| 1. |
- Gusarova, Viktoria, et al.
(författare)
-
Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.
|
|
| 2. |
- Ellinor, Patrick T., et al.
(författare)
-
Meta-analysis identifies six new susceptibility loci for atrial fibrillation
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:6, s. 88-670
-
Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
|
|
| 3. |
- Allentoft, Morten E., et al.
(författare)
-
Population genomics of post-glacial western Eurasia
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
-
Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
|
|
| 4. |
- Bergström, Anders, et al.
(författare)
-
Origins and genetic legacy of prehistoric dogs
- 2020
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6516, s. 557-563
-
Tidskriftsartikel (refereegranskat)abstract
- Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
|
|
| 5. |
- Nettleton, Jennifer A, et al.
(författare)
-
Gene x dietary pattern interactions in obesity : analysis of up to 68 317 adults of European ancestry
- 2015
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 24:16, s. 4728-4738
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
|
|
| 6. |
- Nettleton, Jennifer A., et al.
(författare)
-
Meta-Analysis Investigating Associations Between Healthy Diet and Fasting Glucose and Insulin Levels and Modification by Loci Associated With Glucose Homeostasis in Data From 15 Cohorts
- 2013
-
Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 177:2, s. 103-115
-
Forskningsöversikt (refereegranskat)abstract
- Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 US and European cohort studies comprising 51,289 persons without diabetes to test whether genotype and diet interact to influence FG or FI concentration. We constructed a diet score using study-specific quartile rankings for intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (favorable) and red/processed meats, sweets, sugared beverages, and fried potatoes (unfavorable). We used linear regression within studies, followed by inverse-variance-weighted meta-analysis, to quantify 1) associations of diet score with FG and FI levels and 2) interactions of diet score with 16 FG-associated loci and 2 FI-associated loci. Diet score (per unit increase) was inversely associated with FG ( 0.004 mmol/L, 95 confidence interval: 0.005, 0.003) and FI ( 0.008 ln-pmol/L, 95 confidence interval: 0.009, 0.007) levels after adjustment for demographic factors, lifestyle, and body mass index. Genotype variation at the studied loci did not modify these associations. Healthier diets were associated with lower FG and FI concentrations regardless of genotype at previously replicated FG- and FI-associated loci. Studies focusing on genomic regions that do not yield highly statistically significant associations from main-effect genome-wide association studies may be more fruitful in identifying diet-gene interactions.
|
|
| 7. |
- Padmanabhan, Sandosh, et al.
(författare)
-
Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
- 2010
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
-
Tidskriftsartikel (refereegranskat)abstract
- Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
|
|
| 8. |
- Pattaro, Cristian, et al.
(författare)
-
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
|
|
| 9. |
- Smith, Gustav, et al.
(författare)
-
Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure
- 2016
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5
-
Tidskriftsartikel (refereegranskat)abstract
- Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
|
|
| 10. |
- Al Jebali, Ramsey, et al.
(författare)
-
A helium gas scintillator active target for photoreaction measurements
- 2015
-
Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 51:10
-
Tidskriftsartikel (refereegranskat)abstract
- A multi-cell He gas scintillator active target, designed for the measurement of photoreaction cross sections, is described. The target has four main chambers, giving an overall thickness of 0.103 g/cm(3) at an operating pressure of 2MPa. Scintillations are read out by photomultiplier tubes and the addition of small amounts of N-2 to the He, to shift the scintillation emission from UV to visible, is discussed. First results of measurements at the MAX IV Laboratory tagged-photon facility show that the target has a timing resolution of around 1 ns and can cope well with a high-flux photon beam. The determination of reaction cross sections from target yields relies on a Monte Carlo simulation, which considers scintillation light transport, photodisintegration processes in He-4, background photon interactions in target windows and interactions of the reaction-product particles in the gas and target container. The predictions of this simulation are compared to the measured target response.
|
|
| 11. |
- Allard, Christina, et al.
(författare)
-
Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
-
Annan publikation (populärvet., debatt m.m.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
|
|
| 12. |
- Andersson, Jan O., et al.
(författare)
-
A genomic survey of the fish parasite Spironucleus salmonicida indicates genomic plasticity among diplomonads and significant lateral gene transfer in eukaryote genome evolution
- 2007
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 8, s. 51-
-
Forskningsöversikt (refereegranskat)abstract
- Background: Comparative genomic studies of the mitochondrion-lacking protist group Diplomonadida (diplomonads) has been lacking, although Giardia lamblia has been intensively studied. We have performed a sequence survey project resulting in 2341 expressed sequence tags (EST) corresponding to 853 unique clones, 5275 genome survey sequences (GSS), and eleven finished contigs from the diplomonad fish parasite Spironucleus salmonicida (previously described as S. barkhanus). Results: The analyses revealed a compact genome with few, if any, introns and very short 3′ untranslated regions. Strikingly different patterns of codon usage were observed in genes corresponding to frequently sampled ESTs versus genes poorly sampled, indicating that translational selection is influencing the codon usage of highly expressed genes. Rigorous phylogenomic analyses identified 84 genes - mostly encoding metabolic proteins - that have been acquired by diplomonads or their relatively close ancestors via lateral gene transfer (LGT). Although most acquisitions were from prokaryotes, more than a dozen represent likely transfers of genes between eukaryotic lineages. Many genes that provide novel insights into the genetic basis of the biology and pathogenicity of this parasitic protist were identified including 149 that putatively encode variant-surface cysteine-rich proteins which are candidate virulence factors. A number of genomic properties that distinguish S. salmonicida from its human parasitic relative G. lamblia were identified such as nineteen putative lineage-specific gene acquisitions, distinct mutational biases and codon usage and distinct polyadenylation signals. Conclusion: Our results highlight the power of comparative genomic studies to yield insights into the biology of parasitic protists and the evolution of their genomes, and suggest that genetic exchange between distantly-related protist lineages may be occurring at an appreciable rate in eukaryote genome evolution.
|
|
| 13. |
- Backman, Annica C., 1972-, et al.
(författare)
-
Embodying person-centred being and doing : leading towards person-centred care in nursing homes as narrated by managers
- 2020
-
Ingår i: Journal of Clinical Nursing. - : John Wiley & Sons. - 0962-1067 .- 1365-2702. ; 29:1-2, s. 172-183
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS AND OBJECTIVES: To explore how managers describe leading towards person-centred care in Swedish nursing homes.BACKGROUND: Although a growing body of research knowledge exists highlighting the importance of leadership to promote person-centred care, studies focused on nursing home managers' own descriptions of leading their staff towards providing person-centred care is lacking.DESIGN: Descriptive interview study. COREQ guidelines have been applied.METHODS: The study consisted of semi-structured interviews with 12 nursing home managers within 11 highly person-centred nursing homes purposively selected from a nationwide survey of nursing homes in Sweden. Data collection was performed in April 2017, and the data were analysed using content analysis.RESULTS: Leading towards person-centred care involved a main category; embodying person-centred being and doing, with four related categories: operationalising person-centred objectives; promoting a person-centred atmosphere; maximising person-centred team potential; and optimising person-centred support structures.CONCLUSIONS: The findings revealed that leading towards person-centred care was described as having a personal understanding of the PCC concept and how to translate it into practice, and maximising the potential of and providing support to care staff, within a trustful and innovative work place. The findings also describe how managers co-ordinate several aspects of care simultaneously, such as facilitating, evaluating and refining the translation of person-centred philosophy into synchronised care actions.RELEVANCE TO CLINICAL PRACTICE: The findings can be used to inspire nursing home leaders' practices and may serve as a framework for implementing person-centred care within facilities. A reasonable implication of these findings is that if organisations are committed to person-centred care provision, care may need to be organised in a way that enables managers to be present on the units, to enact these strategies and lead person-centred care.
|
|
| 14. |
- Backman, Annica C., 1972-, et al.
