Methotrexate Encephalopathy: Two Cases in Adult Cancer Patients, Who Recovered with Pathophysiologically Based Therapy

Background/Objectives: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. Results: Case 1 : A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate. The clinical scenario and a head magnetic resonance imaging supported a diagnosis of methotrexate encephalopathy. Treatment with dextromethorphan was coincident with recovery. Case 2 : A 65-year-old female with recurrent diffuse large B-cell lymphoma was treated with high- dose intravenous methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of starting dextromethorphan, there was improvement with clinical recovery. Conclusions: These two cases suggest that N -methyl d -aspartate receptor activation by homocysteine may play an important role in the pathogenesis of methotrexate neurotoxicity

Drift Corrected Trends and Periodic Variations in MIPAS IMK/IAA Ozone Measurements

Drifts, trends and periodic variations were calculated from monthly zonally averaged ozone profiles. The ozone profiles were derived from level-1b data of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) by means of the scientific level-2 processor run by the Karlsruhe Institute of Technology (KIT), Institute for Meteorology and Climate Research (IMK). All trend and drift analyses were performed using a multilinear parametric trend model which includes a linear term, several harmonics with period lengths from 3 to 24 months and the quasi-biennial oscillation (QBO). Drifts at 2-sigma significance level were mainly negative for ozone relative to Aura MLS and Odin OSIRIS and negative or near zero for most of the comparisons to lidar measurements. Lidar stations used here include those at Hohenpeissenberg (47.8° N, 11.0 ° E), Lauder (45.0 ° S, 169.7 ° E), Mauna Loa (19.5 ° N, 155.6 ° W), Observatoire Haute Provence (43.9 ° N, 5.7 ° E) and Table Mountain (34.4 ° N, 117.7 ° W). Drifts against the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) were found to be mostly insignificant. The assessed MIPAS ozone trends cover the time period of July 2002 to April 2012 and range from -0.56 ppmv decade-1 to +0.48 ppmv decade-1 (-0.52 ppmv decade-1 to +0.47 ppmv decade-1 when displayed on pressure coordinates) depending on altitude/ pressure and latitude. From the empirical drift analyses we conclude that the real ozone trends might be slightly more positive/ less negative than those calculated from the MIPAS data, by conceding the possibility of MIPAS having a very small (approximately within -0.3 ppmv decade-1 negative drift for ozone. This leads to drift-corrected trends of -0.41 ppmv decade-1 to +0.55 ppmv decade-1 (-0.38 ppmv decade-1 to +0.53 ppmv decade-1 when displayed on pressure coordinates) for the time period covered by MIPAS Envisat measurements, with very few negative and large areas of positive trends at mid-latitudes for both hemispheres around and above 30 km (similar to 10 hPa). Negative trends are found in the tropics around 25 and 35 km (similar to 25 and 5 hPa), while an area of positive trends is located right above the tropical tropopause. These findings are in good agreement with the recent literature. Differences of the trends compared with the recent literature could be explained by a possible shift of the subtropical mixing barriers. Results for the altitude-latitude distribution of amplitudes of the quasi-biennial, annual and the semi-annual oscillation are overall in very good agreement with recent findings

Slow Molecules Produced by Photodissociation

A simple method to control molecular translation with a chemical reaction is demonstrated. Slow NO molecules have been produced by partially canceling the molecular beam velocity of NO$_2$ with the recoil velocity of the NO photofragment. The NO$_2$ molecules were photodissociated using a UV laser pulse polarized parallel to the molecular beam. The spatial profiles of NO molecules showed two peaks corresponding to decelerated and accelerated molecules, in agreement with theoretical prediction. A significant portion of the decelerated NO molecules stayed around the initial dissociation positions even several hundred nanoseconds after their production.Comment: 17 pages, 4 figure

First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip

Objective: The overall objective of this clinical study was to validate an implantable oxygen sensor, called the ‘OxyChip’, as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing. Methods: Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO2) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry. Results: Twenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4–128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO2 values were variable with overall median 15.7 mmHg (range 0.6–73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO2 was 31.8 mmHg (range 1.5–144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation. Conclusions: Measurement of baseline pO2 and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes

Machine Learning based histology phenotyping to investigate the epidemiologic and genetic basis of adipocyte morphology and cardiometabolic traits

