Medication Responsiveness of Motor Symptoms in a Population-Based Study of Parkinson Disease

We assessed degree of Parkinson disease motor symptom improvement with medication among subjects enrolled in an ongoing, population-based study in Central California. The motor section of the unified Parkinson disease rating scale (UPDRS) was performed on subjects in both OFF and ON medication states, and difference between these scores was used as an indicator of symptomatic benefit. Higher OFF minus ON scores correlated with more severe baseline symptoms. There was equivalent improvement on the motor UPDRS scale for subjects divided according to medication classes used: levodopa alone 7.3 points, levodopa plus other medications 8.5 points, and dopamine agonists but not levodopa 6.1 points. In addition, there was no difference in the magnitude of improvement when subjects were divided according to Parkinson disease subtype, defined as tremor dominant, akinetic-rigid, or mixed. In this community-based sample, these values are within the range of a clinically important difference as defined by previous studies

When Analysis Fails: Heuristic Mechanism Design via Self-Correcting Procedures

Computational mechanism design (CMD) seeks to understand how to design game forms that induce desirable outcomes in multi-agent systems despite private information, self-interest and limited computational resources. CMD finds application in many settings, in the public sector for wireless spectrum and airport landing rights, to Internet advertising, to expressive sourcing in the supply chain, to allocating computational resources. In meeting the demands for CMD in these rich domains, we often need to bridge from the theory of economic mechanism design to the practice of deployable, computational mechanisms. A compelling example of this need arises in dynamic combinatorial environments, where classic analytic approaches fail and heuristic, computational approaches are required. In this talk I outline the direction of self-correcting mechanisms, which dynamically modify decisions via “output ironing" to ensure truthfulness and provide a fully computational approach to mechanism design. For an application, I suggest heuristic mechanisms for dynamic auctions in which bids arrive over time and supply may also be uncertain.Engineering and Applied Science

Welfare and Revenue Guarantees for Competitive Bundling Equilibrium

We study equilibria of markets with $m$ heterogeneous indivisible goods and $n$ consumers with combinatorial preferences. It is well known that a competitive equilibrium is not guaranteed to exist when valuations are not gross substitutes. Given the widespread use of bundling in real-life markets, we study its role as a stabilizing and coordinating device by considering the notion of \emph{competitive bundling equilibrium}: a competitive equilibrium over the market induced by partitioning the goods for sale into fixed bundles. Compared to other equilibrium concepts involving bundles, this notion has the advantage of simulatneous succinctness ($O(m)$ prices) and market clearance. Our first set of results concern welfare guarantees. We show that in markets where consumers care only about the number of goods they receive (known as multi-unit or homogeneous markets), even in the presence of complementarities, there always exists a competitive bundling equilibrium that guarantees a logarithmic fraction of the optimal welfare, and this guarantee is tight. We also establish non-trivial welfare guarantees for general markets, two-consumer markets, and markets where the consumer valuations are additive up to a fixed budget (budget-additive). Our second set of results concern revenue guarantees. Motivated by the fact that the revenue extracted in a standard competitive equilibrium may be zero (even with simple unit-demand consumers), we show that for natural subclasses of gross substitutes valuations, there always exists a competitive bundling equilibrium that extracts a logarithmic fraction of the optimal welfare, and this guarantee is tight. The notion of competitive bundling equilibrium can thus be useful even in markets which possess a standard competitive equilibrium

On the Efficiency of All-Pay Mechanisms

We study the inefficiency of mixed equilibria, expressed as the price of anarchy, of all-pay auctions in three different environments: combinatorial, multi-unit and single-item auctions. First, we consider item-bidding combinatorial auctions where m all-pay auctions run in parallel, one for each good. For fractionally subadditive valuations, we strengthen the upper bound from 2 [Syrgkanis and Tardos STOC'13] to 1.82 by proving some structural properties that characterize the mixed Nash equilibria of the game. Next, we design an all-pay mechanism with a randomized allocation rule for the multi- unit auction. We show that, for bidders with submodular valuations, the mechanism admits a unique, 75% efficient, pure Nash equilibrium. The efficiency of this mechanism outperforms all the known bounds on the price of anarchy of mechanisms used for multi-unit auctions. Finally, we analyze single-item all-pay auctions motivated by their connection to contests and show tight bounds on the price of anarchy of social welfare, revenue and maximum bid.Comment: 26 pages, 2 figures, European Symposium on Algorithms(ESA) 201

