WorldWideScience

Sample records for clinical target validation

  1. Clinical validation of targeted next-generation sequencing for inherited disorders.

    Science.gov (United States)

    Yohe, Sophia; Hauge, Adam; Bunjer, Kari; Kemmer, Teresa; Bower, Matthew; Schomaker, Matthew; Onsongo, Getiria; Wilson, Jon; Erdmann, Jesse; Zhou, Yi; Deshpande, Archana; Spears, Michael D; Beckman, Kenneth; Silverstein, Kevin A T; Thyagarajan, Bharat

    2015-02-01

    Although next-generation sequencing (NGS) can revolutionize molecular diagnostics, several hurdles remain in the implementation of this technology in clinical laboratories. To validate and implement an NGS panel for genetic diagnosis of more than 100 inherited diseases, such as neurologic conditions, congenital hearing loss and eye disorders, developmental disorders, nonmalignant diseases treated by hematopoietic cell transplantation, familial cancers, connective tissue disorders, metabolic disorders, disorders of sexual development, and cardiac disorders. The diagnostic gene panels ranged from 1 to 54 genes with most of panels containing 10 genes or fewer. We used a liquid hybridization-based, target-enrichment strategy to enrich 10 067 exons in 568 genes, followed by NGS with a HiSeq 2000 sequencing system (Illumina, San Diego, California). We successfully sequenced 97.6% (9825 of 10 067) of the targeted exons to obtain a minimum coverage of 20× at all bases. We demonstrated 100% concordance in detecting 19 pathogenic single-nucleotide variations and 11 pathogenic insertion-deletion mutations ranging in size from 1 to 18 base pairs across 18 samples that were previously characterized by Sanger sequencing. Using 4 pairs of blinded, duplicate samples, we demonstrated a high degree of concordance (>99%) among the blinded, duplicate pairs. We have successfully demonstrated the feasibility of using the NGS platform to multiplex genetic tests for several rare diseases and the use of cloud computing for bioinformatics analysis as a relatively low-cost solution for implementing NGS in clinical laboratories.

  2. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry : A worldwide collaborative project

    NARCIS (Netherlands)

    McHugh, David M. S.; Cameron, Cynthia A.; Abdenur, Jose E.; Abdulrahman, Mahera; Adair, Ona; Al Nuaimi, Shahira Ahmed; Ahlman, Henrik; Allen, Jennifer J.; Antonozzi, Italo; Archer, Shaina; Au, Sylvia; Auray-Blais, Christiane; Baker, Mei; Bamforth, Fiona; Beckmann, Kinga; Pino, Gessi Bentz; Berberich, Stanton L.; Binard, Robert; Boemer, Francois; Bonham, Jim; Breen, Nancy N.; Bryant, Sandra C.; Caggana, Michele; Caldwell, S. Graham; Camilot, Marta; Campbell, Carlene; Carducci, Claudia; Cariappa, Rohit; Carlisle, Clover; Caruso, Ubaldo; Cassanello, Michela; Miren Castilla, Ane; Castineiras Ramos, Daisy E.; Chakraborty, Pranesh; Chandrasekar, Ram; Ramos, Alfredo Chardon; Cheillan, David; Chien, Yin-Hsiu; Childs, Thomas A.; Chrastina, Petr; Sica, Yuri Cleverthon; Cocho de Juan, Jose Angel; Elena Colandre, Maria; Cornejo Espinoza, Veronica; Corso, Gaetano; Currier, Robert; Cyr, Denis; Czuczy, Noemi; D'Apolito, Oceania; Davis, Tim; de Sain-Van der Velden, Monique G.; Delgado Pecellin, Carmen; Di Gangi, Iole Maria; Di Stefano, Cristina Maria; Dotsikas, Yannis; Downing, Melanie; Downs, Stephen M.; Dy, Bonifacio; Dymerski, Mark; Rueda, Inmaculada; Elvers, Bert; Eaton, Roger; Eckerd, Barbara M.; El Mougy, Fatma; Eroh, Sarah; Espada, Mercedes; Evans, Catherine; Fawbush, Sandy; Fijolek, Kristel F.; Fisher, Lawrence; Franzson, Leifur; Frazier, Dianne M.; Garcia, Luciana R. C.; Garcia-Valdecasas Bermejo, Maria Sierra; Gavrilov, Dimitar; Gerace, Rosemarie; Giordano, Giuseppe; Irazabal, Yolanda Gonzalez; Greed, Lawrence C.; Grier, Robert; Grycki, Elyse; Gu, Xuefan; Gulamali-Majid, Fizza; Hagar, Arthur F.; Han, Lianshu; Hannon, W. Harry; Haslip, Christa; Hassan, Fayza Abdelhamid; He, Miao; Hietala, Amy; Himstedt, Leslie; Hoffman, Gary L.; Hoffman, William; Hoggatt, Philis; Hopkins, Patrick V.; Hougaard, David M.; Hughes, Kerie; Hunt, Patricia R.; Hwu, Wuh-Liang; Hynes, June; Ibarra-Gonzalez, Isabel; Ingham, Cindy A.; Ivanova, Maria; Jacox, Ward B.; John, Catharine; Johnson, John P.; Jonsson, Jon J.; Karg, Eszter; Kasper, David; Klopper, Brenda; Katakouzinos, Dimitris; Khneisser, Issam; Knoll, Detlef; Kobayashi, Hirinori; Koneski, Ronald; Kozich, Viktor; Kouapei, Rasoul; Kohlmueller, Dirk; Kremensky, Ivo; la Marca, Giancarlo; Lavochkin, Marcia; Lee, Soo-Youn; Lehotay, Denis C.; Lemes, Aida; Lepage, Joyce; Lesko, Barbara; Lewis, Barry; Lim, Carol; Linard, Sharon; Lindner, Martin; Lloyd-Puryear, Michele A.; Lorey, Fred; Loukas, Yannis L.; Luedtke, Julie; Maffitt, Neil; Magee, J. Fergall; Manning, Adrienne; Manos, Shawn; Marie, Sandrine; Hadachi, Sonia Marchezi; Marquardt, Gregg; Martin, Stephen J.; Matern, Dietrich; Gibson, Stephanie K. Mayfield; Mayne, Philip; McCallister, Tonya D.; McCann, Mark; McClure, Julie; McGill, James J.; McKeever, Christine D.; McNeilly, Barbara; Morrissey, Mark A.; Moutsatsou, Paraskevi; Mulcahy, Eleanor A.; Nikoloudis, Dimitris; Norgaard-Pedersen, Bent; Oglesbee, Devin; Oltarzewski, Mariusz; Ombrone, Daniela; Ojodu, Jelili; Papakonstantinou, Vagelis; Reoyo, Sherly Pardo; Park, Hyung-Doo; Pasquali, Marzia; Pasquini, Elisabetta; Patel, Pallavi; Pass, Kenneth A.; Peterson, Colleen; Pettersen, Rolf D.; Pitt, James J.; Poh, Sherry; Pollak, Arnold; Porter, Cory; Poston, Philip A.; Price, Ricky W.; Queijo, Cecilia; Quesada, Jonessy; Randell, Edward; Ranieri, Enzo; Raymond, Kimiyo; Reddic, John E.; Reuben, Alejandra; Ricciardi, Charla; Rinaldo, Piero; Rivera, Jeff D.; Roberts, Alicia; Rocha, Hugo; Roche, Geraldine; Greenberg, Cheryl Rochman; Egea Mellado, Jose Maria; Jess Juan-Fita, Maria; Ruiz, Consuelo; Ruoppolo, Margherita; Rutledge, S. Lane; Ryu, Euijung; Saban, Christine; Sahai, Inderneel; Salazar Garcia-Blanco, Maria Isabel; Santiago-Borrero, Pedro; Schenone, Andrea; Schoos, Roland; Schweitzer, Barb; Scott, Patricia; Seashore, Margretta R.; Seeterlin, Mary A.; Sesser, David E.; Sevier, Darrin W.; Shone, Scott M.; Sinclair, Graham; Skrinska, Victor A.; Stanley, Eleanor L.; Strovel, Erin T.; Jones, April L. Studinski; Sunny, Sherlykutty; Takats, Zoltan; Tanyalcin, Tijen; Teofoli, Francesca; Thompson, J. Robert; Tomashitis, Kathy; Domingos, Mouseline Torquado; Torres, Jasmin; Torres, Rosario; Tortorelli, Silvia; Turi, Sandor; Turner, Kimberley; Tzanakos, Nick; Valiente, Alf G.; Vallance, Hillary; Vela-Amieva, Marcela; Vilarinho, Laura; von Doebeln, Ulrika; Vincent, Marie-Francoise; Vorster, B. Chris; Watson, Michael S.; Webster, Dianne; Weiss, Sheila; Wilcken, Bridget; Wiley, Veronica; Williams, Sharon K.; Willis, Sharon A.; Woontner, Michael; Wright, Katherine; Yahyaoui, Raquel; Yamaguchi, Seiji; Yssel, Melissa; Zakowicz, Wendy M.

    Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742

  3. External Validation and Optimization of International Consensus Clinical Target Volumes for Adjuvant Radiation Therapy in Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Abhinav V. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Christodouleas, John P. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Wu, Tianming [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Smith, Norman D.; Steinberg, Gary D. [Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States)

    2017-03-15

    Purpose: International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. Methods and Materials: Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review. Images with LRF were exported into a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF with respect to both the patient and each of 6 pelvic subsites: common iliac (CI) region, obturator region (OR), external and internal iliac region, presacral region, cystectomy bed, or other pelvic site. Revisions to the IC contours were proposed based on the findings. Results: Of the 52 patients with documented LRF, 13 (25%) had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the external and internal iliac region, and 6 near the cystectomy bed. The 5 CI failures were located superior to the CTV, and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, as well as increasing the medial extension of the OR by an additional 9 mm, decreased the number of patients with LRF outside of the IC CTV to 7 (13%). Conclusions: Modified IC CTVs inclusive of a slight adjustment superiorly for the CI region and medially for the OR may reduce the risk of pelvic failure in patients treated with adjuvant radiation therapy.

  4. Atlas-based automatic segmentation of head and neck organs at risk and nodal target volumes: a clinical validation

    International Nuclear Information System (INIS)

    Daisne, Jean-François; Blumhofer, Andreas

    2013-01-01

    Intensity modulated radiotherapy for head and neck cancer necessitates accurate definition of organs at risk (OAR) and clinical target volumes (CTV). This crucial step is time consuming and prone to inter- and intra-observer variations. Automatic segmentation by atlas deformable registration may help to reduce time and variations. We aim to test a new commercial atlas algorithm for automatic segmentation of OAR and CTV in both ideal and clinical conditions. The updated Brainlab automatic head and neck atlas segmentation was tested on 20 patients: 10 cN0-stages (ideal population) and 10 unselected N-stages (clinical population). Following manual delineation of OAR and CTV, automatic segmentation of the same set of structures was performed and afterwards manually corrected. Dice Similarity Coefficient (DSC), Average Surface Distance (ASD) and Maximal Surface Distance (MSD) were calculated for “manual to automatic” and “manual to corrected” volumes comparisons. In both groups, automatic segmentation saved about 40% of the corresponding manual segmentation time. This effect was more pronounced for OAR than for CTV. The edition of the automatically obtained contours significantly improved DSC, ASD and MSD. Large distortions of normal anatomy or lack of iodine contrast were the limiting factors. The updated Brainlab atlas-based automatic segmentation tool for head and neck Cancer patients is timesaving but still necessitates review and corrections by an expert

  5. Atlas-based automatic segmentation of head and neck organs at risk and nodal target volumes: a clinical validation.

    Science.gov (United States)

    Daisne, Jean-François; Blumhofer, Andreas

    2013-06-26

    Intensity modulated radiotherapy for head and neck cancer necessitates accurate definition of organs at risk (OAR) and clinical target volumes (CTV). This crucial step is time consuming and prone to inter- and intra-observer variations. Automatic segmentation by atlas deformable registration may help to reduce time and variations. We aim to test a new commercial atlas algorithm for automatic segmentation of OAR and CTV in both ideal and clinical conditions. The updated Brainlab automatic head and neck atlas segmentation was tested on 20 patients: 10 cN0-stages (ideal population) and 10 unselected N-stages (clinical population). Following manual delineation of OAR and CTV, automatic segmentation of the same set of structures was performed and afterwards manually corrected. Dice Similarity Coefficient (DSC), Average Surface Distance (ASD) and Maximal Surface Distance (MSD) were calculated for "manual to automatic" and "manual to corrected" volumes comparisons. In both groups, automatic segmentation saved about 40% of the corresponding manual segmentation time. This effect was more pronounced for OAR than for CTV. The edition of the automatically obtained contours significantly improved DSC, ASD and MSD. Large distortions of normal anatomy or lack of iodine contrast were the limiting factors. The updated Brainlab atlas-based automatic segmentation tool for head and neck Cancer patients is timesaving but still necessitates review and corrections by an expert.

  6. Clinical Validation of Atlas-Based Auto-Segmentation of Multiple Target Volumes and Normal Tissue (Swallowing/Mastication) Structures in the Head and Neck

    International Nuclear Information System (INIS)

    Teguh, David N.; Levendag, Peter C.; Voet, Peter W.J.; Al-Mamgani, Abrahim; Han Xiao; Wolf, Theresa K.; Hibbard, Lyndon S.; Nowak, Peter; Akhiat, Hafid; Dirkx, Maarten L.P.; Heijmen, Ben J.M.; Hoogeman, Mischa S.

    2011-01-01

    Purpose: To validate and clinically evaluate autocontouring using atlas-based autosegmentation (ABAS) of computed tomography images. Methods and Materials: The data from 10 head-and-neck patients were selected as input for ABAS, and neck levels I-V and 20 organs at risk were manually contoured according to published guidelines. The total contouring times were recorded. Two different ABAS strategies, multiple and single subject, were evaluated, and the similarity of the autocontours with the atlas contours was assessed using Dice coefficients and the mean distances, using the leave-one-out method. For 12 clinically treated patients, 5 experienced observers edited the autosegmented contours. The editing times were recorded. The Dice coefficients and mean distances were calculated among the clinically used contours, autocontours, and edited autocontours. Finally, an expert panel scored all autocontours and the edited autocontours regarding their adequacy relative to the published atlas. Results: The time to autosegment all the structures using ABAS was 7 min/patient. No significant differences were observed in the autosegmentation accuracy for stage N0 and N+ patients. The multisubject atlas performed best, with a Dice coefficient and mean distance of 0.74 and 2 mm, 0.67 and 3 mm, 0.71 and 2 mm, 0.50 and 2 mm, and 0.78 and 2 mm for the salivary glands, neck levels, chewing muscles, swallowing muscles, and spinal cord-brainstem, respectively. The mean Dice coefficient and mean distance of the autocontours vs. the clinical contours was 0.8 and 2.4 mm for the neck levels and salivary glands, respectively. For the autocontours vs. the edited autocontours, the mean Dice coefficient and mean distance was 0.9 and 1.6 mm, respectively. The expert panel scored 100% of the autocontours as a “minor deviation, editable” or better. The expert panel scored 88% of the edited contours as good compared with 83% of the clinical contours. The total editing time was 66 min

  7. Clinical Validation of Atlas-Based Auto-Segmentation of Multiple Target Volumes and Normal Tissue (Swallowing/Mastication) Structures in the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Teguh, David N. [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Levendag, Peter C., E-mail: p.levendag@erasmusmc.nl [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Voet, Peter W.J.; Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Han Xiao; Wolf, Theresa K.; Hibbard, Lyndon S. [Elekta-CMS Software, Maryland Heights, MO 63043 (United States); Nowak, Peter; Akhiat, Hafid; Dirkx, Maarten L.P.; Heijmen, Ben J.M.; Hoogeman, Mischa S. [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2011-11-15

    Purpose: To validate and clinically evaluate autocontouring using atlas-based autosegmentation (ABAS) of computed tomography images. Methods and Materials: The data from 10 head-and-neck patients were selected as input for ABAS, and neck levels I-V and 20 organs at risk were manually contoured according to published guidelines. The total contouring times were recorded. Two different ABAS strategies, multiple and single subject, were evaluated, and the similarity of the autocontours with the atlas contours was assessed using Dice coefficients and the mean distances, using the leave-one-out method. For 12 clinically treated patients, 5 experienced observers edited the autosegmented contours. The editing times were recorded. The Dice coefficients and mean distances were calculated among the clinically used contours, autocontours, and edited autocontours. Finally, an expert panel scored all autocontours and the edited autocontours regarding their adequacy relative to the published atlas. Results: The time to autosegment all the structures using ABAS was 7 min/patient. No significant differences were observed in the autosegmentation accuracy for stage N0 and N+ patients. The multisubject atlas performed best, with a Dice coefficient and mean distance of 0.74 and 2 mm, 0.67 and 3 mm, 0.71 and 2 mm, 0.50 and 2 mm, and 0.78 and 2 mm for the salivary glands, neck levels, chewing muscles, swallowing muscles, and spinal cord-brainstem, respectively. The mean Dice coefficient and mean distance of the autocontours vs. the clinical contours was 0.8 and 2.4 mm for the neck levels and salivary glands, respectively. For the autocontours vs. the edited autocontours, the mean Dice coefficient and mean distance was 0.9 and 1.6 mm, respectively. The expert panel scored 100% of the autocontours as a 'minor deviation, editable' or better. The expert panel scored 88% of the edited contours as good compared with 83% of the clinical contours. The total editing time was 66 min

  8. Literature evidence in open targets - a target validation platform.

    Science.gov (United States)

    Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

    2017-06-06

    We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information. The confidence score of a given document represents how valuable the document is in the scope of target validation for a given target-disease association by taking into account the credibility of the association based on the properties of the text. The component serves the platform regularly with the up-to-date data since December, 2015. Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining. This component helps the platform's users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually through https://www.targetvalidation.org and all the evidence data is available for download in json format from https://www.targetvalidation.org/downloads/data .

  9. Multi-institutional Quantitative Evaluation and Clinical Validation of Smart Probabilistic Image Contouring Engine (SPICE) Autosegmentation of Target Structures and Normal Tissues on Computer Tomography Images in the Head and Neck, Thorax, Liver, and Male Pelvis Areas

    DEFF Research Database (Denmark)

    Zhu, Mingyao; Bzdusek, Karl; Brink, Carsten

    2013-01-01

    Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE).......Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE)....

  10. Common pitfalls in preclinical cancer target validation.

    Science.gov (United States)

    Kaelin, William G

    2017-07-01

    An alarming number of papers from laboratories nominating new cancer drug targets contain findings that cannot be reproduced by others or are simply not robust enough to justify drug discovery efforts. This problem probably has many causes, including an underappreciation of the danger of being misled by off-target effects when using pharmacological or genetic perturbants in complex biological assays. This danger is particularly acute when, as is often the case in cancer pharmacology, the biological phenotype being measured is a 'down' readout (such as decreased proliferation, decreased viability or decreased tumour growth) that could simply reflect a nonspecific loss of cellular fitness. These problems are compounded by multiple hypothesis testing, such as when candidate targets emerge from high-throughput screens that interrogate multiple targets in parallel, and by a publication and promotion system that preferentially rewards positive findings. In this Perspective, I outline some of the common pitfalls in preclinical cancer target identification and some potential approaches to mitigate them.

  11. Validating EHR clinical models using ontology patterns.

    Science.gov (United States)

    Martínez-Costa, Catalina; Schulz, Stefan

    2017-12-01

    Clinical models are artefacts that specify how information is structured in electronic health records (EHRs). However, the makeup of clinical models is not guided by any formal constraint beyond a semantically vague information model. We address this gap by advocating ontology design patterns as a mechanism that makes the semantics of clinical models explicit. This paper demonstrates how ontology design patterns can validate existing clinical models using SHACL. Based on the Clinical Information Modelling Initiative (CIMI), we show how ontology patterns detect both modeling and terminology binding errors in CIMI models. SHACL, a W3C constraint language for the validation of RDF graphs, builds on the concept of "Shape", a description of data in terms of expected cardinalities, datatypes and other restrictions. SHACL, as opposed to OWL, subscribes to the Closed World Assumption (CWA) and is therefore more suitable for the validation of clinical models. We have demonstrated the feasibility of the approach by manually describing the correspondences between six CIMI clinical models represented in RDF and two SHACL ontology design patterns. Using a Java-based SHACL implementation, we found at least eleven modeling and binding errors within these CIMI models. This demonstrates the usefulness of ontology design patterns not only as a modeling tool but also as a tool for validation. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Circulating tumor cells: clinical validity and utility.

    Science.gov (United States)

    Cabel, Luc; Proudhon, Charlotte; Gortais, Hugo; Loirat, Delphine; Coussy, Florence; Pierga, Jean-Yves; Bidard, François-Clément

    2017-06-01

    Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed-(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.

  13. Neuroinflammatory targets and treatments for epilepsy validated in experimental models.

    Science.gov (United States)

    Aronica, Eleonora; Bauer, Sebastian; Bozzi, Yuri; Caleo, Matteo; Dingledine, Raymond; Gorter, Jan A; Henshall, David C; Kaufer, Daniela; Koh, Sookyong; Löscher, Wolfgang; Louboutin, Jean-Pierre; Mishto, Michele; Norwood, Braxton A; Palma, Eleonora; Poulter, Michael O; Terrone, Gaetano; Vezzani, Annamaria; Kaminski, Rafal M

    2017-07-01

    A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  14. Roll-up of validation results to a target application.

    Energy Technology Data Exchange (ETDEWEB)

    Hills, Richard Guy

    2013-09-01

    Suites of experiments are preformed over a validation hierarchy to test computational simulation models for complex applications. Experiments within the hierarchy can be performed at different conditions and configurations than those for an intended application, with each experiment testing only part of the physics relevant for the application. The purpose of the present work is to develop methodology to roll-up validation results to an application, and to assess the impact the validation hierarchy design has on the roll-up results. The roll-up is accomplished through the development of a meta-model that relates validation measurements throughout a hierarchy to the desired response quantities for the target application. The meta-model is developed using the computation simulation models for the experiments and the application. The meta-model approach is applied to a series of example transport problems that represent complete and incomplete coverage of the physics of the target application by the validation experiments.

  15. Multi-institutional Quantitative Evaluation and Clinical Validation of Smart Probabilistic Image Contouring Engine (SPICE) Autosegmentation of Target Structures and Normal Tissues on Computer Tomography Images in the Head and Neck, Thorax, Liver, and Male Pelvis Areas

    NARCIS (Netherlands)

    Zhu, Mingyao; Bzdusek, Karl; Brink, Carsten; Eriksen, Jesper Grau; Hansen, Olfred; Jensen, Helle Anita; Gay, Hiram A.; Thorstad, Wade; Widder, Joachim; Brouwer, Charlotte L.; Steenbakkers, Roel J. H. M.; Vanhauten, Hubertus A. M.; Cao, Jeffrey Q.; McBrayne, Gail; Patel, Salil H.; Cannon, Donald M.; Hardcastle, Nicholas; Tome, Wolfgang A.; Guckenberg, Matthias; Parikh, Parag J.

    2013-01-01

    Purpose: Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE). Methods and Materials: CT images of 125 treated patients (32 head and neck [HN], 40 thorax, 23 liver, and 30 prostate) in 7

  16. The target landscape of clinical kinase drugs.

    Science.gov (United States)

    Klaeger, Susan; Heinzlmeir, Stephanie; Wilhelm, Mathias; Polzer, Harald; Vick, Binje; Koenig, Paul-Albert; Reinecke, Maria; Ruprecht, Benjamin; Petzoldt, Svenja; Meng, Chen; Zecha, Jana; Reiter, Katrin; Qiao, Huichao; Helm, Dominic; Koch, Heiner; Schoof, Melanie; Canevari, Giulia; Casale, Elena; Depaolini, Stefania Re; Feuchtinger, Annette; Wu, Zhixiang; Schmidt, Tobias; Rueckert, Lars; Becker, Wilhelm; Huenges, Jan; Garz, Anne-Kathrin; Gohlke, Bjoern-Oliver; Zolg, Daniel Paul; Kayser, Gian; Vooder, Tonu; Preissner, Robert; Hahne, Hannes; Tõnisson, Neeme; Kramer, Karl; Götze, Katharina; Bassermann, Florian; Schlegl, Judith; Ehrlich, Hans-Christian; Aiche, Stephan; Walch, Axel; Greif, Philipp A; Schneider, Sabine; Felder, Eduard Rudolf; Ruland, Juergen; Médard, Guillaume; Jeremias, Irmela; Spiekermann, Karsten; Kuster, Bernhard

    2017-12-01

    Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  17. [Target volume margins for lung cancer: internal target volume/clinical target volume].

    Science.gov (United States)

    Jouin, A; Pourel, N

    2013-10-01

    The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. Copyright © 2013. Published by Elsevier SAS.

  18. [Targeting high-risk drugs to optimize clinical pharmacists' intervention].

    Science.gov (United States)

    Mouterde, Anne-Laure; Bourdelin, Magali; Maison, Ophélie; Coursier, Sandra; Bontemps, Hervé

    2016-12-01

    By the Order of 6 April 2011, the pharmacist must validate all the prescriptions containing "high-risk drugs" or those of "patients at risk". To optimize this clinical pharmacy activity, we identified high-risk drugs. A list of high-risk drugs has been established using literature, pharmacists' interventions (PI) performed in our hospital and a survey sent to hospital pharmacists. In a prospective study (analysis of 100 prescriptions for each high-risk drug selected), we have identified the most relevant to target. We obtained a statistically significant PI rate (P<0.05) for digoxin, oral anticoagulants direct, oral methotrexate and colchicine. This method of targeted pharmaceutical validation based on high-risk drugs is relevant to detect patients with high risk of medicine-related illness. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  19. Validation of Clinical Testing for Warfarin Sensitivity

    Science.gov (United States)

    Langley, Michael R.; Booker, Jessica K.; Evans, James P.; McLeod, Howard L.; Weck, Karen E.

    2009-01-01

    Responses to warfarin (Coumadin) anticoagulation therapy are affected by genetic variability in both the CYP2C9 and VKORC1 genes. Validation of pharmacogenetic testing for warfarin responses includes demonstration of analytical validity of testing platforms and of the clinical validity of testing. We compared four platforms for determining the relevant single nucleotide polymorphisms (SNPs) in both CYP2C9 and VKORC1 that are associated with warfarin sensitivity (Third Wave Invader Plus, ParagonDx/Cepheid Smart Cycler, Idaho Technology LightCycler, and AutoGenomics Infiniti). Each method was examined for accuracy, cost, and turnaround time. All genotyping methods demonstrated greater than 95% accuracy for identifying the relevant SNPs (CYP2C9 *2 and *3; VKORC1 −1639 or 1173). The ParagonDx and Idaho Technology assays had the shortest turnaround and hands-on times. The Third Wave assay was readily scalable to higher test volumes but had the longest hands-on time. The AutoGenomics assay interrogated the largest number of SNPs but had the longest turnaround time. Four published warfarin-dosing algorithms (Washington University, UCSF, Louisville, and Newcastle) were compared for accuracy for predicting warfarin dose in a retrospective analysis of a local patient population on long-term, stable warfarin therapy. The predicted doses from both the Washington University and UCSF algorithms demonstrated the best correlation with actual warfarin doses. PMID:19324988

  20. Automatic target validation based on neuroscientific literature mining for tractography

    Directory of Open Access Journals (Sweden)

    Xavier eVasques

    2015-05-01

    Full Text Available Target identification for tractography studies requires solid anatomical knowledge validated by an extensive literature review across species for each seed structure to be studied. Manual literature review to identify targets for a given seed region is tedious and potentially subjective. Therefore, complementary approaches would be useful. We propose to use text-mining models to automatically suggest potential targets from the neuroscientific literature, full-text articles and abstracts, so that they can be used for anatomical connection studies and more specifically for tractography. We applied text-mining models to three structures: two well studied structures, since validated deep brain stimulation targets, the internal globus pallidus and the subthalamic nucleus and, the nucleus accumbens, an exploratory target for treating psychiatric disorders. We performed a systematic review of the literature to document the projections of the three selected structures and compared it with the targets proposed by text-mining models, both in rat and primate (including human. We ran probabilistic tractography on the nucleus accumbens and compared the output with the results of the text-mining models and literature review. Overall, text-mining the literature could find three times as many targets as two man-weeks of curation could. The overall efficiency of the text-mining against literature review in our study was 98% recall (at 36% precision, meaning that over all the targets for the three selected seeds, only one target has been missed by text-mining. We demonstrate that connectivity for a structure of interest can be extracted from a very large amount of publications and abstracts. We believe this tool will be useful in helping the neuroscience community to facilitate connectivity studies of particular brain regions. The text mining tools used for the study are part of the HBP Neuroinformatics Platform, publicly available at http://connectivity-brainer.rhcloud.com/.

  1. Enhanced clinical pharmacy service targeting tools: risk-predictive algorithms.

    Science.gov (United States)

    El Hajji, Feras W D; Scullin, Claire; Scott, Michael G; McElnay, James C

    2015-04-01

    This study aimed to determine the value of using a mix of clinical pharmacy data and routine hospital admission spell data in the development of predictive algorithms. Exploration of risk factors in hospitalized patients, together with the targeting strategies devised, will enable the prioritization of clinical pharmacy services to optimize patient outcomes. Predictive algorithms were developed using a number of detailed steps using a 75% sample of integrated medicines management (IMM) patients, and validated using the remaining 25%. IMM patients receive targeted clinical pharmacy input throughout their hospital stay. The algorithms were applied to the validation sample, and predicted risk probability was generated for each patient from the coefficients. Risk threshold for the algorithms were determined by identifying the cut-off points of risk scores at which the algorithm would have the highest discriminative performance. Clinical pharmacy staffing levels were obtained from the pharmacy department staffing database. Numbers of previous emergency admissions and admission medicines together with age-adjusted co-morbidity and diuretic receipt formed a 12-month post-discharge and/or readmission risk algorithm. Age-adjusted co-morbidity proved to be the best index to predict mortality. Increased numbers of clinical pharmacy staff at ward level was correlated with a reduction in risk-adjusted mortality index (RAMI). Algorithms created were valid in predicting risk of in-hospital and post-discharge mortality and risk of hospital readmission 3, 6 and 12 months post-discharge. The provision of ward-based clinical pharmacy services is a key component to reducing RAMI and enabling the full benefits of pharmacy input to patient care to be realized. © 2014 John Wiley & Sons, Ltd.

  2. Quality of clinical trials: A moving target

    Science.gov (United States)

    Bhatt, Arun

    2011-01-01

    Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

  3. Quality of clinical trials: A moving target

    Directory of Open Access Journals (Sweden)

    Arun Bhatt

    2011-01-01

    Full Text Available Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials.

  4. Integrative analysis to select cancer candidate biomarkers to targeted validation

    Science.gov (United States)

    Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2015-01-01

    Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

  5. Preclinical validation of Aurora kinases-targeting drugs in osteosarcoma

    NARCIS (Netherlands)

    Tavanti, E.; Sero, V.; Vella, S.; Fanelli, M.; Michelacci, F.; Landuzzi, L.; Magagnoli, G.; Versteeg, R.; Picci, P.; Hattinger, C. M.; Serra, M.

    2013-01-01

    Aurora kinases are key regulators of cell cycle and represent new promising therapeutic targets in several human tumours. Biological relevance of Aurora kinase-A and -B was assessed on osteosarcoma clinical samples and by silencing these genes with specific siRNA in three human osteosarcoma cell

  6. Imbalanced target prediction with pattern discovery on clinical data repositories.

    Science.gov (United States)

    Chan, Tak-Ming; Li, Yuxi; Chiau, Choo-Chiap; Zhu, Jane; Jiang, Jie; Huo, Yong

    2017-04-20

    Clinical data repositories (CDR) have great potential to improve outcome prediction and risk modeling. However, most clinical studies require careful study design, dedicated data collection efforts, and sophisticated modeling techniques before a hypothesis can be tested. We aim to bridge this gap, so that clinical domain users can perform first-hand prediction on existing repository data without complicated handling, and obtain insightful patterns of imbalanced targets for a formal study before it is conducted. We specifically target for interpretability for domain users where the model can be conveniently explained and applied in clinical practice. We propose an interpretable pattern model which is noise (missing) tolerant for practice data. To address the challenge of imbalanced targets of interest in clinical research, e.g., deaths less than a few percent, the geometric mean of sensitivity and specificity (G-mean) optimization criterion is employed, with which a simple but effective heuristic algorithm is developed. We compared pattern discovery to clinically interpretable methods on two retrospective clinical datasets. They contain 14.9% deaths in 1 year in the thoracic dataset and 9.1% deaths in the cardiac dataset, respectively. In spite of the imbalance challenge shown on other methods, pattern discovery consistently shows competitive cross-validated prediction performance. Compared to logistic regression, Naïve Bayes, and decision tree, pattern discovery achieves statistically significant (p-values repositories with imbalance and noise. The prediction results and interpretable patterns can provide insights in an agile and inexpensive way for the potential formal studies.

  7. Multi-institutional Quantitative Evaluation and Clinical Validation of Smart Probabilistic Image Contouring Engine (SPICE) Autosegmentation of Target Structures and Normal Tissues on Computer Tomography Images in the Head and Neck, Thorax, Liver, and Male Pelvis Areas

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Mingyao [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Bzdusek, Karl [Philips Healthcare, Fitchburg, Wisconsin (United States); Brink, Carsten [Institute of Clinical Research, University of Southern Denmark, Odense (Denmark); Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Eriksen, Jesper Grau [Department of Oncology, Odense University Hospital, Odense (Denmark); Hansen, Olfred [Institute of Clinical Research, University of Southern Denmark, Odense (Denmark); Department of Oncology, Odense University Hospital, Odense (Denmark); Jensen, Helle Anita [Department of Oncology, Odense University Hospital, Odense (Denmark); Gay, Hiram A.; Thorstad, Wade [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Widder, Joachim; Brouwer, Charlotte L.; Steenbakkers, Roel J.H.M.; Vanhauten, Hubertus A.M. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Cao, Jeffrey Q.; McBrayne, Gail [London Regional Cancer Centre, Ontario (Canada); Patel, Salil H. [Department of Radiation Oncology, Rhode Island Hospital, Providence, Rhode Island (United States); Cannon, Donald M. [Department of Human Oncology, University of Wisconsin—Madison (United States); Hardcastle, Nicholas [Department of Physical Science, Peter MacCallum Cancer Centre, Melbourne (Australia); Tomé, Wolfgang A. [Montefiore Medical Center and Institute of Onco-Physics, Albert Einstein College of Medicine, Bronx, New York (United States); Guckenberg, Matthias [University of Würzburg, Department of Radiation Oncology, Würzburg (Germany); Parikh, Parag J., E-mail: pparikh@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2013-11-15

    Purpose: Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE). Methods and Materials: CT images of 125 treated patients (32 head and neck [HN], 40 thorax, 23 liver, and 30 prostate) in 7 independent institutions were autosegmented using SPICE and computational times were recorded. The number of structures autocontoured were 25 for the HN, 7 for the thorax, 3 for the liver, and 6 for the male pelvis regions. Using the clinical contours as reference, autocontours of 22 selected structures were quantitatively evaluated using Dice Similarity Coefficient (DSC) and Mean Slice-wise Hausdorff Distance (MSHD). All 40 autocontours were evaluated by a radiation oncologist from the institution that treated the patients. Results: The mean computational times to autosegment all the structures using SPICE were 3.1 to 11.1 minutes per patient. For the HN region, the mean DSC was >0.70 for all evaluated structures, and the MSHD ranged from 3.2 to 10.0 mm. For the thorax region, the mean DSC was 0.95 for the lungs and 0.90 for the heart, and the MSHD ranged from 2.8 to 12.8 mm. For the liver region, the mean DSC was >0.92 for all structures, and the MSHD ranged from 5.2 to 15.9 mm. For the male pelvis region, the mean DSC was >0.76 for all structures, and the MSHD ranged from 4.8 to 10.5 mm. Out of the 40 autocontoured structures reviews by experts, 25 were scored useful as autocontoured or with minor edits for at least 90% of the patients and 33 were scored useful autocontoured or with minor edits for at least 80% of the patients. Conclusions: Compared with manual contouring, autosegmentation using SPICE for the HN, thorax, liver, and male pelvis regions is efficient and shows significant promise for clinical utility.

  8. Multi-institutional Quantitative Evaluation and Clinical Validation of Smart Probabilistic Image Contouring Engine (SPICE) Autosegmentation of Target Structures and Normal Tissues on Computer Tomography Images in the Head and Neck, Thorax, Liver, and Male Pelvis Areas

    International Nuclear Information System (INIS)

    Zhu, Mingyao; Bzdusek, Karl; Brink, Carsten; Eriksen, Jesper Grau; Hansen, Olfred; Jensen, Helle Anita; Gay, Hiram A.; Thorstad, Wade; Widder, Joachim; Brouwer, Charlotte L.; Steenbakkers, Roel J.H.M.; Vanhauten, Hubertus A.M.; Cao, Jeffrey Q.; McBrayne, Gail; Patel, Salil H.; Cannon, Donald M.; Hardcastle, Nicholas; Tomé, Wolfgang A.; Guckenberg, Matthias; Parikh, Parag J.

    2013-01-01

    Purpose: Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE). Methods and Materials: CT images of 125 treated patients (32 head and neck [HN], 40 thorax, 23 liver, and 30 prostate) in 7 independent institutions were autosegmented using SPICE and computational times were recorded. The number of structures autocontoured were 25 for the HN, 7 for the thorax, 3 for the liver, and 6 for the male pelvis regions. Using the clinical contours as reference, autocontours of 22 selected structures were quantitatively evaluated using Dice Similarity Coefficient (DSC) and Mean Slice-wise Hausdorff Distance (MSHD). All 40 autocontours were evaluated by a radiation oncologist from the institution that treated the patients. Results: The mean computational times to autosegment all the structures using SPICE were 3.1 to 11.1 minutes per patient. For the HN region, the mean DSC was >0.70 for all evaluated structures, and the MSHD ranged from 3.2 to 10.0 mm. For the thorax region, the mean DSC was 0.95 for the lungs and 0.90 for the heart, and the MSHD ranged from 2.8 to 12.8 mm. For the liver region, the mean DSC was >0.92 for all structures, and the MSHD ranged from 5.2 to 15.9 mm. For the male pelvis region, the mean DSC was >0.76 for all structures, and the MSHD ranged from 4.8 to 10.5 mm. Out of the 40 autocontoured structures reviews by experts, 25 were scored useful as autocontoured or with minor edits for at least 90% of the patients and 33 were scored useful autocontoured or with minor edits for at least 80% of the patients. Conclusions: Compared with manual contouring, autosegmentation using SPICE for the HN, thorax, liver, and male pelvis regions is efficient and shows significant promise for clinical utility

  9. Generalizing Evidence From Randomized Clinical Trials to Target Populations

    Science.gov (United States)

    Cole, Stephen R.; Stuart, Elizabeth A.

    2010-01-01

    Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

  10. Targeted resequencing and variant validation using pxlence PCR assays

    Directory of Open Access Journals (Sweden)

    Frauke Coppieters

    2016-01-01

    Full Text Available The advent of next-generation sequencing technologies had a profound impact on molecular diagnostics. PCR is a popular method for target enrichment of disease gene panels. Using our proprietary primer-design pipeline, primerXL, we have created almost one million assays covering over 98% of the human exome. Here we describe the assay specification and both in silico and wet-lab validation of a selected set of 2294 assays using both next-generation sequencing and Sanger sequencing. Using a universal PCR protocol without optimization, these assays result in high coverage uniformity and limited non-specific coverage. In addition, data indicates a positive correlation between the predictive in silico specificity score and the amount of assay non-specific coverage.

  11. Validating relationships among attachment, emotional intelligence and clinical communication.

    Science.gov (United States)

    Cherry, M Gemma; Fletcher, Ian; O'Sullivan, Helen

    2014-10-01

    In a previous study, we found that emotional intelligence (EI) mediates the negative influences of Year 1 medical students' attachment styles on their provider-patient communication (PPC). However, in that study, students were examined on a relatively straightforward PPC skill set and were not assessed on their abilities to elicit relevant clinical information from standardised patients. The influence of these psychological variables in more demanding and realistic clinical scenarios warrants investigation. This study aimed to validate previous research findings by exploring the mediating effect of EI on the relationship between medical students' attachment styles and their PPC across an ecologically valid PPC objective structured clinical examination (OSCE). Year 2 medical students completed measures of attachment (the Experiences in Close Relationships-Short Form [ECR-SF], a 12-item measure which provides attachment avoidance and attachment anxiety dimensional scores) and EI (the Mayer-Salovey-Caruso Emotional Intelligence Test [MSCEIT], a 141-item measure on the perception, use, understanding and management of emotions), prior to their summative PPC OSCE. Provider-patient communication was assessed using OSCE scores. Structural equation modelling (SEM) was used to validate our earlier model of the relationships between attachment style, EI and PPC. A total of 296 of 382 (77.5%) students participated. Attachment avoidance was significantly negatively correlated with total EI scores (r = -0.23, p < 0.01); total EI was significantly positively correlated with OSCE scores (r = 0.32, p < 0.01). Parsimonious SEM confirmed that EI mediated the negative influence of attachment avoidance on OSCE scores. It significantly predicted 14% of the variance in OSCE scores, twice as much as the 7% observed in the previous study. In more demanding and realistic clinical scenarios, EI makes a greater contribution towards effective PPC. Attachment is perceived to be stable

  12. Clinical targeting recombinant immunotoxins for cancer therapy

    Directory of Open Access Journals (Sweden)

    Li M

    2017-07-01

    Full Text Available Meng Li,1,* Zeng-Shan Liu,1,* Xi-Lin Liu,1,* Qi Hui,2,* Shi-Ying Lu,1 Lin-Lin Qu,1 Yan-Song Li,1 Yu Zhou,1 Hong-Lin Ren,1 Pan Hu1 1Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, China-Japan Union Hospital, The First Hospital, Jilin University, Changchun, 2School of Pharmacy, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Recombinant immunotoxins (RITs are proteins that contain a toxin fused to an antibody or small molecules and are constructed by the genetic engineering technique. RITs can bind to and be internalized by cells and kill cancerous or non-cancerous cells by inhibiting protein synthesis. A wide variety of RITs have been tested against different cancers in cell culture, xenograft models, and human patients during the past several decades. RITs have shown activity in therapy of several kinds of cancers, but different levels of side effects, mainly related to vascular leak syndrome, were also observed in the treated patients. High immunogenicity of RITs limited their long-term or repeat applications in clinical cases. Recent advances in the design of immunotoxins, such as humanization of antibody fragment, PEGylation, and modification of human B- and T-cell epitopes, are overcoming the above mentioned problems, which predict the use of these immunotoxins as a potential therapeutic method to treat cancer patients. Keywords: targeted therapy, hematologic malignancies, solid tumors, vascular leak syndrome, immunogenicity 

  13. Clinical validation of the Tempus xO assay

    Science.gov (United States)

    Beaubier, Nike; Tell, Robert; Huether, Robert; Bontrager, Martin; Bush, Stephen; Parsons, Jerod; Shah, Kaanan; Baker, Tim; Selkov, Gene; Taxter, Tim; Thomas, Amber; Bettis, Sam; Khan, Aly; Lau, Denise; Lee, Christina; Barber, Matthew; Cieslik, Marcin; Frankenberger, Casey; Franzen, Amy; Weiner, Ali; Palmer, Gary; Lonigro, Robert; Robinson, Dan; Wu, Yi-Mi; Cao, Xuhong; Lefkofsky, Eric; Chinnaiyan, Arul; White, Kevin P.

    2018-01-01

    We have developed a clinically validated NGS assay that includes tumor, germline and RNA sequencing. We apply this assay to clinical specimens and cell lines, and we demonstrate a clinical sensitivity of 98.4% and positive predictive value of 100% for the clinically actionable variants measured by the assay. We also demonstrate highly accurate copy number measurements and gene rearrangement identification. PMID:29899824

  14. Target validation: linking target and chemical properties to desired product profile.

    Science.gov (United States)

    Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D; Fairlamb, Alan H

    2011-01-01

    The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

  15. Application of RNAi to Genomic Drug Target Validation in Schistosomes.

    Directory of Open Access Journals (Sweden)

    Alessandra Guidi

    2015-05-01

    Full Text Available Concerns over the possibility of resistance developing to praziquantel (PZQ, has stimulated efforts to develop new drugs for schistosomiasis. In addition to the development of improved whole organism screens, the success of RNA interference (RNAi in schistosomes offers great promise for the identification of potential drug targets to initiate drug discovery. In this study we set out to contribute to RNAi based validation of putative drug targets. Initially a list of 24 target candidates was compiled based on the identification of putative essential genes in schistosomes orthologous of C. elegans essential genes. Knockdown of Calmodulin (Smp_026560.2 (Sm-Calm, that topped this list, produced a phenotype characterised by waves of contraction in adult worms but no phenotype in schistosomula. Knockdown of the atypical Protein Kinase C (Smp_096310 (Sm-aPKC resulted in loss of viability in both schistosomula and adults and led us to focus our attention on other kinase genes that were identified in the above list and through whole organism screening of known kinase inhibitor sets followed by chemogenomic evaluation. RNAi knockdown of these kinase genes failed to affect adult worm viability but, like Sm-aPKC, knockdown of Polo-like kinase 1, Sm-PLK1 (Smp_009600 and p38-MAPK, Sm-MAPK p38 (Smp_133020 resulted in an increased mortality of schistosomula after 2-3 weeks, an effect more marked in the presence of human red blood cells (hRBC. For Sm-PLK-1 the same effects were seen with the specific inhibitor, BI2536, which also affected viable egg production in adult worms. For Sm-PLK-1 and Sm-aPKC the in vitro effects were reflected in lower recoveries in vivo. We conclude that the use of RNAi combined with culture with hRBC is a reliable method for evaluating genes important for larval development. However, in view of the slow manifestation of the effects of Sm-aPKC knockdown in adults and the lack of effects of Sm-PLK-1 and Sm-MAPK p38 on adult viability

  16. Creation and Validation of Sintered PTFE BRDF Targets & Standards.

    Science.gov (United States)

    Durell, Christopher; Scharpf, Dan; McKee, Greg; L'Heureux, Michelle; Georgiev, Georgi; Obein, Gael; Cooksey, Catherine

    2015-09-21

    Sintered polytetrafluoroethylene (PTFE) is an extremely stable, near-perfect Lambertian reflecting diffuser and calibration standard material that has been used by national labs, space, aerospace and commercial sectors for over two decades. New uncertainty targets of 2 % on-orbit absolute validation in the Earth Observing Systems community have challenged the industry to improve is characterization and knowledge of almost every aspect of radiometric performance (space and ground). Assuming "near perfect" reflectance for angular dependent measurements is no longer going to suffice for many program needs. The total hemispherical spectral reflectance provides a good mark of general performance; but, without the angular characterization of bidirectional reflectance distribution function (BRDF) measurements, critical data is missing from many applications and uncertainty budgets. Therefore, traceable BRDF measurement capability is needed to characterize sintered PTFE's angular response and provide a full uncertainty profile to users. This paper presents preliminary comparison measurements of the BRDF of sintered PTFE from several laboratories to better quantify the BRDF of sintered PTFE, assess the BRDF measurement comparability between laboratories, and improve estimates of measurement uncertainties under laboratory conditions.

  17. Comprehensive clinical validation of the nuclear stethoscope

    Energy Technology Data Exchange (ETDEWEB)

    Caruana, M.; Jones, R.; Lahiri, A.; Brigden, G.; Rodrigues, E.; Dore, C.; Raftery, E.B.

    1986-10-01

    Five studies were conducted to examine the degree of variability to be expected during the use of the non-imaging nuclear probe (BIOS Inc.) under a variety of clinical conditions. Comparison of the ejection fraction (EF) readings between the nuclear probe and a gamma camera showed good agreement, with the nuclear probe tending to underestimate lower, and overestimate higher camera EF values. It is concluded that the portable, low cost nuclear probe produces accurate EF measurements when compared with the gamma camera.

  18. Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

    Science.gov (United States)

    2017-10-01

    prostate cancer . Cancer Res 70: 7992-8002, 2010 8. Nelson PS: Molecular states underlying an- drogen receptor activation: A framework for thera- peutics...targeting androgen signaling in prostate cancer . J Clin Oncol 30:644-646, 2012 9. Thadani-Mulero M, Nanus DM, Giannakakou P: Androgen receptor on the... prostate cancer . Clin Cancer Res 21:795-807, 2015 17. van Soest RJ, de Morrée ES, Kweldam CF, et al: Targeting the androgen receptor confers in vivo

  19. Transition questions in clinical practice - validity and reproducibility

    DEFF Research Database (Denmark)

    Lauridsen, Henrik Hein

    2008-01-01

    Transition questions in CLINICAL practice - validity and reproducibility Lauridsen HH1, Manniche C3, Grunnet-Nilsson N1, Hartvigsen J1,2 1   Clinical Locomotion Science, Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark. e-mail: hlauridsen......@health.sdu.dk 2   Nordic Institute of Chiropractic and Clinical Biomechanics, Part of Clinical Locomotion Science, Odense, Denmark 3   Backcenter Funen, Part of Clinical Locomotion Science, Ringe, Denmark   Abstract  Understanding a change score is indispensable for interpretation of results from clinical studies...... are reproducible in patients with low back pain and/or leg pain. Despite critique of several biases, our results have reinforced the construct validity of TQ’s as an outcome measure since only 1 hypothesis was rejected. On the basis of our findings we have outlined a proposal for a standardised use of transition...

  20. The validity and clinical utility of purging disorder.

    Science.gov (United States)

    Keel, Pamela K; Striegel-Moore, Ruth H

    2009-12-01

    To review evidence of the validity and clinical utility of Purging Disorder and examine options for the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-V). Articles were identified by computerized and manual searches and reviewed to address five questions about Purging Disorder: Is there "ample" literature? Is the syndrome clearly defined? Can it be measured and diagnosed reliably? Can it be differentiated from other eating disorders? Is there evidence of syndrome validity? Although empirical classification and concurrent validity studies provide emerging support for the distinctiveness of Purging Disorder, questions remain about definition, diagnostic reliability in clinical settings, and clinical utility (i.e., prognostic validity). We discuss strengths and weaknesses associated with various options for the status of Purging Disorder in the DSM-V ranging from making no changes from DSM-IV to designating Purging Disorder a diagnosis on equal footing with Anorexia Nervosa and Bulimia Nervosa.

  1. Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

    Science.gov (United States)

    2016-10-01

    Physics of Cancer Metabolism This application seeks to put together a multidiscipline team of experts in various institutions in USA to assemble and...of this project is to build a research cohort of engaged volunteers that reflects the racial , ethnic, and socioeconomic diversity of New York City...assessed in a randomized, phase III clinical trial. Conflict of interest: Advisory Board: Joe O’Sullivan holds consulting/ advisory roles with Bayer

  2. Target Acquisition: Human Observer Performance Studies and TARGAC Model Validation

    Science.gov (United States)

    1994-06-01

    complete Scenario I run were displayed on a monitor. A transparent sheet was attached to the face of the monitor, the approach route was sketched on...track, passed a mark on the monitor face , the target was at a stop-sign location. The IRIG-B time of that instance was noted, and, since the distance of...route right 100- 80- 60 - 40 C.) 20 [- ion, A20 recognitio 0 0 . identification,C.) . 1I . I - - -• , 4) 1000 2000 3000 4000 SP Target G Q Target I0

  3. CRISPR/Cas9-mediated target validation of the Splicing Inhibitor Pladienolide B

    KAUST Repository

    Aouida, Mustapha; Eid, Ayman; Mahfouz, Magdy M.

    2016-01-01

    CRISPR/Cas9 system confers molecular immunity in archeal and bacterial species against invading foreign nucleic acids. CRISPR/Cas9 system is used for genome engineering applications across diverse eukaryotic species. In this study, we demonstrate the utility of the CRISPR/Cas9 genome engineering system for drug target validation in human cells. Pladienolide B is a natural macrolide with antitumor activities mediated through the inhibition of pre-mRNA splicing. To validate the spliceosomal target of Pladienolide B, we employed the CRSIPR/Cas9 system to introduce targeted mutations in the subunits of the SF3B complex in the HEK293T cells. Our data reveal that targeted mutagenesis of the SF3b1 subunit exhibited higher levels of resistance to Pladienolide B. Therefore, our data validate the spliceosomal target of Pladienolide B and provide a proof of concept on using the CRISPR/Cas9 system for drug target identification and validation.

  4. CRISPR/Cas9-mediated target validation of the Splicing Inhibitor Pladienolide B

    KAUST Repository

    Aouida, Mustapha

    2016-02-24

    CRISPR/Cas9 system confers molecular immunity in archeal and bacterial species against invading foreign nucleic acids. CRISPR/Cas9 system is used for genome engineering applications across diverse eukaryotic species. In this study, we demonstrate the utility of the CRISPR/Cas9 genome engineering system for drug target validation in human cells. Pladienolide B is a natural macrolide with antitumor activities mediated through the inhibition of pre-mRNA splicing. To validate the spliceosomal target of Pladienolide B, we employed the CRSIPR/Cas9 system to introduce targeted mutations in the subunits of the SF3B complex in the HEK293T cells. Our data reveal that targeted mutagenesis of the SF3b1 subunit exhibited higher levels of resistance to Pladienolide B. Therefore, our data validate the spliceosomal target of Pladienolide B and provide a proof of concept on using the CRISPR/Cas9 system for drug target identification and validation.

  5. Development, Validation, and Implementation of a Clinic Nurse Staffing Guideline.

    Science.gov (United States)

    Deeken, Debra Jean; Wakefield, Douglas; Kite, Cora; Linebaugh, Jeanette; Mitchell, Blair; Parkinson, Deidre; Misra, Madhukar

    2017-10-01

    Ensuring that the level of nurse staffing used to care for patients is appropriate to the setting and service intensity is essential for high-quality and cost-effective care. This article describes the development, validation, and implementation of the clinic technical skills permission list developed specifically to guide nurse staffing decisions in physician clinics of an academic medical center. Results and lessons learned in using this staffing guideline are presented.

  6. Completeness and validity in a national clinical thyroid cancer database

    DEFF Research Database (Denmark)

    Londero, Stefano Christian; Mathiesen, Jes Sloth; Krogdahl, Annelise

    2014-01-01

    cancer database: DATHYRCA. STUDY DESIGN AND SETTING: National prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used...... to appraise the validity. For validity assessment 100 cases were randomly selected from the DATHYRCA database; medical records were used as a reference. RESULT: The database held 1934 cases of thyroid carcinoma and completeness of case ascertainment was estimated to 90.9%. Completeness of registration......BACKGROUND: Although a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid...

  7. Validation of a clinical assessment tool for spinal anaesthesia.

    LENUS (Irish Health Repository)

    Breen, D

    2011-07-01

    There is a need for a procedure-specific means of assessment of clinical performance in anaesthesia. The aim of this study was to devise a tool for assessing the performance of spinal anaesthesia, which has both content and construct validity.

  8. Clinical Validation of Point-Source Corneal Topography in Keratoplasty

    NARCIS (Netherlands)

    Vrijling, A C L; Braaf, B.; Snellenburg, J.J.; de Lange, F.; Zaal, M.J.W.; van der Heijde, G.L.; Sicam, V.A.D.P.

    2011-01-01

    Purpose. To validate the clinical performance of point-source corneal topography (PCT) in postpenetrating keratoplasty (PKP) eyes and to compare it with conventional Placido-based topography. Methods. Corneal elevation maps of the anterior corneal surface were obtained from 20 post-PKP corneas using

  9. Content Validation of Athletic Therapy Clinical Presentations in Canada

    Science.gov (United States)

    Lafave, Mark R.; Yeo, Michelle; Westbrook, Khatija; Valdez, Dennis; Eubank, Breda; McAllister, Jenelle

    2016-01-01

    Context: Competency-based education requires strong planning and a vehicle to deliver and track students' progress across their undergraduate programs. Clinical presentations (CPs) are proposed as 1 method to deliver a competency-based curriculum in a Canadian undergraduate athletic therapy program. Objective: Validation of 253 CPs. Setting:…

  10. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress.

