164 research outputs found

    Stereotactic ablative radiotherapy for medically inoperable early stage lung cancer: early outcomes

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    Objective To evaluate the clinical outcome and safety of stereotactic ablative radiotherapy for medically inoperable stage I non- small-cell lung carcinoma. Design Retrospective case series. Setting Pamela Youde Nethersole Eastern Hospital, Hong Kong. Patients All patients with medically inoperable stage I non-small-cell lung carcinoma receiving stereotactic ablative radiotherapy since its establishment in 2008. Main outcome measures Disease control rate, overall survival, and treatment toxicities. Results Sixteen stage I non-small-cell lung carcinoma patients underwent the procedure from June 2008 to November 2011. The median patient age was 82 years and the majority (81%) had moderate-tosevere co-morbidity based on the Adult Comorbidity Evaluation 27 index. With a median follow-up of 22 months, the 2-year primary tumour control rate, disease-free survival and overall survival rates were 91%, 71% and 87%, respectively. No grade 3 (National Cancer Institute Common Terminology Criteria for Adverse Events) or higher treatment-related complications were reported. Conclusion Stereotactic ablative radiotherapy can achieve a high degree of local control safely in medically inoperable patients with early lung cancer.published_or_final_versio

    Progress report no. 5

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    Includes bibliographical referencesProgress report; June 30, 1974U.S. Atomic Energy Commission contract AT(11-1)225

    A study of a culturally focused psychiatric consultation service for Asian American and Latino American primary care patients with depression

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    <p>Abstract</p> <p>Background</p> <p>Ethnic minorities with depression are more likely to seek mental health care through primary care providers (PCPs) than mental health specialists. However, both provider and patient-specific challenges exist. PCP-specific challenges include unfamiliarity with depressive symptom profiles in diverse patient populations, limited time to address mental health, and limited referral options for mental health care. Patient-specific challenges include stigma around mental health issues and reluctance to seek mental health treatment. To address these issues, we implemented a multi-component intervention for Asian American and Latino American primary care patients with depression at Massachusetts General Hospital (MGH).</p> <p>Methods/Design</p> <p>We propose a randomized controlled trial to evaluate a culturally appropriate intervention to improve the diagnosis and treatment of depression in our target population. Our goals are to facilitate a) primary care providers' ability to provide appropriate, culturally informed care of depression, and b) patients' knowledge of and resources for receiving treatment for depression. Our two-year long intervention targets Asian American and Latino American adult (18 years of age or older) primary care patients at MGH screening positive for symptoms of depression. All eligible patients in the intervention arm of the study who screen positive will be offered a culturally focused psychiatric (CFP) consultation. Patients will meet with a study clinician and receive toolkits that include psychoeducational booklets, worksheets and community resources. Within two weeks of the initial consultation, patients will attend a follow-up visit with the CFP clinicians. Primary outcomes will determine the feasibility and cost associated with implementation of the service, and evaluate patient and provider satisfaction with the CFP service. Exploratory aims will describe the study population at screening, recruitment, and enrollment and identify which variables influenced patient participation in the program.</p> <p>Discussion</p> <p>The study involves an innovative yet practical intervention that builds on existing resources and strives to improve quality of care for depression for minorities. Additionally, it complements the current movement in psychiatry to enhance the treatment of depression in primary care settings. If found beneficial, the intervention will serve as a model for care of Asian American and Latino American patients.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01239407">NCT01239407</a></p

    Geometric Interpretation of Gene Coexpression Network Analysis

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    The merging of network theory and microarray data analysis techniques has spawned a new field: gene coexpression network analysis. While network methods are increasingly used in biology, the network vocabulary of computational biologists tends to be far more limited than that of, say, social network theorists. Here we review and propose several potentially useful network concepts. We take advantage of the relationship between network theory and the field of microarray data analysis to clarify the meaning of and the relationship among network concepts in gene coexpression networks. Network theory offers a wealth of intuitive concepts for describing the pairwise relationships among genes, which are depicted in cluster trees and heat maps. Conversely, microarray data analysis techniques (singular value decomposition, tests of differential expression) can also be used to address difficult problems in network theory. We describe conditions when a close relationship exists between network analysis and microarray data analysis techniques, and provide a rough dictionary for translating between the two fields. Using the angular interpretation of correlations, we provide a geometric interpretation of network theoretic concepts and derive unexpected relationships among them. We use the singular value decomposition of module expression data to characterize approximately factorizable gene coexpression networks, i.e., adjacency matrices that factor into node specific contributions. High and low level views of coexpression networks allow us to study the relationships among modules and among module genes, respectively. We characterize coexpression networks where hub genes are significant with respect to a microarray sample trait and show that the network concept of intramodular connectivity can be interpreted as a fuzzy measure of module membership. We illustrate our results using human, mouse, and yeast microarray gene expression data. The unification of coexpression network methods with traditional data mining methods can inform the application and development of systems biologic methods

