| 1. |
- Mullins, Niamh, et al.
(författare)
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GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
- 2019
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 176:8, s. 651-660
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Tidskriftsartikel (refereegranskat)abstract
- Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.
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| 2. |
- Arnold, S. V., et al.
(författare)
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Recognition of Incident Diabetes Mellitus During an Acute Myocardial Infarction
- 2015
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Ingår i: Circulation-Cardiovascular Quality and Outcomes. - : Ovid Technologies (Wolters Kluwer Health). - 1941-7705 .- 1941-7713. ; 8:3, s. 260-267
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Tidskriftsartikel (refereegranskat)abstract
- Background-Diabetes mellitus (DM) is common in patients hospitalized with an acute myocardial infarction (AMI), representing in some cases the first opportunity to recognize and treat DM. We report the incidence of new DM and its recognition among patients with AMI. Methods and Results-Patients in a 24-site US AMI registry (2005-08) had glycosylated hemoglobin assessed at a core laboratory, with results blinded to clinicians and local clinical measurements left to the discretion of the treating providers. Among 2854 AMI patients without known DM on admission, 287 patients (10%) met criteria for previously unknown DM, defined by a core laboratory glycosylated hemoglobin of >= 6.5%. Among these, 186 (65%) were unrecognized by treating clinicians, receiving neither DM education, glucose-lowering medications at discharge, nor documentation of DM in the chart (median glycosylated hemoglobin of unrecognized patients, 6.7%; range, 6.5-12.3%). Six months after discharge, only 5% of those not recognized as having DM during hospitalization had been initiated on glucose-lowering medications versus 66% of those recognized (P< 0.001). Conclusions-Underlying DM that has not been previously diagnosed is common among AMI patients, affecting 1 in 10 patients, yet is recognized by the care team only one third of the time. Given its frequency and therapeutic implications, including but extending beyond the initiation of glucose-lowering treatment, consideration should be given to screening all AMI patients for DM during hospitalization. Inexpensive, ubiquitous, and endorsed as an acceptable screen for DM, glycosylated hemoglobin testing should be considered for this purpose.
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| 3. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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| 4. |
- Benjamin, Daniel J., et al.
(författare)
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Redefine statistical significance
- 2018
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Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 2:1, s. 6-10
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
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| 6. |
- Bignert, Anders, et al.
(författare)
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Comments Concerning the National Swedish Contaminant Monitoring Programme in Marine Biota, 2015
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The environmental toxicants examined in this report can be classified into five groups – heavy metals, chlorinated compounds, brominated flame retardants, polyaromatic hydrocarbons and perfluorinated compounds. Each of these contaminants have been examined from various sites for up to six different fish species, in blue mussels, and in guillemot eggs, for varying lengths of time. The following summary examines overall trends, spatial and temporal, for the five groups.Condition and Fat ContentCondition and fat content in different species tended to follow the same pattern at the same sites, with a few exceptions. Most of the fish species generally displayed a decreasing trend in both condition and fat content at most sites examined. Exceptions to this were increases in condition factor seen in cod liver at Fladen, perch muscle at Kvädöfjärden, and for herring at Ängskärsklubb in spring. Also, an increase in fat content was seen during the most recent ten years for herring at Ängskärsklubb in spring. There were also some sites where no log linear trends were seen.Heavy MetalsDue to a change in methods for metal analysis (not mercury) in 2004, values between 2003 and 2007 should be interpreted with care. From 2009 metals are analyzed at ACES, Stockholm University.Generally, higher mercury concentrations are found in the Bothnian Bay, but also from one station in the Northern parts of Baltic Proper, compared to other parts of the Swedish coastline. The time series show varying concentrations over the study period. The longer time series in guillemot egg and spring-caught herring from the southern Bothnian Sea and southern Baltic Proper show significant decreases of mercury. On the other hand, increasing concentrations are seen in e.g., cod muscle, but the concentrations are fairly low compared to measured concentrations in perch from fresh water and coastal sites. In most cases, the mercury concentrations are above the EQSbiota of 20 ng/g wet weight.Lead is generally decreasing over the study period (in time series of sufficient length), supposedly due to the elimination of lead in gasoline. The highest concentrations are seen in the southern part of the Baltic Sea. Elevated lead concentrations between 2003 and 2007 (e.g. Harufjärden) should be viewed with caution (see above regarding change in analysis methods). Lead concentrations are below the suggested target level at all stations.Cadmium concentrations show varying non-linear trends over the monitored period. It is worth noting that despite several measures taken to reduce discharges of cadmium, generally the most recent concentrations are similar