| 1. |
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| 2. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 3. |
- Aimo, Alberto, et al.
(författare)
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High-sensitivity troponin T, NT-proBNP and glomerular filtration rate : A multimarker strategy for risk stratification in chronic heart failure
- 2019
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 277, s. 166-172
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a recent individual patient data meta-analysis, high-sensitivity troponin T (hs-TnT) emerged as robust predictor of prognosis in stable chronic heart failure (HF). In the same population, we compared the relative predictive performances of hs-TnT, N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), hs-C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) for prognosis.Methods and results: 9289 patients (66 ± 12 years, 77% men, 85% LVEF <40%, 60% ischemic HF) were evaluated over a 2.4-year median follow-up. Median eGFR was 58 mL/min/1.73 m2 (interquartile interval 46–70; n = 9220), hs-TnT 16 ng/L (8–20; n = 9289), NT-proBNP 1067 ng/L (433–2470; n = 8845), and hs-CRP 3.3 mg/L (1.4–7.8; n = 7083). In a model including all 3 biomarkers, only hs-TnT and NT-proBNP were independent predictors of all-cause and cardiovascular mortality and cardiovascular hospitalization. hs-TnT was a stronger predictor than NT-proBNP: for example, the risk for all-cause death increased by 54% per doubling of hs-TnT vs. 24% per doubling of NT-proBNP. eGFR showed independent prognostic value from both hs-TnT and NT-proBNP. The best hs-TnT and NT-proBNP cut-offs for the prediction of all-cause death increased progressively with declining renal function (eGFR ≥ 90: hs-TnT 13 ng/L and NT-proBNP 825 ng/L; eGFR < 30: hs-TnT 40 ng/L and NT-proBNP 4608 ng/L). Patient categorization according to these cut-offs effectively stratified patient prognosis across all eGFR classes.Conclusions: hs-TnT conveys independent prognostic information from NT-proBNP, while hs-CRP does not. Concomitant assessment of eGFR may further refine risk stratification. Patient classification according to hs-TnT and NT-proBNP cut-offs specific for the eGFR classes holds prognostic significance.
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| 4. |
- Aimo, Alberto, et al.
(författare)
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Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure : An Individual Patient Data Meta-Analysis
- 2018
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 137:3, s. 286-297
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach.Methods: Medline, EMBASE, Cochrane Library, and Scopus were searched in April 2017 by 2 independent authors. The terms were “troponin” AND “heart failure” OR “cardiac failure” OR “cardiac dysfunction” OR “cardiac insufficiency” OR “left ventricular dysfunction.” Inclusion criteria were English language, clinical stability, use of a high-sensitivity troponin assay, follow-up studies, and availability of individual patient data after request to authors. Data retrieved from articles and provided by authors were used in agreement with the PRISMA statement. The end points were all-cause death, cardiovascular death, and hospitalization for cardiovascular cause.Results: Ten studies were included, reporting data on 11 cohorts and 9289 patients (age 66±12 years, 77% men, 60% ischemic heart failure, 85% with left ventricular ejection fraction <40%). High-sensitivity troponin T data were available for all patients, whereas only 209 patients also had high-sensitivity troponin I assayed. When added to a prognostic model including established risk markers (sex, age, ischemic versus nonischemic etiology, left ventricular ejection fraction, estimated glomerular filtration rate, and N-terminal fraction of pro-B-type natriuretic peptide), high-sensitivity troponin T remained independently associated with all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.41–1.55), cardiovascular mortality (hazard ratio, 1.40; 95% confidence interval, 1.33–1.48), and cardiovascular hospitalization (hazard ratio, 1.42; 95% confidence interval, 1.36–1.49), over a median 2.4-year follow-up (all P<0.001). High-sensitivity troponin T significantly improved risk prediction when added to a prognostic model including the variables above. It also displayed an independent prognostic value for all outcomes in almost all population subgroups. The area under the curve–derived 18 ng/L cutoff yielded independent prognostic value for the 3 end points in both men and women, patients with either ischemic or nonischemic etiology, and across categories of renal dysfunction.Conclusions: In chronic heart failure, high-sensitivity troponin T is a strong and independent predictor of all-cause and cardiovascular mortality, and of hospitalization for cardiovascular causes, as well. This biomarker then represents an additional tool for prognostic stratification.
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| 5. |
- Aimo, Alberto, et al.