(författare)
-
Exploring the impact of nursing home managers' leadership on staff job satisfaction, health and intention to leave in nursing homes
- 2023
-
Ingår i: Journal of Clinical Nursing. - : John Wiley & Sons. - 0962-1067 .- 1365-2702.
-
Tidskriftsartikel (refereegranskat)abstract
- Aims and ObjectivesTo explore the impact of nursing home leadership and staffing characteristics on staff job satisfaction, health and intention to leave. BackgroundThe number of older people has outpaced growth in the nursing home workforce worldwide. Identifying predictors with the potential to positively impact staff job satisfaction, health and intentions to leave are important. Leadership of the nursing home manager can be one such predictor. DesignCross-sectional design. MethodsA sample of 2985 direct care staff in 190 nursing homes in 43 randomly selected municipalities in Sweden completed surveys on leadership, job satisfaction, self-rated health and intention to leave (response rate 52%). Descriptive statistics and Generalised Estimating Equations were conducted. The STROBE reporting checklist was applied. ResultsNursing home managers' leadership was positively related to job satisfaction, self-rated health and low intention to leave. Lower staff educational levels were related to poorer health and lower job satisfaction. ConclusionsNursing home leadership plays a significant role in the job satisfaction, self-reported health and intention to leave of direct care staff. Low education levels among staff seem to negatively influence staff health and job satisfaction, suggesting that educational initiatives for less-educated staff could be beneficial for improving staff health and job satisfaction. Relevance to clinical practiceManagers seeking to improve staff job satisfaction can consider how they support, coach and provide feedback. Recognising staff achievement at work can contribute to high job satisfaction. One important implication for managers is to offer continuing education to staff with lower or no education, given the large amount of uneducated direct care workers in aged care and the impact this may have on staff job satisfaction and health. No patient or public contributionNo patient or public contribution was required to outcome measures in this study. Direct care staff and managers contributed with data.
|
|
| 15. |
|
|
| 16. |
- Backman, Annica C., 1972-, et al.
(författare)
-
Longitudinal changes in nursing home leadership, direct care staff job strain and social support in Swedish nursing homes : findings from the U-AGE SWENIS study
- 2023
-
Ingår i: International Journal of Older People Nursing. - : John Wiley & Sons. - 1748-3735 .- 1748-3743. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Promoting healthy work environment as a manager in nursing homes is important to safeguard staff health and well-being as well as care quality when facing increasing demands. The impact of leadership on staff work environment needs further exploration.Objectives: To describe longitudinal changes in nursing home leadership, direct care staff characteristics, job strain and social support.Methods: This study has a repeated cross-sectional design, a five-year follow-up study. Nursing home staff in 181 corresponding units (n = 1253 in 2014 and n = 1176 in 2019) completed surveys about leadership, staff job strain and social support in a five-year follow-up study. Descriptive and regression analyses were conducted.Results: A higher degree of leadership defined by coaching and providing direct feedback to care staff, handling conflicts in a constructive way and having control of the clinical work, was significantly associated with a lower degree of job strain and a higher degree of social support among staff, with stronger associations at follow-up. The proportion of enrolled nurses increased significantly at follow-up.Conclusions: Leadership is increasingly important for staff work environment, especially in times of increased workload and decreasing collegiality and deteriorating work atmosphere at work. Implications for Practice: Stakeholder and policy makers in nursing home care may reflect on how managers' leadership is prioritised in these environments because such leadership is associated with staff job strain and social support. Managers striving to improve the work situation of staff may consider their own role and allow flexibility in how and when the work can be performed.
|
|
| 17. |
- Backman, Annica C., 1972-, et al.
(författare)
-
Moving between doing and being-Meanings of person-centredness as narrated by nursing home managers. A phenomenological hermeneutical study
- 2024
-
Ingår i: NURSING OPEN. - : John Wiley & Sons. - 2054-1058. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- AimThis study aimed to illuminate meanings of person-centredness as narrated by nursing home managers in nursing homes rated as highly person-centred.DesignA phenomenological hermeneutical approach was used.MethodsTwelve nursing home managers in 11 highly person-centred nursing homes in 7 municipalities in Sweden were included in this interview study. The findings were interpreted, reflected and discussed through the lens of Ricoeur.ResultsMeanings of person-centredness could be understand as moving between doing and being through knowing, sensing, sharing and giving for person-centredness. These aspects contributed via knowledge, understanding, interaction and action that involved doing for and being with older persons through these caring dimensions. By moving between doing for, being with and being part of the overall nursing home narrative, knowing, sensing, sharing and giving could support the persons' identity in different ways. This may also contribute to sense-making, preserving dignity and promoting self-esteem when aiming to provide a good life for older persons in nursing homes, within an ever-present ethical frame.No Patient or Public ContributionThis study illuminated meanings of person-centredness as narrated by nursing home managers. No patient of public contribution was investigated.
|
|
| 18. |
- Backman, Annica C., 1972-, et al.
(författare)
-
The influence of nursing home managers’ leadership on person-centred care and stress of conscience: A cross-sectional study
- 2021
-
Ingår i: BMC Nursing. - : BioMed Central. - 1472-6955. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Leadership and stress are common concepts in nursing, and this study explores empirically the connection between leadership and stress of conscience in the context of aged care practice. Previous literature has shown that when staff are unable to carry out their ethical liabilities towards the residents, feelings of guilt may occur among staff, which may be an expression of stress of conscience. Although leadership has been described as crucial for staff’s work perceptions of stress as well as for person-centred practices, the influence of nursing home managers’ leadership on stress of conscience among staff and person-centred practices is still not fully explored. This study attempts to address that knowledge gap by exploring the relationship between leadership, person-centred care, and stress of conscience.Methods: This study was based on a cross-sectional national survey of 2985 staff and their managers in 190 nursing homes throughout Sweden. Descriptive statistics and regression modelling were used to explore associations.Results: Leadership was associated with a higher degree of person-centred care and less stress of conscience. A higher degree of person-centred care was also associated with less stress of conscience. The results also showed that leadership as well as person-centred care were individually associated with lower levels of stress of conscience when adjusting for potential confounders.Conclusion: Nursing home managers’ leadership was significantly associated with less staff stress of conscience and more person-centred care. This indicates that a leadership most prominently characterised by coaching and giving feedback, relying on staff and handling conflicts constructively, experimenting with new ideas, and controlling work individually can contribute to less staff stress as well as higher degree of person-centred care provision.
|
|
| 19. |
- Backman, Annica C., 1972-, et al.
