| 1. |
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
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| 6. |
- 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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| 7. |
- Haas, Brian J., et al.
(författare)
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Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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| 8. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 9. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 10. |
- 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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| 11. |
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| 12. |
- Akbari, Parsa, et al.
(författare)
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Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 373:6550
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ∼4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.
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| 13. |
- 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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| 14. |
- Arnold, S. V., et al.
(författare)
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The reliability of in-hospital diagnoses of diabetes mellitus in the setting of an acute myocardial infarction
- 2014
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Incident diabetes mellitus (DM) is important to recognize in patients with acute myocardial infarction (AMI). To develop an efficient screening strategy, we explored the use of random plasma glucose (RPG) at admission and fasting plasma glucose (FPG) to select patients with AMI for glycosylated hemoglobin (HbA1c) testing. DESIGN SETTING ANDPARTICIPANTS: Prospective registry of 1574 patients with AMI not taking glucose-lowering medication from 24 US hospitals. All patients had HbA1c measured at a core laboratory and admission RPG and >/=2 FPGs recorded during hospitalization. We examined potential combinations of RPG and FPG and compared these with HbA1c>/=6.5%-considered the gold standard for DM diagnosis in these analyses. RESULTS: An RPG>140 mg/dL or FPG>/=126 mg/dL had high sensitivity for DM diagnosis. Combining these into a screening protocol (if admission RPG>140, check HbA1c; or if FPG>/=126 on a subsequent day, check HbA1c) led to HbA1c testing in 50% of patients and identified 86% with incident DM (number needed to screen (NNS)=3.3 to identify 1 case of DM; vs NNS=5.6 with universal HbA1c screening). Alternatively, using an RPG>180 led to HbA1c testing in 40% of patients with AMI and identified 82% of DM (NNS=2.7). CONCLUSIONS: We have established two potential selective screening methods for DM in the setting of AMI that could identify the vast majority of incident DM by targeted screening of 40-50% of patients with AMI with HbA1c testing. Using these methods may efficiently identify patients with AMI with DM so that appropriate education and treatment can be promptly initiated.
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| 15. |
- Atun, Rifat, et al.
(författare)
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Sustainable care for children with cancer : a Lancet Oncology Commission
- 2020
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Ingår i: The Lancet Oncology. - 1470-2045. ; 21:4, s. 185-224
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Forskningsöversikt (refereegranskat)abstract
- We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020–50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.
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| 16. |
- Bansal, Sheel, et al.
(författare)
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Practical Guide to Measuring Wetland Carbon Pools and Fluxes
- 2023
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Ingår i: Wetlands (Wilmington, N.C.). - : SPRINGER. - 0277-5212 .- 1943-6246. ; 43:8
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Forskningsöversikt (refereegranskat)abstract
- Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first define each of the major C pools and fluxes and provide rationale for their importance to wetland C dynamics. For each approach, we clarify what component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as where and when an approach is typically used, who can conduct the measurements (expertise, training requirements), and how approaches are conducted, including considerations on equipment complexity and costs. Finally, we review key covariates and ancillary measurements that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions.
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| 17. |
- Bateman, Marcus, et al.
(författare)
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Development of a core outcome set for lateral elbow tendinopathy (COS-LET) using best available evidence and an international consensus process
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:12, s. 657-666
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To develop a core outcome set for lateral elbow tendinopathy (COS-LET) and to provide guidance for outcome evaluation in future studies.METHODS: We implemented a multi-stage mixed-methods design combining two systematic reviews, domain mapping of outcome measurement instruments to the core domains of tendinopathy, psychometric analysis of instruments, two patient focus groups and a Delphi study incorporating two surveys and an international consensus meeting. Following the OMERACT guidelines, we used a 70% threshold for consensus.RESULTS: 38 clinicians/researchers and 9 patients participated. 60 instruments were assessed for inclusion. The only instrument that was recommended for the COS-LET was Patient Rated Tennis Elbow Evaluation (PRTEE) for the disability domain. Interim recommendations were made to use: the PRTEE function subscale for the function domain; PRTEE pain subscale items 1, 4 and 5 for the pain over a specified time domain; pain-free grip strength for the physical function capacity domain; a Numerical Rating Scale measuring pain on gripping for the pain on activity/loading domain; and time off work for the participation in life activities domain. No recommendations could be made for the quality-of-life, patient rating of condition and psychological factors domains.CONCLUSIONS: The COS-LET comprises the PRTEE for the disability domain. Interim-use recommendations included PRTEE subscales, time off work, pain-free grip strength and a Numerical Rating Scale measuring pain on gripping. Further work is required to validate these interim measures and develop suitable measures to capture the other domains.