Genetic studies have recently highlighted the importance of fat distribution, as well as overall adiposity, in the pathogenesis of obesity-associated diseases. Using a large study (n = 1,288) from 4 independent cohorts, we aimed to investigate the relationship between mean adipocyte area and obesity-related traits, and identify genetic factors associated with adipocyte cell size. To perform the first large-scale study of automatic adipocyte phenotyping using both histological and genetic data, we developed a deep learning-based method, the Adipocyte U-Net, to rapidly derive mean adipocyte area estimates from histology images. We validate our method using three state-of-the-art approaches; CellProfiler, Adiposoft and floating adipocytes fractions, all run blindly on two external cohorts. We observe high concordance between our method and the state-of-the-art approaches (Adipocyte U-net vs. CellProfiler: R2visceral = 0.94, P < 2.2 × 10-16, R2subcutaneous = 0.91, P < 2.2 × 10-16), and faster run times (10,000 images: 6mins vs 3.5hrs). We applied the Adipocyte U-Net to 4 cohorts with histology, genetic, and phenotypic data (total N = 820). After meta-analysis, we found that mean adipocyte area positively correlated with body mass index (BMI) (Psubq = 8.13 × 10-69, βsubq = 0.45; Pvisc = 2.5 × 10-55, βvisc = 0.49; average R2 across cohorts = 0.49) and that adipocytes in subcutaneous depots are larger than their visceral counterparts (Pmeta = 9.8 × 10-7). Lastly, we performed the largest GWAS and subsequent meta-analysis of mean adipocyte area and intra-individual adipocyte variation (N = 820). Despite having twice the number of samples than any similar study, we found no genome-wide significant associations, suggesting that larger sample sizes and a homogenous collection of adipose tissue are likely needed to identify robust genetic associations.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.C.A.G received a pump priming grant from Novo Nordisk to carry out this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.published version, accepted versio

Speech Communication

Contains reports on five research projects.C.J. Lebel FellowshipNational Institutes of Health (Grant 5 T32 NS07040)National Institutes of Health (Grant 5 R01 NS04332)National Science Foundation (Grant 1ST 80-17599)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0254)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0341)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0290

Speech Communication

Contains reports on five research projects.C.J. Lebel FellowshipNational Institutes of Health (Grant 5 T32 NSO7040)National Institutes of Health (Grant 5 R01 NS04332)National Institutes of Health (Grant 5 R01 NS21183)National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Grant 1 PO1-NS23734)National Science Foundation (Grant BNS 8418733)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0254)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0341)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0290)National Institutes of Health (Grant RO1-NS21183), subcontract with Boston UniversityNational Institutes of Health (Grant 1 PO1-NS23734), subcontract with the Massachusetts Eye and Ear Infirmar

First steps of a new methodology for integrating ground-based ozone profile data

A new methodology is developed for integrating complementary ground-based data sources to provide consistent ozone vertical distribution time series as well as tropospheric and stratospheric ozone partial columns. Primary results are presented for the Alpine station of the Network for the Detection of Atmospheric Composition Changes (NDACC). Ozone measurements from the lidar at Haute-Provence Observatory, the microwave spectrometer at Bern and the FTIR spectrometer at the Jungfrauch station are used for this purpose. First step is to evaluate the validity domain of ozone profile data considered here by assessing instrumental error and vertical resolution. Each instrument has its own vertical resolution; therefore adjustments need to be done for the creation of an homogeneous data set. Indeed, because of the higher resolution of lidar measurements, smoothing of the data is necessary for the comparison with FTIR and microwave measurements. However, smoothing the data induces a loss of scientific information. Therefore a compromise has to be established and discussed. The various intercomparisons provide an evaluation of the differences due to instrumental error and atmospheric variability. The statistical method used for combining the different measurements in order to obtain ozone vertical profile time series consistent with total ozone measurements is then discussed

Integrating science and research in a HCI design course

Undergraduate computer science students have few opportunities to experience scientific investigation and computer science research. A human-computer interaction (HCI) course can offer many opportunities for research that are accessible to undergraduate students, and because of the similarity between the design and research processes, a design project based HCI course is particularly suited to introducing undergraduate computer science students to the research process. In this paper, we describe and discuss the challenges of integrating research projects into a design HCI course. We also present example research projects and discuss the feedback form students attending the course. Copyright 2005 ACM