources and performance than self-rated and leader/third-party-rated studies.
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| 5. |
- Antonescu, Irina E, et al.
(författare)
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The Permeation of Acamprosate Is Predominantly Caused by Paracellular Diffusion across Caco-2 Cell Monolayers : A Paracellular Modeling Approach
- 2019
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 16:11, s. 4636-4650
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Tidskriftsartikel (refereegranskat)abstract
- In drug development, estimating fraction absorbed (Fa) in man for permeability-limited compounds is important but challenging. To model Fa of such compounds from apparent permeabilities (Papp) across filter-grown Caco-2 cell monolayers, it is central to elucidate the intestinal permeation mechanism(s) of the compound. The present study aims to refine a computational permeability model to investigate the relative contribution of paracellular and transcellular routes to the Papp across Caco-2 monolayers of the permeability-limited compound acamprosate having a bioavailability of ∼11%. The Papp values of acamprosate and of several paracellular marker molecules were measured. These Papp values were used to refine system-specific parameters of the Caco-2 monolayers, that is, paracellular pore radius, pore capacity, and potential drop. The refined parameters were subsequently used as an input in modeling the permeability (Pmodeled) of the tested compounds using mathematical models collected from two published permeability models. The experimental data show that acamprosate Papp across Caco-2 monolayers is low and similar in both transport directions. The obtained acamprosate Papp, 1.56 ± 0.28 × 10-7 cm·s-1, is similar to the Papp of molecular markers for paracellular permeability, namely, mannitol (2.72 ± 0.24 × 10-7 cm·s-1), lucifer yellow (1.80 ± 0.35 × 10-7 cm·s-1), and fluorescein (2.10 ± 0.28 × 10-7 cm·s-1), and lower than that of atenolol (7.32 ± 0.60 × 10-7 cm·s-1; mean ± SEM, n = 3-6), while the end-point amount of acamprosate internalized by the cell monolayer, Qmonolayer, was lower than that of mannitol. Acamprosate did not influence the barrier function of the monolayers since it altered neither the Papp of the three paracellular markers nor the transepithelial electrical resistance (TEER) of the cell monolayer. The Pmodeled for all the paracellular markers and acamprosate was dominated by the Ppara component and matched the experimentally obtained Papp. Furthermore, acamprosate did not inhibit the uptake of probe substrates for solute carriers PEPT1, TAUT, PAT1, EAAT1, B0,+AT/rBAT, OATP2B1, and ASBT expressed in Caco-2 cells. Thus, the Pmodeled estimated well Ppara, and the paracellular route appears to be the predominant mechanism for acamprosate Papp across Caco-2 monolayers, while the alternative transcellular routes, mediated by passive diffusion or carriers, are suggested to only play insignificant roles.
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| 6. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
- 2023
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Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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| 7. |
- Brandão, Andreia, et al.
(författare)
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The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
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| 8. |
- Brem, Jürgen, et al.
(författare)
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Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
- 2022
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Ingår i: Nature Chemistry. - : Springer Nature. - 1755-4330 .- 1755-4349. ; 14:1, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.
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| 9. |
- Burisch, Johan, et al.
(författare)
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Disease course of inflammatory bowel disease unclassified in a European population-based inception cohort : an Epi-IBD study
- 2019
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Ingår i: Journal of Gastroenterology and Hepatology. - : John Wiley & Sons. - 0815-9319 .- 1440-1746. ; 34:6, s. 996-1003
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following five years.METHODS: The Epi-IBD study is a prospective population-based cohort of 1,289 IBD patients diagnosed in centres across Europe. Clinical data were captured prospectively throughout the follow-up period.RESULTS: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n=20, 71%) or CD (n=8, 29%) after a median of six months (IQR: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n=6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n=107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU.CONCLUSIONS: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after five years of follow-up. One in four patients with IBDU eventually were classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.
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| 10. |
- Burisch, Johan, et al.
(författare)
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Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study
- 2019
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 13:2, s. 198-208
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.
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| 11. |
- Canton, Sophie, et al.
(författare)
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Toward Highlighting the Ultrafast Electron Transfer Dynamics at the Optically Dark Sites of Photocatalysts
- 2013
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Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 4:11, s. 1972-1976
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Tidskriftsartikel (refereegranskat)abstract
- Building a detailed understanding of the structure function relationship is a crucial step in the optimization of molecular photocatalysts employed in water splitting schemes. The optically dark nature of their active sites usually prevents a complete mapping of the photoinduced dynamics. In this work, transient X-ray absorption spectroscopy highlights the electronic and geometric changes that affect such a center in a bimetallic model complex. Upon selective excitation of the ruthenium chromophore, the cobalt moiety is reduced through intramolecular electron transfer and undergoes a spin flip accompanied by an average bond elongation of 0.20 +/- 0.03 angstrom. The analysis is supported by simulations based on density functional theory structures (B3LYP*/TZVP) and FEFF 9.0 multiple scattering calculations. More generally, these results exemplify the large potential of the technique for tracking elusive intermediates that impart unique functionalities in photochemical devices.