(författare)
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Revisiting the obesity paradox in heart failure : Per cent body fat as predictor of biomarkers and outcome
- 2019
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Ingår i: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 26:16, s. 1751-1759
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Tidskriftsartikel (refereegranskat)abstract
- Aims Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure. We assessed whether another anthropometric measure, per cent body fat (PBF), reveals different associations with outcome and heart failure biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenesis-2 (sST2)). Methods In an individual patient dataset, BMI was calculated as weight (kg)/height (m) (2) , and PBF through the Jackson-Pollock and Gallagher equations. Results Out of 6468 patients (median 68 years, 78% men, 76% ischaemic heart failure, 90% reduced ejection fraction), 24% died over 2.2 years (1.5-2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4-33.0%) with the Jackson-Pollock equation, and 28.0% (23.8-33.5%) with the Gallagher equation, with an extremely strong correlation (r = 0.996, p < 0.001). Patients in the first PBF tertile had the worst prognosis, while patients in the second and third tertile had similar survival. The risks of all-cause and cardiovascular death decreased by up to 36% and 27%, respectively, per each doubling of PBF. Furthermore, prognosis was better in the second or third PBF tertiles than in the first tertile regardless of model variables. Both BMI and PBF were inverse predictors of NT-proBNP, but not hs-TnT. In obese patients (BMI >= 30 kg/m(2), third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome. Conclusion In parallel with increasing BMI or PBF there is an improvement in patient prognosis and a decrease in NT-proBNP, but not hs-TnT or sST2. hs-TnT or sST2 are stronger predictors of outcome than NT-proBNP among obese patients.
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| 6. |
- Gjerstad, Karl-Idar, et al.
(författare)
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NORDUST : Nordic Road Dust Project
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Road dust is an important contributor to airborne particle pollution, especially in the Nordic countries where high road surface wear, due to studded tyre useas well as winter maintenance and operations including sanding and salting are important contributors. Even though the road dust problems are similar, the countries have tackled different parts of the problem with different research approaches, resulting in a complex knowledgebase in need of compilation. A former project, NORTRIP, started this work and implemented the knowledge into an emission model with a specially elaborated road dust focus. The model work has been used to identify knowledge gaps, intended to be filled within the NorDust project. Laboratory tests and controlled and uncontrolled field measurements as well as parametrisation and modelling has been used as tools to find, describe and implement issues concerning road dust formation, suspension and dynamics and road operation effects on emissions in facilities and sites in Finland and Sweden. The NORTRIP model has been implemented and evaluated in Iceland, not previously involved in the model development, to identify input data needs. The project has resulted in an array of findings, of which some have been possible to implement in new parametrisations in the NORTRIP model. In the complex research area of road dust dynamics, the project has also resulted in a lot of practical experiences concerning experimental and measurement designs and evaluation possibilities that future research will be able to benefit from.
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| 7. |
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| 8. |
- Gustafsson, Ida, et al.
(författare)
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Midwives' lived experience of caring for new mothers with initial breastfeeding difficulties: A phenomenological study
- 2017
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Ingår i: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 12, s. 9-15
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study is to obtain a deeper understanding of midwives’ lived experiences of caring for new mothers with initial breastfeeding difficulties.Methods: A reflective lifeworld approach was used. Six midwives were recruited from a hospital in western Sweden. Data were collected via individual lifeworld interviews and analysed using phenomenological methods.Results: The essential meaning can be described as a midwife’s wish to help new mothers reach their breastfeeding goals by trying to interact with them as individual women in unique breastfeeding situations. This wish constitutes a contradiction to the midwife’s own desire to succeed in enabling mothers to breastfeed and the perceived risk of failure as a midwife if the mothers decide not to breastfeed. This is further described by five constituents: striving to provide individualised care, collegial and personal responsibility both enables and prevents care, a struggle to be sufficient, an uphill struggle and mutual joy becomes the motivation to care.Conclusions: Caring for new mothers with initial breastfeeding difficulties is a balancing act between the midwife’s personal desire to succeed in enabling mothers to breastfeed, the mothers’ wishes, the infants’ needs, the importance of collective collegial competence and the limitations in the health care organisation. This makes the midwife’s efforts to provide individualised care frustrating and demanding as well as motivating.
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| 9. |
- Gustafsson, Ida, et al.