    Science.gov (United States)

    Lammers, Twan; Kiessling, Fabian; Hennink, Wim E; Storm, Gert

    2012-07-20

    Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells, active drug targeting to endothelial cells and triggered drug delivery. Significant progress has been made in this area of research both at the preclinical and at the clinical level, and a number of (primarily passively tumor-targeted) nanomedicine formulations have been approved for clinical use. Significant progress has also been made with regard to better understanding the (patho-) physiological principles of drug targeting to tumors. This has led to the identification of several important pitfalls in tumor-targeted drug delivery, including I) overinterpretation of the EPR effect; II) poor tumor and tissue penetration of nanomedicines; III) misunderstanding of the potential usefulness of active drug targeting; IV) irrational formulation design, based on materials which are too complex and not broadly applicable; V) insufficient incorporation of nanomedicine formulations in clinically relevant combination regimens; VI) negligence of the notion that the highest medical need relates to metastasis, and not to solid tumor treatment; VII) insufficient integration of non-invasive imaging techniques and theranostics, which could be used to personalize nanomedicine-based therapeutic interventions; and VIII) lack of (efficacy analyses in) proper animal models, which are physiologically more relevant and more predictive for the clinical situation. These insights strongly suggest that besides making ever more nanomedicine formulations, future efforts should also address some of the conceptual drawbacks of drug targeting to tumors, and that strategies should be developed to overcome these shortcomings. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Polymerase chain reaction with two molecular targets in mucosal leishmaniasis' diagnosis: a validation study

    Directory of Open Access Journals (Sweden)

    Clemencia Ovalle Bracho

    2007-08-01

    Full Text Available We validated the polymerase chain reaction (PCR with a composite reference standard in 61 patients clinically suspected of having mucosal leishmaniasis, 36 of which were cases and 25 were non-cases according to this reference standard. Patient classification and test application were carried out independently by two blind observers. One pair of primers was used to amplify a fragment of 120 bp in the conserved region of kDNA and another pair was used to amplify the internal transcript spacers (ITS rDNA. PCR showed 68.6% (95% CI 59.2-72.6 sensitivity and 92% (95% CI 78.9-97.7 specificity; positive likelihood ratio: 8.6 (95% CI 2.8-31.3 and negative likelihood ratio: 0.3 (95% CI 0.3-0.5, when kDNA molecular target was amplified. The test performed better on sensitivity using this target compared to the ITS rDNA molecular target which showed 40% (95% CI 31.5-42.3 sensitivity and 96% (95% CI 84.1-99.3 specificity; positive likelihood ratio: 10 (95% CI 2.0-58.8 and negative likelihood ratio: 0.6 (95% CI 0.6-0.8. The inter-observer agreement was excellent for both tests. Based upon results obtained and due to low performance of conventional methods for diagnosing mucosal leishmaniasis, we consider PCR with kDNA as molecular target is a useful diagnostic test and the ITS rDNA molecular target is useful when the aim is to identify species.

  12. Targeting dormant micrometastases: rationale, evidence to date and clinical implications.

    Science.gov (United States)

    Hurst, Robert E; Bastian, Anja; Bailey-Downs, Lora; Ihnat, Michael A

    2016-03-01

    In spite of decades of research, cancer survival has increased only modestly. This is because most research is based on models of primary tumors. Slow recognition has begun that disseminated, dormant cancer cells (micrometastatic cells) that are generally resistant to chemotherapy are the culprits in recurrence, and until these are targeted effectively we can expect only slow progress in increasing overall survival from cancer. This paper reviews efforts to understand the mechanisms by which cancer cells can become dormant, and thereby identify potential targets and drugs either on the market or in clinical trials that purport to prevent metastasis. This review targets the most recent literature because several excellent reviews have covered the literature from more than two years ago. The paper also describes recent work in the authors' laboratories to develop a screening-based approach that does not require understanding of mechanisms of action or the molecular target. Success of this approach shows that targeting micrometastatic cells is definitely feasible.

  13. Targeted estimation of nuisance parameters to obtain valid statistical inference.

    Science.gov (United States)

    van der Laan, Mark J

    2014-01-01

    In order to obtain concrete results, we focus on estimation of the treatment specific mean, controlling for all measured baseline covariates, based on observing independent and identically distributed copies of a random variable consisting of baseline covariates, a subsequently assigned binary treatment, and a final outcome. The statistical model only assumes possible restrictions on the conditional distribution of treatment, given the covariates, the so-called propensity score. Estimators of the treatment specific mean involve estimation of the propensity score and/or estimation of the conditional mean of the outcome, given the treatment and covariates. In order to make these estimators asymptotically unbiased at any data distribution in the statistical model, it is essential to use data-adaptive estimators of these nuisance parameters such as ensemble learning, and specifically super-learning. Because such estimators involve optimal trade-off of bias and variance w.r.t. the infinite dimensional nuisance parameter itself, they result in a sub-optimal bias/variance trade-off for the resulting real-valued estimator of the estimand. We demonstrate that additional targeting of the estimators of these nuisance parameters guarantees that this bias for the estimand is second order and thereby allows us to prove theorems that establish asymptotic linearity of the estimator of the treatment specific mean under regularity conditions. These insights result in novel targeted minimum loss-based estimators (TMLEs) that use ensemble learning with additional targeted bias reduction to construct estimators of the nuisance parameters. In particular, we construct collaborative TMLEs (C-TMLEs) with known influence curve allowing for statistical inference, even though these C-TMLEs involve variable selection for the propensity score based on a criterion that measures how effective the resulting fit of the propensity score is in removing bias for the estimand. As a particular special

  14. Clinical validity of prototype personality disorder ratings in adolescents.

    Science.gov (United States)

    Defife, Jared A; Haggerty, Greg; Smith, Scott W; Betancourt, Luis; Ahmed, Zain; Ditkowsky, Keith

    2015-01-01

    A growing body of research shows that personality pathology in adolescents is clinically distinctive and frequently stable into adulthood. A reliable and useful method for rating personality pathology in adolescent patients has the potential to enhance conceptualization, dissemination, and treatment effectiveness. The aim of this study is to examine the clinical validity of a prototype matching approach (derived from the Shedler Westen Assessment Procedure-Adolescent Version) for quantifying personality pathology in an adolescent inpatient sample. Sixty-six adolescent inpatients and their parents or legal guardians completed forms of the Child Behavior Checklist (CBCL) assessing emotional and behavioral problems. Clinical criterion variables including suicide history, substance use, and fights with peers were also assessed. Patients' individual and group therapists on the inpatient unit completed personality prototype ratings. Prototype diagnoses demonstrated substantial reliability (median intraclass correlation coefficient =.75) across independent ratings from individual and group therapists. Personality prototype ratings correlated with the CBCL scales and clinical criterion variables in anticipated and meaningful ways. As seen in prior research with adult samples, prototype personality ratings show clinical validity across independent clinician raters previously unfamiliar with the approach, and they are meaningfully related to clinical symptoms, behavioral problems, and adaptive functioning.

  15. Review on clinical trials of targeted treatments in malignant mesothelioma

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Sørensen, Jens Benn

    2011-01-01

    Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all...

  16. Validation of a clinical critical thinking skills test in nursing

    OpenAIRE

    Shin, Sujin; Jung, Dukyoo; Kim, Sungeun

    2015-01-01

    Purpose: The purpose of this study was to develop a revised version of the clinical critical thinking skills test (CCTS) and to subsequently validate its performance. Methods: This study is a secondary analysis of the CCTS. Data were obtained from a convenience sample of 284 college students in June 2011. Thirty items were analyzed using item response theory and test reliability was assessed. Test-retest reliability was measured using the results of 20 nursing college and graduate school stud...

  17. Validation of a clinical critical thinking skills test in nursing

    Directory of Open Access Journals (Sweden)

    Sujin Shin

    2015-01-01

    Full Text Available Purpose: The purpose of this study was to develop a revised version of the clinical critical thinking skills test (CCTS and to subsequently validate its performance. Methods: This study is a secondary analysis of the CCTS. Data were obtained from a convenience sample of 284 college students in June 2011. Thirty items were analyzed using item response theory and test reliability was assessed. Test-retest reliability was measured using the results of 20 nursing college and graduate school students in July 2013. The content validity of the revised items was analyzed by calculating the degree of agreement between instrument developer intention in item development and the judgments of six experts. To analyze response process validity, qualitative data related to the response processes of nine nursing college students obtained through cognitive interviews were analyzed. Results: Out of initial 30 items, 11 items were excluded after the analysis of difficulty and discrimination parameter. When the 19 items of the revised version of the CCTS were analyzed, levels of item difficulty were found to be relatively low and levels of discrimination were found to be appropriate or high. The degree of agreement between item developer intention and expert judgments equaled or exceeded 50%. Conclusion: From above results, evidence of the response process validity was demonstrated, indicating that subjects respondeds as intended by the test developer. The revised 19-item CCTS was found to have sufficient reliability and validity and will therefore represents a more convenient measurement of critical thinking ability.

  18. Validation of a clinical critical thinking skills test in nursing.

    Science.gov (United States)

    Shin, Sujin; Jung, Dukyoo; Kim, Sungeun

    2015-01-27

    The purpose of this study was to develop a revised version of the clinical critical thinking skills test (CCTS) and to subsequently validate its performance. This study is a secondary analysis of the CCTS. Data were obtained from a convenience sample of 284 college students in June 2011. Thirty items were analyzed using item response theory and test reliability was assessed. Test-retest reliability was measured using the results of 20 nursing college and graduate school students in July 2013. The content validity of the revised items was analyzed by calculating the degree of agreement between instrument developer intention in item development and the judgments of six experts. To analyze response process validity, qualitative data related to the response processes of nine nursing college students obtained through cognitive interviews were analyzed. Out of initial 30 items, 11 items were excluded after the analysis of difficulty and discrimination parameter. When the 19 items of the revised version of the CCTS were analyzed, levels of item difficulty were found to be relatively low and levels of discrimination were found to be appropriate or high. The degree of agreement between item developer intention and expert judgments equaled or exceeded 50%. From above results, evidence of the response process validity was demonstrated, indicating that subjects respondeds as intended by the test developer. The revised 19-item CCTS was found to have sufficient reliability and validity and will therefore represents a more convenient measurement of critical thinking ability.

  19. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy

    Science.gov (United States)

    Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J.; Rivière, Isabelle

    2009-01-01

    Summary Based on promising pre-clinical data demonstrating the eradication of systemic B cell malignancies by CD19-targeted T lymphocytes in vivo in SCID beige mouse models, we are launching Phase 1 clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). We present here the validation of the bioprocess we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads® CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semi-closed culture system using the Wave bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in SCID beige mice bearing disseminated tumors. The validation requirements in terms of T cell expansion, T cell transduction with the 1928z CAR, biological activity, quality control testing and release criteria were met for all four validation runs using apheresis products from patients with CLL. Additionally, following expansion of the T cells, the diversity of the skewed Vβ T cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemo-refractory CLL and in patients with relapsed ALL. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any chimeric antigen receptor or T cell receptor. PMID:19238016

  20. Clinical and psychosocial predictors of exceeding target length of stay during inpatient stroke rehabilitation.

    Science.gov (United States)

    Lai, Wesley; Buttineau, Mackenzie; Harvey, Jennifer K; Pucci, Rebecca A; Wong, Anna P M; Dell'Erario, Linda; Bosnyak, Stephanie; Reid, Shannon; Salbach, Nancy M

    2017-10-01

    In Ontario, Canada, patients admitted to inpatient rehabilitation hospitals post-stroke are classified into rehabilitation patient groups based on age and functional level. Clinical practice guidelines, called quality-based procedures, recommend a target length of stay (LOS) for each group. The study objective was to evaluate the extent to which patients post-stroke at an inpatient rehabilitation hospital are meeting LOS targets and to identify patient characteristics that predict exceeding target LOS. A quantitative, longitudinal study from an inpatient rehabilitation hospital was conducted. Participants included adult patients (≥18 years) with stroke, admitted to an inpatient rehabilitation hospital between 2014 and 2015. The percentage of patients exceeding the recommended target LOS was determined. Logistic regression was performed to identify clinical and psychosocial patient characteristics associated with exceeding target LOS after adjusting for stroke severity. Of 165 patients, 38.8% exceeded their target LOS. Presence of ataxia, recurrent stroke, living alone, absence of a caregiver at admission, and acquiring a caregiver during hospital LOS was each associated with significantly higher odds of exceeding target LOS in comparison to patients without these characteristics after adjusting for stroke severity (p stroke-specific factors may be helpful to adjust LOS expectations and promote efficient resource allocation. This exploratory study was limited to findings from one inpatient rehabilitation hospital. Cross-validation of results using data-sets from multiple rehabilitation hospitals across Ontario is recommended.

  1. Targeting small airways in asthma: Improvement in clinical benefit?

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2010-01-01

    Background and Aim:  Disease control is not achieved in a substantial proportion of patients with asthma. Recent advances in aerosol formulations and delivery devices may offer more effective therapy. This review will focus on the importance and potential clinical benefit of targeting the lung...... half the daily dose with no increased risk of systemic effects. Clinical studies of adults with asthma have shown a greater effect of ultrafine ICS, compared with non-ultrafine ICS, on quality of life, small airway patency, and markers of pulmonary and systemic inflammation, but no difference...... with regard to conventional clinical indices of lung function and asthma control. Conclusions:  Asthma patients treated with ultrafine ICS, compared with non-ultrafine ICS, have at least similar chance of achieving asthma control at a lower daily dose. Further clinical studies are needed to explore whether...

  2. Targeting small airways in asthma: Improvement in clinical benefit?

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2010-01-01

    Background and Aim: Disease control is not achieved in a substantial proportion of patients with asthma. Recent advances in aerosol formulations and delivery devices may offer more effective therapy. This review will focus on the importance and potential clinical benefit of targeting the lung...... half the daily dose with no increased risk of systemic effects. Clinical studies of adults with asthma have shown a greater effect of ultrafine ICS, compared with non-ultrafine ICS, on quality of life, small airway patency, and markers of pulmonary and systemic inflammation, but no difference...... with regard to conventional clinical indices of lung function and asthma control. Conclusions: Asthma patients treated with ultrafine ICS, compared with non-ultrafine ICS, have at least similar chance of achieving asthma control at a lower daily dose. Further clinical studies are needed to explore whether...

  3. Clinical endpoint adjudication in a contemporary all-comers coronary stent investigation: methodology and external validation.

    Science.gov (United States)

    Vranckx, Pascal; McFadden, Eugene; Cutlip, Donald E; Mehran, Roxana; Swart, Michael; Kint, P P; Zijlstra, Felix; Silber, Sigmund; Windecker, Stephan; Serruys, Patrick W C J

    2013-01-01

    Globalisation in coronary stent research calls for harmonization of clinical endpoint definitions and event adjudication. Little has been published about the various processes used for event adjudication or their impact on outcome reporting. We performed a validation of the clinical event committee (CEC) adjudication process on 100 suspected events in the RESOLUTE All-comers trial (Resolute-AC). Two experienced Clinical Research Organisations (CRO) that had already extensive internal validation processes in place, participated in the study. After initial adjudication by the primary-CEC, events were cross-adjudicated by an external-CEC using the same definitions. Major discrepancies affecting the primary end point of target-lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), or clinically-indicated target-lesion revascularization (CI-TLR), were analysed by an independent oversight committee who provided recommendations for harmonization. Discordant adjudications were reconsidered by the primary CEC. Subsequently, the RAC database was interrogated for cases that based on these recommendations merited re-adjudication and these cases were also re-adjudicated by the primary CEC. Final discrepancies in adjudication of individual components of TLF occurred in 7 out of 100 events in 5 patients. Discrepancies for the (hierarchical) primary endpoint occurred in 5 events (2 cardiac deaths and 3 TV-MI). After application of harmonization recommendations to the overall RAC population (n=2292), the primary CEC adjudicated 3 additional clinical-TLRs and considered 1 TV-MI as no event. A harmonization process provided a high level of concordance for event adjudication and improved accuracy for final event reporting. These findings suggest it is feasible to pool clinical event outcome data across clinical trials even when different CECs are responsible for event adjudication. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Validation of Clinical Observations of Mastication in Persons with ALS.

    Science.gov (United States)

    Simione, Meg; Wilson, Erin M; Yunusova, Yana; Green, Jordan R

    2016-06-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that can result in difficulties with mastication leading to malnutrition, choking or aspiration, and reduced quality of life. When evaluating mastication, clinicians primarily observe spatial and temporal aspects of jaw motion. The reliability and validity of clinical observations for detecting jaw movement abnormalities is unknown. The purpose of this study is to determine the reliability and validity of clinician-based ratings of chewing performance in neuro-typical controls and persons with varying degrees of chewing impairments due to ALS. Adults chewed a solid food consistency while full-face video were recorded along with jaw kinematic data using a 3D optical motion capture system. Five experienced speech-language pathologists watched the videos and rated the spatial and temporal aspects of chewing performance. The jaw kinematic data served as the gold-standard for validating the clinicians' ratings. Results showed that the clinician-based rating of temporal aspects of chewing performance had strong inter-rater reliability and correlated well with comparable kinematic measures. In contrast, the reliability of rating the spatial and spatiotemporal aspects of chewing (i.e., range of motion of the jaw, consistency of the chewing pattern) was mixed. Specifically, ratings of range of motion were at best only moderately reliable. Ratings of chewing movement consistency were reliable but only weakly correlated with comparable measures of jaw kinematics. These findings suggest that clinician ratings of temporal aspects of chewing are appropriate for clinical use, whereas ratings of the spatial and spatiotemporal aspects of chewing may not be reliable or valid.

  5. Clinical target volume for rectal cancer. Preoperative radiotherapy

    International Nuclear Information System (INIS)

    Lorchel, F.; Bossel, J.F.; Baron, M.H.; Goubard, O.; Bartholomot, B.; Mantion, G.; Pelissier, E.P.; Maingon, P.

    2001-01-01

    The total meso-rectal excision allows the marked increase of the local control rate in rectal cancer. Therefore, the meso-rectal space is the usual field for the spread of rectal cancer cells. It could therefore be considered as the clinical target volume in the preoperative plan by the radiation oncologist. We propose to identify the mesorectum on anatomical structures of a treatment-position CT scan. (authors)

  6. Approaches to Validate and Manipulate RNA Targets with Small Molecules in Cells.

    Science.gov (United States)

    Childs-Disney, Jessica L; Disney, Matthew D

    2016-01-01

    RNA has become an increasingly important target for therapeutic interventions and for chemical probes that dissect and manipulate its cellular function. Emerging targets include human RNAs that have been shown to directly cause cancer, metabolic disorders, and genetic disease. In this review, we describe various routes to obtain bioactive compounds that target RNA, with a particular emphasis on the development of small molecules. We use these cases to describe approaches that are being developed for target validation, which include target-directed cleavage, classic pull-down experiments, and covalent cross-linking. Thus, tools are available to design small molecules to target RNA and to identify the cellular RNAs that are their targets.

  7. Clinical Evaluation of Stereotactic Target Localization Using 3-Tesla MRI for Radiosurgery Planning

    International Nuclear Information System (INIS)

    MacFadden, Derek; Zhang Beibei; Brock, Kristy K.; Hodaie, Mojgan; Laperriere, Normand; Schwartz, Michael; Tsao, May; Stainsby, Jeffrey; Lockwood, Gina; Mikulis, David; Menard, Cynthia

    2010-01-01

    Purpose: Increasing the magnetic resonance imaging (MRI) field strength can improve image resolution and quality, but concerns remain regarding the influence on geometric fidelity. The objectives of the present study were to spatially investigate the effect of 3-Tesla (3T) MRI on clinical target localization for stereotactic radiosurgery. Methods and Materials: A total of 39 patients were enrolled in a research ethics board-approved prospective clinical trial. Imaging (1.5T and 3T MRI and computed tomography) was performed after stereotactic frame placement. Stereotactic target localization at 1.5T vs. 3T was retrospectively analyzed in a representative cohort of patients with tumor (n = 4) and functional (n = 5) radiosurgical targets. The spatial congruency of the tumor gross target volumes was determined by the mean discrepancy between the average gross target volume surfaces at 1.5T and 3T. Reproducibility was assessed by the displacement from an averaged surface and volume congruency. Spatial congruency and the reproducibility of functional radiosurgical targets was determined by comparing the mean and standard deviation of the isocenter coordinates. Results: Overall, the mean absolute discrepancy across all patients was 0.67 mm (95% confidence interval, 0.51-0.83), significantly .4), and the gross target volume surface mean displacements were similar within and between users. The overall average isocenter coordinate discrepancy for the functional targets at 1.5T and 3T was 0.33 mm (95% confidence interval, 0.20-0.48), with no patient-specific differences between the mean values (p >.2) or standard deviations (p >.1). Conclusion: Our results have provided clinically relevant evidence supporting the spatial validity of 3T MRI for use in stereotactic radiosurgery under the imaging conditions used.

  8. Patient Experiences with the Preoperative Assessment Clinic (PEPAC): validation of an instrument to measure patient experiences

    NARCIS (Netherlands)

    Edward, G. M.; Lemaire, L. C.; Preckel, B.; Oort, F. J.; Bucx, M. J. L.; Hollmann, M. W.; de Haes, J. C. J. M.

    2007-01-01

    Background. Presently, no comprehensive and validated questionnaire to measure patient experiences of the preoperative assessment clinic (PAC) is available. We developed and validated the Patient Experiences with the Preoperative Assessment Clinic (PEPAC) questionnaire, which can be used for

  9. Peptide deformylase as an antibacterial drug target: target validation and resistance development.

    Science.gov (United States)

    Apfel, C M; Locher, H; Evers, S; Takács, B; Hubschwerlen, C; Pirson, W; Page, M G; Keck, W

    2001-04-01

    New inhibitors of peptide deformylase (PDF) which are very potent against the isolated enzyme and show a certain degree of antibacterial activity have recently been synthesized by our group. Several lines of experimental evidence indicate that these inhibitors indeed interfere with the target enzyme in the bacterial cell. (i) The inhibition of Escherichia coli growth could be counteracted by overexpression of PDF from different organisms, including E. coli, Streptococcus pneumoniae, and Haemophilus influenzae. Conversely, reduced expression of PDF in S. pneumoniae resulted in an increased susceptibility to the inhibitors. (ii) Proteome analysis on two-dimensional gels revealed a shift for many proteins towards lower pI in the presence of PDF inhibitors, as would be expected if the proteins still carry their N-formyl-Met terminus. (iii) PDF inhibitors show no antimicrobial activity against E. coli under conditions that make growth independent of formylation and deformylation. The antibacterial activity in E. coli was characterized as bacteriostatic. Furthermore, the development of resistance in E. coli was observed to occur with high frequency (10(-7)). Resistant mutants show a reduced growth rate, and DNA sequence analysis revealed mutations in their formyl transferase gene. Taking all these aspects into account, we conclude that PDF may not be an optimal target for broad-spectrum antibacterial agents.

  10. External validation and comparison of three pediatric clinical dehydration scales.

    Directory of Open Access Journals (Sweden)

    Joshua Jauregui

    Full Text Available OBJECTIVE: To prospectively validate three popular clinical dehydration scales and overall physician gestalt in children with vomiting or diarrhea relative to the criterion standard of percent weight change with rehydration. METHODS: We prospectively enrolled a non-consecutive cohort of children ≤ 18 years of age with an acute episode of diarrhea or vomiting. Patient weight, clinical scale variables and physician clinical impression, or gestalt, were recorded before and after fluid resuscitation in the emergency department and upon hospital discharge. The percent weight change from presentation to discharge was used to calculate the degree of dehydration, with a weight change of ≥ 5% considered significant dehydration. Receiver operating characteristics (ROC curves were constructed for each of the three clinical scales and physician gestalt. Sensitivity and specificity were calculated based on the best cut-points of the ROC curve. RESULTS: We approached 209 patients, and of those, 148 were enrolled and 113 patients had complete data for analysis. Of these, 10.6% had significant dehydration based on our criterion standard. The Clinical Dehydration Scale (CDS and Gorelick scales both had an area under the ROC curve (AUC statistically different from the reference line with AUCs of 0.72 (95% CI 0.60, 0.84 and 0.71 (95% CI 0.57, 0.85 respectively. The World Health Organization (WHO scale and physician gestalt had AUCs of 0.61 (95% CI 0.45, 0.77 and 0.61 (0.44, 0.78 respectively, which were not statistically significant. CONCLUSION: The Gorelick scale and Clinical Dehydration Scale were fair predictors of dehydration in children with diarrhea or vomiting. The World Health Organization scale and physician gestalt were not helpful predictors of dehydration in our cohort.

  11. External validation and comparison of three pediatric clinical dehydration scales.

    Science.gov (United States)

    Jauregui, Joshua; Nelson, Daniel; Choo, Esther; Stearns, Branden; Levine, Adam C; Liebmann, Otto; Shah, Sachita P

    2014-01-01

    To prospectively validate three popular clinical dehydration scales and overall physician gestalt in children with vomiting or diarrhea relative to the criterion standard of percent weight change with rehydration. We prospectively enrolled a non-consecutive cohort of children ≤ 18 years of age with an acute episode of diarrhea or vomiting. Patient weight, clinical scale variables and physician clinical impression, or gestalt, were recorded before and after fluid resuscitation in the emergency department and upon hospital discharge. The percent weight change from presentation to discharge was used to calculate the degree of dehydration, with a weight change of ≥ 5% considered significant dehydration. Receiver operating characteristics (ROC) curves were constructed for each of the three clinical scales and physician gestalt. Sensitivity and specificity were calculated based on the best cut-points of the ROC curve. We approached 209 patients, and of those, 148 were enrolled and 113 patients had complete data for analysis. Of these, 10.6% had significant dehydration based on our criterion standard. The Clinical Dehydration Scale (CDS) and Gorelick scales both had an area under the ROC curve (AUC) statistically different from the reference line with AUCs of 0.72 (95% CI 0.60, 0.84) and 0.71 (95% CI 0.57, 0.85) respectively. The World Health Organization (WHO) scale and physician gestalt had AUCs of 0.61 (95% CI 0.45, 0.77) and 0.61 (0.44, 0.78) respectively, which were not statistically significant. The Gorelick scale and Clinical Dehydration Scale were fair predictors of dehydration in children with diarrhea or vomiting. The World Health Organization scale and physician gestalt were not helpful predictors of dehydration in our cohort.

  12. Implementation of Targeted Next Generation Sequencing in Clinical Diagnostics

    DEFF Research Database (Denmark)

    Larsen, Martin Jakob; Burton, Mark; Thomassen, Mads

    Accurate mutation detection is essential in clinical genetic diagnostics of monogenic hereditary diseases. Targeted next generation sequencing (NGS) provides a promising and cost-effective alternative to Sanger sequencing and MLPA analysis currently used in most diagnostic laboratories. One...... of mutation positive controls previously characterized by Sanger/MLPA analysis. Agilent SureSelect Target-Enrichment kits were used for capturing a set of genes associated with hereditary breast and ovarian cancer syndrome and a compilation of genes involved in multiple rare single gene disorders......, respectively. For diagnostics, the sequencing coverage is essential, wherefore a minimum coverage of 30x per nucleotide in the coding regions was used as our primary quality criterion. For the majority of the included genes, we obtained adequate gene coverage, in which we were able to detect 100% of the known...

  13. Genomic Biomarkers for Personalized Medicine: Development and Validation in Clinical Studies

    Directory of Open Access Journals (Sweden)

    Shigeyuki Matsui

    2013-01-01

    Full Text Available The establishment of high-throughput technologies has brought substantial advances to our understanding of the biology of many diseases at the molecular level and increasing expectations on the development of innovative molecularly targeted treatments and molecular biomarkers or diagnostic tests in the context of clinical studies. In this review article, we position the two critical statistical analyses of high-dimensional genomic data, gene screening and prediction, in the framework of development and validation of genomic biomarkers or signatures, through taking into consideration the possible different strategies for developing genomic signatures. A wide variety of biomarker-based clinical trial designs to assess clinical utility of a biomarker or a new treatment with a companion biomarker are also discussed.

  14. Experience of targeted Usher exome sequencing as a clinical test

    Science.gov (United States)

    Besnard, Thomas; García-García, Gema; Baux, David; Vaché, Christel; Faugère, Valérie; Larrieu, Lise; Léonard, Susana; Millan, Jose M; Malcolm, Sue; Claustres, Mireille; Roux, Anne-Françoise

    2014-01-01

    We show that massively parallel targeted sequencing of 19 genes provides a new and reliable strategy for molecular diagnosis of Usher syndrome (USH) and nonsyndromic deafness, particularly appropriate for these disorders characterized by a high clinical and genetic heterogeneity and a complex structure of several of the genes involved. A series of 71 patients including Usher patients previously screened by Sanger sequencing plus newly referred patients was studied. Ninety-eight percent of the variants previously identified by Sanger sequencing were found by next-generation sequencing (NGS). NGS proved to be efficient as it offers analysis of all relevant genes which is laborious to reach with Sanger sequencing. Among the 13 newly referred Usher patients, both mutations in the same gene were identified in 77% of cases (10 patients) and one candidate pathogenic variant in two additional patients. This work can be considered as pilot for implementing NGS for genetically heterogeneous diseases in clinical service. PMID:24498627

  15. Design and Validation of CRISPR/Cas9 Systems for Targeted Gene Modification in Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Lee, Ciaran M; Zhu, Haibao; Davis, Timothy H; Deshmukh, Harshahardhan; Bao, Gang

    2017-01-01

    The CRISPR/Cas9 system is a powerful tool for precision genome editing. The ability to accurately modify genomic DNA in situ with single nucleotide precision opens up new possibilities for not only basic research but also biotechnology applications and clinical translation. In this chapter, we outline the procedures for design, screening, and validation of CRISPR/Cas9 systems for targeted modification of coding sequences in the human genome and how to perform genome editing in induced pluripotent stem cells with high efficiency and specificity.

  16. Multimodality molecular imaging - from target description to clinical studies

    International Nuclear Information System (INIS)

    Schober, O.; Rahbar, K.; Riemann, B.

    2009-01-01

    This highlight lecture was presented at the closing session of the Annual Congress of the European Association of Nuclear Medicine (EANM) in Munich on 15 October 2008. The Congress was a great success: there were more than 4,000 participants, and 1,597 abstracts were submitted. Of these, 1,387 were accepted for oral or poster presentation, with a rejection rate of 14%. In this article a choice was made from 100 of the 500 lectures which received the highest scores by the scientific review panel. This article outlines the major findings and trends at the EANM 2008, and is only a brief summary of the large number of outstanding abstracts presented. Among the great number of oral and poster presentations covering nearly all fields of nuclear medicine some headlines have to be defined highlighting the development of nuclear medicine in the 21st century. This review focuses on the increasing impact of molecular and multimodality imaging in the field of nuclear medicine. In addition, the question may be asked as to whether the whole spectrum of nuclear medicine is nothing other than molecular imaging and therapy. Furthermore, molecular imaging will and has to go ahead to multimodality imaging. In view of this background the review was structured according to the single steps of molecular imaging, i.e. from target description to clinical studies. The following topics are addressed: targets, radiochemistry and radiopharmacy, devices and computer science, animals and preclinical evaluations, and patients and clinical evaluations. (orig.)

  17. Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

    Directory of Open Access Journals (Sweden)

    Peleg Rider

    2016-01-01

    Full Text Available Proinflammatory cytokines are potent mediators of numerous biological processes and are tightly regulated in the body. Chronic uncontrolled levels of such cytokines can initiate and derive many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. Over the past few years, new innovative biological agents for blocking and regulating cytokine activities have emerged. Here, we review some of the most recent approaches of cytokine targeting, focusing on anti-TNF antibodies or recombinant TNF decoy receptor, recombinant IL-1 receptor antagonist (IL-1Ra and anti-IL-1 antibodies, anti-IL-6 receptor antibodies, and TH17 targeting antibodies. We discuss their effects as biologic drugs, as evaluated in numerous clinical trials, and highlight their therapeutic potential as well as emphasize their inherent limitations and clinical risks. We suggest that while systemic blocking of proinflammatory cytokines using biological agents can ameliorate disease pathogenesis and progression, it may also abrogate the hosts defense against infections. Moreover, we outline the rational need to develop new therapies, which block inflammatory cytokines only at sites of inflammation, while enabling their function systemically.

  18. Validation of a next-generation sequencing assay for clinical molecular oncology.

    Science.gov (United States)

    Cottrell, Catherine E; Al-Kateb, Hussam; Bredemeyer, Andrew J; Duncavage, Eric J; Spencer, David H; Abel, Haley J; Lockwood, Christina M; Hagemann, Ian S; O'Guin, Stephanie M; Burcea, Lauren C; Sawyer, Christopher S; Oschwald, Dayna M; Stratman, Jennifer L; Sher, Dorie A; Johnson, Mark R; Brown, Justin T; Cliften, Paul F; George, Bijoy; McIntosh, Leslie D; Shrivastava, Savita; Nguyen, Tudung T; Payton, Jacqueline E; Watson, Mark A; Crosby, Seth D; Head, Richard D; Mitra, Robi D; Nagarajan, Rakesh; Kulkarni, Shashikant; Seibert, Karen; Virgin, Herbert W; Milbrandt, Jeffrey; Pfeifer, John D

    2014-01-01

    Currently, oncology testing includes molecular studies and cytogenetic analysis to detect genetic aberrations of clinical significance. Next-generation sequencing (NGS) allows rapid analysis of multiple genes for clinically actionable somatic variants. The WUCaMP assay uses targeted capture for NGS analysis of 25 cancer-associated genes to detect mutations at actionable loci. We present clinical validation of the assay and a detailed framework for design and validation of similar clinical assays. Deep sequencing of 78 tumor specimens (≥ 1000× average unique coverage across the capture region) achieved high sensitivity for detecting somatic variants at low allele fraction (AF). Validation revealed sensitivities and specificities of 100% for detection of single-nucleotide variants (SNVs) within coding regions, compared with SNP array sequence data (95% CI = 83.4-100.0 for sensitivity and 94.2-100.0 for specificity) or whole-genome sequencing (95% CI = 89.1-100.0 for sensitivity and 99.9-100.0 for specificity) of HapMap samples. Sensitivity for detecting variants at an observed 10% AF was 100% (95% CI = 93.2-100.0) in HapMap mixes. Analysis of 15 masked specimens harboring clinically reported variants yielded concordant calls for 13/13 variants at AF of ≥ 15%. The WUCaMP assay is a robust and sensitive method to detect somatic variants of clinical significance in molecular oncology laboratories, with reduced time and cost of genetic analysis allowing for strategic patient management. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  19. Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

    Science.gov (United States)

    Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

    2015-10-13

    Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

  20. [Multicenter validation of the clinical dehydration scale for children].

    Science.gov (United States)

    Gravel, J; Manzano, S; Guimont, C; Lacroix, L; Gervaix, A; Bailey, B

    2010-12-01

    Dehydration is an important complication for sick children. The Clinical Dehydration Scale for children (CDS) measures dehydration based on 4 clinical signs: general appearance, eyes, saliva, and tears. To validate the association between the CDS and markers of dehydration in children aged 1 month to 5 years visiting emergency departments (EDs) for vomiting and/or diarrhea. An international prospective cohort study conducted in 3 university-affiliated EDs in 2009. Participants were a convenience sample of children aged 1-60 months presenting to the ED for acute vomiting and/or diarrhea. Following triage, a research nurse obtained informed consent and evaluated dehydration using the CDS. A few days after recovery, another research assistant weighed participants at home. The primary outcome was the percentage of dehydration calculated by the difference in weight at first evaluation and after recovery. Secondary outcomes included proportion of blood test measurements, intravenous use, hospitalization, and inter-rater agreement. During the study period, 264 children were recruited and data regarding weight and dehydration scores were complete for 219 (83%). According to the CDS, 88 had no dehydration, 159 some dehydration, and 15 moderate or severe dehydration. A Chi-square test showed a statistical association between CDS and weight gain, the occurrence of blood tests, intravenous rehydration, hospitalization, and abnormal plasmatic bicarbonate. Good inter-rater correlation was found among participants (linear weighted Kappa score of 0.65; (95% CI, 0.43-0.87). CDS categories correlate with markers of dehydration for young children complaining of vomiting and/or diarrhea in the ED. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  1. SPIE 9639-49 Creation and Validation of Sintered PTFE BRDF Targets & Standards

    OpenAIRE

    Durell, Christopher; Scharpf, Dan; McKee, Greg; L’Heureux, Michelle; Georgiev, Georgi; Obein, Gael; Cooksey, Catherine

    2015-01-01

    Sintered polytetrafluoroethylene (PTFE) is an extremely stable, near-perfect Lambertian reflecting diffuser and calibration standard material that has been used by national labs, space, aerospace and commercial sectors for over two decades. New uncertainty targets of 2 % on-orbit absolute validation in the Earth Observing Systems community have challenged the industry to improve is characterization and knowledge of almost every aspect of radiometric performance (space and ground). Assuming “n...

  2. A targeted metabolomics approach for clinical diagnosis of inborn errors of metabolism.

    Science.gov (United States)

    Jacob, Minnie; Malkawi, Abeer; Albast, Nour; Al Bougha, Salam; Lopata, Andreas; Dasouki, Majed; Abdel Rahman, Anas M

    2018-09-26

    Metabolome, the ultimate functional product of the genome, can be studied through identification and quantification of small molecules. The global metabolome influences the individual phenotype through clinical and environmental interventions. Metabolomics has become an integral part of clinical research and allowed for another dimension of better understanding of disease pathophysiology and mechanism. More than 95% of the clinical biochemistry laboratory routine workload is based on small molecular identification, which can potentially be analyzed through metabolomics. However, multiple challenges in clinical metabolomics impact the entire workflow and data quality, thus the biological interpretation needs to be standardized for a reproducible outcome. Herein, we introduce the establishment of a comprehensive targeted metabolomics method for a panel of 220 clinically relevant metabolites using Liquid chromatography-tandem mass spectrometry (LC-MS/MS) standardized for clinical research. The sensitivity, reproducibility and molecular stability of each targeted metabolite (amino acids, organic acids, acylcarnitines, sugars, bile acids, neurotransmitters, polyamines, and hormones) were assessed under multiple experimental conditions. The metabolic tissue distribution was determined in various rat organs. Furthermore, the method was validated in dry blood spot (DBS) samples collected from patients known to have various inborn errors of metabolism (IEMs). Using this approach, our panel appears to be sensitive and robust as it demonstrated differential and unique metabolic profiles in various rat tissues. Also, as a prospective screening method, this panel of diverse metabolites has the ability to identify patients with a wide range of IEMs who otherwise may need multiple, time-consuming and expensive biochemical assays causing a delay in clinical management. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

    Science.gov (United States)

    Scott, Robert A.; Freitag, Daniel F.; Li, Li; Chu, Audrey Y.; Surendran, Praveen; Young, Robin; Grarup, Niels; Stancáková, Alena; Chen, Yuning; V.Varga, Tibor; Yaghootkar, Hanieh; Luan, Jian'an; Zhao, Jing Hua; Willems, Sara M.; Wessel, Jennifer; Wang, Shuai; Maruthur, Nisa; Michailidou, Kyriaki; Pirie, Ailith; van der Lee, Sven J.; Gillson, Christopher; Olama, Ali Amin Al; Amouyel, Philippe; Arriola, Larraitz; Arveiler, Dominique; Aviles-Olmos, Iciar; Balkau, Beverley; Barricarte, Aurelio; Barroso, Inês; Garcia, Sara Benlloch; Bis, Joshua C.; Blankenberg, Stefan; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Borecki, Ingrid B.; Bork-Jensen, Jette; Bowden, Sarah; Caldas, Carlos; Caslake, Muriel; Cupples, L. Adrienne; Cruchaga, Carlos; Czajkowski, Jacek; den Hoed, Marcel; Dunn, Janet A.; Earl, Helena M.; Ehret, Georg B.; Ferrannini, Ele; Ferrieres, Jean; Foltynie, Thomas; Ford, Ian; Forouhi, Nita G.; Gianfagna, Francesco; Gonzalez, Carlos; Grioni, Sara; Hiller, Louise; Jansson, Jan-Håkan; Jørgensen, Marit E.; Jukema, J. Wouter; Kaaks, Rudolf; Kee, Frank; Kerrison, Nicola D.; Key, Timothy J.; Kontto, Jukka; Kote-Jarai, Zsofia; Kraja, Aldi T.; Kuulasmaa, Kari; Kuusisto, Johanna; Linneberg, Allan; Liu, Chunyu; Marenne, Gaëlle; Mohlke, Karen L.; Morris, Andrew P.; Muir, Kenneth; Müller-Nurasyid, Martina; Munroe, Patricia B.; Navarro, Carmen; Nielsen, Sune F.; Nilsson, Peter M.; Nordestgaard, Børge G.; Packard, Chris J.; Palli, Domenico; Panico, Salvatore; Peloso, Gina M.; Perola, Markus; Peters, Annette; Poole, Christopher J.; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Salomaa, Veikko; Sánchez, María-José; Sattar, Naveed; Sharp, Stephen J.; Sims, Rebecca; Slimani, Nadia; Smith, Jennifer A.; Thompson, Deborah J.; Trompet, Stella; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.; Virtamo, Jarmo; Walker, Mark; Walter, Klaudia; Abraham, Jean E.; Amundadottir, Laufey T.; Aponte, Jennifer L.; Butterworth, Adam S.; Dupuis, Josée; Easton, Douglas F.; Eeles, Rosalind A.; Erdmann, Jeanette; Franks, Paul W.; Frayling, Timothy M.; Hansen, Torben; Howson, Joanna M. M.; Jørgensen, Torben; Kooner, Jaspal; Laakso, Markku; Langenberg, Claudia; McCarthy, Mark I.; Pankow, James S.; Pedersen, Oluf; Riboli, Elio; Rotter, Jerome I.; Saleheen, Danish; Samani, Nilesh J.; Schunkert, Heribert; Vollenweider, Peter; O'Rahilly, Stephen; Deloukas, Panos; Danesh, John; Goodarzi, Mark O.; Kathiresan, Sekar; Meigs, James B.; Ehm, Margaret G.; Wareham, Nicholas J.; Waterworth, Dawn M.

    2016-01-01

    Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to inform development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in 6 genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing, and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr;rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and lower T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomised controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process. PMID:27252175

  4. The accomplishments of lithium target and test facility validation activities in the IFMIF/EVEDA phase

    Science.gov (United States)

    Arbeiter, Frederik; Baluc, Nadine; Favuzza, Paolo; Gröschel, Friedrich; Heidinger, Roland; Ibarra, Angel; Knaster, Juan; Kanemura, Takuji; Kondo, Hiroo; Massaut, Vincent; Saverio Nitti, Francesco; Miccichè, Gioacchino; O'hira, Shigeru; Rapisarda, David; Sugimoto, Masayoshi; Wakai, Eiichi; Yokomine, Takehiko

    2018-01-01

    As part of the engineering validation and engineering design activities (EVEDA) phase for the international fusion materials irradiation facility IFMIF, major elements of a lithium target facility and the test facility were designed, prototyped and validated. For the lithium target facility, the EVEDA lithium test loop was built at JAEA and used to test the stability (waves and long term) of the lithium flow in the target, work out the startup procedures, and test lithium purification and analysis. It was confirmed by experiments in the Lifus 6 plant at ENEA that lithium corrosion on ferritic martensitic steels is acceptably low. Furthermore, complex remote handling procedures for the remote maintenance of the target in the test cell environment were successfully practiced. For the test facility, two variants of a high flux test module were prototyped and tested in helium loops, demonstrating their good capabilities of maintaining the material specimens at the desired temperature with a low temperature spread. Irradiation tests were performed for heated specimen capsules and irradiation instrumentation in the BR2 reactor at SCK-CEN. The small specimen test technique, essential for obtaining material test results with limited irradiation volume, was advanced by evaluating specimen shape and test technique influences.

  5. Targeting NK cells for anti-cancer immunotherapy: clinical and pre-clinical approaches

    Directory of Open Access Journals (Sweden)

    Sebastian eCarotta

    2016-04-01

    Full Text Available The recent success of checkpoint blockade has highlighted the potential of immunotherapy approaches for cancer treatment. While the majority of approved immunotherapy drugs target T cell subsets, it is appreciated that other components of the immune system have important roles in tumor immune-surveillance as well and thus represent promising additional targets for immunotherapy. Natural killer cells are the body’s first line of defense against infected or transformed cells as they kill target cells in an antigen-independent manner. Although several studies have clearly demonstrated the active role of NK cells in cancer-immune surveillance, only few clinically approved therapies currently exist that harness their potential. Our increased understanding of NK cell biology over the past few years has renewed the interest in NK cell based anti-cancer therapies, which has lead to a steady increase of NK cell based clinical and pre-clinical trials. Here, the role of NK cells in cancer immunesurveillance is summarized and several novel approaches to enhance NK cell cytotoxicity against cancer are discussed.

  6. Systems biology-embedded target validation: improving efficacy in drug discovery.

    Science.gov (United States)

    Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

    2014-01-01

    The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.

  7. Assessing Discriminative Performance at External Validation of Clinical Prediction Models.

    Directory of Open Access Journals (Sweden)

    Daan Nieboer

    Full Text Available External validation studies are essential to study the generalizability of prediction models. Recently a permutation test, focusing on discrimination as quantified by the c-statistic, was proposed to judge whether a prediction model is transportable to a new setting. We aimed to evaluate this test and compare it to previously proposed procedures to judge any changes in c-statistic from development to external validation setting.We compared the use of the permutation test to the use of benchmark values of the c-statistic following from a previously proposed framework to judge transportability of a prediction model. In a simulation study we developed a prediction model with logistic regression on a development set and validated them in the validation set. We concentrated on two scenarios: 1 the case-mix was more heterogeneous and predictor effects were weaker in the validation set compared to the development set, and 2 the case-mix was less heterogeneous in the validation set and predictor effects were identical in the validation and development set. Furthermore we illustrated the methods in a case study using 15 datasets of patients suffering from traumatic brain injury.The permutation test indicated that the validation and development set were homogenous in scenario 1 (in almost all simulated samples and heterogeneous in scenario 2 (in 17%-39% of simulated samples. Previously proposed benchmark values of the c-statistic and the standard deviation of the linear predictors correctly pointed at the more heterogeneous case-mix in scenario 1 and the less heterogeneous case-mix in scenario 2.The recently proposed permutation test may provide misleading results when externally validating prediction models in the presence of case-mix differences between the development and validation population. To correctly interpret the c-statistic found at external validation it is crucial to disentangle case-mix differences from incorrect regression coefficients.

  8. Clinical trials in hospitalized heart failure patients: targeting interventions to optimal phenotypic subpopulations.

    Science.gov (United States)

    Vaduganathan, Muthiah; Butler, Javed; Roessig, Lothar; Fonarow, Gregg C; Greene, Stephen J; Metra, Marco; Cotter, Gadi; Kupfer, Stuart; Zalewski, Andrew; Sato, Naoki; Filippatos, Gerasimos; Gheorghiade, Mihai

    2015-07-01

    With one possible exception, the last decade of clinical trials in hospitalized heart failure (HHF) patients has failed to demonstrate improvement in long-term clinical outcomes. This trend necessitates a need to evaluate optimal drug development strategies and standards of trial conduct. It has become increasingly important to recognize the heterogeneity among HHF patients and the differential characterization of novel drug candidates. Targeting these agents to specific subpopulations may afford optimal net response related to the particular mode of action of the drug. Analyses of previous trials demonstrate profound differences in the baseline characteristics of patients enrolled across global regions and participating sites. Such differences may influence risks for events and interpretation of results. Therefore, the actual execution of trials and the epidemiology of HHF populations at the investigative sites must be taken into consideration. Collaboration among participating sites including the provision of registry data tailored to the planned development program will optimize trial conduct. Observational data prior to study initiation may enable sites to feedback and engage in protocol development to allow for feasible and valid clinical trial conduct. This site-centered, epidemiology-based network environment may facilitate studies in specific patient populations and promote optimal data collection and clear interpretation of drug safety and efficacy. This review summarizes the roundtable discussion held by a multidisciplinary team of representatives from academia, National Institutes of Health, industry, regulatory agencies, payers, and contract and academic research organizations to answer the question: Who should be targeted for novel therapies in HHF?

  9. Validation of a new design of tellurium dioide-irradiated target

    Energy Technology Data Exchange (ETDEWEB)

    Fllaoui, Aziz; Ghamad, Younes; Zoubir, Brahim; Ayaz, Zinel Abidine; El Morabiti, Aissam; Amayoud, Hafid [Centre National de l' Energie des Sciences et des Techniques Nucleaires, Rabat (Morocco); Chakir, El Mahjoub [Nuclear Physics Department, University Ibn Toufail, Kenitra (Morocco)

    2016-10-15

    Production of iodine-131 by neutron activation of tellurium in tellurium dioxide (TeO{sub 2}) material requires a target that meets the safety requirements. In a radiopharmaceutical production unit, a new lid for a can was designed, which permits tight sealing of the target by using tungsten inert gas welding. The leakage rate of all prepared targets was assessed using a helium mass spectrometer. The accepted leakage rate is ≤ 10 - 4 mbr.L/s, according to the approved safety report related to iodine-131 production in the TRIGA Mark II research reactor (TRIGA: Training, Research, Isotopes, General Atomics). To confirm the resistance of the new design to the irradiation conditions in the TRIGA Mark II research reactor's central thimble, a study of heat effect on the sealed targets for 7 hours in an oven was conducted and the leakage rates were evaluated. The results show that the tightness of the targets is ensured up to 600 .deg. C with the appearance of deformations on lids beyond 450 .deg. C. The study of heat transfer through the target was conducted by adopting a one-dimensional approximation, under consideration of the three transfer modes-convection, conduction, and radiation. The quantities of heat generated by gamma and neutron heating were calculated by a validated computational model for the neutronic simulation of the TRIGA Mark II research reactor using the Monte Carlo N-Particle transport code. Using the heat transfer equations according to the three modes of heat transfer, the thermal study of I-131 production by irradiation of the target in the central thimble showed that the temperatures of materials do not exceed the corresponding melting points. To validate this new design, several targets have been irradiated in the central thimble according to a preplanned irradiation program, going from 4 hours of irradiation at a power level of 0.5 MW up to 35 hours (7 h/d for 5 days a week) at 1.5 MW. The results show that the irradiated targets are

  10. Validation of a New Design of Tellurium Dioxide-Irradiated Target

    Directory of Open Access Journals (Sweden)

    Aziz Fllaoui

    2016-10-01

    Full Text Available Production of iodine-131 by neutron activation of tellurium in tellurium dioxide (TeO2 material requires a target that meets the safety requirements. In a radiopharmaceutical production unit, a new lid for a can was designed, which permits tight sealing of the target by using tungsten inert gas welding. The leakage rate of all prepared targets was assessed using a helium mass spectrometer. The accepted leakage rate is ≤ 10−4 mbr.L/s, according to the approved safety report related to iodine-131 production in the TRIGA Mark II research reactor (TRIGA: Training, Research, Isotopes, General Atomics. To confirm the resistance of the new design to the irradiation conditions in the TRIGA Mark II research reactor's central thimble, a study of heat effect on the sealed targets for 7 hours in an oven was conducted and the leakage rates were evaluated. The results show that the tightness of the targets is ensured up to 600°C with the appearance of deformations on lids beyond 450°C. The study of heat transfer through the target was conducted by adopting a one-dimensional approximation, under consideration of the three transfer modes—convection, conduction, and radiation. The quantities of heat generated by gamma and neutron heating were calculated by a validated computational model for the neutronic simulation of the TRIGA Mark II research reactor using the Monte Carlo N-Particle transport code. Using the heat transfer equations according to the three modes of heat transfer, the thermal study of I-131 production by irradiation of the target in the central thimble showed that the temperatures of materials do not exceed the corresponding melting points. To validate this new design, several targets have been irradiated in the central thimble according to a preplanned irradiation program, going from 4 hours of irradiation at a power level of 0.5 MW up to 35 hours (7 h/d for 5 days a week at 1.5 MW. The results show that the irradiated targets are

  11. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

    Directory of Open Access Journals (Sweden)

    Smolej L

    2014-12-01

    Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival

  12. Identification and validation nucleolin as a target of curcumol in nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Wang, Juan; Wu, Jiacai; Li, Xumei; Liu, Haowei; Qin, Jianli; Bai, Zhun; Chi, Bixia; Chen, Xu

    2018-06-30

    Identification of the specific protein target(s) of a drug is a critical step in unraveling its mechanisms of action (MOA) in many natural products. Curcumol, isolated from well known Chinese medicinal plant Curcuma zedoary, has been shown to possess multiple biological activities. It can inhibit nasopharyngeal carcinoma (NPC) proliferation and induce apoptosis, but its target protein(s) in NPC cells remains unclear. In this study, we employed a mass spectrometry-based chemical proteomics approach reveal the possible protein targets of curcumol in NPC cells. Cellular thermal shift assay (CETSA), molecular docking and cell-based assay was used to validate the binding interactions. Chemical proteomics capturing uncovered that NCL is a target of curcumol in NPC cells, Molecular docking showed that curcumol bound to NCL with an -7.8 kcal/mol binding free energy. Cell function analysis found that curcumol's treatment leads to a degradation of NCL in NPC cells, and it showed slight effects on NP69 cells. In conclusion, our results providing evidences that NCL is a target protein of curcumol. We revealed that the anti-cancer effects of curcumol in NPC cells are mediated, at least in part, by NCL inhibition. Many natural products showed high bioactivity, while their mechanisms of action (MOA) are very poor or completely missed. Understanding the MOA of natural drugs can thoroughly exploit their therapeutic potential and minimize their adverse side effects. Identification of the specific protein target(s) of a drug is a critical step in unraveling its MOA. Compound-centric chemical proteomics is a classic chemical proteomics approach which integrates chemical synthesis with cell biology and mass spectrometry (MS) to identify protein targets of natural products determine the drug mechanism of action, describe its toxicity, and figure out the possible cause of off-target. It is an affinity-based chemical proteomics method to identify small molecule-protein interactions

  13. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress

    NARCIS (Netherlands)

    Lammers, Twan Gerardus Gertudis Maria; Kiessling, F.; Hennink, W.E.; Storm, Gerrit

    2012-01-01

    Abstract Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells,

  14. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Petri, Michelle; Orbai, Ana-Maria; Alarcón, Graciela S

    2012-01-01

    The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new...

  15. Advances in Antisense Oligonucleotide Development for Target Identification, Validation, and as Novel Therapeutics

    Directory of Open Access Journals (Sweden)

    Moizza Mansoor

    2008-01-01

    Full Text Available Antisense oligonucleotides (As-ODNs are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18–21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt, 13 for RNA and 17 for DNA, normally occurs only once. The potential applications of As-ODNs are numerous because mRNA is ubiquitous and is more accessible to manipulation than DNA. With the publication of the human genome sequence, it has become theoretically possible to inhibit mRNA of almost any gene by As-ODNs, in order to get a better understanding of gene function, investigate its role in disease pathology and to study novel therapeutic targets for the diseases caused by dysregulated gene expression. The conceptual simplicity, the availability of gene sequence information from the human genome, the inexpensive availability of synthetic oligonucleotides and the possibility of rational drug design makes As-ODNs powerful tools for target identification, validation and therapeutic intervention. In this review we discuss the latest developments in antisense oligonucleotide design, delivery, pharmacokinetics and potential side effects, as well as its uses in target identification and validation, and finally focus on the current developments of antisense oligonucleotides in therapeutic intervention in various diseases.

  16. Engineering validation for lithium target facility of the IFMIF under IFMIF/EVEDA project

    Directory of Open Access Journals (Sweden)

    E. Wakai

    2016-12-01

    Full Text Available The International Fusion Materials Irradiation Facility (IFMIF, presently in the Engineering Validation and Engineering Design Activities (EVEDA phase was started from 2007 under the frame of the Broader Approach (BA agreement. In the activities, a prototype Li loop with the world's highest flow rate of 3000L/min was constructed in 2010, and it succeeded in generating a 100mm wide and 25mm thick with a free-surface lithium flow along a concave back plate steadily at a high-speed of 15m/s at 250°C for 1300h. In the demonstration operation it was needed to develop the Li flowing measurement system with precious resolution less than 0.1mm, and a new wave height measuring method which is laser-probe method was developed for measurements of the 3D geometry of the liquid Li target surface. Using the device, the stability of the variation in the Li flowing thickness which is required in the IFMIF specification was ±1mm or less as the liquid Li target, and the result was satisfied with it and the feasibility of the long-term stable liquid Li flow was also verified. The results of the other engineering validation tests such as lithium purification tests of lithium target facility have also been evaluated and summarized.

  17. Validity of randomized clinical trials in gastroenterology from 1964-2000

    DEFF Research Database (Denmark)

    Kjaergard, Lise L; Frederiksen, Sarah L; Gluud, Christian

    2002-01-01

    The internal validity of clinical trials depends on the adequacy of the reported methodological quality. We assessed the methodological quality of all 383 randomized clinical trials published in GASTROENTEROLOGY as original articles from 1964 to 2000.......The internal validity of clinical trials depends on the adequacy of the reported methodological quality. We assessed the methodological quality of all 383 randomized clinical trials published in GASTROENTEROLOGY as original articles from 1964 to 2000....

  18. Predictive Validity of DSM-IV Oppositional Defiant and Conduct Disorders in Clinically Referred Preschoolers

    Science.gov (United States)

    Keenan, Kate; Boeldt, Debra; Chen, Diane; Coyne, Claire; Donald, Radiah; Duax, Jeanne; Hart, Katherine; Perrott, Jennifer; Strickland, Jennifer; Danis, Barbara; Hill, Carri; Davis, Shante; Kampani, Smita; Humphries, Marisha

    2011-01-01

    Background: Diagnostic validity of oppositional defiant and conduct disorders (ODD and CD) for preschoolers has been questioned based on concerns regarding the ability to differentiate normative, transient disruptive behavior from clinical symptoms. Data on concurrent validity have accumulated, but predictive validity is limited. Predictive…

  19. What should we mean by empirical validation in hypnotherapy: evidence-based practice in clinical hypnosis.

    Science.gov (United States)

    Alladin, Assen; Sabatini, Linda; Amundson, Jon K

    2007-04-01

    This paper briefly surveys the trend of and controversy surrounding empirical validation in psychotherapy. Empirical validation of hypnotherapy has paralleled the practice of validation in psychotherapy and the professionalization of clinical psychology, in general. This evolution in determining what counts as evidence for bona fide clinical practice has gone from theory-driven clinical approaches in the 1960s and 1970s through critical attempts at categorization of empirically supported therapies in the 1990s on to the concept of evidence-based practice in 2006. Implications of this progression in professional psychology are discussed in the light of hypnosis's current quest for validation and empirical accreditation.