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| 12. |
- Canton, Sophie, et al.
(författare)
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Visualizing the non-equilibrium dynamics of photoinduced intramolecular electron transfer with femtosecond X-ray pulses.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Ultrafast photoinduced electron transfer preceding energy equilibration still poses many experimental and conceptual challenges to the optimization of photoconversion since an atomic-scale description has so far been beyond reach. Here we combine femtosecond transient optical absorption spectroscopy with ultrafast X-ray emission spectroscopy and diffuse X-ray scattering at the SACLA facility to track the non-equilibrated electronic and structural dynamics within a bimetallic donor-acceptor complex that contains an optically dark centre. Exploiting the 100-fold increase in temporal resolution as compared with storage ring facilities, these measurements constitute the first X-ray-based visualization of a non-equilibrated intramolecular electron transfer process over large interatomic distances. Experimental and theoretical results establish that mediation through electronically excited molecular states is a key mechanistic feature. The present study demonstrates the extensive potential of femtosecond X-ray techniques as diagnostics of non-adiabatic electron transfer processes in synthetic and biological systems, and some directions for future studies, are outlined.
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| 13. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 14. |
- Hasson, Henna, et al.
(författare)
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Are We All in the Same Boat? : The Role of Perceptual Distance in Organizational Health Interventions
- 2016
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Ingår i: Stress and Health. - : Wiley. - 1532-3005 .- 1532-2998. ; 32:4, s. 294-303
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Tidskriftsartikel (refereegranskat)abstract
- The study investigates how agreement between leaders' and their team's perceptions influence intervention outcomes in a leadership-training intervention aimed at improving organizational learning. Agreement, i.e. perceptual distance was calculated for the organizational learning dimensions at baseline. Changes in the dimensions from pre-intervention to post-intervention were evaluated using polynomial regression analysis with response surface analysis. The general pattern of the results indicated that the organizational learning improved when leaders and their teams agreed on the level of organizational learning prior to the intervention. The improvement was greatest when the leader's and the team's perceptions at baseline were aligned and high rather than aligned and low. The least beneficial scenario was when the leader's perceptions were higher than the team's perceptions. These results give insights into the importance of comparing leaders' and their team's perceptions in intervention research. Polynomial regression analyses with response surface methodology allow three-dimensional examination of relationship between two predictor variables and an outcome. This contributes with knowledge on how combination of predictor variables may affect outcome and allows studies of potential non-linearity relating to the outcome. Future studies could use these methods in process evaluation of interventions.
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| 15. |
- Heath, Alicia K, et al.
(författare)
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Soft Drink and Juice Consumption and Renal Cell Carcinoma Incidence and Mortality in the European Prospective Investigation into Cancer and Nutrition
- 2021
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - : American Association for Cancer Research. - 1538-7755 .- 1055-9965. ; 30:6, s. 1270-1274
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC).METHODS: A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991-2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks.RESULTS: A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment = 1.03; 95% CI, 0.97-1.09), total soft drinks (HR = 1.01; 95% CI, 0.98-1.05), sugar-sweetened soft drinks (HR = 0.99; 95% CI, 0.94-1.05), or artificially sweetened soft drinks (HR = 1.02; 95% CI, 0.96-1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97-1.16; 1.03, 0.98-1.09; 0.97, 0.89-1.07; and 1.06, 0.99-1.14, respectively).CONCLUSIONS: Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity.IMPACT: Soft drink and juice intakes are unlikely to play an independent role in RCC development or mortality.
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| 16. |
- Hindy, George, et al.
