Interfering directed paths and the sign phase transition

We revisit the question of the "sign phase transition" for interfering directed paths with real amplitudes in a random medium. The sign of the total amplitude of the paths to a given point may be viewed as an Ising order parameter, so we suggest that a coarse-grained theory for system is a dynamic Ising model coupled to a Kardar-Parisi-Zhang (KPZ) model. It appears that when the KPZ model is in its strong-coupling ("pinned") phase, the Ising model does not have a stable ferromagnetic phase, so there is no sign phase transition. We investigate this numerically for the case of {\ss}1+1 dimensions, demonstrating the instability of the Ising ordered phase there.Comment: 4 pages, 4 figure

Communication Lower Bounds for Statistical Estimation Problems via a Distributed Data Processing Inequality

We study the tradeoff between the statistical error and communication cost of distributed statistical estimation problems in high dimensions. In the distributed sparse Gaussian mean estimation problem, each of the $m$ machines receives $n$ data points from a $d$-dimensional Gaussian distribution with unknown mean $\theta$ which is promised to be $k$-sparse. The machines communicate by message passing and aim to estimate the mean $\theta$. We provide a tight (up to logarithmic factors) tradeoff between the estimation error and the number of bits communicated between the machines. This directly leads to a lower bound for the distributed \textit{sparse linear regression} problem: to achieve the statistical minimax error, the total communication is at least $\Omega(\min\{n,d\}m)$, where $n$ is the number of observations that each machine receives and $d$ is the ambient dimension. These lower results improve upon [Sha14,SD'14] by allowing multi-round iterative communication model. We also give the first optimal simultaneous protocol in the dense case for mean estimation. As our main technique, we prove a \textit{distributed data processing inequality}, as a generalization of usual data processing inequalities, which might be of independent interest and useful for other problems.Comment: To appear at STOC 2016. Fixed typos in theorem 4.5 and incorporated reviewers' suggestion

Early adoption of transoral robotic surgical program: preliminary outcomes.

OBJECTIVE: The objective of this study is to demonstrate the feasibility and safety of establishing a transoral robotic surgical (TORS) program in the post-Food and Drug Administration (FDA) approval setting. Early outcomes are compared with the previously reported results of pioneering centers. STUDY DESIGN: Clinical data from a prospective TORS study. SETTING: Academic university institution. SUBJECTS AND METHODS: Sixty-one patients treated with 63 TORS procedures. Main outcome measures: intraoperative times, margin status, complications, time to diet, and percutaneous endoscopic gastrostomy (PEG) tube retention rate. The authors also report oncologic outcomes on their first 30 patients. RESULTS: The spectrum of subsites included tongue base, tonsil, parapharyngeal space, retromolar trigone, supraglottis, and posterior pharyngeal wall. Surgical console time averaged 79 ± 53 minutes. After re-resection of 4 patients, final negative margin status was 94% (50/53). A subset of 30 patients with squamous cell carcinoma reaching an average of 18 months of follow-up had a local regional control rate of 97% with a disease-free survival rate of 90%. The PEG tube retention rate was 7%. Complications included 2 readmissions with dehydration, 1 aspiration pneumonia, and 2 with minor oropharyngeal bleeding. Ninety-one percent of patients resumed an oral diet by the first postoperative visit. CONCLUSION: The initiation of a TORS program in the post-FDA setting can be achieved in a safe and efficient manner. Early results of pioneering TORS centers are reproducible. Continued investigation of TORS as a treatment option for oropharyngeal carcinoma is warranted

Stereoselective pharmacokinetics of stable isotope (+/-)-[13C]-pantoprazole: Implications for a rapid screening phenotype test of CYP2C19 activity