to concentrations measured 30 yearsago in the longer time series. Cadmium concentrations in herring and perch are all below the suggested target level of 160 μg/kg wet weight.The reported nickel concentrations show no consistent decreasing trends. Some series begin with two elevated values that exert a strong leverage effect on the regression line and may give a false impression of decreasing trends. Chromium generally shows decreasing concentrations, possibly explained by a shift in analytical method. The essential trace metals, copper and zinc, show no consistent trends during the monitored period.Generally higher concentrations of arsenic and silver are found along the west coast compared to other parts of the Sweadish coast line. However for silver a few stations in the Bothnian Sea and Bothnian Bay show comparable concentrations to the west coast stations.Chlorinated CompoundsGenerally, a decreasing concentrations were observed for all compounds (DDT’s, PCB’s, HCH’s, HCB) in all species examined, with a few exceptions, such as no change in TCDD-equivalents being seen in herring muscle (except at Änskärsklubb where very high concentrations at the beginning of the sampling period were seen and also at the west coast station Fladen). The longer time-series in guillemot also show a marked decrease in TCDD-equivalents from the start in the late 1960s until about 1985 from where no change occurred for many years, however, during the most recent ten years a decrease in the concentration is seen. Concentrations of DDE and CB-118 are for some species and sites still above their respective target levels.The chlorinated compounds generally show higher concentrations in the Bothnian Sea and/or Baltic Proper when compared to the Bothnian Bay and the Swedish west coast.Brominated Flame RetardantsElevated levels of HBCDD are seen in sites from the Baltic Proper, while the investigated PBDEs show higher concentrations in the Bothnian Bay. In addition, lower concentrations of all investigated PBDEs and HBCDD are seen on the Swedish west coast compared to the east coast. Temporally, significant increases in BDE-47, -99 and -100 have been seen in guillemot eggs since the late 1960s until the early 1990s, where concentrations then began to show decreases. Also, the concentration of HBCDD in guillemot eggs shows a decrease during the most recent ten years. For fish and blue mussels, BDE-47, -99, and -153 decreased at some sites and showed no trend at other sites. The concentration of HBCDD in fish and blue mussels showed inconsistent trends. The concentration of HBCDD is below the EQSbiota of 167 μg/kg wet weight for all fish species from all areas, while the concentration of BDE-47 alone is above the EQSbiota for sumPBDE of 0.0085 ng/g wet weight.PAHsOnly blue mussels have been examined for spatial differences in PAH concentrations. Concentration of ΣPAH was found to be higher from Kvädöfjärden in the Baltic Proper compared to stations at the West coast, but individual PAHs showed varying spatial patterns. Over time, acenaphthalene was rarely found above the detection limit. Significant decreasing trends were observed for ΣPAH, chrysene, fluoranthene and pyrene at Fjällbacka; for naphthalene at Kvädöfjärden; and for pyrene at Fladen.All time series where concentrations of various PAHs were compared with the target value based on OSPAR Ecological Assessment Criteria, or EC Environmental Quality Standards were below the target value.PFASsPFHxS and PFOS show a similar spatial pattern, but PFOS concentrations were approximately 25 times higher than PFHxS levels. The distribution of PFOS is quite homogenous along the Swedish coast but with somewhat higher concentrations in the Baltic Proper. PFOS concentrations in guillemot eggs are about 100-200 times higher than in herring liver. An overall increasing concentration of PFOS in guillemot eggs has been observed throughout the whole time period, however, during the most recent ten years, a change of direction is detected. The longer herring time series from Harufjärden, Landsort, and Utlängan show increasing concentrations for PFOS and most carboxylates. For FOSA, on the other hand, decreasing concentrations are seen during the most recent ten years.Organotin compoundsThe majority of the analysed tinorganic compounds showed concentrations below LOQ. However TBT and DPhT showed concentrations above LOQ at all stations with highest reported concentrations in fish from Örefjärden in the northern part of Bothnian Sea.
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| 7. |
- Bood, Mattias, et al.
(författare)
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Pentacyclic adenine: a versatile and exceptionally bright fluorescent DNA base analogue
- 2018
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 9:14, s. 3494-3502
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Tidskriftsartikel (refereegranskat)abstract
- Emissive base analogs are powerful tools for probing nucleic acids at the molecular level. Herein we describe the development and thorough characterization of pentacyclic adenine (pA), a versatile base analog with exceptional fluorescence properties. When incorporated into DNA, pA pairs selectively with thymine without perturbing the B-form structure and is among the brightest nucleobase analogs reported so far. Together with the recently established base analog acceptor qAnitro, pA allows accurate distance and orientation determination via Forster resonance energy transfer (FRET) measurements. The high brightness at emission wavelengths above 400 nm also makes it suitable for fluorescence microscopy, as demonstrated by imaging of single liposomal constructs coated with cholesterolanchored pA-dsDNA, using total internal reflection fluorescence microscopy. Finally, pA is also highly promising for two-photon excitation at 780 nm, with a brightness (5.3 GM) that is unprecedented for a base analog.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- de Goffau, Marcus C., et al.