(författare)
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Reflekterande Loggbok : Stöd i lärande med livsvärldsteoretisk grund
- 2019
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Ingår i: PUHB-konferens, Högskolan i Borås, 25 april 2019.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- På sektionen för vård används ofta loggböcker i samband med verksamhetsförlagd utbildning. Tanken med loggböckerna är att studenterna ska få möjlighet att reflektera kring sina upplevelser i klinisk praktik samt stödjas i sammanvävning av teori och praktik. Denna tanke vilar på livsvärldsdidaktisk forskning från sektionen. I vårt arbete som universitetsadjunkter har vi sett att reflektionen i loggböckerna ofta stannar på en ytlig nivå. Studenterna uttrycker också i kursvärderingar att de inte riktigt förstår syftet med uppgiften. Därför ser vi ett behov av att utveckla och teorianknyta loggböckerna, för att bättre stödja studenternas lärandeprocess.
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| 10. |
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| 11. |
- Gustafsson, Mats, 1966-, et al.
(författare)
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Driftåtgärder mot PM10 i Stockholm : utvärdering av vintersäsongen 2015–2016
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sedan 2011 pågår ett särskilt arbete i Stockholm för att minska PM10-halterna i staden. Insatserna omfattar främst dammbindning med CMA (kalciummagnesiumacetat) och vakuumsugning med en kraftig, torr vakuumsugningsmaskin. Denna rapport sammanfattar effekter på partikelhalter och vägdammsförråd, av de åtgärder som Stockholms stad utfört under säsongen 2015–2016 och diskuterar hur åtgärderna kan ytterligare förbättras. Miljökvalitetsnormen klarades säsongen 2015–2016 för tredje året i rad, men antalet dagar med PM10-halter över miljökvalitetsnormens gränsvärde var högre än föregående säsong, som hade rekordlågt antal överskridanden. Utvärderingen av dagtids dammbindning försvårades av att CMA även lades ut på referensgatan, vilket medförde alltför stora osäkerheter för att kunna göra någon kvantitativ analys av dess effekt denna säsong. Kvartersvis dammbindning och vakuumsugning kunde inte utvärderas på grund av att en byggarbetsplats kontaminerade mätningarna. Dammförrådet på gatorna varierar från några enstaka g/m2 till cirka 250 g/m2 beroende på gata och årstid och är som högst under vintern (dec–jan). En trend mot lägre dammängder bryts denna säsong på flera gator, vilket möjligen kan bero på jämförelsevis fuktigare gator på våren denna säsong. Analyserna tyder på att dammbindning på våren är viktigt för att hålla PM10-halterna nere, medan dammbindning på hösten och vintern oftare görs ”i onödan” (då halterna sannolikt inte skulle ha överskridit gränsvärdet även utan dammbindning).
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| 12. |
- Gustafsson, Mats, 1966-, et al.
(författare)
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Driftåtgärder mot PM10 i Stockholm : utvärdering av vintersäsongen 2016/2017
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Stockholms stad bedriver sedan 2011 ett arbete med att, genom förbättrade och specifika gatudriftsåtgärder minska uppvirvlingen av vägdamm för att minska partikelhalter i luften. Sedan starten har effekterna på såväl dammförråd som luftkvalitet följts upp av VTI och SLB-analys vid Miljöförvaltningen i Stockholm.Specifika åtgärder har omfattat främst dammbindning med kalciummagnesiumacetat (CMA) och städning med vakuumsug (Disa-Clean). Luftkvalitetsmätningarna visar att miljökvalitetsnormen för PM10 klaras för fjärde året i Stockholm vilket delvis bedöms beror på driftåtgärderna. Den extra dagtida dammbindningen kunde visas sänka dygnsmedelvärdet av PM10 med 6 %, medan den kvartersvisa behandlingen inte kunde visas ha någon tydlig effekt. Vägdammsmängderna mätt som DL180 (vägdamm mindre än 180 μm) tenderar att i genomsnitt ha ökat något jämfört med föregående säsong, särskilt i ytorna mellan hjulspåren. Omläggningen av Folkungagatan har resulterat i kraftigt ökade vägdammsmängder, men också lägre PM10-halter än föregående säsonger. Utvärderingen av möjligheterna att optimera dammbindningen visar att flera dagar med överskridanden på hösten missas, medan flera dagar i januari behandlas med CMA utan att behov egentligen föreligger. Högre precision med prognosbaserade åtgärder behövs för optimering av insatserna.
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| 13. |
- Gustafsson, Mats, 1966-, et al.