AIMS: We have previously shown that the (±)-[(13) C]-pantoprazole breath test is a promising noninvasive probe of CYP2C19 activity. As part of that trial, plasma, breath test indices and CYP2C19 (*2, *3, and *17) genotype were collected. Here, we examined whether [(13) C]-pantoprazole exhibits enantioselective pharmacokinetics and whether this enantioselectivity is correlated with indices of breath test. METHODS: Plasma (-)- and (+)-[(13) C]-pantoprazole that were measured using a chiral HPLC were compared between CYP2C19 genotypes and correlated with breath test indices. RESULTS: The AUC( 0-∞) of (+)-[(13) C]-pantoprazole in PM (*2/*2, n = 4) was 10.1- and 5.6-fold higher that EM (*1/*1or *17, n = 10) and IM (*1/*2or *3, n = 10) of CYP2C19, respectively (P < 0.001). The AUC( 0-∞) of (-)-[(13) C]-pantoprazole only significantly differed between PMs and EMs (1.98-fold; P = 0.05). The AUC( 0-∞) ratio of (+)-/(-)-[(13) C]-pantoprazole was 3.45, 0.77, and 0.67 in PM, IM, and EM genotypes, respectively. Breath test index, delta over baseline show significant correlation with AUC( 0-∞) of (+)-[(13) C]-pantoprazole (Pearson's r = 0.62; P < 0.001). CONCLUSIONS: [(13) C]-pantoprazole exhibits enantioselective elimination. (+)-[(13) C]-pantoprazole is more dependent on CYP2C19 metabolic status and may serve as a more attractive probe of CYP2C19 activity than (-)-[(13) C]-pantoprazole or the racemic mixture

Prevalence of Dyskinesia and OFF by 30-Minute Intervals Through the Day and Assessment of Daily Episodes of Dyskinesia and OFF: Novel Analyses of Diary Data from Gocovri Pivotal Trials.

BACKGROUND: Parkinson\u27s disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life. OBJECTIVE: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes. METHODS: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12. RESULTS: Diaries were evaluable for 162 patients. At baseline, 67% of patients woke up OFF, with prevalence decreasing to 13% at 2 hours and then remaining relatively steady at ∼12% (range, 6-17%) across half-hour intervals thereafter. Troublesome dyskinesia prevalence rose steadily from 5% to 24% over the first 2 hours, then fluctuated between 20% and 44% through the rest of the waking day. At baseline, patients experienced a mean of 3.0 daily episodes of troublesome dyskinesia (average duration 2.0 hours each), and 2.2 daily episodes of OFF (average duration 1.1 hour each). At week 12, Gocovri-treated patients showed greater reductions than placebo in troublesome dyskinesia and OFF episodes per day (treatment difference: -1.0 episodes and -0.4 episodes, respectively) and average episode duration (treatment difference: -0.6 hours and -0.3 hours, respectively). Mean duration of individual episodes of ON without troublesome dyskinesia (Good ON) increased by 5.0 hours for Gocovri, compared with 2.0 hours for placebo. Patients taking Gocovri experienced 2.2 fewer transitions between states than patients taking placebo. CONCLUSIONS: Troublesome dyskinesia and OFF occurred in the morning and throughout the waking day. Gocovri-treated patients experienced fewer, shorter episodes of both troublesome dyskinesia and OFF, thereby increasing the duration of continuous Good ON episodes and reducing the frequency of transitions between motor states

Navigator channel adaptation to reconstruct three dimensional heart volumes from two dimensional radiotherapy planning data

