Characterization of Vitamin B12 Supplementation and Correlation with Clinical Outcomes in a Large Longitudinal Study of Early Parkinson's Disease.

ObjectiveIn Parkinson's disease (PD), vitamin B12 levels are lower, and comorbid B12 deficiency has been associated with the development of neuropathy and early gait instability. Because little is known about B12 supplement use in PD, we sought to evaluate its use in a large PD cohort and, as an exploratory analysis, to determine whether baseline characteristics or disease progression differed according to B12 supplementation.MethodsWe utilized data collected as part of the National Institutes of Health Exploratory Trials in PD (NET-PD) Long-term Study (LS-1), a longitudinal study of 1,741 participants. We stratified subjects into 4 groups according to daily supplement use: no B12, multivitamin (MVI) containing < 100 μg B12, B12 ≥ 100 μg, and MVI + B12 ≥ 100 μg. Clinical outcomes were assessed at 3 years for each group using the Unified Parkinson's Disease Rating Scale (UPDRS), its subscores, and selected individual questions.ResultsOf the 1,147 participants who completed the 3-year visit, 41% took an MVI, 2% took B12, 3% took MVI + B12, and 54% reported taking no supplements. At 3 years, no significant differences in clinical outcomes were observed. However, there was a trend toward lower hazard ratios for developing sensory symptoms (UPDRS Item 17) in the MVI (p = 0.08) and B12 + MVI (p = 0.08) groups compared to that in the no supplement group.ConclusionThese results show that supplementation with vitamin B12 ≥ 100 μg is uncommon in early PD. The finding of a trend toward a lower hazard ratio for the development of sensory symptoms in those taking an MVI or B12 + MVI warrants further study

Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer.

Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of-care therapy for patients with stage III unresectable non-small cell lung cancer (NSCLC). Although cCRT is potentially curative, 5-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. Here, we discuss the clinical and translational implications of integrating PD-1/PD-L1 inhibitors in the management of patients with unresectable stage III NSCLC

Identifying Prognostic Indicators for Electrical Treeing in Solid Insulation through PD Analysis

This paper presents early results from an experimental study of electrical treeing on commercially available pre-formed silicone samples. A needle-plane test arrangement was set up using hypodermic needles. Partial discharge (PD) data was captured using both the IEC 60270 electrical method and radio frequency (RF) sensors, and visual observations are made using a digital microscope. Features of the PD plot that corresponded to electrical tree growth were assessed, evaluating the similarities and differences of both PD measurement techniques. Three univariate phase distributions were extracted from the partial discharge phase-resolved (PRPD) plot and the first four statistical moments were determined. The implications for automated lifetime prediction of insulation samples due to electrical tree development are discussed

Identifying Prognostic Indicators for Electrical Treeing in Solid Insulation through PD Analysis

This paper presents early results from an experimental study of electrical treeing on commercially available pre-formed silicone samples. A needle-plane test arrangement was set up using hypodermic needles. Partial discharge (PD) data was captured using both the IEC 60270 electrical method and radio frequency (RF) sensors, and visual observations are made using a digital microscope. Features of the PD plot that corresponded to electrical tree growth were assessed, evaluating the similarities and differences of both PD measurement techniques. Three univariate phase distributions were extracted from the partial discharge phase-resolved (PRPD) plot and the first four statistical moments were determined. The implications for automated lifetime prediction of insulation samples due to electrical tree development are discussed

3D Simulation of Partial Discharge in High Voltage Power Networks

Open accessPartial discharge (PD) events arise inside power cables due to defects of cable’s insulation material, characterized by a lower electrical breakdown strength than the surrounding dielectric material. These electrical discharges cause signals to propagate along the cable, manifesting as noise phenomena. More significantly, they contribute to insulation degradation and can produce a disruptive effect with a consequent interruption of power network operation. PD events are, therefore, one of the best ‘early warning’ indicators of insulation degradation and, for this reason, the modeling and studying of such phenomena, together with the development of on-line PDs location methods, are important topics for network integrity assessment, and to define methods to improve the power networks’ Electricity Security. This paper presents a 3D model of PD events inside a void in epoxy-resin insulation cables for High Voltage (HV) power networks. The 3D model has been developed using the High Frequency (HF) Solver of CST Studio Suite® software. PD events of a few µs duration have been modelled and analyzed. The PD behavior has been investigated using varying electrical stress. A first study of the PD signal propagation in a power network is described

