Background Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense variants were described, their pathogenic role yet remains inconclusive. Methods and results We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort. Conclusions Our study apart from identifying the p.Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide.
Abstract Overstated generalizability (external validity) is common in research. It may coexist with inflation of the magnitude and statistical support for effects and dismissal of internal validity problems. Generalizability may be secured before attempting replication of proposed discoveries or replication may precede efforts to generalize. These opposite approaches may decrease or increase, respectively, the use of inferential statistics with advantages and disadvantages.
The rates of viral load increase among patients with viral rebound while receiving less than triple therapy are similar to those reported in patients interrupting therapy. Variability among patients may depend on viral fitness, target cell availability and extent of immune reconstitution.
In a cohort of 204 unselected consecutive human immunodeficiency virus type 1 (HIV-1)-infected patients, the association of circulating autoantibodies to endogenous erythropoietin (EPO) with HIV-1-related anemia was studied. Circulating autoantibodies to EPO were present in 48 (23.5%) of the 204 patients studied. Circulating autoantibodies were an independent predictor of anemia (odds ratio [OR]=5.0; 95% confidence interval [CI], 2.5-9.9), as strong as other known causes of anemia. The association of anti-EPO antibodies with anemia became stronger when the analysis was limited to the group of patients without any medical condition causing anemia (OR=10.4; 95% CI, 3.2-33.9). Moreover, the effect on hemoglobin levels remained significant even after adjusting for other anemia parameters. Anti-EPO autoantibodies were associated with higher EPO levels (r=.25, P=.012) and with a more prominent EPO response to anemia. Our findings suggest that autoimmunity, among other factors, may contribute to the pathogenesis of HIV-1-related anemia.
Systematic reviews and meta-analyses have reached a critical point. Their success is solid and dreadful at the same time. They are widely considered the highest level of evidence. There are tens of thousands of systematic reviews already published, but their production is still increasing geometrically. The problem is that the majority of systematic reviews are flawed, misleading, redundant, useless or all of the above,1 and this applies to almost all medical fields, including sports and exercise medicine. Part of the problem with systematic reviews stems from the poor, misleading primary evidence2 that authors try to synthesise and make sense of. However, if this were the only major problem, systematic reviews and meta-analyses would still be extremely useful. They could focus exactly on showing how flawed, misleading and useless this evidence is. This could lead to suggestions on how to improve research in the field. Instead, systematic reviews often sanctify results from poor studies, by making these seem even more statistically significant and (spuriously) conclusive. They can also compound the problems seen in the primary studies, if they are driven by reviewers and sponsors with conflicts of interest, financial or academic. There are four types of ‘next-generation’ systematic reviews that may raise the bar and help shape a new generation of more reliable evidence synthesis: prospective meta-analysis, individual-level data, network meta-analyses and umbrella reviews. They are not necessarily brand new ideas, but in the current circumstances of uncontrollable overproduction and unchecked quality, they have a fresh opportunity for impact. This large-scale impact would have been unimaginable in the past due to constrains in access to data, limited availability of sophisticated methods and fewer opportunities for their application. None of these next-generation tools are bullet proof, but they hold promise and some distinct advantages. Their disadvantages also need to be …
Citation metrics are widely used and misused. We have created a publicly available database of 100,000 top-scientists that provides standardized information on citations, h-index, co-authorship adjusted hm-index, citations to papers in different authorship positions and a composite indicator. Separate data are shown for career-long and single year impact. Metrics with and without self-citations and ratio of citations to citing papers are given. Scientists are classified into 22 scientific fields and 176 sub-fields. Field- and subfield-specific percentiles are also provided for all scientists who have published at least 5 papers. Career-long data are updated to end-of-2019. \n\nThe dataset and code provides an update to previously released (version 1) data under https://doi.org/10.17632/btchxktzyw.1; The version 2 dataset is based on the May 06, 2020 snapshot from Scopus and is updated to citation year 2019. In addition to the time period and datacut update, it provides a longer list of authors: it also includes the top 2% for every subfield.
Data for: Redundant meta-analyses are common in genetic epidemiology
Objectives Meta-analyses are considered generally as the highest level of evidence, but concerns have been voiced about their massive, low-quality production. This paper aimed to evaluate the landscape of meta-analyses in the field of occupational and environmental health and medicine. Methods Using relevant search terms, all meta-analyses were searched for, but those published in 2015 were assessed for their origin, whether they included randomised trials and individual-level data and whether they had authors from the industry or consultancy firms. Results PubMed searches (last update February 2017) identified 1251 eligible meta-analyses in this field. There was a rapid increase over time (n=16 published in 1995 vs n=163 published in 2015). Of the 163 eligible meta-analyses published in 2015, 49 were from China, followed at a distance by the USA (n=19). Only 16 considered randomised (intervention) trials and 13 included individual-level data. Only 1 of the 150 meta-analyses had industry authors and none had consultancy firm authors. As an example of conflicting findings, 12 overlapping meta-analyses addressed mobile phones and brain cancer risk and they differed substantially in number of studies included, eligibility criteria and conclusions. Conclusions There has been a major increase in the publication of meta-analyses in occupational and environmental health over time, with the majority of these studies focusing on observational data, while a commendable fraction used individual-level data. Authorship is still limited largely to academic and non-profit authors. With massive production of meta-analyses, redundancy needs to be anticipated and efforts should be made to safeguard quality and protect from bias.
This paper presents a new architecture style for the design of a parallel floating point multiplier. The proposed architecture is a synergy of trees and arrays. Architectural models were designed to implement the 53-bit mantissa path of the IEEE standard 754 for floating point multiplication, and tested for functionality in Verilog. The design, which was done in dual-rail domino, simulated in HSpice with estimated capacitive load models in a 1 /spl mu/m CMOS technology. Multiplication latency of 10 ns (23.3 FO4) at 4.3 V supply and 120/spl deg/C can be achieved with the best topology of the array-of-arrays architecture. The estimated multiplier area is 3 mm/spl times/6 mm.