(författare)
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Driftåtgärder mot PM10 i Stockholm : utvärdering av vintersäsongen 2017–2018
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Stockholms stad bedriver sedan 2011 ett arbete med att, genom förbättrade och specifika gatudriftsåtgärder, minska uppvirvlingen av vägdamm för att minska partikelhalter i luften. Sedan starten har effekterna på såväl dammförråd som luftkvalitet följts upp av VTI och SLB-analys vid Miljöförvaltningen i Stockholm. Specifika åtgärder har omfattat främst dammbindning med kalciummagnesiumacetat (CMA) och städning med vakuumsug (Disa-Clean). Innevarande säsong har vakuumsugen dock inte använts. Luftkvalitetsmätningarna visar att miljökvalitetsnormen för PM10 klaras för femte året i Stockholm, men halterna är högre än föregående år. Vägdammsmängderna mätt som DL180 (vägdamm mindre än 180 μm) har generellt ökat vilket varit utvecklingen sedan säsongen 2014–2015. Folkungagatan, som fick en ny beläggning 2016, har fortsatt höga vägdammsmängder, men också lägre PM10-halter än före beläggningsbytet. Utvärderingen av möjligheterna att optimera dammbindningen visar att CMA ofta läggs ut trots att PM10-halterna inte skulle överskridits. Maj var särskilt torr och flera överskridanden kunde då ha förhindrats med CMA, men åtgärden avslutas sista april på grund av risk för halka. Högre precision med till exempel prognosbaserade åtgärder skulle sannolikt vara gynnsamt för optimering av insatserna.
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| 14. |
- Gustafsson, Mats, 1966-, et al.
(författare)
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Optidrift : optimerad vinter- och barmarksdrift för bättre luftkvalitet
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Drift av gator och vägar påverkar, förutom framkomlighet och säkerhet, även miljöaspekter som luftkvalitet. Åtgärder som sandning och saltning påverkar halten av inandningsbara partiklar (PM10) i luften. Driftåtgärder som görs för att minska uppvirvlingen av partiklar på våren kan å andra sidan ha effekt på vinterdriften, genom att de saltlösningar som används också fungerar som halkbekämpningsmedel. Projektet har undersökt möjligheterna att optimera gatudriften ur dessa aspekter, med ett fokus på luftkvalitet. I olika aktiviteter inhämtades synpunkter och erfarenheter kring problembild och lösningar från bransch, väghållare och praktiker. En provtagare för vägdamm, WDS II, vidareutvecklades. Utvärderingar av olika spol- och städvarianters effekt på dammförrådet visade att en positiv effekt av metoderna kräver att det finns förhållandevis mycket damm på vägytan. Optimeringstester visade att god prognosstyrning av insatserna är viktigt för ett bra resultat. En kriteriebaserad analys visade att ingen optimering av dammbindningen skett under projektperioden. Sammantaget har projektets ursprungliga mål att kunna föreslå en optimerad gatudrift i en stadsdel i Stockholm inte nåtts, främst beroende av gällande driftkontrakt och av miljökvalitetsmålets (PM10) och framkomlighetens höga prioritet i staden. Däremot har Optidrift identifierat framgångsfaktorer och problem med gatudriften, resulterat i ökad kunskap om gatudriftens effekter på dammförråd och luftkvalitet samt tagit fram användbara utvärderingsmetoder och scenarioanalyser användbara i fortsatt arbete med att förbättra och optimera vinter- och barmarksdrift.
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| 15. |
- Gustafsson, Mats, 1966-, et al.
(författare)
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Road dust load dynamics and influencing factors for six winter seasons in Stockholm, Sweden
- 2019
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Ingår i: Atmospheric Environment: X. - : Elsevier BV. - 2590-1621.
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Tidskriftsartikel (refereegranskat)abstract
- Traffic related non-exhaust particulate sources and road dust are an increasingly important source for PM10 air pollution as exhaust sources are decreasing due to regulations. In the Nordic countries, the road dust problem is enhanced by use of studded tyres, causing increased road wear and winter road maintenance including gritting. Efforts to reduce road dust emissions requires knowledge on temporal and spatial road dust load dynamics. The city of Stockholm, Sweden, has therefore financed seasonal (October to May) road dust sampling to be able to optimize their winter and spring time street operation measures for reduced road dust emissions. This work describes the outcome of six seasons (2011/2012–2016/2017) of road dust sampling in five central streets using the VTI wet dust sampler (WDS).The results show that road dust load, expressed as DL180 (dust load smaller than 180 μm) has a seasonal variation with the highest loads (up to 200 g/m2) in late winter and early spring and a minimum (down to about 15 g/m2) in early autumn and late spring. The dust load varies between streets and is depending on pavement surface properties. On a smaller scale the dust load has a high variability across streets due to differences in rates of suspension from different parts of the road surface, with low amounts in wheel tracks and higher in-between and outside the tracks. Between 2 and 30% of the DL180 is smaller than 10 μm and could directly contribute to PM10 emissions. In general, higher road surface texture leads to higher dust loads, but the condition of the pavement (e.g. cracks, aggregate loss) might also have an effect. A new, wear resistant pavement accumulated markedly higher road dust amounts than a several years old pavement. This paper closes with a discussion on the complex relation between road dust load and PM10 concentrations and a discussion on the challenges and comparability of road dust sampling techniques and measures.
