| 1. |
- Benzinou, Michael, et al.
(författare)
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Common nonsynonymous variants in PCSK1 confer risk of obesity.
- 2008
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:8, s. 943-5
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.
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| 2. |
- Dina, Christian, et al.
(författare)
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Variation in FTO contributes to childhood obesity and severe adult obesity.
- 2007
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:6, s. 724-6
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Tidskriftsartikel (refereegranskat)abstract
- We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.
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| 3. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Jernås, Margareta, 1961, et al.
(författare)
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Regulation of carboxylesterase 1 (CES1) in human adipose tissue.
- 2009
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 383:1, s. 63-7
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Tidskriftsartikel (refereegranskat)abstract
- Carboxylesterase 1 (CES1) has recently been suggested to play a role in lipolysis. Our aim was to study the regulation of CES1 expression in human adipose tissue. In the SOS Sib Pair Study, CES1 expression was higher in obese compared with lean sisters (n=78 pairs, P=8.7x10(-18)) and brothers (n=12 pairs, P=0.048). CES1 expression was higher in subcutaneous compared with omental adipose tissue in lean (P=0.027) and obese subjects (P=0.00036), and reduced during diet-induced weight loss (n=24, weeks 8, 16, and 18 compared to baseline, P<0.0001 for all time points). CES1 expression was higher in isolated adipocytes compared with intact adipose tissue (P=0.0018) and higher in large compared with small adipocytes (P=4.1x10(-6)). Basal and stimulated lipolysis was not different in individuals with high, intermediate, and low expression of CES1. Thus, CES1 expression was linked to body fat and adipocyte fat content but not to lipolytic activity.
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| 8. |
- Abrahamsson, Niclas, et al.
(författare)
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Fördomar skadar många med fetma
- 2018
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Ingår i: Svenska Dagbladet Debatt. - 1101-2412.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Adler, Mats, et al.
(författare)
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Diagnosdiskussion
- 2016
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Ingår i: Tidskriften för Svensk Psykiatri. - 1653-8579. ; 2016:1, s. 77-78
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Senaste halvåret har en arbetsgrupp på Svenska Psykiatriska Föreningens uppdrag arbetat med problem som finns runt psykiatriska diagnoser. En viktig del av arbetet har varit att ta fram ett diskussionsunderlag främst riktat till dem som i sitt arbete sätter psykiatriska diagnoser. Detta underlag syftar till att problematisera, inte till att polemisera. Självklart har vi i gruppen uppfattningar, men vi har inte alltid samma uppfattningar inom detta område. En sak är vi dock helt överens om – psykiatrisk diagnostik är svårt! samt att det idag finns uppenbara problem.
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| 10. |
- Ahlin, Sofie, 1985, et al.
(författare)
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Fracture risk after three bariatric surgery procedures in Swedish obese subjects : up to 26 years follow-up of a controlled intervention study
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:5, s. 546-557
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have reported an increased fracture risk after bariatric surgery. Objective: To investigate the association between different bariatric surgery procedures and fracture risk. Methods: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups. Results: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02–3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41–2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66–2.79; P < 0.001). Conclusions: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment.
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| 11. |
- Ahlin, Sofie, 1985, et al.
(författare)
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Macrophage Gene Expression in Adipose Tissue is Associated with Insulin Sensitivity and Serum Lipid Levels Independent of Obesity.
- 2013
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Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-739X .- 1930-7381. ; 21:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. Design and Methods: Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group. Results: The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group. Conclusion: Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia.
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| 12. |
- Andersson, Anders
(författare)
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Extensions for Distributed Moving Base Driving Simulators
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Modern vehicles are complex systems. Different design stages for such a complex system include evaluation using models and submodels, hardware-in-the-loop systems and complete vehicles. Once a vehicle is delivered to the market evaluation continues by the public. One kind of tool that can be used during many stages of a vehicle lifecycle is driving simulators.The use of driving simulators with a human driver is commonly focused on driver behavior. In a high fidelity moving base driving simulator it is possible to provide realistic and repetitive driving situations using distinctive features such as: physical modelling of driven vehicle, a moving base, a physical cabin interface and an audio and visual representation of the driving environment. A desired but difficult goal to achieve using a moving base driving simulator is to have behavioral validity. In other words, \A driver in a moving base driving simulator should have the same driving behavior as he or she would have during the same driving task in a real vehicle.".In this thesis the focus is on high fidelity moving base driving simulators. The main target is to improve the behavior validity or to maintain behavior validity while adding complexity to the simulator. One main assumption in this thesis is that systems closer to the final product provide better accuracy and are perceived better if properly integrated. Thus, the approach in this thesis is to try to ease incorporation of such systems using combinations of the methods hardware-in-the-loop and distributed simulation. Hardware-in-the-loop is a method where hardware is interfaced into a software controlled environment/simulation. Distributed simulation is a method where parts of a simulation at physically different locations are connected together. For some simulator laboratories distributed simulation is the only feasible option since some hardware cannot be moved in an easy way.Results presented in this thesis show that a complete vehicle or hardware-in-the-loop test laboratory can successfully be connected to a moving base driving simulator. Further, it is demonstrated that using a framework for distributed simulation eases communication and integration due to standardized interfaces. One identified potential problem is complexity in interface wrappers when integrating hardware-in-the-loop in a distributed simulation framework. From this aspect, it is important to consider the model design and the intersections between software and hardware models. Another important issue discussed is the increased delay in overhead time when using a framework for distributed simulation.
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| 13. |
- Andersson-Assarsson, Johanna C., 1974, et al.
