Toward understanding ambulatory activity decline in Parkinson disease

BACKGROUND: Declining ambulatory activity represents an important facet of disablement in Parkinson disease (PD). OBJECTIVE: The primary study aim was to compare the 2-year trajectory of ambulatory activity decline with concurrently evolving facets of disability in a small cohort of people with PD. The secondary aim was to identify baseline variables associated with ambulatory activity at 1- and 2-year follow-up assessments. DESIGN: This was a prospective, longitudinal cohort study. METHODS: Seventeen people with PD (Hoehn and Yahr stages 1-3) were recruited from 2 outpatient settings. Ambulatory activity data were collected at baseline and at 1- and 2-year annual assessments. Motor, mood, balance, gait, upper extremity function, quality of life, self-efficacy, and levodopa equivalent daily dose data and data on activities of daily living also were collected. RESULTS: Participants displayed significant 1- and 2-year declines in the amount and intensity of ambulatory activity concurrently with increasing levodopa equivalent daily dose. Worsening motor symptoms and slowing of gait were apparent only after 2 years. Concurrent changes in the remaining clinical variables were not observed. Baseline ambulatory activity and physical performance variables had the strongest relationships with 1- and 2-year mean daily steps. LIMITATIONS: The sample was small and homogeneous. CONCLUSIONS: Future research that combines ambulatory activity monitoring with a broader and more balanced array of measures would further illuminate the dynamic interactions among evolving facets of disablement and help determine the extent to which sustained patterns of recommended daily physical activity might slow the rate of disablement in PD.This study was funded primarily by the Davis Phinney Foundation and the Parkinson Disease Foundation. Additional funding was provided by Boston University Building Interdisciplinary Research Careers in Women's Health (K12 HD043444), the National Institutes of Health (R01NS077959), the Utah Chapter of the American Parkinson Disease Association (APDA), the Greater St Louis Chapter of the APDA, and the APDA Center for Advanced PD Research at Washington University. (Davis Phinney Foundation; Parkinson Disease Foundation; K12 HD043444 - Boston University Building Interdisciplinary Research Careers in Women's Health; R01NS077959 - National Institutes of Health; Utah Chapter of the American Parkinson Disease Association (APDA); Greater St Louis Chapter of the APDA; APDA Center for Advanced PD Research at Washington University

An Empirically Derived Three-Dimensional Laplace Resonance in the Gliese 876 Planetary System

We report constraints on the three-dimensional orbital architecture for all four planets known to orbit the nearby M dwarf Gliese 876 based solely on Doppler measurements and demanding long-term orbital stability. Our dataset incorporates publicly available radial velocities taken with the ELODIE and CORALIE spectrographs, HARPS, and Keck HIRES as well as previously unpublished HIRES velocities. We first quantitatively assess the validity of the planets thought to orbit GJ 876 by computing the Bayes factors for a variety of different coplanar models using an importance sampling algorithm. We find that a four-planet model is preferred over a three-planet model. Next, we apply a Newtonian MCMC algorithm to perform a Bayesian analysis of the planet masses and orbits using an n-body model in three-dimensional space. Based on the radial velocities alone, we find that a 99% credible interval provides upper limits on the mutual inclinations for the three resonant planets ($\Phi_{cb}<6.20^\circ$ for the "c" and "b" pair and $\Phi_{be}<28.5^\circ$ for the "b" and "e" pair). Subsequent dynamical integrations of our posterior sample find that the GJ 876 planets must be roughly coplanar ($\Phi_{cb}<2.60^\circ$ and $\Phi_{be}<7.87^\circ$), suggesting the amount of planet-planet scattering in the system has been low. We investigate the distribution of the respective resonant arguments of each planet pair and find that at least one argument for each planet pair and the Laplace argument librate. The libration amplitudes in our three-dimensional orbital model supports the idea of the outer-three planets having undergone significant past disk migration.Comment: 19 pages, 11 figures, 8 tables. Accepted to MNRAS. Posterior samples available at https://github.com/benelson/GJ87

