| 1. |
- Lahrouchi, Najim, et al.
(författare)
-
Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome
- 2020
-
Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 142:4, s. 324-338
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
|
|
| 2. |
- Lundin, Anette
(författare)
-
Rättfärdigade prioriteringar : en kvalitativ analys av hur personal i äldreomsorgen hanterar motstridiga verksamhetslogiker
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation aims at contributing to social scientific knowledge about prevailing prioritizations in eldercarepractice by looking at an economic and a caring logic, and how these logics are overlapping, contradictory or comein conflict with each other. A more concrete aim is to understand how the personnel describe their work with orfor balance between the logics and their justifications prioritizations made in the care of older persons. The researchquestion is: How do personnel and care unit manager at a public nursing home understand and handle the twologics that govern care work for facilitating wellbeing of the residents. The aim and research question led to threesub-aims: 1) to analyze the personnel’s experiences of and meaning making about the care work they carry out, 2)to illuminate and problematize the two logics above, and 3)to analyze how the personnel justify their prioritizationsin prevailing context, and how their accountability have an effect on their professional identities.Empirical material was gathered through 13 individual interviews with care personnel and their care unitmanager at a public nursing home in Sweden. These interviews were complemented by a group interview. Thematerial was analyzed by the use of three methods: phenomenology (Paper I and II), reflexive analysis (Paper III),and a positioning analysis (Paper IV). Paper I found that the personnel understands the residents’ well-being asbeing characterized by feeling of being existentially touched. This essence is constituted by feeling freedom ofchoice, pleasure, and closeness to someone or something. In Paper II, the work for facilitating this kind of wellbeingwas characterized by three ambiguities: (i) freedom of choice for the older persons vs. institutionalconstraints, (ii) the residents' need for activation vs. wanting not to be activated, and (iii) the residents' need forroutine vs. the eldercarers' not being able to know what the residents need. Paper III showed that the care unitmanager created a hybrid of the two logics (economy is care and vice versa) and that the personnel oppose thishybrid. The opposition is shaped as the personnel divides their work in care and “those other things”. Thesefindings showed how interaction between the logics expresses itself in practice and that it is the personnel who hasto handle contradictions between the logics in their everyday care work. The positioning analysis in Paper IV hadthree levels. The first level showed how the carers align with their peers and that they find the organizationalframe, within which they have agency, changed due to increased workload. This change led to an order of priorities.The second level showed that the carers relate to three aspects when making accounts: the care itself, the olderpersons, and the media. The third level showed that the carers share a view of administration, cleaning, servingmeals, and filling up supplies, as not being parts of caring.The dissertation’s theoretical framework focused on theories on logics, accountability, and professionalidentity. The conclusion is that both logics are needed in order to facilitate the well-being of the older persons. Therelationships between the two logics are not always clear and if their contradictions are not illuminated, there is arisk for a care practice that does not facilitate the well-being of their residents. An important theoreticalcontribution is that logics of activities should be understood vertically (form political, through management, anddown to the level of practice) instead of horizontally. The practical implications emphasize the importance ofsupporting the personnel’s professional identity on the one hand, and discussing the logics on the other. Byunderstanding differences between definitions on management-level and practice level, a homogeneity can bereached.
|
|
| 3. |
- Wang, Zhaoming, et al.
(författare)
-
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
|
|
| 4. |
|
|
| 5. |
- Balk, Lennart, et al.
(författare)
-
Widespread episodic thiamine deficiency in Northern Hemisphere wildlife
- 2016
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B-1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiaminedependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.
|
|
| 6. |
- Bendtsen, Katja Maria, et al.
(författare)
-
Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties
- 2020
-
Ingår i: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28, and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black. RESULTS: Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15-22 nm, specific surface area: 152-222 m2/g, and count median mobility diameter: 55-103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12-0.60), polycyclic aromatic hydrocarbon content (1-27 μg/mg) and acid-extractable metal content (0.9-16 μg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28 post-exposure, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in lung on day 28 and in liver on day 90 correlated with acellular particle-induced ROS. CONCLUSIONS: We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights specific surface area, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.
|
|
| 7. |
- Berg, Agneta, et al.