(författare)
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Evolution of age-related mutation-driven clonal haematopoiesis over 20 years is associated with metabolic dysfunction in obesity
- 2023
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Ingår i: Ebiomedicine. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background Haematopoietic clones caused by somatic mutations with >= 2% variant allele frequency (VAF) increase with age and are linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones (VAF<2%) are also associated with adverse outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes in individuals with obesity treated by usual care or bariatric surgery (a treatment that improves metabolic status), and to examine the expansion of clones in relation to age and metabolic dysregulation over up to 20 years.Methods Clonal haematopoiesis-driver mutations (CHDMs) were identified in blood samples from participants of the Swedish Obese Subjects intervention study. Using an ultrasensitive assay, we analysed single-timepoint samples from 1050 individuals treated by usual care and 841 individuals who had undergone bariatric surgery, and multiple-timepoint samples taken over 20 years from a subset (n = 40) of the individuals treated by usual care.Findings In this explorative study, prevalence of CHDMs was similar in the single-timepoint usual care and bariatric surgery groups (20.6% and 22.5%, respectively, P = 0.330), with VAF ranging from 0.01% to 31.15%. Clone sizes increased with age in individuals with obesity, but not in those who underwent bariatric surgery. In the multiple-timepoint analysis, VAF increased by on average 7% (range -4% to 24%) per year and rate of clone growth was negatively associated with HDL-cholesterol (R = -0.68, 1.74 E-04).Interpretation Low HDL-C was associated with growth of haematopoietic clones in individuals with obesity treated by usual care.
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| 14. |
- Andersson, Maria, et al.
(författare)
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Transport av dräktiga djur, transport av unga djur och åldersbestämning av foster
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- De flesta lantbruksdjur transporteras endast enstaka gånger i livet och har därför sällan möjlighet att vänja sig vid transporter på ett sätt som skulle förebygga stress och bidra till en god transportupplevelse. Att skapa förutsättningar som minimerar påverkan på djuren och underlättar drivning av djuren är därför av stor vikt. Livdjurstransport eller transport till slakt kan vara en mycket stressfylld situation för djur. EFSA har under 2022 publicerat tre olika utlåtanden om transport av nötkreatur, små idisslare och gris. EFSA har i sina utlåtanden identifierat följande relevanta välfärdsrisker: social stress i samband med omgruppering, stress då djuren hanteras av ovarsamma människor eller av människor som de inte är vana vid, stress på grund av värme eller kyla, skador, rörelsestress (orsakat av fordonets rörelser), predationsstress (specifikt hos får som drivs med hund), hunger, törst, respiratoriska problem (specifikt hos nötkreatur), begränsade rörelsemöjligheter, svårigheter att vila och sensorisk överstimulering. Sammantaget kan dessa välfärdsrisker leda till ackumulerad och hög stress, rädsla, smärta, obehag och utmattning hos djuren.Nötkreatur, grisar och får är sociala djur som lätt stressas om de separeras från sin grupp. Att ta hänsyn till deras naturliga flockbeteende genom att t.ex. inte driva djur enskilt utan i grupp (undantag för vuxna handjur som ofta behöver hanteras enskilt) är därför viktigt både före, under och efter transport. Omgrupperingar och social stress riskerar att leda till aggressioner och oönskade beteenden då djuren kan komma att skada sig själva eller varandra.Djurs tidigare erfarenheter av att bli hanterade av människor påverkar deras upplevelse och stressnivå vid hantering i samband med transport. En mer vänlig hantering av djuren tidigt i livet kan underlätta hanteringen i samband med transport. Djurens rädsla utgör en välfärdsrisk, både för djuren själva och för den transportör som ska hantera dem. Utlastningsutrymmen och drivvägar behöver vara väl designade för att få ett bra flöde när djuren lastas respektive lastas av och den som hanterar djuren behöver ha god kunskap om djurens naturliga beteenden.Hunger och törst kan uppstå hos djur under tiden från lastning till transport och urlastning. Risken för att djuren ska uppleva hunger och törst ökar med längre transporttider. Unga djur har ett naturligt tätare födointag vilket man kan behöva ta hänsyn till vid transport genom att erbjuda djuren möjlighet att äta och dricka oftare än äldre djur. I nuläget finns det inga optimala lösningar på hur man ska kunna tillgodose behovet av vatten eller annan utfodring på transport då intaget även påverkas av stress och sociala faktorer utöver vana vid utrustningen.Djurtätheten på transportfordonet är en viktig faktor som påverkar djurens möjligheter att hålla balansen och att kunna ligga ned och vila, men även risken för skador och död. Behovet av att kunna ligga ned under transport ökar med transportens längd och huruvida djuren ligger ned är kopplat till vilket utrymme som ges, där större utrymme leder till att fler djur ligger ned.Sen dräktighet räknas som ett tillstånd då det inte är lämpligt att transportera ett djur eftersom transport under denna period kan leda till negativa konsekvenser för djurets välfärd och risker för avkomman. Dräktighet innebär ökad sårbarhet både fysiskt och fysiologiskt. För dräktiga djur innebär därför den stress som förflyttning, lastning, ny miljö, okända människor, rörlig och ostabil transport, transportfordonets förutsättningar, samt avsaknad av foder och vatten under längre perioder, en större påfrestning med en ökad risk för negativa konsekvenser, än för icke-dräktiga