Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.
Circulating proteins can be used to diagnose and predict disease-related outcomes. A deep serum proteome survey recently revealed close associations between serum protein networks and common disease. In the current study, 54,469 low-frequency and common exome-array variants were compared to 4782 protein measurements in the serum of 5343 individuals from the AGES Reykjavik cohort. This analysis identifies a large number of serum proteins with genetic signatures overlapping those of many diseases. More specifically, using a study-wide significance threshold, we find that 2021 independent exome array variants are associated with serum levels of 1942 proteins. These variants reside in genetic loci shared by hundreds of complex disease traits, highlighting serum proteins’ emerging role as biomarkers and potential causative agents of a wide range of diseases.
Whenever students use any drilling system the question arises how much of their learning is meaningful learning, which emphasises understanding and the transferability of prior knowledge, and how much is memorisation through repetition or rote learning. Although both types of learning have their place in an educational system it is important to be able to distinguish between these two approaches to learning and identify options which can dislodge students from rote learning and motivate them towards meaningful learning.The tutor-web is an online drilling system, which has been used by thousands of students from Iceland to Kenya. The design aim of the system is to promote meaningful learning rather than evaluation. This is done by presenting students with multiple-choice questions which are selected randomly but nevertheless linked to the students' performance to ensure that students are appropriately challenged. The questions themselves can be generated for a specific topic by drawing correct and incorrect answers from a collection associated with a general problem statement or heading. With this generating process students may see the same question heading twice but be presented with all new answer options or a mixture of new and old answer options.Data from an introductory university course on probability theory and statistics, taught using the tutorweb during COVID-19, are analysed to separate rote learning from meaningful learning. The analyses show that considerable non-rote learning takes place, but even with fairly large question databases, students' performance is considerably better when they are presented with an answer option they have seen before. An element of rote learning is thus clearly exhibited but a deeper learning is also demonstrated.The item database has been seeded with occasional hints such that some questions contain fairly detailed clues, which should cue the students towards the correct answer. This ties in with the issue of meaningful learning versus rote learning since the hope is that a new hint will work as a cue to coax the student to think harder about the question rather than continue to employ rote learning. The existence of occasional hints allows several comparisons. The simplest analysis is on whether the overall grade on cue questions is higher than on the non-cue questions. A more important issue is whether more learning has occurred and methods are developed to estimate the change rather than status. Preliminary results indicate that hints are particularly useful for students with poor performance metrics, and a power analysis demonstrates the sample sizes needed in future studies to better quantify these effects.
Age-related macular degeneration (AMD) is one of the most frequent causes of visual impairment in the elderly population. The overall etiology of AMD is complex and still poorly understood, though age, obesity, smoking, and high-density lipoprotein are known risk factors. In one of the first successful reported genome-wide association studies (GWAS), common genetic variants were strongly associated with AMD, including variants within the complement factor H (CFH) gene. To date, 34 genomic regions have been linked to AMD; however, the genes that mediate the risk remain largely unknown, indicating that novel approaches to identifying causal candidates are needed. Recent advances in proteomic technology have exposed the serum proteome's depth and complexity. In the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), a broad population-based study of the elderly (N = 5764), levels of 4137 human serum proteins and associated networks were integrated with established genetic risk loci for AMD, revealing many predicted as well as novel proteins and pathways, linked to the disease. Serum proteins were also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study of five proteins associated with AMD found CFHR1, CFHR5, and FUT5 to be causally related to the disease, all of which were directionally consistent with the observational estimates. This study provides a robust and unique framework for elucidating the pathobiology of AMD.
Background Psoriatic arthritis mutilans (PAM) is the most severe phenotype of psoriatic arthritis (PsA). Purpose To describe the radiological features in PAM and explore whether existing scoring systems for radiological damage in psoriatic arthritis are applicable for PAM. Material and Methods Radiographs were scored according to the modified Sharp-van der Heijde (mSvdH) and the Psoriatic Arthritis Ratingen Score (PARS) systems for PsA. Results At inclusion, 55 PAM patients (49% women, mean age 58 ± 12 years) had conventional radiographs of both hands and feet. A total of 869 PAM joints were detected and 193 joints with ankylosis. The mean total mSvdH score was 213.7 ± 137.8 (41% of maximum) with a higher score for hands than for feet: 136.6 ± 90.1 vs. 79.1 ± 60.9. However, the total score was relatively higher in the feet than in the hands when compared to the highest possible scoring (47% vs. 38% of max). The mean total PARS score was 126.3 ± 79.6 (35% of max). Scoring for joint destruction was higher than for proliferation (22% vs. 11% of max). Strong correlation was found between mSvdH and PARS (r2 = 0.913). A significant correlation was found between scoring and duration of arthritis and the Health Assessment Questionnaire. History of smoking, BMI, and gender did not influence the scoring values. Conclusions The two scoring systems studied may not be ideal to indicate progression of PAM in advanced disease since they reach ceiling effects rather early. Therefore, reporting early signs suggestive of PAM, e.g. signs of pencil-in-cup deformities or osteolysis, is crucial. This would reveal the presence of PAM and might lead to improved treatment in order to minimize joint damage.
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