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| 18. |
- 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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| 19. |
- 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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| 20. |
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| 21. |
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| 22. |
- 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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| 23. |
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| 24. |
- 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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| 25. |
- Chng, Kern Rei, et al.
(författare)
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Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
- 2020
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
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Tidskriftsartikel (refereegranskat)abstract
- Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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| 26. |
- Clements, M. A., et al.
(författare)
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Age at diagnosis predicts deterioration in glycaemic control among children and adolescents with type 1 diabetes
- 2014
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897 .- 2052-4897. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Poor glycemic control early in the course of type 1 diabetes mellitus (T1DM) increases the risk for microvascular complications. However, predictors of deteriorating control after diagnosis have not been described, making it difficult to identify high-risk patients and proactively provide aggressive interventions. OBJECTIVE: We examined whether diagnostic age, gender, and race were associated with deteriorating glycemic control during the first 5 years after diagnosis. PARTICIPANTS: 2218 pediatric patients with T1DM. METHODS: We conducted a longitudinal cohort study of pediatric patients with T1DM from the Midwest USA, 1993-2009, evaluating within-patient glycated hemoglobin (HbA1c) trajectories constructed from all available HbA1c values within 5 years of diagnosis. RESULTS: 52.6% of patients were male; 86.1% were non-Hispanic Caucasian. The mean diagnostic age was 9.0+/-4.1 years. The mean number of HbA1c values/year/participant was 2.4+/-0.9. HbA1c trajectories differed markedly across age groups, with older patients experiencing greater deterioration than their younger counterparts (p<0.001). HbA1c trajectories, stratified by age, varied markedly by race (p for racexdiagnostic age <0.001). Non-Hispanic African-American patients experienced higher initial HbA1c (8.7% vs 7.6% (71.6 vs 59.6 mmol/mol); p<0.001), and greater deterioration in HbA1c than non-Hispanic Caucasian patients across diagnostic ages (rise of 2.04% vs 0.99% per year (22.3 vs 10.8 mmol/mol/year); p<0.0001). CONCLUSIONS: Older diagnostic age and black race are major risk factors for deterioration in glycemic control early in the course of T1DM. These findings can inform efforts to explore the reasons behind these differences and develop preventive interventions for high-risk patients.
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| 27. |
- Currie, Mags, et al.
(författare)
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Understanding the response to Covid-19 : exploring options for a resilient social and economic recovery in Scotland’s rural and island communities
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This research considered the impacts of Covid-19 on rural and island communities, how resiliently they have responded; and the most effective ways forward for their recovery. Our research approach involved: interviewing people in key rural sectors then producing a map to identify factors of resilience. This map was used to identify case study communities. Interviews were undertaken in these communities to understand local perspectives.Rural and island communities have been vulnerable to the impacts of Covid. Specific factors that have increased their vulnerability include reliance on limited employment sectors, being located far from centralised services (e.g. hospitals), limited digital connectivity; and an ageing population. Communities with a more resilient response had some or all of the following features: a strong sense of community; community organisations and local businesses that have been responsive to local needs; the existence of strategic partnerships between community organisations and the public/private sector; and good digital connectivity.Covid-19 has brought rural vulnerabilities into sharp focus and these vulnerabilities are often connected. Strategic and joined-up partnerships between community, public and private sector organisations will remain important, as well as novel and flexible funding mechanisms to enable place-based and context-specific responses.This research highlighted nine actions that would assist rural and island communities to thrive in the future. These include: 1. Building on existing and new partnerships and supporting anchor organisations 2. Capitalising on and rewarding community spirit 3. Encouraging and supporting young people to move to rural and island communities 4. Retaining and enhancing digital connectivity opportunities 5. Supporting adaptable local businesses 6. Strategic partnerships with deliver place-based solutions 7. Continue to support diversification of the rural economy 8. Enhancing the knowledge base on local-regional vulnerabilities 9. Retaining a flexible, targeted and responsive approach to financial support.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- de Goffau, Marcus C., et al.
(författare)
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Human placenta has no microbiome but can contain potential pathogens
- 2019
-
Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 572:7769, s. 329-334
-
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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| 32. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
-
Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 33. |
- Dorn, Reinhold J., et al.