djur. Dräktiga djur har en ökad metabolism och värmeproduktion, framförallt under sen dräktighet, vilket gör dräktiga djur mer känsliga för värmestress än icke-dräktiga djur. Vidare blir fysisk ansträngning jobbigare för det dräktiga djuret beroende både på den ökade tyngden och dess påverkan på rörelseapparaten. Även cirkulationssystemet blir mer ansträngt med en förhöjd hjärtfrekvens som följd. Vid värmestress ökar dessutom andningsfrekvensen påtagligt.Kortisol har en viktig roll i slutet av dräktigheten och för att initiera förlossning. I slutet av dräktigheten stiger kortisolnivåerna i moderdjurets blod till följd av att fostrets kortisolproduktion ökar. Förhöjda kortisolnivåer till följd av stress och fysisk ansträngning i samband med lastning, hantering, omgruppering, transport och nya miljöer kan orsaka abort eller för tidig igångsättning av förlossningen. Flera studier visar att det även finns risker under andra delar av dräktigheten. Transport ökar till exempel risken för embryonala förluster under tidig dräktighet hos gris, framför allt under vecka två till fyra, vilket är en kortisolkänslig period. För nötkreatur finns det risk för embryonala förluster vid transporter under dräktighetens första två månader och studier på får har visat på negativa effekter på lamm och ökad risk för fosterdöd vid förhöjda kortisolnivåer hos tackan. Det finns även en risk för epigenetiska effekter hos fostren vid stress hos moderdjuret, vilka kan komma att påverka avkomman senare i livet.När hondjuren ökar i vikt genom fostertillväxt och ökad volym av fostervätskor, påverkas deras rörlighet och förmåga att hålla balansen vilket kan göra att både lastning och transport försvåras samt innebära en ökad risk för halkskador och fläkningsskador. Eventuella led- och klövproblem kan dessutom förvärras eller försvåra rörelsemöjligheterna, även om uppenbar hälta inte alltid kan ses. Den ökade storleken gör att dräktiga djur kräver större plats under transporten, både för att djuren i sig är större, men också för att de ska kunna parera rörelser och hålla balansen. Dräktiga grisar minskar sin aktivitetsnivå och har större behov av att ligga ned och vila vilket behöver tillgodoses under transport.I slutet av dräktigheten, oklart exakt när, sker en uppmjukning av vävnaderna i bäckenregionen vilket är mer påtagligt för nötkreatur än för små idisslare och suggor. Uppmjukningen kvarstår även en tid efter förlossningen. Uppmjukningen ger försämrad stabilitet vid rörelse, vilket innebär risker vid både lastning och transport. Det är därför viktigt att man tar hänsyn till detta och har god tidsmarginal vid transport av dräktiga eller nyförlösta djur, så att djuren inte riskerar att transporteras under den tid som bäckenet är instabilt.Den vetenskapliga evidensen för EU:s regel om 90 % av den förväntade dräktighetstiden som gräns för transport av dräktiga djur förefaller oklar. Rådet ställer sig bakom konklusionen i EFSA:s utlåtande om transport av nötkreatur, små idisslare och gris, om att vetenskapliga belägg för den exakta nu gällande gränsdragningen saknas, samtidigt som det är tydligt att långt gången dräktighet är en riskfaktor för negativ djurvälfärd under transport. I de aktuella utlåtandena finns dock flera studier citerade som visar på sårbarhet för de dräktiga djuren och deras foster under en period som i många fall är längre än de sista 10 % av dräktighetstiden samt att det finns en ökad sårbarhet även under andra delar av dräktigheten och att både moderdjur och foster kan påverkas negativt av att transporteras.Det finns risk för att den stress som en transport innebär kan leda till att det sent dräktiga djuret aborterar eller att förlossningen sätts igång under eller strax efter transport. Då det således föreligger risker för foster och moderdjur vid transport av dräktiga djur under stora delar av dräktighetsperioden anser Rådet att transport av dräktiga djur (nötkreatur, får och gris) om möjligt bör undvikas.Vid transport av unga kalvar, smågrisar och lamm måste hänsyn tas till flera faktorer, såsom ålder, immunförsvarets utveckling, djurens allmänna hälsostatus, huruvida djuren är avvanda eller inte, social stress, etc. Unga djur är generellt känsligare än vuxna djur, och påverkas än mer av att utsättas för hunger och törst, kalla och varma transporter, och begränsade möjligheter att vila under transport. Under perioden då det passiva immunförsvaret går ned samtidigt som det aktiva immunförsvaret är under uppbyggnad är djuren extra känsliga för infektioner.Hur väl ett ungt djur klarar en transport beror bl.a. på längden på transporten (ju längre transport desto större risk för djurens välfärd), samt djurets ålder och vikt. Tiden mellan två och fyra veckor är en känslig ålder för transport av kalvar. Enligt EFSA bör inte kalvar transporteras tidigare än vid fem veckors ålder och de bör väga minst 50 kg. För lamm rekommenderas att djuren transporteras först efter avvänjning. Vidare behöver hänsyn tas till djurens behov av foder och vatten, så att deras närings- samt vätskebehov tillgodoses. Hänsyn behöver även tas till på vilket sätt de är vana vid att inta foder och vatten, och om djuret hålls på liknande sätt i transporten som de är vana vid, exempelvis i samma grupp eller tillsammans med sin mamma. Det kan vara klokt att utfodra djuren innan transport för att minska risken för hunger under transporten. Vid mjölkgiva till kalv behöver tid ges för digestion innan transport för att minska risken för diarré.Icke avvanda djur upplever en större stress runt transport än avvanda djur (vid transport utan moderdjur) och det är därför bättre att företrädesvis transportera djuren efter avvänjning. Unga djur är heller inte motoriskt färdigutvecklade, vilket kan påverka deras balans under transport samt vid på- och avlastning. Yngre djur ligger ned oc
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| 20. |
- Anveden, Åsa, et al.
