Measuring Consensus in Binary Forecasts: NFL Game Predictions

Previous research on defining and measuring consensus (agreement) among forecasters has been concerned with evaluation of forecasts of continuous variables. This previous work is not relevant when the forecasts involve binary decisions: up-down or win-lose. In this paper we use Cohen¡¯s kappa coefficient, a measure of inter-rater agreement involving binary choices, to evaluate forecasts of National Football League games. This statistic is applied to the forecasts of 74 experts and 31 statistical systems that predicted the outcomes of games during two NFL seasons. We conclude that the forecasters, particularly the systems, displayed significant levels of agreement and that levels of agreement in picking game winners were higher than in picking against the betting line. There is greater agreement among statistical systems in picking game winners or picking winners against the line as the season progresses, but no change in levels of agreement among experts. High levels of consensus among forecasters are associated with greater accuracy in picking game winners, but not in picking against the line.binary forecasts, NFL, agreement, consensus, kappa coefficient

Indirect Targeting of Subthalamic Deep Brain Stimulation Guided by Stereotactic Computed Tomography and Microelectrode Recordings in Patients With Parkinson’s Disease

Objective: Magnetic resonance imaging fusion techniques guided by frame-based stereotactic computed tomography and microelectrode recordings are widely used to target the subthalamic nucleus. However, MRI is not always available. The aim of this study was to determine whether the indirect targeting of the subthalamic nucleus for deep brain stimulation using frame-based stereotactic computed tomography and microelectrode recording guidance in patients with advanced idiopathic Parkinson’s disease was an effective and safe treatment and to determine the factors that contributed to outcome.Methods: Thirty-four consecutive patients with Parkinson’s disease who were treated from 2010 to 2012 were enrolled in this retrospective cohort study. The patients were assessed with the Unified Parkinson’s Disease Rating Scale-part III (UPDRS-III) and other clinical profiles peri- and post-operatively. The horizontal and vertical distances between the midpoint of the head frame and the brain midline at the septum pellucidum level and the upper edge of the bilateral lens, respectively, on a thin-section brain computed tomography scan were defined as the horizontal and vertical deviations, respectively.Results: After the deep brain stimulation surgery, the patients’ UPDRS-III scores improved 48 ± 2.8% (range, 20–81%) compared to the patients’ baseline off-levodopa scores. No surgery-associated complications were found. The mean recorded length difference of the subthalamic nucleus between the initial and final single microelectrode recording trajectories was 5.37 ± 0.16 mm (range, 3.99–7.50). Multiple linear regression analyses revealed that the increased lengths of the vertical (regression coefficient [B]: -0.0626; 95% confidence interval [CI]: -0.113 to -0.013) and horizontal deviations (B: -0.0497; 95% CI: -0.083 to -0.017) were associated with less improvement in the patients’ UPDRS scores.Conclusion: These results showed that the indirect targeting of the subthalamic nucleus for deep brain stimulation using frame-based stereotactic computed tomography and microelectrode recording guidance in patients with advanced idiopathic Parkinson’s disease was effective and safe. Greater symmetry of the head frame fixation resulted in better outcomes of the deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease, especially when the horizontal deviation was 2 mm or less and the vertical deviation was 1 mm or less

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are 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 monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Modification of Small Hepatitis Delta Virus Antigen by SUMO Protein▿

Hepatitis delta antigen (HDAg) is a nuclear protein that is intimately involved in hepatitis delta virus (HDV) RNA replication. HDAg consists of two protein species, the small form (S-HDAg) and the large form (L-HDAg). Previous studies have shown that posttranslational modifications of S-HDAg, such as phosphorylation, acetylation, and methylation, can modulate HDV RNA replication. In this study, we show that S-HDAg is a small ubiquitin-like modifier 1 (SUMO1) target protein. Mapping data showed that multiple lysine residues are SUMO1 acceptors within S-HDAg. Using a genetic fusion strategy, we found that conjugation of SUMO1 to S-HDAg selectively enhanced HDV genomic RNA and mRNA synthesis but not antigenomic RNA synthesis. This result supports our previous proposition that the cellular machinery involved in the synthesis of HDV antigenomic RNA is different from that for genomic RNA synthesis and mRNA transcription, requiring different modified forms of S-HDAg. Sumoylation represents a new type of modification for HDAg