Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration

Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders

Sub-wavelength surface IR imaging of soft-condensed matter

Outlined here is a technique for sub-wavelength infrared surface imaging performed using a phase matched optical parametric oscillator laser and an atomic force microscope as the detection mechanism. The technique uses a novel surface excitation illumination approach to perform simultaneously chemical mapping and AFM topography imaging with an image resolution of 200 nm. This method was demonstrated by imaging polystyrene micro-structures

A factor analytic study of the Italian National Institute of Health Quality of Life – Core Evaluation Form (ISSQoL-CEF)

Objectives: The Italian National Institute of Health Quality of Life - Core Evaluation Form (ISSQoL-CEF) is a specific questionnaire measuring health-related quality of life for human immunodeficiency virus-infected people in the era of highly active antiretroviral therapy. The main goal of this study was to examine the construct validity of this questionnaire by confirmation of its hypothesized dimensional structure. Methods: Baseline quality of life data from four clinical studies were collected and a confirmatory factor analysis of the ISSQoL-CEF items was carried out. Both first-order and secondorder factor models were tested: Model 1 with nine correlated first-order factors; Model 2 with three correlated second-order factors (Physical, Mental, and Social Health); Model 3 with two correlated second-order factors (Physical and Mental/Social Health); Model 4 with only one second-order factor (General Health). Results: A total of 261 patients were surveyed. Model 1 had a good fit to the data. Model 2 had an acceptable fit to the data and it was the best of all hierarchical models. However, Model 2 fitted the data worse than Model 1. Conclusions: The findings of in this study, consistent with the results of previous study, pointed out the construct validity of the ISSQoL-CEF. © 2010 Lauriola et al, publisher and licensee Dove Medical Press Ltd

Seven Key Principles of Program and Project Success: A Best Practices Survey

The National Aeronautics and Space Administration (NASA) Organization Design Team (ODT), consisting of 20 seasoned program and project managers and systems engineers from a broad spectrum of the aerospace industry, academia, and government, was formed to support the Next Generation Launch Technology (NGLT) Program and the Constellation Systems Program. The purpose of the ODT was to investigate organizational factors that can lead to success or failure of complex government programs, and to identify tools and methods for the design, modeling, and analysis of new and more-efficient program and project organizations. The ODT conducted a series of workshops featuring invited lectures from seasoned program and project managers representing 25 significant technical programs spanning 50 years of experience. The result was the identification of seven key principles of program success that can be used to help design and operate future program organizations. This paper presents the success principles and examples of best practices that can significantly improve the design of program, project, and performing technical line organizations, the assessment of workforce needs and organization performance, and the execution of programs and projects

Paediatric Barcelona Olfactory Test-6 (pBOT-6): Validation of a Combined Odour Identification and Threshold Screening Test in Healthy Spanish Children and Adolescents

Background: Few odour tests have been created for children. Objectives: The aim of the present study was to develop and validate a simple and quick olfactory test, suitable for the evaluation of odour identification and threshold in a Spanish paediatric population, the paediatric Barcelona Olfactory Test-6 (pBOT-6).The pBOT-6 consisted in a set of 6 odorants for a forced-choice identification test (IT), and a 6 dilutions phenyl ethyl alcohol geometric series for the threshold test (TT). The pBOT-6 was compared with the U-sniff test (a validated international paediatric smell test) in 131 Spanish healthy volunteers aged 6-17 years. A Bland-Altman plot was used to determine the agreement between two tests. Reliability was analyzed in fifteenvolunteers using the intraclass correlation coefficient (ICC). Normative data was obtained and 8 children diagnosed with subjective smell loss were tested for validation.Bland-Altman analysis demonstrated a minimal bias of -1.71% with upper and lower limit of agreement of -31.1% and 27.6%, respectively. The ICC was 0.83 (95% CI 0.6-0.96) for the IT and 0.73 (95% CI 0.36-0.9) for the TT, showing excellent and good consistency between measurements over time. Mean pBOT-6 scores were significantly higher in healthy volunteers compared with patients with smell loss. Discrimination between normosmia and smell loss was achieved with a sensitivity of 96.9% and a specificity of 100%.The pBOT-6 offers an effectiveand fast method useful in clinical routine to distinguish, with high sensitivity and specificity, between paediatric patients with normosmia and those with smell dysfunction

The development and evaluation of programmatic performance indicators associated with maintenance at nuclear power plants

This report summarizes the development and evaluation of programmatic performance indicators of maintenance. These indicators were selected by: (1) creating a formal framework of plant processes; (2) identifying features of plant behavior considered important to safety; (3) evaluating existing indicators against these features; and (4) performing statistical analyses for the selected indicators. The report recommends additional testing. This document provides the appendices to the report. These appendices are: synopsis of process model; detailed results of statistical analysis; and signal processing analysis of daily power loss indicator

Probabilistic risk assessment of the Space Shuttle. Phase 3: A study of the potential of losing the vehicle during nominal operation. Volume 5: Auxiliary shuttle risk analyses

Volume 5 is Appendix C, Auxiliary Shuttle Risk Analyses, and contains the following reports: Probabilistic Risk Assessment of Space Shuttle Phase 1 - Space Shuttle Catastrophic Failure Frequency Final Report; Risk Analysis Applied to the Space Shuttle Main Engine - Demonstration Project for the Main Combustion Chamber Risk Assessment; An Investigation of the Risk Implications of Space Shuttle Solid Rocket Booster Chamber Pressure Excursions; Safety of the Thermal Protection System of the Space Shuttle Orbiter - Quantitative Analysis and Organizational Factors; Space Shuttle Main Propulsion Pressurization System Probabilistic Risk Assessment, Final Report; and Space Shuttle Probabilistic Risk Assessment Proof-of-Concept Study - Auxiliary Power Unit and Hydraulic Power Unit Analysis Report

Probabilistic risk assessment of the Space Shuttle. Phase 3: A study of the potential of losing the vehicle during nominal operation. Volume 2: Integrated loss of vehicle model

The application of the probabilistic risk assessment methodology to a Space Shuttle environment, particularly to the potential of losing the Shuttle during nominal operation is addressed. The different related concerns are identified and combined to determine overall program risks. A fault tree model is used to allocate system probabilities to the subsystem level. The loss of the vehicle due to failure to contain energetic gas and debris, to maintain proper propulsion and configuration is analyzed, along with the loss due to Orbiter, external tank failure, and landing failure or error

Probabilistic risk assessment of the Space Shuttle. Phase 3: A study of the potential of losing the vehicle during nominal operation. Volume 4: System models and data analysis

In this volume, volume 4 (of five volumes), the discussion is focussed on the system models and related data references and has the following subsections: space shuttle main engine, integrated solid rocket booster, orbiter auxiliary power units/hydraulics, and electrical power system