(författare)
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Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study
- 2017
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 145:2, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To examine the long-term effects of bariatric surgery on female-specific cancer in women with obesity. Methods. The prospective, matched Swedish Obese Subjects (SOS) study was designed to examine outcomes after bariatric surgery. This study includes 1420 women from the SOS cohort that underwent bariatric surgery and 1447 contemporaneously matched controls who received conventional obesity treatment. Age was 3760 years and BMI was >= 38 kg/m(2). Information on cancer events was obtained from the Swedish National Cancer Registry. Median follow-up time was 18.1 years (interquartile range 14.8-20.9 years, maximum 26 years). This study is registered with ClinicalTrials.gov, NCT01479452. Results. Bariatric surgery was associated with reduced risk of overall cancer (hazard ratio = 0.71; 95% CI 0.59-0.85; p < 0.001). About half of the observed cancers were female-specific, and the incidence of these were lower in the surgery group compared with the control group (hazard ratio = 0.68; 95% CI 0.52-0.88; p = 0.004). The surgical treatment benefit with respect to female-specific cancer was significantly associated with baseline serum insulin (interaction p value = 0.022), with greater relative treatment benefit in patients with medium or high insulin levels. Separate analyses of different types of female-specific cancers showed that bariatric surgery was associated with reduced risk of endometrial cancer (hazard ratio = 0.56: 95% CI 035-0.89; p = 0.014). Conclusions. In this long-term study, bariatric surgery was associated with reduced risk of female-specific cancer, especially in women with hyperinsulinemia at baseline.
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| 21. |
- Baker, Naomi L., et al.
(författare)
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Molecular consequences of dominant Bethlem myopathy collagen VI mutations
- 2007
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 62:4, s. 390-405
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dominant mutations in the three collagen VI genes cause Bethlem myopathy, a disorder characterized by proximal muscle weakness and commonly contractures of the fingers, wrists, and ankles. Although more than 20 different dominant mutations have been identified in Bethlem myopathy patients, the biosynthetic consequences of only a subset of these have been studied, and in many cases, the pathogenic mechanisms remain unknown. Methods: We have screened fourteen Bethlem myopathy patients for collagen VI mutations and performed detailed analyses of collagen VI biosynthesis and intracellular and extracellular assembly. Results: Collagen VI abnormalities were identified in eight patients. One patient produced around half the normal amount of alpha 1(VI) messenger RNA and reduced amounts of collagen VI protein. Two patients had a previously reported mutation causing skipping of COL6A1 exon 14, and three patients had novel mutations leading to in-frame deletions toward the N-terminal end of the triple-helical domain. These mutations have different and complex effects on collagen VI intracellular and extracellular assembly. Two patients had single amino acid substitutions in the A-domains of COL6A2 and COL6A3. Collagen VI intracellular and extracellular assembly was normal in one of these patients. Interpretation: The key to dissecting the pathogenic mechanisms of collagen VI mutations lies in detailed analysis of collagen VI biosynthesis and assembly. The majority of mutations result in secretion and deposition of structurally abnormal collagen VI. However, one A-domain mutation had no detectable effect on assembly, suggesting that it acts by compromising collagen VI interactions in the extracellular matrix of muscle.
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| 24. |
- Burza, Maria Antonella, 1980, et al.
(författare)
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PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals
- 2012
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 44:12, s. 1037-1041
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a risk factor for cancer, including hepatocellular carcinoma. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with chronic alcohol abuse or hepatic viral infection. In the present study we examined the association between the PNPLA3I148M genetic variant and hepatocellular carcinoma in obese individuals from the Swedish Obese Subjects cohort (n=4047). Methods: We performed a matched, prospective, controlled, interventional trial, investigating the effect of bariatric surgery (surgery group) compared to conventional treatment (control group) for obesity. Results: A total of 9 events were observed in the 15-year median follow up (5 in the control group and 4 in the surgery group). A significantly higher incidence of hepatocellular carcinoma in PNPLA3 148M allele carriers was found in obese individuals in the control group (log-rank P-value=0.001), but not in the surgery group (log-rank P-value=0.783). Consistently, an increased risk (for each PNPLA3 148M allele, hazard ratio: 5.9; 95% confidence interval 1.5-23.8; P-value=0.013) of developing hepatocellular carcinoma was observed only in the control group. Conclusion: The current study is the first prospective report showing the association of the PNPLA3I148M genetic variant and hepatocellular carcinoma in severely obese individuals.
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| 25. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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ALK7 expression is specific for adipose tissue, reduced in obesity and correlates to factors implicated in metabolic disease.
- 2009
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 382:2, s. 309-14
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Tidskriftsartikel (refereegranskat)abstract
- Human adipose tissue is a major site of expression of inhibin beta B (INHBB) which homodimerizes to form the novel adipokine activin B. Our aim was to determine if molecules needed for a local action of activin B are expressed in adipose tissue. Microarray analysis showed that adipose tissue expressed activin type I and II receptors and that the expression of activin receptor-like kinase 7 (ALK7) was adipose tissue specific. In obesity discordant siblings from the SOS Sib Pair study, adipose tissue ALK7 expression was higher in lean (n=90) compared to obese (n=90) subjects (p=4 x 10(-31)). Adipose tissue ALK7 expression correlated with several measures of body fat, carbohydrate metabolism and lipids. In addition, ALK7 and INHBB expression correlated but only in lean subjects and in subjects with normal glucose tolerance. We conclude that activin B may have local effects in adipose tissue and thereby influence obesity and its comorbidities.
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| 26. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects.
- 2012
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 367:8, s. 695-704
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes.
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| 27. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.
- 2023
-
Ingår i: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8
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Tidskriftsartikel (refereegranskat)abstract
- To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study.The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n=265), banding (n=376), or vertical banded gastroplasty (n=1369). The control group (n=2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n=392 surgery patients/n=305 controls) or non-T2D (n=1609 surgery patients/n=1726 controls) during a median follow-up 26 years.In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR)=0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p=0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR=0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p=0.516)).Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.
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| 28. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Long-term incidence of microvascular disease after bariatric surgery or usual care in patients with obesity, stratified by baseline glycaemic status: a post-hoc analysis of participants from the Swedish Obese Subjects study.
