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)

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

Effects of Transverse Seat Vibration on Near-Viewing Readability of Alphanumeric Symbology

We measured the impacts on human visual function of a range of vibration levels (0.15, 0.3, 0.5, and 0.7 g) at the frequency and along the axis of the anticipated Ares thrust oscillation. We found statistically significant and equivalent decrements in performance on a reading and a numeric processing task at tested vibration levels above 0.3 g (0-to-peak), but no evidence of after-effects. At the smallest font and highest vibration level tested, the average effect was a 50 percent increase in response time and six-fold increase in errors. Our findings support a preliminary trade space in which currently planned Orion font sizes and text spacing appear to be too small to support accurate and efficient reading at the tested vibration levels above 0.3 g, but not too small to support reading at 0.3 g. This study does not address potential impacts on crew cognitive decision-making or motor control and does not test either the full induced Orion-Ares environment with its sustained Gx-loading or the full complexity of the final Orion seat-helmet-suit interface. A final determination of the Orion-Ares program limit on vibration must take these additional factors into consideration and, thus, may need to be lower than that needed to support effective reading at 1-Gx bias

DNA, RNA, Lipid Phosphorus, and Acid Soluble Phosphorus in Normal A-Jax Mouse Livers

The concentrations of these substances in wet liver tissue from randomly selected, adult mice were determined colorimetrically. DNA exhibits a modal concentration near 320 mg. per 100 gm. of wet tissue. Cytoplasmic constituents do not exhibit modal concentrations. Preliminary measurements performed upon mice fed carbon tetrachloride in olive oil indicate lower concentrations of RNA, acid soluble phosphates, and lipid phosphates in experimental mice

Debt Maturity Choices, Multi-stage Investments and Financing Constraints

We develop a dynamic investment options framework with optimal capital structure and analyze the effect of debt maturity. We find that in the absence of financing constraints short-term debt maximizes firm value. In contrast with most literature results, in the absence of constraints, higher volatility may increase initial debt for firms with low initial revenues, issuing long term debt that expires after the investment option maturity. This effect, which is due to the option value of receiving the value of assets and remaining tax savings, does not hold for short term debt and firms with high profitability, where an increase in volatility reduces the firm value. The importance of short-term debt is reduced in the presence of non-negative equity net worth or debt financing constraints and firms behave more conservatively in the use of initial debt. With non-negative equity net worth, higher volatility has adverse effects on the firm value, while with debt financing constraints higher volatility may enhance firm value for firms with relatively low revenue that have out-of-the-money investment options

BoostMe accurately predicts DNA methylation values in whole-genome bisulfite sequencing of multiple human tissues

Abstract Background Bisulfite sequencing is widely employed to study the role of DNA methylation in disease; however, the data suffer from biases due to coverage depth variability. Imputation of methylation values at low-coverage sites may mitigate these biases while also identifying important genomic features associated with predictive power. Results Here we describe BoostMe, a method for imputing low-quality DNA methylation estimates within whole-genome bisulfite sequencing (WGBS) data. BoostMe uses a gradient boosting algorithm, XGBoost, and leverages information from multiple samples for prediction. We find that BoostMe outperforms existing algorithms in speed and accuracy when applied to WGBS of human tissues. Furthermore, we show that imputation improves concordance between WGBS and the MethylationEPIC array at low WGBS depth, suggesting improved WGBS accuracy after imputation. Conclusions Our findings support the use of BoostMe as a preprocessing step for WGBS analysis.https://deepblue.lib.umich.edu/bitstream/2027.42/143848/1/12864_2018_Article_4766.pd

Influence of Combined Whole-Body Vibration Plus G-Loading on Visual Performance

Recent engineering analyses of the integrated Ares-Orion stack show that vibration levels for Orion crews have the potential to be much higher than those experienced in Gemini, Apollo, and Shuttle vehicles. Of particular concern to the Constellation Program (CxP) is the 12 Hz thrust oscillation (TO) that the Ares-I rocket develops during the final ~20 seconds preceding first-stage separation, at maximum G-loading. While the structural-dynamic mitigations being considered can assure that vibration due to TO is reduced to below the CxP crew health limit, it remains to be determined how far below this limit vibration must be reduced to enable effective crew performance during launch. Moreover, this "performance" vibration limit will inform the operations concepts (and crew-system interface designs) for this critical phase of flight. While Gemini and Apollo studies provide preliminary guidance, the data supporting the historical limits were obtained using less advanced interface technologies and very different operations concepts. In this study, supported by the Exploration Systems Mission Directorate (ESMD) Human Research Program, we investigated display readability-a fundamental prerequisite for any interaction with electronic crew-vehicle interfaces-while observers were subjected to 12 Hz vibration superimposed on the 3.8 G loading expected for the TO period of ascent. Two age-matched groups of participants (16 general population and 13 Crew Office) performed a numerical display reading task while undergoing sustained 3.8 G loading and whole-body vibration at 0, 0.15, 0.3, 0.5, and 0.7 g in the eyeballs in/out (x-axis) direction. The time-constrained reading task used an Orion-like display with 10- and 14-pt non-proportional sans-serif fonts, and was designed to emulate the visual acquisition and processing essential for crew system monitoring. Compared to the no-vibration baseline, we found no significant effect of vibration at 0.15 and 0.3 g on task error rates (ER) or response times (RT). Significant degradations in both ER and RT, however, were observed at 0.5 and 0.7 g for 10-pt, and at 0.7 g for 14-pt font displays. These objective performance measures were mirrored by participants' subjective ratings. Interestingly, we found that the impact of vibration on ER increased with distance from the center of the display, but only for vertical displacements. Furthermore, no significant ER or RT aftereffects were detected immediately following vibration, regardless of amplitude. Lastly, given that our reading task required no specialized spaceflight expertise, our finding that effects were not statistically distinct between our two groups is not surprising. The results from this empirical study provide initial guidance for evaluating the display readability trade-space between text-font size and vibration amplitude. However, the outcome of this work should be considered preliminary in nature for a number of reasons: 1. The single 12 Hz x-axis vibration employed was based on earlier load-cycle models of the induced TO environment at the end of Ares-I first stage flight. Recent analyses of TO mitigation designs suggest that significant concurrent off-axis vibration may also occur. 2. The shirtsleeve environment in which we tested fails to capture the full kinematic and dynamic complexity of the physical interface between crewmember and the still-to-bematured helmet-suit-seat designs, and the impact these will have for vibration transmission and consequent performance. 3. By examining performance in this reading and number processing task, we are only assessing readability, a first and necessary step that in itself does not directly address the performance of more sophisticated operational tasks such as vehicle-health monitoring or manual control of the vehicle

Reaching Errors Under G-Loading (and Vibration)

Humans show increased systematic and random errors when reaching for targets at 3.8Gx with or without added vibration