818 research outputs found
CEP906835 Supplemental table 1 - Supplemental material for Mitochondrial genome-wide association study of migraine – the HUNT Study
No full textSupplemental material, CEP906835 Supplemental table 1 for Mitochondrial genome-wide association study of migraine – the HUNT Study by Sigrid Børte, John-Anker Zwart, Anne Heidi Skogholt, Maiken Elvestad Gabrielsen, Laurent F Thomas, Lars G Fritsche, Ida Surakka, Jonas B Nielsen, Wei Zhou, Brooke N Wolford, Magnus D Vigeland, Knut Hagen, Espen Saxhaug Kristoffersen, Dale R Nyholt, Daniel I Chasman, Ben M Brumpton, Cristen J Willer and Bendik S Winsvold in Cephalalgia</p
Imbalance of complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age related macular degeneration (AMD)
No full textThe Role of Percutaneous Tibial Nerve Stimulation (PTNS) in Low Anterior Resection Syndrome (LARS): A Systematic Review and Meta-analysis
No full textPurpose: The aim of the present study was to evaluate the pooled efficacy of percutaneous tibial nerve stimulation (PTNS) in patients with low anterior resection syndrome (LARS). Material and Methods: This study was based on the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. The primary endpoint was the pooled effect size of PTNS in LARS score (LARSS). Secondary endpoints included incontinence (Fecal Incontinence Score—FIC, Obstructive Defecation Syndrome—ODS), sexual functionality and quality of life (QoL) questionnaires, and manometric evaluations. Continuous outcomes were reported as weighted mean difference (WMD), with the corresponding 95% confidence interval (95% CI). Quality evaluation was performed via the National Institutes of Health (NIH) quality assessment tool. Results: Overall, 5 studies were included. PTNS resulted to reduced LARSS values (WMD: − 5.68, 95%CI: − 7.73, − 3.63, p < 0.001). A similar effect was noted in St Mark’s FIC (p < 0.001) and ODS (p = 0.02) score. An improvement in several QoL scales was found. There was no effect in sexual functionality and manometric measurements. Compared to sham, PTNS significantly improved LARSS. Conclusions: The application of PTNS in patients with LARS results in an improvement in multiple clinical parameters, including defecation functionality and quality of life. Due to several study limitations, further high quality RCTs are required to delineate the exact efficacy of PTNS. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature
An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD)
No full textA frequent deletion of complement factor H (CFH)-related genes CFHR3 and CFHR1 (Delta CFHR3/CFHR1) is considered to have a protective effect against age-related macular degeneration (AMD), although the underlying mechanism remains elusive. The deletion seems to be linked to one of the two protective CFH haplotypes which are both tagged by the protective allele of single nucleotide polymorphism rs2274700 (CFH:A473A). In a German cohort of 530 AMD patients, we now show that protection against AMD conferred by Delta CFHR3/CFHR1 is independent of the effects of rs2274700 and rs1061170 (CFH:Y402H). This suggests a functional role of CFHR1 and/or CFHR3 in disease pathogenesis. We therefore characterized the CFHR3 function and identified CFHR3 as a novel human complement regulator that inhibits C3 convertase activity. CFHR3 displays anti-inflammatory effects by blocking C5a generation and C5a-mediated chemoattraction of neutrophils. In addition, CFHR3 and CFHR1 compete with factor H for binding to the central complement component C3. Thus, deficiency of CFHR3 and CFHR1 results in a loss of complement control but enhances local regulation by factor H. Our findings allude to a critical balance between the complement regulators CFHR3, CFHR1 and factor H and further emphasize the central role of complement regulation in AMD pathology
Accelerated Trajectories of Walking Capacity Across the Adult Life Span in Persons With Multiple Sclerosis: An Underrecognized Challenge