(författare)
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Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis
- 2022
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 132:24, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- People with kidney disease are disproportionately affected by atherosclerosis for unclear reasons. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived mediator of kidney disease, levels of which are strongly associated with cardiovascular outcomes. We assessed suPAR’s pathogenic involvement in atherosclerosis using epidemiologic, genetic, and experimental approaches. We found serum suPAR levels to be predictive of coronary artery calcification and cardiovascular events in 5,406 participants without known coronary disease. In a genome-wide association meta-analysis including over 25,000 individuals, we identified a missense variant in the plasminogen activator, urokinase receptor (PLAUR) gene (rs4760), confirmed experimentally to lead to higher suPAR levels. Mendelian randomization analysis in the UK Biobank using rs4760 indicated a causal association between genetically predicted suPAR levels and atherosclerotic phenotypes. In an experimental model of atherosclerosis, proprotein convertase subtilisin/kexin–9 (Pcsk9) transfection in mice overexpressing suPAR (suPARTg) led to substantially increased atherosclerotic plaques with necrotic cores and macrophage infiltration compared with those in WT mice, despite similar cholesterol levels. Prior to induction of atherosclerosis, aortas of suPARTg mice excreted higher levels of CCL2 and had higher monocyte counts compared with WT aortas. Aortic and circulating suPARTg monocytes exhibited a proinflammatory profile and enhanced chemotaxis. These findings characterize suPAR as a pathogenic factor for atherosclerosis acting at least partially through modulation of monocyte function.
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| 17. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 18. |
- Lundmark, Robert, et al.
(författare)
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No leader is an island : contextual antecedents to line managers' constructive and destructive leadership during an organizational intervention
- 2020
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Ingår i: International Journal of Workplace Health Management. - : Emerald Group Publishing Limited. - 1753-8351 .- 1753-836X. ; 13:2, s. 173-188
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Line managers can make or break organizational interventions, yet little is known about what makes them turn in either direction. As leadership does not occur in a vacuum, it has been suggested that the organizational context plays an important role. Building on the intervention and leadership literature, we examine if span of control and employee readiness for change are related to line managers' leadership during an organizational intervention.Design/methodology/approach: Leadership is studied in terms of intervention-specific constructive, as well as passive and active forms of destructive, leadership behaviors. As a sample, we use employees (N = 172) from 37 groups working at a process industry plant. Multilevel analyses over two time points, with both survey and organizational register data were used to analyze the data.Findings: The results revealed that span of control was negatively related to constructive leadership and positively related to passive destructive leadership during the intervention. Employee readiness for change was positively related to constructive leadership, and negatively related to both passive and active destructive leadership.Practical implications: Our findings suggest that contextual factors need to be assessed and considered if we want line managers to engage in constructive rather than destructive leadership during interventions.Originality/value: The present study is the first to address line managers' making or breaking of organizational interventions by examining the influence of context on both their destructive and constructive leadership.
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| 19. |
- Madsen, Karina M., et al.
(författare)
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Linking Genotype and Phenotype of Saccharomyces cerevisiae Strains Reveals Metabolic Engineering Targets and Leads to Triterpene Hyper-Producers
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 6:3, s. e14763-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMetabolic engineering is an attractive approach in order to improve the microbial production of drugs. Triterpenes is a chemically diverse class of compounds and many among them are of interest from a human health perspective. A systematic experimental or computational survey of all feasible gene modifications to determine the genotype yielding the optimal triterpene production phenotype is a laborious and time-consuming process.Methodology/Principal FindingsBased on the recent genome-wide sequencing of Saccharomyces cerevisiae CEN.PK 113-7D and its phenotypic differences with the S288C strain, we implemented a strategy for the construction of a β-amyrin production platform. The genes Erg8, Erg9 and HFA1 contained non-silent SNPs that were computationally analyzed to evaluate the changes that cause in the respective protein structures. Subsequently, Erg8, Erg9 and HFA1 were correlated with the increased levels of ergosterol and fatty acids in CEN.PK 113-7D and single, double, and triple gene over-expression strains were constructed.ConclusionsThe six out of seven gene over-expression constructs had a considerable impact on both ergosterol and β-amyrin production. In the case of β-amyrin formation the triple over-expression construct exhibited a nearly 500% increase over the control strain making our metabolic engineering strategy the most successful design of triterpene microbial producers.
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| 20. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 21. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 22. |
- Mavaddat, Nasim, et al.
(författare)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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| 23. |
- Moslemi, Camous, et al.
(författare)
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A large cohort study of the effects of Lewis, ABO, 13 other blood groups, and secretor status on COVID-19 susceptibility, severity, and long COVID-19
- 2023
-
Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 63:1, s. 47-58
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have reported Blood type O to confer a lower risk of SARS-CoV-2 infection, while secretor status and other blood groups have been suspected to have a similar effect as well. Study design and methods: To determine whether any other blood groups influence testing positive for SARS-CoV-2, COVID-19 severity, or prolonged COVID-19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt. Of these, 36,068 tested positive for SARS-CoV-2 whereas 614,088 tested negative between 2020-02-17 and 2021-08-04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates. Results: The Lewis blood group antigen Lea displayed strongly reduced SARS-CoV-2 susceptibility OR 0.85 CI[0.79–0.93] p <.001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06–1.14] p <.001, 1.17 CI[1.14–1.2] p <.001, and 1.2 CI[1.14–1.26] p <.001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID-19 hospitalization or long COVID-19. No secretor status associations were found. Discussion: This study uncovers a new association to reduced SARS-CoV-2 susceptibility for Lewis type Lea and confirms the previous link to blood group O. The new association to Lea could be explained by a link between mucosal microbiome and SARS-CoV-2.
