On the Reliability of Meta-Analytic Reviews

The article addresses the issue of intercoder reliability in meta-analyses. The current practice of reporting a single, mean intercoder agreement score in meta-analytic research leads to systematic bias and overestimates the true reliability. An alternative approach is recommended in which average intercoder agreement scores or other reliability statistics are calculated within clusters of coded variables. These clusters form a hierarchy in which the correctness of coding decisions at a given level of the hierarchy is contingent on decisions made at higher levels. Two separate studies of intercoder agreement in meta-analysis are presented to assess the validity of the model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67840/2/10.1177_0193841X9301700303.pd

Characterization of electrochemical systems using potential step voltammetry. Part II: Modeling of reversible systems

[EN] This study was carried out to compare the results obtained using potential step voltammetry and linear sweep voltammetry with a rotating gold disc electrode (RDE), when models based on equivalent circuits (EC) were used. The results lead to an equivalent circuit model that allows us to interpret the electrochemical behavior of aqueous solutions containing Fe(CN)(6)(-4) and Fe(CN)(6)(-3). With this model, we determined the values of the electrical resistance of the medium (R-s) as well as its polarization resistance (R-p), and established correlations between these values and the kinetic parameters of the system. The proposal highlights the need to introduce a new component for modeling using EC, which we have called the electrochemical diode. (C) 2019 Elsevier Ltd. All rights reserved.The authors gratefully acknowledge the financial support of BIA2016-78460-C3-3-R, MAT2015-64139-C4-3-R and RTI2018-100910-B-C43 (MINECO/FEDER) projects. We would also like to extend our appreciation for the pre-doctoral FPU scholarships (University Teacher Training scholarship) granted to Ana Martinez Ibernon (FPU 16/00723) and Jose Enrique Ramon Zamora (FPU13/00911) by the Spanish Ministry of Science and Innovation.Martínez-Ibernón, A.; Ramón Zamora, JE.; Gandía-Romero, JM.; Gasch, I.; Valcuende Payá, MO.; Alcañiz Fillol, M.; Soto Camino, J. (2019). Characterization of electrochemical systems using potential step voltammetry. Part II: Modeling of reversible systems. Electrochimica Acta. 328:1-10. https://doi.org/10.1016/j.electacta.2019.135111S11032

Oscillations and dynamics in a two-dimensional prey-predator system

Using Monte Carlo simulations we study two-dimensional prey-predator systems. Measuring the variance of densities of prey and predators on the triangular lattice and on the lattice with eight neighbours, we conclude that temporal oscillations of these densities vanish in the thermodynamic limit. This result suggests that such oscillations do not exist in two-dimensional models, at least when driven by local dynamics. Depending on the control parameter, the model could be either in an active or in an absorbing phase, which are separated by the critical point. The critical behaviour of this model is studied using the dynamical Monte Carlo method. This model has two dynamically nonsymmetric absorbing states. In principle both absorbing states can be used for the analysis of the critical point. However, dynamical simulations which start from the unstable absorbing state suffer from metastable-like effects, which sometimes renders the method inefficient.Comment: 7 eps figures, Phys.Rev.E - in pres

Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4)

Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images

Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival

Introduction: Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts. Methods: Using large ALS whole-genome sequencing and post-mortem RNA sequencing datasets (5,987 and 365 tissue samples, respectively), and iPSC-derived motor neurons from 55 individuals, we investigated the role of CAV1/2 expression and enhancer variants in the ALS phenotype. Results: We report a differential expression analysis between ALS cases and controls for CAV1 and CAV2 genes across various post-mortem brain tissues and three independent datasets. CAV1 and CAV2 expression was consistently higher in ALS patients compared to controls, with significant results across the primary motor cortex, lateral motor cortex, and cerebellum. We also identify increased survival among carriers of CAV1/2 enhancer mutations compared to non-carriers within Project MinE and slower progression as measured by the ALSFRS. Carriers showed a median increase in survival of 345 days. Discussion: These results add to an increasing body of evidence linking CAV1 and CAV2 genes to ALS. We propose that carriers of CAV1/2 enhancer mutations may be conceptualised as an ALS subtype who present a less severe ALS phenotype with a longer survival duration and slower progression. Upregulation of CAV1/2 genes in ALS cases may indicate a causal pathway or a compensatory mechanism. Given prior research supporting the beneficial role of CAV1/2 expression in ALS patients, we consider a compensatory mechanism to better fit the available evidence, although further investigation into the biological pathways associated with CAV1/2 is needed to support this conclusion

The impact of age on genetic testing decisions in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative syndrome. In up to 20% of cases, a family history is observed. Although Mendelian disease gene variants are found in apparently sporadic ALS, genetic testing is usually restricted to those with a family history or younger patients with sporadic disease. With the advent of therapies targeting genetic ALS, it is important that everyone treatable is identified. We therefore sought to determine the probability of a clinically actionable ALS genetic test result by age of onset, globally, but using the UK as an exemplar. Blood-derived DNA was sequenced for ALS genes, and the probability of a clinically actionable genetic test result estimated. For a UK subset, age- and sex-specific population incidence rates were used to determine the number of such results missed by restricting testing by age of onset according to UK’s National Genomic Test Directory criteria. There were 6274 people with sporadic ALS, 1551 from the UK. The proportion with a clinically actionable genetic test result ranged between 0.21 [95% confidence interval (CI) 0.18–0.25] in the youngest age group to 0.15 (95% CI 0.13–0.17) in the oldest age group for a full gene panel. For the UK, the equivalent proportions were 0.23 (95% CI 0.13–0.33) in the youngest age group to 0.17 (95% CI 0.13–0.21) in the oldest age group. By limiting testing in those without a family history to people with onset below 40 years, 115 of 117 (98% of all, 95% CI 96%–101%) clinically actionable test results were missed. There is a significant probability of a clinically actionable genetic test result in people with apparently sporadic ALS at all ages. Although some countries limit testing by age, doing so results in a significant number of missed pathogenic test results. Age of onset and family history should not be a barrier to genetic testing in ALS