  20. Readout electronics validation and target detector assessment for the Neutrinos Angra experiment

    International Nuclear Information System (INIS)

    Alvarenga, T.A.; Anjos, J.C.; Azzi, G.; Cerqueira, A.S.; Chimenti, P.; Costa, J.A.; Dornelas, T.I.; Farias, P.C.M.A.; Guedes, G.P.; Gonzalez, L.F.G.; Kemp, E.; Lima, H.P.; Machado, R.; Nóbrega, R.A.; Pepe, I.M.; Ribeiro, D.B.S.; Simas Filho, E.F.; Valdiviesso, G.A.; Wagner, S.

    2016-01-01

    A compact surface detector designed to identify the inverse beta decay interaction produced by anti-neutrinos coming from near operating nuclear reactors is being developed by the Neutrinos Angra Collaboration. In this document we describe and test the detector and its readout system by means of cosmic rays acquisition. In this measurement campaign, the target detector has been equipped with 16 8-in PMTs and two scintillator paddles have been used to trigger cosmic ray events. The achieved results disclosed the main operational characteristics of the Neutrinos Angra system and have been used to assess the detector and to validate its readout system.

  1. Clinical prediction models for bronchopulmonary dysplasia: a systematic review and external validation study

    NARCIS (Netherlands)

    Onland, Wes; Debray, Thomas P.; Laughon, Matthew M.; Miedema, Martijn; Cools, Filip; Askie, Lisa M.; Asselin, Jeanette M.; Calvert, Sandra A.; Courtney, Sherry E.; Dani, Carlo; Durand, David J.; Marlow, Neil; Peacock, Janet L.; Pillow, J. Jane; Soll, Roger F.; Thome, Ulrich H.; Truffert, Patrick; Schreiber, Michael D.; van Reempts, Patrick; Vendettuoli, Valentina; Vento, Giovanni; van Kaam, Anton H.; Moons, Karel G.; Offringa, Martin

    2013-01-01

    Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Very different models using clinical parameters at an early postnatal age to predict BPD have been developed with little extensive quantitative validation. The objective of this study is to review and validate clinical

  2. A Valid and Reliable Tool to Assess Nursing Students` Clinical Performance

    OpenAIRE

    Mehrnoosh Pazargadi; Tahereh Ashktorab; Sharareh Khosravi; Hamid Alavi majd

    2013-01-01

    Background: The necessity of a valid and reliable assessment tool is one of the most repeated issues in nursing students` clinical evaluation. But it is believed that present tools are not mostly valid and can not assess students` performance properly.Objectives: This study was conducted to design a valid and reliable assessment tool for evaluating nursing students` performance in clinical education.Methods: In this methodological study considering nursing students` performance definition; th...

  3. Multi-Target Screening and Experimental Validation of Natural Products from Selaginella Plants against Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Yin-Hua Deng

    2017-08-01

    Full Text Available Alzheimer's disease (AD is a progressive and irreversible neurodegenerative disorder which is considered to be the most common cause of dementia. It has a greater impact not only on the learning and memory disturbances but also on social and economy. Currently, there are mainly single-target drugs for AD treatment but the complexity and multiple etiologies of AD make them difficult to obtain desirable therapeutic effects. Therefore, the choice of multi-target drugs will be a potential effective strategy inAD treatment. To find multi-target active ingredients for AD treatment from Selaginella plants, we firstly explored the behaviors effects on AD mice of total extracts (TE from Selaginella doederleinii on by Morris water maze test and found that TE has a remarkable improvement on learning and memory function for AD mice. And then, multi-target SAR models associated with AD-related proteins were built based on Random Forest (RF and different descriptors to preliminarily screen potential active ingredients from Selaginella. Considering the prediction outputs and the quantity of existing compounds in our laboratory, 13 compounds were chosen to carry out the in vitro enzyme inhibitory experiments and 4 compounds with BACE1/MAO-B dual inhibitory activity were determined. Finally, the molecular docking was applied to verify the prediction results and enzyme inhibitory experiments. Based on these study and validation processes, we explored a new strategy to improve the efficiency of active ingredients screening based on trace amount of natural product and numbers of targets and found some multi-target compounds with biological activity for the development of novel drugs for AD treatment.

  4. Target validation for FCV technology development in Japan from energy competition point of view

    International Nuclear Information System (INIS)

    ENDO Eiichi

    2006-01-01

    The objective of this work is to validate the technical targets in the governmental hydrogen energy road-map of Japan by analyzing market penetration of fuel cell vehicle(FCV)s and effects of fuel price and carbon tax on it from technology competition point of view. In this analysis, an energy system model of Japan based on MARKAL is used. The results of the analysis show that hydrogen FCVs could not have cost-competitiveness until 2030 without carbon tax, including the governmental actual plan of carbon tax. However, as the carbon tax rate increases, instead of conventional vehicles including gasoline hybrid electric vehicle, hydrogen FCVs penetrate to the market earlier and more. By assuming higher fuel price and severer carbon tax rate, market share of hydrogen FCVs approaches to the governmental goal. This suggests that cheaper vehicle cost and/or hydrogen price than those targeted in the road-map is required. At the same time, achievement of the technical targets in the road-map also allows to attain the market penetration target of hydrogen FCVs in some possible conditions. (authors)

  5. Clinical Validity of the Counseling Center Assessment of Psychological Symptoms-62 (CCAPS-62): Further Evaluation and Clinical Applications

    Science.gov (United States)

    McAleavey, Andrew A.; Nordberg, Samuel S.; Hayes, Jeffrey A.; Castonguay, Louis G.; Locke, Benjamin D.; Lockard, Allison J.

    2012-01-01

    Self-report instruments of psychological symptoms are increasingly used in counseling centers but rely on rigorous evaluation of their clinical validity. Three studies reported here (total N = 26,886) investigated the validity of the Counseling Center Assessment of Psychological Symptoms-62 (CCAPS-62; Locke et al., 2011) as an assessment and…

  6. Clinical and psychometric validation of the psychotic depression assessment scale

    DEFF Research Database (Denmark)

    Østergaard, Søren D; Pedersen, Christina H; Uggerby, Peter

    2015-01-01

    BACKGROUND: Recent studies have indicated that the 11-item Psychotic Depression Assessment Scale (PDAS), consisting of the 6-item melancholia subscale (HAM-D6) of the Hamilton Depression Rating Scale and 5 psychosis items from the Brief Psychiatric Rating Scale (BPRS), is a valid measure for the ...

  7. Validity of Two WPPSI Short Forms in Outpatient Clinic Settings.

    Science.gov (United States)

    Haynes, Jack P.; Atkinson, David

    1983-01-01

    Investigated the validity of subtest short forms for the Wechsler Preschool and Primary Scale of Intelligence in an outpatient population of 116 children. Data showed that the short forms underestimated actual level of intelligence and supported use of a short form only as a brief screening device. (LLL)

  8. Empirical Derivation and Validation of a Clinical Case Definition for Neuropsychological Impairment in Children and Adolescents.

    Science.gov (United States)

    Beauchamp, Miriam H; Brooks, Brian L; Barrowman, Nick; Aglipay, Mary; Keightley, Michelle; Anderson, Peter; Yeates, Keith O; Osmond, Martin H; Zemek, Roger

    2015-09-01

    Neuropsychological assessment aims to identify individual performance profiles in multiple domains of cognitive functioning; however, substantial variation exists in how deficits are defined and what cutoffs are used, and there is no universally accepted definition of neuropsychological impairment. The aim of this study was to derive and validate a clinical case definition rule to identify neuropsychological impairment in children and adolescents. An existing normative pediatric sample was used to calculate base rates of abnormal functioning on eight measures covering six domains of neuropsychological functioning. The dataset was analyzed by varying the range of cutoff levels [1, 1.5, and 2 standard deviations (SDs) below the mean] and number of indicators of impairment. The derived rule was evaluated by bootstrap, internal and external clinical validation (orthopedic and traumatic brain injury). Our neuropsychological impairment (NPI) rule was defined as "two or more test scores that fall 1.5 SDs below the mean." The rule identifies 5.1% of the total sample as impaired in the assessment battery and consistently targets between 3 and 7% of the population as impaired even when age, domains, and number of tests are varied. The NPI rate increases in groups known to exhibit cognitive deficits. The NPI rule provides a psychometrically derived method for interpreting performance across multiple tests and may be used in children 6-18 years. The rule may be useful to clinicians and scientists who wish to establish whether specific individuals or clinical populations present within expected norms versus impaired function across a battery of neuropsychological tests.

  9. Anatomic Boundaries of the Clinical Target Volume (Prostate Bed) After Radical Prostatectomy

    International Nuclear Information System (INIS)

    Wiltshire, Kirsty L.; Brock, Kristy K.; Haider, Masoom A.; Zwahlen, Daniel; Kong, Vickie; Chan, Elisa; Moseley, Joanne; Bayley, Andrew; Catton, Charles; Chung, Peter W.M.; Gospodarowicz, Mary; Milosevic, Michael; Kneebone, Andrew; Warde, Padraig; Menard, Cynthia

    2007-01-01

    Purpose: We sought to derive and validate an interdisciplinary consensus definition for the anatomic boundaries of the postoperative clinical target volume (CTV, prostate bed). Methods and Materials: Thirty one patients who had planned for radiotherapy after radical prostatectomy were enrolled and underwent computed tomography and magnetic resonance imaging (MRI) simulation prior to radiotherapy. Through an iterative process of consultation and discussion, an interdisciplinary consensus definition was derived based on a review of published data, patterns of local failure, surgical practice, and radiologic anatomy. In validation, we analyzed the distribution of surgical clips in reference to the consensus CTV and measured spatial uncertainties in delineating the CTV and vesicourethral anastomosis. Clinical radiotherapy plans were retrospectively evaluated against the consensus CTV (prostate bed). Results: Anatomic boundaries of the consensus CTV (prostate bed) are described. Surgical clips (n = 339) were well distributed throughout the CTV. The vesicourethral anastomosis was accurately localized using central sagittal computed tomography reconstruction, with a mean ± standard deviation uncertainty of 1.8 ± 2.5 mm. Delineation uncertainties were small for both MRI and computed tomography (mean reproducibility, 0-3.8 mm; standard deviation, 1.0-2.3); they were most pronounced in the anteroposterior and superoinferior dimensions and at the superior/posterior-most aspect of the CTV. Retrospectively, the mean ± standard deviation CTV (prostate bed) percentage of volume receiving 100% of prescribed dose was only 77% ± 26%. Conclusions: We propose anatomic boundaries for the CTV (prostate bed) and present evidence supporting its validity. In the absence of gross recurrence, the role of MRI in delineating the CTV remains to be confirmed. The CTV is larger than historically practiced at our institution and should be encompassed by a microscopic tumoricidal dose

  10. Antibody Selection for Cancer Target Validation of FSH-Receptor in Immunohistochemical Settings

    Directory of Open Access Journals (Sweden)

    Nina Moeker

    2017-10-01

    Full Text Available Background: The follicle-stimulating hormone (FSH-receptor (FSHR has been reported to be an attractive target for antibody therapy in human cancer. However, divergent immunohistochemical (IHC findings have been reported for FSHR expression in tumor tissues, which could be due to the specificity of the antibodies used. Methods: Three frequently used antibodies (sc-7798, sc-13935, and FSHR323 were validated for their suitability in an immunohistochemical study for FSHR expression in different tissues. As quality control, two potential therapeutic anti-hFSHR Ylanthia® antibodies (Y010913, Y010916 were used. The specificity criteria for selection of antibodies were binding to native hFSHR of different sources, and no binding to non-related proteins. The ability of antibodies to stain the paraffin-embedded Flp-In Chinese hamster ovary (CHO/FSHR cells was tested after application of different epitope retrieval methods. Results: From the five tested anti-hFSHR antibodies, only Y010913, Y010916, and FSHR323 showed specific binding to native, cell-presented hFSHR. Since Ylanthia® antibodies were selected to specifically recognize native FSHR, as required for a potential therapeutic antibody candidate, FSHR323 was the only antibody to detect the receptor in IHC/histochemical settings on transfected cells, and at markedly lower, physiological concentrations (ex., in Sertoli cells of human testes. The pattern of FSH323 staining noticed for ovarian, prostatic, and renal adenocarcinomas indicated that FSHR was expressed mainly in the peripheral tumor blood vessels. Conclusion: Of all published IHC antibodies tested, only antibody FSHR323 proved suitable for target validation of hFSHR in an IHC setting for cancer. Our studies could not confirm the previously reported FSHR overexpression in ovarian and prostate cancer cells. Instead, specific overexpression in peripheral tumor blood vessels could be confirmed after thorough validation of the antibodies used.

  11. VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets.

    Science.gov (United States)

    Qureshi, Abid; Thakur, Nishant; Monga, Isha; Thakur, Anamika; Kumar, Manoj

    2014-01-01

    Viral microRNAs (miRNAs) regulate gene expression of viral and/or host genes to benefit the virus. Hence, miRNAs play a key role in host-virus interactions and pathogenesis of viral diseases. Lately, miRNAs have also shown potential as important targets for the development of novel antiviral therapeutics. Although several miRNA and their target repositories are available for human and other organisms in literature, but a dedicated resource on viral miRNAs and their targets are lacking. Therefore, we have developed a comprehensive viral miRNA resource harboring information of 9133 entries in three subdatabases. This includes 1308 experimentally validated miRNA sequences with their isomiRs encoded by 44 viruses in viral miRNA ' VIRMIRNA: ' and 7283 of their target genes in ' VIRMIRTAR': . Additionally, there is information of 542 antiviral miRNAs encoded by the host against 24 viruses in antiviral miRNA ' AVIRMIR': . The web interface was developed using Linux-Apache-MySQL-PHP (LAMP) software bundle. User-friendly browse, search, advanced search and useful analysis tools are also provided on the web interface. VIRmiRNA is the first specialized resource of experimentally proven virus-encoded miRNAs and their associated targets. This database would enhance the understanding of viral/host gene regulation and may also prove beneficial in the development of antiviral therapeutics. Database URL: http://crdd.osdd.net/servers/virmirna. © The Author(s) 2014. Published by Oxford University Press.

  12. The Maastricht Clinical Teaching Questionnaire (MCTQ) as a valid and reliable instrument for the evaluation of clinical teachers.

    Science.gov (United States)

    Stalmeijer, Renée E; Dolmans, Diana H J M; Wolfhagen, Ineke H A P; Muijtjens, Arno M M; Scherpbier, Albert J J A

    2010-11-01

    Clinical teaching's importance in the medical curriculum has led to increased interest in its evaluation. Instruments for evaluating clinical teaching must be theory based, reliable, and valid. The Maastricht Clinical Teaching Questionnaire (MCTQ), based on the theoretical constructs of cognitive apprenticeship, elicits evaluations of individual clinical teachers' performance at the workplace. The authors investigated its construct validity and reliability, and they used the underlying factors to test a causal model representing effective clinical teaching. Between March 2007 and December 2008, the authors asked students who had completed clerkship rotations in different departments of two teaching hospitals to use the MCTQ to evaluate their clinical teachers. To establish construct validity, the authors performed a confirmatory factor analysis of the evaluation data, and they estimated reliability by calculating the generalizability coefficient and standard error measurement. Finally, to test a model of the factors, they fitted a structural linear model to the data. Confirmatory factor analysis yielded a five-factor model which fit the data well. Generalizability studies indicated that 7 to 10 student ratings can produce reliable ratings of individual teachers. The hypothesized structural linear model underlined the central roles played by modeling and coaching (mediated by articulation). The MCTQ is a valid and reliable evaluation instrument, thereby demonstrating the usefulness of the cognitive apprenticeship concept for clinical teaching during clerkships. Furthermore, a valuable model of clinical teaching emerged, highlighting modeling, coaching, and stimulating students' articulation and exploration as crucial to effective teaching at the clinical workplace.

  13. Virtual Reality for Enhanced Ecological Validity and Experimental Control in the Clinical, Affective and Social Neurosciences

    Science.gov (United States)

    Parsons, Thomas D.

    2015-01-01

    An essential tension can be found between researchers interested in ecological validity and those concerned with maintaining experimental control. Research in the human neurosciences often involves the use of simple and static stimuli lacking many of the potentially important aspects of real world activities and interactions. While this research is valuable, there is a growing interest in the human neurosciences to use cues about target states in the real world via multimodal scenarios that involve visual, semantic, and prosodic information. These scenarios should include dynamic stimuli presented concurrently or serially in a manner that allows researchers to assess the integrative processes carried out by perceivers over time. Furthermore, there is growing interest in contextually embedded stimuli that can constrain participant interpretations of cues about a target’s internal states. Virtual reality environments proffer assessment paradigms that combine the experimental control of laboratory measures with emotionally engaging background narratives to enhance affective experience and social interactions. The present review highlights the potential of virtual reality environments for enhanced ecological validity in the clinical, affective, and social neurosciences. PMID:26696869

  14. How valid are claims for synergy in published clinical studies?

    Science.gov (United States)

    Ocana, A; Amir, E; Yeung, C; Seruga, B; Tannock, I F

    2012-08-01

    Clinical trials evaluating drug combinations are often stimulated by claims of synergistic interactions in preclinical models. Overuse or misuse of the term synergy could lead to poorly designed clinical studies. We searched PubMed using the terms 'synergy' or 'synergistic' and 'cancer' to select articles published between 2006 and 2010. Eligible studies were those that referred to synergy in preclinical studies to justify a drug combination evaluated in a clinical trial. Eighty-six clinical articles met eligibility criteria and 132 preclinical articles were cited in them. Most of the clinical studies were phase I (43%) or phase II trials (56%). Appropriate methods to evaluate synergy in preclinical studies included isobologram analysis in 18 studies (13.6%) and median effect in 10 studies (7.6%). Only 26 studies using animal models (39%) attempted to evaluate therapeutic index. There was no association between the result of the clinical trial and the use of an appropriate method to evaluate synergy (P=0.25, chi-squared test). Synergy is cited frequently in phase I and phase II studies to justify the evaluation of a specific drug combination. Inappropriate methods for evaluation of synergy and poor assessment of therapeutic index have been used in most preclinical articles.

  15. Target biomarker profile for the clinical management of paracetamol overdose

    Science.gov (United States)

    Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

    2015-01-01

    Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

  16. Target motion measurement without implanted markers and its validation by comparison with manually obtained data

    International Nuclear Information System (INIS)

    Vences, Lucia; Wulf, Joern; Vordermark, Dirk; Sauer, Otto; Berlinger, Kajetan; Roth, Michael

    2005-01-01

    For an effective radiotherapy the exact tumor location must be determined. The localization has to take into account patient's setup position as well as internal organ motion. Among the different localization methods, the use of a computer tomography (CT) scanner in the therapy room has been proposed recently. Achieving a CT with the patient on the therapy couch, a patient's treatment position is captured. We present a method to locate tumor considering internal organ motion and displacements due to respiration. We tested the method with prostate and lung patients. The method found the most probable tumor position as well as, for high-mobility tumors located in the lung, its trajectory during the respiratory cycle. The results of this novel method were validated by comparison with manually determined target position

  17. Site selection and directional models of deserts used for ERBE validation targets

    Science.gov (United States)

    Staylor, W. F.

    1986-01-01

    Broadband shortwave and longwave radiance measurements obtained from the Nimbus 7 Earth Radiation Budget scanner were used to develop reflectance and emittance models for the Sahara, Gibson, and Saudi Deserts. These deserts will serve as in-flight validation targets for the Earth Radiation Budget Experiment being flown on the Earth Radiation Budget Satellite and two National Oceanic and Atmospheric Administration polar satellites. The directional reflectance model derived for the deserts was a function of the sum and product of the cosines of the solar and viewing zenith angles, and thus reciprocity existed between these zenith angles. The emittance model was related by a power law of the cosine of the viewing zenith angle.

  18. Clinical improvement in psoriasis with specific targeting of interleukin-23

    DEFF Research Database (Denmark)

    Kopp, Tamara; Riedl, Elisabeth; Bangert, Christine

    2015-01-01

    Psoriasis is a chronic inflammatory skin disorder that affects approximately 2-3% of the population worldwide and has severe effects on patients' physical and psychological well-being. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent...

  19. Results from the radiometric validation of Sentinel-3 optical sensors using natural targets

    Science.gov (United States)

    Fougnie, Bertrand; Desjardins, Camille; Besson, Bruno; Bruniquel, Véronique; Meskini, Naceur; Nieke, Jens; Bouvet, Marc

    2016-09-01

    The recently launched SENTINEL-3 mission measures sea surface topography, sea/land surface temperature, and ocean/land surface colour with high accuracy. The mission provides data continuity with the ENVISAT mission through acquisitions by multiple sensing instruments. Two of them, OLCI (Ocean and Land Colour Imager) and SLSTR (Sea and Land Surface Temperature Radiometer) are optical sensors designed to provide continuity with Envisat's MERIS and AATSR instruments. During the commissioning, in-orbit calibration and validation activities are conducted. Instruments are in-flight calibrated and characterized primarily using on-board devices which include diffusers and black body. Afterward, vicarious calibration methods are used in order to validate the OLCI and SLSTR radiometry for the reflective bands. The calibration can be checked over dedicated natural targets such as Rayleigh scattering, sunglint, desert sites, Antarctica, and tentatively deep convective clouds. Tools have been developed and/or adapted (S3ETRAC, MUSCLE) to extract and process Sentinel-3 data. Based on these matchups, it is possible to provide an accurate checking of many radiometric aspects such as the absolute and interband calibrations, the trending correction, the calibration consistency within the field-of-view, and more generally this will provide an evaluation of the radiometric consistency for various type of targets. Another important aspect will be the checking of cross-calibration between many other instruments such as MERIS and AATSR (bridge between ENVISAT and Sentinel-3), MODIS (bridge to the GSICS radiometric standard), as well as Sentinel-2 (bridge between Sentinel missions). The early results, based on the available OLCI and SLSTR data, will be presented and discussed.

  20. Real-time non-rigid target tracking for ultrasound-guided clinical interventions

    Science.gov (United States)

    Zachiu, C.; Ries, M.; Ramaekers, P.; Guey, J.-L.; Moonen, C. T. W.; de Senneville, B. Denis

    2017-10-01

    Biological motion is a problem for non- or mini-invasive interventions when conducted in mobile/deformable organs due to the targeted pathology moving/deforming with the organ. This may lead to high miss rates and/or incomplete treatment of the pathology. Therefore, real-time tracking of the target anatomy during the intervention would be beneficial for such applications. Since the aforementioned interventions are often conducted under B-mode ultrasound (US) guidance, target tracking can be achieved via image registration, by comparing the acquired US images to a separate image established as positional reference. However, such US images are intrinsically altered by speckle noise, introducing incoherent gray-level intensity variations. This may prove problematic for existing intensity-based registration methods. In the current study we address US-based target tracking by employing the recently proposed EVolution registration algorithm. The method is, by construction, robust to transient gray-level intensities. Instead of directly matching image intensities, EVolution aligns similar contrast patterns in the images. Moreover, the displacement is computed by evaluating a matching criterion for image sub-regions rather than on a point-by-point basis, which typically provides more robust motion estimates. However, unlike similar previously published approaches, which assume rigid displacements in the image sub-regions, the EVolution algorithm integrates the matching criterion in a global functional, allowing the estimation of an elastic dense deformation. The approach was validated for soft tissue tracking under free-breathing conditions on the abdomen of seven healthy volunteers. Contact echography was performed on all volunteers, while three of the volunteers also underwent standoff echography. Each of the two modalities is predominantly specific to a particular type of non- or mini-invasive clinical intervention. The method demonstrated on average an accuracy of

  1. Clinical validation of a nanodiamond-embedded thermoplastic biomaterial.

    Science.gov (United States)

    Lee, Dong-Keun; Kee, Theodore; Liang, Zhangrui; Hsiou, Desiree; Miya, Darron; Wu, Brian; Osawa, Eiji; Chow, Edward Kai-Hua; Sung, Eric C; Kang, Mo K; Ho, Dean

    2017-11-07

    Detonation nanodiamonds (NDs) are promising drug delivery and imaging agents due to their uniquely faceted surfaces with diverse chemical groups, electrostatic properties, and biocompatibility. Based on the potential to harness ND properties to clinically address a broad range of disease indications, this work reports the in-human administration of NDs through the development of ND-embedded gutta percha (NDGP), a thermoplastic biomaterial that addresses reinfection and bone loss following root canal therapy (RCT). RCT served as the first clinical indication for NDs since the procedure sites involved nearby circulation, localized administration, and image-guided treatment progress monitoring, which are analogous to many clinical indications. This randomized, single-blind interventional treatment study evaluated NDGP equivalence with unmodified GP. This progress report assessed one control-arm and three treatment-arm patients. At 3-mo and 6-mo follow-up appointments, no adverse events were observed, and lesion healing was confirmed in the NDGP-treated patients. Therefore, this study is a foundation for the continued clinical translation of NDs and other nanomaterials for a broad spectrum of applications. Published under the PNAS license.

  2. Validation and clinical application of a nested PCR for paracoccidioidomycosis diagnosis in clinical samples from Colombian patients.

    Science.gov (United States)

    Gaviria, Marcela; Rivera, Vanessa; Muñoz-Cadavid, Cesar; Cano, Luz Elena; Naranjo, Tonny Williams

    2015-01-01

    Paracoccidioidomycosis is a systemic and endemic mycosis, restricted to tropical and subtropical areas of Latin America. The infection is caused by the thermal dimorphic fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. The diagnosis of paracoccidioidomycosis is usually performed by microscopic examination, culture and immunodiagnostic tests to respiratory specimens, body fluids and/or biopsies; however these methods require laboratory personnel with experience and several days to produce a result. In the present study, we have validated and evaluated a nested PCR assay targeting the gene encoding the Paracoccidioides gp43 membrane protein in 191 clinical samples: 115 samples from patients with proven infections other than paracoccidioidomycosis, 51 samples as negative controls, and 25 samples from patients diagnosed with paracoccidioidomycosis. Additionally, the specificity of the nested PCR assay was also evaluated using purified DNA isolated from cultures of different microorganisms (n=35) previously identified by culture and/or sequencing. The results showed that in our hands, this nested PCR assay for gp43 protein showed specificity and sensitivity rates of 100%. The optimized nested PCR conditions in our laboratory allowed detection down to 1fg of P. brasiliensis DNA. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  3. Clinical validation of synthetic brain MRI in children: initial experience

    International Nuclear Information System (INIS)

    West, Hollie; Leach, James L.; Jones, Blaise V.; Care, Marguerite; Radhakrishnan, Rupa; Merrow, Arnold C.; Alvarado, Enrique; Serai, Suraj D.

    2017-01-01

    The purpose of this study was to determine the diagnostic accuracy of synthetic MR sequences generated through post-acquisition processing of a single sequence measuring inherent R1, R2, and PD tissue properties compared with sequences acquired conventionally as part of a routine clinical pediatric brain MR exam. Thirty-two patients underwent routine clinical brain MRI with conventional and synthetic sequences acquired (22 abnormal). Synthetic axial T1, T2, and T2 fluid attenuation inversion recovery or proton density-weighted sequences were made to match the comparable clinical sequences. Two exams for each patient were de-identified. Four blinded reviewers reviewed eight patients and were asked to generate clinical reports on each exam (synthetic or conventional) at two different time points separated by a mean of 33 days. Exams were rated for overall and specific finding agreement (synthetic/conventional and compared to gold standard consensus review by two senior reviewers with knowledge of clinical report), quality, and diagnostic confidence. Overall agreement between conventional and synthetic exams was 97%. Agreement with consensus readings was 84% (conventional) and 81% (synthetic), p = 0.61. There were no significant differences in sensitivity, specificity, or accuracy for specific imaging findings involving the ventricles, CSF, brain parenchyma, or vasculature between synthetic or conventional exams (p > 0.05). No significant difference in exam quality, diagnostic confidence, or noise/artifacts was noted comparing studies with synthetic or conventional sequences. Diagnostic accuracy and quality of synthetically generated sequences are comparable to conventionally acquired sequences as part of a standard pediatric brain exam. Further confirmation in a larger study is warranted. (orig.)

  4. Clinical validation of synthetic brain MRI in children: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    West, Hollie; Leach, James L.; Jones, Blaise V.; Care, Marguerite; Radhakrishnan, Rupa; Merrow, Arnold C.; Alvarado, Enrique; Serai, Suraj D. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

    2017-01-15

    The purpose of this study was to determine the diagnostic accuracy of synthetic MR sequences generated through post-acquisition processing of a single sequence measuring inherent R1, R2, and PD tissue properties compared with sequences acquired conventionally as part of a routine clinical pediatric brain MR exam. Thirty-two patients underwent routine clinical brain MRI with conventional and synthetic sequences acquired (22 abnormal). Synthetic axial T1, T2, and T2 fluid attenuation inversion recovery or proton density-weighted sequences were made to match the comparable clinical sequences. Two exams for each patient were de-identified. Four blinded reviewers reviewed eight patients and were asked to generate clinical reports on each exam (synthetic or conventional) at two different time points separated by a mean of 33 days. Exams were rated for overall and specific finding agreement (synthetic/conventional and compared to gold standard consensus review by two senior reviewers with knowledge of clinical report), quality, and diagnostic confidence. Overall agreement between conventional and synthetic exams was 97%. Agreement with consensus readings was 84% (conventional) and 81% (synthetic), p = 0.61. There were no significant differences in sensitivity, specificity, or accuracy for specific imaging findings involving the ventricles, CSF, brain parenchyma, or vasculature between synthetic or conventional exams (p > 0.05). No significant difference in exam quality, diagnostic confidence, or noise/artifacts was noted comparing studies with synthetic or conventional sequences. Diagnostic accuracy and quality of synthetically generated sequences are comparable to conventionally acquired sequences as part of a standard pediatric brain exam. Further confirmation in a larger study is warranted. (orig.)

  5. Validity, reliability, and feasibility of clinical staging scales in dementia: a systematic review

    DEFF Research Database (Denmark)

    Rikkert, Marcel G M Olde; Tona, Klodiana Daphne; Janssen, Lieneke

    2011-01-01

    New staging systems of dementia require adaptation of disease management programs and adequate staging instruments. Therefore, we systematically reviewed the literature on validity and reliability of clinically applicable, multidomain, and dementia staging instruments. A total of 23 articles...

  6. Clinical reliability and validity of elbow functional assessment in rheumatoid arthritis.

    NARCIS (Netherlands)

    Boer, Y.A. de; Ende, C.H.M. van den; Eygendaal, D.; Jolie, I.M.M.; Hazes, J.M.W.; Rozing, P.M.

    1999-01-01

    OBJECTIVES: (1) To investigate the measurement characteristics of the Hospital for Special Surgery (HSS) and Mayo Clinic elbow assessment instruments, utilizing methodological criteria including feasibility, reliability, validity, and discriminative ability; and (2) to develop an efficient and

  7. Precision and linearity targets for validation of an IFNγ ELISPOT, cytokine flow cytometry, and tetramer assay using CMV peptides

    Directory of Open Access Journals (Sweden)

    Lyerly Herbert K

    2008-03-01

    Full Text Available Abstract Background Single-cell assays of immune function are increasingly used to monitor T cell responses in immunotherapy clinical trials. Standardization and validation of such assays are therefore important to interpretation of the clinical trial data. Here we assess the levels of intra-assay, inter-assay, and inter-operator precision, as well as linearity, of CD8+ T cell IFNγ-based ELISPOT and cytokine flow cytometry (CFC, as well as tetramer assays. Results Precision was measured in cryopreserved PBMC with a low, medium, or high response level to a CMV pp65 peptide or peptide mixture. Intra-assay precision was assessed using 6 replicates per assay; inter-assay precision was assessed by performing 8 assays on different days; and inter-operator precision was assessed using 3 different operators working on the same day. Percent CV values ranged from 4% to 133% depending upon the assay and response level. Linearity was measured by diluting PBMC from a high responder into PBMC from a non-responder, and yielded R2 values from 0.85 to 0.99 depending upon the assay and antigen. Conclusion These data provide target values for precision and linearity of single-cell assays for those wishing to validate these assays in their own laboratories. They also allow for comparison of the precision and linearity of ELISPOT, CFC, and tetramer across a range of response levels. There was a trend toward tetramer assays showing the highest precision, followed closely by CFC, and then ELISPOT; while all three assays had similar linearity. These findings are contingent upon the use of optimized protocols for each assay.

  8. Evidence for the Criterion Validity and Clinical Utility of the Pathological Narcissism Inventory

    Science.gov (United States)

    Thomas, Katherine M.; Wright, Aidan G. C.; Lukowitsky, Mark R.; Donnellan, M. Brent; Hopwood, Christopher J.

    2012-01-01

    In this study, the authors evaluated aspects of criterion validity and clinical utility of the grandiosity and vulnerability components of the Pathological Narcissism Inventory (PNI) using two undergraduate samples (N = 299 and 500). Criterion validity was assessed by evaluating the correlations of narcissistic grandiosity and narcissistic…

  9. Applying Kane's Validity Framework to a Simulation Based Assessment of Clinical Competence

    Science.gov (United States)

    Tavares, Walter; Brydges, Ryan; Myre, Paul; Prpic, Jason; Turner, Linda; Yelle, Richard; Huiskamp, Maud

    2018-01-01

    Assessment of clinical competence is complex and inference based. Trustworthy and defensible assessment processes must have favourable evidence of validity, particularly where decisions are considered high stakes. We aimed to organize, collect and interpret validity evidence for a high stakes simulation based assessment strategy for certifying…

  10. External validation of a clinical scoring system for the risk of gestational diabetes mellitus

    NARCIS (Netherlands)

    van Leeuwen, M.; Opmeer, B. C.; Zweers, E. J. K.; van Ballegooie, E.; ter Brugge, H. G.; de Valk, H. W.; Visser, G. H. A.; Mol, B. W. J.

    Aim: A prediction rule for gestational diabetes mellitus (GDM) could be helpful in early detection and increased efficiency of screening. A prediction rule by means of a clinical scoring system is available, but has never been validated externally. The aim of this study was to validate the scoring

  11. A clinical reasoning model focused on clients' behaviour change with reference to physiotherapists: its multiphase development and validation.

    Science.gov (United States)

    Elvén, Maria; Hochwälder, Jacek; Dean, Elizabeth; Söderlund, Anne

    2015-05-01

    A biopsychosocial approach and behaviour change strategies have long been proposed to serve as a basis for addressing current multifaceted health problems. This emphasis has implications for clinical reasoning of health professionals. This study's aim was to develop and validate a conceptual model to guide physiotherapists' clinical reasoning focused on clients' behaviour change. Phase 1 consisted of the exploration of existing research and the research team's experiences and knowledge. Phases 2a and 2b consisted of validation and refinement of the model based on input from physiotherapy students in two focus groups (n = 5 per group) and from experts in behavioural medicine (n = 9). Phase 1 generated theoretical and evidence bases for the first version of a model. Phases 2a and 2b established the validity and value of the model. The final model described clinical reasoning focused on clients' behaviour change as a cognitive, reflective, collaborative and iterative process with multiple interrelated levels that included input from the client and physiotherapist, a functional behavioural analysis of the activity-related target behaviour and the selection of strategies for behaviour change. This unique model, theory- and evidence-informed, has been developed to help physiotherapists to apply clinical reasoning systematically in the process of behaviour change with their clients.

  12. Emerging techniques for the discovery and validation of therapeutic targets for skeletal diseases.

    Science.gov (United States)

    Cho, Christine H; Nuttall, Mark E

    2002-12-01

    Advances in genomics and proteomics have revolutionised the drug discovery process and target validation. Identification of novel therapeutic targets for chronic skeletal diseases is an extremely challenging process based on the difficulty of obtaining high-quality human diseased versus normal tissue samples. The quality of tissue and genomic information obtained from the sample is critical to identifying disease-related genes. Using a genomics-based approach, novel genes or genes with similar homology to existing genes can be identified from cDNA libraries generated from normal versus diseased tissue. High-quality cDNA libraries are prepared from uncontaminated homogeneous cell populations harvested from tissue sections of interest. Localised gene expression analysis and confirmation are obtained through in situ hybridisation or immunohistochemical studies. Cells overexpressing the recombinant protein are subsequently designed for primary cell-based high-throughput assays that are capable of screening large compound banks for potential hits. Afterwards, secondary functional assays are used to test promising compounds. The same overexpressing cells are used in the secondary assay to test protein activity and functionality as well as screen for small-molecule agonists or antagonists. Once a hit is generated, a structure-activity relationship of the compound is optimised for better oral bioavailability and pharmacokinetics allowing the compound to progress into development. Parallel efforts from proteomics, as well as genetics/transgenics, bioinformatics and combinatorial chemistry, and improvements in high-throughput automation technologies, allow the drug discovery process to meet the demands of the medicinal market. This review discusses and illustrates how different approaches are incorporated into the discovery and validation of novel targets and, consequently, the development of potentially therapeutic agents in the areas of osteoporosis and osteoarthritis

  13. Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Caravatta Luciana

    2012-06-01

    Full Text Available Abstract Background Radiotherapy (RT is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI in the preoperative and definitive treatment of pancreatic cancer. Methods The anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries. Results We proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided. Conclusions The proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs.

  14. Validation of the tool assessment of clinical education (AssCE): A study using Delphi method and clinical experts.

    Science.gov (United States)

    Löfmark, Anna; Mårtensson, Gunilla

    2017-03-01

    The aim of the present study was to establish the validity of the tool Assessment of Clinical Education (AssCE). The tool is widely used in Sweden and some Nordic countries for assessing nursing students' performance in clinical education. It is important that the tools in use be subjected to regular audit and critical reviews. The validation process, performed in two stages, was concluded with a high level of congruence. In the first stage, Delphi technique was used to elaborate the AssCE tool using a group of 35 clinical nurse lecturers. After three rounds, we reached consensus. In the second stage, a group of 46 clinical nurse lecturers representing 12 universities in Sweden and Norway audited the revised version of the AssCE in relation to learning outcomes from the last clinical course at their respective institutions. Validation of the revised AssCE was established with high congruence between the factors in the AssCE and examined learning outcomes. The revised AssCE tool seems to meet its objective to be a validated assessment tool for use in clinical nursing education. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. 15N liver function tests - concept, validity, clinical use

    International Nuclear Information System (INIS)

    Faust, H.; Jung, K.; Krumbiegel, P.; Hirschberg, K.; Reinhardt, R.; Junghans, P.

    1987-01-01

    Several liver function tests using the oral application of a nitrogen compound labelled with 15 N and the subsequent determination of 15 N in a certain fraction of urine by emission spectrometry are described. Because of the key position of the liver in the metabolism of nitrogen compounds the results of these tests allow conclusions concerning disturbances of special liver functions. Instructions for the clinical use of the '[ 15 N]Ammonium Test', '[ 15 N]Hippurate Test' the '[ 15 N]Methacetin Test', and the '[ 15 N]Glycine Test' are given. (author)

  16. A comprehensive clinical validation of the nuclear stethoscope

    International Nuclear Information System (INIS)

    Caruana, M.; Jones, R.; Lahiri, A.; Brigden, G.; Rodrigues, E.; Dore, C.; Raftery, E.B.; Medical Research Council, Harrow

    1986-01-01

    Five studies were conducted to examine the degree of variability to be expected during the use of the non-imaging nuclear probe (BIOS Inc.) under a variety of clinical conditions. Comparison of the ejection fraction (EF) readings between the nuclear probe and a gamma camera showed good agreement, with the nuclear probe tending to underestimate lower, and overestimate higher camera EF values. It is concluded that the portable, low cost nuclear probe produces accurate EF measurements when compared with the gamma camera. (author)

  17. ClinicalCodes: an online clinical codes repository to improve the validity and reproducibility of research using electronic medical records.

    Science.gov (United States)

    Springate, David A; Kontopantelis, Evangelos; Ashcroft, Darren M; Olier, Ivan; Parisi, Rosa; Chamapiwa, Edmore; Reeves, David

    2014-01-01

    Lists of clinical codes are the foundation for research undertaken using electronic medical records (EMRs). If clinical code lists are not available, reviewers are unable to determine the validity of research, full study replication is impossible, researchers are unable to make effective comparisons between studies, and the construction of new code lists is subject to much duplication of effort. Despite this, the publication of clinical codes is rarely if ever a requirement for obtaining grants, validating protocols, or publishing research. In a representative sample of 450 EMR primary research articles indexed on PubMed, we found that only 19 (5.1%) were accompanied by a full set of published clinical codes and 32 (8.6%) stated that code lists were available on request. To help address these problems, we have built an online repository where researchers using EMRs can upload and download lists of clinical codes. The repository will enable clinical researchers to better validate EMR studies, build on previous code lists and compare disease definitions across studies. It will also assist health informaticians in replicating database studies, tracking changes in disease definitions or clinical coding practice through time and sharing clinical code information across platforms and data sources as research objects.

  18. Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial.

    Science.gov (United States)

    Coric, Vladimir; Salloway, Stephen; van Dyck, Christopher H; Dubois, Bruno; Andreasen, Niels; Brody, Mark; Curtis, Craig; Soininen, Hilkka; Thein, Stephen; Shiovitz, Thomas; Pilcher, Gary; Ferris, Steven; Colby, Susan; Kerselaers, Wendy; Dockens, Randy; Soares, Holly; Kaplita, Stephen; Luo, Feng; Pachai, Chahin; Bracoud, Luc; Mintun, Mark; Grill, Joshua D; Marek, Ken; Seibyl, John; Cedarbaum, Jesse M; Albright, Charles; Feldman, Howard H; Berman, Robert M

    2015-11-01

    Early identification of Alzheimer disease (AD) is important for clinical management and affords the opportunity to assess potential disease-modifying agents in clinical trials. To our knowledge, this is the first report of a randomized trial to prospectively enrich a study population with prodromal AD (PDAD) defined by cerebrospinal fluid (CSF) biomarker criteria and mild cognitive impairment (MCI) symptoms. To assess the safety of the γ-secretase inhibitor avagacestat in PDAD and to determine whether CSF biomarkers can identify this patient population prior to clinical diagnosis of dementia. A randomized, placebo-controlled phase 2 clinical trial with a parallel, untreated, nonrandomized observational cohort of CSF biomarker-negative participants was conducted May 26, 2009, to July 9, 2013, in a multicenter global population. Of 1358 outpatients screened, 263 met MCI and CSF biomarker criteria for randomization into the treatment phase. One hundred two observational cohort participants who met MCI criteria but were CSF biomarker-negative were observed during the same study period to evaluate biomarker assay sensitivity. Oral avagacestat or placebo daily. Safety and tolerability of avagacestat. Of the 263 participants in the treatment phase, 132 were randomized to avagacestat and 131 to placebo; an additional 102 participants were observed in an untreated observational cohort. Avagacestat was relatively well tolerated with low discontinuation rates (19.6%) at a dose of 50 mg/d, whereas the dose of 125 mg/d had higher discontinuation rates (43%), primarily attributable to gastrointestinal tract adverse events. Increases in nonmelanoma skin cancer and nonprogressive, reversible renal tubule effects were observed with avagacestat. Serious adverse event rates were higher with avagacestat (49 participants [37.1%]) vs placebo (31 [23.7%]), attributable to the higher incidence of nonmelanoma skin cancer. At 2 years, progression to dementia was more frequent in the PDAD

  19. Validation and Application of a Custom-Designed Targeted Next-Generation Sequencing Panel for the Diagnostic Mutational Profiling of Solid Tumors.

    Directory of Open Access Journals (Sweden)

    Guy Froyen

    Full Text Available The inevitable switch from standard molecular methods to next-generation sequencing for the molecular profiling of tumors is challenging for most diagnostic laboratories. However, fixed validation criteria for diagnostic accreditation are not in place because of the great variability in methods and aims. Here, we describe the validation of a custom panel of hotspots in 24 genes for the detection of somatic mutations in non-small cell lung carcinoma, colorectal carcinoma and malignant melanoma starting from FFPE sections, using 14, 36 and 5 cases, respectively. The targeted hotspots were selected for their present or future clinical relevance in solid tumor types. The target regions were enriched with the TruSeq approach starting from limited amounts of DNA. Cost effective sequencing of 12 pooled libraries was done using a micro flow cell on the MiSeq and subsequent data analysis with MiSeqReporter and VariantStudio. The entire workflow was diagnostically validated showing a robust performance with maximal sensitivity and specificity using as thresholds a variant allele frequency >5% and a minimal amplicon coverage of 300. We implemented this method through the analysis of 150 routine diagnostic samples and identified clinically relevant mutations in 16 genes including KRAS (32%, TP53 (32%, BRAF (12%, APC (11%, EGFR (8% and NRAS (5%. Importantly, the highest success rate was obtained when using also the low quality DNA samples. In conclusion, we provide a workflow for the validation of targeted NGS by a custom-designed pan-solid tumor panel in a molecular diagnostic lab and demonstrate its robustness in a clinical setting.

  20. Curcumin and insulin resistance-Molecular targets and clinical evidences.

    Science.gov (United States)

    Jiménez-Osorio, Angélica Saraí; Monroy, Adriana; Alavez, Silvestre

    2016-11-12

    Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the main component of the Indian spice turmeric, has been used in traditional medicine to improve diabetes and its comorbidities. Since the last two decades, scientific research has shown that in addition to its antioxidant properties, curcumin could also work as protein homeostasis regulator and it is able to modulate other intracellular pathways. Curcumin supplementation has been proposed to improve insulin resistance (IR) through the activation of the insulin receptor and its downstream pathways in several experimental models, pointing out that its clinical use may be a good and innocuous strategy to improve IR-related diseases. IR is associated with many diseases and syndromes like carbohydrate intolerance, diabetes, metabolic syndrome, and cardiovascular disease. Therefore, it is imperative to identify safe therapeutic interventions aimed to reduce side effects that could lead the patient to leave the treatment. To date, many clinical trials have been carried out using turmeric and curcumin to improve metabolic syndrome, carbohydrate intolerance, diabetes, and obesity in individuals with IR. Results so far are inconclusive because dose, time of treatment, and type of curcumin can change the study outcome significantly. However, there is some clinical evidence suggesting a beneficial effect of curcumin on IR. In this review, we discuss the factors that could influence curcumin effects in clinical trials aimed to improve IR and related diseases, and the conclusions that can be drawn from results obtained so far. © 2016 BioFactors, 42(6):561-580, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  1. Statistical model based gender prediction for targeted NGS clinical panels

    Directory of Open Access Journals (Sweden)

    Palani Kannan Kandavel

    2017-12-01

    The reference test dataset are being used to test the model. The sensitivity on predicting the gender has been increased from the current “genotype composition in ChrX” based approach. In addition, the prediction score given by the model can be used to evaluate the quality of clinical dataset. The higher prediction score towards its respective gender indicates the higher quality of sequenced data.

  2. Optimization and in Vivo Validation of Peptide Vectors Targeting the LDL Receptor.

    Science.gov (United States)

    Jacquot, Guillaume; Lécorché, Pascaline; Malcor, Jean-Daniel; Laurencin, Mathieu; Smirnova, Maria; Varini, Karine; Malicet, Cédric; Gassiot, Fanny; Abouzid, Karima; Faucon, Aude; David, Marion; Gaudin, Nicolas; Masse, Maxime; Ferracci, Géraldine; Dive, Vincent; Cisternino, Salvatore; Khrestchatisky, Michel

    2016-12-05

    -VH4127 in wild-type or ldlr -/- mice confirmed their active LDLR targeting in vivo. Overall, this study extends our previous work toward a diversified portfolio of LDLR-targeted peptide vectors with validated LDLR-targeting potential in vivo.

  3. Pragmatic controlled clinical trials in primary care: the struggle between external and internal validity

    Directory of Open Access Journals (Sweden)

    Birtwhistle Richard

    2003-12-01

    Full Text Available Abstract Background Controlled clinical trials of health care interventions are either explanatory or pragmatic. Explanatory trials test whether an intervention is efficacious; that is, whether it can have a beneficial effect in an ideal situation. Pragmatic trials measure effectiveness; they measure the degree of beneficial effect in real clinical practice. In pragmatic trials, a balance between external validity (generalizability of the results and internal validity (reliability or accuracy of the results needs to be achieved. The explanatory trial seeks to maximize the internal validity by assuring rigorous control of all variables other than the intervention. The pragmatic trial seeks to maximize external validity to ensure that the results can be generalized. However the danger of pragmatic trials is that internal validity may be overly compromised in the effort to ensure generalizability. We are conducting two pragmatic randomized controlled trials on interventions in the management of hypertension in primary care. We describe the design of the trials and the steps taken to deal with the competing demands of external and internal validity. Discussion External validity is maximized by having few exclusion criteria and by allowing flexibility in the interpretation of the intervention and in management decisions. Internal validity is maximized by decreasing contamination bias through cluster randomization, and decreasing observer and assessment bias, in these non-blinded trials, through baseline data collection prior to randomization, automating the outcomes assessment with 24 hour ambulatory blood pressure monitors, and blinding the data analysis. Summary Clinical trials conducted in community practices present investigators with difficult methodological choices related to maintaining a balance between internal validity (reliability of the results and external validity (generalizability. The attempt to achieve methodological purity can

  4. Clinical Validation of a Test for the Diagnosis of Vaginitis.

    Science.gov (United States)

    Gaydos, Charlotte A; Beqaj, Sajo; Schwebke, Jane R; Lebed, Joel; Smith, Bonnie; Davis, Thomas E; Fife, Kenneth H; Nyirjesy, Paul; Spurrell, Timothy; Furgerson, Dorothy; Coleman, Jenell; Paradis, Sonia; Cooper, Charles K

    2017-07-01

    Vaginitis may be diagnosed as bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis, or coinfection. A new molecular test assays the vaginal microbiome and organisms that cause three common infections. The objective of the trial was to evaluate the clinical accuracy of the investigational test for vaginal swabs collected by patients (self) or clinicians. The primary and secondary outcomes were to compare the investigational test with reference methods for the three most common causes of vaginitis and compare clinician-collected with self-collected swabs. We conducted a cross-sectional study in which women with symptoms of vaginitis were recruited at ten clinical centers and consented to the investigation between May and September 2015. The woman collected a vaginal swab, sheathed, and then handed it to the clinician. These swabs were to evaluate how self-collected swabs compared with clinician-collected swabs. The clinician collected an investigational test swab and reference test swabs. From 1,740 symptomatic patients, clinician-collected and self-collected vaginal swabs were evaluated by the molecular test and six tests. The reference methods for bacterial vaginosis were Nugent's score and Amsel's criteria for intermediate Nugent results. The reference methods for Candida infection were isolation of any potential Candida microorganisms from inoculation of two culture media: chromogenic and Sabouraud agar and sequencing. The reference methods for trichomoniasis were wet mount and culture. For clinician-collected swabs, by reference methods, bacterial vaginosis was diagnosed in 56.5%, vaginal candidiasis in 32.8%, trichomoniasis in 8%, and none of the three infections in 24% with a coinfection rate of 20%. The investigational test sensitivity was 90.5% (95% confidence interval [CI] 88.3-92.2%) and specificity was 85.8% (95% CI 83.0-88.3%) for bacterial vaginosis. The investigational test sensitivity was 90.9% (95% CI 88.1-93.1%) and specificity was 94

  5. EEG-based motor network biomarkers for identifying target patients with stroke for upper limb rehabilitation and its construct validity.

    Directory of Open Access Journals (Sweden)

    Chun-Chuan Chen

    Full Text Available Rehabilitation is the main therapeutic approach for reducing poststroke functional deficits in the affected upper limb; however, significant between-patient variability in rehabilitation efficacy indicates the need to target patients who are likely to have clinically significant improvement after treatment. Many studies have determined robust predictors of recovery and treatment gains and yielded many great results using linear approachs. Evidence has emerged that the nonlinearity is a crucial aspect to study the inter-areal communication in human brains and abnormality of oscillatory activities in the motor system is linked to the pathological states. In this study, we hypothesized that combinations of linear and nonlinear (cross-frequency network connectivity parameters are favourable biomarkers for stratifying patients for upper limb rehabilitation with increased accuracy. We identified the biomarkers by using 37 prerehabilitation electroencephalogram (EEG datasets during a movement task through effective connectivity and logistic regression analyses. The predictive power of these biomarkers was then tested by using 16 independent datasets (i.e. construct validation. In addition, 14 right handed healthy subjects were also enrolled for comparisons. The result shows that the beta plus gamma or theta network features provided the best classification accuracy of 92%. The predictive value and the sensitivity of these biomarkers were 81.3% and 90.9%, respectively. Subcortical lesion, the time poststroke and initial Wolf Motor Function Test (WMFT score were identified as the most significant clinical variables affecting the classification accuracy of this predictive model. Moreover, 12 of 14 normal controls were classified as having favourable recovery. In conclusion, EEG-based linear and nonlinear motor network biomarkers are robust and can help clinical decision making.

  6. Validation of the Mayo Clinic Staging System in Determining Prognoses of Patients With Perihilar Cholangiocarcinoma

    NARCIS (Netherlands)

    Coelen, Robert J. S.; Gaspersz, Marcia P.; Labeur, Tim A.; van Vugt, Jeroen L. A.; van Dieren, Susan; Willemssen, François E. J. A.; Nio, Chung Y.; Ijzermans, Jan N. M.; Klümpen, Heinz-Josef; Groot Koerkamp, Bas; van Gulik, Thomas M.

    2017-01-01

    BACKGROUND & AIMS: Most systems for staging perihilar cholangiocarcinoma (PHC) have been developed for the minority of patients with resectable disease. The recently developed Mayo Clinic system for staging PHC requires only clinical and radiologic variables, but has not yet been validated. We

  7. The Reliability, Validity, and Evaluation of the Objective Structured Clinical Examination in Podiatry (Chiropody).

    Science.gov (United States)

    Woodburn, Jim; Sutcliffe, Nick

    1996-01-01

    The Objective Structured Clinical Examination (OSCE), initially developed for undergraduate medical education, has been adapted for assessment of clinical skills in podiatry students. A 12-month pilot study found the test had relatively low levels of reliability, high construct and criterion validity, and good stability of performance over time.…

  8. Validity of a short clinical interview for psychiatric diagnosis : the mini-SCAN

    NARCIS (Netherlands)

    Nienhuis, F. J.; van de Willige, G.; Rijnders, C. A. Th.; de Jonge, P.; Wiersma, D.

    Background To promote clinical application of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) system a shorter version (the mini-SCAN) was devised. Its psychometric properties were unknown. Aims To establish the validity and practical properties of the mini-SCAN. Method One hundred

  9. Automated characterization of perceptual quality of clinical chest radiographs: Validation and calibration to observer preference

    International Nuclear Information System (INIS)

    Samei, Ehsan; Lin, Yuan; Choudhury, Kingshuk R.; Page McAdams, H.

    2014-01-01

    Purpose: The authors previously proposed an image-based technique [Y. Lin et al. Med. Phys. 39, 7019–7031 (2012)] to assess the perceptual quality of clinical chest radiographs. In this study, an observer study was designed and conducted to validate the output of the program against rankings by expert radiologists and to establish the ranges of the output values that reflect the acceptable image appearance so the program output can be used for image quality optimization and tracking. Methods: Using an IRB-approved protocol, 2500 clinical chest radiographs (PA/AP) were collected from our clinical operation. The images were processed through our perceptual quality assessment program to measure their appearance in terms of ten metrics of perceptual image quality: lung gray level, lung detail, lung noise, rib–lung contrast, rib sharpness, mediastinum detail, mediastinum noise, mediastinum alignment, subdiaphragm–lung contrast, and subdiaphragm area. From the results, for each targeted appearance attribute/metric, 18 images were selected such that the images presented a relatively constant appearance with respect to all metrics except the targeted one. The images were then incorporated into a graphical user interface, which displayed them into three panels of six in a random order. Using a DICOM calibrated diagnostic display workstation and under low ambient lighting conditions, each of five participating attending chest radiologists was tasked to spatially order the images based only on the targeted appearance attribute regardless of the other qualities. Once ordered, the observer also indicated the range of image appearances that he/she considered clinically acceptable. The observer data were analyzed in terms of the correlations between the observer and algorithmic rankings and interobserver variability. An observer-averaged acceptable image appearance was also statistically derived for each quality attribute based on the collected individual acceptable ranges

  10. Automated characterization of perceptual quality of clinical chest radiographs: Validation and calibration to observer preference

    Energy Technology Data Exchange (ETDEWEB)

    Samei, Ehsan, E-mail: samei@duke.edu [Carl E. Ravin Advanced Imaging Laboratories, Departments of Radiology, Physics, Biomedical Engineering, Electrical and Computer Engineering, Medical Physics Graduate Program, Duke Clinical Imaging Physics Group, Duke University, Durham, North Carolina 27710 (United States); Lin, Yuan [Carl E. Ravin Advanced Imaging Laboratories, Departments of Radiology and Physics, Duke University, Durham, North Carolina 27710 (United States); Choudhury, Kingshuk R. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology and Biostatistics and Bioinformatics, Duke University, Durham, North Carolina 27710 (United States); Page McAdams, H. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University, Durham, North Carolina 27710 (United States)

    2014-11-01

    Purpose: The authors previously proposed an image-based technique [Y. Lin et al. Med. Phys. 39, 7019–7031 (2012)] to assess the perceptual quality of clinical chest radiographs. In this study, an observer study was designed and conducted to validate the output of the program against rankings by expert radiologists and to establish the ranges of the output values that reflect the acceptable image appearance so the program output can be used for image quality optimization and tracking. Methods: Using an IRB-approved protocol, 2500 clinical chest radiographs (PA/AP) were collected from our clinical operation. The images were processed through our perceptual quality assessment program to measure their appearance in terms of ten metrics of perceptual image quality: lung gray level, lung detail, lung noise, rib–lung contrast, rib sharpness, mediastinum detail, mediastinum noise, mediastinum alignment, subdiaphragm–lung contrast, and subdiaphragm area. From the results, for each targeted appearance attribute/metric, 18 images were selected such that the images presented a relatively constant appearance with respect to all metrics except the targeted one. The images were then incorporated into a graphical user interface, which displayed them into three panels of six in a random order. Using a DICOM calibrated diagnostic display workstation and under low ambient lighting conditions, each of five participating attending chest radiologists was tasked to spatially order the images based only on the targeted appearance attribute regardless of the other qualities. Once ordered, the observer also indicated the range of image appearances that he/she considered clinically acceptable. The observer data were analyzed in terms of the correlations between the observer and algorithmic rankings and interobserver variability. An observer-averaged acceptable image appearance was also statistically derived for each quality attribute based on the collected individual acceptable ranges

  11. Validation of the Novaco Anger Scale-Provocation Inventory (Danish) With Nonclinical, Clinical, and Offender Samples

    DEFF Research Database (Denmark)

    Moeller, Stine Bjerrum; Novaco, Raymond; Heinola-Nielsen, Vivian

    2015-01-01

    Anger has high prevalence in clinical and forensic settings, and it is associated with aggressive behavior and ward atmosphere on psychiatric units. Dysregulated anger is a clinical problem in Danish mental health care systems, but no anger assessment instruments have been validated in Danish...... investigated with samples of 477 nonclinical, 250 clinical, 167 male prisoner, and 64 male forensic participants. Anger prevalence and its relationship with other anger measures, anxiety/depression, and aggression were examined. NAS-PI was found to have high reliability, concurrent validity, and discriminant...