- 2017
-
Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595. ; 5:4, s. 271-279
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery is associated with remission of diabetes and prevention of diabetic complications in patients with obesity and type 2 diabetes. Long-term effects of bariatric surgery on microvascular complications in patients with prediabetes are unknown. The aim of this study was to examine the effects of bariatric surgery on incidence of microvascular complications in patients with obesity stratified by baseline glycaemic status.Patients were recruited to the Swedish Obese Subjects (SOS) study between Sept 1, 1987, and Jan 31, 2001. Inclusion criteria were age 37-60 years and BMI of 34 kg/m(2) or greater in men and 38 kg/m(2) or greater in women. Exclusion criteria were identical in surgery and control groups and designed to exclude patients not suitable for surgery. The surgery group (n=2010) underwent gastric bypass (265 [13%]), gastric banding (376 [19%]), or vertical-banded gastroplasty (1369 [68%]). Participants in the control group (n=2037) received usual care. Bodyweight was measured and questionnaires were completed at baseline and at 0·5 years, 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years. Biochemical variables were measured at baseline and at 2 years, 10 years, and 15 years. We categorised participants into subgroups on the basis of baseline glycaemic status (normal [fasting blood glucose concentration <5·0 mmol/L], prediabetes [5·0-6·0 mmol/L], screen-detected diabetes [≥6·1 mmol/L at baseline visit without previous diagnosis], and established diabetes [diagnosis of diabetes before study inclusion]). We obtained data about first incidence of microvascular disease from nationwide registers and about diabetes incidence at study visits at 2 years, 10 years, and 15 years. We did the main analysis by intention to treat, and subgroup analyses after stratification by baseline glycaemic status and by diabetes status at the 15 year follow-up. The SOS study is registered with ClinicalTrials.gov, NCT01479452.4032 of the 4047 participants in the SOS study were included in this analysis. We excluded four patients with suspected type 1 diabetes, and 11 patients with unknown glycaemic status at baseline. At baseline, 2838 patients had normal blood glucose, 591 had prediabetes, 246 had screen-detected diabetes, and 357 had established diabetes. Median follow-up was 19 years (IQR 16-21). We identified 374 incident cases of microvascular disease in the control group and 224 in the surgery group (hazard ratio [HR] 0·56, 95% CI 0·48-0·66; p<0·0001). Interaction between baseline glycaemic status and effect of treatment on incidence of microvascular disease was significant (p=0·0003). Unadjusted HRs were lowest in the subgroup with prediabetes (0·18, 95% CI 0·11-0·30), followed by subgroups with screen-detected diabetes (0·39, 0·24-0·65), established diabetes (0·54, 0·40-0·72), and normoglycaemia (0·63, 0·48-0·81). Surgery was associated with reduced incidence of microvascular events in people with prediabetes regardless of whether they developed diabetes during follow-up.Bariatric surgery was associated with reduced risk of microvascular complications in all subgroups, but the greatest relative risk reduction was observed in patients with prediabetes at baseline. Our results suggest that prediabetes should be treated aggressively to prevent future microvascular events, and effective non-surgical treatments need to be developed for this purpose.US National Institutes of Health, Swedish Research Council, Sahlgrenska University Hospital Regional Agreement on Medical Education and Research, and Swedish Diabetes Foundation.
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| 29. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.
- 2019
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Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937
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Tidskriftsartikel (refereegranskat)abstract
- Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was≥34kg/m2 in men and ≥38kg/m2 in women. The surgery per-protocol group (n=2007) underwent gastric bypass (n=266), banding (n=376), or vertical banded gastroplasty (n=1365), and controls (n=2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P=0.002). The incidence differed between treatment groups (P<0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P<0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.
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| 30. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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The incidence of albuminuria after bariatric surgery and usual care in swedish obese subjects (SOS): a prospective controlled intervention trial.
- 2015
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 39:1, s. 169-175
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Tidskriftsartikel (refereegranskat)abstract
- Background:Obesity is associated with increased risk of chronic kidney disease and albuminuria is a predictor of renal impairment. Bariatric surgery reduces body weight in obese subjects, but it is not known whether surgery can prevent development of albuminuria. This study aims to determine the long-term effect of bariatric surgery on the incidence of albuminuria.Subjects:The Swedish Obese Subjects study is a non-randomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden. Between 1 September 1987 and 31 January 2001, 2010 participants who underwent bariatric surgery and 2037 controls were recruited. Inclusion criteria were age 37-60 years and BMI⩾34 in men and BMI⩾38 in women. In this analysis, we included 1498 patients in the surgery group and 1610 controls without albuminuria at baseline. Patients in the bariatric surgery group underwent banding (18%), vertical banded gastroplasty (69%) or gastric bypass (13%); controls received usual obesity care. Date of analysis was 1 January 2011. Median follow-up was 10 years, and the rates of follow-up were 87%, 74 and 52% at 2, 10 and 15 years, respectively. The main outcome of this report is incidence of albuminuria (defined as urinary albumin excretion >30mg per 24h) over up to 15 years.Results:During the follow-up, albuminuria developed in 246 participants in the control group and in 126 in the bariatric surgery group, corresponding to incidence rates of 20.4 and 9.4 per 1000 person years, respectively (adjusted hazard ratio, 0.37; 95% confidence interval, 0.30-0.47; P<0.001). The expected number of surgeries needed to prevent the development of albuminuria in one patient at 10 years was nine.Conclusions:Bariatric surgery is associated with reduced incidence of albuminuria compared with usual obesity care.International Journal of Obesity advance online publication, 10 June 2014; doi:10.1038/ijo.2014.72.
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| 31. |
- Carrero, Juan Jesus, et al.
