Network Influence of the Cerebellum for Predicting DBS Response in Patients with Advanced Parkinson’s Disease

Introduction: Deep brain stimulation (DBS) is a treatment option for reducing motor symptoms in patients with Parkinson’s Disease (PD) when first-line medication becomes ineffective. Existing literature has hypothesized that the clinical outcome of DBS may depend on brain connectivity profiles of the stimulation site to distant brain regions. However, the potential of brain connectivity profiles to predict response to DBS in PD remains unclear. Objective: This study aimed to investigate how changes in structural and functional connectivity may relate to patient response to DBS, through the examination of brain network changes using graph theory. Methods: Ten patients with advanced PD were included in this study. Diffusion tensor imaging (DTI) and resting-state fMRI scans were acquired prior to DBS implantation. Pre-DBS and post-DBS UPDRS-III scores were obtained. Network analysis of the DTI and fMRI scans was performed using GRETNA to compute structural and functional graph theory metrics, respectively. Metrics were correlated with UPDRS-III improvement to identify significant correlations to UPDRS improvement due to DBS. Results: Combined structural and functional graph theory metrics highlighted 32 structures to be significantly correlated with UPDRS-III improvement. Mainly, connections to the cerebellum were found to be significantly correlated with UPDRS-III improvement across several metrics for both structural and functional connectivity. Discussion: This work combined DTI, fMRI, and graph theory analysis to evaluate improvement with DBS. Several imaging biomarkers were identified that are robust predictors for UPDRS-III improvement. This work warrants investigation into the compensatory effect of the cerebellum and other potential biomarkers for identifying DBS candidates

Integrated Active Fire Retrievals and Biomass Burning Emissions Using Complementary Near-Coincident Ground, Airborne and Spaceborne Sensor Data

Ground, airborne and spaceborne data were collected for a 450 ha prescribed fire implemented on 18 October 2011 at the Henry W. Coe State Park in California. The integration of various data elements allowed near coincident active fire retrievals to be estimated. The Autonomous Modular Sensor-Wildfire (AMS) airborne multispectral imaging system was used as a bridge between ground and spaceborne data sets providing high quality reference information to support satellite fire retrieval error analyses and fire emissions estimates. We found excellent agreement between peak fire radiant heat flux data (less than 1% error) derived from near-coincident ground radiometers and AMS. Both MODIS and GOES imager active fire products were negatively influenced by the presence of thick smoke, which was misclassified as cloud by their algorithms, leading to the omission of fire pixels beneath the smoke, and resulting in the underestimation of their retrieved fire radiative power (FRP) values for the burn plot, compared to the reference airborne data. Agreement between airborne and spaceborne FRP data improved significantly after correction for omission errors and atmospheric attenuation, resulting in as low as 5 difference between AquaMODIS and AMS. Use of in situ fuel and fire energy estimates in combination with a collection of AMS, MODIS, and GOES FRP retrievals provided a fuel consumption factor of 0.261 kg per MJ, total energy release of 14.5 x 10(exp 6) MJ, and total fuel consumption of 3.8 x 10(exp 6) kg. Fire emissions were calculated using two separate techniques, resulting in as low as 15 difference for various specie

Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000

Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m(2) per day) or prednisone (60 mg/m(2) per day) for 3 weeks plus tapering in induction. The 5-year cumulative incidence of relapse (± standard error) was 10.8 ± 0.7% in the dexamethasone and 15.6 ± 0.8% in the prednisone group (P < .0001), showing the largest effect on extramedullary relapses. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate (2.5% vs 0.9%, P = .00013), resulting in 5-year event-free survival rates of 83.9 ± 0.9% for dexamethasone and 80.8 ± 0.9% for prednisone (P = .024). No difference was seen in 5-year overall survival (OS) in the total cohort (dexamethasone, 90.3 ± 0.7%; prednisone, 90.5 ± 0.7%). Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase (prednisone good-response [PGR]) (dexamethasone, 91.4 ± 2.4%; prednisone, 82.6 ± 3.2%; P = .036). In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm. We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse. This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T-cell ALL patients with PGR. This trial was registered at www.clinicaltrials.gov (BFM: NCT00430118, AIEOP: NCT00613457)

N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson\u27s Disease: Preliminary Clinical and Cell Line Data.

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson\u27s disease (PD). METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone. In the clinical study, patients continued their standard of care and were randomized to receive either daily NAC or were a waitlist control. Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter (DAT) binding and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) to measure clinical symptoms. RESULTS: The cell line study showed that NAC exposure resulted in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC, consistent with the protective effects of NAC previously observed. The clinical study showed significantly increased DAT binding in the caudate and putamen (mean increase ranging from 4.4% to 7.8%; p CONCLUSIONS: The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients, and this observation may be associated with positive clinical effects. A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better elucidate the mechanism of action is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02445651