  12. Deorphanization and target validation of cross-tick species conserved novel Amblyomma americanum tick saliva protein.

    Science.gov (United States)

    Mulenga, Albert; Kim, Tae Kwon; Ibelli, Adriana Mércia Guaratini

    2013-05-01

    We previously identified a cross-tick species conserved tick feeding stimuli responsive Amblyomma americanum (Aam) AV422 gene. This study demonstrates that AamAV422 belongs to a novel group of arthropod proteins that is characterized by 14 cysteine amino acid residues: C(23)-X7/9-C(33)-X23/24-C(58)-X8-C(67)-X7-C(75)-X23-C(99)-X15-C(115)-X10-C(126)-X24/25/33-C(150)C(151)-X7-C(159)-X8-C(168)-X23/24-C(192)-X9/10-C(202) predicted to form seven disulfide bonds. We show that AamAV422 protein is a ubiquitously expressed protein that is injected into the host within the first 24h of the tick attaching onto the host as revealed by Western blotting analyses of recombinant (r)AamAV422, tick saliva and dissected tick organ protein extracts using antibodies to 24 and 48 h tick saliva proteins. Native AamAV422 is apparently involved with mediating tick anti-hemostasis and anti-complement functions in that rAamAV422 delayed plasma clotting time in a dose responsive manner by up to ≈ 160 s, prevented platelet aggregation by up to ≈ 16% and caused ≈ 24% reduction in production of terminal complement complexes. Target validation analysis revealed that rAamAV422 is a potential candidate for a cocktail or multivalent tick vaccine preparation in that RNA interference (RNAi)-mediated silencing of AamAV422 mRNA caused a statistically significant (≈ 44%) reduction in tick engorgement weights, which is proxy for amounts of ingested blood. We speculate that AamAV422 is a potential target antigen for development of the highly desired universal tick vaccine in that consistent with high conservation among ticks, antibodies to 24h Ixodes scapularis tick saliva proteins specifically bound rAamAV422. We discuss data in this study in the context of advancing the biology of tick feeding physiology and discovery of potential target antigens for tick vaccine development. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  13. The validation and clinical implementation of BRCAplus: a comprehensive high-risk breast cancer diagnostic assay.

    Directory of Open Access Journals (Sweden)

    Hansook Kim Chong

    Full Text Available Breast cancer is the most commonly diagnosed cancer in women, with 10% of disease attributed to hereditary factors. Although BRCA1 and BRCA2 account for a high percentage of hereditary cases, there are more than 25 susceptibility genes that differentially impact the risk for breast cancer. Traditionally, germline testing for breast cancer was performed by Sanger dideoxy terminator sequencing in a reflexive manner, beginning with BRCA1 and BRCA2. The introduction of next-generation sequencing (NGS has enabled the simultaneous testing of all genes implicated in breast cancer resulting in diagnostic labs offering large, comprehensive gene panels. However, some physicians prefer to only test for those genes in which established surveillance and treatment protocol exists. The NGS based BRCAplus test utilizes a custom tiled PCR based target enrichment design and bioinformatics pipeline coupled with array comparative genomic hybridization (aCGH to identify mutations in the six high-risk genes: BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11. Validation of the assay with 250 previously characterized samples resulted in 100% detection of 3,025 known variants and analytical specificity of 99.99%. Analysis of the clinical performance of the first 3,000 BRCAplus samples referred for testing revealed an average coverage greater than 9,000X per target base pair resulting in excellent specificity and the sensitivity to detect low level mosaicism and allele-drop out. The unique design of the assay enabled the detection of pathogenic mutations missed by previous testing. With the abundance of NGS diagnostic tests being released, it is essential that clinicians understand the advantages and limitations of different test designs.

  14. Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

    Directory of Open Access Journals (Sweden)

    Steven M Yip

    2016-03-01

    Full Text Available Treatment of metastatic renal cell cancer (mRCC currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2, and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.

  15. Development and validation of an instrument to measure nurse educator perceived confidence in clinical teaching.

    Science.gov (United States)

    Nguyen, Van N B; Forbes, Helen; Mohebbi, Mohammadreza; Duke, Maxine

    2017-12-01

    Teaching nursing in clinical environments is considered complex and multi-faceted. Little is known about the role of the clinical nurse educator, specifically the challenges related to transition from clinician, or in some cases, from newly-graduated nurse to that of clinical nurse educator, as occurs in developing countries. Confidence in the clinical educator role has been associated with successful transition and the development of role competence. There is currently no valid and reliable instrument to measure clinical nurse educator confidence. This study was conducted to develop and psychometrically test an instrument to measure perceived confidence among clinical nurse educators. A multi-phase, multi-setting survey design was used. A total of 468 surveys were distributed, and 363 were returned. Data were analyzed using exploratory and confirmatory factor analyses. The instrument was successfully tested and modified in phase 1, and factorial validity was subsequently confirmed in phase 2. There was strong evidence of internal consistency, reliability, content, and convergent validity of the Clinical Nurse Educator Skill Acquisition Assessment instrument. The resulting instrument is applicable in similar contexts due to its rigorous development and validation process. © 2017 The Authors. Nursing & Health Sciences published by John Wiley & Sons Australia, Ltd.

  16. Validity and Reliability of the Clinical Competency Evaluation Instrument for Use among Physiotherapy Students: Pilot study.

    Science.gov (United States)

    Muhamad, Zailani; Ramli, Ayiesah; Amat, Salleh

    2015-05-01

    The aim of this study was to determine the content validity, internal consistency, test-retest reliability and inter-rater reliability of the Clinical Competency Evaluation Instrument (CCEVI) in assessing the clinical performance of physiotherapy students. This study was carried out between June and September 2013 at University Kebangsaan Malaysia (UKM), Kuala Lumpur, Malaysia. A panel of 10 experts were identified to establish content validity by evaluating and rating each of the items used in the CCEVI with regards to their relevance in measuring students' clinical competency. A total of 50 UKM undergraduate physiotherapy students were assessed throughout their clinical placement to determine the construct validity of these items. The instrument's reliability was determined through a cross-sectional study involving a clinical performance assessment of 14 final-year undergraduate physiotherapy students. The content validity index of the entire CCEVI was 0.91, while the proportion of agreement on the content validity indices ranged from 0.83-1.00. The CCEVI construct validity was established with factor loading of ≥0.6, while internal consistency (Cronbach's alpha) overall was 0.97. Test-retest reliability of the CCEVI was confirmed with a Pearson's correlation range of 0.91-0.97 and an intraclass coefficient correlation range of 0.95-0.98. Inter-rater reliability of the CCEVI domains ranged from 0.59 to 0.97 on initial and subsequent assessments. This pilot study confirmed the content validity of the CCEVI. It showed high internal consistency, thereby providing evidence that the CCEVI has moderate to excellent inter-rater reliability. However, additional refinement in the wording of the CCEVI items, particularly in the domains of safety and documentation, is recommended to further improve the validity and reliability of the instrument.

  17. Refining and validating a conceptual model of Clinical Nurse Leader integrated care delivery.

    Science.gov (United States)

    Bender, Miriam; Williams, Marjory; Su, Wei; Hites, Lisle

    2017-02-01

    To empirically validate a conceptual model of Clinical Nurse Leader integrated care delivery. There is limited evidence of frontline care delivery models that consistently achieve quality patient outcomes. Clinical Nurse Leader integrated care delivery is a promising nursing model with a growing record of success. However, theoretical clarity is necessary to generate causal evidence of effectiveness. Sequential mixed methods. A preliminary Clinical Nurse Leader practice model was refined and survey items developed to correspond with model domains, using focus groups and a Delphi process with a multi-professional expert panel. The survey was administered in 2015 to clinicians and administrators involved in Clinical Nurse Leader initiatives. Confirmatory factor analysis and structural equation modelling were used to validate the measurement and model structure. Final sample n = 518. The model incorporates 13 components organized into five conceptual domains: 'Readiness for Clinical Nurse Leader integrated care delivery'; 'Structuring Clinical Nurse Leader integrated care delivery'; 'Clinical Nurse Leader Practice: Continuous Clinical Leadership'; 'Outcomes of Clinical Nurse Leader integrated care delivery'; and 'Value'. Sample data had good fit with specified model and two-level measurement structure. All hypothesized pathways were significant, with strong coefficients suggesting good fit between theorized and observed path relationships. The validated model articulates an explanatory pathway of Clinical Nurse Leader integrated care delivery, including Clinical Nurse Leader practices that result in improved care dynamics and patient outcomes. The validated model provides a basis for testing in practice to generate evidence that can be deployed across the healthcare spectrum. © 2016 John Wiley & Sons Ltd.

  18. Validity, reliability, and feasibility of clinical staging scales in dementia: a systematic review

    DEFF Research Database (Denmark)

    Rikkert, Marcel G M Olde; Tona, Klodiana Daphne; Janssen, Lieneke

    2011-01-01

    New staging systems of dementia require adaptation of disease management programs and adequate staging instruments. Therefore, we systematically reviewed the literature on validity and reliability of clinically applicable, multidomain, and dementia staging instruments. A total of 23 articles...... describing 12 staging instruments were identified (N = 6109 participants, age 65-87). Reliability was studied in most (91%) of the articles and was judged moderate to good. Approximately 78% of the articles evaluated concurrent validity, which was good to very good, while discriminant validity was assessed...... in only 25%. The scales can be applied in ±15 minutes. Clinical Dementia Rating (CDR), Global Deterioration scale (GDS), and Functional Assessment Staging (FAST) have been monitored on reliability and validity, and the CDR currently is the best-evidenced scale, also studied in international perspective...

  19. Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

    Science.gov (United States)

    Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

    2016-01-01

    Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

  20. Identification of clinical target areas in the brainstem of prion‐infected mice

    Science.gov (United States)

    Mirabile, Ilaria; Jat, Parmjit S.; Brandner, Sebastian

    2015-01-01

    Aims While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas. Method We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset). Results We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre‐Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem. Conclusions Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre‐Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic Creutzfeldt–Jakob disease, we suggest that these nuclei represent key clinical target areas in prion diseases. PMID:25311251

  1. Functional characterisation and drug target validation of a mitotic kinesin-13 in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Kuan Yoow Chan

    2010-08-01

    Full Text Available Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation. Therefore, in humans, kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies. Phylogenetic analyses have assigned five of the approximately fifty kinesin motor proteins coded by Trypanosoma brucei genome to the Kinesin-13 family. Kinesins of this family have unusual biochemical properties because they do not transport cargo along microtubules but are able to depolymerise microtubules at their ends, therefore contributing to the regulation of microtubule length. In other eukaryotic genomes sequenced to date, only between one and three Kinesin-13s are present. We have used immunolocalisation, RNAi-mediated protein depletion, biochemical in vitro assays and a mouse model of infection to study the single mitotic Kinesin-13 in T. brucei. Subcellular localisation of all five T. brucei Kinesin-13s revealed distinct distributions, indicating that the expansion of this kinesin family in kinetoplastids is accompanied by functional diversification. Only a single kinesin (TbKif13-1 has a nuclear localisation. Using active, recombinant TbKif13-1 in in vitro assays we experimentally confirm the depolymerising properties of this kinesin. We analyse the biological function of TbKif13-1 by RNAi-mediated protein depletion and show its central role in regulating spindle assembly during mitosis. Absence of the protein leads to abnormally long and bent mitotic spindles, causing chromosome mis-segregation and cell death. RNAi-depletion in a mouse model of infection completely prevents infection with the parasite. Given its essential role in mitosis, proliferation and survival of the parasite and the availability of a simple in vitro activity assay, TbKif13-1 has been identified as an excellent potential drug target.

  2. Performance Validity Testing in Neuropsychology: Scientific Basis and Clinical Application-A Brief Review.

    Science.gov (United States)

    Greher, Michael R; Wodushek, Thomas R

    2017-03-01

    Performance validity testing refers to neuropsychologists' methodology for determining whether neuropsychological test performances completed in the course of an evaluation are valid (ie, the results of true neurocognitive function) or invalid (ie, overly impacted by the patient's effort/engagement in testing). This determination relies upon the use of either standalone tests designed for this sole purpose, or specific scores/indicators embedded within traditional neuropsychological measures that have demonstrated this utility. In response to a greater appreciation for the critical role that performance validity issues play in neuropsychological testing and the need to measure this variable to the best of our ability, the scientific base for performance validity testing has expanded greatly over the last 20 to 30 years. As such, the majority of current day neuropsychologists in the United States use a variety of measures for the purpose of performance validity testing as part of everyday forensic and clinical practice and address this issue directly in their evaluations. The following is the first article of a 2-part series that will address the evolution of performance validity testing in the field of neuropsychology, both in terms of the science as well as the clinical application of this measurement technique. The second article of this series will review performance validity tests in terms of methods for development of these measures, and maximizing of diagnostic accuracy.

  3. Implementing targeted region capture sequencing for the clinical detection of Alagille syndrome: An efficient and cost‑effective method.

    Science.gov (United States)

    Huang, Tianhong; Yang, Guilin; Dang, Xiao; Ao, Feijian; Li, Jiankang; He, Yizhou; Tang, Qiyuan; He, Qing

    2017-11-01

    Alagille syndrome (AGS) is a highly variable, autosomal dominant disease that affects multiple structures including the liver, heart, eyes, bones and face. Targeted region capture sequencing focuses on a panel of known pathogenic genes and provides a rapid, cost‑effective and accurate method for molecular diagnosis. In a Chinese family, this method was used on the proband and Sanger sequencing was applied to validate the candidate mutation. A de novo heterozygous mutation (c.3254_3255insT p.Leu1085PhefsX24) of the jagged 1 gene was identified as the potential disease‑causing gene mutation. In conclusion, the present study suggested that target region capture sequencing is an efficient, reliable and accurate approach for the clinical diagnosis of AGS. Furthermore, these results expand on the understanding of the pathogenesis of AGS.

  4. Prognostic significance of clinical seizures after cardiac arrest and target temperature management

    DEFF Research Database (Denmark)

    Lybeck, Anna; Friberg, Hans; Aneman, Anders

    2017-01-01

    AIM: Clinical seizures are common after cardiac arrest and predictive of a poor neurological outcome. Seizures may be myoclonic, tonic-clonic or a combination of seizure types. This study reports the incidence and prognostic significance of clinical seizures in the target temperature management (...

  5. In Silico Prediction and Validation of Gfap as an miR-3099 Target in Mouse Brain.

    Science.gov (United States)

    Abidin, Shahidee Zainal; Leong, Jia-Wen; Mahmoudi, Marzieh; Nordin, Norshariza; Abdullah, Syahril; Cheah, Pike-See; Ling, King-Hwa

    2017-08-01

    MicroRNAs are small non-coding RNAs that play crucial roles in the regulation of gene expression and protein synthesis during brain development. MiR-3099 is highly expressed throughout embryogenesis, especially in the developing central nervous system. Moreover, miR-3099 is also expressed at a higher level in differentiating neurons in vitro, suggesting that it is a potential regulator during neuronal cell development. This study aimed to predict the target genes of miR-3099 via in-silico analysis using four independent prediction algorithms (miRDB, miRanda, TargetScan, and DIANA-micro-T-CDS) with emphasis on target genes related to brain development and function. Based on the analysis, a total of 3,174 miR-3099 target genes were predicted. Those predicted by at least three algorithms (324 genes) were subjected to DAVID bioinformatics analysis to understand their overall functional themes and representation. The analysis revealed that nearly 70% of the target genes were expressed in the nervous system and a significant proportion were associated with transcriptional regulation and protein ubiquitination mechanisms. Comparison of in situ hybridization (ISH) expression patterns of miR-3099 in both published and in-house-generated ISH sections with the ISH sections of target genes from the Allen Brain Atlas identified 7 target genes (Dnmt3a, Gabpa, Gfap, Itga4, Lxn, Smad7, and Tbx18) having expression patterns complementary to miR-3099 in the developing and adult mouse brain samples. Of these, we validated Gfap as a direct downstream target of miR-3099 using the luciferase reporter gene system. In conclusion, we report the successful prediction and validation of Gfap as an miR-3099 target gene using a combination of bioinformatics resources with enrichment of annotations based on functional ontologies and a spatio-temporal expression dataset.

  6. Prediction of higher cost of antiretroviral therapy (ART) according to clinical complexity. A validated clinical index.

    Science.gov (United States)

    Velasco, Cesar; Pérez, Inaki; Podzamczer, Daniel; Llibre, Josep Maria; Domingo, Pere; González-García, Juan; Puig, Inma; Ayala, Pilar; Martín, Mayte; Trilla, Antoni; Lázaro, Pablo; Gatell, Josep Maria

    2016-03-01

    The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  7. Bayesian Nonparametric Estimation of Targeted Agent Effects on Biomarker Change to Predict Clinical Outcome

    Science.gov (United States)

    Graziani, Rebecca; Guindani, Michele; Thall, Peter F.

    2015-01-01

    Summary The effect of a targeted agent on a cancer patient's clinical outcome putatively is mediated through the agent's effect on one or more early biological events. This is motivated by pre-clinical experiments with cells or animals that identify such events, represented by binary or quantitative biomarkers. When evaluating targeted agents in humans, central questions are whether the distribution of a targeted biomarker changes following treatment, the nature and magnitude of this change, and whether it is associated with clinical outcome. Major difficulties in estimating these effects are that a biomarker's distribution may be complex, vary substantially between patients, and have complicated relationships with clinical outcomes. We present a probabilistically coherent framework for modeling and estimation in this setting, including a hierarchical Bayesian nonparametric mixture model for biomarkers that we use to define a functional profile of pre-versus-post treatment biomarker distribution change. The functional is similar to the receiver operating characteristic used in diagnostic testing. The hierarchical model yields clusters of individual patient biomarker profile functionals, and we use the profile as a covariate in a regression model for clinical outcome. The methodology is illustrated by analysis of a dataset from a clinical trial in prostate cancer using imatinib to target platelet-derived growth factor, with the clinical aim to improve progression-free survival time. PMID:25319212

  8. Interactive adaptation of a volumetric imaging radiotherapy treatment: development and validation of tools for its implementation in clinical routine

    International Nuclear Information System (INIS)

    Huger, Sandrine

    2013-01-01

    Changing anatomy during radiotherapy can lead to significant dosimetric consequences for organs at risk (OARs) and/or target volumes. Adaptive radiotherapy can compensate for these variations however its deployment for clinical work is hampered by the increased workload for the medical staff and there is still no commercialized software available for clinical use. We developed a simple in vivo dosimetric alert tool allowing rapid identification of patients who might benefit from an adaptive radiotherapy. Dosimetric evaluation of delivered treatment has been conducted onto 3D on board imaging (CBCT) whose dose calculation accuracy has been evaluated. The tool does not require a new volume of interest delineation. Tool alert is based on objectives and quantifiable criteria defined by the exceeding volumes of interest dose thresholds. Tool precision and detectability have been validated and applied in a retrospective study on 10 head and neck patients. The tool allows detecting patients where an adaptive treatment could have been considered. In its clinical implementation, adaptive radiotherapy process requires deformable matching algorithms to follow patient local's deformations occurring during treatment. Nevertheless, their use has not been validated. We conducted an evaluation of the Block Matching deformable algorithm, suitable for multimodality imaging (CT/CBCT), in comparison to rigid algorithm. A study has been conducted for 10 head and neck patients based on volume of interest contours comparison for 76 CBCT. Similarity parameters used consisted on Dice Similarity Index, Robust Hausdorff Distance (in mm) and the absolute volume difference (in cc). (author)

  9. Criterion Validation Testing of Clinical Metrology Instruments for Measuring Degenerative Joint Disease Associated Mobility Impairment in Cats.

    Science.gov (United States)

    Gruen, Margaret E; Griffith, Emily H; Thomson, Andrea E; Simpson, Wendy; Lascelles, B Duncan X

    2015-01-01

    Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM). Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period. Activity counts were increased in cats during treatment with daily meloxicam (pdegenerative joint disease.

  10. Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.

    LENUS (Irish Health Repository)

    Gasch, Claudia

    2017-01-01

    It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.

  11. Health status in routine clinical practice: validity of the clinical COPD questionnaire at the individual patient level

    Directory of Open Access Journals (Sweden)

    de Vos Barbara

    2010-11-01

    Full Text Available Abstract Background There is a growing interest to use health status or disease control questionnaires in routine clinical practice. However, the validity of most questionnaires is established using techniques developed for group level validation. This study examines a new method, using patient interviews, to validate a short health status questionnaire, the Clinical COPD Questionnaire (CCQ, at the individual patient level. Methods Patients with COPD who visited an outpatient clinic completed the CCQ before the consultation, and the specialist physician completed it after the consultation. After the consultation all patients had a semi-structured in-depth interview. The patients' CCQ scores were compared with those of the treating clinician, and with mean scores from 5 clinicians from a pool of 20 who scored the CCQ after reading the transcript of the in-depth interviews only. Agreement was assessed using Lin's concordance correlation coefficient (CCC, and Blant and Altman plots. Interviews with patients with low agreement were reviewed for possible explanations. Results A total of 44 COPD patients (32 male, mean age 66 years, FEV1 45% of predicted participated. Agreement between the patients' CCQ scores and those of the treating clinicians (CCC = 0.87 and the mean score of the reviewing clinicians (CCC = 0.86 was very high. No systematic error was detected. No explanation for individuals with low agreement was found. Conclusion The validity of the CCQ on the individual patient level, as assessed by these methods, is good. Individual health status assessment with the CCQ is therefore sufficiently accurate to be used in routine clinical practice.

  12. Validation of the presence of comorbidities in a Danish clinical cohort of children with tourette syndrome

    DEFF Research Database (Denmark)

    Debes, N.M.M.M.; Hjalgrim, H.; Skov, L.

    2008-01-01

    attacks, Sleeping disturbances, and depressive Symptoms in a Danish clinical cohort of 314 children with TS using Validated diagnostic instruments. For the assessment of symptoms of seasonal affective disorder and Stuttering, WC Used a nonvalidated systematic interview. In total, only 10...

  13. Preliminary Validation of a Screening Tool for Adolescent Panic Disorder in Pediatric Primary Care Clinics

    Science.gov (United States)

    Queen, Alexander H.; Ehrenreich-May, Jill; Hershorin, Eugene R.

    2012-01-01

    This study examines the validity of a brief screening tool for adolescent panic disorder (PD) in a primary care setting. A total of 165 participants (ages 12-17 years) seen in two pediatric primary care clinics completed the Autonomic Nervous System Questionnaire (ANS; Stein et al. in Psychosomatic Med 61:359-364, 40). A subset of those screening…

  14. Clinical Validation of the "Sedentary Lifestyle" Nursing Diagnosis in Secondary School Students

    Science.gov (United States)

    de Oliveira, Marcos Renato; da Silva, Viviane Martins; Guedes, Nirla Gomes; de Oliveira Lopes, Marcos Venícios

    2016-01-01

    This study clinically validated the nursing diagnosis of "sedentary lifestyle" (SL) among 564 Brazilian adolescents. Measures of diagnostic accuracy were calculated for defining characteristics, and Mantel--Haenszel analysis was used to identify related factors. The measures of diagnostic accuracy showed that the following defining…

  15. A combination of process of care and clinical target among type 2 diabetes mellitus patients in general medical clinics and specialist diabetes clinics at hospital levels.

    Science.gov (United States)

    Sieng, Sokha; Hurst, Cameron

    2017-08-07

    This study compares a combination of processes of care and clinical targets among patients with type 2 diabetes mellitus (T2DM) between specialist diabetes clinics (SDCs) and general medical clinics (GMCs), and how differences between these two types of clinics differ with hospital type (community, provincial and regional). Type 2 diabetes mellitus patient medical records were collected from 595 hospitals (499 community, 70 provincial, 26 regional) in Thailand between April 1 to June 30, 2012 resulting in a cross-sectional sample of 26,860 patients. Generalized linear mixed modeling was conducted to examine associations between clinic type and quality of care. The outcome variables of interest were split into clinical targets and process of care. A subsequent subgroup analysis was conducted to examine if the nature of clinical target and process of care differences between GMCs and SDCs varied with hospital type (regional, provincial, community). Regardless of the types of hospitals (regional, provincial, or community) patients attending SDCs were considerably more likely to have eye and foot exam. In terms of larger hospitals (regional and provincial) patients attending SDCs were more likely to achieve HbA1c exam, All FACE exam, BP target, and the Num7Q. Interestingly, SDCs performed better than GMCs at only provincial hospitals for LDL-C target and the All7Q. Finally, patients with T2DM who attended community hospital-GMCs had a better chance of achieving the blood pressure target than patients who attended community hospital-SDCs. Specialized diabetes clinics outperform general medical clinics for both regional and provincial hospitals for all quality of care indicators and the number of quality of care indicators achieved was never lower. However, this better performance of SDC was not observed in community hospital. Indeed, GMCs outperformed SDCs for some quality of care indicators in the community level setting.

  16. FORENSIC-CLINICAL INTERVIEW: RELIABILITY AND VALIDITY FOR THE EVALUATION OF PSYCHOLOGICAL INJURY

    Directory of Open Access Journals (Sweden)

    Francisca Fariña

    2013-01-01

    Full Text Available Forensic evaluation of psychological injury involves the use of a multimethod approximation i.e., a psychometric instrument, normally the MMPI-2, and a clinical interview. In terms of the clinical interview, the traditional clinical interview (e.g., SCID is not valid for forensic settings as it does not fulfil the triple objective of forensic evaluation: diagnosis of psychological injury in terms of Post Traumatic Stress Disorder (PTSD, a differential diagnosis of feigning, and establishing a causal relationship between allegations of intimate partner violence (IPV and psychological injury. To meet this requirement, Arce and Fariña (2001 created the forensic-clinical interview based on two techniques that do not contaminate the contents i.e., reinstating the contexts and free recall, and a methodic categorical system of contents analysis for the diagnosis of psychological injury and a differential diagnosis of feigning. The reliability and validity of the forensic-clinical interview designed for the forensic evaluation of psychological injury was assessed in 51 genuine cases of (IPV and 54 mock victims of IPV who were evaluated using a forensic-clinical interview and the MMPI-2. The result revealed that the forensic-clinical interview was a reliable instrument (α = .85 for diagnostic criteria of psychological injury, and α = .744 for feigning strategies. Moreover, the results corroborated the predictive validity (the diagnosis of PTSD was similar to the expected rate; the convergence validity (the diagnosis of PTSD in the interview strongly correlated with the Pk Scale of the MMPI-2, and discriminant validity (the diagnosis of PTSD in the interview did not correlate with the Pk Scale in feigners. The feigning strategies (differential diagnosis also showed convergent validity (high correlation with the Scales and indices of the MMPI2 for the measure of feigning and discriminant validity (no genuine victim was classified as a feigner

  17. Utilize target motion to cover clinical target volume (ctv) - a novel and practical treatment planning approach to manage respiratory motion

    International Nuclear Information System (INIS)

    Jin Jianyue; Ajlouni, Munther; Kong Fengming; Ryu, Samuel; Chetty, Indrin J.; Movsas, Benjamin

    2008-01-01

    Purpose: To use probability density function (PDF) to model motion effects and incorporate this information into treatment planning for lung cancers. Material and methods: PDFs were calculated from the respiratory motion traces of 10 patients. Motion effects were evaluated by convolving static dose distributions with various PDFs. Based on a differential dose prescription with relatively lower dose to the clinical target volume (CTV) than to the gross tumor volume (GTV), two approaches were proposed to incorporate PDFs into treatment planning. The first approach uses the GTV-based internal target volume (ITV) as the planning target volume (PTV) to ensure full dose to the GTV, and utilizes the motion-induced dose gradient to cover the CTV. The second approach employs an inhomogeneous static dose distribution within a minimized PTV to best match the prescription dose gradient. Results: Motion effects on dose distributions were minimal in the anterior-posterior (AP) and lateral directions: a 10-mm motion only induced about 3% of dose reduction in the peripheral target region. The motion effect was remarkable in the cranial-caudal direction. It varied with the motion amplitude, but tended to be similar for various respiratory patterns. For the first approach, a 10-15 mm motion would adequately cover the CTV (presumed to be 60-70% of the GTV dose) without employing the CTV in planning. For motions 15-mm. An example of inhomogeneous static dose distribution in a reduced PTV was given, and it showed significant dose reduction in the normal tissue without compromising target coverage. Conclusions: Respiratory motion-induced dose gradient can be utilized to cover the CTV and minimize the lung dose without the need for more sophisticated technologies

  18. Validation by simulation of a clinical trial model using the standardized mean and variance criteria.

    Science.gov (United States)

    Abbas, Ismail; Rovira, Joan; Casanovas, Josep

    2006-12-01

    To develop and validate a model of a clinical trial that evaluates the changes in cholesterol level as a surrogate marker for lipodystrophy in HIV subjects under alternative antiretroviral regimes, i.e., treatment with Protease Inhibitors vs. a combination of nevirapine and other antiretroviral drugs. Five simulation models were developed based on different assumptions, on treatment variability and pattern of cholesterol reduction over time. The last recorded cholesterol level, the difference from the baseline, the average difference from the baseline and level evolution, are the considered endpoints. Specific validation criteria based on a 10% minus or plus standardized distance in means and variances were used to compare the real and the simulated data. The validity criterion was met by all models for considered endpoints. However, only two models met the validity criterion when all endpoints were considered. The model based on the assumption that within-subjects variability of cholesterol levels changes over time is the one that minimizes the validity criterion, standardized distance equal to or less than 1% minus or plus. Simulation is a useful technique for calibration, estimation, and evaluation of models, which allows us to relax the often overly restrictive assumptions regarding parameters required by analytical approaches. The validity criterion can also be used to select the preferred model for design optimization, until additional data are obtained allowing an external validation of the model.

  19. SU-F-J-160: Clinical Evaluation of Targeting Accuracy in Radiosurgery Using Tractography

    Energy Technology Data Exchange (ETDEWEB)

    Juh, R; Han, J; Kim, C; Oh, C [Seoul National University Bundang Hospital, Seongnamsi, GyeonggiDo (Korea, Republic of); Suh, T [The catholic university of Korea, Seoul (Korea, Republic of)

    2016-06-15

    Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 males, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodose line underwent 1.5Tesla MR trigeminal nerve. Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement. Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment

  20. SU-E-J-34: Clinical Evaluation of Targeting Accuracy and Tractogrphy Delineation of Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Juh, R; Suh, T; Kim, Y; Han, J; Kim, C; Oh, C; Kim, D [Seoul National University Bundang Hospital (Korea, Republic of)

    2014-06-01

    Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 male, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodose line underwent 1.5Tesla MR trigeminal nerve . Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.

  1. Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

    Science.gov (United States)

    Magro, G.; Molinelli, S.; Mairani, A.; Mirandola, A.; Panizza, D.; Russo, S.; Ferrari, A.; Valvo, F.; Fossati, P.; Ciocca, M.

    2015-09-01

    This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus® chamber. An EBT3® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

  2. Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

    International Nuclear Information System (INIS)

    Magro, G; Molinelli, S; Mairani, A; Mirandola, A; Panizza, D; Russo, S; Valvo, F; Fossati, P; Ciocca, M; Ferrari, A

    2015-01-01

    This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5–30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo ® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus ® chamber. An EBT3 ® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification. (paper)

  3. Validation of the 'United Registries for Clinical Assessment and Research' [UR-CARE], a European Online Registry for Clinical Care and Research in Inflammatory Bowel Disease.

    Science.gov (United States)

    Burisch, Johan; Gisbert, Javier P; Siegmund, Britta; Bettenworth, Dominik; Thomsen, Sandra Bohn; Cleynen, Isabelle; Cremer, Anneline; Ding, Nik John Sheng; Furfaro, Federica; Galanopoulos, Michail; Grunert, Philip Christian; Hanzel, Jurij; Ivanovski, Tamara Knezevic; Krustins, Eduards; Noor, Nurulamin; O'Morain, Neil; Rodríguez-Lago, Iago; Scharl, Michael; Tua, Julia; Uzzan, Mathieu; Ali Yassin, Nuha; Baert, Filip; Langholz, Ebbe

    2018-04-27

    The 'United Registries for Clinical Assessment and Research' [UR-CARE] database is an initiative of the European Crohn's and Colitis Organisation [ECCO] to facilitate daily patient care and research studies in inflammatory bowel disease [IBD]. Herein, we sought to validate the database by using fictional case histories of patients with IBD that were to be entered by observers of varying experience in IBD. Nineteen observers entered five patient case histories into the database. After 6 weeks, all observers entered the same case histories again. For each case history, 20 key variables were selected to calculate the accuracy for each observer. We assumed that the database was such that ≥ 90% of the entered data would be correct. The overall proportion of correctly entered data was calculated using a beta-binomial regression model to account for inter-observer variation and compared to the expected level of validity. Re-test reliability was assessed using McNemar's test. For all case histories, the overall proportion of correctly entered items and their confidence intervals included the target of 90% (Case 1: 92% [88-94%]; Case 2: 87% [83-91%]; Case 3: 93% [90-95%]; Case 4: 97% [94-99%]; Case 5: 91% [87-93%]). These numbers did not differ significantly from those found 6 weeks later [NcNemar's test p > 0.05]. The UR-CARE database appears to be feasible, valid and reliable as a tool and easy to use regardless of prior user experience and level of clinical IBD experience. UR-CARE has the potential to enhance future European collaborations regarding clinical research in IBD.

  4. Modeling and validating Bayesian accrual models on clinical data and simulations using adaptive priors.

    Science.gov (United States)

    Jiang, Yu; Simon, Steve; Mayo, Matthew S; Gajewski, Byron J

    2015-02-20

    Slow recruitment in clinical trials leads to increased costs and resource utilization, which includes both the clinic staff and patient volunteers. Careful planning and monitoring of the accrual process can prevent the unnecessary loss of these resources. We propose two hierarchical extensions to the existing Bayesian constant accrual model: the accelerated prior and the hedging prior. The new proposed priors are able to adaptively utilize the researcher's previous experience and current accrual data to produce the estimation of trial completion time. The performance of these models, including prediction precision, coverage probability, and correct decision-making ability, is evaluated using actual studies from our cancer center and simulation. The results showed that a constant accrual model with strongly informative priors is very accurate when accrual is on target or slightly off, producing smaller mean squared error, high percentage of coverage, and a high number of correct decisions as to whether or not continue the trial, but it is strongly biased when off target. Flat or weakly informative priors provide protection against an off target prior but are less efficient when the accrual is on target. The accelerated prior performs similar to a strong prior. The hedging prior performs much like the weak priors when the accrual is extremely off target but closer to the strong priors when the accrual is on target or only slightly off target. We suggest improvements in these models and propose new models for future research. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma

    DEFF Research Database (Denmark)

    van de Donk, Niels W C J; Moreau, Philippe; Plesner, Torben

    2016-01-01

    Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM...... of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting...

  6. Is Doubling of Serum Creatinine a Valid Clinical 'Hard' Endpoint in Clinical Nephrology Trials?

    NARCIS (Netherlands)

    Lambers Heerspink, H. J.; Perkovic, V.; de Zeeuw, D.

    2011-01-01

    The composite of end stage renal disease (ESRD), doubling of serum creatinine and (renal) death, is a frequently used endpoint in randomized clinical trials in nephrology. Doubling of serum creatinine is a well-accepted part of this endpoint because a doubling of serum creatinine reflects a large

  7. Statistical inference on censored data for targeted clinical trials under enrichment design.

    Science.gov (United States)

    Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

    2013-01-01

    For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

  8. The Clinical Impression of Severity Index for Parkinson's Disease: international validation study.

    Science.gov (United States)

    Martínez-Martín, Pablo; Rodríguez-Blázquez, Carmen; Forjaz, Maria João; de Pedro, Jesús

    2009-01-30

    This study sought to provide further information about the psychometric properties of the Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD), in a large, international, cross-culturally diverse sample. Six hundred and fourteen patients with PD participated in the study. Apart from the CISI-PD, assessments were based on Hoehn & Yahr (HY) staging, the Scales for Outcomes in PD-Motor (SCOPA-M), -Cognition (SCOPA-COG) and -Psychosocial (SCOPA-PS), the Cumulative Illness Rating Scale-Geriatrics, and the Hospital Anxiety and Depression Scale. The total CISI-PD score displayed no floor or ceiling effects. Internal consistency was 0.81, the test-retest intraclass correlation coefficient was 0.84, and item homogeneity was 0.52. Exploratory and confirmatory factor analysis (CFI = 0.99, RMSEA = 0.07) confirmed CISI-PD's unifactorial structure. The CISI-PD showed adequate convergent validity with SCOPA-COG and SCOPA-M (r(S) = 0.46-0.85, respectively) and discriminative validity for HY stages and disease duration (P validation study, thus showing that the CISI-PD is a valid instrument to measure clinical impression of severity in PD. Its simplicity and easy application make it an attractive and useful tool for clinical practice and research.

  9. The reliability and validity of the Everyday Feelings Questionnaire in a clinical population.

    Science.gov (United States)

    Mann, Joanna; Henley, William; O'Mahen, Heather; Ford, Tamsin

    2013-06-01

    Depression could be considered to be on a continuum with well-being and some have argued that it is important to measure well-being as well as distress. The Everyday Feelings Questionnaire was designed to measure both these aspects. Its validity has been assessed in a nonclinical population. This project aims to assess the validity and reliability of the EFQ in a clinical population. The EFQ was completed by 105 clients within a mental health clinical setting. The following aspects of the EFQ were explored: its internal structure, concurrent validity, re-test reliability and internal consistency. The EFQ had good internal consistency and correlated highly with other measures of anxiety and depression. The correlation between total EFQ scores on the two occasions was reasonable and there was no effect of time during completion. A Bland-Altman plot showed no obvious pattern between the difference between EFQ scores and the mean score. A one factor model showed a moderate fit to the data. This study does not explore the acceptability or sensitivity to change of the EFQ, and a larger sample size would be needed to extend the analysis conducted. The EFQ is a valid and reliable measure when used in this clinical population. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. A critical evaluation of the validity of episodic future thinking: A clinical neuropsychology perspective.

    Science.gov (United States)

    Ward, Amanda M

    2016-11-01

    Episodic future thinking is defined as the ability to mentally simulate a future event. Although episodic future thinking has been studied extensively in neuroscience, this construct has not been explored in depth from the perspective of clinical neuropsychology. The aim of this critical narrative review is to assess the validity and clinical implications of episodic future thinking. A systematic review of episodic future thinking literature was conducted. PubMed and PsycInfo were searched through July 2015 for review and empirical articles with the following search terms: "episodic future thinking," "future mental simulation," "imagining the future," "imagining new experiences," "future mental time travel," "future autobiographical experience," and "prospection." The review discusses evidence that episodic future thinking is important for adaptive functioning, which has implications for neurological populations. To determine the validity of episodic future thinking, the construct is evaluated with respect to related constructs, such as imagination, episodic memory, autobiographical memory, prospective memory, narrative construction, and working memory. Although it has been minimally investigated, there is evidence of convergent and discriminant validity for episodic future thinking. Research has not addressed the incremental validity of episodic future thinking. Practical considerations of episodic future thinking tasks and related constructs in a clinical neuropsychological setting are considered. The utility of episodic future thinking is currently unknown due to the lack of research investigating the validity of episodic future thinking. Future work is discussed, which could determine whether episodic future thinking is an important missing piece in standard clinical neuropsychological assessment. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. Quality Control Assays for Clinical-Grade Human Mesenchymal Stromal Cells: Validation Strategy.

    Science.gov (United States)

    Radrizzani, Marina; Soncin, Sabrina; Bolis, Sara; Lo Cicero, Viviana; Andriolo, Gabriella; Turchetto, Lucia

    2016-01-01

    The present chapter focuses on the validation of the following analytical methods for the control of mesenchymal stromal cells (MSC) for cell therapy clinical trials: Microbiological control for cellular product Endotoxin assay Mycoplasma assay Cell count and viability Immunophenotype Clonogenic potential (CFU-F assay) In our lab, these methods are in use for product release, process control or control of the biological starting materials. They are described in detail in the accompanying Chapter 19.For each method, validation goals and strategy are presented, and a detailed experimental scheme is proposed.

  12. Translation, adaptation, and validation of the Stanford Hypnotic Clinical Scale in Puerto Rico.

    Science.gov (United States)

    Deynes-Exclusa, Yazmin; Sayers-Montalvo, Sean K; Martinez-Taboas, Alfonso

    2011-04-01

    The only hypnotizability scale that has been translated and validated for the Puerto Rican population is the Barber Suggestibility Scale (BSS). In this article, the Stanford Hypnotic Clinical Scale (SHCS) was translated and validated for this population. The translated SHCS ("Escala Stanford de Hipnosis Clinica" [ESHC]) was administered individually to 100 Puerto Rican college students. There were no significant differences found between the norms of the original SHCS samples and the Spanish version of the SHCS. Both samples showed similar distributions. The Spanish version's internal reliability as well as the item discrimination index were adequate. The authors conclude that the ESHC is an adequate instrument to measure hypnotizability in the Puerto Rican population.

  13. Inflammatory therapeutic targets in coronary atherosclerosis – from molecular biology to clinical application

    Directory of Open Access Journals (Sweden)

    Fabian eLinden

    2014-11-01

    Full Text Available Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over three years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecu-lar inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis.

  14. Validating the extract, transform, load process used to populate a large clinical research database.

    Science.gov (United States)

    Denney, Michael J; Long, Dustin M; Armistead, Matthew G; Anderson, Jamie L; Conway, Baqiyyah N

    2016-10-01

    Informaticians at any institution that are developing clinical research support infrastructure are tasked with populating research databases with data extracted and transformed from their institution's operational databases, such as electronic health records (EHRs). These data must be properly extracted from these source systems, transformed into a standard data structure, and then loaded into the data warehouse while maintaining the integrity of these data. We validated the correctness of the extract, load, and transform (ETL) process of the extracted data of West Virginia Clinical and Translational Science Institute's Integrated Data Repository, a clinical data warehouse that includes data extracted from two EHR systems. Four hundred ninety-eight observations were randomly selected from the integrated data repository and compared with the two source EHR systems. Of the 498 observations, there were 479 concordant and 19 discordant observations. The discordant observations fell into three general categories: a) design decision differences between the IDR and source EHRs, b) timing differences, and c) user interface settings. After resolving apparent discordances, our integrated data repository was found to be 100% accurate relative to its source EHR systems. Any institution that uses a clinical data warehouse that is developed based on extraction processes from operational databases, such as EHRs, employs some form of an ETL process. As secondary use of EHR data begins to transform the research landscape, the importance of the basic validation of the extracted EHR data cannot be underestimated and should start with the validation of the extraction process itself. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. The predictive validity of the BioMedical Admissions Test for pre-clinical examination performance.

    Science.gov (United States)

    Emery, Joanne L; Bell, John F

    2009-06-01

    Some medical courses in the UK have many more applicants than places and almost all applicants have the highest possible previous and predicted examination grades. The BioMedical Admissions Test (BMAT) was designed to assist in the student selection process specifically for a number of 'traditional' medical courses with clear pre-clinical and clinical phases and a strong focus on science teaching in the early years. It is intended to supplement the information provided by examination results, interviews and personal statements. This paper reports on the predictive validity of the BMAT and its predecessor, the Medical and Veterinary Admissions Test. Results from the earliest 4 years of the test (2000-2003) were matched to the pre-clinical examination results of those accepted onto the medical course at the University of Cambridge. Correlation and logistic regression analyses were performed for each cohort. Section 2 of the test ('Scientific Knowledge') correlated more strongly with examination marks than did Section 1 ('Aptitude and Skills'). It also had a stronger relationship with the probability of achieving the highest examination class. The BMAT and its predecessor demonstrate predictive validity for the pre-clinical years of the medical course at the University of Cambridge. The test identifies important differences in skills and knowledge between candidates, not shown by their previous attainment, which predict their examination performance. It is thus a valid source of additional admissions information for medical courses with a strong scientific emphasis when previous attainment is very high.

  16. Validation of MC models of spallation reactions in thin and thick targets in the GeV range

    International Nuclear Information System (INIS)

    Goldenbaum, F.; Filges, D.; Neef, R.D.; Nuenighoff, K.; Paul, N.; Schaal, H.; Sterzenbach, G.; Tietze, A.; Wohlmuther, M.; Galin, J.; Letourneau, A.; Lott, B.; Peghaire, A.; Pienkowski, L.

    2001-01-01

    In the framework of new projects of intense spallation neutron sources an extensive experimental and theoretical effort is devoted to the precise prediction and optimization of the targets and shielding in terms of reaction cross sections, hadronic interaction lengths and usable neutrons produced in proton induced spallation reactions. Strong constraints on Monte-Carlo high energy transport codes are put by a measurement campaign of the NESSI (neutron scintillator and silicon detector) collaboration. While the predictive power of inter- and intra-nuclear cascade models coupled to evaporation codes and transport systems is excellent as far as neutron production in thick targets is concerned, there are considerable discrepancies not only between experiments and models, but also among the different codes themselves when regarding charged particle production in thin targets. In the current contribution a representative validation will be executed and possible deficiencies within the codes are elaborated. (orig.)

  17. Are You "Tilting at Windmills" or Undertaking a Valid Clinical Trial?

    Science.gov (United States)

    Zariffa, Jose; Kramer, John L.K.

    2011-01-01

    In this review, several aspects surrounding the choice of a therapeutic intervention and the conduct of clinical trials are discussed. Some of the background for why human studies have evolved to their current state is also included. Specifically, the following questions have been addressed: 1) What criteria should be used to determine whether a scientific discovery or invention is worthy of translation to human application? 2) What recent scientific advance warrants a deeper understanding of clinical trials by everyone? 3) What are the different types and phases of a clinical trial? 4) What characteristics of a human disorder should be noted, tracked, or stratified for a clinical trial and what inclusion /exclusion criteria are important to enrolling appropriate trial subjects? 5) What are the different study designs that can be used in a clinical trial program? 6) What confounding factors can alter the accurate interpretation of clinical trial outcomes? 7) What are the success rates of clinical trials and what can we learn from previous clinical trials? 8) What are the essential principles for the conduct of valid clinical trials? PMID:21786433

  18. Construction and validation of clinical contents for development of learning objects.

    Science.gov (United States)

    Hortense, Flávia Tatiana Pedrolo; Bergerot, Cristiane Decat; Domenico, Edvane Birelo Lopes de

    2018-01-01

    to describe the process of construction and validation of clinical contents for health learning objects, aimed at patients in the treatment of head and neck cancer. descriptive, methodological study. The development of the script and the storyboard were based on scientific evidence and submitted to the appreciation of specialists for validation of content. The agreement index was checked quantitatively and the suggestions were qualitatively evaluated. The items described in the roadmap were approved by 99% of expert experts. The suggestions for adjustments were inserted in their entirety in the final version. The free-marginal kappa statistical test, for multiple evaluators, presented value equal to 0.68%, granting a substantial agreement. The steps taken in the construction and validation of the content for the production of educational material for patients with head and neck cancer were adequate, relevant and suitable for use in other subjects.

  19. Construction and validation of clinical contents for development of learning objects

    Directory of Open Access Journals (Sweden)

    Flávia Tatiana Pedrolo Hortense

    Full Text Available ABSTRACT Objective: to describe the process of construction and validation of clinical contents for health learning objects, aimed at patients in the treatment of head and neck cancer. Method: descriptive, methodological study. The development of the script and the storyboard were based on scientific evidence and submitted to the appreciation of specialists for validation of content. The agreement index was checked quantitatively and the suggestions were qualitatively evaluated. Results: The items described in the roadmap were approved by 99% of expert experts. The suggestions for adjustments were inserted in their entirety in the final version. The free-marginal kappa statistical test, for multiple evaluators, presented value equal to 0.68%, granting a substantial agreement. Conclusion: The steps taken in the construction and validation of the content for the production of educational material for patients with head and neck cancer were adequate, relevant and suitable for use in other subjects.

  20. Use of clinical simulations for patient education: targeting an untapped audience.

    Science.gov (United States)

    Siwe, Karin; Berterö, Carina; Pugh, Carla; Wijma, Barbro

    2009-01-01

    In most cases, the health professional has been the target for simulation based learning curricula. We have developed a simulation based curriculum for patient education. In our curriculum lay-women learn how to perform the clinical female pelvic examination using a manikin-based trainer. Learner assessments show that prior negative expectations turned into positive expectations regarding future pelvic examinations.

  1. MR coronary angiography with breath-hold targeted volumes : Preliminary clinical results

    NARCIS (Netherlands)

    van Geuns, R J; Wielopolski, P A; de Bruin, Hein G.; Rensing, B J; Hulshoff, Marc; van Ooijen, P M; de Feyter, P J; Oudkerk, M

    2000-01-01

    PURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. MATERIALS AND METHODS: Thirty-eight patients referred for elective

  2. MR coronary angiography with breath-hold targeted volumes: preliminary clinical results

    NARCIS (Netherlands)

    R.J.M. van Geuns (Robert Jan); P.A. Wielopolski (Piotr); H.G. de Bruin (Hein); B.J.W.M. Rensing (Benno); M. Hulshoff (Maarten); P.M.A. van Ooijen (Peter); P.J. de Feyter (Pim); M. Oudkerk (Matthijs)

    2000-01-01

    textabstractPURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. MATERIALS AND METHODS:

  3. A Multi-Center Prospective Derivation and Validation of a Clinical Prediction Tool for Severe Clostridium difficile Infection.

    LENUS (Irish Health Repository)

    Na, Xi

    2015-04-23

    Prediction of severe clinical outcomes in Clostridium difficile infection (CDI) is important to inform management decisions for optimum patient care. Currently, treatment recommendations for CDI vary based on disease severity but validated methods to predict severe disease are lacking. The aim of the study was to derive and validate a clinical prediction tool for severe outcomes in CDI.

  4. The validity and clinical utility of structured diagnoses of antisocial personality disorder with forensic patients.

    Science.gov (United States)

    Marin-Avellan, Luisa E; McGauley, Gillian A; Campbell, Colin D; Fonagy, Peter

    2014-08-01

    Current DSM-based instruments for personality disorders (PDs) limit the investigation of the course and outcome of treatment of these disorders. This study examined the validity of the Shedler-Westen Assessment Procedure-200 (SWAP-200) and the Structured Clinical Interview for DSM-IV Axis II PD (SCID-II) in a sample of forensic PD patients. Results based on 66 participants indicated that the SWAP-200 Q-factors reduced the frequency of diagnostic comorbidity of PD categories by half compared with the SCID-II. Only the SWAP-200's Antisocial PD category showed good convergent and discriminant validity with respect to other instruments describing aspects of PD. The validity of the cutoff score for severe antisocial PD was confirmed, and this category predicted severe incidents in the hospital at 1 year of follow-up. A violence risk scale was constructed, which differentiated violent and nonviolent offenders. The results support the validity of the SWAP-200 and its potential clinical utility with forensic PD patients.

  5. Clinical utility and validity of minoxidil response testing in androgenetic alopecia.

    Science.gov (United States)

    Goren, Andy; Shapiro, Jerry; Roberts, Janet; McCoy, John; Desai, Nisha; Zarrab, Zoulikha; Pietrzak, Aldona; Lotti, Torello

    2015-01-01

    Clinical response to 5% topical minoxidil for the treatment of androgenetic alopecia (AGA) is typically observed after 3-6 months. Approximately 40% of patients will regrow hair. Given the prolonged treatment time required to elicit a response, a diagnostic test for ruling out nonresponders would have significant clinical utility. Two studies have previously reported that sulfotransferase enzyme activity in plucked hair follicles predicts a patient's response to topical minoxidil therapy. The aim of this study was to assess the clinical utility and validity of minoxidil response testing. In this communication, the present authors conducted an analysis of completed and ongoing studies of minoxidil response testing. The analysis confirmed the clinical utility of a sulfotransferase enzyme test in successfully ruling out 95.9% of nonresponders to topical minoxidil for the treatment of AGA. © 2014 Wiley Periodicals, Inc.

  6. Temporomandibular disorders – validity of clinical diagnostics compared to magnetic resonance imaging

    OpenAIRE

    BADEL, TOMISLAV; MAROTTI, MILJENKO; SAVIĆ PAVIČIN, IVANA; DULČIĆ, NIKŠA; ZADRAVEC, DIJANA; KERN, JOSIPA

    2011-01-01

    Background and Purpose: Orthopedic examination techniques of the musculoskeletal system contribute to the successful diagnostics of temporomandibular disorders (TMD). The purpose of this study is to determine the validity of TMD clinical diagnostics by comparing the findings of manual functional analysis (MFA) and the results of MRI of temporomandibular joint (TMJ). The diagnostic significance of limited mouth opening and pain upon passive mouth opening were taken into consideration. M...

  7. Clinical validation of robot simulation of toothbrushing - comparative plaque removal efficacy

    Science.gov (United States)

    2014-01-01

    Background Clinical validation of laboratory toothbrushing tests has important advantages. It was, therefore, the aim to demonstrate correlation of tooth cleaning efficiency of a new robot brushing simulation technique with clinical plaque removal. Methods Clinical programme: 27 subjects received dental cleaning prior to 3-day-plaque-regrowth-interval. Plaque was stained, photographically documented and scored using planimetrical index. Subjects brushed teeth 33–47 with three techniques (horizontal, rotating, vertical), each for 20s buccally and for 20s orally in 3 consecutive intervals. The force was calibrated, the brushing technique was video supported. Two different brushes were randomly assigned to the subject. Robot programme: Clinical brushing programmes were transfered to a 6-axis-robot. Artificial teeth 33–47 were covered with plaque-simulating substrate. All brushing techniques were repeated 7 times, results were scored according to clinical planimetry. All data underwent statistical analysis by t-test, U-test and multivariate analysis. Results The individual clinical cleaning patterns are well reproduced by the robot programmes. Differences in plaque removal are statistically significant for the two brushes, reproduced in clinical and robot data. Multivariate analysis confirms the higher cleaning efficiency for anterior teeth and for the buccal sites. Conclusions The robot tooth brushing simulation programme showed good correlation with clinically standardized tooth brushing. This new robot brushing simulation programme can be used for rapid, reproducible laboratory testing of tooth cleaning. PMID:24996973

  8. Inertial Measurement Units for Clinical Movement Analysis: Reliability and Concurrent Validity

    Directory of Open Access Journals (Sweden)

    Mohammad Al-Amri

    2018-02-01

    Full Text Available The aim of this study was to investigate the reliability and concurrent validity of a commercially available Xsens MVN BIOMECH inertial-sensor-based motion capture system during clinically relevant functional activities. A clinician with no prior experience of motion capture technologies and an experienced clinical movement scientist each assessed 26 healthy participants within each of two sessions using a camera-based motion capture system and the MVN BIOMECH system. Participants performed overground walking, squatting, and jumping. Sessions were separated by 4 ± 3 days. Reliability was evaluated using intraclass correlation coefficient and standard error of measurement, and validity was evaluated using the coefficient of multiple correlation and the linear fit method. Day-to-day reliability was generally fair-to-excellent in all three planes for hip, knee, and ankle joint angles in all three tasks. Within-day (between-rater reliability was fair-to-excellent in all three planes during walking and squatting, and poor-to-high during jumping. Validity was excellent in the sagittal plane for hip, knee, and ankle joint angles in all three tasks and acceptable in frontal and transverse planes in squat and jump activity across joints. Our results suggest that the MVN BIOMECH system can be used by a clinician to quantify lower-limb joint angles in clinically relevant movements.