(författare)
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CRIRES+ on sky : High spectral resolution at infrared wavelength enabling better science at the ESO VLT
- 2022
-
Ingår i: Ground-Based And Airborne Instrumentation For Astronomy IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
-
Konferensbidrag (refereegranskat)abstract
- CRIRES+ extended the capabilities of CRIRES, the CRyogenic InfraRed Echelle Spectrograph. It transformed this VLT instrument into a cross-dispersed spectrograph to increase the wavelength range that is covered simultaneously by a factor of ten. In addition, a new detector focal plane array of three Hawaii 2RG detectors with a 5.3 mu m cut-off wavelength replaced the existing detectors. Amongst many other improvements a new spectropolarimetric unit was added and the calibration system has been enhanced. The instrument was installed at the VLT on Unit Telescope 3 beginning of 2020 and successfully commissioned and verified for science operations during 2021, partly remote from Europe due to the pandemic. The instrument was subsequently offered to the community from October 2021 onwards. This article describes the performance and capabilities of this development and presents on sky results.
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| 34. |
- Evans, Alistair R., et al.
(författare)
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The maximum rate of mammal evolution
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:11, s. 4187-4190
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Tidskriftsartikel (refereegranskat)abstract
- How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000-fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous-Paleogene (K-Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes.
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| 35. |
- 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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| 36. |
- 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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| 37. |
- Gaccioli, Francesca, et al.
(författare)
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Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia
- 2020
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Ingår i: Nature Microbiology. - : Springer Nature. - 2058-5276. ; 5:7, s. 901-908
-
Tidskriftsartikel (refereegranskat)abstract
- Pre-eclampsia (typically characterized by new-onset hypertension and proteinuria in the second half of pregnancy) represents a major determinant of the global burden of disease1,2. Its pathophysiology involves placental dysfunction, but the mechanism is unclear. Viral infection can cause organ dysfunction, but its role in placentally related disorders of human pregnancy is unknown3. We addressed this using RNA sequencing metagenomics4-6 of placental samples from normal and complicated pregnancies. Here, we show that human herpesvirus 6 (HHV-6, A or B) RNA was detected in 6.1% of cases of pre-eclampsia and 2.2% of other pregnancies. Fetal genotyping demonstrated that 70% of samples with HHV-6 RNA in the placenta exhibited inherited, chromosomally integrated HHV-6 (iciHHV-6). We genotyped 467 pre-eclampsia cases and 3,854 controls and found an excess of iciHHV-6 in the cases (odds ratio of 2.8, 95% confidence intervals of 1.4-5.6, P = 0.008). We validated this finding by comparing iciHHV-6 in a further 740 cases with controls from large-scale population studies (odds ratio of 2.5, 95% confidence intervals of 1.4-4.4, P = 0.0013). We conclude that iciHHV-6 results in the transcription of viral RNA in the human placenta and predisposes the mother to pre-eclampsia.
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| 38. |
- Gaccioli, Francesca, et al.
(författare)
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Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants
- 2023
-
Ingår i: Nature Microbiology. - : Springer Nature. - 2058-5276. ; 8:12, s. 2338-2348
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus agalactiae (Group B Streptococcus; GBS) is a common cause of sepsis in neonates. Previous work detected GBS DNA in the placenta in ~5% of women before the onset of labour, but the clinical significance of this finding is unknown. Here we re-analysed this dataset as a case control study of neonatal unit (NNU) admission. Of 436 infants born at term (≥37 weeks of gestation), 7/30 with placental GBS and 34/406 without placental GBS were admitted to the NNU (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.3-7.8). We then performed a validation study using non-overlapping subjects from the same cohort. This included a further 239 cases of term NNU admission and 686 term controls: 16/36 with placental GBS and 223/889 without GBS were admitted to the NNU (OR 2.4, 95% CI 1.2-4.6). Of the 36 infants with placental GBS, 10 were admitted to the NNU with evidence of probable but culture-negative sepsis (OR 4.8, 95% CI 2.2-10.3), 2 were admitted with proven GBS sepsis (OR 66.6, 95% CI 7.3-963.7), 6 were admitted and had chorioamnionitis (inflammation of the foetal membranes) (OR 5.3, 95% CI 2.0-13.4), and 5 were admitted and had funisitis (inflammation of the umbilical cord) (OR 6.7, 95% CI 12.5-17.7). Foetal cytokine storm (two or more pro-inflammatory cytokines >10 times median control levels in umbilical cord blood) was present in 36% of infants with placental GBS DNA and 4% of cases where the placenta was negative (OR 14.2, 95% CI 3.6-60.8). Overall, ~1 in 200 term births had GBS detected in the placenta, which was associated with infant NNU admission and morbidity.
