Air Pollution and Acute Respiratory Response in a Panel of Asthmatic Children along the U.S.–Mexico Border

Background: Concerns regarding the health impact of urban air pollution on asthmatic children are pronounced along the U.S.–Mexico border because of rapid population growth near busy border highways and roads. Objectives: We conducted the first binational study of the impacts of air pollution on asthmatic children in Ciudad Juarez, Mexico, and El Paso, Texas, USA, and compared different exposure metrics to assess acute respiratory response. Methods: We recruited 58 asthmatic children from two schools in Ciudad Juarez and two schools in El Paso. A marker of airway inflammation [exhaled nitric oxide (eNO)], respiratory symptom surveys, and pollutant measurements (indoor and outdoor 48-hr size-fractionated particulate matter, 48-hr black carbon, and 96-hr nitrogen dioxide) were collected at each school for 16 weeks. We examined associations between the pollutants and respiratory response using generalized linear mixed models. Results: We observed small but consistent associations between eNO and numerous pollutant metrics, with estimated increases in eNO ranging from 1% to 3% per interquartile range increase in pollutant concentrations. Effect estimates from models using school-based concentrations were generally stronger than corresponding estimates based on concentrations from ambient air monitors. Both traffic-related and non–traffic-related particles were typically more robust predictors of eNO than was nitrogen dioxide, for which associations were highly sensitive to model specification. Associations differed significantly across the four school-based cohorts, consistent with heterogeneity in pollutant concentrations and cohort characteristics. Models examining respiratory symptoms were consistent with the null. Conclusions: The results indicate adverse effects of air pollution on the subclinical respiratory health of asthmatic children in this region and provide preliminary support for the use of air pollution monitors close to schools to track exposure and potential health risk in this population

Feasibility and Performance of the Staged Z-Pinch: A One-dimensional Study with FLASH and MACH2

Z-pinch platforms constitute a promising pathway to fusion energy research. Here, we present a one-dimensional numerical study of the staged Z-pinch (SZP) concept using the FLASH and MACH2 codes. We discuss the verification of the codes using two analytical benchmarks that include Z-pinch-relevant physics, building confidence on the codes' ability to model such experiments. Then, FLASH is used to simulate two different SZP configurations: a xenon gas-puff liner (SZP1*) and a silver solid liner (SZP2). The SZP2 results are compared against previously published MACH2 results, and a new code-to-code comparison on SZP1* is presented. Using an ideal equation of state and analytical transport coefficients, FLASH yields a fuel convergence ratio (CR) of approximately 39 and a mass-averaged fuel ion temperature slightly below 1 keV for the SZP2 scheme, significantly lower than the full-physics MACH2 prediction. For the new SZP1* configuration, full-physics FLASH simulations furnish large and inherently unstable CRs (> 300), but achieve fuel ion temperatures of many keV. While MACH2 also predicts high temperatures, the fuel stagnates at a smaller CR. The integrated code-to-code comparison reveals how magnetic insulation, heat conduction, and radiation transport affect platform performance and the feasibility of the SZP concept

Air Pollution and Acute Respiratory Response in a Panel of Asthmatic Children along the U.S.–Mexico Border

Background: Concerns regarding the health impact of urban air pollution on asthmatic children are pronounced along the U.S.–Mexico border because of rapid population growth near busy border highways and roads

A Biologically-inspired algorithm for the segmentation of cell nuclei in high resolution histological images

Immunohistochemistry (IHC) images are of high resolution and are stained for ER, PR, KI-67 and p53. Image processing can serve an important role in the diagnosis of disease from histopathological data due to its ability to process and analyze whole-slide digital images. Most of the traditional algorithms do not perform segmentation at a low visual level as the spatial relationship between pixels is not often entirely utilized. We developed an algorithm designed to mimic the visual system that utilizes a set of image features and identifies discontinuities within each feature domain. These features are further combined using a concept in neuroscience to generate an intermediate image that is more amenable to traditional tools for performing nuclear segmentation

A Novel Cross-Disciplinary Multi-Institute Approach to Translational Cancer Research: Lessons Learned from Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC)

Background: The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu) is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1) for bioinformatics and a repository of serum and tissue samples; (2) a data model for biomarker data storage; and (3) a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium’s intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer specific biomarkers and encourage collaborative research efforts among the participating centers.Methods: The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual property/tech transfer agreements, and material transfer agreements that have been approved by each of the member institutions. This was the foundational work that has led to the development of a centralized data warehouse that has met each of the institutions’ IRB/HIPAA standards.Results: Currently, this “virtual biorepository” has over 58,000 annotated samples from 11,467 cancer patients available for research purposes. The clinical annotation of tissue samples is either done manually over the internet or semiautomated batch modes through mapping of local data elements with PCABC common data elements. The database currently holds information on 7188 cases (associated with 9278 specimens and 46,666 annotated blocks and blood samples) of prostate cancer, 2736 cases (associated with 3796 specimens and 9336 annotated blocks and blood samples) of breast cancer and 1543 cases (including 1334 specimens and 2671 annotated blocks and blood samples) of melanoma. These numbers continue to grow, and plans to integrate new tumor sites are in progress. Furthermore, the group has also developed a central web-based tool that allows investigators to share their translational (genomics/proteomics) experiment data on research evaluating potential biomarkers via a central location on the Consortium’s web site.Conclusions: The technological achievements and the statewide informatics infrastructure that have been established by the Consortium will enable robust and efficient studies of biomarkers and their relevance to the clinical course of cancer. Studies resulting from the creation of the Consortium may allow for better classification of cancer types, more accurate assessment of disease prognosis, a better ability to identify the most appropriate individuals for clinical trial participation, and better surrogate markers of disease progression and/or response to therapy