(författare)
-
The significance of nursing home managers' leadership : longitudinal changes, characteristics and qualifications for perceived leadership, person-centredness and climate
- 2022
-
Ingår i: Journal of Clinical Nursing. - : John Wiley & Sons. - 0962-1067 .- 1365-2702. ; 31:9-10, s. 1377-1388
-
Tidskriftsartikel (refereegranskat)abstract
- Aims and objectives: The aim was to explore changes in nursing home managers' leadership, person-centred care and psychosocial climate comparing matched units in a five-year follow-up and to explore the significance of managers' educational qualifications and the ownership of nursing homes for perceived leadership, person-centred care and psychosocial climate in the follow-up data.Background: Leadership has been described as crucial for person-centred care and psychosocial climate even though longitudinal data are lacking. The significance of managerial leadership, its characteristics, managerial qualifications and ownership of nursing homes for perceived leadership, person-centred care and psychosocial climate also needs further exploration.Design: Repeated cross-sectional study.Methods: This study used valid and reliable measures of leadership, person-centred care, psychosocial climate and demographic variables collected from managers and staff n = 3605 in 2014 and n = 2985 in 2019. Descriptive and regression analyses were used. The STROBE checklist was used in reporting this study.Results: Leadership was still positively significantly associated to person-centred care in a five-year follow-up, but no changes in strength were seen. Leadership was still positively significantly associated with psychosocial climate, with stronger associations at follow-up. Six leadership characteristics increased over time. It was also shown that a targeted education for nursing home managers was positively associated with person-centred care.Conclusions: Leadership is still pivotal for person-centred care and psychosocial climate. Knowledge of nursing home managers' leadership, characteristics and educational qualifications of significance for person-centred delivery provides important insights when striving to improve such services.Relevance to clinical practice: The findings can be used for management and clinical practice development initiatives because it was shown that nursing home managers' leadership is vital to person-centred care practices and improves the climate for both staff and residents in these environments.
|
|
| 20. |
- Backman, Annica, et al.
(författare)
-
Characteristics of highly rated leadership in nursing homes using item response theory
- 2017
-
Ingår i: Journal of Advanced Nursing. - : John Wiley & Sons. - 0309-2402 .- 1365-2648. ; 73:12, s. 2903-2913
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To identify characteristics of highly rated leadership in nursing homes. Background: An ageing population entails fundamental social, economic and organizational challenges for future aged care. Knowledge is limited of both specific leadership behaviours and organizational and managerial characteristics which have an impact on the leadership of contemporary nursing home care. Design: Cross-sectional. Method: From 290 municipalities, 60 were randomly selected and 35 agreed to participate, providing a sample of 3605 direct-care staff employed in 169 Swedish nursing homes. The staff assessed their managers' (n = 191) leadership behaviours using the Leadership Behaviour Questionnaire. Data were collected from November 2013 - September 2014, and the study was completed in November 2016. A two-parameter item response theory approach and regression analyses were used to identify specific characteristics of highly rated leadership. Results: Five specific behaviours of highly rated nursing home leadership were identified; that the manager: experiments with new ideas; controls work closely; relies on subordinates; coaches and gives direct feedback; and handles conflicts constructively. The regression analyses revealed that managers with social work backgrounds and privately run homes were significantly associated with higher leadership ratings. Conclusion: This study highlights the five most important leadership behaviours that characterize those nursing home managers rated highest in terms of leadership. Managers in privately run nursing homes and managers with social work backgrounds were associated with higher leadership ratings. Further work is needed to explore these behaviours and factors predictive of higher leadership ratings.
|
|
| 21. |
|
|
| 22. |
- Backman, Annica, 1972-, et al.
(författare)
-
Job strain in nursing homes : exploring the impact of leadership
- 2018
-
Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 27:7-8, s. 1552-1560
-
Tidskriftsartikel (refereegranskat)abstract
- Aims and objectives: To explore the association between nursing home managers' leadership, job strain and social support as perceived by direct care staff in nursing homes.Background: It is well known that aged care staff experience high levels of job strain, and that aged care staff experiencing job strain are exposed to increased risk for adverse health effects. Leadership styles have been associated with job strain in the literature; however, the impact of perceived leadership on staff job strain and social support has not been clarified within nursing home contexts.Design: This study had a cross‐sectional design.Methods: Participating staff (n = 3,605) completed surveys which included questions about staff characteristics, valid and reliable measures of nursing home managers' leadership, perceived job strain and social support. Statistical analyses of correlations and multiple regression analysis with interaction terms were conducted.Results: Nursing home managers' leadership were significantly associated with lower level of job strain and higher level of social support among direct care staff. A multiple regression analysis including an interaction term indicated individual and joint effects of nursing home managers' leadership and social support on job strain.Conclusions: Nursing home managers' leadership and social support were both individually and in combination associated with staff perception of lesser job strain. Thus, nursing home managers' leadership are beneficial for the working situation and strain of staff.Relevance to clinical practice: Promoting a supporting work environment through leadership is an important implication for nursing home managers as it can influence staff perception of job strain and social support within the unit. By providing leadership, offering support and strategies towards a healthy work environment, nursing home managers can buffer adverse health effects among staff.
|
|
| 23. |
- Backman, Annica, 1972-
(författare)
-
Leadership : person-centred care and the work situation of staff in Swedish nursing homes
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Swedish nursing home managers, who constitute the empirical focus of this thesis, hold overall operational responsibility for the nursing homes, which includes the care of residents, direct care staff and work environment. Aged care organisations are also expected to provide person-centred care. Working towards a person-centred approach poses new demands and leads to challenges for leaders, and there is currently limited knowledge of what characterises leadership that promotes a person-centred approach. In addition, an ongoing demographic shift in the aged care workforce entails further challenges, as the proportion of professional workers is decreasing. Leading a healthy work environment is therefore important for ensuring and protecting staff health. Based on this, it is important to explore nursing home managers’ leadership in relation to person-centred care and the work situation of staff.Aim: The overall aim was to explore leadership in relation to person-centred care and the work situation of staff in Swedish nursing homes.Methods: This thesis is based on data from two data collections. First, it includes cross-sectional baseline data from a national inventory of health and care in Swedish nursing homes (SWENIS) collected in 2013-2014. The SWENIS dataset consists of a sample of staff n=3605 from 169 nursing homes in 35 municipalities, and nursing home managers n=191. The second data collection consists of 11 semi-structured interviews with 12 nursing home managers in highly person-centred nursing homes that already participated in SWENIS. Data were explored via descriptive statistics, simple and multiple regression analyses, and qualitative content analysis.Results: Leadership was positively associated with person-centred care and psychosocial climate. Highly rated leadership behaviors’ among nursing homes managers was characterized by experimenting with new ideas, controlling work closely, relying on his/her subordinates, coaching and giving direct feedback, and handling conflicts constructively. Leading person-centred care can be outlined by four leadership processes: embodying person-centred being and doing; promoting a person-centred atmosphere; maximizing person-centred team potential and optimising person-centred support structures. Leadership was also positively associated with social support and negatively associated with job strain. Further, the variation in leadership was to a very small extent explained by the nursing home managers’ educational qualification, operational form of the nursing home and the number of employees in a unit.Conclusions: All findings point in the same direction: that leadership, as it is characterized and measured in this thesis, is significantly associated with person-centred care provision as well as with the work situation of staff. This suggests that nursing managers have a central leadership role in developing and supporting person-centred care practices, and also in creating a healthy work environment. The results also highlight five specific leadership behaviours that are most characteristic of highly rated leadership, thereby adding concrete descriptions of behaviours to the literature on existing leadership theories. The findings also include four central processes for leading towards person-centred care in nursing homes. Taken together, it seems important for managers to translate the person-centred philosophy into actions and to promote an atmosphere pervaded by innovation and trust, in which cultural change is enhanced by positive cultural bearers. Utilizing the overall knowledge and competencies among staff and potentiating care teams was also considered important for leading person-centred care, along with optimising supportive structures for supporting and maintaining person-centred care. If aged care organisations are to be committed to person-centred care, an important implication seems to be to organise nursing homes in a way that allows nursing home managers to be close and present in clinical practice and actively lead towards person-centred care. The findings of this thesis contribute to our understanding of leadership in relation to person-centre care and the work situation of staff. These findings can be used in leadership educations and nursing curriculum. Longitudinal studies would be valuable for following leadership, person-centred care and the work situation of staff over time.
|
|
| 24. |
- Backman, Annica, 1972-, et al.