(författare)
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Human placenta has no microbiome but can contain potential pathogens
- 2019
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 572:7769, s. 329-334
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Tidskriftsartikel (refereegranskat)abstract
- We sought to determine whether pre-eclampsia, spontaneous preterm birth or the delivery of infants who are small for gestational age were associated with the presence of bacterial DNA in the human placenta. Here we show that there was no evidence for the presence of bacteria in the large majority of placental samples, from both complicated and uncomplicated pregnancies. Almost all signals were related either to the acquisition of bacteria during labour and delivery, or to contamination of laboratory reagents with bacterial DNA. The exception was Streptococcus agalactiae (group B Streptococcus), for which non-contaminant signals were detected in approximately 5% of samples collected before the onset of labour. We conclude that bacterial infection of the placenta is not a common cause of adverse pregnancy outcome and that the human placenta does not have a microbiome, but it does represent a potential site of perinatal acquisition of S. agalactiae, a major cause of neonatal sepsis.
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| 12. |
- Fisher, Rachel S., et al.
(författare)
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Pulse-shaped two-photon excitation of a fluorescent base analogue approaches single-molecule sensitivity
- 2018
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 20:45, s. 28487-28498
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescent nucleobase analogues (FBAs) have many desirable features in comparison to extrinsic fluorescent labels, but they are yet to find application in ultrasensitive detection. Many of the disadvantages of FBAs arise from their short excitation wavelengths (often in the ultraviolet), making two-photon excitation a potentially attractive approach. Pentacyclic adenine (pA) is a recently developed FBA that has an exceptionally high two-photon brightness. We have studied the two-photon-excited fluorescence properties of pA and how they are affected by incorporation in DNA. We find that pA is more photostable under two-photon excitation than via resonant absorption. When incorporated in an oligonucleotide, pA has a high two-photon cross section and emission quantum yield, varying with sequence context, resulting in the highest reported brightness for such a probe. The use of a two-photon microscope with ultrafast excitation and pulse shaping has allowed the detection of pA-containing oligonucleotides in solution with a limit of detection of ∼5 molecules, demonstrating that practical single-molecule detection of FBAs is now within reach.
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| 13. |
- Freitag, Daniel F., et al.
(författare)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 14. |
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| 15. |
- Grodzinsky, A., et al.
(författare)
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Bleeding risk following percutaneous coronary intervention in patients with diabetes prescribed dual anti-platelet therapy
- 2016
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 182, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with diabetes mellitus (DM) experience higher rates of in-stent restenosis and greater benefit from drug-eluting stents implant at the time of percutaneous coronary intervention (PCI), necessitating prolonged dual anti-platelet therapy (DAPT). While DAPT reduces risk of ischemic events post-PCI, it also increases risk of bleeding. Whether bleeding rates differ among patients with and without DM, receiving long-term DAPT is unknown. Methods Among patients who underwent PCI and were maintained on DAPT for 1 year in a multicenter US registry, we assessed patient-reported bleeding over one year following PCI in patients with and without DM. Multivariable, hierarchical Poisson regression was used to evaluate the association of DM with bleeding during follow-up. Results Among 2334 PCI patients from 10 US hospitals (mean age 64, 54% ACS), 32.6% had DM. In unadjusted analyses, patients with DM had fewer bleeding events over the year following PCI(DMvs no DM: BARC = 1: 78.0% vs 87.7%, P <.001; BARC >= 2: 4.3% vs 5.3%, P = .33). Following adjustment, patients with (vs without DM) had a lower risk of BARC = 1 bleeding during follow-up (relative risk [RR] 0.89, 95% CI 0.83-0.96). This decreased bleeding risk persisted after removing bruising from the endpoint definition. Conclusions In a real-world PCI registry, patients with DM experienced lower risk of bleeding risk on DAPT. As patients with DM also derive greater ischemic benefit from drug-eluting stents, which requires prolonged DAPT, our findings suggest that the balance between benefit and risk of this therapeutic approach may be even more favorable in patients with DM than previously considered.
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| 16. |
- Hiatt, William R, et al.