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| 16. |
- Gustafsson, Per E., et al.
(författare)
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Embodying pervasive discrimination : a decomposition of sexual orientation inequalities in health in a population-based cross-sectional study in Northern Sweden.
- 2017
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Ingår i: International Journal for Equity in Health. - : Springer Science and Business Media LLC. - 1475-9276. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies from Sweden and abroad have established health inequalities between heterosexual and non-heterosexual people. Few studies have examined the underpinnings of such sexual orientation inequalities in health. To expand this literature, the present study aimed to employ decomposition analysis to explain health inequalities between people with heterosexual and non-heterosexual orientation in Sweden, a country with an international reputation for heeding the human rights of non-heterosexual people.METHODS: Participants (N = 23,446) came from a population-based cross-sectional survey in the four northernmost counties in Sweden in 2014. Participants completed self-administered questionnaires, covering sexual orientation, mental and general physical health, social conditions and unmet health care needs, and sociodemographic data was retrieved from total population registers. Sexual orientation inequalities in health were decomposed by Blinder-Oaxaca decomposition analysis.RESULTS: Results showed noticeable mental and general health inequalities between heterosexual and non-heterosexual orientation groups. Health inequalities were partly explained (total explained fraction 64-74%) by inequalities in degrading treatment (24-26% of the explained fraction), but to a considerable degree also by material conditions (38-45%) and unmet care needs (25-43%).CONCLUSIONS: Psychosocial experiences may be insufficient to explain and understand health inequalities by sexual orientation in a reputedly 'gay-friendly' setting. Less overt forms of structural discrimination may need to be considered to capture the pervasive material discrimination that seems to underpin the embodiment of sexual minority inequalities. This ought to be taken into consideration in research, policy-making and monitoring aiming to work towards equity in health across sexual orientations.
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| 17. |
- Janhäll, Sara, 1965-, et al.
(författare)
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Utvärdering av städmaskiners förmåga att reducera vägdammsförrådet i gatu- och tunnelmiljöer i Trondheim
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- För att undvika överskridande av miljökvalitetsnormerna för partiklar (PM10) har Statens vegvesen Vegdirektoratet i Trondheim genomfört ett försök att rengöra en vägtunnel och en vägsträcka med tre olika städmaskiner för att minska mängden vägdamm. Ett stort antal andra tester redovisas i huvudrapporten, medan föreliggande rapport fokuserar på hur stort vägdammsförrådet varit före och efter städningen med olika maskiner i de olika miljöerna.Resultatet visar att städning minskar vägdammsförrådet effektivt i gatumiljö med två av de tre olika maskinerna, medan vägdammsförrådet ökar av städning i tunnelmiljö. En teori kan vara att detta kan bero på att även väggar och tak städas i tunnelmiljön, vilket skulle kunna medföra att städningen flyttar partiklar från tak och väggar till vägytan. Tunnelstädningen utförs med rengöringsmedel, vilket ger en annan kemisk miljö, som kan lösa upp vägdammet längre ner i texturen och tillgängliggöra det för provtagningsutrustningen.
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| 18. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 19. |
- Järlskog, Ida, 1991-, et al.