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| 24. |
- Moslemi, Camous, et al.
(författare)
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Genetic prediction of 33 blood group phenotypes using an existing genotype dataset
- 2023
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Ingår i: Transfusion. - 0041-1132. ; 63:12, s. 2297-2310
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate blood type data are essential for blood bank management, but due to costs, few of 43 blood group systems are routinely determined in Danish blood banks. However, a more comprehensive dataset of blood types is useful in scenarios such as rare blood type allocation. We aimed to investigate the viability and accuracy of predicting blood types by leveraging an existing dataset of imputed genotypes for two cohorts of approximately 90,000 each (Danish Blood Donor Study and Copenhagen Biobank) and present a more comprehensive overview of blood types for our Danish donor cohort. Study Design and Methods: Blood types were predicted from genome array data using known variant determinants. Prediction accuracy was confirmed by comparing with preexisting serological blood types. The Vel blood group was used to test the viability of using genetic prediction to narrow down the list of candidate donors with rare blood types. Results: Predicted phenotypes showed a high balanced accuracy >99.5% in most cases: A, B, C/c, Coa/Cob, Doa/Dob, E/e, Jka/Jkb, Kna/Knb, Kpa/Kpb, M/N, S/s, Sda, Se, and Yta/Ytb, while some performed slightly worse: Fya/Fyb, K/k, Lua/Lub, and Vel ~99%–98% and CW and P1 ~96%. Genetic prediction identified 70 potential Vel negatives in our cohort, 64 of whom were confirmed correct using polymerase chain reaction (negative predictive value: 91.5%). Discussion: High genetic prediction accuracy in most blood groups demonstrated the viability of generating blood types using preexisting genotype data at no cost and successfully narrowed the pool of potential individuals with the rare Vel-negative phenotype from 180,000 to 70.
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| 25. |
- Nielsen, Karina, et al.
(författare)
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Comparing working conditions and physical and psychological health complaints in four occupational groups working in female-dominated workplaces
- 2009
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Ingår i: International Archives of Occupational and Environmental Health. - 0340-0131 .- 1432-1246. - 0340-0131 ; 82:10, s. 1229-1239
-
Tidskriftsartikel (refereegranskat)abstract
- Background Dominant theories of working conditions and their effects on poor employee health have been criticized for failing to consider how psychosocial factors interact and how such relationships may differ across occupational groups. Goal This paper examines the associations between psychosocial factors and physical and psychological health complaints while at the same time taking into account differences between occupational groups in female-dominated professions. Method Four female-dominated occupational groups were included: nurses, health care assistants, cleaners, and dairy industry workers. The relationships between influence, emotional and quantitative demands, social support, back pain, and behavioural stress were examined using structural equation modelling. Results Results supported a group-specific model: the overall pattern remained the same across groups while psychosocial factors had different impacts on poor health and interacted differently across groups. The results also indicated links between psychosocial factors and poor physical health. Conclusion The study confirmed the importance of differentiating between female-dominated occupations rather than talking about women's working conditions as such. The study also emphasized the importance of considering psychosocial risk factors when examining physical health, in this case back pain.
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| 26. |
- Nielsen, Karina, et al.
(författare)
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In the Eye of the Beholder : How Self-Other Agreements Influence Leadership Training Outcomes as Perceived by Leaders and Their Followers
- 2022
-
Ingår i: Journal of business and psychology. - : Springer. - 0889-3268 .- 1573-353X. ; 37, s. 73-90
-
Tidskriftsartikel (refereegranskat)abstract
- Based on Yammarino and Atwater's self-other agreement typology of leaders, we explored whether leaders' and followers' agreement influenced their ratings of leadership behaviors after training where leaders received multi-source feedback to stimulate behavior change. We used a prospective study design including 68 leaders and 237 followers from a Swedish forest industry company. Leaders underwent training to increase their transformational leadership and contingent reward styles and reduce management-by-exception passive and laissez-faire leadership. We found that self-other agreement influences followers and leaders reporting changes in leadership styles. We also found that although some leader types were perceived to improve their leadership behaviors, leaders and followers reported differential patterns in which types of leaders improved the most. Our results have important implications for how feedback should be used to support training to achieve changes in leadership styles.
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| 27. |
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| 28. |
- Nielsen, Karina, et al.