SF-36 includes less Parkinson Disease (PD)-targeted content but is more responsive to change than two PD-targeted health-related quality of life measures

To compare validity including responsiveness, and internal consistency reliability and scaling assumptions of a generic (SF-36) and Parkinson Disease (PD)-targeted (PDQ-39; PDQUALIF) health-related quality of life (HRQOL) measures. Ninety-six PD patients were administered for all HRQOL measures by telephonic interview at baseline and 18 months. Relative efficiency and responsiveness were compared relative to four external criteria (self-ratings of PD’s daily effects, global Quality of Life, PD symptom severity, and a depression screener). We examined whether PD-targeted measures explained unique variance beyond the SF-36 by regressing criterion variables on HRQOL scales/items. Adequacy of PD-targeted measures’ original scaling was explored by item-scale correlations. Relative efficiency estimates were similar for generic and PD-targeted measures across all criteria. Responsiveness analyses showed that the SF-36 yielded large (>0.8) effect sizes (ES) for three of eight scales for each of two criterion variables, compared to only one large ES for any scale in either PD-targeted measure. Adjusted R 2 increased from 14 to 27% in regression models that included PD-targeted items compared to models with only SF-36 scales. Item-scale correlations showed significant cross-loading of items across scales of the PD-targeted measures. SF-36 responsiveness was better than that of two PD-targeted measures, yet those measures had content that significantly explains PD patients’ HRQOL

Epistatic and Combinatorial Effects of Pigmentary Gene Mutations in the Domestic Pigeon

SummaryUnderstanding the molecular basis of phenotypic diversity is a critical challenge in biology, yet we know little about the mechanistic effects of different mutations and epistatic relationships among loci that contribute to complex traits. Pigmentation genetics offers a powerful model for identifying mutations underlying diversity and for determining how additional complexity emerges from interactions among loci. Centuries of artificial selection in domestic rock pigeons (Columba livia) have cultivated tremendous variation in plumage pigmentation through the combined effects of dozens of loci. The dominance and epistatic hierarchies of key loci governing this diversity are known through classical genetic studies [1–6], but their molecular identities and the mechanisms of their genetic interactions remain unknown. Here we identify protein-coding and cis-regulatory mutations in Tyrp1, Sox10, and Slc45a2 that underlie classical color phenotypes of pigeons and present a mechanistic explanation of their dominance and epistatic relationships. We also find unanticipated allelic heterogeneity at Tyrp1 and Sox10, indicating that color variants evolved repeatedly though mutations in the same genes. These results demonstrate how a spectrum of coding and regulatory mutations in a small number of genes can interact to generate substantial phenotypic diversity in a classic Darwinian model of evolution [7]

Confirmatory Factor Analysis of the Motor Unified Parkinson’s Disease Rating Scale

The motor examination section of the unified Parkinson's disease rating scale (UPDRS) is widely used in research but few studies have examined whether subscales exist that tap relatively distinct motor abnormalities. We analyzed data from 193 persons enrolled in a population-based study in Central California. Patients were examined after overnight PD medication washout (“OFF” state) and approximately one hour after taking medication (“ON” state). We performed confirmatory factor analysis of the UPDRS for OFF and ON state examinations; correlations, reliability, and relative validity of resulting subscales were evaluated. A model with five factors (gait/posture, tremor, rigidity, bradykinesia affecting the left extremities, bradykinesia affecting the right extremities) fit the data well, with similar results for OFF and ON states. Internal consistency reliability coefficients were 0.90 or higher for all subscales. The gait/posture subscale most strongly discriminated across levels of patient reported PD symptom severity and of how PD affects them on a daily basis. Compared to the right sided bradykinesia subscale, the left sided bradykinesia subscale had higher discrimination across levels of self-reported PD symptom severity and functional impairment. This supports motor UPDRS containing multiple subscales that can be analyzed separately and provide information distinct from the total score that may be useful in clinical studies