Balance differences in people with Parkinson disease with and without freezing of gait

Published in final edited form as: Gait Posture. 2015 September ; 42(3): 306–309. doi:10.1016/j.gaitpost.2015.06.007.BACKGROUND: Freezing of gait (FOG) is a relatively common and remarkably disabling impairment associated with Parkinson disease (PD). Laboratory-based measures indicate that individuals with FOG (PD+FOG) have greater balance deficits than those without FOG (PD-FOG). Whether such differences also can be detected using clinical balance tests has not been investigated. We sought to determine if balance and specific aspects of balance, measured using Balance Evaluation Systems Test (BESTest), differs between PD+FOG and PD-FOG. Furthermore, we aimed to determine if time-efficient clinical balance measures (i.e. Mini-BESTest, Berg Balance Scale (BBS)) could detect balance differences between PD+FOG and PD-FOG. METHODS: Balance of 78 individuals with PD, grouped as either PD+FOG (n=32) or PD-FOG (n=46), was measured using the BESTest, Mini-BESTest, and BBS. Between-groups comparisons were conducted for these measures and for the six sections of the BESTest using analysis of covariance. A PD composite score was used as a covariate. RESULTS: Controlling for motor sign severity, PD duration, and age, PD+FOG had worse balance than PD-FOG when measured using the BESTest (p=0.008, F=7.35) and Mini-BESTest (p=0.002, F=10.37), but not the BBS (p=0.27, F=1.26). BESTest section differences were noted between PD+FOG and PD-FOG for reactive postural responses (p<0.001, F=14.42) and stability in gait (p=0.003, F=9.18). CONCLUSIONS: The BESTest and Mini-BESTest, which specifically assessed reactive postural responses and stability in gait, were more likely than the BBS to detect differences in balance between PD+FOG and PD-FOG. Because it is more time efficient to administer, the Mini-BESTest may be the preferred tool for assessing balance deficits associated with FOG.This study was conducted with funding from the Davis Phinney Foundation, Parkinson's Disease Foundation, NIH R01 NS077959, NIH UL1 TR000448, Greater St. Louis American Parkinson Disease Association (APDA), APDA Center for Advanced PD Research at Washington University in St. Louis. The funding sources had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. (Davis Phinney Foundation; Parkinson's Disease Foundation; R01 NS077959 - NIH; UL1 TR000448 - NIH; Greater St. Louis American Parkinson Disease Association (APDA); APDA Center for Advanced PD Research at Washington University in St. Louis

Two-year trajectory of fall risk in people with Parkinson disease: a latent class analysis

Published in final edited form as: Arch Phys Med Rehabil. 2016 March ; 97(3): 372–379.e1. doi:10.1016/j.apmr.2015.10.105.OBJECTIVE: To examine fall risk trajectories occurring naturally in a sample of individuals with early to middle stage Parkinson disease (PD). DESIGN: Latent class analysis, specifically growth mixture modeling (GMM), of longitudinal fall risk trajectories. SETTING: Assessments were conducted at 1 of 4 universities. PARTICIPANTS: Community-dwelling participants with PD of a longitudinal cohort study who attended at least 2 of 5 assessments over a 2-year follow-up period (N=230). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fall risk trajectory (low, medium, or high risk) and stability of fall risk trajectory (stable or fluctuating). Fall risk was determined at 6 monthly intervals using a simple clinical tool based on fall history, freezing of gait, and gait speed. RESULTS: The GMM optimally grouped participants into 3 fall risk trajectories that closely mirrored baseline fall risk status (P=.001). The high fall risk trajectory was most common (42.6%) and included participants with longer and more severe disease and with higher postural instability and gait disability (PIGD) scores than the low and medium fall risk trajectories (P<.001). Fluctuating fall risk (posterior probability <0.8 of belonging to any trajectory) was found in only 22.6% of the sample, most commonly among individuals who were transitioning to PIGD predominance. CONCLUSIONS: Regardless of their baseline characteristics, most participants had clear and stable fall risk trajectories over 2 years. Further investigation is required to determine whether interventions to improve gait and balance may improve fall risk trajectories in people with PD.Supported by the Davis Phinney Foundation, the Parkinson's Disease Foundation, National Institutes of Health (NIH) (grant nos. NIH R01 NS077959 and NIH UL1 TR000448), the Massachusetts and Utah Chapters of the American Parkinson Disease Association (APDA), the Greater St Louis Chapter of the APDA, and the APDA Center for Advanced Research at Washington University. (Davis Phinney Foundation; Parkinson's Disease Foundation; NIH R01 NS077959 - National Institutes of Health (NIH); NIH UL1 TR000448 - National Institutes of Health (NIH); Utah Chapter of the American Parkinson Disease Association (APDA); Greater St Louis Chapter of the APDA; APDA Center for Advanced Research at Washington University; Massachusetts Chapter of the American Parkinson Disease Association (APDA)