  9. Adapting social neuroscience measures for schizophrenia clinical trials, part 3: fathoming external validity.

    Science.gov (United States)

    Olbert, Charles M; Penn, David L; Kern, Robert S; Lee, Junghee; Horan, William P; Reise, Steven P; Ochsner, Kevin N; Marder, Stephen R; Green, Michael F

    2013-11-01

    It is unknown whether measures adapted from social neuroscience linked to specific neural systems will demonstrate relationships to external variables. Four paradigms adapted from social neuroscience were administered to 173 clinically stable outpatients with schizophrenia to determine their relationships to functionally meaningful variables and to investigate their incremental validity beyond standard measures of social and nonsocial cognition. The 4 paradigms included 2 that assess perception of nonverbal social and action cues (basic biological motion and emotion in biological motion) and 2 that involve higher level inferences about self and others' mental states (self-referential memory and empathic accuracy). Overall, social neuroscience paradigms showed significant relationships to functional capacity but weak relationships to community functioning; the paradigms also showed weak correlations to clinical symptoms. Evidence for incremental validity beyond standard measures of social and nonsocial cognition was mixed with additional predictive power shown for functional capacity but not community functioning. Of the newly adapted paradigms, the empathic accuracy task had the broadest external validity. These results underscore the difficulty of translating developments from neuroscience into clinically useful tasks with functional significance.

  10. Measuring clinical management by physicians and nurses in European hospitals: development and validation of two scales.

    Science.gov (United States)

    Plochg, Thomas; Arah, Onyebuchi A; Botje, Daan; Thompson, Caroline A; Klazinga, Niek S; Wagner, Cordula; Mannion, Russell; Lombarts, Kiki

    2014-04-01

    Clinical management is hypothesized to be critical for hospital management and hospital performance. The aims of this study were to develop and validate professional involvement scales for measuring the level of clinical management by physicians and nurses in European hospitals. Testing of validity and reliability of scales derived from a questionnaire of 21 items was developed on the basis of a previous study and expert opinion and administered in a cross-sectional seven-country research project 'Deepening our Understanding of Quality improvement in Europe' (DUQuE). A sample of 3386 leading physicians and nurses working in 188 hospitals located in Czech Republic, France, Germany, Poland, Portugal, Spain and Turkey. Validity and reliability of professional involvement scales and subscales. Psychometric analysis yielded four subscales for leading physicians: (i) Administration and budgeting, (ii) Managing medical practice, (iii) Strategic management and (iv) Managing nursing practice. Only the first three factors applied well to the nurses. Cronbach's alpha for internal consistency ranged from 0.74 to 0.86 for the physicians, and from 0.61 to 0.81 for the nurses. Except for the 0.74 correlation between 'Administration and budgeting' and 'Managing medical practice' among physicians, all inter-scale correlations were measurement instrument can be used for international research on clinical management.

  11. Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studies.

    Science.gov (United States)

    Stuchlik, Ales; Radostová, Dominika; Hatalova, Hana; Vales, Karel; Nekovarova, Tereza; Koprivova, Jana; Svoboda, Jan; Horacek, Jiri

    2016-01-01

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with 1-3% prevalence. OCD is characterized by recurrent thoughts (obsessions) and repetitive behaviors (compulsions). The pathophysiology of OCD remains unclear, stressing the importance of pre-clinical studies. The aim of this article is to critically review a proposed animal model of OCD that is characterized by the induction of compulsive checking and behavioral sensitization to the D2/D3 dopamine agonist quinpirole. Changes in this model have been reported at the level of brain structures, neurotransmitter systems and other neurophysiological aspects. In this review, we consider these alterations in relation to the clinical manifestations in OCD, with the aim to discuss and evaluate axes of validity of this model. Our analysis shows that some axes of validity of quinpirole sensitization model (QSM) are strongly supported by clinical findings, such as behavioral phenomenology or roles of brain structures. Evidence on predictive validity is contradictory and ambiguous. It is concluded that this model is useful in the context of searching for the underlying pathophysiological basis of the disorder because of the relatively strong biological similarities with OCD.

  12. Prostate bed target interfractional motion using RTOG consensus definitions and daily CT on rails. Does target motion differ between superior and inferior portions of the clinical target volume

    International Nuclear Information System (INIS)

    Verma, Vivek; Zhou, Sumin; Enke, Charles A.; Wahl, Andrew O.; Chen, Shifeng

    2017-01-01

    Using high-quality CT-on-rails imaging, the daily motion of the prostate bed clinical target volume (PB-CTV) based on consensus Radiation Therapy Oncology Group (RTOG) definitions (instead of surgical clips/fiducials) was studied. It was assessed whether PB motion in the superior portion of PB-CTV (SUP-CTV) differed from the inferior PB-CTV (INF-CTV). Eight pT2-3bN0-1M0 patients underwent postprostatectomy intensity-modulated radiotherapy, totaling 300 fractions. INF-CTV and SUP-CTV were defined as PB-CTV located inferior and superior to the superior border of the pubic symphysis, respectively. Daily pretreatment CT-on-rails images were compared to the planning CT in the left-right (LR), superoinferior (SI), and anteroposterior (AP) directions. Two parameters were defined: ''total PB-CTV motion'' represented total shifts from skin tattoos to RTOG-defined anatomic areas; ''PB-CTV target motion'' (performed for both SUP-CTV and INF-CTV) represented shifts from bone to RTOG-defined anatomic areas (i. e., subtracting shifts from skin tattoos to bone). Mean (± standard deviation, SD) total PB-CTV motion was -1.5 (± 6.0), 1.3 (± 4.5), and 3.7 (± 5.7) mm in LR, SI, and AP directions, respectively. Mean (± SD) PB-CTV target motion was 0.2 (±1.4), 0.3 (±2.4), and 0 (±3.1) mm in the LR, SI, and AP directions, respectively. Mean (± SD) INF-CTV target motion was 0.1 (± 2.8), 0.5 (± 2.2), and 0.2 (± 2.5) mm, and SUP-CTV target motion was 0.3 (± 1.8), 0.5 (± 2.3), and 0 (± 5.0) mm in LR, SI, and AP directions, respectively. No statistically significant differences between INF-CTV and SUP-CTV motion were present in any direction. There are no statistically apparent motion differences between SUP-CTV and INF-CTV. Current uniform planning target volume (PTV) margins are adequate to cover both portions of the CTV. (orig.) [de

  13. The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research.

    Science.gov (United States)

    Roy, Neeta S; Wei, Yi; Kuklinski, Eric; Asbell, Penny A

    2017-05-01

    Biomarkers with minimally invasive and reproducible objective metrics provide the key to future paradigm shifts in understanding of the underlying causes of dry eye disease (DED) and approaches to treatment of DED. We review biomarkers and their validity in providing objective metrics for DED clinical research and patient care. The English-language literature in PubMed primarily over the last decade was surveyed for studies related to identification of biomarkers of DED: (1) inflammation, (2) point-of-care, (3) ocular imaging, and (4) genetics. Relevant studies in each group were individually evaluated for (1) methodological and analytical details, (2) data and concordance with other similar studies, and (3) potential to serve as validated biomarkers with objective metrics. Significant work has been done to identify biomarkers for DED clinical trials and for patient care. Interstudy variation among studies dealing with the same biomarker type was high. This could be attributed to biologic variations and/or differences in processing, and data analysis. Correlation with other signs and symptoms of DED was not always clear or present. Many of the biomarkers reviewed show the potential to serve as validated and objective metrics for clinical research and patient care in DED. Interstudy variation for a given biomarker emphasizes the need for detailed reporting of study methodology, including information on subject characteristics, quality control, processing, and analysis methods to optimize development of nonsubjective metrics. Biomarker development offers a rich opportunity to significantly move forward clinical research and patient care in DED. DED is an unmet medical need - a chronic pain syndrome associated with variable vision that affects quality of life, is common with advancing age, interferes with the comfortable use of contact lenses, and can diminish results of eye surgeries, such as cataract extraction, LASIK, and glaucoma procedures. It is a worldwide

  14. Development and validation of a survey to measure features of clinical networks.

    Science.gov (United States)

    Brown, Bernadette Bea; Haines, Mary; Middleton, Sandy; Paul, Christine; D'Este, Catherine; Klineberg, Emily; Elliott, Elizabeth

    2016-09-30

    Networks of clinical experts are increasingly being implemented as a strategy to improve health care processes and outcomes and achieve change in the health system. Few are ever formally evaluated and, when this is done, not all networks are equally successful in their efforts. There is a need to formatively assess the strategic and operational management and leadership of networks to identify where functioning could be improved to maximise impact. This paper outlines the development and psychometric evaluation of an Internet survey to measure features of clinical networks and provides descriptive results from a sample of members of 19 diverse clinical networks responsible for evidence-based quality improvement across a large geographical region. Instrument development was based on: a review of published and grey literature; a qualitative study of clinical network members; a program logic framework; and consultation with stakeholders. The resulting domain structure was validated for a sample of 592 clinical network members using confirmatory factor analysis. Scale reliability was assessed using Cronbach's alpha. A summary score was calculated for each domain and aggregate level means and ranges are reported. The instrument was shown to have good construct validity across seven domains as demonstrated by a high level of internal consistency, and all Cronbach's α coefficients were equal to or above 0.75. In the survey sample of network members there was strong reported commitment and belief in network-led quality improvement initiatives, which were perceived to have improved quality of care (72.8 %) and patient outcomes (63.2 %). Network managers were perceived to be effective leaders and clinical co-chairs were perceived as champions for change. Perceived external support had the lowest summary score across the seven domains. This survey, which has good construct validity and internal reliability, provides a valid instrument to use in future research related to

  15. Clinical Validity, Understandability, and Actionability of Online Cardiovascular Disease Risk Calculators: Systematic Review.

    Science.gov (United States)

    Bonner, Carissa; Fajardo, Michael Anthony; Hui, Samuel; Stubbs, Renee; Trevena, Lyndal

    2018-02-01

    Online health information is particularly important for cardiovascular disease (CVD) prevention, where lifestyle changes are recommended until risk becomes high enough to warrant pharmacological intervention. Online information is abundant, but the quality is often poor and many people do not have adequate health literacy to access, understand, and use it effectively. This project aimed to review and evaluate the suitability of online CVD risk calculators for use by low health literate consumers in terms of clinical validity, understandability, and actionability. This systematic review of public websites from August to November 2016 used evaluation of clinical validity based on a high-risk patient profile and assessment of understandability and actionability using Patient Education Material Evaluation Tool for Print Materials. A total of 67 unique webpages and 73 unique CVD risk calculators were identified. The same high-risk patient profile produced widely variable CVD risk estimates, ranging from as little as 3% to as high as a 43% risk of a CVD event over the next 10 years. One-quarter (25%) of risk calculators did not specify what model these estimates were based on. The most common clinical model was Framingham (44%), and most calculators (77%) provided a 10-year CVD risk estimate. The calculators scored moderately on understandability (mean score 64%) and poorly on actionability (mean score 19%). The absolute percentage risk was stated in most (but not all) calculators (79%), and only 18% included graphical formats consistent with recommended risk communication guidelines. There is a plethora of online CVD risk calculators available, but they are not readily understandable and their actionability is poor. Entering the same clinical information produces widely varying results with little explanation. Developers need to address actionability as well as clinical validity and understandability to improve usefulness to consumers with low health literacy.

  16. Target acquisition: Human observer performance studies and TARGAC model validation (Final Report)

    NARCIS (Netherlands)

    Valeton, J.M.; Bijl, P.; Gillespie, P.

    1995-01-01

    Human target acquisition performance was studied using the thermal imagery that was collected during Battlefield Emissives Sources Trials under the European Theater Weather and Obscurants, (BEST TWO), organized by NATO AC243/Panel4/RSG.l5 in 1990. Recognition and identification probabilities were

  17. An efficient numerical target strength prediction model: Validation against analysis solutions

    NARCIS (Netherlands)

    Fillinger, L.; Nijhof, M.J.J.; Jong, C.A.F. de

    2014-01-01

    A decade ago, TNO developed RASP (Rapid Acoustic Signature Prediction), a numerical model for the prediction of the target strength of immersed underwater objects. The model is based on Kirchhoff diffraction theory. It is currently being improved to model refraction, angle dependent reflection and

  18. Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine. Part 3: Technical Validation of Immunohistochemistry (IHC) Assays in Clinical IHC Laboratories.

    Science.gov (United States)

    Torlakovic, Emina E; Cheung, Carol C; D'Arrigo, Corrado; Dietel, Manfred; Francis, Glenn D; Gilks, C Blake; Hall, Jacqueline A; Hornick, Jason L; Ibrahim, Merdol; Marchetti, Antonio; Miller, Keith; van Krieken, J Han; Nielsen, Soren; Swanson, Paul E; Vyberg, Mogens; Zhou, Xiaoge; Taylor, Clive R

    2017-03-01

    Validation of immunohistochemistry (IHC) assays is a subject that is of great importance to clinical practice as well as basic research and clinical trials. When applied to clinical practice and focused on patient safety, validation of IHC assays creates objective evidence that IHC assays used for patient care are "fit-for-purpose." Validation of IHC assays needs to be properly informed by and modeled to assess the purpose of the IHC assay, which will further determine what sphere of validation is required, as well as the scope, type, and tier of technical validation. These concepts will be defined in this review, part 3 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

  19. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

    Science.gov (United States)

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T.

    2018-01-01

    Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted. PMID:28271910

  20. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

    Science.gov (United States)

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T

    2017-04-01

    Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

  1. Validity of a short clinical interview for psychiatric diagnosis: the mini-SCAN.

    Science.gov (United States)

    Nienhuis, F J; van de Willige, G; Rijnders, C A Th; de Jonge, P; Wiersma, D

    2010-01-01

    To promote clinical application of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) system a shorter version (the mini-SCAN) was devised. Its psychometric properties were unknown. To establish the validity and practical properties of the mini-SCAN. One hundred and six participants were interviewed twice, once with the SCAN and once with the mini-SCAN. The level of agreement was established for the categories: no disorder, affective disorders, anxiety disorders, non-affective psychotic disorders, affective psychotic disorders. The mini-SCAN is a valid instrument. Most kappa values were around 0.90. Only for the class of affective psychotic disorders was the agreement moderate. Mean duration of the mini-SCAN interviews was 25 min shorter than the SCAN interviews. Participants and interviewers were generally satisfied with the interview format and questions. The mini-SCAN can be used as a diagnostic instrument for clinical purposes and for clinical studies when the present episode is the focus of attention.

  2. Development and validation of a set of German stimulus- and target words for an attachment related semantic priming paradigm.

    Directory of Open Access Journals (Sweden)

    Anke Maatz

    Full Text Available Experimental research in adult attachment theory is faced with the challenge to adequately activate the adult attachment system. In view of the multitude of methods employed for this purpose so far, this paper suggests to further make use of the methodological advantages of semantic priming. In order to enable the use of such a paradigm in a German speaking context, a set of German words belonging to the semantic categories 'interpersonal closeness', 'interpersonal distance' and 'neutral' were identified and their semantics were validated combining production- and rating method. 164 university students answered corresponding online-questionnaires. Ratings were analysed using analysis of variance (ANOVA and cluster analysis from which three clearly distinct groups emerged. Beyond providing validated stimulus- and target words which can be used to activate the adult attachment system in a semantic priming paradigm, the results of this study point at important links between attachment and stress which call for further investigation in the future.

  3. An integrated miRNA functional screening and target validation method for organ morphogenesis.

    Science.gov (United States)

    Rebustini, Ivan T; Vlahos, Maryann; Packer, Trevor; Kukuruzinska, Maria A; Maas, Richard L

    2016-03-16

    The relative ease of identifying microRNAs and their increasing recognition as important regulators of organogenesis motivate the development of methods to efficiently assess microRNA function during organ morphogenesis. In this context, embryonic organ explants provide a reliable and reproducible system that recapitulates some of the important early morphogenetic processes during organ development. Here we present a method to target microRNA function in explanted mouse embryonic organs. Our method combines the use of peptide-based nanoparticles to transfect specific microRNA inhibitors or activators into embryonic organ explants, with a microRNA pulldown assay that allows direct identification of microRNA targets. This method provides effective assessment of microRNA function during organ morphogenesis, allows prioritization of multiple microRNAs in parallel for subsequent genetic approaches, and can be applied to a variety of embryonic organs.

  4. Reliability, construct and discriminative validity of clinical testing in subjects with and without chronic neck pain

    DEFF Research Database (Denmark)

    Jørgensen, René; Ris Hansen, Inge; Falla, Deborah

    2014-01-01

    -retest reliability in people with and without chronic neck pain. Moreover, construct and between-group discriminative validity of the tests were examined. METHODS: Twenty-one participants with chronic neck pain and 21 asymptomatic participants were included. Intra- and inter-reliability were evaluated for the Cranio-Cervical...... Flexion Test (CCFT), Range of Movement (ROM), Joint Position Error (JPE), Gaze Stability (GS), Smooth Pursuit Neck Torsion Test (SPNTT), and neuromuscular control of the Deep Cervical Extensors (DCE). Test-retest reliability was assessed for Postural Control (SWAY) and Pressure Pain Threshold (PPT) over......BACKGROUND: The reliability of clinical tests for the cervical spine has not been adequately evaluated. Six cervical clinical tests, which are low cost and easy to perform in clinical settings, were tested for intra- and inter-examiner reliability, and two performance tests were assessed for test...

  5. How to measure the unsecured money market? The Eurosystem's implementation and validation using TARGET2 data

    OpenAIRE

    Luca Arciero; Ronald Heijmans; Richard Heuver; Marco Massarenti; Cristina Picillo; Francesco Vacirca

    2013-01-01

    This paper develops a methodology, based on Furfine (1999), to identify unsecured interbank money market loans from transaction data of the most important euro processing payment system, TARGET2, for maturity ranging from one day (overnight) up to three months. The implementation has been verified with (i) interbank money market transactions executed on the Italian trading platform e-MID and (ii) aggregated reporting by the EONIA panel banks. The Type 2 (false negative) error for the best per...

  6. Thin and thick target benchmark investigations to validate spallation physics models

    International Nuclear Information System (INIS)

    Filges, D.; Neef, R.D.; Goldenbaum, F.; Nuenighoff, K.; Galin, J.; Letourneau, A.; Lott, B.; Patois, Y.; Schroeder, W.N.

    1999-01-01

    In the ESS (European Spallation Source) study report several areas have been identified where further spallation physics research and code validation is urgently needed: Neutron and charged particle production and multiplicities above one GeV incident protons, energy deposition and heating, material damage parameters, radioactivity and after heat, and high energy source shielding. All simulation calculations will be done using the Juelich HERMES code system. For this purpose various collaborations were organised. One of the collaborations is NESSI (Neutron Scintillator Silicon Detector), which concerns fundamental data as cross-section measurements on neutron multiplicities and charged particles for different ESS relevant materials. (author)

  7. Validation of a clinical leadership qualities framework for managers in aged care: a Delphi study.

    Science.gov (United States)

    Jeon, Yun-Hee; Conway, Jane; Chenoweth, Lynn; Weise, Janelle; Thomas, Tamsin Ht; Williams, Anna

    2015-04-01

    To establish validity of a clinical leadership framework for aged care middle managers (The Aged care Clinical Leadership Qualities Framework). Middle managers in aged care have responsibility not only for organisational governance also and operational management but also quality service delivery. There is a need to better define clinical leadership abilities in aged care middle managers, in order to optimise their positional authority to lead others to achieve quality outcomes. A Delphi method. Sixty-nine experts in aged care were recruited, representing rural, remote and metropolitan community and residential aged care settings. Panellists were asked to rate the proposed framework in terms of the relevance and importance of each leadership quality using four-point Likert scales, and to provide comments. Three rounds of consultation were conducted. The number and corresponding percentage of the relevance and importance rating for each quality was calculated for each consultation round, as well as mean scores. Consensus was determined to be reached when a percentage score reached 70% or greater. Twenty-three panellists completed all three rounds of consultation. Following the three rounds of consultation, the acceptability and face validity of the framework was confirmed. The study confirmed the framework as useful in identifying leadership requirements for middle managers in Australian aged care settings. The framework is the first validated framework of clinical leadership attributes for middle managers in aged care and offers an initial step forward in clarifying the aged care middle manager role. The framework provides clarity in the breadth of role expectations for the middle managers and can be used to inform an aged care specific leadership program development, individuals' and organisations' performance and development processes; and policy and guidelines about the types of activities required of middle managers in aged care. © 2014 John Wiley & Sons Ltd.

  8. Validity and Reliability of Clinical Dementia Rating Scale among the Elderly in Iran

    Directory of Open Access Journals (Sweden)

    Nahid Sadeghi

    2012-10-01

    Full Text Available Background: The most common cause of dementia among the elderly is Alzheimer’s disease. Given the increasing population of the elderly, achieving a screening tool with high reliability and validity is an essential need for all communities. The main objective of the project was to determine the Persian version of Clinical Dementia Rating Scale (P-CDR1. Materials and Methods: Twenty subjects were randomly selected from among 150, 50-70 year old people, who were illiterate and not mentally retarded, residing in the nursing home; and they were given the Persian version of CDR scale (test. After three months, the group was given the test again. Results: The findings showed that from the specialists’ standpoint CDR scale had acceptable validity, and the test validity was achieved 0.05 at the significant level with Cronbach’s alpha and reliability coefficients 73% and 89%, respectively. Conclusion: CDR scale is a reliable instrument for evaluation of clinical dementia rating among the elderly in Iran. It can be used in screening dementia, Alzheimer, and diagnosis of the severity and stages of Alzheimer.

  9. Anomalies in target-controlled infusion: an analysis after 20 years of clinical use.

    Science.gov (United States)

    Engbers, F H M; Dahan, A

    2018-05-01

    Although target-controlled infusion has been in use for more than two decades, its benefits are being obscured by anomalies in clinical practice caused by a number of important problems. These include: a variety of pharmacokinetic models available in open target-controlled infusion systems, which often confuse the user; the extrapolation of anthropomorphic data which provokes anomalous adjustments of dosing by such systems; and the uncertainty of regulatory requirements for the application of target-controlled infusion which causes uncontrolled exploitation of drugs and pharmacokinetic models in target-controlled infusion devices. Comparison of performance of pharmacokinetic models is complex and mostly inconclusive. However, a specific behaviour of a model in a target-controlled infusion system that is neither intended nor supported by scientific data can be considered an artefact or anomaly. Several of these anomalies can be identified in the current commercially available target-controlled infusion systems and are discussed in this review. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

  10. Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

    Science.gov (United States)

    Erten, Mujde Z; Fernandez, Luca P; Ng, Hank K; McKinnon, Wendy C; Heald, Brandie; Koliba, Christopher J; Greenblatt, Marc S

    2016-10-01

    Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. We compared targeted versus universal screening of CRCs for Lynch syndrome. In 2010-2011, we employed targeted screening (age Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

  11. A Structured Clinical Interview for Kleptomania (SCI-K): preliminary validity and reliability testing.

    Science.gov (United States)

    Grant, Jon E; Kim, Suck Won; McCabe, James S

    2006-06-01

    Kleptomania presents difficulties in diagnosis for clinicians. This study aimed to develop and test a DSM-IV-based diagnostic instrument for kleptomania. To assess for current kleptomania the Structured Clinical Interview for Kleptomania (SCI-K) was administered to 112 consecutive subjects requesting psychiatric outpatient treatment for a variety of disorders. Reliability and validity were determined. Classification accuracy was examined using the longitudinal course of illness. The SCI-K demonstrated excellent test-retest (Phi coefficient = 0.956 (95% CI = 0.937, 0.970)) and inter-rater reliability (phi coefficient = 0.718 (95% CI = 0.506, 0.848)) in the diagnosis of kleptomania. Concurrent validity was observed with a self-report measure using DSM-IV kleptomania criteria (phi coefficient = 0.769 (95% CI = 0.653, 0.850)). Discriminant validity was observed with a measure of depression (point biserial coefficient = -0.020 (95% CI = -0.205, 0.166)). The SCI-K demonstrated both high sensitivity and specificity based on longitudinal assessment. The SCI-K demonstrated excellent reliability and validity in diagnosing kleptomania in subjects presenting with various psychiatric problems. These findings require replication in larger groups, including non-psychiatric populations, to examine their generalizability. Copyright (c) 2006 John Wiley & Sons, Ltd.

  12. MO-B-BRB-02: 3D Dosimetry in the Clinic: IMRT Technique Validation in Sweden

    International Nuclear Information System (INIS)

    Ceberg, S.

    2016-01-01

    Full three-dimensional (3D) dosimetry using volumetric chemical dosimeters probed by 3D imaging systems has long been a promising technique for the radiation therapy clinic, since it provides a unique methodology for dose measurements in the volume irradiated using complex conformal delivery techniques such as IMRT and VMAT. To date true 3D dosimetry is still not widely practiced in the community; it has been confined to centres of specialized expertise especially for quality assurance or commissioning roles where other dosimetry techniques are difficult to implement. The potential for improved clinical applicability has been advanced considerably in the last decade by the development of improved 3D dosimeters (e.g., radiochromic plastics, radiochromic gel dosimeters and normoxic polymer gel systems) and by improved readout protocols using optical computed tomography or magnetic resonance imaging. In this session, established users of some current 3D chemical dosimeters will briefly review the current status of 3D dosimetry, describe several dosimeters and their appropriate imaging for dose readout, present workflow procedures required for good dosimetry, and analyze some limitations for applications in select settings. We will review the application of 3D dosimetry to various clinical situations describing how 3D approaches can complement other dose delivery validation approaches already available in the clinic. The applications presented will be selected to inform attendees of the unique features provided by full 3D techniques. Learning Objectives: L. John Schreiner: Background and Motivation Understand recent developments enabling clinically practical 3D dosimetry, Appreciate 3D dosimetry workflow and dosimetry procedures, and Observe select examples from the clinic. Sofie Ceberg: Application to dynamic radiotherapy Observe full dosimetry under dynamic radiotherapy during respiratory motion, and Understand how the measurement of high resolution dose data in an

  13. MO-B-BRB-03: 3D Dosimetry in the Clinic: Validating Special Techniques

    International Nuclear Information System (INIS)

    Juang, T.

    2016-01-01

    Full three-dimensional (3D) dosimetry using volumetric chemical dosimeters probed by 3D imaging systems has long been a promising technique for the radiation therapy clinic, since it provides a unique methodology for dose measurements in the volume irradiated using complex conformal delivery techniques such as IMRT and VMAT. To date true 3D dosimetry is still not widely practiced in the community; it has been confined to centres of specialized expertise especially for quality assurance or commissioning roles where other dosimetry techniques are difficult to implement. The potential for improved clinical applicability has been advanced considerably in the last decade by the development of improved 3D dosimeters (e.g., radiochromic plastics, radiochromic gel dosimeters and normoxic polymer gel systems) and by improved readout protocols using optical computed tomography or magnetic resonance imaging. In this session, established users of some current 3D chemical dosimeters will briefly review the current status of 3D dosimetry, describe several dosimeters and their appropriate imaging for dose readout, present workflow procedures required for good dosimetry, and analyze some limitations for applications in select settings. We will review the application of 3D dosimetry to various clinical situations describing how 3D approaches can complement other dose delivery validation approaches already available in the clinic. The applications presented will be selected to inform attendees of the unique features provided by full 3D techniques. Learning Objectives: L. John Schreiner: Background and Motivation Understand recent developments enabling clinically practical 3D dosimetry, Appreciate 3D dosimetry workflow and dosimetry procedures, and Observe select examples from the clinic. Sofie Ceberg: Application to dynamic radiotherapy Observe full dosimetry under dynamic radiotherapy during respiratory motion, and Understand how the measurement of high resolution dose data in an

  14. MO-B-BRB-03: 3D Dosimetry in the Clinic: Validating Special Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Juang, T. [Stanford Cancer Center (United States)

    2016-06-15

    Full three-dimensional (3D) dosimetry using volumetric chemical dosimeters probed by 3D imaging systems has long been a promising technique for the radiation therapy clinic, since it provides a unique methodology for dose measurements in the volume irradiated using complex conformal delivery techniques such as IMRT and VMAT. To date true 3D dosimetry is still not widely practiced in the community; it has been confined to centres of specialized expertise especially for quality assurance or commissioning roles where other dosimetry techniques are difficult to implement. The potential for improved clinical applicability has been advanced considerably in the last decade by the development of improved 3D dosimeters (e.g., radiochromic plastics, radiochromic gel dosimeters and normoxic polymer gel systems) and by improved readout protocols using optical computed tomography or magnetic resonance imaging. In this session, established users of some current 3D chemical dosimeters will briefly review the current status of 3D dosimetry, describe several dosimeters and their appropriate imaging for dose readout, present workflow procedures required for good dosimetry, and analyze some limitations for applications in select settings. We will review the application of 3D dosimetry to various clinical situations describing how 3D approaches can complement other dose delivery validation approaches already available in the clinic. The applications presented will be selected to inform attendees of the unique features provided by full 3D techniques. Learning Objectives: L. John Schreiner: Background and Motivation Understand recent developments enabling clinically practical 3D dosimetry, Appreciate 3D dosimetry workflow and dosimetry procedures, and Observe select examples from the clinic. Sofie Ceberg: Application to dynamic radiotherapy Observe full dosimetry under dynamic radiotherapy during respiratory motion, and Understand how the measurement of high resolution dose data in an

  15. MO-B-BRB-02: 3D Dosimetry in the Clinic: IMRT Technique Validation in Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Ceberg, S. [Lund University (Sweden)

    2016-06-15

    Full three-dimensional (3D) dosimetry using volumetric chemical dosimeters probed by 3D imaging systems has long been a promising technique for the radiation therapy clinic, since it provides a unique methodology for dose measurements in the volume irradiated using complex conformal delivery techniques such as IMRT and VMAT. To date true 3D dosimetry is still not widely practiced in the community; it has been confined to centres of specialized expertise especially for quality assurance or commissioning roles where other dosimetry techniques are difficult to implement. The potential for improved clinical applicability has been advanced considerably in the last decade by the development of improved 3D dosimeters (e.g., radiochromic plastics, radiochromic gel dosimeters and normoxic polymer gel systems) and by improved readout protocols using optical computed tomography or magnetic resonance imaging. In this session, established users of some current 3D chemical dosimeters will briefly review the current status of 3D dosimetry, describe several dosimeters and their appropriate imaging for dose readout, present workflow procedures required for good dosimetry, and analyze some limitations for applications in select settings. We will review the application of 3D dosimetry to various clinical situations describing how 3D approaches can complement other dose delivery validation approaches already available in the clinic. The applications presented will be selected to inform attendees of the unique features provided by full 3D techniques. Learning Objectives: L. John Schreiner: Background and Motivation Understand recent developments enabling clinically practical 3D dosimetry, Appreciate 3D dosimetry workflow and dosimetry procedures, and Observe select examples from the clinic. Sofie Ceberg: Application to dynamic radiotherapy Observe full dosimetry under dynamic radiotherapy during respiratory motion, and Understand how the measurement of high resolution dose data in an

  16. A novel clinically translatable fluorescent nanoparticle for targeted molecular imaging of tumors in living subjects.

    Science.gov (United States)

    Gao, Jinhao; Chen, Kai; Luong, Richard; Bouley, Donna M; Mao, Hua; Qiao, Tiecheng; Gambhir, Sanjiv S; Cheng, Zhen

    2012-01-11

    The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QD as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance, and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding nontumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD(2) to integrin α(v)β(3)-positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD-modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron-based nanoprobes in the clinical setting in the near future. © 2011 American Chemical Society

  17. Patient-reported outcome measures for systemic lupus erythematosus clinical trials: a review of content validity, face validity and psychometric performance.

    Science.gov (United States)

    Holloway, Laura; Humphrey, Louise; Heron, Louise; Pilling, Claire; Kitchen, Helen; Højbjerre, Lise; Strandberg-Larsen, Martin; Hansen, Brian Bekker

    2014-07-22

    Despite overall progress in treatment of autoimmune diseases, patients with systemic lupus erythematosus (SLE) experience many inflammatory symptoms representing an unmet medical need. This study aimed to create a conceptual model of the humanistic and economic burden of SLE, and review the patient-reported outcomes (PROs) used to measure such concepts in SLE clinical trials. A conceptual model for SLE was developed from structured review of published articles from 2007 to August 2013 identified from literature databases (MEDLINE, EMBASE, PsycINFO, EconLit) plus other sources (PROLabels, FDA/EMA websites, Clinicaltrials.gov). PROs targeting key symptoms/impacts were identified from the literature. They were reviewed in the context of available guidance and assessed for face and content validity and psychometric properties to determine appropriateness for use in SLE trials. The conceptual model identified fatigue, pain, cognition, daily activities, emotional well-being, physical/social functioning and work productivity as key SLE concepts. Of the 68 articles reviewed, 38 reported PRO data. From these and the other sources, 15 PROs were selected for review, including SLE-specific health-related quality of life (HRQoL) measures (n = 5), work productivity (n = 1), and generic measures of fatigue (n = 3), pain (n = 2), depression (n = 2) and HRQoL (n = 2). The Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue), Brief Pain Inventory (BPI-SF) and LupusQoL demonstrated the strongest face validity, conceptual coverage and psychometric properties measuring key concepts in the conceptual model. All PROs reviewed, except for three Lupus-specific measures, lacked qualitative SLE patient involvement during development. The Hospital Anxiety and Depression Scale (HADS), Short Form [36 item] Health Survey version 2 (SF-36v2), EuroQoL 5-dimensions (EQ-5D-3L and EQ-5D-5L) and Work Productivity and Activity Impairment Questionnaire: Lupus (WPAI

  18. Patient-reported outcome measures for systemic lupus erythematosus clinical trials: a review of content validity, face validity and psychometric performance

    Science.gov (United States)

    2014-01-01

    Background Despite overall progress in treatment of autoimmune diseases, patients with systemic lupus erythematosus (SLE) experience many inflammatory symptoms representing an unmet medical need. This study aimed to create a conceptual model of the humanistic and economic burden of SLE, and review the patient-reported outcomes (PROs) used to measure such concepts in SLE clinical trials. Methods A conceptual model for SLE was developed from structured review of published articles from 2007 to August 2013 identified from literature databases (MEDLINE, EMBASE, PsycINFO, EconLit) plus other sources (PROLabels, FDA/EMA websites, Clinicaltrials.gov). PROs targeting key symptoms/impacts were identified from the literature. They were reviewed in the context of available guidance and assessed for face and content validity and psychometric properties to determine appropriateness for use in SLE trials. Results The conceptual model identified fatigue, pain, cognition, daily activities, emotional well-being, physical/social functioning and work productivity as key SLE concepts. Of the 68 articles reviewed, 38 reported PRO data. From these and the other sources, 15 PROs were selected for review, including SLE-specific health-related quality of life (HRQoL) measures (n = 5), work productivity (n = 1), and generic measures of fatigue (n = 3), pain (n = 2), depression (n = 2) and HRQoL (n = 2). The Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue), Brief Pain Inventory (BPI-SF) and LupusQoL demonstrated the strongest face validity, conceptual coverage and psychometric properties measuring key concepts in the conceptual model. All PROs reviewed, except for three Lupus-specific measures, lacked qualitative SLE patient involvement during development. The Hospital Anxiety and Depression Scale (HADS), Short Form [36 item] Health Survey version 2 (SF-36v2), EuroQoL 5-dimensions (EQ-5D-3L and EQ-5D-5L) and Work Productivity and

  19. Development and Initial Validation of the Caregiver Perceptions About Communication With Clinical Team Members (CAPACITY) Measure.

    Science.gov (United States)

    Van Houtven, Courtney Harold; Miller, Katherine E M; O'Brien, Emily C; Wolff, Jennifer L; Lindquist, Jennifer; Kabat, Margaret; Campbell-Kotler, Margaret; Henius, Jennifer; Voils, Corrine I

    2017-12-01

    Despite the important role that family caregivers play managing the care of persons with complex health needs, little is known about how caregivers perceive themselves to be recognized and valued by health care professionals. Our objective was to develop and validate a novel measure, the CAregiver Perceptions About Commun Ication with Clinical Team members (CAPACITY) instrument. Questions focus on perceived quality of communication with the health care team and the extent to which caregivers believe that the health care team considers their capacity and preferences in decision making. A confirmatory factor analysis supported a two-factor solution addressing communication and capacity. Internal consistency reliability was .90 for the communication domain and .93 for the capacity domain. Correlations between these two subscales and individual difference measures provided evidence of convergent and discriminant validity. The CAPACITY instrument may be a useful performance measure that quantifies the extent to which caregivers' experience person- and family-centered health care.

  20. Validity and reliability of the Structured Clinical Interview for Depersonalization–Derealization Spectrum (SCI-DER

    Directory of Open Access Journals (Sweden)

    Marco Mula

    2008-08-01

    Full Text Available Marco Mula, Stefano Pini, Simona Calugi, Matteo Preve, Matteo Masini, Ilaria Giovannini, Ciro Conversano, Paola Rucci, Giovanni B CassanoDepartment of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, ItalyAbstract: This study evaluates the validity and reliability of a new instrument developed to assess symptoms of depersonalization: the Structured Clinical Interview for the Depersonalization-Derealization Spectrum (SCI-DER. The instrument is based on a spectrum model that emphasizes soft-signs, sub-threshold syndromes as well as clinical and subsyndromal manifestations. Items of the interview include, in addition to DSM-IV criteria for depersonalization, a number of features derived from clinical experience and from a review of phenomenological descriptions. Study participants included 258 consecutive patients with mood and anxiety disorders, 16.7% bipolar I disorder, 18.6% bipolar II disorder, 32.9% major depression, 22.1% panic disorder, 4.7% obsessive compulsive disorder, and 1.5% generalized anxiety disorder; 2.7% patients were also diagnosed with depersonalization disorder. A comparison group of 42 unselected controls was enrolled at the same site. The SCI-DER showed excellent reliability and good concurrent validity with the Dissociative Experiences Scale. It significantly discriminated subjects with any diagnosis of mood and anxiety disorders from controls and subjects with depersonalization disorder from controls. The hypothesized structure of the instrument was confirmed empirically.Keywords: depersonalization, derealization, mood disorders, anxiety disorders

  1. Clinical examinations to validate self-completion questionnaires: dermatitis in the UK printing industry.

    Science.gov (United States)

    Livesley, E J; Rushton, L; English, J S C; Williams, H C

    2002-07-01

    A self-completion questionnaire sent to 2600 Nottinghamshire members of the Graphical Paper and Media Union elicited a 62% response. Forty one per cent of respondents reported suffering a skin complaint at some time and 11% had a current skin problem on the hand. This paper reports the validation stage of the study. Samples of 45 'cases' of self-reported dermatitis and 60 'controls', who reported they had never suffered a skin complaint, were clinically examined. All 45 self-reported cases were clinically confirmed as dermatitis. Occupationally related irritant contact dermatitis (ICD) was diagnosed in 20 (44%); 26 (58%) complaints were thought to be induced or exacerbated by occupation. Of the controls, 21 (35%) were also diagnosed with a skin complaint, the majority being mild, with an occupational association in 17, the majority (15) being ICD. Sixteen ICD cases were patch tested resulting in positive reactions to colophony, neomycin, nickel and potassium dichromate (2 of each). Two cases of basal cell carcinoma on the face were also identified, of which the participants were unaware. Although there was no false positive self-reporting there was a considerable number of false negatives, demonstrating the importance of clinical validation of questionnaires relating to industrial skin disease. This study has highlighted the need for improvement in skin care provision in the printing industry.

  2. Clinical Validation of Non-Invasive Cardiac Output Monitoring in Healthy Pregnant Women.

    Science.gov (United States)

    McLaughlin, Kelsey; Wright, Stephen P; Kingdom, John C P; Parker, John D

    2017-11-01

    Non-invasive hemodynamic monitoring has the potential to be a valuable clinical tool for the screening and management of hypertensive disorders of pregnancy. The objective of this study was to validate the clinical utility of the non-invasive cardiac output monitoring (NICOM) system in pregnant women. Twenty healthy pregnant women with a singleton pregnancy at 22 to 26 weeks' gestation were enrolled in this study. Measures of heart rate, stroke volume, and cardiac output were obtained through NICOM and compared with Doppler echocardiography. NICOM significantly overestimated measures of both stroke volume and cardiac output compared with Doppler echocardiography (95 ± 4 vs. 73 ± 4 mL, P gold standard for the measurement of cardiac output in the setting of pregnancy. However, once normal values have been established, NICOM has the potential to be a useful clinical tool for monitoring maternal hemodynamics in pregnant women. Further investigation regarding the validity of NICOM is required in larger populations of healthy and hypertensive pregnant women to determine whether this device is appropriate for maternal hemodynamic assessment during pregnancy. Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

  3. Utilisation, Reliability and Validity of Clinical Evaluation Exercise in Otolaryngology Training.

    Science.gov (United States)

    Awad, Z; Hayden, L; Muthuswamy, K; Tolley, N S

    2015-10-01

    To investigate the utilisation, reliability and validity of clinical evaluation exercise (CEX) in otolaryngology training. Retrospective database analysis. Online assessment database. We analysed all CEXs submitted by north London core (CT) and speciality trainees (ST) in otolaryngology from 2010 to 2013. Internal consistency of the 7 CEX items rated as either O: outstanding, S: satisfactory or D: development required. Overall performance rating (pS) of 1-4 assessed against completion of training level. Receiver operating characteristic was used to describe CEX sensitivity and specificity. Overall score (cS), pS and the number of 'D'-rated items were used to investigate construct validity. One thousand one hundred and sixty CEXs from 45 trainees were included. CEX showed good internal consistency (Cronbach's alpha= 0.85). CEX was highly sensitive (99%), yet not specific (6%). cS and pS for ST was higher than CT (99.1% ± 0.4 versus 96.6% ± 0.8 and 3.06 ± 0.05 versus 1.92 ± 0.04, respectively P reliable in assessing early years otolaryngology trainees in clinical examination, but not at higher level. It has the potential to be used in a summative capacity in selecting trainees for ST positions. This would also encourage trainees to master all domains of otolaryngology clinical examination by end of CT. © 2015 John Wiley & Sons Ltd.

  4. Validity of a new assessment rubric for a short-answer test of clinical reasoning.

    Science.gov (United States)

    Yeung, Euson; Kulasagarem, Kulamakan; Woods, Nicole; Dubrowski, Adam; Hodges, Brian; Carnahan, Heather

    2016-07-26

    The validity of high-stakes decisions derived from assessment results is of primary concern to candidates and certifying institutions in the health professions. In the field of orthopaedic manual physical therapy (OMPT), there is a dearth of documented validity evidence to support the certification process particularly for short-answer tests. To address this need, we examined the internal structure of the Case History Assessment Tool (CHAT); this is a new assessment rubric developed to appraise written responses to a short-answer test of clinical reasoning in post-graduate OMPT certification in Canada. Fourteen physical therapy students (novices) and 16 physical therapists (PT) with minimal and substantial OMPT training respectively completed a mock examination. Four pairs of examiners (n = 8) participated in appraising written responses using the CHAT. We conducted separate generalizability studies (G studies) for all participants and also by level of OMPT training. Internal consistency was calculated for test questions with more than 2 assessment items. Decision studies were also conducted to determine optimal application of the CHAT for OMPT certification. The overall reliability of CHAT scores was found to be moderate; however, reliability estimates for the novice group suggest that the scale was incapable of accommodating for scores of novices. Internal consistency estimates indicate item redundancies for several test questions which will require further investigation. Future validity studies should consider discriminating the clinical reasoning competence of OMPT trainees strictly at the post-graduate level. Although rater variance was low, the large variance attributed to error sources not incorporated in our G studies warrant further investigations into other threats to validity. Future examination of examiner stringency is also warranted.

  5. A Miniaturized Chemical Proteomic Approach for Target Profiling of Clinical Kinase Inhibitors in Tumor Biopsies

    Science.gov (United States)

    Chamrád, Ivo; Rix, Uwe; Stukalov, Alexey; Gridling, Manuela; Parapatics, Katja; Müller, André C.; Altiok, Soner; Colinge, Jacques; Superti-Furga, Giulio; Haura, Eric B.; Bennett, Keiryn L.

    2014-01-01

    While targeted therapy based on the idea of attenuating the activity of a preselected, therapeutically relevant protein has become one of the major trends in modern cancer therapy, no truly specific targeted drug has been developed and most clinical agents have displayed a degree of polypharmacology. Therefore, the specificity of anticancer therapeutics has emerged as a highly important but severely underestimated issue. Chemical proteomics is a powerful technique combining postgenomic drug-affinity chromatography with high-end mass spectrometry analysis and bioinformatic data processing to assemble a target profile of a desired therapeutic molecule. Due to high demands on the starting material, however, chemical proteomic studies have been mostly limited to cancer cell lines. Herein, we report a down-scaling of the technique to enable the analysis of very low abundance samples, as those obtained from needle biopsies. By a systematic investigation of several important parameters in pull-downs with the multikinase inhibitor bosutinib, the standard experimental protocol was optimized to 100 µg protein input. At this level, more than 30 well-known targets were detected per single pull-down replicate with high reproducibility. Moreover, as presented by the comprehensive target profile obtained from miniaturized pull-downs with another clinical drug, dasatinib, the optimized protocol seems to be extendable to other drugs of interest. Sixty distinct human and murine targets were finally identified for bosutinib and dasatinib in chemical proteomic experiments utilizing core needle biopsy samples from xenotransplants derived from patient tumor tissue. Altogether, the developed methodology proves robust and generic and holds many promises for the field of personalized health care. PMID:23901793

  6. Development and validation of Dutch version of Lasater Clinical Judgment Rubric in hospital practice: An instrument design study

    NARCIS (Netherlands)

    Vreugdenhil, Jettie; Spek, Bea

    2017-01-01

    Clinical reasoning in patient care is a skill that cannot be observed directly. So far, no reliable, valid instrument exists for the assessment of nursing students' clinical reasoning skills in hospital practice. Lasater's clinical judgment rubric (LCJR), based on Tanner's model "Thinking like a

  7. Review of the Reported Measures of Clinical Validity and Clinical Utility as Arguments for the Implementation of Pharmacogenetic Testing: A Case Study of Statin-Induced Muscle Toxicity

    Directory of Open Access Journals (Sweden)

    Marleen E. Jansen

    2017-08-01

    Full Text Available Advances from pharmacogenetics (PGx have not been implemented into health care to the expected extent. One gap that will be addressed in this study is a lack of reporting on clinical validity and clinical utility of PGx-tests. A systematic review of current reporting in scientific literature was conducted on publications addressing PGx in the context of statins and muscle toxicity. Eighty-nine publications were included and information was selected on reported measures of effect, arguments, and accompanying conclusions. Most authors report associations to quantify the relationship between a genetic variation an outcome, such as adverse drug responses. Conclusions on the implementation of a PGx-test are generally based on these associations, without explicit mention of other measures relevant to evaluate the test's clinical validity and clinical utility. To gain insight in the clinical impact and select useful tests, additional outcomes are needed to estimate the clinical validity and utility, such as cost-effectiveness.

  8. Statistical Validation for Clinical Measures: Repeatability and Agreement of Kinect™-Based Software.

    Science.gov (United States)

    Lopez, Natalia; Perez, Elisa; Tello, Emanuel; Rodrigo, Alejandro; Valentinuzzi, Max E

    2018-01-01

    The rehabilitation process is a fundamental stage for recovery of people's capabilities. However, the evaluation of the process is performed by physiatrists and medical doctors, mostly based on their observations, that is, a subjective appreciation of the patient's evolution. This paper proposes a tracking platform of the movement made by an individual's upper limb using Kinect sensor(s) to be applied for the patient during the rehabilitation process. The main contribution is the development of quantifying software and the statistical validation of its performance, repeatability, and clinical use in the rehabilitation process. The software determines joint angles and upper limb trajectories for the construction of a specific rehabilitation protocol and quantifies the treatment evolution. In turn, the information is presented via a graphical interface that allows the recording, storage, and report of the patient's data. For clinical purposes, the software information is statistically validated with three different methodologies, comparing the measures with a goniometer in terms of agreement and repeatability. The agreement of joint angles measured with the proposed software and goniometer is evaluated with Bland-Altman plots; all measurements fell well within the limits of agreement, meaning interchangeability of both techniques. Additionally, the results of Bland-Altman analysis of repeatability show 95% confidence. Finally, the physiotherapists' qualitative assessment shows encouraging results for the clinical use. The main conclusion is that the software is capable of offering a clinical history of the patient and is useful for quantification of the rehabilitation success. The simplicity, low cost, and visualization possibilities enhance the use of the software Kinect for rehabilitation and other applications, and the expert's opinion endorses the choice of our approach for clinical practice. Comparison of the new measurement technique with established

  9. Measurement-based Treatment of Residual Symptoms Using Clinically Useful Depression Outcome Scale: Korean Validation Study

    Science.gov (United States)

    Jeon, Sang Won; Han, Changsu; Ko, Young-Hoon; Yoon, Seo Young; Pae, Chi-Un; Choi, Joonho; Park, Yong Chon; Kim, Jong-Woo; Yoon, Ho-Kyoung; Ko, Seung-Duk; Patkar, Ashwin A.; Zimmerman, Mark

    2017-01-01

    Objective This study was aimed at evaluating the diagnostic validity of the Korean version of the Clinically Useful Depression Outcome Scale (CUDOS) with varying follow-up in a typical clinical setting in multiple centers. Methods In total, 891 psychiatric outpatients were enrolled at the time of their intake appointment. Current diagnostic characteristics were examined using the Structured Clinical Interview for DSM-IV (41% major depressive disorder). The CUDOS was measured and compared with three clinician rating scales and four self-report scales. Results The CUDOS showed excellent results for internal consistency (Cronbach’s α, 0.91), test-retest reliability (patients at intake, r=0.81; depressed patients in ongoing treatment, r=0.89), and convergent and discriminant validity (measures of depression, r=0.80; measures of anxiety and somatization, r=0.42). The CUDOS had a high ability to discriminate between different levels of depression severity based on the rating of Clinical Global Impression for depression severity and the diagnostic classification of major depression, minor depression, and non-depression. The ability of the CUDOS to identify patients with major depression was high (area under the receiver operating characteristic curve=0.867). A score of 20 as the optimal cutoff point was suggested when screening for major depression using the CUDOS (sensitivity=89.9%, specificity=69.5%). The CUDOS was sensitive to change after antidepressant treatment: patients with greater improvement showed a greater decrease in CUDOS scores (p<0.001). Conclusion The results of this multi-site outpatient study found that the Korean version of the CUDOS is a very useful measurement for research and for clinical practice. PMID:28138107

  10. Validation of assessment of intraoral digital photography for evaluation of dental restorations in clinical research.

    Science.gov (United States)

    Signori, Cácia; Collares, Kauê; Cumerlato, Catarina B F; Correa, Marcos B; Opdam, Niek J M; Cenci, Maximiliano S

    2018-04-01

    The aim of this study was to investigate the validity of assessment of intraoral digital photography in the evaluation of dental restorations. Intraoral photographs of anterior and posterior restorations were classified based on FDI criteria according to the need for intervention: no intervention, repair and replacement. Evaluations were performed by an experienced expert in restorative dentistry (gold standard evaluator) and 3 trained dentists (consensus). The clinical inspection was the reference standard method. The prevalence of failures was explored. Cohen's kappa statistic was used. Validity was accessed by sensitivity, specificity, likelihood ratio and predictives values. Higher prevalence of failed restorations intervention was identified by the intraoral photography (17.7%) in comparison to the clinical evaluation (14.1%). Moderate agreement in the diagnosis of total failures was shown between the methods for the gold standard evaluator (kappa = 0.51) and consensus of evaluators (kappa = 0.53). Gold standard evaluator and consensus showed substantial and moderate agreement for posterior restorations (kappa = 0.61; 0.59), and fair and moderate agreement for anterior restorations (kappa = 0.36; 0.43), respectively. The accuracy was 84.8% in the assessment by intraoral photographs. Sensitivity and specificity values of 87.5% and 89.3% were found. Under the limits of this study, the assessment of digital photography performed by intraoral camera is an indirect diagnostic method valid for the evaluation of dental restorations, mainly in posterior teeth. This method should be employed taking into account the higher detection of defects provided by the images, which are not always clinically relevant. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. The Adequacy of the Q Methodology for Clinical Validation of Nursing Diagnoses Related to Subjective Foci.

    Science.gov (United States)

    Miguel, Susana; Caldeira, Sílvia; Vieira, Margarida

    2018-04-01

    This article describes the adequacy of the Q methodology as a new option for the validation of nursing diagnoses related to subjective foci. Discussion paper about the characteristics of the Q methodology. This method has been used in nursing research particularly related to subjective concepts and includes both a quantitative and qualitative dimension. The Q methodology seems to be an adequate and innovative method for the clinical validation of nursing diagnoses. The validation of nursing diagnoses related to subjective foci using the Q methodology could improve the level of evidence and provide nurses with clinical indicators for clinical reasoning and for the planning of effective interventions. Descrever a adequação da metodologia Q como uma nova opção para a validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos. MÉTODOS: Artigo de discussão sobre as características da metodologia Q. Este método tem sido utilizado na pesquisa em enfermagem relacionada com conceitos subjetivos e inclui em simultâneo uma vertente qualitativa e quantitativa. CONCLUSÕES: A metodologia Q parece ser uma opção metodológica adequada para a validação clínica de diagnósticos de enfermagem. IMPLICAÇÕES PARA A PRÁTICA: A utilização da metodologia Q na validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos pode melhorar o nível e evidência e facilitar o raciocínio clínico dos enfermeiros, ao providenciar indicadores clínicos também necessários ao desenvolvimento de intervenções efetivas. © 2016 NANDA International, Inc.

  12. [Validation of a questionnaire to evaluate patient safety in clinical laboratories].

    Science.gov (United States)

    Giménez Marín, Ángeles; Rivas-Ruiz, Francisco

    2012-01-01

    The aim of this study was to prepare, pilot and validate a questionnaire to evaluate patient safety in the specific context of clinical laboratories. A specific questionnaire on patient safety in the laboratory, with 62 items grouped into six areas, was developed, taking into consideration the diverse human and laboratory contextual factors which may contribute to producing errors. A pilot study of 30 interviews was carried out, including validity and reliability analyses using principal components factor analysis and Cronbach's alpha. Subsequently, 240 questionnaires were sent to 21 hospitals, followed by a test-retest of 41 questionnaires with the definitive version. The sample analyzed was composed of 225 questionnaires (an overall response rate of 80%). Of the 62 items initially assessed, 17 were eliminated due to non-compliance with the criteria established before the principal components factor analysis was performed. For the 45 remaining items, 12 components were identified, with an cumulative variance of 69.5%. In seven of the 10 components with two or more items, Cronbach's alpha was higher than 0.7. The questionnaire items assessed in the test-retest were found to be stable. We present the first questionnaire with sufficiently proven validity and reliability for evaluating patient safety in the specific context of clinical laboratories. This questionnaire provides a useful instrument to perform a subsequent macrostudy of hospital clinical laboratories in Spain. The questionnaire can also be used to monitor and promote commitment to patient safety within the search for continuous quality improvement. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.

  13. A Serious Game for Clinical Assessment of Cognitive Status: Validation Study.

    Science.gov (United States)

    Tong, Tiffany; Chignell, Mark; Tierney, Mary C; Lee, Jacques

    2016-05-27

    We propose the use of serious games to screen for abnormal cognitive status in situations where it may be too costly or impractical to use standard cognitive assessments (eg, emergency departments). If validated, serious games in health care could enable broader availability of efficient and engaging cognitive screening. The objective of this work is to demonstrate the feasibility of a game-based cognitive assessment delivered on tablet technology to a clinical sample and to conduct preliminary validation against standard mental status tools commonly used in elderly populations. We carried out a feasibility study in a hospital emergency department to evaluate the use of a serious game by elderly adults (N=146; age: mean 80.59, SD 6.00, range 70-94 years). We correlated game performance against a number of standard assessments, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Confusion Assessment Method (CAM). After a series of modifications, the game could be used by a wide range of elderly patients in the emergency department demonstrating its feasibility for use with these users. Of 146 patients, 141 (96.6%) consented to participate and played our serious game. Refusals to play the game were typically due to concerns of family members rather than unwillingness of the patient to play the game. Performance on the serious game correlated significantly with the MoCA (r=-.339, P games in a clinical setting. Further research is required to demonstrate the validity and reliability of game-based assessments for clinical decision making.

  14. [Multicenter validation of an evaluation tool for clinical training activities (SVAT) of the nursing students].

    Science.gov (United States)

    Finotto, Sergio; Gradellini, Cinzia; Bandini, Stefania; Burrai, Francesco; Lucchi Casadei, Sandra; Villani, Carolina; Vincenzi, Simone; Mecugni, Daniela

    2017-01-01

    To evaluate the psychometric characteristics of the Scheda di Valutazione delle Attività di Tirocinio (SVAT). The degree courses in Nursing of the University of Modena and Reggio Emilia, site of Reggio Emilia, the University of Bologna Formative Section BO1, Imola and training center of Cesena, the University of Ferrara training centers of Ferrara and Codigoro were all enrolled in the research. For the content validation the reactive Delphi method was chosen. The panel of experts expressed a qualitative-intuitive judgment on the adequacy of language and on the stimulus material (SVAT). For internal consistency Cronbach's alpha was calculated the. The test-retest method was used for the reliability of stability. all indicators of the SVAT have achieved a degree of consensus not less than 80% demonstrating its content validity. The face validity is demonstrated by an average score equal to or greater than 7 obtained by all indicators. The reliability of internal consistency of the SVAT was appraised by Cronbach's alpha that was 0.987 for the entire instrument. The reliability of the stability has been calculated through the correlation's coefficient expressed by Pearson's r that was 0.983 (p = 1.3E-198). in Italy there is no a "gold standard" tool to evaluate the clinical performance of nursing students during and at the end of their clinical training. The SVAT proves to be a valuable and reliable tool it furthermore could stimulate the discussion and the debate among educators and nurses, so that also in our country, it may be possible develop and refine tools that support the evaluation of clinical skills of nursing students.