No full textBackground. In the general population, trajectories of walking capacity is accelerated and nonlinear with advanced age. Whether this is more pronounced in persons with multiple sclerosis (pwMS), along with the prevalence of dismobility (ie, slow gait speed), are currently unknown. Our objective was to investigate trajectories of walking capacity and prevalence of dismobility across the adult life span in pwMS versus healthy controls (HC). Methods. Data on maximal timed 25-foot walk test (T25FWT), 2-minute walk test (2MWT), and 6-minute walk test (6MWT) along with prevalence of dismobility were assembled from 2 RIMS multicenter studies (n = 502 pwMS; age range 21-77 years, 6 age groups: 20-29, 30-39, 40-49, 50-59, 60-69, and 70-79 years). HC data were extracted from studies containing normative reference values (n = 1070-3780 HC). Results. Age trajectories of walking capacity was nonlinear and accelerated in pwMS versus HC. While measures of walking capacity in pwMS were suppressed already early in life, the gap between pwMS and HC significantly widened across the 6 age groups (pwMS performed 64%, 70%, 57%, 59%, 51%, and 37% of HC, respectively). This coincided with high prevalences of dismobility in pwMS across the 6 age groups when using usual gait speed cut-point values <1.0 m/s (corresponding to 33%, 32%, 51%, 59%, 75%, and 100%) and <0.6 m/s (corresponding to 19%, 12%, 26%, 23%, 33%, and 43%), markedly exceeding that observed in HC. Conclusion. The present data on walking capacity provide evidence for an accelerated deterioration in pwMS with advanced age, coinciding with high prevalences of dismobility (ie, slow gait speed).The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was partially funded via an unrestricted educational grant from Novartis Pharma AG to Rehabilitation in Multiple Sclerosis, the European network for best practice and research in MS rehabilitation (eurims.org).Hvid, LG (reprint author), Aarhus Univ, Sect Sport Sci, Dept Publ Hlth, Dalgas Ave 4, DK-8000 Aarhus C, Denmark.
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Modelling the Genetic Risk in Age-Related Macular Degeneration
No full textLate-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05) than patients aged 75 and above (1.45, 95% CI: 1.36-1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96) for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available
Author Correction: A new ape from Türkiye and the radiation of late Miocene hominines
No full textCorrection to: Communications Biology, published online 23 August 2023. In the original version of the Article, two authors and their affiliations were omitted. In the original version of the Article, author first names were not provided for all authors. The corrected author list and affiliations are provided below. This has now been corrected in the HTML and PDF versions of the article. Ayla Sevim-Erol1, David R. Begun2, Alper Yavuz3, Erhan Tarhan4, Çilem Sönmez Sözer1, Serdar Mayda5, Lars W. van den Hoek Ostende6, Robert M. G. Martin2 ; M. Cihat Alçiçek7 1 Ankara University, Faculty of Languages History and Geography, Department of Anthropology, Ankara, Türkiye 2 Department of Anthropology, University of Toronto, Toronto, ON, Canada 3 Mehmet Akif Ersoy University of Science and Letters, Department of Anthropology, Burdur, Türkiye 4 Hitit University Faculty of Science and Letters, Department of Anthropology, Çorum, Türkiye 5 Ege University Fakulty of Science, Department of Biology, İzmir, Türkiye 6 Naturalis Biodiversity Center, Leiden, The Netherlands 7 Pamukkale University, Department of Geology, 20070 Denizli, Türkiye The Author Contributions section should read “A.S.E. is the PR of the project, secured funding for excavations and lab analysis and directed excavations. A.S.E. and D.R.B. are responsible for data curation, acquired funding and supervised research. D.R.B. conceptualized the analysis, conducted the investigation, developed the methodology, prepared the original draft and all subsequent versions. C.S.S., S.M., L.W.vdH. and C.A. contributed their analysis of geological and paleontological results. R.M.G.M. was responsible for the segmentation and analysis of the scans of the mandible. A.Y and E.T. participated in the excavations.” This has now been corrected in the HTML and PDF versions of the article. © 2023, Springer Nature Limited
Exploring healthy retinal aging with deep learning
No full textPurpose
To study the individual course of retinal changes caused by healthy aging using deep learning.