Retired A Stars and Their Companions VI. A Pair of Interacting Exoplanet Pairs Around the Subgiants 24 Sextanis and HD200964

We report radial velocity measurements of the G-type subgiants 24 Sextanis (=HD90043) and HD200964. Both are massive, evolved stars that exhibit periodic variations due to the presence of a pair of Jovian planets. Photometric monitoring with the T12 0.80m APT at Fairborn Observatory demonstrates both stars to be constant in brightness to <= 0.002 mag, thus strengthening the planetary interpretation of the radial velocity variations. 24 Sex b,c have orbital periods of 453.8 days and 883~days, corresponding to semimajor axes 1.333 AU and 2.08 AU, and minimum masses (Msini) 1.99 Mjup and 0.86 Mjup, assuming a stellar mass 1.54 Msun. HD200964 b,c have orbital periods of 613.8 days and 825 days, corresponding to semimajor axes 1.601 AU and 1.95 AU, and minimum masses 1.85 Mjup and 0.90 Mjup, assuming M* = 1.44 Msun. We also carry out dynamical simulations to properly account for gravitational interactions between the planets. Most, if not all, of the dynamically stable solutions include crossing orbits, suggesting that each system is locked in a mean motion resonance that prevents close encounters and provides long-term stability. The planets in the 24 Sex system likely have a period ratio near 2:1, while the HD200964 system is even more tightly packed with a period ratio close to 4:3. However, we caution that further radial velocity observations and more detailed dynamical modelling will be required to provide definitive and unique orbital solutions for both cases, and to determine whether the two systems are truly resonant.Comment: AJ accepte

Transit Timing Observations from Kepler: VI. Potentially interesting candidate systems from Fourier-based statistical tests

We analyze the deviations of transit times from a linear ephemeris for the Kepler Objects of Interest (KOI) through Quarter six (Q6) of science data. We conduct two statistical tests for all KOIs and a related statistical test for all pairs of KOIs in multi-transiting systems. These tests identify several systems which show potentially interesting transit timing variations (TTVs). Strong TTV systems have been valuable for the confirmation of planets and their mass measurements. Many of the systems identified in this study should prove fruitful for detailed TTV studies.Comment: 32 pages, 6 of text and one long table, Accepted to Ap

A new physical interpretation of optical and infrared variability in quasars

Changing-look quasars are a recently identified class of active galaxies in which the strong UV continuum and/or broad optical hydrogen emission lines associated with unobscured quasars either appear or disappear on timescales of months to years. The physical processes responsible for this behaviour are still debated, but changes in the black hole accretion rate or accretion disk structure appear more likely than changes in obscuration. Here we report on four epochs of spectroscopy of SDSS J110057.70-005304.5, a quasar at a redshift of $z=0.378$ whose UV continuum and broad hydrogen emission lines have faded, and then returned over the past $\approx$20 years. The change in this quasar was initially identified in the infrared, and an archival spectrum from 2010 shows an intermediate phase of the transition during which the flux below rest-frame $\approx$3400\AA\ has decreased by close to an order of magnitude. This combination is unique compared to previously published examples of changing-look quasars, and is best explained by dramatic changes in the innermost regions of the accretion disk. The optical continuum has been rising since mid-2016, leading to a prediction of a rise in hydrogen emission line flux in the next year. Increases in the infrared flux are beginning to follow, delayed by a $\sim$3 year observed timescale. If our model is confirmed, the physics of changing-look quasars are governed by processes at the innermost stable circular orbit (ISCO) around the black hole, and the structure of the innermost disk. The easily identifiable and monitored changing-look quasars would then provide a new probe and laboratory of the nuclear central engine.Comment: 13 pages, 4 figures, 3 tables. Published in MNRAS. All code and data links on GitHub, https://github.com/d80b2t/WISE_L