(författare)
-
Leading towards person-centred care – Nursing home managers' experiences of leading person-centred care in highly person-centred Swedish nursing homes
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background:Although a growing body of research knowledge exists highlighting the importance of leadership for person-centred care, studies focused on nursing home managers’ own descriptions of leading their staff to provide person-centred care is lacking. This study aims to explore the process of nursing home managers’ leading person-centred care in Swedish nursing homes.Methods:The methods of the study consisted of semi-structured interviews with 12 nursing home managers within 11 highly person-centred nursing homes purposively selected from a national wide survey of nursing homes in Sweden. A qualitative content analysis was performed for data analyses.Results:The study revealed that the leading person-centred care in nursing homes can be outlined as comprising four processes: Embodying person-centred being and doing; promoting a person-centred atmosphere; maximizing person-centred team potential; and finally, optimizing person-centred support structures.Conclusion:This study contributes to the literature by providing concrete descriptions of how person-centred care can be operationalised and supported in everyday practice by the leadership of nursing home managers. The study is significant in that it provides evidence on how the provision of person centred care can be facilitated by managers and the important role they play in developing and maintaining this philosophy of care within nursing homes.
|
|
| 25. |
- Backman, Annica, et al.
(författare)
-
Towards person-centredness in aged-care : exploring the impact of leadership
- 2016
-
Ingår i: Journal of Nursing Management. - : Hindawi Limited. - 0966-0429 .- 1365-2834. ; 24:6, s. 766-774
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore the association between leadership behaviours among managers in aged care, and person‐centredness of care and the psychosocial climate.Background: Theory suggests that leadership is important for improving person‐centredness in aged care, however, empirical evidence is lacking.Methods: A cross‐sectional design was used to collect data from Swedish aged care staff (n = 3661). Valid and reliable questionnaires assessing leadership behaviours, person‐centeredness of care and the psychosocial climate were used. Data were analysed using multiple linear regression including interaction terms.Results: Leadership behaviours were significantly related to the person‐centredness of care and the psychosocial climate. The level of person‐centredness of care moderated the impact of leadership on the psychosocial climate.Conclusions and implications for nursing management: The leadership behaviour of managers significantly impacts person‐centred care practice and contributes to the psychosocial climate for both staff and residents in aged care. This study is the first empirically to confirm that middle managers have a central leadership role in developing and supporting person‐centred care practice, thereby creating a positive psychosocial climate and high quality care.
|
|
| 26. |
- Baxter, Rebecca, et al.
(författare)
-
The thriving of older people assessment scale : Psychometric evaluation and short‐form development
- 2019
-
Ingår i: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 75:12, s. 3831-3843
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate the psychometric properties and performance of the 32‐item Thriving of Older People Assessment Scale (TOPAS) and to explore reduction into a short‐form.Background: The 32‐item TOPAS has been used in studies of place‐related well‐being as a positive measure in long‐term care to assess nursing home resident thriving; however, item redundancy has not previously been explored.Design: Cross‐sectional.Method: Staff members completed the 32‐item TOPAS as proxy‐raters for a random sample of Swedish nursing home residents (N = 4,831) between November 2013 and September 2014. Reliability analysis, exploratory factor analysis and item response theory‐based analysis were undertaken. Items were systematically identified for reduction using statistical and theoretical analysis. Correlation testing, means comparison and model fit evaluation confirmed scale equivalence.Results: Psychometric properties of the 32‐item TOPAS were satisfactory and several items were identified for scale reduction. The proposed short‐form TOPAS exhibited a high level of internal consistency (α=0.90) and strong correlation (r=0.98) to the original scale, while also retaining diversity among items in terms of factor structure and item difficulties.Conclusion: The 32‐item and short‐form TOPAS' indicated sound validity and reliability to measure resident thriving in the nursing home context.Impact: There is a lack of positive life‐world measures for use in nursing homes. The short‐form TOPAS indicated sound validity and reliability to measure resident thriving, providing a feasible measure with enhanced functionality for use in aged care research, assessments and care planning for health promoting purposes in nursing homes.
|
|
| 27. |
- Berg, Anne, 1981-
(författare)
-
Kampen om befolkningen : Den svenska nationsformeringens utveckling och sociopolitiska förutsättningar ca 1780–1860
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to problematize the western type of nation formation by characterizing and explaining the Swedish process of national identity construction during the Age of Revolution. Thus, the thesis sets out to investigate the political-hegemonic process of identity formation, redefinition and struggle between different political forces. In practise, the thesis develops a typology over different ideological identity projects according to their object of identity formation and their political content. Instead of classifying the projects into civic or cultural types of nationalisms, the scheme of official and counter-hegemonic ideological projects are used. The thesis also sets out to explain the character of the process studied. This is done by analyzing the socio-political conditions of existence of the different national ideological projects. This includes their relationship to the state, their social milieus and the social composition of the agents of nationalization. The thesis shows that the Swedish process can be characterized as a constant battle over the population: a battle over the national self-understanding amongst different layers of the population. The explanation of this character has to do with two existing conditions. Firstly, the existence of a state that supported some identity projects and prohibited others. The state produced a sphere of contest by, partially, allowing the establishment of a sphere of political communication. It also acted as an authority by facilitating the different agents with the political language of nationalism as the main arena of social struggle. The other important condition was the increasing economic modernization, which caused both social mobilization and differentiation – the pre-conditions for intra-class conflicts and inter-class conflicts. In the end this thesis argues, in contrast to the modernist theories in the field, which has underpinned the importance of social communication and state- or bourgeois-led cultural integration, that Sweden, as one of the so-called old continuous nations, was not a top-down project during this particular era. It was a project created from the top as well as from below – inside as well as outside the objects of national politics. It is this simultaneousness that is the main feature of identity formation. And, its explanation lies in the emerging liberal class society as a difference- and community-machine. Consequently, the thesis problematizes the common picture of how and why people became nationals in the western states during the great transformation.
|
|
| 28. |
- Betancourt, Lazaro Hiram, et al.
(författare)
-
The human melanoma proteome atlas-Defining the molecular pathology
- 2021
-
Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
-
Tidskriftsartikel (refereegranskat)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
|
|
| 29. |
- Björn, Norlin, 1976-, et al.
(författare)
-
Educational history in the age of apology : The Church of Sweden's "White book" on historical relations to the Sami, the significance of education and scientific complexities in reconciling the past
- 2019
-
Ingår i: Educare. - Malmö : Malmo University Library. - 1653-1868 .- 2004-5190. ; :1, s. 69-95
-
Tidskriftsartikel (refereegranskat)abstract
- Reconciliation processes – wherein governments and other organizations examine their past institutional practices to understand contemporary problems in relation to minorities or indigenous groups – have become a widespread international phenomenon in recent decades. In Sweden, such an ongoing process is the reconciliation work between the Church of Sweden and the Sami. In this process, which recently resulted in the publication of a scholarly anthology (or a “white book”), educational history has come to play a vital part. The present article uses the Church of Sweden’s White Book as an empirical object of study to examine in more detail the role and significance of knowledge of educational history for this specific reconciliation process. By focusing on various scientific complexities and epistemological tensions that tend to arise in these kinds of undertakings, this paper also aims to problematize the white book genre itself as a path to historical knowledge. By doing this, this article’s overall ambition is to contribute to future scholarly work in reconciliation activities, white papers and truth commissions. This study applies a qualitative content analysis and connects theoretically to the growing field of transitional justice research.
|
|
| 30. |
- Brorsson, Caroline, et al.