(författare)
-
Dementia care nurses experiences of systematic clinical group supervision and supervised individually planned nursing care
- 2000
-
Ingår i: Journal of Nursing Management. - 0966-0429 .- 1365-2834. ; 8:6, s. 357-368
-
Tidskriftsartikel (refereegranskat)abstract
- AimTo reveal 13 nurses' experiences of systematic clinical group supervision and supervised individually planned nursing care, while working with people suffering from severe dementia.BackgroundClinical supervision is a major issue in nursing, however empirical knowledge of the subject is limited. Nurse's narrations about their experiences may extend the knowledge available and serve as a basis for creating models of support systems for nurses in their care provision.MethodsOpen-ended interviews were performed and the text was analysed through content analysis. A questionnaire was used to evaluate the views of the effects of clinical supervision.FindingsTwo main themes were found. Confirmed uniqueness included two sub-themes: confirming the nurses as a person and as a professional and confirming the patient as a unique human being. Consolidated sense of community included three sub-themes: closer relationship between the nurses, changed organization of nursing care and improved individualizing in routines of nursing care. The questionnaire result showed improvements in co-operation and in providing professional nursing care and personal development.ConclusionInterventions to improve working conditions for the nurses and care quality for the patients may well focus the core process, i.e. feedback and support for the nurse–patient interaction and person-orientated nursing care, taking into account the constellation and conditions of the group.
|
|
| 8. |
- Berg, Agneta, 1950-, et al.
(författare)
-
Nurses' creativity, tedium and burnout during 1 year of clinical supervision and implementation of individually planned nursing care : comparisons between a ward for severely demented patients and a similar control ward
- 1994
-
Ingår i: Journal of Advanced Nursing. - 0309-2402 .- 1365-2648. ; 20:4, s. 742-749
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to study creativity and innovative climate, tedium and burnout among the nurses on two wards during 1 year of systematic clinic supervision combined with the implementation of individualized care on an experimental ward (EW) for severely demented patients, as compared with a similar control ward (CW) EW nurses had systematic clinic supervision and each patient had his/her nursing care carefully planned, documented and evaluated The intervention was evaluated by means of the Creative Climate Questionnaire, Burnout Measure and the Maslach Burnout Inventory Creativity and innovative climate improved significantly among the EW nurses (n= 19) in eight out of 10 factors during the year of intervention while there was no change on the control ward (n= 20) Tedium and burnout decreased significantly among the EW nurses while no change was seen in this respect among the CW nurses It seems reasonable to assume that systematic clinical supervision and individualized planned care decreases the negative outcome of stress caused by the psychological burden imposed by nursing care It also increases nurses' creativity, which, in turn, may benefit patient care The findings of this study point to the necessity for a support system that focuses on the work itself, i e the nursing care Individualized planned care and systematic clinical supervision may offer this kind of support.
|
|
| 9. |
- Berg, Agneta, et al.
(författare)
-
Nurses' creativity, tedium and burnout during 1 year of clinical supervision and implementation of individually planned nursing care : comparisons between a ward for severely demented patients and a similar control ward
- 1994
-
Ingår i: Journal of Advanced Nursing. - : Wiley-Blackwell Publishing Ltd. - 0309-2402 .- 1365-2648. ; 20:4, s. 742-749
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to study creativity and innovative climate, tedium and burnout among the nurses on two wards during 1 year of systematic clinic supervision combined with the implementation of individualized care on an experimental ward (EW) for severely demented patients, as compared with a similar control ward (CW) EW nurses had systematic clinic supervision and each patient had his/her nursing care carefully planned, documented and evaluated The intervention was evaluated by means of the Creative Climate Questionnaire, Burnout Measure and the Maslach Burnout Inventory Creativity and innovative climate improved significantly among the EW nurses (n= 19) in eight out of 10 factors during the year of intervention while there was no change on the control ward (n= 20) Tedium and burnout decreased significantly among the EW nurses while no change was seen in this respect among the CW nurses It seems reasonable to assume that systematic clinical supervision and individualized planned care decreases the negative outcome of stress caused by the psychological burden imposed by nursing care It also increases nurses' creativity, which, in turn, may benefit patient care The findings of this study point to the necessity for a support system that focuses on the work itself, i e the nursing care Individualized planned care and systematic clinical supervision may offer this kind of support.
|
|
| 10. |
- Berg, Elisabeth, 1951-, et al.
(författare)
-
Uppdrag Språklyft med matematik : Högläsningstexter och elevuppdrag med problemlösning
- 2013. - 1
-
Bok (populärvet., debatt m.m.)abstract
- Boken vänder sig till lärare från förskoleklass till årskurs 3.Med utgångspunkt i spännande och inspirerande högläsningstexter får eleverna ta sig an kreativa och roliga matematiska uppdrag att utföra i grupp eller individuellt. Eleverna får arbeta med och lösa problem där de själva eller tillsammans i grupp väljer lämpliga lösningsstrategier. De får förklara hur de har tänkt och jämföra sina olika lösningar.Uppdrag Språklyft med matematik utgår från det centrala innehållet i kursplanen i matematik samt Skolverkets bedömningsstöd Nya Språket lyfter! och ger eleverna tillfällen att ur olika perspektiv öva matematiska och språkliga förmågor.Elevuppdragen som finns i boken är kopieringsunderlag. I anslutning till varje uppdrag finns en handledning till läraren.Boken har två teman, Leksaksfabiken (Fk-3) samt Detektivbyrån (årskurs 2-3).
|
|