  15. Validation of the clinical dehydration scale for children with acute gastroenteritis.

    Science.gov (United States)

    Goldman, Ran D; Friedman, Jeremy N; Parkin, Patricia C

    2008-09-01

    We previously created a clinical dehydration scale. Our objective was to validate the clinical dehydration scale with a new cohort of patients with acute gastroenteritis who were assessed in a tertiary emergency department in a developed country. A prospective observational study was performed in an emergency department at a large pediatric tertiary center in Canada. Children 1 month to 5 years of age with symptoms of acute gastroenteritis who were assessed in the emergency department were enrolled consecutively during a 4-month period. The main outcome measures were length of stay, proportion of children receiving intravenous fluid rehydration, and proportions of children with abnormal serum pH values or bicarbonate levels. A total of 205 children were enrolled, with a mean age of 22.4 +/- 14.9 months; 103 (50%) were male. The distribution of severity categories was as follows: no dehydration (score of 0), n = 117 (57%); some dehydration (score of 1-4), n = 83 (41%); moderate/severe dehydration (score of 5-8), n = 5 (2%). The 3 dehydration categories were significantly different with respect to the validation hypotheses (length of stay, mean +/- SD: none, 245 +/- 181 minutes; some, 397 +/- 302 minutes; moderate/severe, 501 +/- 389 minutes; treatment with intravenous fluids: none, n =17, 15%; some, n = 41, 49%; moderate/severe, n = 4, 80%; number of vomiting episodes in the 7 days before the emergency department visit: none, 8.4 +/- 7.7 episodes; some, 13 +/- 10.7 episodes; moderate/severe, 30.2 +/- 14.8 episodes). The clinical dehydration scale and the 3 severity categories were valid for a prospectively enrolled cohort of patients who were assessed in our tertiary emergency department. The scoring system was valuable in predicting a longer length of stay and the need for intravenous fluid rehydration for children with symptoms of acute gastroenteritis.

  16. Assessing decentering: validation, psychometric properties, and clinical usefulness of the Experiences Questionnaire in a Spanish sample.

    Science.gov (United States)

    Soler, Joaquim; Franquesa, Alba; Feliu-Soler, Albert; Cebolla, Ausias; García-Campayo, Javier; Tejedor, Rosa; Demarzo, Marcelo; Baños, Rosa; Pascual, Juan Carlos; Portella, Maria J

    2014-11-01

    Decentering is defined as the ability to observe one's thoughts and feelings in a detached manner. The Experiences Questionnaire (EQ) is a self-report instrument that originally assessed decentering and rumination. The purpose of this study was to evaluate the psychometric properties of the Spanish version of EQ-Decentering and to explore its clinical usefulness. The 11-item EQ-Decentering subscale was translated into Spanish and psychometric properties were examined in a sample of 921 adult individuals, 231 with psychiatric disorders and 690 without. The subsample of nonpsychiatric participants was also split according to their previous meditative experience (meditative participants, n=341; and nonmeditative participants, n=349). Additionally, differences among these three subgroups were explored to determine clinical validity of the scale. Finally, EQ-Decentering was administered twice in a group of borderline personality disorder, before and after a 10-week mindfulness intervention. Confirmatory factor analysis indicated acceptable model fit, sbχ(2)=243.8836 (p.46; and divergent validity: r<-.35). The scale detected changes in decentering after a 10-session intervention in mindfulness (t=-4.692, p<.00001). Differences among groups were significant (F=134.8, p<.000001), where psychiatric participants showed the lowest scores compared to nonpsychiatric meditative and nonmeditative participants. The Spanish version of the EQ-Decentering is a valid and reliable instrument to assess decentering either in clinical and nonclinical samples. In addition, the findings show that EQ-Decentering seems an adequate outcome instrument to detect changes after mindfulness-based interventions. Copyright © 2014. Published by Elsevier Ltd.

  17. A Serious Game for Clinical Assessment of Cognitive Status: Validation Study

    Science.gov (United States)

    Chignell, Mark; Tierney, Mary C.; Lee, Jacques

    2016-01-01

    Background We propose the use of serious games to screen for abnormal cognitive status in situations where it may be too costly or impractical to use standard cognitive assessments (eg, emergency departments). If validated, serious games in health care could enable broader availability of efficient and engaging cognitive screening. Objective The objective of this work is to demonstrate the feasibility of a game-based cognitive assessment delivered on tablet technology to a clinical sample and to conduct preliminary validation against standard mental status tools commonly used in elderly populations. Methods We carried out a feasibility study in a hospital emergency department to evaluate the use of a serious game by elderly adults (N=146; age: mean 80.59, SD 6.00, range 70-94 years). We correlated game performance against a number of standard assessments, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Confusion Assessment Method (CAM). Results After a series of modifications, the game could be used by a wide range of elderly patients in the emergency department demonstrating its feasibility for use with these users. Of 146 patients, 141 (96.6%) consented to participate and played our serious game. Refusals to play the game were typically due to concerns of family members rather than unwillingness of the patient to play the game. Performance on the serious game correlated significantly with the MoCA (r=–.339, P games in a clinical setting. Further research is required to demonstrate the validity and reliability of game-based assessments for clinical decision making. PMID:27234145

  18. Validity of the WISC-IV Spanish for a clinically referred sample of Hispanic children.

    Science.gov (United States)

    San Miguel Montes, Liza E; Allen, Daniel N; Puente, Antonio E; Neblina, Cris

    2010-06-01

    The Wechsler Intelligence Scale for Children (WISC) is the most commonly used intelligence test for children. Five years ago, a Spanish version of the WISC-IV was published (WISC-IV Spanish; Wechsler, 2005), but a limited amount of published information is available regarding its utility when assessing clinical samples. The current study included 107 children who were Spanish speaking and of Puerto Rican descent that had been administered the WISC-IV Spanish. They were subdivided into a clinical sample of 35 children with diagnoses of various forms of brain dysfunction (primarily learning disability, attention-deficit/hyperactivity disorder, and epilepsy) and a comparison group made up of 72 normal children who were part of the WISC-IV Spanish version standardization sample. Comparisons between these groups and the standardization sample were performed for the WISC-IV Spanish index and subtest scores. Results indicated that the clinical sample performed worse than the comparison samples on the Working Memory and Processing Speed Indexes, although findings varied to some extent depending on whether the clinical group was compared with the normal comparison group or the standardization sample. These findings provide support for the criterion validity of the WISC-IV Spanish when it is used to assess a clinically referred sample with brain dysfunction.

  19. Validation of a clinical assessment of spectral-ripple resolution for cochlear implant users.

    Science.gov (United States)

    Drennan, Ward R; Anderson, Elizabeth S; Won, Jong Ho; Rubinstein, Jay T

    2014-01-01

    Nonspeech psychophysical tests of spectral resolution, such as the spectral-ripple discrimination task, have been shown to correlate with speech-recognition performance in cochlear implant (CI) users. However, these tests are best suited for use in the research laboratory setting and are impractical for clinical use. A test of spectral resolution that is quicker and could more easily be implemented in the clinical setting has been developed. The objectives of this study were (1) To determine whether this new clinical ripple test would yield individual results equivalent to the longer, adaptive version of the ripple-discrimination test; (2) To evaluate test-retest reliability for the clinical ripple measure; and (3) To examine the relationship between clinical ripple performance and monosyllabic word recognition in quiet for a group of CI listeners. Twenty-eight CI recipients participated in the study. Each subject was tested on both the adaptive and the clinical versions of spectral ripple discrimination, as well as consonant-nucleus-consonant word recognition in quiet. The adaptive version of spectral ripple used a two-up, one-down procedure for determining spectral ripple discrimination threshold. The clinical ripple test used a method of constant stimuli, with trials for each of 12 fixed ripple densities occurring six times in random order. Results from the clinical ripple test (proportion correct) were then compared with ripple-discrimination thresholds (in ripples per octave) from the adaptive test. The clinical ripple test showed strong concurrent validity, evidenced by a good correlation between clinical ripple and adaptive ripple results (r = 0.79), as well as a correlation with word recognition (r = 0.7). Excellent test-retest reliability was also demonstrated with a high test-retest correlation (r = 0.9). The clinical ripple test is a reliable nonlinguistic measure of spectral resolution, optimized for use with CI users in a clinical setting. The test

  20. VALIDATION OF A CLINICAL ASSESSMENT OF SPECTRAL RIPPLE RESOLUTION FOR COCHLEAR-IMPLANT USERS

    Science.gov (United States)

    Drennan, Ward. R.; Anderson, Elizabeth S.; Won, Jong Ho; Rubinstein, Jay T.

    2013-01-01

    Objectives Non-speech psychophysical tests of spectral resolution, such as the spectral-ripple discrimination task, have been shown to correlate with speech recognition performance in cochlear implant (CI) users (Henry et al., 2005; Won et al. 2007, 2011; Drennan et al. 2008; Anderson et al. 2011). However, these tests are best suited for use in the research laboratory setting and are impractical for clinical use. A test of spectral resolution that is quicker and could more easily be implemented in the clinical setting has been developed. The objectives of this study were 1) To determine if this new clinical ripple test would yield individual results equivalent to the longer, adaptive version of the ripple discrimination test; 2) To evaluate test-retest reliability for the clinical ripple measure; and 3) To examine the relationship between clinical ripple performance and monosyllabic word recognition in quiet for a group of CI listeners. Design Twenty-eight CI recipients participated in the study. Each subject was tested on both the adaptive and the clinical versions of spectral ripple discrimination, as well as CNC word recognition in quiet. The adaptive version of spectral ripple employed a 2-up, 1-down procedure for determining spectral ripple discrimination threshold. The clinical ripple test used a method of constant stimuli, with trials for each of 12 fixed ripple densities occurring six times in random order. Results from the clinical ripple test (proportion correct) were then compared to ripple discrimination thresholds (in ripples per octave) from the adaptive test. Results The clinical ripple test showed strong concurrent validity, evidenced by a good correlation between clinical ripple and adaptive ripple results (r=0.79), as well as a correlation with word recognition (r = 0.7). Excellent test-retest reliability was also demonstrated with a high test-retest correlation (r = 0.9). Conclusions The clinical ripple test is a reliable non-linguistic measure

  1. Measurement of glomerular filtration rate by impulse synthesis: Clinical validation and optimization

    International Nuclear Information System (INIS)

    Palagi, B.; Verga, P.; Broggi, A.; Picozzi, R.; Villa, F.; Guzzini, F.; Cozzi, C.; Tomasi, A.

    1988-01-01

    Impulse synthesis is a technique which relies upon the logic of continuous infusion but extracts the clearance value from single-injection data by shifting and adding them until an asymptotic value is attained. This study has been aimed at validating and optimizing clinically the measurement of glomerular filtration rate by impulse synthesis. A single intravenous injection of 51 Cr-EDTA has been made in 32 patients and plasma activity monitored over the next 6 h. Glomerular filtration rate computed by a single-exponential fit method (GFR-SEF) has been shown to be significantly (p [de

  2. Clinical validation of nursing outcome mobility in patients with cerebrovascular accidents.

    Science.gov (United States)

    Moreira, Rafaella Pessoa; Araujo, Thelma Leite de; Lopes, Marcos Venicios de Oliveira; Cavalcante, Tahissa Frota; Guedes, Nirla Gomes; Chaves, Emília Soares; Portela, Regiane Campos; Holanda, Rose-Eloise

    2016-12-15

    To clinically validate the nursing outcome Mobility in patients with cerebrovascular accidents. Descriptive study, conducted in July 2011, with 38 outpatients, in northeastern Brazil. Data collection took place by evaluating two pairs of specialist nurses, where one pair used the instrument containing the constitutive and operational definitions of the indicators and magnitudes of the Mobility Outcome and the other pair without such definitions. When analyzing the evaluations among nurses, all indicators showed significant differences by the Friedman test (p cerebrovascular accident patient's mobility state.

  3. Validation of the walking index for spinal cord injury in a US and European clinical population

    DEFF Research Database (Denmark)

    Ditunno, J.F.; Scivoletto, G.; Patrick, M.

    2008-01-01

    OBJECTIVE: To demonstrate the prospective construct validity of the walking index for spinal cord injury (WISCI) in US/European clinical population. DESIGN: Prospective Cohort in Denmark, Germany, Italy and the USA. PARTICIPANTS/METHOD: Participants with acute complete/incomplete (ASIA Impairment...... Scale (AIS) A, B, C and D) traumatic spinal cord injuries were enrolled from four centers. Lower extremity motor scores (LEMS), WISCI level and Locomotor Functional Independence Measure (LFIM) levels were assessed with change in ambulatory status. WISCI progression was assessed for monotonic direction...

  4. In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes.

    Directory of Open Access Journals (Sweden)

    Mahmoud ElHefnawi

    Full Text Available RNA interference (RNAi is a post-transcriptional gene silencing mechanism that mediates the sequence-specific degradation of targeted RNA and thus provides a tremendous opportunity for development of oligonucleotide-based drugs. Here, we report on the design and validation of small interfering RNAs (siRNAs targeting highly conserved regions of the hepatitis C virus (HCV genome. To aim for therapeutic applications by optimizing the RNAi efficacy and reducing potential side effects, we considered different factors such as target RNA variations, thermodynamics and accessibility of the siRNA and target RNA, and off-target effects. This aim was achieved using an in silico design and selection protocol complemented by an automated MysiRNA-Designer pipeline. The protocol included the design and filtration of siRNAs targeting highly conserved and accessible regions within the HCV internal ribosome entry site, and adjacent core sequences of the viral genome with high-ranking efficacy scores. Off-target analysis excluded siRNAs with potential binding to human mRNAs. Under this strict selection process, two siRNAs (HCV353 and HCV258 were selected based on their predicted high specificity and potency. These siRNAs were tested for antiviral efficacy in HCV genotype 1 and 2 replicon cell lines. Both in silico-designed siRNAs efficiently inhibited HCV RNA replication, even at low concentrations and for short exposure times (24h; they also exceeded the antiviral potencies of reference siRNAs targeting HCV. Furthermore, HCV353 and HCV258 siRNAs also inhibited replication of patient-derived HCV genotype 4 isolates in infected Huh-7 cells. Prolonged treatment of HCV replicon cells with HCV353 did not result in the appearance of escape mutant viruses. Taken together, these results reveal the accuracy and strength of our integrated siRNA design and selection protocols. These protocols could be used to design highly potent and specific RNAi-based therapeutic

  5. Predictive validity of measurements of clinical competence using the team objective structured bedside assessment (TOSBA): assessing the clinical competence of final year medical students.

    LENUS (Irish Health Repository)

    Meagher, Frances M

    2009-11-01

    The importance of valid and reliable assessment of student competence and performance is gaining increased recognition. Provision of valid patient-based formative assessment is an increasing challenge for clinical teachers in a busy hospital setting. A formative assessment tool that reliably predicts performance in the summative setting would be of value to both students and teachers.

  6. Validation of the Rowland Universal Dementia Assessment Scale for multicultural screening in Danish memory clinics.

    Science.gov (United States)

    Nielsen, T Rune; Andersen, Birgitte Bo; Gottrup, Hanne; Lützhøft, Jan H; Høgh, Peter; Waldemar, Gunhild

    2013-01-01

    The Rowland Universal Dementia Assessment Scale (RUDAS) is a brief cognitive screening test that was developed to detect dementia in multicultural populations. The RUDAS has not previously been validated in multicultural populations outside of Australia. The aim of this study was to evaluate the diagnostic accuracy of the RUDAS in a multicultural sample of patients referred to Danish memory clinics. Data were collected from 137 consecutive patients (34 with an immigrant background) in three Danish memory clinics. All patients were given the RUDAS as a supplement to the standard diagnostic workup. Diagnostic accuracy for the RUDAS [area under the curve (AUC) = 0.838] was similar to that of the Mini-Mental State Examination (MMSE; AUC = 0.840). The cutoff score with the best balance of sensitivity, specificity and accuracy was multicultural patient populations. © 2013 S. Karger AG, Basel.

  7. Validation and Assessment of a Technology Familiarity Score in Patients Attending a Symptomatic Breast Clinic.

    Science.gov (United States)

    O'Brien, C; Kelly, J; Lehane, E A; Livingstone, V; Cotter, B; Butt, A; Kelly, L; Corrigan, M A

    2015-10-01

    New media technologies (computers, mobile phones and the internet) have the potential to transform the healthcare information needs of patients with breast disease (Ferlay et al. in Eur J Cancer 49:1374-1403, 2013). However, patients' current level of use and their willingness to accept new media for education and communication remain unknown. This was a single-centre clinic-based prospective cross-sectional study. A previously developed instrument was modified, validated and tested on patients attending a symptomatic breast clinic. The instrument was evaluated on 200 symptomatic breast patients. The commonest outlets for education were staff (95 %), leaflets (69 %) and websites (59 %). Websites are more likely to be consulted by younger patients (higher education were more likely to favour apps, websites and email (p technology use among breast patients is expanding as expected along generational trends. As such its' further integration into healthcare systems can potentially ameliorate patient education and communication.

  8. Next-generation negative symptom assessment for clinical trials: validation of the Brief Negative Symptom Scale.

    Science.gov (United States)

    Strauss, Gregory P; Keller, William R; Buchanan, Robert W; Gold, James M; Fischer, Bernard A; McMahon, Robert P; Catalano, Lauren T; Culbreth, Adam J; Carpenter, William T; Kirkpatrick, Brian

    2012-12-01

    The current study examined the psychometric properties of the Brief Negative Symptom Scale (BNSS), a next-generation rating instrument developed in response to the NIMH sponsored consensus development conference on negative symptoms. Participants included 100 individuals with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who completed a clinical interview designed to assess negative, positive, disorganized, and general psychiatric symptoms, as well as functional outcome. A battery of anhedonia questionnaires and neuropsychological tests were also administered. Results indicated that the BNSS has excellent internal consistency and temporal stability, as well as good convergent and discriminant validity in its relationships with other symptom rating scales, functional outcome, self-reported anhedonia, and neuropsychological test scores. Given its brevity (13-items, 15-minute interview) and good psychometric characteristics, the BNSS can be considered a promising new instrument for use in clinical trials. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Clinical validity of a disease-specific health status questionnaire: the peripheral artery questionnaire.

    Science.gov (United States)

    Hoeks, Sanne E; Smolderen, Kim G; Scholte Op Reimer, Wilma J M; Verhagen, Hence J M; Spertus, John A; Poldermans, Don

    2009-02-01

    Measuring patient-centered outcomes is becoming increasingly important in patients with peripheral arterial disease (PAD), both as a means of determining the benefits of treatment and as an aid for disease management. In order to monitor health status in a reliable and sensitive way, the disease-specific measure Peripheral Artery Questionnaire (PAQ) was developed. However, to date, its correlation with traditional clinical indices is unknown. The primary aim of this study was to better establish the clinical validity of the PAQ by examining its association with functional indices related to PAD. Furthermore, we hypothesized that the clinical validity of this disease-specific measure is better as compared with the EuroQol-5-dimensional (EQ-5D), a standardized generic instrument. Data on 711 consecutive PAD patients undergoing surgery were collected from 11 Dutch hospitals in 2004. At 3-year follow-up, questionnaires including the PAQ, EQ-5D, and EuroQol-Visual Analogue Scale (EQ VAS) were completed in 84% of survivors. The PAQ was analyzed according to three domains, as established by a factor analyses in the Dutch population, and the summary score. Baseline clinical indices included the presence and severity of claudication intermittent (CI) and the Lee Cardiac Risk Index. All three PAQ domains (Physical Function, Perceived Disability, and Treatment Satisfaction) were significantly associated with CI symptoms (P values PAQ summary scores as compared with asymptomatic patients (58.6 +/- 27.8 vs 68.6 +/- 27.8, P = PAQ summary score and the subscale scores for Physical Functioning and Perceived Disability demonstrated a clear dose-response relation for walking distance and the Lee Risk Index (P values PAQ proved to be good as the PAQ subscales discriminated well between patients with or without symptomatic PAD and its severity as defined by walking distance. Furthermore, the PAQ subscales were directly proportional to the presence and number of risk factors relevant

  10. Evaluation of Peritumoral Edema in the Delineation of Radiotherapy Clinical Target Volumes for Glioblastoma

    International Nuclear Information System (INIS)

    Chang, Eric L.; Akyurek, Serap; Avalos, Tedde C; Rebueno, Neal C; Spicer, Chris C; Garcia, John C; Famiglietti, Robin; Allen, Pamela K.; Chao, K.S. Clifford; Mahajan, Anita; Woo, Shiao Y.; Maor, Moshe H.

    2007-01-01

    Purpose: To evaluate the spatial relationship between peritumoral edema and recurrence pattern in patients with glioblastoma (GBM). Methods and Materials: Forty-eight primary GBM patients received three-dimensional conformal radiotherapy that did not intentionally include peritumoral edema within the clinical target volume between July 2000 and June 2001. All 48 patients have subsequently recurred, and their original treatment planning parameters were used for this study. New theoretical radiation treatment plans were created for the same 48 patients, based on Radiation Therapy Oncology Group (RTOG) target delineation guidelines that specify inclusion of peritumoral edema. Target volume and recurrent tumor coverage, as well as percent volume of normal brain irradiated, were assessed for both methods of target delineation using dose-volume histograms. Results: A comparison between the location of recurrent tumor and peritumoral edema volumes from all 48 cases failed to show correlation by linear regression modeling (r 2 0.0007; p = 0.3). For patients with edema >75 cm 3 , the percent volume of brain irradiated to 46 Gy was significantly greater in treatment plans that intentionally included peritumoral edema compared with those that did not (38% vs. 31%; p = 0.003). The pattern of failure was identical between the two sets of plans (40 central, 3 in-field, 3 marginal, and 2 distant recurrence). Conclusion: Clinical target volume delineation based on a 2-cm margin rather than on peritumoral edema did not seem to alter the central pattern of failure for patients with GBM. For patients with peritumoral edema >75 cm 3 , using a constant 2-cm margin resulted in a smaller median percent volume of brain being irradiated to 30 Gy, 46 Gy, and 50 Gy compared with corresponding theoretical RTOG plans that deliberately included peritumoral edema

  11. The Reliability and Validity of the Outcome Rating Scale: A Replication Study of a Brief Clinical Measure

    National Research Council Canada - National Science Library

    Bringhurst, David L; Watson, Curtis W; Miller, Scott D; Duncan, Barry L

    2004-01-01

    ... (Miller, Duncan, Brown, Sparks, AND Claud, 2003). This article reports the findings of an independent replication study evaluating the reliability and concurrent validity of the ORS as studied in a non-clinical sample...

  12. The Air Force Mobile Forward Surgical Team (MFST): Using the Estimating Supplies Program to Validate Clinical Requirement

    National Research Council Canada - National Science Library

    Nix, Ralph E; Onofrio, Kathleen; Konoske, Paula J; Galarneau, Mike R; Hill, Martin

    2004-01-01

    .... The primary objective of the study was to provide the Air Force with the ability to validate clinical requirements of the MFST assemblage, with the goal of using NHRC's Estimating Supplies Program (ESP...

  13. World Workshop on Oral Medicine VI: an international validation study of clinical competencies for advanced training in oral medicine.

    Science.gov (United States)

    Steele, John C; Clark, Hadleigh J; Hong, Catherine H L; Jurge, Sabine; Muthukrishnan, Arvind; Kerr, A Ross; Wray, David; Prescott-Clements, Linda; Felix, David H; Sollecito, Thomas P

    2015-08-01

    To explore international consensus for the validation of clinical competencies for advanced training in Oral Medicine. An electronic survey of clinical competencies was designed. The survey was sent to and completed by identified international stakeholders during a 10-week period. To be validated, an individual competency had to achieve 90% or greater consensus to keep it in its current format. Stakeholders from 31 countries responded. High consensus agreement was achieved with 93 of 101 (92%) competencies exceeding the benchmark for agreement. Only 8 warranted further attention and were reviewed by a focus group. No additional competencies were suggested. This is the first international validated study of clinical competencies for advanced training in Oral Medicine. These validated clinical competencies could provide a model for countries developing an advanced training curriculum for Oral Medicine and also inform review of existing curricula. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Diagnostic Validity of Clinical Signs Associated with a Large Exophoria at Near

    Directory of Open Access Journals (Sweden)

    Pilar Cacho-Martínez

    2013-01-01

    Full Text Available Purpose. To analyze the diagnostic validity of accommodative and binocular tests in a sample of patients with a large near exophoria with moderate to severe symptoms. Methods. Two groups of patients between 19 and 35 years were recruited from a university clinic: 33 subjects with large exophoria at near vision and moderate or high visual discomfort and 33 patients with normal heterophoria and low visual discomfort. Visual discomfort was defined using the Conlon survey. A refractive exam and an exhaustive evaluation of accommodation and vergence were assessed. Diagnostic validity by means of receiver operator characteristic (ROC curves, sensitivity (S, specificity (Sp, and positive and negative likelihood ratios (LR+, LR− were assessed. This analysis was also carried out considering multiple tests as serial testing strategy. Results. ROC analysis showed the best diagnostic accuracy for receded near point of convergence (NPC recovery (area = 0.929 and binocular accommodative facility (BAF (area = 0.886. Using the cut-offs obtained with ROC analysis, the best diagnostic validity was obtained for the combination of NPC recovery and BAF (S  =  0.77, Sp = 1, LR+ = value tending to infinity, LR− = 0.23 and the combination of NPC break and recovery with BAF (S  =  0.73, Sp = 1, LR+ = tending to infinity, LR− = 0.27. Conclusions. NPC and BAF tests were the tests with the best diagnostic accuracy for subjects with large near exophoria and moderate to severe symptoms.

  15. Validation of a new strength measurement device for amyotrophic lateral sclerosis clinical trials.

    Science.gov (United States)

    Andres, Patricia L; Skerry, Linda M; Munsat, Theodore L; Thornell, Brenda J; Szymonifka, Jackie; Schoenfeld, David A; Cudkowicz, Merit E

    2012-01-01

    Strength measures with reduced variability and higher sensitivity could improve efficiency in clinical trials of amyotrophic lateral sclerosis (ALS). The Accurate Test of Limb Isometric Strength (ATLIS) was developed to precisely and conveniently measure force in 12 muscle groups. In this study we evaluate the reliability and validity of the ATLIS testing protocol. Twenty healthy adults and 10 patients with ALS were tested twice by the same or by different evaluators to determine test-retest and interrater reliability. Twenty healthy adults were examined using ATLIS and a well-validated strength testing protocol (TQNE) to assess criterion-based validity. Mean absolute variation between tests was 8.6%, and intraclass correlation coefficients for each muscle group were high (range 0.82-0.99). The Pearson correlation coefficient of mean ATLIS and TQNE scores was 0.90. A subject survey demonstrated high user acceptance of ATLIS. ATLIS is convenient for patients and evaluators, produces precise strength measurements, and is easily moved between examining rooms. Copyright © 2011 Wiley Periodicals, Inc.

  16. Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project.

    NARCIS (Netherlands)

    Cluzeau, F.A.; Burgers, J.S.; Brouwers, M.M.; Grol, R.P.T.M.; et al.,

    2003-01-01

    BACKGROUND: International interest in clinical practice guidelines has never been greater but many published guidelines do not meet the basic quality requirements. There have been renewed calls for validated criteria to assess the quality of guidelines. OBJECTIVE: To develop and validate an

  17. Construct Validity of Medical Clinical Competence Measures: A Multitrait-Multimethod Matrix Study Using Confirmatory Factor Analysis.

    Science.gov (United States)

    Forsythe, George B.; And Others

    1986-01-01

    Construct validity was investigated for three tests of clinical competence in medicine: National Board of Medical Examiners examination (NBME), California Psychological Inventory (CPI), and Resident Evaluation Form (REF). Scores from 166 residents were analyzed. Results suggested low construct validity for CPI and REF scales, and moderate…

  18. 'Mechanical restraint-confounders, risk, alliance score': testing the clinical validity of a new risk assessment instrument.

    Science.gov (United States)

    Deichmann Nielsen, Lea; Bech, Per; Hounsgaard, Lise; Alkier Gildberg, Frederik

    2017-08-01

    Unstructured risk assessment, as well as confounders (underlying reasons for the patient's risk behaviour and alliance), risk behaviour, and parameters of alliance, have been identified as factors that prolong the duration of mechanical restraint among forensic mental health inpatients. To clinically validate a new, structured short-term risk assessment instrument called the Mechanical Restraint-Confounders, Risk, Alliance Score (MR-CRAS), with the intended purpose of supporting the clinicians' observation and assessment of the patient's readiness to be released from mechanical restraint. The content and layout of MR-CRAS and its user manual were evaluated using face validation by forensic mental health clinicians, content validation by an expert panel, and pilot testing within two, closed forensic mental health inpatient units. The three sub-scales (Confounders, Risk, and a parameter of Alliance) showed excellent content validity. The clinical validations also showed that MR-CRAS was perceived and experienced as a comprehensible, relevant, comprehensive, and useable risk assessment instrument. MR-CRAS contains 18 clinically valid items, and the instrument can be used to support the clinical decision-making regarding the possibility of releasing the patient from mechanical restraint. The present three studies have clinically validated a short MR-CRAS scale that is currently being psychometrically tested in a larger study.

  19. Clinical validation of the CHRONIOUS wearable system in patients with chronic disease.

    Science.gov (United States)

    Bellos, Christos; Papadopoulos, Athanassios; Rosso, Roberto; Fotiadis, Dimitrios I

    2013-01-01

    The CHRONIOUS system defines a powerful and easy to use framework which has been designed to provide services to clinicians and their patients suffering from chronic diseases. The system is composed of a wearable shirt that integrate several body sensors, a portable smart device and a central sub-system that is responsible for the long term storage of the collected patient's data. A multi-parametric expert system is developed for the analysis of the collected data using intelligent algorithms and complex techniques. Apart for the vital signals, dietary habits, drug intake, activity data, environmental and biochemical parameters are recorded. The CHRONIOUS platform is validated through clinical trials in several medical centers and patient's home environments recruiting patients suffering from Chronic Obstructive pulmonary disease (COPD) and Chronic Kidney Disease (CKD) diseases. The clinical trials contribute in improving the system's accuracy, while Pulmonologists and Nephrologists experts utilized the CHRONIOUS platform to evaluate its efficiency and performance. The results of the utilization of the system were very encouraging. The CHRONIOUS system has been proven to be a well-validated real-time patient monitoring and supervision platform, providing a useful tool for the clinician and the patient that would contribute to the more effective management of chronic diseases.

  20. The Depressive Experiences Questionnaire: validity and psychological correlates in a clinical sample.

    Science.gov (United States)

    Riley, W T; McCranie, E W

    1990-01-01

    This study sought to compare the original and revised scoring systems of the Depressive Experiences Questionnaire (DEQ) and to assess the construct validity of the Dependent and Self-Critical subscales of the DEQ in a clinically depressed sample. Subjects were 103 depressed inpatients who completed the DEQ, the Beck Depression Inventory (BDI), the Hopelessness Scale, the Automatic Thoughts Questionnaire (ATQ), the Rathus Assertiveness Schedule (RAS), and the Minnesota Multiphasic Personality Inventory (MMPI). The original and revised scoring systems of the DEQ evidenced good concurrent validity for each factor scale, but the revised system did not sufficiently discriminate dependent and self-critical dimensions. Using the original scoring system, self-criticism was significantly and positively related to severity of depression, whereas dependency was not, particularly for males. Factor analysis of the DEQ scales and the other scales used in this study supported the dependent and self-critical dimensions. For men, the correlation of the DEQ with the MMPI scales indicated that self-criticism was associated with psychotic symptoms, hostility/conflict, and a distress/exaggerated response set, whereas dependency did not correlate significantly with any MMPI scales. Females, however, did not exhibit a differential pattern of correlations between either the Dependency or the Self-Criticism scales and the MMPI. These findings suggest possible gender differences in the clinical characteristics of male and female dependent and self-critical depressive subtypes.

  1. Clinical validation of a quality of life questionnaire in angina pectoris patients.

    Science.gov (United States)

    Marquis, P; Fayol, C; Joire, J E

    1995-11-01

    Angina pectoris impairs patients' quality of life. In order to assess its impact on quality of life, a questionnaire was developed using a literature review and interviews with patients and clinicians. It consisted of a general profile (SF-36) which measured functional status, well-being, perceived health, and a specific index, the Angina Pectoris Quality of Life Questionnaire, supplemented by new items. The acceptability, internal consistency reliability and clinical validity of this 70-item questionnaire were analysed in a cross-sectional study. Of 197 coronary patients approached, 93% (n = 184) agreed to participate and 86% (n = 170) returned the mailed questionnaire. Mean age of patients was 67 years (+/- 10); 79% were male and 70% were retired. Sixty patients were asymptomatic and 110 reported anginal crises (Canadian Cardiovascular Society Classification: class I: 48; II: 37; III: 13; IV: 0; V: 12). Globally, angina pectoris was found to affect each quality of life concept measured: physical functioning, well-being, and perceived health. Quality of life profiles worsened in accordance with increasing severity of the condition, as stratified by angina pectoris class. Asymptomatic patients reported better general and specific profiles. These results support the feasibility and usefulness of evaluating quality of life using the questionnaire. The validation of the data is very encouraging and enables the questionnaire to be used in clinical trials.

  2. RELIABILITY AND VALIDITY OF CLINICAL AND ULTRASOUND EXAMINATIONS OF DEVELOPMENTAL HIP DYSPLASIA

    Directory of Open Access Journals (Sweden)

    Predrag Grubor

    2011-03-01

    Full Text Available Developmental dysplasia of the hip (DDH is the most common congenital deformation of the musculoskeletal system and its successful treatment is closely related to early diagnosis. The study is aimed at examining the incidence of developmental dysplasia of the hip (DDH and at analysing the validity of clinical examination, which is used for the early detection of DDH in the neonatal period, compared to ultrasound examination.The study involved 400 neonates born in the Banja Luka Region. A new questionnaire was open during the first regular ultrasound and clinical examination of the neonates’ hips and anamnestic and clinical data were recorded in it: the asymmetry of the gluteal, inguinal and femoral folds (Bade sign, the result of abduction testseparately for each hip, the Ortolani sign of luxation and the Palmen sign of reposition, then hip sonography. A Toshiba ultrasound machine with a 7.5 MHz linear probe was used. The method employed was Professor Reinhard Graf’s. Out of the total number of the children with a positive sonographic finding for DDH, 63.16% of them have one of the clinical signs of DDH. The ability of a clinical finding to identify those patients who do not have DDH and have a negative sonographic finding is 79.8%. Out of the total number of the examined children with a positive clinical finding, only 15.58% of them also have a positive sonographic finding for DDH. This research has showed that clinical examination of the hips is of low sensitivity, specificity and reliability, and that not all types of DDH can be detected. Clinical examination must remain an integral part of every infant’s examination, but it constitutes a complementary diagnostic procedure to ultrasound examination. The ultrasound examination of DDH has created new possibilities and has filled the void that existed due to the deficiency of clinical tests, and at the same time it has reduced the number of X-ray examinations of the hips. This research has

  3. The improved Clinical Global Impression Scale (iCGI: development and validation in depression

    Directory of Open Access Journals (Sweden)

    Kadouri Alane

    2007-02-01

    Full Text Available Abstract Background The Clinical Global Impression scale (CGI is frequently used in medical care and clinical research because of its face validity and practicability. This study proposes to improve the reliability of the Clinical Global Impression (CGI scale in depressive disorders by the use of a semi-standardized interview, a new response format, and a Delphi procedure. Methods Thirty patients hospitalised for a major depressive episode were filmed at T1 (first week in hospital and at T2 (2 weeks later during a 5' specific interview. The Hamilton Depressive Rating Scale and the Symptom Check List were also rated. Eleven psychiatrists rated these videos using either the usual CGI response format or an improved response format, with or without a Delphi procedure. Results The new response format slightly improved (but not significantly the interrater agreement, the Delphi procedure did not. The best results were obtained when ratings by 4 independent raters were averaged. In this situation, intraclass correlation coefficients were about 0.9. Conclusion The Clinical Global Impression is a useful approach in psychiatry since it apprehends patients in their entirety. This study shows that it is possible to quantify such impressions with a high level of interrater agreement.

  4. The Berlin Inventory of Gambling behavior - Screening (BIG-S): Validation using a clinical sample.

    Science.gov (United States)

    Wejbera, Martin; Müller, Kai W; Becker, Jan; Beutel, Manfred E

    2017-05-18

    Published diagnostic questionnaires for gambling disorder in German are either based on DSM-III criteria or focus on aspects other than life time prevalence. This study was designed to assess the usability of the DSM-IV criteria based Berlin Inventory of Gambling Behavior Screening tool in a clinical sample and adapt it to DSM-5 criteria. In a sample of 432 patients presenting for behavioral addiction assessment at the University Medical Center Mainz, we checked the screening tool's results against clinical diagnosis and compared a subsample of n=300 clinically diagnosed gambling disorder patients with a comparison group of n=132. The BIG-S produced a sensitivity of 99.7% and a specificity of 96.2%. The instrument's unidimensionality and the diagnostic improvements of DSM-5 criteria were verified by exploratory and confirmatory factor analysis as well as receiver operating characteristic analysis. The BIG-S is a reliable and valid screening tool for gambling disorder and demonstrated its concise and comprehensible operationalization of current DSM-5 criteria in a clinical setting.

  5. Clinical validity of a population database definition of remission in patients with major depression.

    Science.gov (United States)

    Sicras-Mainar, Antoni; Blanca-Tamayo, Milagrosa; Gutiérrez-Nicuesa, Laura; Salvatella-Pasant, Jordi; Navarro-Artieda, Ruth

    2010-02-11

    Major depression (MD) is one of the most frequent diagnoses in Primary Care. It is a disabling illness that increases the use of health resources. To describe the concordance between remission according to clinical assessment and remission obtained from the computerized prescription databases of patients with MD in a Spanish population. multicenter cross-sectional. The population under study was comprised of people from six primary care facilities, who had a MD episode between January 2003 and March 2007. A specialist in psychiatry assessed a random sample of patient histories and determined whether a certain patient was in remission according to clinical criteria (ICPC-2). Regarding the databases, patients were considered in remission when they did not need further prescriptions of AD for at least 6 months after completing treatment for a new episode. Validity indicators (sensitivity [S], specificity [Sp]) and clinical utility (positive and negative probability ratio [PPR] and [NPR]) were calculated. The concordance index was established using Cohen's kappa coefficient. Significance level was p Reliability analysis: Cronbach's alpha: 90.6% (CI was 95%: 85.6 - 95.6%). Results show an acceptable level of concordance between remission obtained from the computerized databases and clinical criteria. The major discrepancies were found in diagnostic accuracy.

  6. Validated Measures of Insomnia, Function, Sleepiness, and Nasal Obstruction in a CPAP Alternatives Clinic Population.

    Science.gov (United States)

    Lam, Austin S; Collop, Nancy A; Bliwise, Donald L; Dedhia, Raj C

    2017-08-15

    Although efficacious in the treatment of obstructive sleep apnea (OSA), continuous positive airway pressure (CPAP) can be difficult to tolerate, with long-term adherence rates approaching 50%. CPAP alternatives clinics specialize in the evaluation and treatment of CPAP-intolerant patients; yet this population has not been studied in the literature. To better understand these patients, we sought to assess insomnia, sleep-related functional status, sleepiness, and nasal obstruction, utilizing data from validated instruments. After approval from the Emory University Institutional Review Board, a retrospective chart review was performed from September 2015 to September 2016 of new patient visits at the Emory CPAP alternatives clinic. Patient demographics and responses were recorded from the Insomnia Severity Index, Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), Epworth Sleepiness Scale, and Nasal Obstruction Symptom Evaluation questionnaires. A total of 172 patients were included, with 81% having moderate-severe OSA. Most of the patients demonstrated moderate-severe clinical insomnia and at least moderate nasal obstruction. FOSQ-10 scores indicated sleep-related functional impairment in 88%. However, most patients did not demonstrate excessive daytime sleepiness. This patient population demonstrates significant symptomatology and functional impairment. Because of the severity of their OSA, they are at increased risk of complications. In order to mitigate the detrimental effects of OSA, these significantly impacted patients should be identified and encouraged to seek CPAP alternatives clinics that specialize in the treatment of this population. © 2017 American Academy of Sleep Medicine

  7. Cross-cultural validation of Lupus Impact Tracker in five European clinical practice settings.

    Science.gov (United States)

    Schneider, Matthias; Mosca, Marta; Pego-Reigosa, José-Maria; Gunnarsson, Iva; Maurel, Frédérique; Garofano, Anna; Perna, Alessandra; Porcasi, Rolando; Devilliers, Hervé

    2017-05-01

    The aim was to evaluate the cross-cultural validity of the Lupus Impact Tracker (LIT) in five European countries and to assess its acceptability and feasibility from the patient and physician perspectives. A prospective, observational, cross-sectional and multicentre validation study was conducted in clinical settings. Before the visit, patients completed LIT, Short Form 36 (SF-36) and care satisfaction questionnaires. During the visit, physicians assessed disease activity [Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI], organ damage [SLICC/ACR damage index (SDI)] and flare occurrence. Cross-cultural validity was assessed using the Differential Item Functioning method. Five hundred and sixty-nine SLE patients were included by 25 specialists; 91.7% were outpatients and 89.9% female, with mean age 43.5 (13.0) years. Disease profile was as follows: 18.3% experienced flares; mean SELENA-SLEDAI score 3.4 (4.5); mean SDI score 0.8 (1.4); and SF-36 mean physical and mental component summary scores: physical component summary 42.8 (10.8) and mental component summary 43.0 (12.3). Mean LIT score was 34.2 (22.3) (median: 32.5), indicating that lupus moderately impacted patients' daily life. A cultural Differential Item Functioning of negligible magnitude was detected across countries (pseudo- R 2 difference of 0.01-0.04). Differences were observed between LIT scores and Physician Global Assessment, SELENA-SLEDAI, SDI scores = 0 (P cultural invariability across countries. They suggest that LIT can be used in routine clinical practice to evaluate and follow patient-reported outcomes in order to improve patient-physician interaction. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Estimation of skull table thickness with clinical CT and validation with microCT.

    Science.gov (United States)

    Lillie, Elizabeth M; Urban, Jillian E; Weaver, Ashley A; Powers, Alexander K; Stitzel, Joel D

    2015-01-01

    Brain injuries resulting from motor vehicle crashes (MVC) are extremely common yet the details of the mechanism of injury remain to be well characterized. Skull deformation is believed to be a contributing factor to some types of traumatic brain injury (TBI). Understanding biomechanical contributors to skull deformation would provide further insight into the mechanism of head injury resulting from blunt trauma. In particular, skull thickness is thought be a very important factor governing deformation of the skull and its propensity for fracture. Current computed tomography (CT) technology is limited in its ability to accurately measure cortical thickness using standard techniques. A method to evaluate cortical thickness using cortical density measured from CT data has been developed previously. This effort validates this technique for measurement of skull table thickness in clinical head CT scans using two postmortem human specimens. Bone samples were harvested from the skulls of two cadavers and scanned with microCT to evaluate the accuracy of the estimated cortical thickness measured from clinical CT. Clinical scans were collected at 0.488 and 0.625 mm in plane resolution with 0.625 mm thickness. The overall cortical thickness error was determined to be 0.078 ± 0.58 mm for cortical samples thinner than 4 mm. It was determined that 91.3% of these differences fell within the scanner resolution. Color maps of clinical CT thickness estimations are comparable to color maps of microCT thickness measurements, indicating good quantitative agreement. These data confirm that the cortical density algorithm successfully estimates skull table thickness from clinical CT scans. The application of this technique to clinical CT scans enables evaluation of cortical thickness in population-based studies. © 2014 Anatomical Society.

  9. The Clinical Validation of the Athlete Sleep Screening Questionnaire: an Instrument to Identify Athletes that Need Further Sleep Assessment.

    Science.gov (United States)

    Bender, Amy M; Lawson, Doug; Werthner, Penny; Samuels, Charles H

    2018-06-04

    Previous research has established that general sleep screening questionnaires are not valid and reliable in an athlete population. The Athlete Sleep Screening Questionnaire (ASSQ) was developed to address this need. While the initial validation of the ASSQ has been established, the clinical validity of the ASSQ has yet to be determined. The main objective of the current study was to evaluate the clinical validity of the ASSQ. Canadian National Team athletes (N = 199; mean age 24.0 ± 4.2 years, 62% females; from 23 sports) completed the ASSQ. A subset of athletes (N = 46) were randomized to the clinical validation sub-study which required subjects to complete an ASSQ at times 2 and 3 and to have a clinical sleep interview by a sleep medicine physician (SMP) who rated each subjects' category of clinical sleep problem and provided recommendations to improve sleep. To assess clinical validity, the SMP category of clinical sleep problem was compared to the ASSQ. The internal consistency (Cronbach's alpha = 0.74) and test-retest reliability (r = 0.86) of the ASSQ were acceptable. The ASSQ demonstrated good agreement with the SMP (Cohen's kappa = 0.84) which yielded a diagnostic sensitivity of 81%, specificity of 93%, positive predictive value of 87%, and negative predictive value of 90%. There were 25.1% of athletes identified to have clinically relevant sleep disturbances that required further clinical sleep assessment. Sleep improved from time 1 at baseline to after the recommendations at time 3. Sleep screening athletes with the ASSQ provides a method of accurately determining which athletes would benefit from preventative measures and which athletes suffer from clinically significant sleep problems. The process of sleep screening athletes and providing recommendations improves sleep and offers a clinical intervention output that is simple and efficient for teams and athletes to implement.

  10. Clinical efficacy of local targeted chemotherapy for triple-negative breast cancer

    International Nuclear Information System (INIS)

    He, Jinsong; Wang, Xianming; Guan, Hong; Chen, Weicai; Wang, Ming; Wu, Huisheng; Wang, Zun; Zhou, Ruming; Qiu, Shuibo

    2011-01-01

    The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer. A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m 2 ]; E: epirubicin [90 mg/m 2 ]; F: 5-fluorouracil [600 mg/m 2 ]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined. The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group. As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses

  11. Prostate bed target interfractional motion using RTOG consensus definitions and daily CT on rails. Does target motion differ between superior and inferior portions of the clinical target volume

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Vivek; Zhou, Sumin; Enke, Charles A.; Wahl, Andrew O. [University of Nebraska Medical Center, Department of Radiation Oncology, Omaha (United States); Chen, Shifeng [University of Maryland School of Medicine, Department of Radiation Oncology, Baltimore, MD (United States)

    2017-01-15

    Using high-quality CT-on-rails imaging, the daily motion of the prostate bed clinical target volume (PB-CTV) based on consensus Radiation Therapy Oncology Group (RTOG) definitions (instead of surgical clips/fiducials) was studied. It was assessed whether PB motion in the superior portion of PB-CTV (SUP-CTV) differed from the inferior PB-CTV (INF-CTV). Eight pT2-3bN0-1M0 patients underwent postprostatectomy intensity-modulated radiotherapy, totaling 300 fractions. INF-CTV and SUP-CTV were defined as PB-CTV located inferior and superior to the superior border of the pubic symphysis, respectively. Daily pretreatment CT-on-rails images were compared to the planning CT in the left-right (LR), superoinferior (SI), and anteroposterior (AP) directions. Two parameters were defined: ''total PB-CTV motion'' represented total shifts from skin tattoos to RTOG-defined anatomic areas; ''PB-CTV target motion'' (performed for both SUP-CTV and INF-CTV) represented shifts from bone to RTOG-defined anatomic areas (i. e., subtracting shifts from skin tattoos to bone). Mean (± standard deviation, SD) total PB-CTV motion was -1.5 (± 6.0), 1.3 (± 4.5), and 3.7 (± 5.7) mm in LR, SI, and AP directions, respectively. Mean (± SD) PB-CTV target motion was 0.2 (±1.4), 0.3 (±2.4), and 0 (±3.1) mm in the LR, SI, and AP directions, respectively. Mean (± SD) INF-CTV target motion was 0.1 (± 2.8), 0.5 (± 2.2), and 0.2 (± 2.5) mm, and SUP-CTV target motion was 0.3 (± 1.8), 0.5 (± 2.3), and 0 (± 5.0) mm in LR, SI, and AP directions, respectively. No statistically significant differences between INF-CTV and SUP-CTV motion were present in any direction. There are no statistically apparent motion differences between SUP-CTV and INF-CTV. Current uniform planning target volume (PTV) margins are adequate to cover both portions of the CTV. (orig.) [German] Zur Evaluation der interfraktionellen Variabilitaet des klinischen Zielvolumens der Prostataloge

  12. Validation of the Portuguese version of the Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS-P) in clinical and non-clinical samples.

    Science.gov (United States)

    Curcio, Cristiane Schumann Silva; Lucchetti, Giancarlo; Moreira-Almeida, Alexander

    2015-04-01

    Despite Brazil's high levels of religious involvement, there is a scarcity of validated religiousness/spirituality (R/S) measures in Portuguese, particularly multidimensional ones. This study presents the validation of the Portuguese version of the "Brief Multidimensional Measure in Religiousness and Spirituality" (BMMRS) within the Brazilian context. Inpatients (262) and caregivers (389) at two hospitals of Brazil answered the BMMRS, the DUREL-p, and a sociodemographic questionnaire. The internal and convergent validity and test-retest reliability for major dimensions were good. Discriminant validity was high (except for the Forgiveness dimension). The Portuguese version of the BMMRS is a reliable and valid instrument to assess multiple R/S dimensions in clinical and non-clinical samples.

  13. Development and validation of Dutch version of Lasater Clinical Judgment Rubric in hospital practice: An instrument design study.

    Science.gov (United States)

    Vreugdenhil, Jettie; Spek, Bea

    2018-03-01

    Clinical reasoning in patient care is a skill that cannot be observed directly. So far, no reliable, valid instrument exists for the assessment of nursing students' clinical reasoning skills in hospital practice. Lasater's clinical judgment rubric (LCJR), based on Tanner's model "Thinking like a nurse" has been tested, mainly in academic simulation settings. The aim is to develop a Dutch version of the LCJR (D-LCJR) and to test its psychometric properties when used in a hospital traineeship context. A mixed-model approach was used to develop and to validate the instrument. Ten dedicated educational units in a university hospital. A well-mixed group of 52 nursing students, nurse coaches and nurse educators. A Delphi panel developed the D-LCJR. Students' clinical reasoning skills were assessed "live" by nurse coaches, nurse educators and students who rated themselves. The psychometric properties tested during the assessment process are reliability, reproducibility, content validity and construct validity by testing two hypothesis: 1) a positive correlation between assessed and self-reported sum scores (convergent validity) and 2) a linear relation between experience and sum score (clinical validity). The obtained D-LCJR was found to be internally consistent, Cronbach's alpha 0.93. The rubric is also reproducible with intraclass correlations between 0.69 and 0.78. Experts judged it to be content valid. The two hypothesis were both tested significant, supporting evidence for construct validity. The translated and modified LCJR, is a promising tool for the evaluation of nursing students' development in clinical reasoning in hospital traineeships, by students, nurse coaches and nurse educators. More evidence on construct validity is necessary, in particular for students at the end of their hospital traineeship. Based on our research, the D-LCJR applied in hospital traineeships is a usable and reliable tool. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Clinical roundtable monograph: unmet needs in the treatment of chronic lymphocytic leukemia: integrating a targeted approach.

    Science.gov (United States)

    O'Brien, Susan M; Furman, Richard R; Byrd, John C; Smith, Ashbel

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed hematologic malignancy in the United States. Although several features can be useful in the diagnosis of CLL, the most important is the immunophenotype.Two staging systems--the Binet system and the Rai classification--are used to assess risk. After diagnosis, the first major therapeutic decision is when to initiate therapy, as a watchful waiting approach is often appropriate for patients with asymptomatic disease. Once a patient has met the criteria for treatment, the choice of therapy is the next major decision. Younger patients (<65 years) often receive more aggressive treatment that typically consists of cytotoxic chemotherapy. There is a great unmet need concerning treatment of older patients with CLL, who often present with more comorbid conditions that can decrease their ability to tolerate particular regimens. The current standard of care for older patients with CLL is rituximab plus chlorambucil. The concept of targeted agents is currently an area of intense interest in CLL. The Bruton’s tyrosine kinase inhibitor ibrutinib is the targeted agent that is furthest along in clinical development. It is associated with an overall survival rate of 83%. Idelalisib targets the phosphatidyl inositol 3-kinase and is under evaluation in pivotal trials. Targeted agents offer much promise in terms of efficacy, toxicity, and oral availability. They will change the management of patients with CLL.

  15. Using Ground Targets to Validate S-NPP VIIRS Day-Night Band Calibration

    Science.gov (United States)

    Chen, Xuexia; Wu, Aisheng; Xiong, Xiaoxiong; Lei, Ning; Wang, Zhipeng; Chiang, Kwofu

    2016-01-01

    In this study, the observations from S-NPP VIIRS Day-Night band (DNB) and Moderate resolution bands (M bands) of Libya 4 and Dome C over the first four years of the mission are used to assess the DNB low gain calibration stability. The Sensor Data Records produced by NASA Land Product Evaluation and Algorithm Testing Element (PEATE) are acquired from nearly nadir overpasses for Libya 4 desert and Dome C snow surfaces. A kernel-driven bidirectional reflectance distribution function (BRDF) correction model is used for both Libya 4 and Dome C sites to correct the surface BRDF influence. At both sites, the simulated top-of-atmosphere (TOA) DNB reflectances based on SCIAMACHY spectral data are compared with Land PEATE TOA reflectances based on modulated Relative Spectral Response (RSR). In the Libya 4 site, the results indicate a decrease of 1.03% in Land PEATE TOA reflectance and a decrease of 1.01% in SCIAMACHY derived TOA reflectance over the period from April 2012 to January 2016. In the Dome C site, the decreases are 0.29% and 0.14%, respectively. The consistency between SCIAMACHY and Land PEATE data trends is good. The small difference between SCIAMACHY and Land PEATE derived TOA reflectances could be caused by changes in the surface targets, atmosphere status, and on-orbit calibration. The reflectances and radiances of Land PEATE DNB are also compared with matching M bands and the integral M bands based on M4, M5, and M7. The fitting trends of the DNB to integral M bands ratios indicate a 0.75% decrease at the Libya 4 site and a 1.89% decrease at the Dome C site. Part of the difference is due to an insufficient number of sampled bands available within the DNB wavelength range. The above results indicate that the Land PEATE VIIRS DNB product is accurate and stable. The methods used in this study can be used on other satellite instruments to provide quantitative assessments for calibration stability.

  16. Using Ground Targets to Validate S-NPP VIIRS Day-Night Band Calibration

    Directory of Open Access Journals (Sweden)

    Xuexia Chen

    2016-11-01

    Full Text Available In this study, the observations from S-NPP VIIRS Day-Night band (DNB and Moderate resolution bands (M bands of Libya 4 and Dome C over the first four years of the mission are used to assess the DNB low gain calibration stability. The Sensor Data Records produced by NASA Land Product Evaluation and Algorithm Testing Element (PEATE are acquired from nearly nadir overpasses for Libya 4 desert and Dome C snow surfaces. A kernel-driven bidirectional reflectance distribution function (BRDF correction model is used for both Libya 4 and Dome C sites to correct the surface BRDF influence. At both sites, the simulated top-of-atmosphere (TOA DNB reflectances based on SCIAMACHY spectral data are compared with Land PEATE TOA reflectances based on modulated Relative Spectral Response (RSR. In the Libya 4 site, the results indicate a decrease of 1.03% in Land PEATE TOA reflectance and a decrease of 1.01% in SCIAMACHY derived TOA reflectance over the period from April 2012 to January 2016. In the Dome C site, the decreases are 0.29% and 0.14%, respectively. The consistency between SCIAMACHY and Land PEATE data trends is good. The small difference between SCIAMACHY and Land PEATE derived TOA reflectances could be caused by changes in the surface targets, atmosphere status, and on-orbit calibration. The reflectances and radiances of Land PEATE DNB are also compared with matching M bands and the integral M bands based on M4, M5, and M7. The fitting trends of the DNB to integral M bands ratios indicate a 0.75% decrease at the Libya 4 site and a 1.89% decrease at the Dome C site. Part of the difference is due to an insufficient number of sampled bands available within the DNB wavelength range. The above results indicate that the Land PEATE VIIRS DNB product is accurate and stable. The methods used in this study can be used on other satellite instruments to provide quantitative assessments for calibration stability.

  17. panelcn.MOPS: Copy-number detection in targeted NGS panel data for clinical diagnostics.