(författare)
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What about me? The impact of employee change agents’ person-role fit on their job satisfaction during organisational change
- 2021
-
Ingår i: Work & Stress. - : Informa UK Limited. - 0267-8373 .- 1464-5335. ; 35:1, s. 57-73
-
Tidskriftsartikel (refereegranskat)abstract
- Organisational changes do not always achieve their intended outcomes and have been found to have negative consequences on employee wellbeing. It has been argued that this is because change processes need to support employees adopting the change. In the present study, we study an organisational change aimed to improve employee capacity to provide eHealth services. To support the change, employees were appointed change agents and trained in running seminars to facilitate the change. Using Person-Job fit as our theoretical framework, we proposed that change agents who perceived they possess the necessary competencies to deal with the change agent role (Person-Role fit) would feel more efficacious in this role and be more satisfied with their jobs post-change. We suggested that role-specific self-efficacy mediated the relationship between person-role fit and job satisfaction and that the most dissatisfied pre-change would perceive the greatest improvements in job satisfaction. Using a paired t-test, repeated measures analyses and mixed methods mediation testing, we found that change agents (N = 110) reported increased job satisfaction post-change. Change agents who were dissatisfied with their jobs pre-change, but perceived a good fit to the change agent role, reported the greatest improvements in job satisfaction. No significant results were found for self-efficacy.
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| 29. |
- Perez-Gonzalez, Pablo G., et al.
(författare)
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Life beyond 30 : Probing the-20 < M (UV) <-17 Luminosity Function at 8 < z < 13 with the NIRCam Parallel Field of the MIRI Deep Survey
- 2023
-
Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 951:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present the ultraviolet luminosity function and an estimate of the cosmic star formation rate density at 8 < z < 13 derived from deep NIRCam observations taken in parallel with the MIRI Deep Survey of the Hubble Ultra Deep Field (HUDF), NIRCam covering the parallel field 2. Our deep (40 hr) NIRCam observations reach an F277W magnitude of 30.8 (5 & sigma;), more than 2 mag deeper than JWST public data sets already analyzed to find high-redshift galaxies. We select a sample of 44 z > 8 galaxy candidates based on their dropout nature in the F115W and/or F150W filters, a high probability for their photometric redshifts, estimated with three different codes, being at z > 8, good fits based on & chi; (2) calculations, and predominant solutions compared to z < 8 alternatives. We find mild evolution in the luminosity function from z & SIM; 13 to z & SIM; 8, i.e., only a small increase in the average number density of & SIM;0.2 dex, while the faint-end slope and absolute magnitude of the knee remain approximately constant, with values & alpha; = - 2.2 & PLUSMN; 0.1, and M * = - 20.8 & PLUSMN; 0.2 mag. Comparing our results with the predictions of state-of-the-art galaxy evolution models, we find two main results: (1) a slower increase with time in the cosmic star formation rate density compared to a steeper rise predicted by models; (2) nearly a factor of 10 higher star formation activity concentrated in scales around 2 kpc in galaxies with stellar masses & SIM;10(8) M (& ODOT;) during the first 350 Myr of the universe, z & SIM; 12, with models matching better the luminosity density observational estimations & SIM;150 Myr later, by z & SIM; 9.
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| 30. |
- Rasmussen, Anne Ankerstjerne, et al.
(författare)
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Gender differences in patient-reported outcomes in patients with acute myocardial infarction
- 2022
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Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press. - 1474-5151 .- 1873-1953. ; 21:8, s. 772-781
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Women report worse health-related patient-reported outcomes (PROs) compared with men following acute myocardial infarction (AMI). However, this association is not well established when accounting for demographic and clinical patient characteristics at discharge. This knowledge is essential for clinicians when planning individualised care for patients following AMI. The aim of this study is to examine whether gender is associated with health-related PROs at discharge from a Danish heart centre, combining PROs with data from the national health and administrative registries. Methods and results A cross-sectional study of 2131 patients with AMI discharged from a Danish heart centre responding to the following health-related PRO questionnaires: the Health-survey Short-Form-12 (SF-12), generating a physical component summary (PCS) and a mental component summary (MCS) score; the HeartQoL, providing a global, emotional, and physical score; the EuroQol five-dimensional questionnaire (EQ-5D-5L) and the EQ visual analogue scale (EQ VAS); the Hospital Anxiety and Depression Scale (HADS), generating an anxiety and depression score (HADS-A and HADS-D); the Edmonton Symptom Assessment Scale (ESAS); the Brief Illness Perception Questionnaire (B-IPQ). Patient-reported outcomes were linked to registry-based information adjusting for potential demographic and clinical confounding factors. In adjusted regression models, women reported worse health-related PROs compared with men in SF-12 PCS and SF-12 MCS, HeartQoL global, the HeartQoL emotional and HeartQoL physical score, EQ-5D-5L and EQ VAS, the HADS-A, ESAS, and in six out of eight B-IPQ items. Conclusions Women reported worse health-related PROs compared with men. Health-related PROs have the potential to be further investigated to facilitate a more individualised healthcare follow-up after AMI.
