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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Hollo, G, et al.
(författare)
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Referral for first glaucoma surgery in Europe, the ReF-GS study
- 2019
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Ingår i: European journal of ophthalmology. - : SAGE Publications. - 1724-6016 .- 1120-6721. ; 29:4, s. 406-416
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Tidskriftsartikel (refereegranskat)abstract
- To analyze the appropriateness of referrals for incisional glaucoma-surgery in Europe. Methods: Referrals for the first open-angle glaucoma surgery between January and October 2017 were analyzed in 18 countries: 8 “old” European Union, 7 “new” European Union and 3 non-European Union European countries. Results: Most eyes had primary open-angle or exfoliative glaucoma. The average mean deviation was −13.8 dB with split fixation in 44.3%. No structural progression analysis was made before the referrals. The most common medications were the combination of a prostaglandin analog, timolol and a carbonic anhydrase inhibitor (30.0%), and all other combinations comprising ⩾ 3 molecules (33.8%). Laser trabeculoplasty was reported in only 18.4%. Of the 294 referrals, 41.5% were appropriate and timely, 35.0% appropriate but later than optimal, and 17.6% appropriate but too late (minimal vision maintained). The treatment period was significantly longer (median: 7 years) in the “old” European Union countries than in the other groups (3 and 2 years, respectively). No between-group differences were seen in intraocular pressure and mean deviation, but the non-European Union group referred the patients at significantly lower cup/disk ratio and eye drop usage than the other groups. Split fixation was significantly more common in the “old” (60.6%) than the “new” European Union countries (38.7%), and in both EU country-groups than in the non-European Union countries (13.6%). Conclusions: Of 294 European open-angle glaucoma referrals for first glaucoma-surgery, 41.5% were completely satisfactory. The damage was typically advanced, and the care varied considerably among the countries. This suggests that further efforts are necessary to improve glaucoma care in Europe.
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- Fuchs, A., et al.
(författare)
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Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications.
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- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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- Wheeler, Eleanor, et al.
(författare)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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- Eberhardt, Mirjam, et al.
(författare)
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H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway.
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5:Jul 15
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Tidskriftsartikel (refereegranskat)abstract
- Nitroxyl (HNO) is a redox sibling of nitric oxide (NO) that targets distinct signalling pathways with pharmacological endpoints of high significance in the treatment of heart failure. Beneficial HNO effects depend, in part, on its ability to release calcitonin gene-related peptide (CGRP) through an unidentified mechanism. Here we propose that HNO is generated as a result of the reaction of the two gasotransmitters NO and H2S. We show that H2S and NO production colocalizes with transient receptor potential channel A1 (TRPA1), and that HNO activates the sensory chemoreceptor channel TRPA1 via formation of amino-terminal disulphide bonds, which results in sustained calcium influx. As a consequence, CGRP is released, which induces local and systemic vasodilation. H2S-evoked vasodilatatory effects largely depend on NO production and activation of HNO-TRPA1-CGRP pathway. We propose that this neuroendocrine HNO-TRPA1-CGRP signalling pathway constitutes an essential element for the control of vascular tone throughout the cardiovascular system.
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- Sefah, IA, et al.
(författare)
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Rapid Assessment of the Potential Paucity and Price Increases for Suggested Medicines and Protection Equipment for COVID-19 Across Developing Countries With a Particular Focus on Africa and the Implications
- 2021
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Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11, s. 588106-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Countries across Africa and Asia have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE). However, there has been considerable controversy surrounding some treatments including hydroxychloroquine where the initial hype and misinformation led to shortages, price rises and suicides. Price rises and shortages were also seen for PPE. Such activities can have catastrophic consequences especially in countries with high co-payment levels. Consequently, there is a need to investigate this further.Objective: Assess changes in utilisation, prices, and shortages of pertinent medicines and PPE among African and Asian countries since the start of pandemic.Our approach: Data gathering among community pharmacists to assess changes in patterns from the beginning of March until principally the end of May 2020. In addition, suggestions on ways to reduce misinformation.Results: One hundred and thirty one pharmacists took part building on the earlier studies across Asia. There were increases in the utilisation of principally antimalarials (hydroxychloroquine) and antibiotics (azithromycin) especially in Nigeria and Ghana. There were limited changes in Namibia and Vietnam reflecting current initiatives to reduce inappropriate prescribing and dispensing of antimicrobials. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries where documented. In addition, generally limited change in the utilisation of herbal medicines. However, shortages have resulted in appreciable price increases in some countries although moderated in others through government initiatives. Suggestions in Namibia going forward included better planning and educating patients.Conclusion: Encouraging to see increases in the utilisation of vitamins/immune boosters and PPE. However, concerns with increased utilisation of antimicrobials needs addressing alongside misinformation, unintended consequences from the pandemic and any appreciable price rises. Community pharmacists and patient organisations can play key roles in providing evidence-based advice, helping moderate prices through improved stock management, and helping address unintended consequences of the pandemic.
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- Trompoukis, C., et al.