    Science.gov (United States)

    Povysil, Gundula; Tzika, Antigoni; Vogt, Julia; Haunschmid, Verena; Messiaen, Ludwine; Zschocke, Johannes; Klambauer, Günter; Hochreiter, Sepp; Wimmer, Katharina

    2017-07-01

    Targeted next-generation-sequencing (NGS) panels have largely replaced Sanger sequencing in clinical diagnostics. They allow for the detection of copy-number variations (CNVs) in addition to single-nucleotide variants and small insertions/deletions. However, existing computational CNV detection methods have shortcomings regarding accuracy, quality control (QC), incidental findings, and user-friendliness. We developed panelcn.MOPS, a novel pipeline for detecting CNVs in targeted NGS panel data. Using data from 180 samples, we compared panelcn.MOPS with five state-of-the-art methods. With panelcn.MOPS leading the field, most methods achieved comparably high accuracy. panelcn.MOPS reliably detected CNVs ranging in size from part of a region of interest (ROI), to whole genes, which may comprise all ROIs investigated in a given sample. The latter is enabled by analyzing reads from all ROIs of the panel, but presenting results exclusively for user-selected genes, thus avoiding incidental findings. Additionally, panelcn.MOPS offers QC criteria not only for samples, but also for individual ROIs within a sample, which increases the confidence in called CNVs. panelcn.MOPS is freely available both as R package and standalone software with graphical user interface that is easy to use for clinical geneticists without any programming experience. panelcn.MOPS combines high sensitivity and specificity with user-friendliness rendering it highly suitable for routine clinical diagnostics. © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.

  18. Development of lithium target system in engineering validation and engineering design activity of the international fusion materials irradiation facility (IFMIF/EVEDA)

    International Nuclear Information System (INIS)

    Wakai, Eiichi; Kondo, Hiroo; Sugimoto, Masayoshi; Ida, Mizuho; Kanemura, Takuji; Watanabe, Kazuyoshi; Fujishiro, Kouji; Edao, Yuuki; Niitsuma, Shigeto; Kimura, Haruyuki; Fukada, Satoshi; Hiromoto, Tetsushi; Shigeharu, Satoshi; Yagi, Jyuro; Furukawa, Tomohiro; Hirakawa, Yasushi; Suzuki, Akihiro; Terai, Takayuki; Horiike, Hiroshi; Hoashi, Eiji; Suzuki, Sachiko; Yamaoka, Nobuo; Serizawa, Hisashi; Kawahito, Yosuke; Tsuji, Yoshiyuki; Furuya, Kazuyuki; Takeo, Fumio

    2012-01-01

    Engineering validation and engineering design activity (EVEDA) for the international fusion materials irradiation facility (IFMIF) has been conducted since 2007. Research and development of the Lithium target facility is an important part of this activity. We constructed a world largest liquid Lithium test loop with a capacity of 5000 L in 2010 and successfully completed the first stage validation tests (functional tests of components and Lithium flow test (flow velocity 15 m/s at the target). In the present article, recent results of the EVEDA activity for the Lithium target facility and related technologies on liquid Lithium are reviewed. (author)

  19. Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

    Science.gov (United States)

    Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

    2013-01-01

    Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

  20. Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

    CERN Document Server

    Magro, G; Mairani, A; Mirandola, A; Panizza, D; Russo, S; Ferrari, A; Valvo, F; Fossati, P; Ciocca, M

    2015-01-01

    This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5–30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus® chamber. An EBT3® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size r...

  1. Development of the TeamOBS-PPH - targeting clinical performance in postpartum hemorrhage.

    Science.gov (United States)

    Brogaard, Lise; Hvidman, Lone; Hinshaw, Kim; Kierkegaard, Ole; Manser, Tanja; Musaeus, Peter; Arafeh, Julie; Daniels, Kay I; Judy, Amy E; Uldbjerg, Niels

    2018-06-01

    This study aimed to develop a valid and reliable TeamOBS-PPH tool for assessing clinical performance in the management of postpartum hemorrhage (PPH). The tool was evaluated using video-recordings of teams managing PPH in both real-life and simulated settings. A Delphi panel consisting of 12 obstetricians from the UK, Norway, Sweden, Iceland, and Denmark achieved consensus on (i) the elements to include in the assessment tool, (ii) the weighting of each element, and (iii) the final tool. The validity and reliability were evaluated according to Cook and Beckman. (Level 1) Four raters scored four video-recordings of in situ simulations of PPH. (Level 2) Two raters scored 85 video-recordings of real-life teams managing patients with PPH ≥1000 mL in two Danish hospitals. (Level 3) Two raters scored 15 video-recordings of in situ simulations of PPH from a US hospital. The tool was designed with scores from 0 to 100. (Level 1) Teams of novices had a median score of 54 (95% CI 48-60), whereas experienced teams had a median score of 75 (95% CI 71-79; p < 0.001). (Level 2) The intra-rater [intra-class correlation (ICC) = 0.96] and inter-rater (ICC = 0.83) agreements for real-life PPH were strong. The tool was applicable in all cases: atony, retained placenta, and lacerations. (Level 3) The tool was easily adapted to in situ simulation settings in the USA (ICC = 0.86). The TeamOBS-PPH tool appears to be valid and reliable for assessing clinical performance in real-life and simulated settings. The tool will be shared as the free TeamOBS App. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

  2. Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients

    Science.gov (United States)

    Zhou, Ting; Wang, Bangyan; Liu, Huiquan; Yang, Kaixiang; Thapa, Sudip; Zhang, Haowen; Li, Lu

    2018-01-01

    Abstract Background Cachexia is a multifactorial syndrome that is highly prevalent in advanced cancer patients and leads to progressive functional impairments. The classification of cachexia stages is essential for diagnosing and treating cachexia. However, there is a lack of simple tools with good discrimination for classifying cachexia stages. Therefore, our study aimed to develop a clinically applicable cachexia staging score (CSS) and validate its discrimination of clinical outcomes for different cachexia stages. Methods Advanced cancer patients were enrolled in our study. A CSS comprising the following five components was developed: weight loss, a simple questionnaire of sarcopenia (SARC‐F), Eastern Cooperative Oncology Group, appetite loss, and abnormal biochemistry. According to the CSS, patients were classified into non‐cachexia, pre‐cachexia, cachexia, and refractory cachexia stages, and clinical outcomes were compared among the four groups. Results Of the 297 participating patients, data from 259 patients were ultimately included. Based on the CSS, patients were classified into non‐cachexia (n = 69), pre‐cachexia (n = 68), cachexia (n = 103), and refractory cachexia (n = 19) stages. Patients with more severe cachexia stages had lower skeletal muscle indexes (P = 0.002 and P = 0.004 in male and female patients, respectively), higher prevalence of sarcopenia (P = 0.017 and P = 0.027 in male and female patients, respectively), more severe symptom burden (P cachexia stages. This score is extremely useful for the clinical treatment and prognosis of cachexia and for designing clinical trials. PMID:29372594

  3. Clinical validation of immunoglobulin A nephropathy diagnosis in Swedish biopsy registers

    Directory of Open Access Journals (Sweden)

    Jarrick S

    2017-01-01

    Full Text Available Simon Jarrick,1,2 Sigrid Lundberg,3,4 Adina Welander,5,6 C Michael Fored,6 Jonas F Ludvigsson2,7,8 1Department of Pediatrics, Faculty of Health and Medicine, Örebro University, 2Department of Pediatrics, Örebro University Hospital, Örebro, 3Department of Nephrology, Karolinska University Hospital, 4Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 5Boston Consulting Group, 6Clinical Epidemiology Unit, Department of Medicine, 7Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 8Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK Aims: The aims of this study were to validate the diagnosis of IgA nephropathy (IgAN in Swedish biopsy registers against patient charts and to describe the clinical characteristics of patients with a biopsy indicating IgAN. Methods: This is a population-based cohort study. Out of 4,069 individuals with a renal biopsy consistent with IgAN (biopsies performed in 1974–2011, this study reviewed patient charts of a random subset of 127 individuals. Clinical and biopsy characteristics at the time of biopsy were evaluated, and positive predictive values (PPV were calculated with 95% confidence intervals (CI. Results: Out of 127 individuals with a renal biopsy consistent with IgAN, 121 had a likely or confirmed clinical diagnosis of IgAN, primary or secondary to Henoch–Schönlein purpura, yielding a PPV of 95% (95% CI =92%–99%. The median age at biopsy was 39 years (range: 4–79 years; seven patients (6% were <16 years. The male to female ratio was 2.8:1. The most common causes for consultation were macroscopic hematuria (n=37; 29%, screening (n=33; 26%, and purpura (n=14, 11%. In patients with available data, the median creatinine level was 104 µmol/L (range 26–986 µmol/L, n=110 and glomerular filtration rate 75 mL/min/1.73m² (range 5–173 mL/min/1.73m², n=114. Hypertension was

  4. Validation of clinical case definition of acute intussusception in infants in Viet Nam and Australia.

    Science.gov (United States)

    Bines, Julie E; Liem, Nguyen Thanh; Justice, Frances; Son, Tran Ngoc; Carlin, John B; de Campo, Margaret; Jamsen, Kris; Mulholland, Kim; Barnett, Peter; Barnes, Graeme L

    2006-07-01

    To test the sensitivity and specificity of a clinical case definition of acute intussusception in infants to assist health-care workers in settings where diagnostic facilities are not available. Prospective studies were conducted at a major paediatric hospital in Viet Nam (the National Hospital of Pediatrics, Hanoi) from November 2002 to December 2003 and in Australia (the Royal Children's Hospital, Melbourne) from March 2002 to March 2004 using a clinical case definition of intussusception. Diagnosis of intussusception was confirmed by air enema or surgery and validated in a subset of participants by an independent clinician who was blinded to the participant's status. Sensitivity of the definition was evaluated in 584 infants agedclinical features consistent with intussusception but for whom another diagnosis was established (234 infants in Hanoi; 404 in Melbourne). In both locations the definition used was sensitive (96% sensitivity in Hanoi; 98% in Melbourne) and specific (95% specificity in Hanoi; 87% in Melbourne) for intussusception among infants with sufficient data to allow classification (449/533 in Hanoi; 50/51 in Melbourne). Reanalysis of patients with missing data suggests that modifying minor criteria would increase the applicability of the definition while maintaining good sensitivity (96-97%) and specificity (83-89%). The clinical case definition was sensitive and specific for the diagnosis of acute intussusception in infants in both a developing country and a developed country but minor modifications would enable it to be used more widely.

  5. Mock Pages Are a Valid Construct for Assessment of Clinical Decision Making and Interprofessional Communication.

    Science.gov (United States)

    Boehler, Margaret L; Schwind, Cathy J; Markwell, Stephen J; Minter, Rebecca M

    2017-01-01

    Answering pages from nurses about patients in need of immediate attention is one of the most difficult challenges a resident faces during their first days as a physician. A Mock Page program has been developed and adopted into a national surgical resident preparatory curriculum to prepare senior medical students for this important skill. The purpose of this study is to assess standardized mock page cases as a valid construct to assess clinical decision making and interprofessional communication skills. Mock page cases (n = 16) were administered to 213 senior medical students from 12 medical schools participating in a national surgical resident preparatory curriculum in 2013 and 2014. Clinical decision making and interprofessional communication were measured by case-specific assessments evaluating these skills which have undergone rigorous standard-setting to determine pass/fail cut points. Students' performance improved in general for both communication and clinical decision making over the 4-week course. Cases have been identified that seem to be best suited for differentiating high- from low-performing students. Chest pain, pulmonary embolus, and mental status change cases posed the greatest difficulty for student learners. Simulated mock pages demonstrate an innovative technique for training students in both effective interprofessional communication and management of common postoperative conditions they will encounter as new surgical interns.

  6. Reflective THz and MR imaging of burn wounds: a potential clinical validation of THz contrast mechanisms

    Science.gov (United States)

    Bajwa, Neha; Nowroozi, Bryan; Sung, Shijun; Garritano, James; Maccabi, Ashkan; Tewari, Priyamvada; Culjat, Martin; Singh, Rahul; Alger, Jeffry; Grundfest, Warren; Taylor, Zachary

    2012-10-01

    Terahertz (THz) imaging is an expanding area of research in the field of medical imaging due to its high sensitivity to changes in tissue water content. Previously reported in vivo rat studies demonstrate that spatially resolved hydration mapping with THz illumination can be used to rapidly and accurately detect fluid shifts following induction of burns and provide highly resolved spatial and temporal characterization of edematous tissue. THz imagery of partial and full thickness burn wounds acquired by our group correlate well with burn severity and suggest that hydration gradients are responsible for the observed contrast. This research aims to confirm the dominant contrast mechanism of THz burn imaging using a clinically accepted diagnostic method that relies on tissue water content for contrast generation to support the translation of this technology to clinical application. The hydration contrast sensing capabilities of magnetic resonance imaging (MRI), specifically T2 relaxation times and proton density values N(H), are well established and provide measures of mobile water content, lending MRI as a suitable method to validate hydration states of skin burns. This paper presents correlational studies performed with MR imaging of ex vivo porcine skin that confirm tissue hydration as the principal sensing mechanism in THz burn imaging. Insights from this preliminary research will be used to lay the groundwork for future, parallel MRI and THz imaging of in vivo rat models to further substantiate the clinical efficacy of reflective THz imaging in burn wound care.

  7. Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

    Science.gov (United States)

    Lam, Phillip H; Dooley, Daniel J; Fonarow, Gregg C; Butler, Javed; Bhatt, Deepak L; Filippatos, Gerasimos S; Deedwania, Prakash; Forman, Daniel E; White, Michel; Fletcher, Ross D; Arundel, Cherinne; Blackman, Marc R; Adamopoulos, Chris; Kanonidis, Ioannis E; Aban, Inmaculada B; Patel, Kanan; Aronow, Wilbert S; Allman, Richard M; Anker, Stefan D; Pitt, Bertram; Ahmed, Ali

    2018-02-01

    To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  8. Exploring the validity and reliability of a questionnaire for evaluating veterinary clinical teachers' supervisory skills during clinical rotations

    NARCIS (Netherlands)

    Boerboom, T. B. B.; Dolmans, D. H. J. M.; Jaarsma, Debbie; Muijtjens, A. M. M.; Van Beukelen, P.; Scherpbier, A. J. J. A.; Jaarsma, Debbie

    2011-01-01

    Background: Feedback to aid teachers in improving their teaching requires validated evaluation instruments. When implementing an evaluation instrument in a different context, it is important to collect validity evidence from multiple sources. Aim: We examined the validity and reliability of the

  9. Antibodies to autoantigen targets in myasthenia and their value in clinical practice

    Directory of Open Access Journals (Sweden)

    S. I. Dedaev

    2014-01-01

    Full Text Available Myasthenia gravis is a classic autoimmune disease, which clinical manifestations in the form of weakness and abnormal muscle fatigue, due to the damaging effect of polyclonal antibodies to different structures of the neuromuscular synapse and muscles. The study of autoimmune substrate with myasthenia is routine in many clinics dealing with the problems of neuromuscular pathology, and the identification of high concentration of serum antibodies to a number of antigenic structures is the gold standard in diagnosis.Determination of serum antibodies to various autoimmune targets is an important tool in clinical practice. The majority of patients shows the high concentration of antibodies to AchR that gives the opportunity to use it as an important diagnostic criterion. The specificity of changes in the concentration of AchR-antibodies due to pathogenetic treatment allows to objectify the suppression of autoimmune aggression and evaluate the reliability of remission. However, the absence of AchR-antibodies when there are clear clinical and electromyography signs of myasthenia gravis suggests an autoimmune attack against a number of other targets, the most studied of which is the MuSK. On the contrary, patients with myasthenia gravis associated with thymoma, almost always have a higher level of AchR-antibodies. The presence of thymoma is accompanied by the generation of antibodies to titin and RyR, which is also observed in persons with late-onset myasthenia without thymoma. High concentration of antibodies to these structures can be interpreted as a reliable sign of thymoma in patients younger than 60 years.

  10. Development, validation and clinical assessment of a short questionnaire to assess disease-related knowledge in inflammatory bowel disease patients.

    LENUS (Irish Health Repository)

    Keegan, Denise

    2013-02-01

    Only two inflammatory bowel disease (IBD) knowledge scales are available, both primarily aimed at evaluating the effectiveness of clinical education programs. The aim of this study was to develop and validate a short knowledge questionnaire for clinical and academic research purposes.

  11. A validated risk score to estimate mortality risk in patients with dementia and pneumonia: barriers to clinical impact

    NARCIS (Netherlands)

    van der Steen, J.T.; Albers, G.; Strunk, E.; Muller, M.T.; Ribbe, M.W.

    2011-01-01

    Background: The clinical impact of risk score use in end-of-life settings is unknown, with reports limited to technical properties. Methods: We conducted a mixed-methods study to evaluate clinical impact of a validated mortality risk score aimed at informing prognosis and supporting clinicians in

  12. Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation

    Directory of Open Access Journals (Sweden)

    Mathavan Sinnakaruppan

    2010-03-01

    Full Text Available Abstract Background Mercury is a prominent environmental contaminant that causes detrimental effects to human health. Although the liver has been known to be a main target organ, there is limited information on in vivo molecular mechanism of mercury-induced toxicity in the liver. By using transcriptome analysis, phenotypic anchoring and validation of targeted gene expression in zebrafish, mercury-induced hepatotoxicity was investigated and a number of perturbed cellular processes were identified and compared with those captured in the in vitro human cell line studies. Results Hepato-transcriptome analysis of mercury-exposed zebrafish revealed that the earliest deregulated genes were associated with electron transport chain, mitochondrial fatty acid beta-oxidation, nuclear receptor signaling and apoptotic pathway, followed by complement system and proteasome pathway, and thereafter DNA damage, hypoxia, Wnt signaling, fatty acid synthesis, gluconeogenesis, cell cycle and motility. Comparative meta-analysis of microarray data between zebrafish liver and human HepG2 cells exposed to mercury identified some common toxicological effects of mercury-induced hepatotoxicity in both models. Histological analyses of liver from mercury-exposed fish revealed morphological changes of liver parenchyma, decreased nucleated cell count, increased lipid vesicles, glycogen and apoptotic bodies, thus providing phenotypic evidence for anchoring of the transcriptome analysis. Validation of targeted gene expression confirmed deregulated gene-pathways from enrichment analysis. Some of these genes responding to low concentrations of mercury may serve as toxicogenomic-based markers for detection and health risk assessment of environmental mercury contaminations. Conclusion Mercury-induced hepatotoxicity was triggered by oxidative stresses, intrinsic apoptotic pathway, deregulation of nuclear receptor and kinase activities including Gsk3 that deregulates Wnt signaling

  13. Identification and Validation of Clinically Relevant Clusters of Severe Fatigue in Rheumatoid Arthritis.

    Science.gov (United States)

    Basu, Neil; Jones, Gareth T; Macfarlane, Gary J; Druce, Katie L

    The considerable heterogeneity of rheumatoid arthritis (RA)-related fatigue is the greatest challenge to determining pathogenesis. The identification of homogenous subtypes of severe fatigue would inform the design and analysis of experiments seeking to characterize the likely numerous causal pathways that underpin the symptom. This study aimed to identify and validate such fatigue subtypes in patients with RA. Data were obtained from patients recruited to the British Society for Rheumatology Biologics register for RA, as either receiving traditional disease-modifying antirheumatic drugs (DMARD cohort, n = 522) or commencing anti-tumor necrosis factor therapy (anti-TNF cohort, n = 3909). In those reporting severe fatigue (Short-Form 36 vitality ≤ 12.5), this cross-sectional analysis applied hierarchical clustering with weighted-average linkage identified clusters of pain, fatigue, mental health (all Short-Form 36), disability (Health Assessment Questionnaire), and inflammation (erythrocyte sedimentation rate) in the DMARD cohort. K-means clustering sought to validate the solution in the anti-TNF cohort. Clusters were characterized using a priori generated symptom definitions and between-cluster comparisons. Four severe fatigue clusters, labeled as basic (46%), affective (40%), inflammatory (4.5%), and global (8.9%) were identified in the DMARD cohort. All clusters had severe levels of pain and disability and were distinguished by the presence/absence of poor mental health and high inflammation. The same symptom clusters were present in the anti-TNF cohort, although the proportion of participants in each cluster differed (basic = 28.7%; affective = 30.2%; global = 24.1%; inflammatory = 16.9%). Among RA patients with severe fatigue, recruited to two diverse RA cohorts, clinically relevant clusters were identified and validated. These may provide the basis for future mechanistic studies and ultimately support a stratified approach to fatigue management.

  14. A newer and broader definition of burnout: validation of the "Burnout Clinical Subtype Questionnaire (BCSQ-36)".

    Science.gov (United States)

    Montero-Marín, Jesús; García-Campayo, Javier

    2010-06-02

    Burnout syndrome has been clinically characterised by a series of three subtypes: frenetic, underchallenged, and worn-out, with reference to coping strategies for stress and frustration at work with different degrees of dedication. The aims of the study are to present an operating definition of these subtypes in order to assess their reliability and convergent validity with respect to a standard burnout criterion and to examine differences with regard to sex and the temporary nature of work contracts. An exploratory factor analysis was performed by the main component method on a range of items devised by experts. The sample was composed of 409 employees of the University of Zaragoza, Spain. The reliability of the scales was assessed with Cronbach's alpha, convergent validity in relation to the Maslach Burnout Inventory with Pearson's r, and differences with Student's t-test and the Mann-Whitney U test. The factorial validity and reliability of the scales were good. The subtypes presented relations of differing degrees with the criterion dimensions, which were greater when dedication to work was lower. The frenetic profile presented fewer relations with the criterion dimensions while the worn-out profile presented relations of the greatest magnitude. Sex was not influential in establishing differences. However, the temporary nature of work contracts was found to have an effect: temporary employees exhibited higher scores in the frenetic profile (p < 0.001), while permanent employees did so in the underchallenged (p = 0.018) and worn-out (p < 0.001) profiles. The classical Maslach description of burnout does not include the frenetic profile; therefore, these patients are not recognised. The developed questionnaire may be a useful tool for the design and appraisal of specific preventive and treatment approaches based on the type of burnout experienced.

  15. A newer and broader definition of burnout: Validation of the "Burnout Clinical Subtype Questionnaire (BCSQ-36"

    Directory of Open Access Journals (Sweden)

    García-Campayo Javier

    2010-06-01

    Full Text Available Abstract Background Burnout syndrome has been clinically characterised by a series of three subtypes: frenetic, underchallenged and worn-out, with reference to coping strategies for stress and frustration at work with different degrees of dedication. The aims of the study are to present an operating definition of these subtypes in order to assess their reliability and convergent validity with respect to a standard burnout criterion and to examine differences with regard to sex and the temporary nature of work contracts. Method An exploratory factor analysis was performed by the main component method on a range of items devised by experts. The sample was composed of 409 employees of the University of Zaragoza, Spain. The reliability of the scales was assessed with Cronbach's α, convergent validity in relation to the Maslach Burnout Inventory with Pearson's r, and differences with Student's t-test and the Mann-Whitney U test. Results The factorial validity and reliability of the scales were good. The subtypes presented relations of differing degrees with the criterion dimensions, which were greater when dedication to work was lower. The frenetic profile presented fewer relations with the criterion dimensions while the worn-out profile presented relations of the greatest magnitude. Sex was not influential in establishing differences. However, the temporary nature of work contracts was found to have an effect: temporary employees exhibited higher scores in the frenetic profile (p p = 0.018 and worn-out (p Conclusions The classical Maslach description of burnout does not include the frenetic profile; therefore, these patients are not recognised. The developed questionnaire may be a useful tool for the design and appraisal of specific preventive and treatment approaches based on the type of burnout experienced.

  16. External validation of a biomarker and clinical prediction model for hospital mortality in acute respiratory distress syndrome.

    Science.gov (United States)

    Zhao, Zhiguo; Wickersham, Nancy; Kangelaris, Kirsten N; May, Addison K; Bernard, Gordon R; Matthay, Michael A; Calfee, Carolyn S; Koyama, Tatsuki; Ware, Lorraine B

    2017-08-01

    Mortality prediction in ARDS is important for prognostication and risk stratification. However, no prediction models have been independently validated. A combination of two biomarkers with age and APACHE III was superior in predicting mortality in the NHLBI ARDSNet ALVEOLI trial. We validated this prediction tool in two clinical trials and an observational cohort. The validation cohorts included 849 patients from the NHLBI ARDSNet Fluid and Catheter Treatment Trial (FACTT), 144 patients from a clinical trial of sivelestat for ARDS (STRIVE), and 545 ARDS patients from the VALID observational cohort study. To evaluate the performance of the prediction model, the area under the receiver operating characteristic curve (AUC), model discrimination, and calibration were assessed, and recalibration methods were applied. The biomarker/clinical prediction model performed well in all cohorts. Performance was better in the clinical trials with an AUC of 0.74 (95% CI 0.70-0.79) in FACTT, compared to 0.72 (95% CI 0.67-0.77) in VALID, a more heterogeneous observational cohort. The AUC was 0.73 (95% CI 0.70-0.76) when FACTT and VALID were combined. We validated a mortality prediction model for ARDS that includes age, APACHE III, surfactant protein D, and interleukin-8 in a variety of clinical settings. Although the model performance as measured by AUC was lower than in the original model derivation cohort, the biomarker/clinical model still performed well and may be useful for risk assessment for clinical trial enrollment, an issue of increasing importance as ARDS mortality declines, and better methods are needed for selection of the most severely ill patients for inclusion.

  17. The dutch social interaction anxiety scale and the social phobia scale: reliability, validity, and clinical utility.

    Science.gov (United States)

    de Beurs, Edwin; Tielen, Deirdre; Wollmann, Lisa

    2014-01-01

    The social interaction anxiety scale (SIAS) and the social phobia scale (SPS) assess anxiety in social interactions and fear of scrutiny by others. This study examines the psychometric properties of the Dutch versions of the SIAS and SPS using data from a large group of patients with social phobia and a community-based sample. Confirmatory factor analysis revealed that the SIAS is unidimensional, whereas the SPS is comprised of three subscales. The internal consistency of the scales and subscales was good. The concurrent and discriminant validity was supported and the scales were well able to discriminate between patients and community-based respondents. Cut-off values with excellent sensitivity and specificity are presented. Of all self-report measures included, the SPS was the most sensitive for treatment effects. Normative data are provided which can be used to assess whether clinically significant change has occurred in individual patients.

  18. The Dutch Social Interaction Anxiety Scale and the Social Phobia Scale: Reliability, Validity, and Clinical Utility

    Directory of Open Access Journals (Sweden)

    Edwin de Beurs

    2014-01-01

    Full Text Available The social interaction anxiety scale (SIAS and the social phobia scale (SPS assess anxiety in social interactions and fear of scrutiny by others. This study examines the psychometric properties of the Dutch versions of the SIAS and SPS using data from a large group of patients with social phobia and a community-based sample. Confirmatory factor analysis revealed that the SIAS is unidimensional, whereas the SPS is comprised of three subscales. The internal consistency of the scales and subscales was good. The concurrent and discriminant validity was supported and the scales were well able to discriminate between patients and community-based respondents. Cut-off values with excellent sensitivity and specificity are presented. Of all self-report measures included, the SPS was the most sensitive for treatment effects. Normative data are provided which can be used to assess whether clinically significant change has occurred in individual patients.

  19. Validity of Newborn Clinical Assessment to Determine Gestational Age in Bangladesh.

    Science.gov (United States)

    Lee, Anne Cc; Mullany, Luke C; Ladhani, Karima; Uddin, Jamal; Mitra, Dipak; Ahmed, Parvez; Christian, Parul; Labrique, Alain; DasGupta, Sushil K; Lokken, R Peter; Quaiyum, Mohammed; Baqui, Abdullah H

    2016-07-01

    Gestational age (GA) is frequently unknown or inaccurate in pregnancies in low-income countries. Early identification of preterm infants may help link them to potentially life-saving interventions. We conducted a validation study in a community-based birth cohort in rural Bangladesh. GA was determined by pregnancy ultrasound (distribution, agreement, and diagnostic accuracy of different clinical methods of GA assessment were determined compared with early ultrasound dating. In the live-born cohort (n = 1066), the mean ultrasound GA was 39.1 weeks (SD 2.0) and prevalence of preterm birth (births (community health worker prematurity scorecard [sensitivity/specificity: 70%/27%]; Capurro [5%/96%]; Eregie [75%/58%]; Bhagwat [18%/87%], foot length birth weight rates of fetal growth restriction. Copyright © 2016 by the American Academy of Pediatrics.

  20. Noninvasive assessment of mitral inertness [correction of inertance]: clinical results with numerical model validation.

    Science.gov (United States)

    Firstenberg, M S; Greenberg, N L; Smedira, N G; McCarthy, P M; Garcia, M J; Thomas, J D

    2001-01-01

    Inertial forces (Mdv/dt) are a significant component of transmitral flow, but cannot be measured with Doppler echo. We validated a method of estimating Mdv/dt. Ten patients had a dual sensor transmitral (TM) catheter placed during cardiac surgery. Doppler and 2D echo was performed while acquiring LA and LV pressures. Mdv/dt was determined from the Bernoulli equation using Doppler velocities and TM gradients. Results were compared with numerical modeling. TM gradients (range: 1.04-14.24 mmHg) consisted of 74.0 +/- 11.0% inertial forcers (range: 0.6-12.9 mmHg). Multivariate analysis predicted Mdv/dt = -4.171(S/D (RATIO)) + 0.063(LAvolume-max) + 5. Using this equation, a strong relationship was obtained for the clinical dataset (y=0.98x - 0.045, r=0.90) and the results of numerical modeling (y=0.96x - 0.16, r=0.84). TM gradients are mainly inertial and, as validated by modeling, can be estimated with echocardiography.

  1. Validation of the Danish Addenbrooke's Cognitive Examination as a screening test in a memory clinic.

    Science.gov (United States)

    Stokholm, Jette; Vogel, Asmus; Johannsen, Peter; Waldemar, Gunhild

    2009-01-01

    Addenbrooke's Cognitive Examination (ACE) is a cognitive screening test developed to detect dementia. It has been validated in several countries. Validation studies have predominantly included patients with various degrees of dementia and healthy controls. The aim of this study was to evaluate the Danish version of ACE as a screening test for early dementia in an outpatient memory clinic. Further, we wanted to investigate the ability of the ACE to discriminate patients with early Alzheimer's disease (AD) from patients with depression. 78 patients with mild AD (MMSE >or=20), 30 non-demented patients diagnosed with depression (originally referred for evaluation of cognitive symptoms), and 63 healthy volunteers, all between 60 and 85 years of age, were included. All patients were given the ACE as a supplement to the standard diagnostic work-up. The cut-off points for optimal trade-off between sensitivity and specificity for ACE were 85/86 (sensitivity 0.99, specificity 0.94). When these cut-off points were applied to the group of depressive patients, the specificity dropped to 0.64, indicating a great overlap in individual test scores for demented and depressed patients. The optimal cut-off points for ACE found in this Danish study were close to what is reported in most other European studies. The great overlap in ACE scores for demented and depressed patients emphasize that test scores must be interpreted with great caution when used in diagnostic work-up.

  2. Validation of the Balance Board for Clinical Evaluation of Balance During Serious Gaming Rehabilitation Exercises.

    Science.gov (United States)

    Bonnechère, Bruno; Jansen, Bart; Omelina, Lubos; Sholukha, Victor; Van Sint Jan, Serge

    2016-09-01

    Balance and posture can be affected in various conditions or become decreased with aging. A diminution of balance control induces an increase of fall's risk. The Nintendo Wii Balance Board™ (WBB) is used in rehabilitation to perform balance exercises (using commercial video games). The WBB has also been validated to assess balance and posture in static conditions. However, there is currently no study investigating the use of WBB to assess balance during the realization of balance exercises using this device. The aim of this study was to validate the use of WBB, coupled with specially developed serious games, to assess dynamic balance during rehabilitation exercises. Thirty five subjects participated in this study. Subjects were asked to play two specially developed serious games. Center of pressure (CP) displacements were simultaneously recorded with a WBB and a gold standard force plate (FP). Nine parameters were derived from CP displacement. Bland and Altman plots, paired-sample t tests, intraclass correlation coefficient's, and Pearson's coefficient correlations were computed. Excellent correlation between both devices was found for each parameter for the two games (R = 0.95 and 0.96). Unlike previous work on the WBB, these excellent results were obtained without using any calibration procedure. Despite this, results were highly correlated between the WBB and the FP. The WBB could be used in clinics to assess balance during rehabilitation exercises and, thus, allows a more regular patient follow-up.

  3. Clinical validation of a non-heteronormative version of the Social Interaction Anxiety Scale (SIAS).

    Science.gov (United States)

    Lindner, Philip; Martell, Christopher; Bergström, Jan; Andersson, Gerhard; Carlbring, Per

    2013-12-19

    Despite welcomed changes in societal attitudes and practices towards sexual minorities, instances of heteronormativity can still be found within healthcare and research. The Social Interaction Anxiety Scale (SIAS) is a valid and reliable self-rating scale of social anxiety, which includes one item (number 14) with an explicit heteronormative assumption about the respondent's sexual orientation. This heteronormative phrasing may confuse, insult or alienate sexual minority respondents. A clinically validated version of the SIAS featuring a non-heteronormative phrasing of item 14 is thus needed. 129 participants with diagnosed social anxiety disorder, enrolled in an Internet-based intervention trial, were randomly assigned to responding to the SIAS featuring either the original or a novel non-heteronormative phrasing of item 14, and then answered the other item version. Within-subject, correlation between item versions was calculated and the two scores were statistically compared. The two items' correlations with the other SIAS items and other psychiatric rating scales were also statistically compared. Item versions were highly correlated and scores did not differ statistically. The two items' correlations with other measures did not differ statistically either. The SIAS can be revised with a non-heteronormative formulation of item 14 with psychometric equivalence on item and scale level. Implications for other psychiatric instruments with heteronormative phrasings are discussed.

  4. Validation of autism spectrum disorder diagnoses recorded in the Clinical Practice Research Datalink, 1990–2014

    Directory of Open Access Journals (Sweden)

    Hagberg KW

    2017-09-01

    Full Text Available Katrina Wilcox Hagberg, Susan S Jick Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA Background: Prior studies have reported that the validity of autism spectrum disorder (ASD diagnoses recorded in the Clinical Practice Research Datalink (CPRD was high; however, diagnostic criteria and screening practices have changed since the last study was published in 2004.Objectives: 1 To calculate the positive predictive value (PPV of ASD diagnoses recorded in the CPRD compared to original medical records and 2 to describe characteristics of cases and use of clinical codes that support the ASD diagnosis as recorded in the electronic data by general practitioners over time.Methods: We identified children with a code for ASD (autism spectrum disorder, autism, Asperger’s, or pervasive developmental disorder in the CPRD from 1990 to 2014. We evaluated presence of codes in the electronic medical record indicating the presence of developmental delay, speech delay, behavioral problems, and other supporting clinical codes (e.g., therapy, referrals, etc.. We also evaluated changes in recording of these clinical codes over time. We compared the information present in the electronic medical record to original medical records for a sample of cases and calculated PPVs of ASD diagnoses recorded in the CPRD.Results: We identified 2154 children with a code for ASD. The mean age at diagnosis was 5.8 years, and 84% of cases were male. The majority (78.4% had 1 ASD diagnosis code in their electronic medical record. Approximately half of the cases had a code indicating behavioral problem, developmental delay, or speech delay, and 24.7% had a code indicating specialist referral or visit. After review of original medical records, the PPV of ASD diagnoses recorded in the CPRD was 91.9%. Conclusion: The results of this study suggest that ASD diagnoses recorded in the CPRD are reliable and can be used with confidence

  5. Central Pressure Appraisal: Clinical Validation of a Subject-Specific Mathematical Model.

    Directory of Open Access Journals (Sweden)

    Francesco Tosello

    Full Text Available Current evidence suggests that aortic blood pressure has a superior prognostic value with respect to brachial pressure for cardiovascular events, but direct measurement is not feasible in daily clinical practice.The aim of the present study is the clinical validation of a multiscale mathematical model for non-invasive appraisal of central blood pressure from subject-specific characteristics.A total of 51 young male were selected for the present study. Aortic systolic and diastolic pressure were estimated with a mathematical model and were compared to the most-used non-invasive validated technique (SphygmoCor device, AtCor Medical, Australia. SphygmoCor was calibrated through diastolic and systolic brachial pressure obtained with a sphygmomanometer, while model inputs consist of brachial pressure, height, weight, age, left-ventricular end-systolic and end-diastolic volumes, and data from a pulse wave velocity study.Model-estimated systolic and diastolic central blood pressures resulted to be significantly related to SphygmoCor-assessed central systolic (r = 0.65 p <0.0001 and diastolic (r = 0.84 p<0.0001 blood pressures. The model showed a significant overestimation of systolic pressure (+7.8 (-2.2;14 mmHg, p = 0.0003 and a significant underestimation of diastolic values (-3.2 (-7.5;1.6, p = 0.004, which imply a significant overestimation of central pulse pressure. Interestingly, model prediction errors mirror the mean errors reported in large meta-analysis characterizing the use of the SphygmoCor when non-invasive calibration is performed.In conclusion, multi-scale mathematical model predictions result to be significantly related to SphygmoCor ones. Model-predicted systolic and diastolic aortic pressure resulted in difference of less than 10 mmHg in the 51% and 84% of the subjects, respectively, when compared with SphygmoCor-obtained pressures.

  6. Clinical validity of a population database definition of remission in patients with major depression

    Directory of Open Access Journals (Sweden)

    Salvatella-Pasant Jordi

    2010-02-01

    Full Text Available Abstract Background Major depression (MD is one of the most frequent diagnoses in Primary Care. It is a disabling illness that increases the use of health resources. Aim: To describe the concordance between remission according to clinical assessment and remission obtained from the computerized prescription databases of patients with MD in a Spanish population. Methods Design: multicenter cross-sectional. The population under study was comprised of people from six primary care facilities, who had a MD episode between January 2003 and March 2007. A specialist in psychiatry assessed a random sample of patient histories and determined whether a certain patient was in remission according to clinical criteria (ICPC-2. Regarding the databases, patients were considered in remission when they did not need further prescriptions of AD for at least 6 months after completing treatment for a new episode. Validity indicators (sensitivity [S], specificity [Sp] and clinical utility (positive and negative probability ratio [PPR] and [NPR] were calculated. The concordance index was established using Cohen's kappa coefficient. Significance level was p Results 133 patient histories were reviewed. The kappa coefficient was 82.8% (confidence intervals [CI] were 95%: 73.1 - 92.6, PPR 9.8% and NPR 0.1%. Allocation discrepancies between both criteria were found in 11 patients. S was 92.5% (CI was 95%: 88.0 - 96.9% and Sp was 90.6% (CI was 95%: 85.6 - 95.6%, p Conclusions Results show an acceptable level of concordance between remission obtained from the computerized databases and clinical criteria. The major discrepancies were found in diagnostic accuracy.

  7. CGRP as the target of new migraine therapies - successful translation from bench to clinic.

    Science.gov (United States)

    Edvinsson, Lars; Haanes, Kristian Agmund; Warfvinge, Karin; Krause, Diana N

    2018-06-01

    Treatment of migraine is on the cusp of a new era with the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are expected to receive approval for use in migraine headache in 2018 and 2019. CGRP-related therapies offer considerable improvements over existing drugs as they are the first to be designed specifically to act on the trigeminal pain system, they are more specific and they seem to have few or no adverse effects. CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. As these drugs come into clinical use, we provide an overview of knowledge that has led to successful development of these drugs. We describe the biology of CGRP signalling, summarize key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatment, and synthesize what is known about the role of CGRP in the trigeminovascular system. Finally, we consider how the latest findings provide new insight into the central role of the trigeminal ganglion in the pathophysiology of migraine.

  8. Enteric Glial Cells: A New Frontier in Neurogastroenterology and Clinical Target for Inflammatory Bowel Diseases.

    Science.gov (United States)

    Ochoa-Cortes, Fernando; Turco, Fabio; Linan-Rico, Andromeda; Soghomonyan, Suren; Whitaker, Emmett; Wehner, Sven; Cuomo, Rosario; Christofi, Fievos L

    2016-02-01

    The word "glia" is derived from the Greek word "γλoια," glue of the enteric nervous system, and for many years, enteric glial cells (EGCs) were believed to provide mainly structural support. However, EGCs as astrocytes in the central nervous system may serve a much more vital and active role in the enteric nervous system, and in homeostatic regulation of gastrointestinal functions. The emphasis of this review will be on emerging concepts supported by basic, translational, and/or clinical studies, implicating EGCs in neuron-to-glial (neuroglial) communication, motility, interactions with other cells in the gut microenvironment, infection, and inflammatory bowel diseases. The concept of the "reactive glial phenotype" is explored as it relates to inflammatory bowel diseases, bacterial and viral infections, postoperative ileus, functional gastrointestinal disorders, and motility disorders. The main theme of this review is that EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target. New technological innovations in neuroimaging techniques are facilitating progress in the field, and an update is provided on exciting new translational studies. Gaps in our knowledge are discussed for further research. Restoring normal EGC function may prove to be an efficient strategy to dampen inflammation. Probiotics, palmitoylethanolamide (peroxisome proliferator-activated receptor-α), interleukin-1 antagonists (anakinra), and interventions acting on nitric oxide, receptor for advanced glycation end products, S100B, or purinergic signaling pathways are relevant clinical targets on EGCs with therapeutic potential.

  9. Impact of Different CT Slice Thickness on Clinical Target Volume for 3D Conformal Radiation Therapy

    International Nuclear Information System (INIS)

    Prabhakar, Ramachandran; Ganesh, Tharmar; Rath, Goura K.; Julka, Pramod K.; Sridhar, Pappiah S.; Joshi, Rakesh C.; Thulkar, Sanjay

    2009-01-01

    The purpose of this study was to present the variation of clinical target volume (CTV) with different computed tomography (CT) slice thicknesses and the impact of CT slice thickness on 3-dimensional (3D) conformal radiotherapy treatment planning. Fifty patients with brain tumors were selected and CT scans with 2.5-, 5-, and 10-mm slice thicknesses were performed with non-ionic contrast enhancement. The patients were selected with tumor volume ranging from 2.54 cc to 222 cc. Three-dimensional treatment planning was performed for all three CT datasets. The target coverage and the isocenter shift between the treatment plans for different slice thickness were correlated with the tumor volume. An important observation from our study revealed that for volume 25 cc, the target underdosage was less than 6.7% for 5-mm slice thickness and 8% for 10-mm slice thickness. For 3D conformal radiotherapy treatment planning (3DCRT), a CT slice thickness of 2.5 mm is optimum for tumor volume 25 cc

  10. Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

    Science.gov (United States)

    Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

    Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

  11. Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Gao XF

    2017-05-01

    Full Text Available Xiao-Fei Gao,1 Jun-Jie Zhang,1,2 Xiao-Min Jiang,1 Zhen Ge,1,2 Zhi-Mei Wang,1 Bing Li,1 Wen-Xing Mao,1 Shao-Liang Chen1,2 1Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Cardiology, Nanjing Heart Center, Nanjing, People’s Republic of China Background: Pulmonary arterial hypertension (PAH is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs, phosphodiesterase 5 inhibitors (PDE-5Is, and soluble guanylate cyclase stimulator (sGCS, have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH.Methods: Medline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD.Results: Thirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003 vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008 vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028 vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001 vs prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001 vs ERAs, 3.38 mmHg (95% CI: -6.30, -0.47; P=0.023 vs

  12. Adaptation and validation of the instrument Clinical Learning Environment and Supervision for medical students in primary health care

    Directory of Open Access Journals (Sweden)

    Eva Öhman

    2016-12-01

    Full Text Available Abstract Background Clinical learning takes place in complex socio-cultural environments that are workplaces for the staff and learning places for the students. In the clinical context, the students learn by active participation and in interaction with the rest of the community at the workplace. Clinical learning occurs outside the university, therefore is it important for both the university and the student that the student is given opportunities to evaluate the clinical placements with an instrument that allows evaluation from many perspectives. The instrument Clinical Learning Environment and Supervision (CLES was originally developed for evaluation of nursing students’ clinical learning environment. The aim of this study was to adapt and validate the CLES instrument to measure medical students’ perceptions of their learning environment in primary health care. Methods In the adaptation process the face validity was tested by an expert panel of primary care physicians, who were also active clinical supervisors. The adapted CLES instrument with 25 items and six background questions was sent electronically to 1,256 medical students from one university. Answers from 394 students were eligible for inclusion. Exploratory factor analysis based on principal component methods followed by oblique rotation was used to confirm the adequate number of factors in the data. Construct validity was assessed by factor analysis. Confirmatory factor analysis was used to confirm the dimensions of CLES instrument. Results The construct validity showed a clearly indicated four-factor model. The cumulative variance explanation was 0.65, and the overall Cronbach’s alpha was 0.95. All items loaded similarly with the dimensions in the non-adapted CLES except for one item that loaded to another dimension. The CLES instrument in its adapted form had high construct validity and high reliability and internal consistency. Conclusion CLES, in its adapted form, appears

  13. Clinical roundtable monograph: CD30 in lymphoma: its role in biology, diagnostic testing, and targeted therapy.

    Science.gov (United States)

    Sotomayor, Eduardo M; Young, Ken H; Younes, Anas

    2014-04-01

    CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane glycoprotein receptor consisting of an extracellular domain, a transmembrane domain, and an intracellular domain. CD30 has emerged as an important molecule in the field of targeted therapy because its expression is generally restricted to specific disease types and states. The major cancers with elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell lymphoma, and CD30 expression is considered essential to the differential diagnosis of these malignancies. Most commonly, CD30 expression is detected and performed by immunohistochemical staining of biopsy samples. Alternatively, flow cytometry analysis has also been developed for fresh tissue and cell aspiration specimens, including peripheral blood and bone marrow aspirate. Over the past several years, several therapeutic agents were developed to target CD30, with varying success in clinical trials. A major advance in the targeting of CD30 was seen with the development of the antibody-drug conjugate brentuximab vedotin, which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic antitubulin agent monomethyl auristatin E. In 2011, brentuximab vedotin was approved by the US Food and Drug Administration for use in Hodgkin lymphoma and anaplastic large cell lymphoma based on clinical trial data showing high response rates in these indications. Ongoing trials are examining brentuximab vedotin after autologous stem cell transplantation, as part of chemotherapy combination regimens, and in other CD30-expressing malignancies, including primary mediastinal large B-cell lymphomas, diffuse large B-cell lymphoma, lymphoma positive for Epstein-Barr virus, peripheral T-cell lymphoma not otherwise specified, and cutaneous anaplastic large cell lymphoma.

  14. Design and validation of standardized clinical and functional remission criteria in schizophrenia

    Science.gov (United States)

    Mosolov, Sergey N; Potapov, Andrey V; Ushakov, Uriy V; Shafarenko, Aleksey A; Kostyukova, Anastasiya B

    2014-01-01

    Background International Remission Criteria (IRC) for schizophrenia were developed recently by a group of internationally known experts. The IRC detect only 10%–30% of cases and do not cover the diversity of forms and social functioning. Our aim was to design a more applicable tool and validate its use – the Standardized Clinical and Functional Remission Criteria (SCFRC). Methods We used a 6-month follow-up study of 203 outpatients from two Moscow centers and another further sample of stable patients from a 1-year controlled trial of atypical versus typical medication. Diagnosis was confirmed by International Classification of Diseases Version 10 (ICD10) criteria and the Mini-International Neuropsychiatric Interview (MINI). Patients were assessed by the Positive and Negative Syndrome Scale, including intensity threshold, and further classified using the Russian domestic remission criteria and the level of social and personal functioning, according to the Personal and Social Performance Scale (PSP). The SCFRC were formulated and were validated by a data reanalysis on the first population sample and on a second independent sample (104 patients) and in an open-label prospective randomized 12-month comparative study of risperidone long-acting injectable (RLAI) versus olanzapine. Results Only 64 of the 203 outpatients (31.5%) initially met the IRC, and 53 patients (26.1%) met the IRC after 6 months, without a change in treatment. Patients who were in remission had episodic and progressive deficit (39.6%), or remittent (15%) paranoid schizophrenia, or schizoaffective disorder (17%). In addition, 105 patients of 139 (51.7%), who did not meet symptomatic IRC, remained stable within the period. Reanalysis of data revealed that 65.5% of the patients met the SCFRC. In the controlled trial, 70% of patients in the RLAI group met the SCFRC and only 19% the IRC. In the routine treatment group, 55.9% met the SCFRC and only 5.7% the IRC. Results of the further independent

  15. The validity of a professional competence tool for physiotherapy students in simulation-based clinical education: a Rasch analysis.

    Science.gov (United States)

    Judd, Belinda K; Scanlan, Justin N; Alison, Jennifer A; Waters, Donna; Gordon, Christopher J

    2016-08-05

    Despite the recent widespread adoption of simulation in clinical education in physiotherapy, there is a lack of validated tools for assessment in this setting. The Assessment of Physiotherapy Practice (APP) is a comprehensive tool used in clinical placement settings in Australia to measure professional competence of physiotherapy students. The aim of the study was to evaluate the validity of the APP for student assessment in simulation settings. A total of 1260 APPs were collected, 971 from students in simulation and 289 from students in clinical placements. Rasch analysis was used to examine the construct validity of the APP tool in three different simulation assessment formats: longitudinal assessment over 1 week of simulation; longitudinal assessment over 2 weeks; and a short-form (25 min) assessment of a single simulation scenario. Comparison with APPs from 5 week clinical placements in hospital and clinic-based settings were also conducted. The APP demonstrated acceptable fit to the expectations of the Rasch model for the 1 and 2 week clinical simulations, exhibiting unidimensional properties that were able to distinguish different levels of student performance. For the short-form simulation, nine of the 20 items recorded greater than 25 % of scores as 'not-assessed' by clinical educators which impacted on the suitability of the APP tool in this simulation format. The APP was a valid assessment tool when used in longitudinal simulation formats. A revised APP may be required for assessment in short-form simulation scenarios.

  16. Heterogeneity in head and neck IMRT target design and clinical practice

    International Nuclear Information System (INIS)

    Hong, Theodore S.; Tomé, Wolfgang A.; Harari, Paul M.

    2012-01-01

    Purpose: To assess patterns of H and N IMRT practice with particular emphasis on elective target delineation. Materials and methods: Twenty institutions with established H and N IMRT expertise were solicited to design clinical target volumes for the identical H and N cancer case. To limit contouring variability, a primary tonsil GTV and ipsilateral level II node were pre-contoured. Participants were asked to accept this GTV, and contour their recommended CTV and PTV. Dose prescriptions, contouring time, and recommendations regarding chemotherapy were solicited. Results: All 20 institutions responded. Remarkable heterogeneity in H and N IMRT design and practice was identified. Seventeen of 20 centers recommended treatment of bilateral necks whereas 3/20 recommended treatment of the ipsilateral neck only. The average CTV volume was 250 cm 3 (range 37–676 cm 3 ). Although there was high concordance in coverage of ipsilateral neck levels II and III, substantial variation was identified for levels I, V, and the contralateral neck. Average CTV expansion was 4.1 mm (range 0–15 mm). Eight of 20 centers recommended chemotherapy (cisplatin), whereas 12/20 recommended radiation alone. Responders prescribed on average 69 and 68 Gy to the tumor and metastatic node GTV, respectively. Average H and N target volume contouring time was 102.5 min (range 60–210 min). Conclusion: This study identifies substantial heterogeneity in H and N IMRT target definition, prescription, neck treatment, and use of chemotherapy among practitioners with established H and N IMRT expertise. These data suggest that continued efforts to standardize and simplify the H and N IMRT process are desirable for the safe and effective global advancement of H and N IMRT practice.

  17. Clinical benefit of drugs targeting mitochondrial function as an adjunct to reperfusion in ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Campo, Gianluca; Pavasini, Rita; Morciano, Giampaolo

    2017-01-01

    AIMS: To perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. METHODS...

  18. The Arabic Mood and Feelings Questionnaire: psychometrics and validity in a clinical sample.

    Science.gov (United States)

    Tavitian, Lucy; Atwi, Mia; Bawab, Soha; Hariz, Nayla; Zeinoun, Pia; Khani, Munir; Maalouf, Fadi T

    2014-06-01

    The purpose of this study was to provide clinicians in the Arab World with a child and adolescent depression screening tool. Child and parent versions of the Mood and Feelings Questionnaire (CMFQ and PMFQ respectively) were translated to Arabic and administered along with the Strengths and Difficulties Questionnaire (SDQ) to 30 children and adolescents and with mood disorders and 76 children and adolescents with other psychiatric disorders seeking treatment at a child and adolescent psychiatry clinic. DSM-IV diagnoses were generated through clinical interviews by a psychiatrist blinded to self-reports. Internal consistency for both versions was excellent with moderate inter-informant agreement and good convergent validity with the SDQ emotional symptoms subscales on the child and parent forms. The CMFQ and PMFQ significantly differentiated between currently depressed participants and those with other psychiatric disorders. CMFQ scores were a stronger predictor of categorization into depressed and non-depressed groups than the PMFQ. Two modes of cutoffs were calculated with one favoring sensitivity (a score of 26 for the CMFQ and 22 for the PMFQ) and another favoring specificity (a score of 31 for the CMFQ and 28 for the PMFQ).

  19. [Validation of a clinical prediction rule to distinguish bacterial from aseptic meningitis].

    Science.gov (United States)

    Agüero, Gonzalo; Davenport, María C; Del Valle, María de la P; Gallegos, Paulina; Kannemann, Ana L; Bokser, Vivian; Ferrero, Fernando

    2010-02-01

    Despite most meningitis are not bacterial, antibiotics are usually administered on admission because bacterial meningitis is difficult to be rule-out. Distinguishing bacterial from aseptic meningitis on admission could avoid inappropriate antibiotic use and hospitalization. We aimed to validate a clinical prediction rule to distinguish bacterial from aseptic meningitis in children, on arriving to the emergency room. This prospective study included patients aged or = 1000 cells/mm(3), CSF protein > or = 80 mg/dl, peripheral blood absolute neutrophil count > or = 10.000/mm(3), seizure = 1 point each. Sensitivity (S), specificity (E), positive and negative predictive values (PPV and NPV), positive and negative likelihood ratios (PLR and NLR) of the BMS to predict bacterial meningitis were calculated. Seventy patients with meningitis were included (14 bacterial meningitis). When BMS was calculated, 25 patients showed a BMS= 0 points, 11 BMS= 1 point, and 34 BMS > or = 2 points. A BMS = 0 showed S: 100%, E: 44%, VPP: 31%, VPN: 100%, RVP: 1,81 RVN: 0. A BMS > or = 2 predicted bacterial meningitis with S: 100%, E: 64%, VPP: 41%, VPN: 100%, PLR: 2.8, NLR:0. Using BMS was simple, and allowed identifying children with very low risk of bacterial meningitis. It could be a useful tool to assist clinical decision making.

  20. HPLC determination of plasma dimethylarginines: method validation and preliminary clinical application.

    Science.gov (United States)

    Ivanova, Mariela; Artusi, Carlo; Boffa, Giovanni Maria; Zaninotto, Martina; Plebani, Mario

    2010-11-11

    Asymmetric dimethylarginine (ADMA) has been suggested as a possible marker of endothelial dysfunction, and interest in its use in clinical practice is increasing. However, the potential role of symmetric dimethylarginine (SDMA) as an endogenous marker of renal function, has been less widely investigated. The aims of the present study were therefore to determine reference values for dimethylarginines in plasma after method validation, and to ascertain ADMA plasma concentrations in patients with disorders characterized by endothelial dysfunction; a further end-point was to investigate the relationship between SDMA plasma concentrations and estimated GFR (eGFR) as well as plasmatic creatinine in patients with chronic kidney disease (CKD). HPLC with fluorescence detection was used for the determination of plasma dimethylarginines. To verify the clinical usefulness of ADMA and SDMA, values from 4 groups of patients at a high risk of cardiovascular complications as well renal dysfunction (chronic heart failure n=126; type II diabetes n=43; pulmonary arterial hypertension n=17; chronic kidney disease n=42) were evaluated, and compared with the reference values, obtained from 225 blood donors. The intra- and inter-assay CVs (peadiatric populations, for which the use of eGFR is not recommended. 2010 Elsevier B.V. All rights reserved.

  1. Clinical validation of the planar radionuclide ventriculography in patients with right ventricular dysfunction.

    Science.gov (United States)

    Bontemps, L; Merabet, Y; Chevalier, P; Itti, R

    2013-01-01

    Gated radionuclide ventriculography (RNV) may be used for the evaluation of the right ventricular function. However, the accuracy of the method should be clinically validated in patients suffering from diseases with specific pathology of the right ventricle (RV) and with possible left ventricular (LV) interaction. Three groups of 15 patients each, diagnosed with arrhythmogenic right ventricular dysplasia (ARVD), pulmonary artery hypertension (PAH) or atrial septal defect (ASD) were compared to a group of normal subjects. The parameters for both ventricles were evaluated separately (ejection fractions: LVEF and RVEF, and intraventricular synchronism quantified as phase standard deviation: LVPSD and RVPSD) as well as the relation or interdependence of the right to left ventricle (RV/LV volume ratio, LV/RV ejection fraction and stroke volume ratios, and interventricular synchronism). All the variables as a whole were analyzed to identify groups of patients according to their functional behaviour. Significant differences were found between the patients and control group for the RV function while the LV function remained mostly within normal limits. When the RV function was considered, the control group and ASD patient group showed differences regarding the ARVD and PAH patients. On evaluating the RV/LV ratios, differences were found between the control group and the ASD group. In the PAH patients, LV function showed differences in relation to the rest of the groups. RNV is a reliable clinical tool to evaluate RV function in patients with RV abnormality. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  2. Model-based PSF and MTF estimation and validation from skeletal clinical CT images.