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| 31. |
- Roczniewska, Marta, et al.
(författare)
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Simple roads to failure, complex paths to success : an evaluation of conditions explaining perceived fit of an organizational occupational health intervention
- 2024
-
Ingår i: Applied Psychology. - : John Wiley & Sons. - 0269-994X .- 1464-0597. ; 73:3, s. 1103-1130
-
Tidskriftsartikel (refereegranskat)abstract
- Organizational occupational health interventions (OOHIs) that are perceived by employees as relevant for their workplace are more likely to be implemented successfully, yet little is known about the conditions that produce such perceptions. This study identifies the conditions that create a perception among employees that an intervention fits their organization as well as the conditions that result in low levels of perceived fit. We used two-wave data from 40 Danish preschools that underwent a quasi-experimental OOHI. Perceived fit was assessed through employee ratings at follow-up, while survey responses from implementation team members at five time points were used to assess four context and 14 process factors. The results of a coincidence analysis showed that high levels of perceived fit were achieved through two paths. Each path consisted of a lack of co-occurring changes together with either very high levels of managerial support (path_1) or a combination of implementation team role clarity, staff involvement, and team learning (path_2). In contrast, low levels of perceived fit were brought about by single factors: limited leader support, low degree of role clarity, or concurrent organizational changes. The findings reveal the complexity involved in implementing OOHIs and offer insights into reasons they may fail.
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| 32. |
- Simonsen Abildgaard, Johan, et al.
(författare)
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Can job insecurity be managed? Evaluating an organizational-level intervention addressing the negative effects of restructuring
- 2018
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Ingår i: Work & Stress. - : Informa UK Limited. - 0267-8373 .- 1464-5335. ; 32:2, s. 105-123
-
Tidskriftsartikel (refereegranskat)abstract
- Although downsizing and reorganisation are recognised as serious threats to the psychological well-being of employees, intervention strategies for addressing these events are limited. This study evaluated the effects of a participatory organisational-level intervention in which employees and managers chose to address the psychosocial consequences, specifically job insecurity, of restructuring. The intervention was conducted among postal service letter carriers in Denmark and was evaluated based on quantitative and qualitative data. Using interviews (N = 24) and observations, the programme theory of the intervention and to what extent the intervention had been implemented were assessed. Using survey data (N = 238), repeated measures ANOVAs were conducted to test for differences in the development of job insecurity between the intervention group and a comparison group. The results indicate that the intervention group had a significantly smaller increase in one dimension of job insecurity as compared to the comparison group. Therefore, we conclude that employees’ experiencing of job insecurity, which typically follows in the wake of restructuring, can be addressed by planned efforts at the workplace level.
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| 33. |
- Skotte, Line, et al.
(författare)
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Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
- 2022
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:2, s. 555-568
-
Tidskriftsartikel (refereegranskat)abstract
- Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 × 10-10. Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (rg = 0.39, P = 1.68 × 10-4). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.
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| 34. |
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| 35. |
- Stenling, Andreas, 1982-, et al.
(författare)
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Need-supportive leadership behaviors and sickness absence among employees : the mediating role of basic psychological need satisfaction
- 2024
-
Ingår i: Applied Psychology. - : John Wiley & Sons. - 0269-994X .- 1464-0597.
-
Tidskriftsartikel (refereegranskat)abstract
- Research exploring relationships between leadership behaviors and sickness absence is scarce. Grounded in self-determination theory (SDT), the present study examined: (i) the relationship between need-supportive leadership and sickness absence; and (ii) whether satisfaction of the basic psychological needs mediates the relationship between need-supportive leadership and sickness absence. Municipal employees (n = 347, 78% women, age span = 19–66 years) provided baseline data on perceived need-supportive leadership and reported their need satisfaction at work 8 weeks later. Sickness absence data were obtained from municipality records. Two-part regression models showed that need-supportive leadership was negatively associated with sick days (b = −0.28, 95% CI [−0.45, −0.11]). Need-supportive leadership had an indirect effect on the number of sick days through a composite score of need satisfaction (ab = −1.96, 95% CI [−5.11, −0.12]). Mediation models with each need separately indicated that autonomy (ab = −2.12, 95% CI [−5.33, −0.23]) and relatedness (ab = −1.33, 95% CI [−3.41, −0.11]) mediated the relationship between need-supportive leadership and number of sick days. Need-supportive leadership and need satisfaction at work may function as protective factors that provide followers with opportunities to deal with symptoms of ill health and reduce the risk of prolonged sickness absence.