(författare)
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Photonic nanostructures for advanced light trapping in thin crystalline silicon solar cells
- 2015
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Ingår i: Physica Status Solidi (A) Applications and Materials Science. - : Wiley. - 1862-6319 .- 1862-6300. ; 212:1, s. 140-155
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Tidskriftsartikel (refereegranskat)abstract
- We report on the fabrication, integration, and simulation, both optical and optoelectrical, of two-dimensional photonic nanostructures for advanced light trapping in thin crystalline silicon (c-Si) solar cells. The photonic nanostructures are fabricated by the combination of various lithography (nanoimprint, laser interference, and hole mask colloidal) and etching (dry plasma and wet chemical) techniques. The nanopatterning possibilities thus range from periodic to random corrugations and from inverted nanopyramids to high aspect ratio profiles. Optically, the nanopatterning results in better performance than the standard pyramid texturing, showing a more robust behavior with respect to light incidence angle. Electrically, wet etching results in higher minority carrier lifetimes compared to dry etching. From the integration of the photonic nanostructures into a micron-thin c-Si solar cell certain factors limiting the efficiencies are identified. More precisely: (a) the parasitic absorption is limiting the short circuit current, (b) the conformality of thin-film coatings on the nanopatterned surface is limiting the fill factor, and (c) the material damage from dry etching is limiting the open circuit voltage. From optical simulations, the optimal pattern parameters are identified. From optoelectrical simulations, cell design considerations are discussed, suggesting to position the junction on the opposite side of the nanopattern.
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- Černok, Ana, et al.
(författare)
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Lunar samples record an impact 4.2 billion years ago that may have formed the Serenitatis Basin
- 2021
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Ingår i: Communications Earth & Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Impact cratering on the Moon and the derived size-frequency distribution functions of lunar impact craters are used to determine the ages of unsampled planetary surfaces across the Solar System. Radiometric dating of lunar samples provides an absolute age baseline, however, crater-chronology functions for the Moon remain poorly constrained for ages beyond 3.9 billion years. Here we present U–Pb geochronology of phosphate minerals within shocked lunar norites of a boulder from the Apollo 17 Station 8. These minerals record an older impact event around 4.2 billion years ago, and a younger disturbance at around 0.5 billion years ago. Based on nanoscale observations using atom probe tomography, lunar cratering records, and impact simulations, we ascribe the older event to the formation of the large Serenitatis Basin and the younger possibly to that of the Dawes crater. This suggests the Serenitatis Basin formed unrelated to or in the early stages of a protracted Late Heavy Bombardment.
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- Kaiser, Vera B, et al.
(författare)
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Homozygous loss-of-function variants in European cosmopolitan and isolate populations
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:19, s. 5464-5475
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Tidskriftsartikel (refereegranskat)abstract
- Homozygous Loss of Function (HLOF) variants provide a valuable window on gene function in humans, as well as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown - as are the phenotypic effects of losing function for most human genes. Here, we make use of 1,432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, which we show are enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to show that most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation.
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- Osmancevic, Amar, et al.
(författare)
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Levels of Sex Hormones and Abdominal Muscle Composition in Men from The Multi-Ethnic Study of Atherosclerosis
- 2024
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Ingår i: SCIENTIFIC REPORTS. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Information on the associations of testosterone levels with abdominal muscle volume and density in men is limited, while the role of estradiol and SHBG on these muscle characteristics are unclear. Therefore, this study aimed to investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Conducted as a cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis, our analyses focused on a community-based sample of 907 men aged 45-84 years, with 878 men having complete data. CT scans of the abdomen were interrogated for muscle characteristics, and multivariable linear regressions were used to test the associations. After adjustment for relevant factors, higher levels of both total testosterone and estradiol were associated with higher abdominal muscle area (1.74, 0.1-3.4, and 1.84, 0.4-3.3, respectively). In the final analyses, levels of total testosterone showed a positive association, while an inverse relationship was observed for SHBG with abdominal muscle radiodensity (0.3, 0.0-0.6, and - 0.33, - 0.6 to - 0.1, respectively). Our results indicate a complex association between sex hormones and abdominal muscle characteristics in men. Specifically, total testosterone and estradiol were associated with abdominal muscle area, while only total testosterone was associated with muscle radiodensity and SHBG was inversely associated with muscle radiodensity.
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- Rosano, Caterina, et al.
(författare)
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Sex differences in Alzheimer's disease blood biomarkers in a Caribbean population of African ancestry: The Tobago Health Study
- 2024
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Ingår i: ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS. - 2352-8737. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Alzheimer's disease (AD) is increasing in the Caribbean, especially for persons of African ancestry (PAA) and women. However, studies have mostly utilized surveys without AD biomarkers. METHODS: In the Tobago Health Study (n = 309; 109 women, mean age 70.3 +/- 6.6), we assessed sex differences and risk factors for serum levels of phosphorylated tau-181 (p-tau181), amyloid-beta (A beta)42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Blood samples were from 2010 to 2013 for men and from 2019 to 2023 for women. RESULTS: Women were more obese, hypertensive, and sedentary but reported less smoking and alcohol use than men (age-adjusted p < 0.04). Compared to men, women had worse levels of AD biomarkers, with higher p-tau181 and lower A beta 42/40, independent of covariates (p < 0.001). In sex-stratified analyses, higher p-tau181 was associated with older age in women and with hypertension in men. GFAP and NfL did not differ by sex. DISCUSSION: Women had worse AD biomarkers than men, unexplained by age, cardiometabolic diseases, or lifestyle. Studying risk factors for AD in PAA is warranted, especially for women earlier in life.
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