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| 39. |
- Garpe, Kajsa, 1970-
(författare)
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Effects of habitat structure on tropical fish assemblages
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rates of habitat alteration and degradation are increasing worldwide due to anthropogenic influence. On coral reefs, the loss of live coral reduces structural complexity while facilitating algal increase. In many coastal lagoons seagrass and corals are cleared to make room for cultivated macroalgae. This thesis deals with reef and lagoon habitat structure and how fish assemblage patterns may be related to physical and biological features of the habitat. It further examines assemblage change following habitat disturbance. Four studies on East African coral reefs concluded that both the abundance and species richness of recruit and adult coral reef fish were largely predicted by the presence of live coral cover and structural complexity (Papers I-III, VI). Typically, recruits were more selective than adults, as manifested by limited distributions to degraded sites. Paper VI compared short- and long-term responses of fish assemblages to the 1997-1998 bleaching event. The short-term response to coral mortality included the loss of coral dwelling species in favour of species which feed on algae or associated detrital resources. Counterintuitively, fish abundance and taxonomic richness increased significantly at one of two sites shortly after the bleaching. However, the initial increase was later reversed and six years after the death of the coral, only a limited number of fish remained. The influence of fleshy algae on fish assemblages was studied in algal farms (Paper IV), and examined experimentally (Paper V). The effects of algal farming in Zanzibar were significant. Meanwhile, manually clearing algal-dominated patch reefs in Belize from macroalgae resulted in short-term increases of abundance, biomass and activity of a few species, including major herbivores. The findings of this thesis demonstrate the significance of habitat as a structuring factor for tropical fish assemblages and predicts that coral death, subsequent erosion and algal overgrowth may have substantial deleterious impacts on fish assemblage composition, abundance and taxonomic richness, with recovery being slow and related to the recovery of the reef framework.
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| 40. |
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| 41. |
- Glass, Jayne, et al.
(författare)
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Case studies of island repopulation initiatives
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The Scottish Government made several policy commitments to stem rural depopulation and attract more people to live and work in rural and island communities. This report presents Scottish and international examples of successful policy interventions to support repopulation of island and remote rural communities, which could be piloted in similar communities in Scotland. The report considers examples from six countries, including Scotland.
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| 42. |
- Glass, Jayne, et al.
(författare)
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Facilitating local resilience : case studies of place-based approaches in rural Scotland
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report explores the extent to which place-based approaches can deliver positive economic and social outcomes in Scotland’s rural areas and small towns. We studied five case studies of place-based approaches in rural Scotland:1. Tackling the climate emergency in Callander2. Strengthening Communities in the Western Isles3. A Heart for Duns: the changing role of a local development trust4. Partnership working for place-based policy: lessons from Initiative at the Edge5. Land reform policy and transformational community changePlace-based approaches in rural Scotland have enabled community capacity building, community ownership/management of land and assets, and partnership-working to deliver local outcomes and services. A flexible national and regional place-based policy framework can be supportive of local place-based approaches, but should acknowledge different local circumstances, assets and needs, and the lived experiences of local people.Place-based approaches require financial and other development support/advice in the early stages. This might be particularly in relation to locally-led community planning to address place-based needs, acquiring local community assets and creating links between local actors and broader regional/national policy processes. More flexible place-based policy frameworks should be developed at national and regional level which facilitate cross-sectoral working, break down silos and encourage collaboration between different actors and governance levels (including communities and local authorities).The research identifies four recommendations to enhance rural place-based approaches:1. Long-term, flexible investment in place-based approaches is needed to ensure the delivery of solutions rooted in community needs and local action.2. Communities need to be able to operate with a degree of autonomy to increase competence, capacity and confidence at the local level.3. This local autonomy needs support from national/regional levels over the long-term, by transferring resources, ensuring that the voices and experiences of communities are heard, and working in (equal) partnership across governance levels.4. There is a need for mechanisms by which the key features and requirements of national and regional policy are translated into something tangible and relevant at the local level.
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| 43. |
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| 44. |
- 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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| 45. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 46. |
- 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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| 47. |
- 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
-
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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| 48. |
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| 49. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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