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| 36. |
- Tafvelin, Susanne, 1975-, et al.
(författare)
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Employees' and line managers' active involvement in participatory organizational interventions : Examining direct, reversed, and reciprocal effects on well-being
- 2019
-
Ingår i: Stress and Health. - : John Wiley & Sons. - 1532-3005 .- 1532-2998. ; 35:1, s. 69-80
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Tidskriftsartikel (refereegranskat)abstract
- This study examined how employee participation and perceptions of line managers' support during a participatory organizational intervention were related to well-being over time. Although previous studies suggest that employees' and managers' active involvement in participatory organizational interventions may be related to well-being, little is known about the temporal aspects, such as at which time during the intervention these factors matter, or possible reciprocal effects. Building on conservation of resources theory, we tested hypotheses concerning direct, reversed, and reciprocal relationships between employee participation and perceptions of line manager support in relation to well-being. We used a four-wave panel design consisting of 159 hospital workers. Cross-lagged analyses showed that perceived line managers' support in the initiation and active phase was related to participation in the active phase. Participation in the initiation and active phase was related to well-being in the active and sustained phase, respectively. Results also revealed that participation in the initiation phase was related to perceived line managers' support in the active phase, which in turn predicted participation in the active phase, which translated into job satisfaction in the sustained phase supporting reversed and reciprocal effects in the form of resource caravans. Theoretical implications for research and practice are discussed.
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| 37. |
- Tafvelin, Susanne, 1975-, et al.
(författare)
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Integrating a transfer perspective into evaluations of leadership training
- 2021
-
Ingår i: Leadership & Organization Development Journal. - : Emerald Group Publishing Limited. - 0143-7739 .- 1472-5347. ; 42:6, s. 856-868
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: In previous studies, outcomes of leadership training have varied, with some studies suggesting large effects and others small. Although the transfer of training literature suggests a number of factors that influence training outcomes, this knowledge has seldom been used when evaluating the outcomes of leadership training. The purpose of the present study is therefore to examine how factors related to transfer of training influence outcomes of leadership training.Design/methodology/approach: In the present research, follower-rated outcomes of a leadership training program in Denmark (N = 298) was examined from a transfer of training perspective.Findings: Using Baldwin and Ford's transfer of training model as a framework, analyses revealed that leaders' utility reactions (i.e. perception of usefulness) and learning were linked to transfer of training. In addition, leaders' perceptions of transfer were associated with post-intervention follower-rated transformational leadership and collective self-efficacy.Practical implications: Making sure that leaders find the training useful for their everyday activities (i.e. positive utility reactions) and that they have time to learn the training content is important to enable transfer and for leaders to use trained skills back at work.Originality/value: The findings indicate the importance of understanding how leaders' perception of training content influences leadership training outcomes and that these perceptions need to be a part of the evaluation of leadership training. In addition, the findings suggest that factors predicting transfer of leadership training differ from other types of training.
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| 38. |
- Tafvelin, Susanne, 1975-, et al.
(författare)
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Leading well is a matter of resources : Leader vigour and peer support augments the relationship between transformational leadership and burnout
- 2019
-
Ingår i: Work & Stress. - : TAYLOR & FRANCIS LTD. - 0267-8373 .- 1464-5335. ; 33:2, s. 156-172
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Tidskriftsartikel (refereegranskat)abstract
- Although studies suggest that transformational leaders play an important role in employee health and well-being, the relationship between transformational leadership and employee burnout remains unclear. One reason may be that moderators may play an important role. Building on conservation of resources theory, we examined if leaders' perceptions of internal and external resources in terms of vigour and peer support augmented the relationship between transformational leadership and employee burnout in a sample of municipality workers and their leaders in Sweden (N = 217). Multilevel analyses over two time points revealed that both vigour and peer support enhance this relationship, such that when leaders experience high levels of vigour or peer support, the negative relationship between transformational leadership behaviours and employee burnout was strengthened. Our findings suggest that both personal and contextual resources may help leaders to better engage in transformational leadership, which is important in order to protect employees from burning out.