External validation of a simple clinical tool used to predict falls in people with Parkinson disease

Published in final edited form as: Parkinsonism Relat Disord. 2015 August ; 21(8): 960–963. doi:10.1016/j.parkreldis.2015.05.008.BACKGROUND: Assessment of fall risk in an individual with Parkinson disease (PD) is a critical yet often time consuming component of patient care. Recently a simple clinical prediction tool based only on fall history in the previous year, freezing of gait in the past month, and gait velocity <1.1 m/s was developed and accurately predicted future falls in a sample of individuals with PD. METHODS: We sought to externally validate the utility of the tool by administering it to a different cohort of 171 individuals with PD. Falls were monitored prospectively for 6 months following predictor assessment. RESULTS: The tool accurately discriminated future fallers from non-fallers (area under the curve [AUC] = 0.83; 95% CI 0.76–0.89), comparable to the developmental study. CONCLUSION: The results validated the utility of the tool for allowing clinicians to quickly and accurately identify an individual's risk of an impending fall.Davis Phinney Foundation, Parkinson Disease Foundation, NIH, APDA. (Davis Phinney Foundation; Parkinson Disease Foundation; NIH; APDA

Are the average gait speeds during the 10 meter and 6 minute walk tests redundant in Parkinson disease?

Published in final edited form as: Gait Posture. 2017 February ; 52: 178–182. doi:10.1016/j.gaitpost.2016.11.033.We investigated the relationships between average gait speed collected with the 10Meter Walk Test (Comfortable and Fast) and 6Minute Walk Test (6MWT) in 346 people with Parkinson disease (PD) and how the relationships change with increasing disease severity. Pearson correlation and linear regression analyses determined relationships between 10Meter Walk Test and 6MWT gait speed values for the entire sample and for sub-samples stratified by Hoehn & Yahr (H&Y) stage I (n=53), II (n=141), III (n=135) and IV (n=17). We hypothesized that redundant tests would be highly and significantly correlated (i.e. r>0.70, p<0.05) and would have a linear regression model slope of 1 and intercept of 0. For the entire sample, 6MWT gait speed was significantly (p<0.001) related to the Comfortable 10 Meter Walk Test (r=0.75) and Fast 10Meter Walk Test (r=0.79) gait speed, with 56% and 62% of the variance in 6MWT gait speed explained, respectively. The regression model of 6MWT gait speed predicted by Comfortable 10 Meter Walk gait speed produced slope and intercept values near 1 and 0, respectively, especially for participants in H&Y stages II-IV. In contrast, slope and intercept values were further from 1 and 0, respectively, for the Fast 10Meter Walk Test. Comfortable 10 Meter Walk Test and 6MWT gait speeds appeared to be redundant in people with moderate to severe PD, suggesting the Comfortable 10 Meter Walk Test can be used to estimate 6MWT distance in this population.This study was funded by the Davis Phinney Foundation, the Parkinson's Disease Foundation, and the National Institutes of Health (R01 NS077959, K12 HD055931, UL1 TR000448). The funding sources had no input related to study design, data collection, or decision to submit for publication. (Davis Phinney Foundation; Parkinson's Disease Foundation; R01 NS077959 - National Institutes of Health; K12 HD055931 - National Institutes of Health; UL1 TR000448 - National Institutes of Health