(författare)
-
A non-synonymous variant in SLC30A8 is not associated with type 1 diabetes in the Danish population
- 2008
-
Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 94:3, s. 386-388
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association scans in type 2 diabetes (T2D) have identified a risk variant, rs13266634 (Arg325Trp), in SLC30A8 on chromosome 8. SLC30A8 encodes a beta-cell specific zinc-ion transporter and rs13266634 has been shown to affect insulin secretion. Recently, autoantibodies for Slc30A8 with high predictive value were demonstrated in individuals with type 1 diabetes (T1 D), making this gene an interesting T1 D candidate gene. We genotyped rs13266634 in 3008 cases and controls and 246 families from Denmark. Association to T1 D could not be demonstrated.
|
|
| 31. |
- Brundin, Malin, et al.
(författare)
-
DNA Binding to hydroxyapatite : a potential mechanism for preservation of microbial DNA
- 2013
-
Ingår i: Journal of Endodontics. - : Elsevier. - 0099-2399 .- 1878-3554. ; 39:2, s. 211-216
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Molecular methods are increasingly being deployed for analysis of the microbial flora in the root canal. Such methods are based on the assumption that recovered DNA is associated with the active endodontic infection, yet paleomicrobiology research is based on the recovery of ancient DNA from centuriesold tooth and bone samples, which points to considerable longevity of the DNA molecule in these tissues. The main component of dentin and bone is the mineral hydroxyapatite. This study assessed DNA binding to hydroxyapatite and whether thiS binding affinity stabilizes the DNA molecule in various media.Methods: DNA was extracted from Fusobacterium nucleatum and added to ceramic hydroxyapatite for 90 minutes. The DNA-bound hydroxyapatite was incubated in different media (ie, water, sera, and DNase I) for up to 3 months. At predetermined intervals, the recovery of detectable DNA was assessed by releasing the DNA from the hydroxyapatite using EDTA and evaluating the presence of DNA by gel electrophoresis and polymerase chain reaction (PCR) amplification.Results: When incubated with hydroxyapatite, nonamplified DNA was detectable after 3 months in water, sera, and DNase I. In contrast, DNA incubated in the same media (without hydroxyapatite) decomposed to levels below the detection level of PCR within 3 weeks, with the exception of DNA in sera in which PCR revealed a weak positive amplification product.Conclusions: These results confirm a specific binding affinity of hydroxyapatite for DNA. Hydroxyapatite-bound DNA is more resistant to decay and less susceptible to degradation by serum and nucleases, which may account for the long-term persistence of DNA in bone and tooth.
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
- Brundin, Malin, et al.
(författare)
-
Preservation of bacterial dna by human dentin
- 2014
-
Ingår i: Journal of Endodontics. - : Elsevier BV. - 0099-2399 .- 1878-3554. ; 40:2, s. 241-245
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The capacity of dentin and collagen to bind DNA and protect against spontaneous and nuclease-induced degradation was evaluated individually and by the incubation of DNA with nuclease-producing bacteria in a mixed culture.METHODS: Extracted Fusobacterium nucleatum DNA was incubated with dentin shavings or collagen for 90 minutes. The DNA-bound substrates were incubated in different media (water, sera, and DNase I) for up to 3 months. Amplifiable DNA was released from dentin using EDTA,or from collagen using proteinase K, and evaluated by polymerase chain reaction (PCR). The stability of dentin-bound DNA was also assessed in a mixed culture (Parvimonas micra and Pseudoramibacter alactolyticus) containing a DNase-producing species, Prevotella intermedia. Samples were analyzed for amplifiable DNA.RESULTS: In water, dentin-bound DNA was recoverable by PCR at 3 months compared with no detectable DNA after 4 weeks in controls (no dentin). DNA bound to collagen was detectable by PCR after 3 months of incubation in water. In 10% human sera, amplifiable DNA was detectable at 3 months when dentin bound and in controls (no dentin). In mixed bacterial culture, dentin-bound DNA was recoverable throughout the experimental period (3 months), compared with no recoverable F. nucleatum DNA within 24 hours in controls (no dentin).CONCLUSIONS: There is a strong binding affinity between DNA and dentin, and between DNA and serum proteins or collagen. These substrates preserve DNA against natural decomposition and protect DNA from nuclease activity, factors that may confound molecular analysis of the endodontic microbiota yet favor paleomicrobiological studies of ancient DNA.
|
|
| 35. |
- Brundin, Malin, 1972-, et al.
(författare)
-
Preservation of Fusobacterium nucleatum and Peptostreptococcus anaerobius DNA after loss of cell viability
- 2015
-
Ingår i: International Endodontic Journal. - : Wiley-Blackwell. - 0143-2885 .- 1365-2591. ; 48:1, s. 37-45
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To investigate whether DNA from two obligate anaerobes, Fusobacterium nucleatum and Peptostreptococcus anaerobius, is recoverable after loss of cell viability induced by air exposure. Methodology: Harvested cultures of F. nucleatum and P. anaerobius were killed by exposure to air and stored in phosphate-buffered saline. Dead cells were incubated aerobically for up to 6 months. Every month, the presence of detectable DNA in the cell pellet and supernatant was assessed by conventional and quantitative PCR. Cell staining techniques were used to characterize the cell wall permeability of air-killed cells. Scanning electron microscopy was used to examine viable, freshly killed and stored cells. Results: With conventional PCR, amplifiable DNA was detectable over 6 months in all samples. Quantitative PCR showed a progressive fall in DNA concentration in nonviable cell pellets and a concomitant rise in DNA concentration in the supernatant. DNA staining showed that some air-killed cells retained an intact cell wall. After storage, SEM of both air-killed species revealed shrivelling of the cells, but some cells of P. anaerobius retained their initial form. Conclusion: Amplifiable DNA from F. nucleatum and P. anaerobius was detectable 6 months after loss of viability. Air-killed anaerobes initially retained their cell form, but cells gradually shriveled over time. The morphological changes were more pronounced with the gram-negative F. nucleatum than the gram-positive P. anaerobius. Over 6 months, there was a gradual increase in cell wall permeability with progressive leakage of DNA. Bacterial DNA was recoverable long after loss of cell viability.
|
|
| 36. |
- Brundin, Malin, 1972-
(författare)
-
Stability of bacterial DNA in relation to microbial detection in teeth
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The fate of DNA from dead cells is an important issue when interpreting results from root canal infections analysed by the PCR technique. DNA from dead bacterial cells is known to be detectable long time after cell death and its stability is dependent on many different factors. This work investigated factors found in the root canal that could affect the recovery of microbial DNA. In an ex vivo experiment, DNA from non-viable gram-positive Enterococcus faecalis was inoculated in instrumented root canals and recovery of DNA was assessed by PCR over a two-year period. DNA was still recoverable two years after cell death in 21/25 teeth. The fate of DNA from the gram-negative bacteria Fusobacterium nucleatum and the gram-positive Peptostreptococcus anaerobius was assessed in vitro. DNA from dead F. nucleatum and P. anaerobius could be detected by PCR six months post cell death even though it was clear that the DNA was released from the cells due to lost of cell wall integrity during the experimental period. The decomposition rate of extracellular DNA was compared to cell-bound and it was evident that DNA still located inside the bacterium was much less prone to decay than extracellular DNA.Free (extracellular) DNA is very prone to decay in a naked form. Binding to minerals is known to protect DNA from degradation. The fate of extracellular DNA was assessed after binding to ceramic hydroxyapatite and dentine. The data showed that free DNA, bound to these materials, was protected from spontaneous decay and from enzymatic decomposition by nucleases.The main conclusions from this thesis were: i) DNA from dead bacteria can be detected by PCR years after cell death ex vivo and in vitro. ii) Cell-bound DNA is less prone to decomposition than extracellular DNA. iii) DNA is released from the bacterium some time after cell death. iv) Extracellular DNA bound to hydroxyapatite or dentine is protected from spontaneous decomposition and enzymatic degradation.
|
|
| 37. |
- Brundin, Malin, et al.
