| 1. |
- Kuehlewein, Laura, et al.
(författare)
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Clinical phenotype and course of PDE6A-associated retinitis pigmentosa disease, characterized in preparation for a gene supplementation trial
- 2020
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Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 138:12, s. 1241-1250
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Treatment trials require sound knowledge on the natural course of disease. OBJECTIVE To assess clinical features, genetic findings, and genotype-phenotype correlations in patients with retinitis pigmentosa (RP) associated with biallelic sequence variations in the PDE6A gene in preparation for a gene supplementation trial. DESIGN, SETTING, AND PARTICIPANTS This prospective, longitudinal, observational cohort study was conducted from January 2001 to December 2019 in a single center (Centre for Ophthalmology of the University of Tübingen, Germany) with patients recruited multinationally from 12 collaborating European tertiary referral centers. Patients with retinitis pigmentosa, sequence variants in PDE6A, and the ability to provide informed consent were included. EXPOSURES Comprehensive ophthalmological examinations; validation of compound heterozygosity and biallelism by familial segregation analysis, allelic cloning, or assessment of next-generation sequencing-read data, where possible. MAIN OUTCOMES AND MEASURES Genetic findings and clinical features describing the entire cohort and comparing patients harboring the 2 most common disease-causing variants in a homozygous state (c.304C>A;p.(R102S) and c.998 + 1G>A;p.?). RESULTS Fifty-seven patients (32 female patients [56%]; mean [SD], 40 [14] years) from 44 families were included. All patients completed the study. Thirty patients were homozygous for disease-causing alleles. Twenty-seven patients were heterozygous for 2 different PDE6A variants each. The most frequently observed alleles were c.304C>A;p.(R102S), c.998 + 1G>A;p.?, and c.2053G>A;p.(V685M). The mean (SD) best-corrected visual acuity was 0.43 (0.48) logMAR (Snellen equivalent, 20/50). The median visual field area with object III4e was 660 square degrees (5th and 95th percentiles, 76 and 11 019 square degrees; 25th and 75th percentiles, 255 and 3923 square degrees). Dark-adapted and light-adapted full-field electroretinography showed no responses in 88 of 108 eyes (81.5%). Sixty-nine of 108 eyes (62.9%) showed additional findings on optical coherence tomography imaging (eg, cystoid macular edema or macular atrophy). The variant c.998 + 1G>A;p.? led to a more severe phenotype when compared with the variant c.304C>A;p.(R102S). CONCLUSIONS AND RELEVANCE Seventeen of the PDE6A variants found in these patients appeared to be novel. Regarding the clinical findings, disease was highly symmetrical between the right and left eyes and visual impairment was mild or moderate in 90% of patients, providing a window of opportunity for gene therapy.
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| 2. |
- Weisschuh, Nicole, et al.
(författare)
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Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing.
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes.
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| 3. |
- Bozorgmehr, Kayvan, et al.
(författare)
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Analysing horizontal equity in enrolment in Disease Management Programmes for coronary heart disease in Germany 2008-2010
- 2015
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Ingår i: International Journal for Equity in Health. - : BioMed Central. - 1475-9276. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disease Management Programmes (DMPs) have been introduced in Germany ten years ago with the aim to improve effectiveness and equity of care, but little is known about the degree to which enrolment in the programme meets the principles of equity in health care. We aimed to analyse horizontal equity in DMP enrolment among patients with coronary heart disease (CHD). Methods: Cross-sectional analysis of horizontal inequities in physician-reported enrolment in the DMP for CHD in a large population-based cohort-study in Germany (2008-2010). We calculated horizontal inequity indices (HII) and their 95% confidence intervals [95% CI] for predicted need-standardised DMP enrolment across two measures of socio-economic status (SES) (educational attainment, regional deprivation) stratified by sex. Need-standardised DMP enrolment was predicted in multi-level logistic regression models. Results: Among N = 1,280 individuals aged 55-84 years and diagnosed with CHD, DMP enrolment rates were 22.2% (women) and 35.0% (men). Education-related inequities in need-standardised DMP enrolment favoured groups with lower education, but HII estimates were not significant. Deprivation-related inequities among women significantly favoured groups with higher SES (HII = 0.086 [0.007; 0.165]. No such deprivation-related inequities were seen among men (HII = 0.014 [-0.048; 0.077]). Deprivation-related inequities across the whole population favoured groups with higher SES (HII estimates not significant). Conclusion: Need-standardised DMP enrolment was fairly equitable across educational levels. Deprivation-related inequities in DMP enrolment favoured women living in less deprived areas relative to those living in areas with higher deprivation. Further research is needed to gain a better understanding of the mechanisms that contribute to deprivation-related horizontal inequities in DMP enrolment among women.
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| 4. |
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Die inszenierte Stadt : zur Praxis und Theorie kultureller Konstruktionen
- 2001. - 1
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- In diesem Band sind zwölf kultur-, literatur- und geschichtswissenschaftliche Beiträge versammelt, die das Thema Stadt in unterschiedlichen Kontexten zum Inhalt haben.Der Schwierpunkt liegt auf Nordeuropa, auf Städten wie Stockholm, Kopenhagen oder St. Petersburg. Erfasst werden urbane Spezifika sowie historische Verbindungen und gegenwärtige Beziehungen, nich zuletzt stehen die künstlerischen Annäherungen an Städte im Fokus.Das gemeinsame Thema is die Herstellung von Bildern des Städtischen, ihre bewusste Erzeugung und Zielgerichtete Verwendung, woraus sich der Begriff der „inszenierten“ Stadt ableitet.Dabei ist nicht nur an massenmediale Umsetzungen und Städtemarketing zu denken oder an der „entwirklichte“ oder „entstofflichte“ Darstellung der Stadt in Literatur und Film, sondern gerade auch an die Städtebilder, welche die urbane Wahrnehmung mit Hilfe von Kollektivsymbolen, Stereotypen, Metaphem oder elementaren narrativen Einheiten vorstrukturieren.
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| 5. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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| 6. |
- Lembrechts, Jonas J., et al.
(författare)
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Global maps of soil temperature
- 2022
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:9, s. 3110-3144
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Tidskriftsartikel (refereegranskat)abstract
- Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean=3.0±2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6±2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7±2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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