    Progress report no. 4

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    Statement of responsibility on title-page reads: editors: M.J. Driscoll, D.D. Lanning, I. Kaplan, A.T. Supple ; contributors: A. Alvim, G.J. Brown, J.K. Chan, T.P. Choong, M.J. Driscoll, G. A. Ducat, I.A. Forbes, M.V. Gregory, S.Y. Ho, C.M. Hove, O. K. Kadiroglu, R.J. Kennerley, D.D. Lanning, J.L. Lazewatsky, L. Lederman, A.S. Leveckis, V.A. Miethe, P. A. Scheinert, A.M. Thompson, N.E. Todreas, C.P. Tzanos, and P.J. WoodIncludes bibliographical referencesProgress report; June 30, 1973U.S. Atomic Energy Commission contract: AT(11-1)225

    Quantitative determination of vitamin D metabolites in plasma using UHPLC-MS/MS

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    Vitamin D is an important determinant of bone health at all ages. The plasma concentrations of 25-hydroxy vitamin D (25-OH D) and other metabolites are used as biomarkers for vitamin sufficiency and function. To allow for the simultaneous determination of five vitamin D metabolites, 25-OH D3, 25-OH D2, 24,25-(OH)2 D3, 1,25-(OH)2 D3, and 1,25-(OH)2 D2, in low volumes of human plasma, an assay using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) was established. Plasma samples were spiked with isotope-labeled internal standards and pretreated using protein precipitation, solid-phase extraction (SPE) and a Diels–Alder derivatization step with 4-phenyl-1,2,4-triazoline-3,5-dione. The SPE recovery rates ranged from 55% to 85%, depending on the vitamin D metabolite; the total sample run time was <5 min. Mass spectrometry was conducted using positive ion electrospray ionization in the multiple reaction monitoring mode on a quadrupole–quadrupole-linear ion trap instrument after pre-column addition of methylamine to increase the ionization efficiency. The intra- and inter-day relative standard deviations were 1.6–4.1% and 3.7–6.8%, respectively. The limit of quantitation for these compounds was determined to be between 10 and 20 pg/mL. The 25-OH D results were compared with values obtained for reference materials (DEQAS). In addition, plasma samples were analyzed with two additional Diasorin antibody assays. All comparisons with conventional methods showed excellent correlations (r2 = 0.9738) for DEQAS samples, demonstrating the high degree of comparability of the new UHPLC-MS/MS technique to existing methods

    Understanding network concepts in modules

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    <p>Abstract</p> <p>Background</p> <p>Network concepts are increasingly used in biology and genetics. For example, the clustering coefficient has been used to understand network architecture; the connectivity (also known as degree) has been used to screen for cancer targets; and the topological overlap matrix has been used to define modules and to annotate genes. Dozens of potentially useful network concepts are known from graph theory.</p> <p>Results</p> <p>Here we study network concepts in special types of networks, which we refer to as approximately factorizable networks. In these networks, the pairwise connection strength (adjacency) between 2 network nodes can be factored into node specific contributions, named node 'conformity'. The node conformity turns out to be highly related to the connectivity. To provide a formalism for relating network concepts to each other, we define three types of network concepts: fundamental-, conformity-based-, and approximate conformity-based concepts. Fundamental concepts include the standard definitions of connectivity, density, centralization, heterogeneity, clustering coefficient, and topological overlap. The approximate conformity-based analogs of fundamental network concepts have several theoretical advantages. First, they allow one to derive simple relationships between seemingly disparate networks concepts. For example, we derive simple relationships between the clustering coefficient, the heterogeneity, the density, the centralization, and the topological overlap. The second advantage of approximate conformity-based network concepts is that they allow one to show that fundamental network concepts can be approximated by simple functions of the connectivity in module networks.</p> <p>Conclusion</p> <p>Using protein-protein interaction, gene co-expression, and simulated data, we show that a) many networks comprised of module nodes are approximately factorizable and b) in these types of networks, simple relationships exist between seemingly disparate network concepts. Our results are implemented in freely available R software code, which can be downloaded from the following webpage: <url>http://www.genetics.ucla.edu/labs/horvath/ModuleConformity/ModuleNetworks</url></p
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