(författare)
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Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation
- 2014
-
Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:9, s. 919-928
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Conflicting evidence exists regarding the association between warfarin treatment, death, and ischemic stroke incidence in patients with advanced chronic kidney disease (CKD) and atrial fibrillation. OBJECTIVE To study outcomes associated with warfarin treatment in relation to kidney function among patients with established cardiovascular disease and atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Observational, prospective, multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry (2003-2010), which includes all Swedish hospitals that provide care for acute cardiac diseases. Participants included consecutive survivors of an acute myocardial infarction (MI) with atrial fibrillation and known serum creatinine (N = 24 317), including 21.8% who were prescribed warfarin at discharge. Chronic kidney disease stages were classified according to estimated glomerular filtration rate (eGFR). MAIN OUTCOMES AND MEASURES (1) Composite end point analysis of death, readmission due to MI, or ischemic stroke; (2) bleeding (composite of readmission due to hemorrhagic stroke, gastrointestinal bleeding, bleeding causing anemia, and others); or (3) the aggregate of these 2 outcomes within 1 year from discharge date. RESULTS A total of 5292 patients (21.8%) were treated with warfarin at discharge, and 51.7% had manifest CKD (eGFR <60 mL/min/1.73 m(2) [eGFR(<60)]). Compared with no warfarin use, warfarin was associated with a lower risk of the first composite outcome (n = 9002 events) in each CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 28.0 for warfarin vs 36.1 for no warfarin; adjusted hazard ratio (HR), 0.73 (95% CI, 0.65 to 0.81); eGFR(>30-60): event rate, 48.5 for warfarin vs 63.8 for no warfarin; HR, 0.73 (95% CI, 0.66 to 0.80); eGFR(>15-30): event rate, 84.3 for warfarin vs 110.1 for no warfarin; HR, 0.84 (95% CI, 0.70-1.02); eGFR(<= 15): event rate, 83.2 for warfarin vs 128.3 for no warfarin; HR, 0.57 (95% CI, 0.37-0.86). The risk of bleeding (n = 1202 events) was not significantly higher in patients treated with warfarin in any CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 5.0 for warfarin vs 4.8 for no warfarin; HR, 1.10 (95% CI, 0.86-1.41); eGFR(>30-60) event rate, 6.8 forwarfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR(>15-30) event rate, 9.3 forwarfarin vs 10.4 for nowarfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR(<= 15) event rate, 9.1 forwarfarin vs 13.5 for nowarfarin; HR, 0.52 (95% CI, 0.16-1.65). Warfarin use in each CKD stratum was associated with lower hazards of the aggregate outcome (n = 9592 events) for event rates per 100 person-years: eGFR(>60) event rate, 32.1 for warfarin vs 40.0 for no warfarin; HR, 0.76 (95% CI, 0.69-0.84); eGFR(>30-60) event rate, 53.6 forwarfarin vs 69.0 for nowarfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR(>15-30) event rate, 90.2 forwarfarin vs 117.7 for nowarfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR(<= 15) event rate, 86.2 forwarfarin vs 138.2 for nowarfarin; HR, 0.55 (95% CI, 0.37-0.83). CONCLUSIONS AND RELEVANCE Warfarin treatment was associated with a lower 1-year risk for the composite outcome of death, MI, and ischemic stroke without a higher risk of bleeding in consecutive acute MI patients with atrial fibrillation. This association was not related to the severity of concurrent CKD.
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| 32. |
- Clark, Stephen J, et al.
(författare)
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Association of Sirtuin 1 (SIRT1) Gene SNPs and Transcript Expression Levels With Severe Obesity.
- 2012
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 20:1, s. 178-85
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have reported associations of sirtuin 1 (SIRT1) single nucleotide polymorphisms (SNPs) to both obesity and BMI. This study was designed to investigate association between SIRT1 SNPs, SIRT1 gene expression and obesity. Case-control analyses were performed using 1,533 obese subjects (896 adults, BMI >40kg/m(2) and 637 children, BMI >97th percentile for age and sex) and 1,237 nonobese controls, all French Caucasians. Two SNPs (in high linkage disequilibrium (LD), r(2) = 0.96) were significantly associated with adult obesity, rs33957861 (P value = 0.003, odds ratio (OR) = 0.75, confidence interval (CI) = 0.61-0.92) and rs11599176 (P value: 0.006, OR = 0.74, CI = 0.61-0.90). Expression of SIRT1 mRNA was measured in BMI-discordant siblings from 154 Swedish families. Transcript expression was significantly correlated to BMI in the lean siblings (r(2) = 0.13, P value = 3.36 × 10(-7)) and lower SIRT1 expression was associated with obesity (P value = 1.56 × 10(-35)). There was also an association between four SNPs (rs11599176, rs12413112, rs33957861, and rs35689145) and BMI (P values: 4 × 10(-4), 6 × 10(-4), 4 × 10(-4), and 2 × 10(-3)) with the rare allele associated with a lower BMI. However, no SNP was associated with SIRT1 transcript expression level. In summary, both SNPs and SIRT1 gene expression are associated with severe obesity.
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| 33. |
- Edrén, Johannes, 1983-, et al.
(författare)
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Road friction effect on the optimal vehicle control strategy in two critical manoeuvres
- 2014
-
Ingår i: International Journal of Vehicle Safety. - 1479-3105 .- 1479-3113. ; Vol. 7:No. 2, s. pp 107-130
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents a research study on the optimal way to negotiate safety-critical vehicle manoeuvres depending on the available actuators and road friction level. The motive is to provide viable knowledge of the limitations of vehicle capability under the presence of environmental preview sensors. In this paper, an optimal path is found by optimising the sequence of actuator requests during the manoeuvres. Particular attention is paid to how the vehicle control strategy depends on friction. This study shows that the actuation of all the forces and torques on and around the vehicle centre of gravity is approximately scaled with friction, whereas at individual wheel level, the optimal force allocation will differ under different friction conditions. A lower friction level leads to lower velocities and load transfer, which influences the individual wheels’ tyre force constraints. However, the actuator response compared to the whole system is increased at a lower friction level.