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| 39. |
- Tafvelin, Susanne, 1975-
(författare)
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The Transformational Leadership Process : Antecedents, Mechanisms, and Outcomes in the Social Services
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Social service organizations have changed dramatically during the last decade in an effort to increase effectiveness and control. This has placed new demands on those in leadership roles, and the need for knowledge of how to lead these transformed organizations has increased. Transformational leadership is a leadership model based on vision and empowerment, one suggested to increase both employee effectiveness and well-being, but the usefulness of this model in the public sector has been questioned. The general aim of this thesis is therefore to increase our understanding of the transformational leadership process in the context of social service organizations by investigating factors that explain when and why transformational leadership emerges and is effective. Questionnaire data from social service employees as well as interview data from managers were used in three empirical studies. Results from Studies 1 & 2 show that transformational leadership is positively associated with employee outcomes including commitment, role clarity, and well-being. Factors that might influence the effectiveness of transformational leadership were addressed in Study 1. It was found that leader continuity enhanced the effect of transformational leadership on role clarity and commitment, indicating that it takes time before transformational leaders actually have an effect on employees. Furthermore, co-worker support enhanced the effect on commitment, reflecting the role of followers in the transformational leadership process. The way in which transformational leaders influence employees was examined in Study 2, and climate for innovation mediated the relationship between transformational leadership and well-being both cross-sectionally and one year later. Finally, organizational factors that may hinder the emergence of transformational leadership were addressed in Study 3, and newly recruited managers were interviewed during their first year of leadership. Eight hindering factors in the organization to exhibit transformational leadership were identified, including the organizational structure, ongoing change, and the leaders’ working conditions. In all, this thesis has demonstrated the usefulness of transformational leadership in social services in terms of being associated with employee positive attitudes and well-being, and has also identified factors that may both help and hinder the transformational leadership process in this context.
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| 40. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 41. |
- von Thiele Schwarz, Ulrica, 1975-, et al.
(författare)
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How to design, implement and evaluate organizational interventions for maximum impact : the Sigtuna Principles
- 2021
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Ingår i: European Journal of Work and Organizational Psychology. - Abingdon : Routledge. - 1359-432X .- 1464-0643. ; 30:3, s. 415-427
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Tidskriftsartikel (refereegranskat)abstract
- Research on organizational interventions needs to meet the objectives of both researchers and participating organizations. This duality means that real-world impact has to be considered throughout the research process, simultaneously addressing both scientific rigour and practical relevance. This discussion paper aims to offer a set of principles, grounded in knowledge from various disciplines that can guide researchers in designing, implementing, and evaluating organizational interventions. Inspired by Mode 2 knowledge production, the principles were developed through a transdisciplinary, participatory and iterative process where practitioners and academics were invited to develop, refine and validate the principles. The process resulted in 10 principles: 1) Ensure active engagement and participation among key stakeholders; 2) Understand the situation (starting points and objectives); 3) Align the intervention with existing organizational objectives; 4) Explicate the program logic; 5) Prioritize intervention activities based on effort-gain balance; 6) Work with existing practices, processes, and mindsets; 7) Iteratively observe, reflect, and adapt; 8) Develop organizational learning capabilities; 9) Evaluate the interaction between intervention, process, and context; and 10) Transfer knowledge beyond the specific organization. The principles suggest how the design, implementation, and evaluation of organizational interventions can be researched in a way that maximizes both practical and scientific impact. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 42. |
- von Thiele Schwarz, Ulrica, 1975-, et al.
(författare)
-
Using kaizen to improve employee well-being : Results from two organizational intervention studies
- 2017
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Ingår i: Human Relations. - : SAGE Publications. - 0018-7267 .- 1741-282X. ; 70:8, s. 966-993
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Tidskriftsartikel (refereegranskat)abstract
- Participatory intervention approaches that are embedded in existing organizational structures may improve the efficiency and effectiveness of organizational interventions, but concrete tools are lacking. In the present article, we use a realist evaluation approach to explore the role of kaizen, a lean tool for participatory continuous improvement, in improving employee well-being in two cluster-randomized, controlled participatory intervention studies. Case 1 is from the Danish Postal Service, where kaizen boards were used to implement action plans. The results of multi-group structural equation modeling showed that kaizen served as a mechanism that increased the level of awareness of and capacity to manage psychosocial issues, which, in turn, predicted increased job satisfaction and mental health. Case 2 is from a regional hospital in Sweden that integrated occupational health processes with a pre-existing kaizen system. Multi-group structural equation modeling revealed that, in the intervention group, kaizen work predicted better integration of organizational and employee objectives after 12 months, which, in turn, predicted increased job satisfaction and decreased discomfort at 24 months. The findings suggest that participatory and structured problem-solving approaches that are familiar and visual to employees can facilitate organizational interventions.
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| 43. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 44. |
- Watts, Eleanor L., et al.
(författare)
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Observational and genetic associations between cardiorespiratory fitness and cancer : a UK Biobank and international consortia study
- 2024
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130, s. 114-124
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association of fitness with cancer risk is not clear.Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.
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