Large-scale computations on histology images reveal grade-differentiating parameters for breast cancer

BACKGROUND: Tumor classification is inexact and largely dependent on the qualitative pathological examination of the images of the tumor tissue slides. In this study, our aim was to develop an automated computational method to classify Hematoxylin and Eosin (H&E) stained tissue sections based on cancer tissue texture features. METHODS: Image processing of histology slide images was used to detect and identify adipose tissue, extracellular matrix, morphologically distinct cell nuclei types, and the tubular architecture. The texture parameters derived from image analysis were then applied to classify images in a supervised classification scheme using histologic grade of a testing set as guidance. RESULTS: The histologic grade assigned by pathologists to invasive breast carcinoma images strongly correlated with both the presence and extent of cell nuclei with dispersed chromatin and the architecture, specifically the extent of presence of tubular cross sections. The two parameters that differentiated tumor grade found in this study were (1) the number density of cell nuclei with dispersed chromatin and (2) the number density of tubular cross sections identified through image processing as white blobs that were surrounded by a continuous string of cell nuclei. Classification based on subdivisions of a whole slide image containing a high concentration of cancer cell nuclei consistently agreed with the grade classification of the entire slide. CONCLUSION: The automated image analysis and classification presented in this study demonstrate the feasibility of developing clinically relevant classification of histology images based on micro- texture. This method provides pathologists an invaluable quantitative tool for evaluation of the components of the Nottingham system for breast tumor grading and avoid intra-observer variability thus increasing the consistency of the decision-making process

Hyperbaric oxygen therapy ameliorates TNBS-induced acute distal colitis in rats

Abstract\ud \ud Background\ud This study investigated the therapeutic effects of hyperbaric oxygen in experimental acute distal colitis focusing on its effect on the production of pro-inflammatory cytokines, nitric oxide and hypoxia-inducible factor 1alpha.\ud \ud \ud Methods\ud Colitis was induced with a rectal infusion of 150 mg/kg of TNBS under anesthesia with Ketamine (50 mg/kg) and Xylazine (10 mg/kg). Control animals received only rectal saline. After colitis induction, animals were subjected to two sessions of hyperbaric oxygen and were then euthanized. The distal intestine was resected for macroscopic analysis, determination of myeloperoxidase activity, western-blotting analyses of inducible nitric oxide synthase and cyclooxygenase-2 expression and immunohistochemical analysis of hypoxia-inducible factor 1alpha and cyclooxygenase-2. Cytokines levels in the distal intestine were measured using an enzyme-linked immunosorbent assay.\ud \ud \ud Results\ud Hyperbaric oxygen therapy attenuated the severity of acute distal colitis, with reduced macroscopic damage score. This effect was associated with prevention in the increase of pro-inflammatory cytokine production; myeloperoxidase activity, in the expression of inducible nitric oxide synthase and cyclooxygenase-2. Finally, hyperbaric oxygen inhibited the acute distal colitis-induced up-regulation of hypoxia-inducible factor 1alpha.\ud \ud \ud Conclusions\ud The results indicate that hyperbaric oxygen attenuates the severity of acute distal colitis through the down-regulation of pro-inflammatory events.This work was supported by FAEPA\ud (Fundação de Apoio ao Ensino, Pesquisa e Assistência), Ribeirão Preto\ud Medical School University of Sao Paulo, Brazil and Grant 2011/19670-0 from\ud São Paulo Research Foundation (FAPESP)

Dissociation of Motor Task-Induced Cortical Excitability and Pain Perception Changes in Healthy Volunteers

Background: There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks. Methodology/Principal Findings Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements. Conclusions/Significance: Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training

The Ly6 Protein Coiled Is Required for Septate Junction and Blood Brain Barrier Organisation in Drosophila

Background: Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. Methodology/Principal Findings: In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. Conclusion/Significance: We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose tha

Translocation detection in lymphoma diagnosis by split-signal FISH: a standardised approach

Lymphomas originating from the lymphatic system comprise about 30 entities classified according to the World Health Organization (WHO). The histopathological diagnosis is generally considered difficult and prone to mistakes. Since non-random chromosomal translocations are specifically involved in different lymphoma entities, their detection will be increasingly important. Hence, a split-signal fluorescence in situ hybridisation (FISH) procedure would be helpful in discriminating the most difficult classifications. The Euro-FISH programme, a concerted action of nine European laboratories, has validated a robust, standardised protocol to improve the diagnostic approach on lymphoma entities. Therefore, 16 fluorescent probes and 10 WHO entities, supplemented with reactive cases, were selected. The results of the Euro-FISH programme show that all probes were correctly cytogenetically located, that the standardised protocol is robust, resulting in reliable results in approximately 90% of cases, and that the procedure could be implemented in every laboratory, bringing the relatively easy interpretation of split-signal probes within the reach of many pathology laboratories