(författare)
-
Starvation response and growth in serum of Fusobacterium nucleatum, Peptostreptococcus anaerobius, Prevotella intermedia, and Pseudoramibacter alactolyticus.
- 2009
-
Ingår i: Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. - : Elsevier BV. - 1079-2104 .- 1528-395X. ; 108:1, s. 129-34
-
Tidskriftsartikel (refereegranskat)abstract
- The microbiota inhabiting the untreated root canal differ markedly from those found in post-treatment disease, yet there is limited information on the microbial characteristics distinguishing the different infections. We hypothesized that starvation survival is a key microbial property in species selection. This study analyzed starvation-survival behavior over 60 days of species representative of the untreated root canal infection: Fusobacterium nucleatum, Peptostreptococcus anaerobius, Prevotella intermedia and Pseudoramibacter alactolyticus. All species did not survive 1 day in water. In 1% serum, the 4 species could not survive beyond 2-3 weeks. They required a high initial cell density and >or=10% serum to survive the observation period. The results highlight a poor starvation-survival capacity of these 4 species compared with species prevalent in post-treatment infection, which are well equipped to endure starvation and survive in low numbers on minimal serum. These findings point to starvation-survival capacity as a selection factor for microbial participation in post-treatment disease.
|
|
| 38. |
- Chambers, John C., et al.
(författare)
-
Genetic loci influencing kidney function and chronic kidney disease
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 373-375
-
Tidskriftsartikel (refereegranskat)abstract
- Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.
|
|
| 39. |
- Corneliusson, Laura, et al.
(författare)
-
'100 metres to the liquor store and 300 meters to the cemetary' : individual, social, environmental and organizational facilitators and barriers to thriving in Swedish sheltered housing models
- 2023
-
Ingår i: Ageing & Society. - : Cambridge University Press. - 0144-686X .- 1469-1779. ; 43:5, s. 1068-1088
-
Tidskriftsartikel (refereegranskat)abstract
- In Sweden, sheltered housing is a housing model that provides accessible apartments with elevated social possibilities for older people. The environment within sheltered housing is expected to support resident health and reduce the need for care services. A previous study has shown that with increasing levels of depressive mood and decreasing levels of self-rated health and functional status, those residing in sheltered housing report higher levels of thriving compared to those ageing in place. Therefore, the aim of this study was to illuminate aspects of sheltered housing that are facilitators and/or barriers to thriving. Seven semi-structured group interviews in five different sheltered housing accommodations in Sweden were conducted between April 2019 and January 2020 (N = 38). The results, analysed using qualitative content analysis and presented in a model developed by Grol and Wensing, illuminate the four main categories of facilitators and barriers to thriving: individual factors, social context, environmental factors and organisational context. The results of this study show that the factors that influence experiences of thriving in sheltered housing are multifaceted and interconnected. Although the supportive environment provided in sheltered housing seems to contribute to thriving, the limited consideration towards the shifting health of residents is a barrier to thriving. The results of this study may assist in implementing tailored interventions to help support thriving on various levels.
|
|
| 40. |
- Corneliusson, Laura, 1989-
(författare)
-
Exploring resident health, wellbeing, and thriving in Swedish sheltered housing
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: As the population of older people is expected to increase in the coming decades, an increase in service demand will likely follow. Aging in place is common in Sweden, but may be associated with loneliness, anxiety, and other negative health effects. Swedish sheltered housing began to emerge around 2008, and was aimed at older people who felt socially isolated, anxious, or unsafe aging in place. Swedish sheltered housing was to be a form of independent housing, providing accommodation with increased opportunities for social participation and accessible spaces, but with no provision of health care services. Despite the emergence of such housing, and policy documents outlining anticipated benefits, the national and international scientific body of knowledge is small.Aim: The overall aim of this thesis was to explore the health, wellbeing and thriving of residents living in Swedish sheltered housing.Methods: This thesis is based on data from two data collections and registry data. The first data collection, the U-Age Sheltered Housing Survey Study, took place between October 2016 and January 2017, and consisted of surveys sent to residents living in Swedish sheltered housing, and to a matched control group. The matching criteria was age, sex and municipality of residence. The sample for the U-Age Sheltered Housing Survey Study consisted of 3,805 individuals: 1, 955 individuals living in sheltered housing, and 1,850 aging in place. The second data collection took place between April 2019 and January 2020, and consisted of semi-structured interviews in five sheltered housing accommodations which had participated in the U-age Sheltered Housing Survey Study. This data collection consisted of a total of seven group interviews with a sample of 38 residents. In addition, to enable longitudinal analyses, registry data on social services resource utilization and mortality was obtained from The Department of Health and Welfare in Sweden and Statistics Sweden. Data were analyzed using descriptive statistics, linear regression analyses with interaction variables, logistic regressions, and qualitative content analysis.Results: Residents living in Swedish sheltered housing generally reported lower self-rated health, lower health-related quality of life, lower functional status, and higher depressive mood, compared to those aging in place. With increasing level of depressive mood, and decreasing levels of self-rated health and functional status, those residing in sheltered housing generally reported higher levels of thriving, compared to those aging in place. A higher proportion of those living in Swedish sheltered housing received home care services, and received on average more home care service hours, compared to those aging in place. Furthermore, a higher proportion of residents living in sheltered housing had relocated to a nursing home and deceased over a 3-year period, compared to those aging in place. Rates of relocation to a nursing home and mortality were higher among those who lived in Swedish sheltered housing and received home care services, compared to those living in Swedish sheltered housing who did not receive home care services. Interviews with residents living in Swedish sheltered housing revealed four different levels to the experienced facilitators and barriers to thriving in Swedish sheltered housing: individual factors, social context, environmental factors and organizational context.Conclusions: There seems to be both a want, and a potential need, for health care related support among residents living in Swedish sheltered housing. Although residents in Swedish sheltered housing reported slightly lower self-rated wellbeing than older people aging in place, differences in wellbeing did not seem to be explained by type of accommodation per se. There do however seem to be aspects in Swedish sheltered housing that support thriving specifically among those with lower levels of health, lower functional status, and higher depressive mood, when compared to those aging in place. It seems possible that thriving in Swedish sheltered housing may be influenced by the interplay of various especially influential aspects, such as, but not limited to, levels of health, the services provided, the experience of the social environment, and the perceived support. Thereby, providing residents of Swedish sheltered housing with more health care related support and information could further support resident health and thriving. The findings of this thesis contribute to the currently limited pool of knowledge on health, wellbeing, and thriving in Swedish sheltered housing, and may assist in developing tailored services, support, and interventions for the demographic residing in this type of housing.
|
|
| 41. |
- Corneliusson, Laura, et al.