(författare)
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Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease
- 2017
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Ingår i: The New England journal of medicine. - 0028-4793 .- 1533-4406. ; 376, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease.METHODS: In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months.RESULTS: The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49).CONCLUSIONS: In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).
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| 17. |
- Ji, Yingjie, et al.
(författare)
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Genome-wide and abdominal MRI data provide evidence that a genetically determined favorable adiposity phenotype is characterized by lower ectopic liver fat and lower risk of type 2 diabetes, heart disease, and hypertension
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:1, s. 207-219
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Tidskriftsartikel (refereegranskat)abstract
- Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.
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| 18. |
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| 19. |
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| 20. |
- Mikusinski, Grzegorz, et al.
(författare)
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Managing Diversity: The Challenges of Inter-University Cooperation in Sustainability Education
- 2019
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- One of the main challenges in sustainability discourse is its multifaceted nature often requiring that many different disciplines must cooperate in order to achieve progress. This issue also concerns sustainability education. In the article, we highlighted the experiences from the international cooperation of university teachers and researchers with highly diverse professional backgrounds who worked together on developing educational materials for university students in sustainability-oriented courses. The study is based on qualitative, participatory evaluation research, applying two rounds of open-ended questionnaires distributed to the same respondents (n = 18). For the analysis, we used the open-coding procedure for identifying the main categories. The results show some of the opportunities and barriers that emerged in the process of this cooperation. In particular, we discuss the issues related to the high heterogeneity of the group, such as the clashes of the different perspectives on the topics covered, group dynamics issues, trust, facilitation challenges, and also opportunities that such heterogeneity offers. We highlight the importance of open reflectivity in sustainability-oriented educational projects as the key to their successful implementation. Finally, we believe that results of this participatory study are useful in designing new projects aiming at further improvement of academic education in sustainability and sustainable development.
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| 21. |
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| 22. |
- Price, David B., et al.
(författare)
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Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility : a randomised controlled trial
- 2018
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Ingår i: The Lancet Respiratory Medicine. - : ELSEVIER SCI LTD. - 2213-2600 .- 2213-2619. ; 6:1, s. 29-39
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic non-specific respiratory symptoms are difficult to manage. This trial aimed to evaluate the association between baseline fractional exhaled nitric oxide (FENO) and the response to inhaled corticosteroids in patients with non-specific respiratory symptoms.Methods: In this double-blind randomised placebo-controlled trial, we enrolled undiagnosed patients, aged 18-80 years, with cough, wheeze, or dyspnoea and less than 20% bronchodilator reversibility across 26 primary care centres and hospitals in the UK and Singapore. Patients were assessed for 2 weeks before being randomly assigned (1: 1) to 4 weeks of treatment with extrafine inhaled corticosteroids (QVAR 80 mu g, two puffs twice per day, equivalent to 800 mu g per day beclomethasone dipropionate) or placebo. Randomisation was stratified by baseline FENO measurement: normal (<= 25 parts per billion [ppb]), intermediate (>25 tp <40 ppb), and high (>= 40 ppb). The primary endpoint was change in Asthma Control Questionnaire (ACQ7) mean score. We used generalised linear modelling to assess FENO as a predictor of response, estimating an interaction effect between FENO and treatment on change in ACQ7. We did our primary and secondary analyses in the per-protocol set, which excluded patients with non-completion of the primary endpoint, non-compliance to treatment (ascertained by patient report), and study visits made outside the predefined visit windows. This study is registered on ClinicalTrials.gov, number NCT02294279.Findings: Between Feb 4, 2015, and July 12, 2016, we randomly assigned 294 patients to extrafine inhaled corticosteroid treatment (n=148) or placebo (n=146). Following exclusions due to protocol violations, we analysed 214 patients (114 extrafine inhaled corticosteroids and 100 placebo). We observed a significant interaction between baseline FENO and treatment group for every 10 ppb increase in baseline FENO, with the change in ACQ7 greater in the extrafine inhaled corticosteroids group than in the placebo group (difference between groups 0.071, 95% CI 0.002 to 0.139; p=0.044). The most common adverse events were nasopharyngitis (18 [12%] patients in the treatment group vs 13 [9%] in the placebo group), infections and infestations (25 [17%] vs 21 [14%]), and respiratory, thoracic, and mediastinal disorders (13 [9%] vs 17 [12%]).Interpretation: FENO measurement is an easy and non-invasive tool to use in clinical practice in patients with nonspecific respiratory symptoms to predict response to inhaled corticosteroids. Further research is needed to examine its role in patients with evidence of other airway diseases, such as chronic obstructive pulmonary disease.
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