(författare)
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Utvärdering av städmaskiners förmåga att reducera vägdammsförrådet i gatu- och tunnelmiljöer : En fältstudie i Trondheim 2016
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- VTI har i maj 2016 på uppdrag av Statens vegvesen i Trondheim genomfört en fältstudie i Strindheimtunnelen samt på Haakon VII gate med syfte att jämföra och utvärdera städmaskiners och teknikers förmåga att reducera vägdammsförrådet i gatu- och tunnelmiljöer. VTI genomförde provtagningar med dammprovtagaren Wet Dust Sampler II (WDS II) före och efter städinsatserna. Studien visade att vägdammsförrådet blev större efter en första städinsats med BEAM rotorclean i tunneln (endast vägbana) än före städning. Detta antas bero på att vägdamm spolas ut från kanten alternativt att cementerat vägdamm i beläggningstexturen lösgjorts. Efter en andra städinsats då väggar och tak först städades varefter vägbanan städades igen kunde en sänkning av dammförrådet uppmätas, dock endast i vägbanan, inte närmast kanten.På Haakon VII gate testades två olika städmaskiner: Disa Clean och Val’Air rotor cleaner. Den förstnämnda är en torr vakuumsug medan den sistnämnda utför roterande högtryckstvättning kombinerad med vakuumsug. Körbanan delades upp i sex sektioner, där en specifik städstrategi användes i varje sektion (kallas fält i denna studie). Provtagning genomfördes i varje fält före och efter städinsats. Resultatet i denna studie visade att störst effekt erhålls vid användande av Disa Clean i kombination med högtrycksspolning samt vid användande av Val’Air rotor cleaner med en körhastighet på 3 kilometer i timmen. I båda fall uppmättes en markant skillnad i dammförråd före och efter städning.
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| 20. |
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| 21. |
- Lundberg, Joacim, 1991-, et al.
(författare)
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Wet Dust Sampler : a Sampling Method for Road Dust Quantification and Analyses
- 2019
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Ingår i: Water, Air and Soil Pollution. - : Springer. - 0049-6979 .- 1573-2932. ; 230:8
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Tidskriftsartikel (refereegranskat)abstract
- In northern countries, the climate, and consequently the use of studded tyres and winter traction sanding, causes accumulation of road dust over winter and spring, resulting in high PM10 concentrations during springtime dusting events. To quantify the dust at the road surface, a method—the wet dust sampler (WDS)—was developed allowing repeatable sampling also under wet and snowy conditions. The principle of operation is flushing high-pressurised water over a defined surface area and transferring the dust laden water into a container for further analyses.In this paper, the latest version of the WSD is presented together with an evaluation of its performance. To evaluate the WDS, the ejected water amount was measured, as well as water losses in different parts of the sampling system, together with indicative dust measurement using turbidity as a proxy for dust concentration. The results show that the WDS, when accounting for all losses, have a predictable and repeatable water performance, with no impact on performance based on the variety of asphalt surface types included in this study, given undamaged surfaces. The largest loss was found to be water retained on the surface, and the dust measurements imply that this might not have as large impact on the sampled dust as could be expected. A theoretical particle mass balance shows small particle losses, while field measurements show higher losses. Several tests are suggested to validate and improve on the mass balances. Finally, the WDS is found to perform well and is able to contribute to further knowledge regarding road dust implications for air pollution.
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| 22. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 23. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 24. |
- Nielsen, Jonas B., et al.
(författare)
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Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 102:1, s. 103-115
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10−18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10−11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.
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| 25. |
- Poelzl, Gerhard, et al.
(författare)
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Repetitive use of levosimendan in advanced heart failure : need for stronger evidence in a field in dire need of a useful therapy
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 243, s. 389-395
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Tidskriftsartikel (refereegranskat)abstract
- Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminalprohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.
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| 26. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 27. |
- Rosengren, Kristina, et al.
(författare)
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Every Second Counts: Women’s Experience of Living with ALS in the End-of-Life Situations.
- 2015
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Ingår i: Home Health Care Management & Practice. - : SAGE Publications. - 1084-8223 .- 1552-6739. ; 27:2, s. 76-82
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects patients with a loss of speech and mobility. The aim of this study was to describe patients’ experiences of living with ALS in the end-of-life situations. A manifest content analysis was chosen for analysis narratives from four biographies by women who had ALS. The categories Suffering, Meaningfulness, and Experiences of a Limited life were identified as describing patients’ understanding of living with ALS. Nurses need to be trained in communication skills to maintain human dignity for patients who lost their speech regarding an intellect in shape. There is a need for information among family members about severe diseases, such as ALS, to improve high quality of care and well-being for all involved. Home health care has to invite and facilitate patients’ and relatives’ participation regarding the end-of-care processes to improve a sense of coherence to handle everyday life situation in the future.
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| 28. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 29. |
- Surakka, Ida, et al.
(författare)
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The impact of low-frequency and rare variants on lipid levels.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:6, s. 589-597
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Tidskriftsartikel (refereegranskat)abstract
- Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
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