BACKGROUND: Biologically-based models that utilize 3D radiation dosimetry data to estimate the risk of late cardiac effects could have significant utility for planning radiotherapy in young patients. A major challenge arises from having only 2D treatment planning data for patients with long-term follow-up. In this study, we evaluate the accuracy of an advanced deformable image registration (DIR) and navigator channels (NC) adaptation technique to reconstruct 3D heart volumes from 2D radiotherapy planning images for Hodgkin's Lymphoma (HL) patients. METHODS: Planning CT images were obtained for 50 HL patients who underwent mediastinal radiotherapy. Twelve image sets (6 male, 6 female) were used to construct a male and a female population heart model, which was registered to 23 HL "Reference" patients' CT images using a DIR algorithm, MORFEUS. This generated a series of population-to-Reference patient specific 3D deformation maps. The technique was independently tested on 15 additional "Test" patients by reconstructing their 3D heart volumes using 2D digitally reconstructed radiographs (DRR). The technique involved: 1) identifying a matching Reference patient for each Test patient using thorax measurements, 2) placement of six NCs on matching Reference and Test patients' DRRs to capture differences in significant heart curvatures, 3) adapting the population-to-Reference patient-specific deformation maps to generate population-to-Test patient-specific deformation maps using linear and bilinear interpolation methods, 4) applying population-to-Test patient specific deformation to the population model to reconstruct Test-patient specific 3D heart models. The percentage volume overlap between the NC-adapted reconstruction and actual Test patient's true heart volume was calculated using the Dice coefficient. RESULTS: The average Dice coefficient expressed as a percentage between the NC-adapted and actual Test model was 89.4 ± 2.8%. The modified NC adaptation technique made significant improvements to the population deformation heart models (p = 0.01). As standard evaluation, the residual Dice error after adaptation was comparable to the volumetric differences observed in free-breathing heart volumes (p = 0.62). CONCLUSIONS: The reconstruction technique described generates accurate 3D heart models from limited 2D planning data. This development could potentially be used to retrospectively calculate delivered dose to the heart for historically treated patients and thereby provide a better understanding of late radiation-related cardiac effects

Facilitators and Barriers to Prescribing PreExposure Prophylaxis (PrEP) for the Prevention of HIV

Background: What is PrEP and who gets it? PrEP is the use of medication by individuals to prevent HIV contraction, approved in 2012 after demonstrating safety and efficacy in the iPrEx study and Partners PrEP2 trials. HIV infection risk is 92% lower in patients using PrEP. Truvada®, a combination of tenofovir and emtricitabine taken orally daily, is the only approved PrEP regimen and is intended to compliment other prevention strategies such as condoms. HIV negative-individuals at risk for exposure to HIV have been identified as men who have sex with men (MSM), IV drug users, heterosexuals who have unprotected sex with partners of unknown HIV status, and those in serodiscordant relationships. Barriers to PrEP Implementation PrEP is effective when patients adhere; however, both the medical community and some high-risk populations have been slow to adopt it as an HIV prevention strategy. Surveys have shown clinicians perceived barriers to PrEP such as adverse side effects, viral drug resistance, increased high-risk behavior, cost, and training. HIV in Vermont New diagnoses of HIV among Vermont residents has remained relatively stable over the last twenty years. Vermont CARES, a non-profit, offers free and anonymous HIV tests and in-person risk-reduction counseling. Clients are increasingly asking about PrEP as a prevention strategy, but the response from the medical community is difficult to ascertain.https://scholarworks.uvm.edu/comphp_gallery/1235/thumbnail.jp

The Calibration of AVHRR Visible Dual Gain using Meteosat-8 for NOAA-16 to 18

The NOAA AVHRR program has given the remote sensing community over 25 years of imager radiances to retrieve global cloud, vegetation, and aerosol properties. This dataset can be used for long-term climate research, if the AVHRR instrument is well calibrated. Unfortunately, the AVHRR instrument does not have onboard visible calibration and does degrade over time. Vicarious post-launch calibration is necessary to obtain cloud properties that are not biased over time. The recent AVHRR-3 instrument has a dual gain in the visible channels in order to achieve greater radiance resolution in the clear-sky. This has made vicarious calibration of the AVHRR-3 more difficult to unravel. Reference satellite radiances from well-calibrated instruments, usually equipped with solar diffusers, such as MODIS, have been used to successfully vicariously calibrate other visible instruments. Transfer of calibration from one satellite to another using co-angled, collocated, coincident radiances has been well validated. Terra or Aqua MODIS and AVHRR comparisons can only be performed over the poles during summer. However, geostationary satellites offer a transfer medium that captures both parts of the dual gain. This AVHRR-3 calibration strategy uses, calibrated with MODIS, Meteosat-8 radiances simultaneously to determine the dual gains using 50km regions. The dual gain coefficients will be compared with the nominal coefficients. Results will be shown for all visible channels for NOAA-17