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| 34. |
- Eidemüller, Markus, et al.
(författare)
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Breast cancer risk after radiation treatment at infancy: potential consequences of radiation-induced genomic instability.
- 2011
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Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 143:2-4, s. 375-9
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Tidskriftsartikel (refereegranskat)abstract
- Swedish hemangioma patients were treated in infancy mainly by external application of radium-226 starting from 1920. This work analysed the radiation risk among 17,158 women with a total of 678 breast cancer incidence cases with models of carcinogenesis and empirical excess relative risk models. Models incorporating effects of genomic instability were developed and applied to the hemangioma cohort. The description of the radiation risk was significantly improved with a model of genomic instability at an early stage of carcinogenesis.
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| 35. |
- Eleftherohorinou, Hariklia, et al.
(författare)
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famCNV: copy number variant association for quantitative traits in families.
- 2011
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Ingår i: Bioinformatics (Oxford, England). - : Oxford University Press (OUP). - 1367-4811 .- 1367-4803. ; 27:13, s. 1873-5
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Tidskriftsartikel (refereegranskat)abstract
- A program package to enable genome-wide association of copy number variants (CNVs) with quantitative phenotypes in families of arbitrary size and complexity. Intensity signals that act as proxies for the number of copies are modeled in a variance component framework and association with traits is assessed through formal likelihood testing. AVAILABILITY AND IMPLEMENTATION: The Java package is made available at www.imperial.ac.uk/medicine/people/m.falchi/. CONTACT: m.falchi@imperial.ac.uk.
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| 36. |
- Falchi, M., et al.
(författare)
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Low copy number of the salivary amylase gene predisposes to obesity
- 2014
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:5, s. 492-497
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Tidskriftsartikel (refereegranskat)abstract
- Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10-14) and serum enzyme levels (P < 2.20 × 10-16), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy =-0.15 (0.02) kg/m 2; P = 6.93 × 10-10) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10-10). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies. © 2014 Nature America, Inc. All rights reserved.
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| 37. |
- Fitzsimmons-Craft, Ellen E., et al.
(författare)
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Harnessing mobile technology to reduce mental health disorders in college populations : A randomized controlled trial study protocol
- 2021
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Ingår i: Contemporary Clinical Trials. - : ELSEVIER SCIENCE INC. - 1551-7144 .- 1559-2030. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- About a third of college students struggle with anxiety, depression, or an eating disorder, and only 20?40% of college students with mental disorders receive treatment. Inadequacies in mental health care delivery result in prolonged illness, disease progression, poorer prognosis, and greater likelihood of relapse, highlighting the need for a new approach to detect mental health problems and engage college students in services. We have developed a transdiagnostic, low-cost mobile mental health targeted prevention and intervention platform that uses population-level screening to engage college students in tailored services that address common mental health problems. We will test the impact of this mobile mental health platform for service delivery in a large-scale trial across 20+ colleges. Students who screen positive or at high-risk for clinical anxiety, depression, or an eating disorder and who are not currently engaged in mental health services (N = 7884) will be randomly assigned to: 1) intervention via the mobile mental health platform; or 2) referral to usual care (i.e., campus health or counseling center). We will test whether the mobile mental health platform, compared to referral, is associated with improved uptake, reduced clinical cases, disorder-specific symptoms, and improved quality of life and functioning. We will also test mediators, predictors, and moderators of improved mental health outcomes, as well as stakeholder-relevant outcomes, including cost-effectiveness and academic performance. This population-level approach to service engagement has the potential to improve mental health outcomes for the millions of students enrolled in U.S. colleges and universities.
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| 38. |
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| 39. |
- Forsberg, Peter, 1983-
(författare)
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Combustion Valve Wear : A Tribological Study of Combustion Valve Sealing Interfaces
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The exhaust valve system of combustion engines experiences a very complex contact situation of frequent impact involving micro sliding, high and varying temperatures, complex exhaust gas chemistry and possible particulates, etc. In addition, the tribological situation in the exhaust valve system is expected to become even worse due to strict future emission regulations, which will require enhanced combustion and cleaner fuels. This will substantially reduce the formation of combustion products that might ease the contact conditions by forming tribofilms on the contacting surfaces. The lack of protective films is expected to result in increased wear of the contact surfaces.The aim of the work presented in this thesis has been to increase the tribological understanding of the valves. The wear that takes place in the valve sealing interface and how the change in operating conditions affects it have been studied. Such understanding will facilitate the development of future valve designs.A test rig has been developed. It has a unique design with the ability to insert ppm amounts of media into a hot air flow, in order to simulate different environmental changes, e.g. varying amount and composition of combustion residue particles.PVD coated valves were evaluated in a dry atmosphere. It was concluded that although some of the coatings showed potential, the substrate could not support the thin, hard coatings.Investigations with an addition of different oils have been performed. Fully formulated oils proved to build up a protective oil residue tribofilm. This tribofilm has been in-depth analysed and proved to have similar composition and appearance as tribofilms found on low wear field tested valves. With a non-additivated oil, wear particles from the valve seat insert formed a wear particle tribofilm on top of the valve sealing surface. Without any oil the surfaces showed severe wear with wear particles spread over the surfaces.The results presented give a hint about what to be expected in the future, when the engine oils are replaced with ash less oils with reduced amount of additives and the consumed amount of oil within the cylinders are reduced.
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| 40. |
- Forsberg, Peter, 1983-, et al.