Design
Retrospective analysis of a large data set of retinal OCT images.
Participants
A total of 85 709 adults between the age of 40 and 75 years of whom OCT images were acquired in the scope of the UK Biobank population study.
Methods
We created a counterfactual generative adversarial network (GAN), a type of neural network that learns from cross-sectional, retrospective data. It then synthesizes high-resolution counterfactual OCT images and longitudinal time series. These counterfactuals allow visualization and analysis of hypothetical scenarios in which certain characteristics of the imaged subject, such as age or sex, are altered, whereas other attributes, crucially the subject’s identity and image acquisition settings, remain fixed.
Main Outcome Measures
Using our counterfactual GAN, we investigated subject-specific changes in the retinal layer structure as a function of age and sex. In particular, we measured changes in the retinal nerve fiber layer (RNFL), combined ganglion cell layer plus inner plexiform layer (GCIPL), inner nuclear layer to the inner boundary of the retinal pigment epithelium (INL-RPE), and retinal pigment epithelium (RPE).
Results
Our counterfactual GAN is able to smoothly visualize the individual course of retinal aging. Across all counterfactual images, the RNFL, GCIPL, INL-RPE, and RPE changed by −0.1 μm ± 0.1 μm, −0.5 μm ± 0.2 μm, −0.2 μm ± 0.1 μm, and 0.1 μm ± 0.1 μm, respectively, per decade of age. These results agree well with previous studies based on the same cohort from the UK Biobank population study. Beyond population-wide average measures, our counterfactual GAN allows us to explore whether the retinal layers of a given eye will increase in thickness, decrease in thickness, or stagnate as a subject ages.
Conclusion
This study demonstrates how counterfactual GANs can aid research into retinal aging by generating high-resolution, high-fidelity OCT images, and longitudinal time series. Ultimately, we envision that they will enable clinical experts to derive and explore hypotheses for potential imaging biomarkers for healthy and pathologic aging that can be refined and tested in prospective clinical trials.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found after the references
The Role of High-Tech Capital Formation for Swedish Productivity Growth
No full textWhile using new data and standard growth-accounting techniques, this paper takes a closer look at the Swedish productivity revival in the second half of the 1990s. In particular, I find large total factor productivity growth in high-tech producing sectors and capital deepening associated with high-tech equipment elsewhere. In addition, for high-tech producers, high-tech capital deepening has as a rule contributed negatively to labor productivity growth - a result above all driven by large increases in hours worked in this sector. I also find that in the business sector, the contribution from high-tech capital deepening to labor productivity growth increased from about 1 percent 1994 to 9 percent 1999.
Future Waste Scenarios for Sweden based on a CGE-model
No full textOver the last decades, waste quantities have grown steadily in close relation to economic growth. To tackle the problem of continuing waste growth within the EU, waste prevention was listed among four top priorities in the EU Sixth environment Action Programme. A Computable General Equilibrium (CGE) model is here used for projecting future quantities of hazardous and non-hazardous waste in Sweden to 2030. The effects of driving forces behind waste generation are illustrated by comparing the results of waste projections for a Baseline scenario and four alternative scenarios. The scenarios differ mainly in GDP growth rates and in the assumptions about future waste intensities of the economic activities of firms and households. We use a high-resolution data set on waste flows of 18 various types of non-hazardous waste and 16 various types of hazardous waste attributed to six waste-generating sources for the base year 2006. Waste generated in the scenarios, thus, relate to firms’ material input, output, employees, capital scrapping and fuel combustion as well as households’ consumption. The impact of economic growth in increasing the generation of nonhazardous and hazardous waste is apparent when comparing the growth of waste from 2006 to 2030 in the five scenarios. On the contrary, technological change resulting in less waste intensive production processes and changed behaviour among households, making their activities less waste intensive, have a strong reducing effect, especially on generation of non-hazardous waste relating to firms’ material input.general equilibrium model; waste generation; decoupling; waste intensities waste scenarios.
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