Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS.

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A novel turning and barrier course was superior to FW in eliciting FOG. Greater unpredictability in subthalamic beta rhythms was evident during stepping without freezing episodes in Freezers compared to Non-Freezers, whereas greater unpredictability in alpha rhythms was evident in Freezers during FOG. Non-linear analysis of dynamic neural signals during gait in freely moving people with PD may yield greater insight into the pathophysiology of FOG; whether the increases in STN entropy are causative or compensatory remains to be determined. Some beta LFP power may be useful for rhythmic, symmetric gait and DBS parameters, which completely attenuate STN beta power may worsen rather than improve FOG.

References1. Rango M, Arighi A, Bresolin N. Brain temperature: what do we know? Neuroreport 2012;23:483-487. 2. Rango M, Arighi A, Bonifati C, Bresolin N. Increased brain temperature in Parkinson disease. Neuroreport 2012;23:129-133. 3. Powers WJ, Videen TO, Markham J. Cerebral mitochondrial metabolism in early Parkinson's disease. J Celeb Blood Flow Metab 2008;28:1754-1760. 4. Jezek J, Jaburek M, Zelenka Y, Jezek P. Mitochondrial phospholipase A 2 activated by reactive oxygen species in heart mitochondria induces mild uncoupling. Physiol Res 2010;59:737-747. 5. Seleznev K, Zhao C, Zhang XH, et al. Calcium-independent phospholipase A2 localizes in and protects mitochondria during apoptotic induction by staurosporine. Biol Chem 2006;201:22275-22288. 6. Dlaskov a A, Hlavat a L, Jezek J, et al. Mitohondrial complex I superoxide production is attenuated by uncoupling. Int J Biochem Cell Biol 2008;40:2098-2109. 7. Whitworth AJ, Pallanck LJ. The PINK1/Parkin pathway: a mitochondrial quality control system? J Bioenerg Biomembr 2009;41: 499-503.

These novel results obtained from freely moving PD subjects demonstrated that both 140- and 60-Hz DBS improved bradykinesia and attenuated high beta oscillations; however, 60-Hz DBS amplified a subband of alpha/low-beta oscillations, and DBS at a beta-band frequency did not worsen bradykinesia. Based on recent literature, we suggest that both 140- and 60-Hz DBS decouple the cortico-STN hyperdirect pathway, whereas 60-Hz DBS increases coupling within striato-STN circuitry. These results inform future algorithms for closed-loop DBS in PD. © 2016 International Parkinson and Movement Disorder Society.

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Biomarkers for disease-specific survival (DSS) in earlystage melanoma are needed to select patients for adjuvant immunotherapy and accelerate clinical trial design. We present a pathology-based computational method using a deep neural network architecture for DSS prediction.Experimental Design: The model was trained on 108 patients from four institutions and tested on 104 patients from Yale School of Medicine (YSM, New Haven, CT). A receiver operating characteristic (ROC) curve was generated on the basis of vote aggregation of individual image sequences, an optimized cutoff was selected, and the computational model was tested on a third independent population of 51 patients from Geisinger Health Systems (GHS).Results: Area under the curve (AUC) in the YSM patients was 0.905 (P < 0.0001). AUC in the GHS patients was 0.880 (P < 0.0001). Using the cutoff selected in the YSM cohort, the computational model predicted DSS in the GHS cohort based on Kaplan-Meier (KM) analysis (P < 0.0001).Conclusions: The novel method presented is applicable to digital images, obviating the need for sample shipment and manipulation and representing a practical advance over current genetic and IHC-based methods.