Magnitude estimation for early warning applications using the initial part of P waves: A case study on the 2008 Wenchuan sequence

A period parameter τ_c and an amplitude parameter Pd determined from the very beginning of P wave are important for earthquake early warning (EEW), yet their dependence on source mechanism, focal depth and epicentral distance has not been fully studied. After the devastating Mw7.9 Wenchuan earthquake, hundreds of M4-6 earthquakes occurred with diverse focal mechanisms and depth range of 2–20 km. We calculate τ_c and Pd of these aftershocks and examine their dependence on magnitude, τ_c, distance, and depth. We find that τ_c correlates well with magnitude, but joint regression including distance and depth does not significantly improve the correlation. The effect of focal mechanism on the τ_c-magnitude correlation is not obvious. When P wave is nodal, τ_c measurement becomes inaccurate. Also, τ_c is systematically greater for slow earthquakes, leading to a possible false alarm. Thus, more studies are required to discriminate slow earthquakes for robust early warning

Sleep dysfunction and EEG alterations in mice overexpressing alpha-synuclein.

BackgroundSleep disruptions occur early and frequently in Parkinson's disease (PD). PD patients also show a slowing of resting state activity. Alpha-synuclein is causally linked to PD and accumulates in sleep-related brain regions. While sleep problems occur in over 75% of PD patients and severely impact the quality of life of patients and caregivers, their study is limited by a paucity of adequate animal models.ObjectiveThe objective of this study was to determine whether overexpression of wildtype alpha-synuclein could lead to alterations in sleep patterns reminiscent of those observed in PD by measuring sleep/wake activity with rigorous quantitative methods in a well-characterized genetic mouse model.MethodsAt 10 months of age, mice expressing human wildtype alpha-synuclein under the Thy-1 promoter (Thy1-aSyn) and wildtype littermates underwent the subcutaneous implantation of a telemetry device (Data Sciences International) for the recording of electromyograms (EMG) and electroencephalograms (EEG) in freely moving animals. Surgeries and data collection were performed without knowledge of mouse genotype.ResultsThy1-aSyn mice showed increased non-rapid eye movement sleep during their quiescent phase, increased active wake during their active phase, and decreased rapid eye movement sleep over a 24-h period, as well as a shift in the density of their EEG power spectra toward lower frequencies with a significant decrease in gamma power during wakefulness.ConclusionsAlpha-synuclein overexpression in mice produces sleep disruptions and altered oscillatory EEG activity reminiscent of PD, and this model provides a novel platform to assess mechanisms and therapeutic strategies for sleep dysfunction in PD

Structural MRI Correlates of Episodic Memory Processes in Parkinson's Disease Without Mild Cognitive Impairment.

BackgroundChanges in episodic memory are common early in Parkinson's disease (PD) and may be a risk factor for future cognitive decline. Although medial temporal lobe (MTL) memory and frontostriatal (FS) executive systems are thought to play different roles in distinct components of episodic memory impairment in PD, no study has investigated whether different aspects of memory functioning are differentially associated with MTL and FS volumes in nondemented patients without mild cognitive impairment (PD-woMCI).ObjectivesThe present study investigated MRI markers of different facets of memory functioning in 48 PD-woMCI patients and 42 controls.MethodsRegional volumes were measured in structures comprising the MTL and FS systems and then correlated with key indices of memory from the California Verbal Learning Test.ResultsIn PD-woMCI patients, memory was impaired only for verbal learning, which was not associated with executive, attention/working memory, or visuospatial functioning. Despite an absence of cortical atrophy, smaller right MTL volumes in patients were associated with poorer verbal learning, long delayed free recall, long delayed cued recall, and recognition memory hits and false positives. Smaller right pars triangularis (inferior frontal) volumes were also associated with poorer long delayed cued recall and recognition memory hits. These relationships were not found in controls.ConclusionsThe findings indicate that MTL volumes are sensitive to subtle changes in almost all facets of memory in PD-woMCI, whereas FS volumes are sensitive only to memory performances in cued-testing formats

The Dixmier property and tracial states for C*-algebras

A.T. was partially supported by an NSERC Postdoctoral Fellowship and through the EPSRC grant EP/N00874X/1. Acknowledgements We are grateful to Luis Santiago for helpful discussions at an early stage of this investigation. We would also like to thank the referee for providing helpful comments, which have led to a number of improvements.Peer reviewedPublisher PD