(författare)
-
Relocation patterns and predictors of relocation and mortality in Swedish sheltered housing and aging in place
- 2023
-
Ingår i: Journal of Aging and Environment. - : Routledge. - 2689-2618 .- 2689-2626. ; 37:4, s. 386-402
-
Tidskriftsartikel (refereegranskat)abstract
- A reported objective of Swedish sheltered housing is to postpone care needs and relocation. The aim of this study was to describe migration patterns and explore predictors of relocation to nursing homes and mortality, in a sample of residents in sheltered housing and aging in place. To explore longitudinal differences between groups, study data were combined with registry data. The results showed that a higher percentage of residents in sheltered housing had relocated to a nursing home and deceased over a three-year time period, compared to aging in place, implying further interventions may be required to promote health in sheltered housing.
|
|
| 42. |
- Corneliusson, Laura, et al.
(författare)
-
Residing in sheltered housing versus ageing in place : population characteristics, health status and social participation
- 2019
-
Ingår i: Health & Social Care in the Community. - : John Wiley & Sons. - 0966-0410 .- 1365-2524. ; 27:4, s. E313-E322
-
Tidskriftsartikel (refereegranskat)abstract
- Sheltered housing is a housing model that provides accessible apartments with elevated social possibilities for older people, which is expected to increase resident health and independence, reducing the need for care. As previous research on sheltered housing is scarce, the aim of this study was to explore the characteristics, health status and social participation of older people living in sheltered housing, compared to ageing in place. The study utilised baseline data from a matched cohort study survey on a nationally representative total population of residents in all sheltered housings in Sweden, and a matched control group (n = 3,805). The data collection took place between October 2016 and January 2017. The survey assessed functional capability using the Katz ADL and Lawton IADL scale, self-rated health using the EQ5D scale, and depressive mood using the GDS-4 scale. Descriptive statistics, frequencies, mean scores, independent t tests, p-values and effect sizes were utilised to compare the two groups. The results of the study show that older people living in sheltered housing, compared to ageing in place, had lower self-reported health (M = 64.68/70.08, p = <0.001), lower self-reported quality of life (M = 0.73/0.81, p = <0.001), lower functional status concerning activities of daily living (M = 5.19/5.40, p = <0.001), lower functional status concerning instrumental activities of daily living (M = 4.98/5.42 p = <0.001,), and higher probability of depressive mood (M = 0.80/0.58, p = <0.001). The results imply that residents in sheltered housing may have more care needs than those ageing in place. Further longitudinal comparative studies are needed to explore the impact residence in sheltered housing has on resident health and well-being.
|
|
| 43. |
- Corneliusson, Laura, et al.
(författare)
-
Well‐being and Thriving in Sheltered Housing versus Ageing in Place : Results from the U‐Age Sheltered Housing Study
- 2020
-
Ingår i: Journal of Advanced Nursing. - : John Wiley & Sons. - 0309-2402 .- 1365-2648. ; 73:3, s. 856-866
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To explore to what extent type of residence (sheltered housing or ageing in place) contributes to thriving and well-being in older adults, when controlling for age, sex, living alone, being a widow and adjusting for functional status, self-rated health, and depressive mood.Design: A matched cohort study.Methods A self-report survey was sent out to a total population of residents in all sheltered housings in Sweden and a matched control group ageing in place (N = 3,805). The data collection took place between October 2016-January 2017.Results: The interaction analyses related to thriving showed that with increasing level of depressive mood and decreasing levels of self-rated health and functional status, those residing in sheltered housing generally reported higher levels of thriving, as compared with those ageing in place. Well-being was not found to be significantly associated with type of accommodation.Conclusion: There may be features in sheltered housing that are associated with resident thriving especially among individuals with impairments of function, health or mood, although further studies are required to identify these specific features.Impact: This study informs staff and policymakers about thriving and well-being in sheltered housing accommodations. These findings may be used to further the development of sheltered housing accommodations.
|
|
| 44. |
- Dahlgren, David
(författare)
-
Biopharmaceutical aspects of intestinal drug absorption : Regional permeability and absorption-modifying excipients
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Before an orally administered drug reaches the systemic circulation, it has to dissolve in the intestinal fluids, permeate across the intestinal epithelial cell barrier, and pass through the liver. The permeation rate of drug compounds can be low and show regional differences.The thesis had two general aims. The first of these was, to determine and compare regional intestinal permeability values of model compounds in human and dog. The second was to understand the possible effects of absorption-modifying pharmaceutical excipients (AMEs) on the intestinal permeability of the model compounds. The usefulness of several preclinical animal models for predicting the impact of regional intestinal permeability and AMEs in human was also investigated.There was a good correlation between human and dog permeability values in the small intestines for the model compounds. The colon in dog was substantially more permeable than the human colon to the low permeability drug, atenolol. This difference in colonic permeability may have implications for the use of dog as a model species for prediction of human intestinal drug absorption.There were no effects of AMEs on the intestinal permeability of any of the high permeability compounds, in any animal model. In the rat single-pass intestinal perfusion model, there was a substantial increase in permeability of all low permeability drugs, induced by two AMEs, chitosan and SDS. This AME-induced increase was substantially lower in the more in vivo relevant rat and dog intraintestinal bolus models. A shorter AME exposure-time in the rat single-pass intestinal perfusion model (15 vs. 75 min) could, however, predict the result from the bolus studies in rat and dog. This illustrates the impact of intestinal transit and mucosal exposure time on AME effects in vivo. The intestinal luminal conditions and enteric neural activity also had an impact on determinations of drug permeability in the rat single-pass intestinal perfusion model, which can have implications for its in vivo relevance.In summary, this thesis used multiple in vivo models to evaluate the impact of several biopharmaceutical processes on intestinal drug absorption. This has led to an increased understanding of these absorption mechanisms.
|
|
| 45. |
- Dahlgren, David, et al.
(författare)
-
Direct In Vivo Human Intestinal Permeability (P-eff) Determined with Different Clinical Perfusion and Intubation Methods
- 2015
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 104:9, s. 2702-2726
-
Forskningsöversikt (refereegranskat)abstract
- Regional in vivo human intestinal effective permeability (P-eff) is calculated by measuring the disappearance rate of substances during intestinal perfusion. P-eff is the most relevant parameter in the prediction of rate and extent of drug absorption from all parts of the intestine. Today, human intestinal perfusions are not performed on a routine basis in drug development. Therefore, it would be beneficial to increase the accuracy of the in vitro and in silico tools used to evaluate the intestinal P-eff of novel drugs. This review compiles historical P-eff data from 273 individual measurements of 80 substances from 61 studies performed in all parts of the human intestinal tract. These substances include: drugs, monosaccharaides, amino acids, dipeptides, vitamins, steroids, bile acids, ions, fatty acids, and water. The review also discusses the determination and prediction of P-eff using in vitro and in silico methods such as quantitative structure-activity relationship, Caco-2, Ussing chamber, animal intestinal perfusion, and physiologically based pharmacokinetic (PBPK) modeling. Finally, we briefly outline how to acquire accurate human intestinal P-eff data by deconvolution of plasma concentration-time profiles following regional intestinal bolus dosing.
|
|
| 46. |
- Dahlgren, David, et al.
(författare)
-
Effect of absorption-modifying excipients, hypotonicity, and enteric neural activity in an in vivo model for small intestinal transport.