(författare)
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Comparison and analysis of protective tribofilms found on heavy duty exhaust valves from field service and made in test rig
- 2013
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Ingår i: Wear. - : Elsevier. - 0043-1648 .- 1873-2577. ; 302:1-2 SI, s. 1351-1359
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Tidskriftsartikel (refereegranskat)abstract
- Increasing demands from environmental legislations are changing the conditions that the valve system is exposed to in heavy duty engines. Increased pressures, higher temperatures and lower amounts of particulates which can build up a protective film are some of the increasing challenges which the system has to endure. Thick protective tribofilms found on heavy duty exhaust valve surfaces have been analysed with SEM, TEM, EFTEM, STEM-EDS, Nano-indenter and XPS in order to get a better understanding for the tribofilms properties. Two analysed samples are presented in this paper, from a field service truck and another from atest rig which uses vaporised engine oil to simulate the particle flow. The tribofilms are built upfrom several layers with varying compositions. Most of the material originates from oil additives, but also metallic oxides and other carbon compounds produced in the combustion system. The similarities between the rig generated tribofilm and the tribofilm found on the field tested valve verify the test rig behaviour and opens up for realistic wear testing where the importance ofthe protective tribofilm can be investigated in detail that is not possible in motor tests.
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| 41. |
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| 42. |
- Forsberg, Peter, 1983-, et al.
(författare)
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Performance of DLC coatings in heated commercial engine oil
- 2013
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Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 304:1-2, s. 211-222
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Tidskriftsartikel (refereegranskat)abstract
- Multilayer Diamond Like Coatings (DLC) are widely used to protect highly loaded components from wear and/or to reduce the friction losses in combustion engines. The uppermost layer of the coating controls the chemical situation in the contact and is therefore a very important part of modern multilayer coatings. To examine the individual performances and assess differences and potentials of modern DLC coatings, four commercially available DLCs designed for automotive components with different doping elements together with an uncoated reference were tested in high performance engine oils heated to 90 °C at two different initial contact pressures. The coefficient of friction generally was higher in the tests with the lower initial contact pressure (approximately 20% for all combinations) and the specific wear rate was also up to 100% higher for some combinations. It was also found that a used motor oil showed up to 30% higher friction than when fresh and at the same time reduced the wear in most cases. The tungsten doped coating showed the highest wear, but also the lowest coefficient of friction. The Si doped coating showed the best wear results, most probably due to the ability to make use of the additives in the oil to form a protecting tribofilm.
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| 43. |
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| 44. |
- Forsberg, Peter, 1983-, et al.
(författare)
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Quantification of Combustion Valve Sealing Interface Sliding - A Novel Experimental Technique and Simulations
- 2014
-
Ingår i: Tribology International. - : Elsevier BV. - 0301-679X .- 1879-2464. ; 69, s. 150-155
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Tidskriftsartikel (refereegranskat)abstract
- The rapid sharpening of the environmental legislation during the last decades has forced engine manufacturers to radical design modifications. It has been shown that the sliding in the sealing interface is one of the major reasons for wear. The sliding wear is expected to have an even more important role in modern engines. This paper presents unique experimental data, acquired using a dedicated technique in a test-rig. The experimental data is complemented by FEM-simulations. The simulations involve validation of the test-rig valve sealing interface sliding behaviour and investigations on how different parameters influence the sliding length. These parameters include combustion pressure, contact angle, contact length, valve head thickness, coefficient of friction, running-in wear, and change of elastic modulus due to temperature variations.
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| 45. |
- Forsberg, Peter, 1983-, et al.
(författare)
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The importance of oil and particle flow for exhaust valve wear - An experimental study
- 2014
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Ingår i: Tribology International. - : Elsevier BV. - 0301-679X .- 1879-2464. ; 69, s. 176-183
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Tidskriftsartikel (refereegranskat)abstract
- Oil residue particles have a large impact in protecting the sealing surfaces of heavy duty exhaust valves. To increase the understanding of the mechanism behind this, the wear behavior of exhaust valves subjected to a flow of hot air with controlled amounts of oil particles of three different compositions has been investigated. Air flow without addition of oil was used as a reference. The degree and mechanisms of surface damage proved to be sensitive to the test parameters. Residues from the oils containing additives proved to form protective tribofilms, while the oil without additives promoted agglomeration of wear debris on the sealing surfaces. The dry reference showed severe wear with debris scattered over the surfaces.
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| 46. |
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| 47. |
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| 48. |
- Forsberg, Peter, et al.
(författare)
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Wear mechanism study of exhaust valve system in modern heavy duty combustion engines
- 2011
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Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 271:9-10, s. 2477-2484
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Tidskriftsartikel (refereegranskat)abstract
- The increasing demands from environmental legislations are changing the conditions that the valve system is exposed to in heavy duty engines. Increased pressures, higher temperatures and lower amounts of soot which can build up a protective film are some of the increasing challenges which the system has to endure. Three pairs of valves and valve seat inserts with the same material and design properties but with different service condition have been analyzed with a variety of analytical instruments to gain information of how the wear occurs. The wear mechanisms found were a combination of oxidation, where many different oxides were found, adhesive wear, which was seen both in form of material transfer and flow lines. On top of Sample Mild and Hard there were tribo films of thickness varying from 1 to 5 mu m consisting of Ca, O, P, S and Zn. The film has in all cases protected the underlying surface from wear but in some cases seems to have a corrosive impact instead.
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| 49. |
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| 50. |
- Froguel, Philippe, et al.
(författare)
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A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far. We used a genome-wide association study initially conducted in 631 French children followed by a replication in three additional European sample sets and we identified a common single nucleotide polymorphism (SNP), rs2000999 located in the Haptoglobin gene (HP) as a strong genetic predictor of circulating Haptoglobin levels (P overall = 8.1×10 -59), explaining 45.4% of its genetic variability (11.8% of Hp global variance). The functional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels (β = 0.23±0.08, P = 0.007). Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789 European children (P total cholesterol = 0.002 and P LDL = 0.0008). Given the central position of haptoglobin in many inflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobin concentration should be further investigated in order to improve its diagnostic/therapeutic and/or prevention impact. © 2012 Froguel et al.
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