- 2018
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 549:1-2, s. 239-248
-
Tidskriftsartikel (refereegranskat)abstract
- The small intestine mucosal barrier is physiologically regulated by the luminal conditions, where intestinal factors, such as diet and luminal tonicity, can affect mucosal permeability. The intestinal barrier may also be affected by absorption-modifying excipients (AME) in oral drug delivery systems. Currently, there is a gap in the understanding of how AMEs interact with the physiological regulation of intestinal electrolyte transport and fluid flux, and epithelial permeability. Therefore, the objective of this single-pass perfusion study in rat was to investigate the effect of three AMEs on the intestinal mucosal permeability at different luminal tonicities (100, 170, and 290 mOsm). The effect was also evaluated following luminal administration of a nicotinic receptor antagonist, mecamylamine, and after intravenous administration of a COX-2 inhibitor, parecoxib, both of which affect the enteric neural activity involved in physiological regulation of intestinal functions. The effect was evaluated by changes in intestinal lumen-to-blood transport of six model compounds, and blood-to-lumen clearance of 51Cr-EDTA (a mucosal barrier marker). Luminal hypotonicity alone increased the intestinal epithelial transport of 51Cr-EDTA. This effect was potentiated by two AMEs (SDS and caprate) and by parecoxib, while it was reduced by mecamylamine. Consequently, the impact of enteric neural activity and luminal conditions may affect nonclinical determinations of intestinal permeability. In vivo predictions based on animal intestinal perfusion models can be improved by considering these effects. The in vivo relevance can be increased by treating rats with a COX-2 inhibitor prior to surgery. This decreases the risk of surgery-induced ileus, which may affect the physiological regulation of mucosal permeability.
|
|
| 47. |
- Dahlgren, David, et al.
(författare)
-
Evaluation of drug permeability calculation based on luminal disappearance and plasma appearance in the rat single-pass intestinal perfusion model
- 2019
-
Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 142, s. 31-37
-
Tidskriftsartikel (refereegranskat)abstract
- The rat single-pass intestinal perfusion (SPIP) model is commonly used to investigate gastrointestinal physiology and membrane drug transport. The SPIP model can be used with the intestinal segment inside or outside the abdomen. The rats can also be treated with parecoxib, a selective cycloxygenase-2 inhibitor that has been shown to affect some intestinal functions following abdominal surgery, such as motility, epithelial permeability, fluid flux and ion transport. However, the impact of extra-abdominal placement of the intestinal segment in combination with parecoxib on intestinal drug transport has not been investigated. There is also uncertainty how well intestinal permeability determinations based on luminal drug disappearance and plasma appearance correlate in the rat SPIP model. The main objective of this rat in vivo study was to investigate the effect of intra- vs. extra abdominal SPIP, with and without, pretreatment with parecoxib. The effect was evaluated by determining the difference in blood-to-lumen Cr-51-EDTA clearance, lumen-to-blood permeability of a cassette-dose of four model compounds (atenolol, enalaprilat, ketoprofen, and metoprolol), and water flux. The second objective was to compare the jejunal permeability values of the model drugs when determined based on luminal disappearance or plasma appearance. The study showed that the placement of the perfused jejunal segment, or the treatment with parecoxib, had minimal effects on membrane permeability and water flux. It was also shown that intestinal permeability of low permeability compounds should be determined on the basis of data from plasma appearance rather than lumina] disappearance. If permeability is calculated on the basis of luminal disappearance, it should preferably include negative values to increase the accuracy in the determinations.
|
|
| 48. |
- Dahlgren, David, et al.
(författare)
-
Intestinal absorption of BCS class II drugs administered as nanoparticles : A review based on in vivo data from intestinal perfusion models
- 2020
-
Ingår i: ADMET & DMPK. - : International Association of Physical Chemists (IAPC). - 1848-7718. ; 8:4, s. 375-390
-
Forskningsöversikt (refereegranskat)abstract
- An established pharmaceutical strategy to increase oral drug absorption of low solubility-high permeability drugs is to create nanoparticles of them. Reducing the size of the solid-state particles increases their dissolution and transport rate across the mucus barrier and the aqueous boundary layer. Suspensions of nanoparticles also sometimes behave differently than those of larger particles in the fed state. This review compares the absorption mechanisms of nano- and larger particles in the lumen at different prandial states, with an emphasis on data derived from in vivo models. Four BSC class II drugs-aprepitant, cyclosporine, danazol and fenofibrate-are discussed in detail based on information from preclinical intestinal perfusion models.
|
|
| 49. |
- Dahlgren, David, et al.
(författare)
-
Preclinical Effect of Absorption Modifying Excipients on Rat Intestinal Transport of Model Compounds and the Mucosal Barrier Marker 51Cr-EDTA
- 2017
-
Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:12, s. 4243-4251
-
Tidskriftsartikel (refereegranskat)abstract
- There is a renewed interest from the pharmaceutical field to develop oral formulations of compounds, such as peptides, oligonucleotides, and polar drugs. However, these often suffer from insufficient absorption across the intestinal mucosal barrier. One approach to circumvent this problem is the use of absorption modifying excipient(s) (AME). This study determined the absorption enhancing effect of four AMEs (sodium dodecyl sulfate, caprate, chitosan, N-acetylcysteine) on five model compounds in a rat jejunal perfusion model. The aim was to correlate the model compound absorption to the blood-to-lumen clearance of the mucosal marker for barrier integrity, 51Cr-EDTA. Sodium dodecyl sulfate and chitosan increased the absorption of the low permeation compounds but had no effect on the high permeation compound, ketoprofen. Caprate and N-acetylcysteine did not affect the absorption of any of the model compounds. The increase in absorption of the model compounds was highly correlated to an increased blood-to-lumen clearance of 51Cr-EDTA, independent of the AME. Thus, 51Cr-EDTA could be used as a general, sensitive, and validated marker molecule for absorption enhancement when developing novel formulations.
|
|
| 50. |
- Dahlgren, David, et al.
(författare)
-
Regional Intestinal Permeability in Dogs : Biopharmaceutical Aspects for Development of Oral Modified-Release Dosage Forms
- 2016
-
Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:9, s. 3022-3033
-
Tidskriftsartikel (refereegranskat)abstract
- The development of oral modified-release (MR) dosage forms requires an active pharmaceutical ingredient (API) with a sufficiently high absorption rate in both the small and large intestine. Dogs are commonly used in preclinical evaluation of regional intestinal absorption and in the development of novel MR dosage forms. This study determined regional intestinal effective permeability (P-eff) in dogs with the aim to improve regional Peff prediction in humans. Four model drugs, atenolol, enalaprilat, metoprolol, and ketoprofen, were intravenously and regionally dosed twice as a solution into the proximal small intestine (P-SI) and large intestine (LI) of three dogs with intestinal stomas. Based on plasma data from two separate study occasions for each dog, regional Peff values were calculated using a validated intestinal deconvolution method. The determined mean P-eff values were 0.62, 0.14, 1.06, and 3.66 X 10(-4) cm/s in the P-SI, and 0.13, 0.02, 1.03, and 2.20 X 10(-4) cm/s in the LI, for atenolol, enalaprilat, metoprolol, and ketoprofen, respectively. The determined P-SI Peff values in dog were highly correlated (R-2 = 0.98) to the historically directly determined human jejunal P-eff after a single-pass perfusion. The determined dog P-SI P-eff values were also successfully implemented in GI-Sim to predict the risk for overestimation of LI absorption of low permeability drugs. We conclude that the dog intestinal stoma model is a useful preclinical tool for determination of regional intestinal permeability. Still, further studies are recommended to evaluate additional APIs, sources of variability, and formulation types, for more accurate determination of the dog model in the drug development process.
|
|