    Science.gov (United States)

    Pakdel, Amirreza; Mainprize, James G; Robert, Normand; Fialkov, Jeffery; Whyne, Cari M

    2014-01-01

    A method was developed to correct for systematic errors in estimating the thickness of thin bones due to image blurring in CT images using bone interfaces to estimate the point-spread-function (PSF). This study validates the accuracy of the PSFs estimated using said method from various clinical CT images featuring cortical bones. Gaussian PSFs, characterized by a different extent in the z (scan) direction than in the x and y directions were obtained using our method from 11 clinical CT scans of a cadaveric craniofacial skeleton. These PSFs were estimated for multiple combinations of scanning parameters and reconstruction methods. The actual PSF for each scan setting was measured using the slanted-slit technique within the image slice plane and the longitudinal axis. The Gaussian PSF and the corresponding modulation transfer function (MTF) are compared against the actual PSF and MTF for validation. The differences (errors) between the actual and estimated full-width half-max (FWHM) of the PSFs were 0.09 ± 0.05 and 0.14 ± 0.11 mm for the xy and z axes, respectively. The overall errors in the predicted frequencies measured at 75%, 50%, 25%, 10%, and 5% MTF levels were 0.06 ± 0.07 and 0.06 ± 0.04 cycles/mm for the xy and z axes, respectively. The accuracy of the estimates was dependent on whether they were reconstructed with a standard kernel (Toshiba's FC68, mean error of 0.06 ± 0.05 mm, MTF mean error 0.02 ± 0.02 cycles/mm) or a high resolution bone kernel (Toshiba's FC81, PSF FWHM error 0.12 ± 0.03 mm, MTF mean error 0.09 ± 0.08 cycles/mm). The method is accurate in 3D for an image reconstructed using a standard reconstruction kernel, which conforms to the Gaussian PSF assumption but less accurate when using a high resolution bone kernel. The method is a practical and self-contained means of estimating the PSF in clinical CT images featuring cortical bones, without the need phantoms or any prior knowledge about the scanner-specific parameters.

  3. Model-based PSF and MTF estimation and validation from skeletal clinical CT images

    International Nuclear Information System (INIS)

    Pakdel, Amirreza; Mainprize, James G.; Robert, Normand; Fialkov, Jeffery; Whyne, Cari M.

    2014-01-01

    Purpose: A method was developed to correct for systematic errors in estimating the thickness of thin bones due to image blurring in CT images using bone interfaces to estimate the point-spread-function (PSF). This study validates the accuracy of the PSFs estimated using said method from various clinical CT images featuring cortical bones. Methods: Gaussian PSFs, characterized by a different extent in the z (scan) direction than in the x and y directions were obtained using our method from 11 clinical CT scans of a cadaveric craniofacial skeleton. These PSFs were estimated for multiple combinations of scanning parameters and reconstruction methods. The actual PSF for each scan setting was measured using the slanted-slit technique within the image slice plane and the longitudinal axis. The Gaussian PSF and the corresponding modulation transfer function (MTF) are compared against the actual PSF and MTF for validation. Results: The differences (errors) between the actual and estimated full-width half-max (FWHM) of the PSFs were 0.09 ± 0.05 and 0.14 ± 0.11 mm for the xy and z axes, respectively. The overall errors in the predicted frequencies measured at 75%, 50%, 25%, 10%, and 5% MTF levels were 0.06 ± 0.07 and 0.06 ± 0.04 cycles/mm for the xy and z axes, respectively. The accuracy of the estimates was dependent on whether they were reconstructed with a standard kernel (Toshiba's FC68, mean error of 0.06 ± 0.05 mm, MTF mean error 0.02 ± 0.02 cycles/mm) or a high resolution bone kernel (Toshiba's FC81, PSF FWHM error 0.12 ± 0.03 mm, MTF mean error 0.09 ± 0.08 cycles/mm). Conclusions: The method is accurate in 3D for an image reconstructed using a standard reconstruction kernel, which conforms to the Gaussian PSF assumption but less accurate when using a high resolution bone kernel. The method is a practical and self-contained means of estimating the PSF in clinical CT images featuring cortical bones, without the need phantoms or any prior knowledge about the

  4. Model-based PSF and MTF estimation and validation from skeletal clinical CT images

    Energy Technology Data Exchange (ETDEWEB)

    Pakdel, Amirreza [Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada and Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3M2 (Canada); Mainprize, James G.; Robert, Normand [Sunnybrook Research Institute, Toronto, Ontario M4N 3M5 (Canada); Fialkov, Jeffery [Division of Plastic Surgery, Sunnybrook Health Sciences Center, Toronto, Ontario M4N 3M5, Canada and Department of Surgery, University of Toronto, Toronto, Ontario M5S 3M2 (Canada); Whyne, Cari M., E-mail: cari.whyne@sunnybrook.ca [Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada and Department of Surgery, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3M2 (Canada)

    2014-01-15

    Purpose: A method was developed to correct for systematic errors in estimating the thickness of thin bones due to image blurring in CT images using bone interfaces to estimate the point-spread-function (PSF). This study validates the accuracy of the PSFs estimated using said method from various clinical CT images featuring cortical bones. Methods: Gaussian PSFs, characterized by a different extent in the z (scan) direction than in the x and y directions were obtained using our method from 11 clinical CT scans of a cadaveric craniofacial skeleton. These PSFs were estimated for multiple combinations of scanning parameters and reconstruction methods. The actual PSF for each scan setting was measured using the slanted-slit technique within the image slice plane and the longitudinal axis. The Gaussian PSF and the corresponding modulation transfer function (MTF) are compared against the actual PSF and MTF for validation. Results: The differences (errors) between the actual and estimated full-width half-max (FWHM) of the PSFs were 0.09 ± 0.05 and 0.14 ± 0.11 mm for the xy and z axes, respectively. The overall errors in the predicted frequencies measured at 75%, 50%, 25%, 10%, and 5% MTF levels were 0.06 ± 0.07 and 0.06 ± 0.04 cycles/mm for the xy and z axes, respectively. The accuracy of the estimates was dependent on whether they were reconstructed with a standard kernel (Toshiba's FC68, mean error of 0.06 ± 0.05 mm, MTF mean error 0.02 ± 0.02 cycles/mm) or a high resolution bone kernel (Toshiba's FC81, PSF FWHM error 0.12 ± 0.03 mm, MTF mean error 0.09 ± 0.08 cycles/mm). Conclusions: The method is accurate in 3D for an image reconstructed using a standard reconstruction kernel, which conforms to the Gaussian PSF assumption but less accurate when using a high resolution bone kernel. The method is a practical and self-contained means of estimating the PSF in clinical CT images featuring cortical bones, without the need phantoms or any prior knowledge

  5. Pressure pain thresholds, clinical assessment, and differential diagnosis: reliability and validity in patients with myogenic pain.

    Science.gov (United States)

    Ohrbach, R; Gale, E N

    1989-11-01

    Four studies are presented testing the validity and reliability of pressure pain thresholds (PPTs) and of examination parameters believed to be important in the clinical assessment of sites commonly used for such measures in patient samples. Forty-five patients with a myogenous temporomandibular disorder were examined clinically prior to PPT measures. Criteria for history and examination included functional aspects of the pain, tissue quality of the pain site, and the type of pain elicited from palpation. Control sites within the same muscle and in the contralateral muscle were also examined. PPTs were measured as an index of tenderness using a strain gauge algometer at these sites. The data from the 5 male subjects were excluded from subsequent analyses due to the higher PPT in the males and to their unequal distribution among the various factorial conditions. The first study demonstrated strong validity in PPT measures between patients (using pain sites replicating the patients' pain) and matched controls (n = 11). The PPT was not significantly different between the primary pain site (referred pain and non-referred pain collapsed) and the no-pain control site in the same muscle (n = 16). The PPT was significantly lower at the pain site compared to the no-pain control site in the contralateral muscle (n = 13). The second study indicated adequate reliability in patient samples of the PPT measures. In the third study, the PPT was significantly lower at sites producing referred pain on palpation compared to sites producing localized pain on palpation. The PPT findings from the control sites were inconsistent on this factor. The fourth study presented preliminary evidence that palpable bands and nodular areas in muscle were most commonly associated with muscle regions that produce pain; such muscle findings were not specific, however, for regions that produce pain. Further, the intraexaminer reliability in reassessing these pain sites qualitatively was only fair

  6. Validation approach for a fast and simple targeted screening method for 75 antibiotics in meat and aquaculture products using LC-MS/MS.

    Science.gov (United States)

    Dubreil, Estelle; Gautier, Sophie; Fourmond, Marie-Pierre; Bessiral, Mélaine; Gaugain, Murielle; Verdon, Eric; Pessel, Dominique

    2017-04-01

    An approach is described to validate a fast and simple targeted screening method for antibiotic analysis in meat and aquaculture products by LC-MS/MS. The strategy of validation was applied for a panel of 75 antibiotics belonging to different families, i.e., penicillins, cephalosporins, sulfonamides, macrolides, quinolones and phenicols. The samples were extracted once with acetonitrile, concentrated by evaporation and injected into the LC-MS/MS system. The approach chosen for the validation was based on the Community Reference Laboratory (CRL) guidelines for the validation of screening qualitative methods. The aim of the validation was to prove sufficient sensitivity of the method to detect all the targeted antibiotics at the level of interest, generally the maximum residue limit (MRL). A robustness study was also performed to test the influence of different factors. The validation showed that the method is valid to detect and identify 73 antibiotics of the 75 antibiotics studied in meat and aquaculture products at the validation levels.

  7. Development and Validation of a Clinically Based Risk Calculator for the Transdiagnostic Prediction of Psychosis

    Science.gov (United States)

    Rutigliano, Grazia; Stahl, Daniel; Davies, Cathy; Bonoldi, Ilaria; Reilly, Thomas; McGuire, Philip

    2017-01-01

    Importance The overall effect of At Risk Mental State (ARMS) services for the detection of individuals who will develop psychosis in secondary mental health care is undetermined. Objective To measure the proportion of individuals with a first episode of psychosis detected by ARMS services in secondary mental health services, and to develop and externally validate a practical web-based individualized risk calculator tool for the transdiagnostic prediction of psychosis in secondary mental health care. Design, Setting, and Participants Clinical register-based cohort study. Patients were drawn from electronic, real-world, real-time clinical records relating to 2008 to 2015 routine secondary mental health care in the South London and the Maudsley National Health Service Foundation Trust. The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and the Maudsley National Health Service Foundation Trust in the period between January 1, 2008, and December 31, 2015. Data analysis began on September 1, 2016. Main Outcomes and Measures Risk of development of nonorganic International Statistical Classification of Diseases and Related Health Problems, Tenth Revision psychotic disorders. Results A total of 91 199 patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within South London and the Maudsley National Health Service Foundation Trust were included in the derivation (n = 33 820) or external validation (n = 54 716) data sets. The mean age was 32.97 years, 50.88% were men, and 61.05% were white race/ethnicity. The mean follow-up was 1588 days. The overall 6-year risk of psychosis in secondary mental health care was 3.02 (95% CI, 2.88-3.15), which is higher than the 6-year risk in the local general population (0.62). Compared with the ARMS designation, all of the International Statistical Classification of Diseases and Related Health Problems

  8. Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Bee Luan Khoo

    Full Text Available Circulating tumor cells (CTCs are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation.Here, we enriched and characterized putative CTCs from blood samples of patients with both advanced stage metastatic breast and lung cancers using a novel multiplexed spiral microfluidic chip. This system detected putative CTCs under high sensitivity (100%, n = 56 (Breast cancer samples: 12-1275 CTCs/ml; Lung cancer samples: 10-1535 CTCs/ml rapidly from clinically relevant blood volumes (7.5 ml under 5 min. Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM, fluorescence in-situ hybridization (FISH (EML4-ALK or targeted somatic mutation analysis. We used an ultra-sensitive mass spectrometry based system to highlight the presence of an EGFR-activating mutation in both isolated CTCs and plasma cell-free DNA (cf-DNA, and demonstrate concordance with the original tumor-biopsy samples.We have clinically validated our multiplexed microfluidic chip for the ultra high-throughput, low-cost and label-free enrichment of CTCs. Retrieved cells were unlabeled and viable, enabling potential propagation and real-time downstream analysis using next generation sequencing (NGS or proteomic analysis.

  9. Proposed definition of the vaginal cuff and paracolpium clinical target volume in postoperative uterine cervical cancer.

    Science.gov (United States)

    Murakami, Naoya; Norihisa, Yoshiki; Isohashi, Fumiaki; Murofushi, Keiko; Ariga, Takuro; Kato, Tomoyasu; Inaba, Koji; Okamoto, Hiroyuki; Ito, Yoshinori; Toita, Takafumi; Itami, Jun

    2016-01-01

    The aim of this study was to develop an appropriate definition for vaginal cuff and paracolpium clinical target volume (CTV) for postoperative intensity modulated radiation therapy in patients with uterine cervical cancer. A working subgroup was organized within the Radiation Therapy Study Group of the Japan Clinical Oncology Group to develop a definition for the postoperative vaginal cuff and paracolpium CTV in December 2013. The group consisted of 5 radiation oncologists who specialized in gynecologic oncology and a gynecologic oncologist. A comprehensive literature review that included anatomy, surgery, and imaging fields was performed and was followed by multiple discreet face-to-face discussions and e-mail messages before a final consensus was reached. Definitions for the landmark structures in all directions that demarcate the vaginal cuff and paracolpium CTV were decided by consensus agreement of the working group. A table was created that showed boundary structures of the vaginal cuff and paracolpium CTV in each direction. A definition of the postoperative cervical cancer vaginal cuff and paracolpium CTV was developed. It is expected that this definition guideline will serve as a template for future radiation therapy clinical trial protocols, especially protocols involving intensity modulated radiation therapy. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  10. Validation Study of the Korean Version of the Brief Clinical Form of the Neuropsychiatric Inventory

    Directory of Open Access Journals (Sweden)

    Hee-Jin Kim

    2016-06-01

    Full Text Available Aim: This study aims to provide a brief questionnaire form of the Neuropsychiatric Inventory (NPI-Q in Korean translated from the original NPI-Q that is intended for the evaluation of behavioral and psychological symptoms of dementia in routine clinical practice. Patients and Methods: We developed a Korean version of the NPI-Q (KNPI-Q and compared subitems with those of the Korean version of the NPI (KNPI in 63 dementia patients; 47 patients had been diagnosed with Alzheimer's disease with dementia, 8 with vascular dementia, and 8 with dementia with Lewy body disease. The diagnosis was based on the National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association criteria for possible and probable Alzheimer's disease and the International Statistical Classification of Diseases and Related Health Problems, 10th revision, criteria for vascular dementia and other dementing diseases. All patients received the Korean version of the Mini-Mental State Examination and the Clinical Dementia Rating within 1 month of the KNPI-Q. Results: Test-retest reliability of the KNPI-Q using a Pearson correlation index was r = 0.89 for the total symptom scale and r = 0.90 for the distress scale. The prevalence of analogous symptom ratings differed by less than 6.7%. Convergent validity between the KNPI-Q and the NPI using a Pearson correlation index was r = 0.879 for the total symptom scale and r = 0.92 for the distress scale. Conclusions: The KNPI-Q is a reliable and brief instrument that can be employed for screening in the evaluation of neuropsychiatric symptoms of dementia and associated caregiver distress. It may be suitable for use in general clinical practice and could be administered as a brief neuropsychiatric interview.

  11. Mycobacterium tuberculosis maltosyltransferase GlgE, a genetically validated antituberculosis target, is negatively regulated by Ser/Thr phosphorylation.

    Science.gov (United States)

    Leiba, Jade; Syson, Karl; Baronian, Grégory; Zanella-Cléon, Isabelle; Kalscheuer, Rainer; Kremer, Laurent; Bornemann, Stephen; Molle, Virginie

    2013-06-07

    GlgE is a maltosyltransferase involved in the biosynthesis of α-glucans that has been genetically validated as a potential therapeutic target against Mycobacterium tuberculosis. Despite also making α-glucan, the GlgC/GlgA glycogen pathway is distinct and allosterically regulated. We have used a combination of genetics and biochemistry to establish how the GlgE pathway is regulated. M. tuberculosis GlgE was phosphorylated specifically by the Ser/Thr protein kinase PknB in vitro on one serine and six threonine residues. Furthermore, GlgE was phosphorylated in vivo when expressed in Mycobacterium bovis bacillus Calmette-Guérin (BCG) but not when all seven phosphorylation sites were replaced by Ala residues. The GlgE orthologues from Mycobacterium smegmatis and Streptomyces coelicolor were phosphorylated by the corresponding PknB orthologues in vitro, implying that the phosphorylation of GlgE is widespread among actinomycetes. PknB-dependent phosphorylation of GlgE led to a 2 orders of magnitude reduction in catalytic efficiency in vitro. The activities of phosphoablative and phosphomimetic GlgE derivatives, where each phosphorylation site was substituted with either Ala or Asp residues, respectively, correlated with negative phosphoregulation. Complementation studies of a M. smegmatis glgE mutant strain with these GlgE derivatives, together with both classical and chemical forward genetics, were consistent with flux through the GlgE pathway being correlated with GlgE activity. We conclude that the GlgE pathway appears to be negatively regulated in actinomycetes through the phosphorylation of GlgE by PknB, a mechanism distinct from that known in the classical glycogen pathway. Thus, these findings open new opportunities to target the GlgE pathway therapeutically.

  12. Non-Clinical Models for Neurodegenerative Diseases: Therapeutic Approach and Drug Validation in Animal Models

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    Caridad Ivette Fernandez

    2017-12-01

    Full Text Available In 2016, 19.8% of the Cuban population was aged 60 or over. As a result, age-associated degenerative diseases and other diseases have become priority targets from a prophylactic, diagnostic and therapeutic perspective. As a result, the Cuban biomedical scientific community has addressed its basic, preclinical and epidemiological research in order to rise up to the challenge. A firm step in this direction has been the international congress “State of the art in non-clinical models for neurodegenerative diseases” which has brought together preclinical and clinical researchers, technicians and regulatory staff members from different countries to review the state of the art in neurodegenerations, find unifying ideas, objectives and collaborations or partnership. The objective is to expose the perspectives of new biotechnological products from Cuba and other countries from the diagnostic, therapeutic and neuroprotective point of view. It is crucial, therefore, that the irreplaceable role of laboratory animals in achieving these objectives is understood but they must be used in rational, adequate and ethical manner. We expose the current development trends in this field, being of common interest to the work directed to the search for potential drugs, diagnostic tools and the promotion of changes in lifestyle as a preventive projection.

  13. Clinical utility of the Neurobehavioral Symptom Inventory validity scales to screen for symptom exaggeration following traumatic brain injury.

    Science.gov (United States)

    Lange, Rael T; Brickell, Tracey A; Lippa, Sara M; French, Louis M

    2015-01-01

    The purpose of this study was to examine the clinical utility of three recently developed validity scales (Validity-10, NIM5, and LOW6) designed to screen for symptom exaggeration using the Neurobehavioral Symptom Inventory (NSI). Participants were 272 U.S. military service members who sustained a mild, moderate, severe, or penetrating traumatic brain injury (TBI) and who were evaluated by the neuropsychology service at Walter Reed Army Medical Center within 199 weeks post injury. Participants were divided into two groups based on the Negative Impression Management scale of the Personality Assessment Inventory: (a) those who failed symptom validity testing (SVT-fail; n = 27) and (b) those who passed symptom validity testing (SVT-pass; n = 245). Participants in the SVT-fail group had significantly higher scores (pscales (range: d = 0.76 to 2.34). Similarly high sensitivity, specificity, positive predictive power (PPP), and negative predictive (NPP) values were found when using all three validity scales to differentiate SVT-fail versus SVT-pass groups. However, the Validity-10 scale consistently had the highest overall values. The optimal cutoff score for the Validity-10 scale to identify possible symptom exaggeration was ≥19 (sensitivity = .59, specificity = .89, PPP = .74, NPP = .80). For the majority of people, these findings provide support for the use of the Validity-10 scale as a screening tool for possible symptom exaggeration. When scores on the Validity-10 exceed the cutoff score, it is recommended that (a) researchers and clinicians do not interpret responses on the NSI, and (b) clinicians follow up with a more detailed evaluation, using well-validated symptom validity measures (e.g., Minnesota Multiphasic Personality Inventory-2 Restructured Form, MMPI-2-RF, validity scales), to seek confirmatory evidence to support an hypothesis of symptom exaggeration.

  14. Reliability and Validity of Objective Structured Clinical Examination for Residents of Obstetrics and Gynecology at Kermanshah University of Medical Sciences

    Directory of Open Access Journals (Sweden)

    Nasrin Jalilian

    2012-11-01

    Full Text Available Introduction: Objective structured clinical examination (OSCE is used for the evaluation of the clinical competence in medicine for which it is essential to measure validity and reliability. This study aimed to investigate the validity and reliability of OSCE for residents of obstetrics and gynecology at Kermanshah University of Medical Sciences in 2011.Methods: A descriptive-correlation study was designed and the data of OSCE for obstetrics and gynecology were collected via learning behavior checklists in method stations and multiple choice questions in question stations. The data were analyzed through Pearson correlation coefficient and Cronbach's alpha, using SPSS software (version 16. To determine the criterion validity, correlation of OSCE scores with scores of resident promotion test, direct observation of procedural skills, and theoretical knowledge was determined; for reliability, however, Cronbach's alpha was used. Total sample consisted of 25 participants taking part in 14 stations. P value of less than 0.05 was considered as significant.Results: The mean OSCE scores was 22.66 (±6.85. Criterion validity of the stations with resident promotion theoretical test, first theoretical knowledge test, second theoretical knowledge, and direct observation of procedural skills (DOPS was 0.97, 0.74, 0.49, and 0.79, respectively. In question stations, criterion validity was 0.15, and total validity of OSCE was 0.77.Conclusion: Findings of the present study indicated acceptable validity and reliability of OSCE for residents of obstetrics and gynecology.

  15. Gross tumor volume and clinical target volume: soft-tissue sarcoma of the extremities

    International Nuclear Information System (INIS)

    Lartigau, E.; Kantor, G.; Lagarde, P.; Taieb, S.; Ceugnart, L.; Vilain, M.O.; Penel, N.; Depadt, G.

    2001-01-01

    Soft tissue sarcomas of the extremities are currently treated with more conservative and functional approaches, combining surgery, radiotherapy and chemotherapy. The role of external beam radiotherapy and brachytherapy has been defined through randomized studies performed in the 80's and 90's. However, the ubiquity of tumour location for these tumours makes difficult a systematic definition of local treatments. Tumour volume definition is based on pre and post surgical imaging (MRI) and on described pathological report. The clinical target volume will take into account quality of the resection and anatomical barriers and will be based on an anatomy and not only on safety margins around the tumour bed. General rules for this irradiation (doses, volumes) and principal results will be presented. (authors)

  16. Validation of a 4D-PET Maximum Intensity Projection for Delineation of an Internal Target Volume

    Energy Technology Data Exchange (ETDEWEB)

    Callahan, Jason, E-mail: jason.callahan@petermac.org [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Kron, Tomas [Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne (Australia); Schneider-Kolsky, Michal [Department of Medical Imaging and Radiation Science, Monash University, Clayton, Victoria (Australia); Dunn, Leon [Department of Applied Physics, RMIT University, Melbourne (Australia); Thompson, Mick [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Siva, Shankar [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Aarons, Yolanda [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne (Australia); Binns, David [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Hicks, Rodney J. [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne (Australia)

    2013-07-15

    Purpose: The delineation of internal target volumes (ITVs) in radiation therapy of lung tumors is currently performed by use of either free-breathing (FB) {sup 18}F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) or 4-dimensional (4D)-CT maximum intensity projection (MIP). In this report we validate the use of 4D-PET-MIP for the delineation of target volumes in both a phantom and in patients. Methods and Materials: A phantom with 3 hollow spheres was prepared surrounded by air then water. The spheres and water background were filled with a mixture of {sup 18}F and radiographic contrast medium. A 4D-PET/CT scan was performed of the phantom while moving in 4 different breathing patterns using a programmable motion device. Nine patients with an FDG-avid lung tumor who underwent FB and 4D-PET/CT and >5 mm of tumor motion were included for analysis. The 3 spheres and patient lesions were contoured by 2 contouring methods (40% of maximum and PET edge) on the FB-PET, FB-CT, 4D-PET, 4D-PET-MIP, and 4D-CT-MIP. The concordance between the different contoured volumes was calculated using a Dice coefficient (DC). The difference in lung tumor volumes between FB-PET and 4D-PET volumes was also measured. Results: The average DC in the phantom using 40% and PET edge, respectively, was lowest for FB-PET/CT (DCAir = 0.72/0.67, DCBackground 0.63/0.62) and highest for 4D-PET/CT-MIP (DCAir = 0.84/0.83, DCBackground = 0.78/0.73). The average DC in the 9 patients using 40% and PET edge, respectively, was also lowest for FB-PET/CT (DC = 0.45/0.44) and highest for 4D-PET/CT-MIP (DC = 0.72/0.73). In the 9 lesions, the target volumes of the FB-PET using 40% and PET edge, respectively, were on average 40% and 45% smaller than the 4D-PET-MIP. Conclusion: A 4D-PET-MIP produces volumes with the highest concordance with 4D-CT-MIP across multiple breathing patterns and lesion sizes in both a phantom and among patients. Freebreathing PET/CT consistently

  17. Validation of a 4D-PET Maximum Intensity Projection for Delineation of an Internal Target Volume

    International Nuclear Information System (INIS)

    Callahan, Jason; Kron, Tomas; Schneider-Kolsky, Michal; Dunn, Leon; Thompson, Mick; Siva, Shankar; Aarons, Yolanda; Binns, David; Hicks, Rodney J.

    2013-01-01

    Purpose: The delineation of internal target volumes (ITVs) in radiation therapy of lung tumors is currently performed by use of either free-breathing (FB) 18 F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) or 4-dimensional (4D)-CT maximum intensity projection (MIP). In this report we validate the use of 4D-PET-MIP for the delineation of target volumes in both a phantom and in patients. Methods and Materials: A phantom with 3 hollow spheres was prepared surrounded by air then water. The spheres and water background were filled with a mixture of 18 F and radiographic contrast medium. A 4D-PET/CT scan was performed of the phantom while moving in 4 different breathing patterns using a programmable motion device. Nine patients with an FDG-avid lung tumor who underwent FB and 4D-PET/CT and >5 mm of tumor motion were included for analysis. The 3 spheres and patient lesions were contoured by 2 contouring methods (40% of maximum and PET edge) on the FB-PET, FB-CT, 4D-PET, 4D-PET-MIP, and 4D-CT-MIP. The concordance between the different contoured volumes was calculated using a Dice coefficient (DC). The difference in lung tumor volumes between FB-PET and 4D-PET volumes was also measured. Results: The average DC in the phantom using 40% and PET edge, respectively, was lowest for FB-PET/CT (DCAir = 0.72/0.67, DCBackground 0.63/0.62) and highest for 4D-PET/CT-MIP (DCAir = 0.84/0.83, DCBackground = 0.78/0.73). The average DC in the 9 patients using 40% and PET edge, respectively, was also lowest for FB-PET/CT (DC = 0.45/0.44) and highest for 4D-PET/CT-MIP (DC = 0.72/0.73). In the 9 lesions, the target volumes of the FB-PET using 40% and PET edge, respectively, were on average 40% and 45% smaller than the 4D-PET-MIP. Conclusion: A 4D-PET-MIP produces volumes with the highest concordance with 4D-CT-MIP across multiple breathing patterns and lesion sizes in both a phantom and among patients. Freebreathing PET/CT consistently underestimates ITV

  18. Radial displacement of clinical target volume in node negative head and neck cancer

    International Nuclear Information System (INIS)

    Jeon, Wan; Wu, Hong Gyun; Song, Sang Hyuk; Kim, Jung In

    2012-01-01

    To evaluate the radial displacement of clinical target volume in the patients with node negative head and neck (H and N) cancer and to quantify the relative positional changes compared to that of normal healthy volunteers. Three node-negative H and N cancer patients and fi ve healthy volunteers were enrolled in this study. For setup accuracy, neck thermoplastic masks and laser alignment were used in each of the acquired computed tomography (CT) images. Both groups had total three sequential CT images in every two weeks. The lymph node (LN) level of the neck was delineated based on the Radiation Therapy Oncology Group (RTOG) consensus guideline by one physician. We use the second cervical vertebra body as a reference point to match each CT image set. Each of the sequential CT images and delineated neck LN levels were fused with the primary image, then maximal radial displacement was measured at 1.5 cm intervals from skull base (SB) to caudal margin of LN level V, and the volume differences at each node level were quantified. The mean radial displacements were 2.26 (±1.03) mm in the control group and 3.05 (±1.97) in the H and N cancer patients. There was a statistically significant difference between the groups in terms of the mean radial displacement (p = 0.03). In addition, the mean radial displacement increased with the distance from SB. As for the mean volume differences, there was no statistical significance between the two groups. This study suggests that a more generous radial margin should be applied to the lower part of the neck LN for better clinical target coverage and dose delivery.

  19. Alpha-1 Antitrypsin Deficiency Targeted Testing and Augmentation Therapy: A Canadian Thoracic Society Clinical Practice Guideline

    Directory of Open Access Journals (Sweden)

    DD Marciniuk

    2012-01-01

    Full Text Available Alpha-1 antitrypsin (A1AT functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD. Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted attributable to emphysema and documented A1AT deficiency (level ≤11 μmol/L who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation because of benefits in computed tomography scan lung density and mortality.

  20. Depression screening with patient-targeted feedback in cardiology: DEPSCREEN-INFO randomised clinical trial.

    Science.gov (United States)

    Löwe, Bernd; Blankenberg, Stefan; Wegscheider, Karl; König, Hans-Helmut; Walter, Dirk; Murray, Alexandra M; Gierk, Benjamin; Kohlmann, Sebastian

    2017-02-01

    International guidelines advocate depression screening in patients with coronary heart disease (CHD) and other chronic illnesses, but evidence is lacking. To test the differential efficacy of written patient-targeted feedback v. no written patient feedback after depression screening. Patients with CHD or hypertension from three cardiology settings were randomised and screened for depression (ClinicalTrials.gov Identifier: NCT01879111). Compared with the control group, where only cardiologists received written feedback, in the intervention group both cardiologists and patients received written feedback regarding depression status. Depression severity was measured 1 month (primary outcome) and 6 months after screening. The control group (n = 220) and the patient-feedback group (n = 155) did not differ in depression severity 1 month after screening. Six months after screening, the patient-feedback group showed significantly greater improvements in depression severity and was twice as likely to seek information about depression compared with the control group. Patient-targeted feedback in addition to screening has a significant but small effect on depression severity after 6 months and may encourage patients to take an active role in the self-management of depression. © The Royal College of Psychiatrists 2017.

  1. Clinical application of Lin's biopsy grasper for intrauterine targeted biopsy and polypectomy during office hysteroscopy.

    Science.gov (United States)

    Cheng, Hsin-Yi; Lin, Bao-Liang; Tseng, Jen-Yu; Ueno, Kazunori; Nakada, Sakura

    2018-06-01

    Hysteroscopy has widely been used for diagnosis of the uterine cavity; however, target biopsy has often been difficult in part to the inherent limitations of ancillary instruments. Lin's biopsy grasper was specifically designed to work in conjunction with a flexible hysteroscope to obtain intrauterine biopsy under transabdominal sonography. Herein, we share our clinical experience in the management of endometrial abnormalities with the use of Lin's biopsy grasper during office-based hysteroscopy. From February 2006 to November 2016, the use of Lin's biopsy grasper for tissue biopsy was attempted on 126 cases. We retrospectively recorded and analyzed the patients' preoperative characteristics and biopsy outcomes to demonstrate the feasibility and efficacy of Lin's biopsy grasper. Out of the one hundred and twenty-six enrolled patients, satisfactory targeted biopsies were achieved; including high diagnostic rate (92.1%, with 116 cases confirmed histologically) and adequate tissue retrieval (77.8%, with 98 cases obtaining optimal specimen volume). All patients tolerated the procedure without analgesics or anesthesia. Diagnostic flexible hysteroscopy combined with the use of Lin's biopsy grasper has proven to be an effective tool for intrauterine evaluation and obtaining tissue sample. Copyright © 2018. Published by Elsevier B.V.

  2. Direct Observation of Clinical Skills Feedback Scale: Development and Validity Evidence.

    Science.gov (United States)

    Halman, Samantha; Dudek, Nancy; Wood, Timothy; Pugh, Debra; Touchie, Claire; McAleer, Sean; Humphrey-Murto, Susan

    2016-01-01

    Construct: This article describes the development and validity evidence behind a new rating scale to assess feedback quality in the clinical workplace. Competency-based medical education has mandated a shift to learner-centeredness, authentic observation, and frequent formative assessments with a focus on the delivery of effective feedback. Because feedback has been shown to be of variable quality and effectiveness, an assessment of feedback quality in the workplace is important to ensure we are providing trainees with optimal learning opportunities. The purposes of this project were to develop a rating scale for the quality of verbal feedback in the workplace (the Direct Observation of Clinical Skills Feedback Scale [DOCS-FBS]) and to gather validity evidence for its use. Two panels of experts (local and national) took part in a nominal group technique to identify features of high-quality feedback. Through multiple iterations and review, 9 features were developed into the DOCS-FBS. Four rater types (residents n = 21, medical students n = 8, faculty n = 12, and educators n = 12) used the DOCS-FBS to rate videotaped feedback encounters of variable quality. The psychometric properties of the scale were determined using a generalizability analysis. Participants also completed a survey to gather data on a 5-point Likert scale to inform the ease of use, clarity, knowledge acquisition, and acceptability of the scale. Mean video ratings ranged from 1.38 to 2.96 out of 3 and followed the intended pattern suggesting that the tool allowed raters to distinguish between examples of higher and lower quality feedback. There were no significant differences between rater type (range = 2.36-2.49), suggesting that all groups of raters used the tool in the same way. The generalizability coefficients for the scale ranged from 0.97 to 0.99. Item-total correlations were all above 0.80, suggesting some redundancy in items. Participants found the scale easy to use (M = 4.31/5) and clear

  3. External validation of the clinical dehydration scale for children with acute gastroenteritis.

    Science.gov (United States)

    Bailey, Benoit; Gravel, Jocelyn; Goldman, Ran D; Friedman, Jeremy N; Parkin, Patricia C

    2010-06-01

    The objective was to validate the clinical dehydration scale (CDS) for children with gastroenteritis in a different pediatric emergency department (ED) from where it was initially derived and validated. A prospective cohort study was performed in a tertiary care pediatric ED over a 1-year period. A sample of triage nurses were trained in applying the CDS. The CDS consists of four clinical characteristics (general appearance, eyes, mucous membranes, and tears), each of which are scored 0, 1, or 2 for a total score of 0 to 8, with 0 representing no dehydration; 1 to 4, some dehydration; and 5 to 8, moderate/severe dehydration. Children 1 month to 5 years of age with vomiting and/or diarrhea who had the CDS documented at triage and a final diagnosis of gastroenteritis, gastritis, or enteritis were enrolled. Exclusion criteria included a chronic disease, treatment with intravenous (IV) rehydration within the previous 24 hours, visit to the ED for the same illness in the 7 days prior to arrival, and diarrhea of more than 10 days' duration. The primary outcome was the length of stay (LOS) in the ED from the time of seeing a physician to discharge, analyzed with a Kruskal-Wallis test. From April 2008 to March 2009, 150 patients with a mean (+/-SD) age of 22 (+/-14) months (range = 4 months to 4 years) were enrolled. Fifty-six patients had no dehydration, 74 had some dehydration, and 20 had moderate/severe dehydration. The median LOS in the ED after being seen by a physician was significantly longer as children appeared more dehydrated according to the CDS: 54 minutes (interquartile range [IQR] = 26-175 minutes), 128 minutes (IQR = 25-334 minutes), and 425 minutes (IQR = 218-673 minutes) for the no, some, and moderate/severe dehydration groups, respectively (p children with gastroenteritis in a different pediatric center than the original one where it was developed. It is a good predictor of LOS in the ED after being seen by a physician. (c) 2010 by the Society for

  4. Validation of administrative and clinical case definitions for gestational diabetes mellitus against laboratory results.

    Science.gov (United States)

    Bowker, S L; Savu, A; Donovan, L E; Johnson, J A; Kaul, P

    2017-06-01

    To examine the validity of International Classification of Disease, version 10 (ICD-10) codes for gestational diabetes mellitus in administrative databases (outpatient and inpatient), and in a clinical perinatal database (Alberta Perinatal Health Program), using laboratory data as the 'gold standard'. Women aged 12-54 years with in-hospital, singleton deliveries between 1 October 2008 and 31 March 2010 in Alberta, Canada were included in the study. A gestational diabetes diagnosis was defined in the laboratory data as ≥2 abnormal values on a 75-g oral glucose tolerance test or a 50-g glucose screen ≥10.3 mmol/l. Of 58 338 pregnancies, 2085 (3.6%) met gestational diabetes criteria based on laboratory data. The gestational diabetes rates in outpatient only, inpatient only, outpatient or inpatient combined, and Alberta Perinatal Health Program databases were 5.2% (3051), 4.8% (2791), 5.8% (3367) and 4.8% (2825), respectively. Although the outpatient or inpatient combined data achieved the highest sensitivity (92%) and specificity (97%), it was associated with a positive predictive value of only 57%. The majority of the false-positives (78%), however, had one abnormal value on oral glucose tolerance test, corresponding to a diagnosis of impaired glucose tolerance in pregnancy. The ICD-10 codes for gestational diabetes in administrative databases, especially when outpatient and inpatient databases are combined, can be used to reliably estimate the burden of the disease at the population level. Because impaired glucose tolerance in pregnancy and gestational diabetes may be managed similarly in clinical practice, impaired glucose tolerance in pregnancy is often coded as gestational diabetes. © 2016 Diabetes UK.

  5. Targeting death receptors to fight cancer: from biological rational to clinical implementation.

    Science.gov (United States)

    Mocellin, S

    2010-01-01

    Considering that most currently available chemotherapeutic drugs work by inducing cell apoptosis, it is not surprising that many expectations in cancer research come from the therapeutic exploitation of the naturally occurring death pathways. Receptor mediated apoptosis depends upon the engagement of specific ligands with their respective membrane receptors and - within the frame of complex regulatory networks - modulates some key physiological and pathological processes such as lymphocyte survival, inflammation and infectious diseases. A pivotal observation was that some of these pathways may be over activated in cancer under particular circumstances, which opened the avenue for tumor-specific therapeutic interventions. Although one death-related ligand (e.g., tumor necrosis factor, TNF) is currently the basis of effective anticancer regimens in the clinical setting, the systemic toxicity is hampering its wide therapeutic exploitation. However, strategies to split the therapeutic from the toxic TNF activity are being devised. Furthermore, other death receptor pathways (e.g., Fas/FasL, TRAIL/TRAIL receptor) are being intensively investigated in order to therapeutically exploit their activity against cancer. This article summarizes the current knowledge on the molecular features of death receptor pathways that make them an attractive target for anticancer therapeutics. In addition, the results so far obtained in the clinical oncology setting as well as the issues to be faced while interfering with these pathways for therapeutic purposes will be overviewed.

  6. Design and validation of standardized clinical and functional remission criteria in schizophrenia

    Directory of Open Access Journals (Sweden)

    Mosolov SN

    2014-01-01

    Full Text Available Sergey N Mosolov,1 Andrey V Potapov,1 Uriy V Ushakov,2 Aleksey A Shafarenko,1 Anastasiya B Kostyukova11Department of Mental Disorders Therapy, Moscow Research Institute of Psychiatry, Moscow, Russia; 2Moscow Psychiatric Outpatient Services #21, Moscow, RussiaBackground: International Remission Criteria (IRC for schizophrenia were developed recently by a group of internationally known experts. The IRC detect only 10%–30% of cases and do not cover the diversity of forms and social functioning. Our aim was to design a more applicable tool and validate its use – the Standardized Clinical and Functional Remission Criteria (SCFRC.Methods: We used a 6-month follow-up study of 203 outpatients from two Moscow centers and another further sample of stable patients from a 1-year controlled trial of atypical versus typical medication. Diagnosis was confirmed by International Classification of Diseases Version 10 (ICD10 criteria and the Mini-International Neuropsychiatric Interview (MINI. Patients were assessed by the Positive and Negative Syndrome Scale, including intensity threshold, and further classified using the Russian domestic remission criteria and the level of social and personal functioning, according to the Personal and Social Performance Scale (PSP. The SCFRC were formulated and were validated by a data reanalysis on the first population sample and on a second independent sample (104 patients and in an open-label prospective randomized 12-month comparative study of risperidone long-acting injectable (RLAI versus olanzapine.Results: Only 64 of the 203 outpatients (31.5% initially met the IRC, and 53 patients (26.1% met the IRC after 6 months, without a change in treatment. Patients who were in remission had episodic and progressive deficit (39.6%, or remittent (15% paranoid schizophrenia, or schizoaffective disorder (17%. In addition, 105 patients of 139 (51.7%, who did not meet symptomatic IRC, remained stable within the period. Reanalysis of

  7. Non-clinical models: validation, study design and statistical consideration in safety pharmacology.

    Science.gov (United States)

    Pugsley, M K; Towart, R; Authier, S; Gallacher, D J; Curtis, M J

    2010-01-01

    The current issue of the Journal of Pharmacological and Toxicological Methods (JPTM) focuses exclusively on safety pharmacology methods. This is the 7th year the Journal has published on this topic. Methods and models that specifically relate to methods relating to the assessment of the safety profile of a new chemical entity (NCE) prior to first in human (FIH) studies are described. Since the Journal started publishing on this topic there has been a major effort by safety pharmacologists, toxicologists and regulatory scientists within Industry (both large and small Pharma as well as Biotechnology companies) and also from Contract Research Organizations (CRO) to publish the surgical details of the non-clinical methods utilized but also provide important details related to standard and non-standard (or integrated) study models and designs. These details from core battery and secondary (or ancillary) drug safety assessment methods used in drug development programs have been the focus of these special issues and have been an attempt to provide validation of methods. Similarly, the safety pharmacology issues of the Journal provide the most relevant forum for scientists to present novel and modified methods with direct applicability to determination of drug safety-directly to the safety pharmacology scientific community. The content of the manuscripts in this issue includes the introduction of additional important surgical methods, novel data capture and data analysis methods, improved study design and effects of positive control compounds with known activity in the model. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Mining, Validation, and Clinical Significance of Colorectal Cancer (CRC)-Associated lncRNAs.

    Science.gov (United States)

    Sun, Xiangwei; Hu, Yingying; Zhang, Liang; Hu, Changyuan; Guo, Gangqiang; Mao, Chenchen; Xu, Jianfeng; Ye, Sisi; Huang, Guanli; Xue, Xiangyang; Guo, Aizhen; Shen, Xian

    2016-01-01

    Colorectal cancer (CRC) is one of the deadliest tumours, but its pathogenesis remains unclear. The involvement of differentially expressed long non-coding RNAs (lncRNAs) in CRC tumorigenesis makes them suitable tumour biomarkers. Here, we screened 150 cases of CRC and 85 cases of paracancerous tissues in the GEO database for differentially expressed lncRNAs. The levels of lncRNA candidates in 84 CRC and paracancerous tissue samples were validated by qRT-PCR and their clinical significance was analyzed. We identified 15 lncRNAs with differential expression in CRC tumours; among them, AK098081 was significantly up-regulated, whereas AK025209, BC040303, BC037331, AK026659, and CR749831 were down-regulated in CRC. In a receiver operating characteristic curve analysis, the area under the curve for the six lncRNAs was 0.914. High expression of AK098081 and low expression of BC040303, CR749831, and BC037331 indicated poor CRC differentiation. CRC patients with lymph node metastasis had lower expression of BC037331. In addition, the group with high AK098081 expression presented significantly lower overall survival and disease-free survival rates than the low-expression group, confirming AK098081 as an independent risk factor for CRC patients. In conclusion, we have identified multiple CRC-associated lncRNAs from microarray expression profiles that can serve as novel biomarkers for the diagnosis and prognosis of CRC.

  9. Flexible ex vivo phantoms for validation of diffusion tensor tractography on a clinical scanner.

    Science.gov (United States)

    Watanabe, Makoto; Aoki, Shigeki; Masutani, Yoshitaka; Abe, Osamu; Hayashi, Naoto; Masumoto, Tomohiko; Mori, Harushi; Kabasawa, Hiroyuki; Ohtomo, Kuni

    2006-11-01

    The aim of this study was to develop ex vivo diffusion tensor (DT) flexible phantoms. Materials were bundles of textile threads of cotton, monofilament nylon, rayon, and polyester bunched with spiral wrapping bands and immersed in water. DT images were acquired on a 1.5-Tesla clinical magnetic resonance scanner using echo planar imaging sequences with 15 motion probing gradient directions. DT tractography with seeding and a line-tracking method was carried out by software originally developed on a PC-based workstation. We observed relatively high fractional anisotropy on the polyester phantom and were able to reconstruct tractography. Straight tracts along the bundle were displayed when it was arranged linearly. It was easy to bend arcuately or bifurcate at one end; and tracts followed the course of the bundle, whether it was curved or branched and had good agreement with direct visual observation. Tractography with the other fibers was unsuccessful. The polyester phantom revealed a diffusion anisotropic structure according to its shape and would be utilizable repeatedly under the same conditions, differently from living central neuronal system. It would be useful to validate DT sequences and to optimize an algorithm or parameters of DT tractography software. Additionally, the flexibility of the phantom would enable us to model human axonal projections.

  10. Flexible ex vivo phantoms for validation of diffusion tensor tractography on a clinical scanner

    International Nuclear Information System (INIS)

    Watanabe, Makoto; Aoki, Shigeki; Masutani, Yoshitaka; Abe, Osamu; Hayashi, Naoto; Masumoto, Tomohiko; Mori, Harushi; Kabasawa, Hiroyuki; Ohtomo, Kuni

    2006-01-01

    The aim of this study was to develop ex vivo diffusion tensor (DT) flexible phantoms. Materials were bundles of textile threads of cotton, monofilament nylon, rayon, and polyester bunched with spiral wrapping bands and immersed in water. DT images were acquired on a 1.5-Tesla clinical magnetic resonance scanner using echo planar imaging sequences with 15 motion probing gradient directions. DT tractography with seeding and a line-tracking method was carried out by software originally developed on a PC-based workstation. We observed relatively high fractional anisotropy on the polyester phantom and were able to reconstruct tractography. Straight tracts along the bundle were displayed when it was arranged linearly. It was easy to bend arcuately or bifurcate at one end; and tracts followed the course of the bundle, whether it was curved or branched and had good agreement with direct visual observation. Tractography with the other fibers was unsuccessful. The polyester phantom revealed a diffusion anisotropic structure according to its shape and would be utilizable repeatedly under the same conditions, differently from living central neuronal system. It would be useful to validate DT sequences and to optimize an algorithm or parameters of DT tractography software. Additionally, the flexibility of the phantom would enable us to model human axonal projections. (author)

  11. New clinical validation method for automated sphygmomanometer: a proposal by Japan ISO-WG for sphygmomanometer standard.

    Science.gov (United States)

    Shirasaki, Osamu; Asou, Yosuke; Takahashi, Yukio

    2007-12-01

    Owing to fast or stepwise cuff deflation, or measuring at places other than the upper arm, the clinical accuracy of most recent automated sphygmomanometers (auto-BPMs) cannot be validated by one-arm simultaneous comparison, which would be the only accurate validation method based on auscultation. Two main alternative methods are provided by current standards, that is, two-arm simultaneous comparison (method 1) and one-arm sequential comparison (method 2); however, the accuracy of these validation methods might not be sufficient to compensate for the suspicious accuracy in lateral blood pressure (BP) differences (LD) and/or BP variations (BPV) between the device and reference readings. Thus, the Japan ISO-WG for sphygmomanometer standards has been studying a new method that might improve validation accuracy (method 3). The purpose of this study is to determine the appropriateness of method 3 by comparing immunity to LD and BPV with those of the current validation methods (methods 1 and 2). The validation accuracy of the above three methods was assessed in human participants [N=120, 45+/-15.3 years (mean+/-SD)]. An oscillometric automated monitor, Omron HEM-762, was used as the tested device. When compared with the others, methods 1 and 3 showed a smaller intra-individual standard deviation of device error (SD1), suggesting their higher reproducibility of validation. The SD1 by method 2 (P=0.004) significantly correlated with the participant's BP, supporting our hypothesis that the increased SD of device error by method 2 is at least partially caused by essential BPV. Method 3 showed a significantly (P=0.0044) smaller interparticipant SD of device error (SD2), suggesting its higher interparticipant consistency of validation. Among the methods of validation of the clinical accuracy of auto-BPMs, method 3, which showed the highest reproducibility and highest interparticipant consistency, can be proposed as being the most appropriate.

  12. Feasibility of using ultra-high field (7 T MRI for clinical surgical targeting.

    Directory of Open Access Journals (Sweden)

    Yuval Duchin

    Full Text Available The advantages of ultra-high magnetic field (7 Tesla MRI for basic science research and neuroscience applications have proven invaluable. Structural and functional MR images of the human brain acquired at 7 T exhibit rich information content with potential utility for clinical applications. However, (1 substantial increases in susceptibility artifacts, and (2 geometrical distortions at 7 T would be detrimental for stereotactic surgeries such as deep brain stimulation (DBS, which typically use 1.5 T images for surgical planning. Here, we explore whether these issues can be addressed, making feasible the use of 7 T MRI to guide surgical planning. Twelve patients with Parkinson's disease, candidates for DBS, were scanned on a standard clinical 1.5 T MRI and a 7 T MRI scanner. Qualitative and quantitative assessments of global and regional distortion were evaluated based on anatomical landmarks and transformation matrix values. Our analyses show that distances between identical landmarks on 1.5 T vs. 7 T, in the mid-brain region, were less than one voxel, indicating a successful co-registration between the 1.5 T and 7 T images under these specific imaging parameter sets. On regional analysis, the central part of the brain showed minimal distortion, while inferior and frontal areas exhibited larger distortion due to proximity to air-filled cavities. We conclude that 7 T MR images of the central brain regions have comparable distortions to that observed on a 1.5 T MRI, and that clinical applications targeting structures such as the STN, are feasible with information-rich 7 T imaging.

  13. Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results

    International Nuclear Information System (INIS)

    Baumann, Michael; Krause, Mechthild

    2004-01-01

    Background and purpose: Inhibition of the epidermal growth factor receptor (EGFR) is a fastly developing field in preclinical and clinical cancer research. This review presents the current status of knowledge and discusses radiobiological mechanisms which may underly the efficacy of EGFR inhibitors combined with irradiation. Materials and methods: Preclinical and clinical results on combined targeting of the EGFR and irradiation from the literature and from this laboratory are reviewed. Focus is given to the radiobiological rationale of this approach and to endpoints of experimental radiotherapy. Results: Overexpression of the EGFR is associated with decreased local tumour control after radiotherapy, especially when the overall treatment time is long. Inhibition of the EGFR either alone or in combination with irradiation decreases the growth rate of tumours expressing this receptor. Preclinical data provide proof-of-principle that local tumour control may be improved by combining irradiation with C225 mAb. In a randomised phase III clinical trial, simultaneous irradiation and treatment with the EGFR antibody Cetuximab (Erbitux[reg]; C225) in head and neck cancer patients resulted in significantly improved locoregional tumour control and survival compared to curative irradiation alone. Acute skin reactions increased in the experimental arm. The underlying mechanisms of enhanced radiation effects of combined EGFR inhibition with irradiation and of the partly conflicting results in different studies are poorly understood. There is increasing evidence, that important intertumoral heterogeneity in the response to EGFR inhibition alone and combined with irradiation exists, which appears to be at least partly dependent on specific mutations of the receptor as well as of molecules that are involved in the intracellular signal transduction pathway. Conclusions and outlook: Further investigations at all levels of the translational research chain exploring the mechanisms of

  14. Development and Validation of an HIV Risk Exposure and Indicator Conditions Questionnaire to Support Targeted HIV Screening.

    Science.gov (United States)

    Elías, María Jesús Pérez; Gómez-Ayerbe, Cristina; Elías, Pilar Pérez; Muriel, Alfonso; de Santiago, Alberto Diaz; Martinez-Colubi, María; Moreno, Ana; Santos, Cristina; Polo, Lidia; Barea, Rafa; Robledillo, Gema; Uranga, Almudena; Espín, Agustina Cano; Quereda, Carmen; Dronda, Fernando; Casado, Jose Luis; Moreno, Santiago

    2016-02-01

    The aim of our study was to develop a Spanish-structured HIV risk of exposure and indicator conditions (RE&IC) questionnaire. People attending to an emergency room or to a primary clinical care center were offered to participate in a prospective, 1 arm, open label study, in which all enrolled patients filled out our developed questionnaire and were HIV tested. Questionnaire accuracy, feasibility, and reliability were evaluated.Valid paired 5329 HIV RE&IC questionnaire and rapid HIV tests were performed, 69.3% in the primary clinical care center, 49.6% women, median age 37 years old, 74.9% Spaniards, 20.1% Latin-Americans. Confirmed hidden HIV infection was detected in 4.1%, while HIV RE&IC questionnaire was positive in 51.2%. HIV RE&IC questionnaire sensitivity was 100% to predict HIV infection, with a 100% negative predictive value. When considered separately, RE or IC items sensitivity decreases to 86.4% or 91%, and similarly their negative predictive value to 99.9% for both of them. The majority of people studied, 90.8% self-completed HIV RE&IC questionnaire. Median time to complete was 3 minutes. Overall HIV RE&IC questionnaire test-retest Kappa agreement was 0.82 (almost perfect), likewise for IC items 0.89, while for RE items was lower 0.78 (substantial).A feasible and reliable Spanish HIV RE&IC self questionnaire accurately discriminated all non-HIV-infected people without missing any HIV diagnoses, in a low prevalence HIV infection area. The best accuracy and reliability were obtained when combining HIV RE&IC items.

  15. Clinical validation of a public health policy-making platform for hearing loss (EVOTION): protocol for a big data study.

    Science.gov (United States)

    Dritsakis, Giorgos; Kikidis, Dimitris; Koloutsou, Nina; Murdin, Louisa; Bibas, Athanasios; Ploumidou, Katherine; Laplante-Lévesque, Ariane; Pontoppidan, Niels Henrik; Bamiou, Doris-Eva

    2018-02-15

    The holistic management of hearing loss (HL) requires an understanding of factors that predict hearing aid (HA) use and benefit beyond the acoustics of listening environments. Although several predictors have been identified, no study has explored the role of audiological, cognitive, behavioural and physiological data nor has any study collected real-time HA data. This study will collect 'big data', including retrospective HA logging data, prospective clinical data and real-time data via smart HAs, a mobile application and biosensors. The main objective is to enable the validation of the EVOTION platform as a public health policy-making tool for HL. This will be a big data international multicentre study consisting of retrospective and prospective data collection. Existing data from approximately 35 000 HA users will be extracted from clinical repositories in the UK and Denmark. For the prospective data collection, 1260 HA candidates will be recruited across four clinics in the UK and Greece. Participants will complete a battery of audiological and other assessments (measures of patient-reported HA benefit, mood, cognition, quality of life). Patients will be offered smart HAs and a mobile phone application and a subset will also be given wearable biosensors, to enable the collection of dynamic real-life HA usage data. Big data analytics will be used to detect correlations between contextualised HA usage and effectiveness, and different factors and comorbidities affecting HL, with a view to informing public health decision-making. Ethical approval was received from the London South East Research Ethics Committee (17/LO/0789), the Hippokrateion Hospital Ethics Committee (1847) and the Athens Medical Center's Ethics Committee (KM140670). Results will be disseminated through national and international events in Greece and the UK, scientific journals, newsletters, magazines and social media. Target audiences include HA users, clinicians, policy-makers and the

  16. Design, synthesis, and validation of a β-turn mimetic library targeting protein-protein and peptide-receptor interactions.

    Science.gov (United States)

    Whitby, Landon R; Ando, Yoshio; Setola, Vincent; Vogt, Peter K; Roth, Bryan L; Boger, Dale L

    2011-07-06

    The design and synthesis of a β-turn mimetic library as a key component of a small-molecule library targeting the major recognition motifs involved in protein-protein interactions is described. Analysis of a geometric characterization of 10,245 β-turns in the protein data bank (PDB) suggested that trans-pyrrolidine-3,4-dicarboxamide could serve as an effective and synthetically accessible library template. This was confirmed by initially screening select compounds against a series of peptide-activated GPCRs that recognize a β-turn structure in their endogenous ligands. This validation study was highlighted by identification of both nonbasic and basic small molecules with high affinities (K(i) = 390 and 23 nM, respectively) for the κ-opioid receptor (KOR). Consistent with the screening capabilities of collaborators and following the design validation, the complete library was assembled as 210 mixtures of 20 compounds, providing a total of 4200 compounds designed to mimic all possible permutations of 3 of the 4 residues in a naturally occurring β-turn. Unique to the design and because of the C(2) symmetry of the template, a typical 20 × 20 × 20-mix (8000 compounds prepared as 400 mixtures of 20 compounds) needed to represent 20 variations in the side chains of three amino acid residues reduces to a 210 × 20-mix, thereby simplifying the library synthesis and subsequent screening. The library was prepared using a solution-phase synthetic protocol with liquid-liquid or liquid-solid extractions for purification and conducted on a scale that insures its long-term availability for screening campaigns. Screening the library against the human opioid receptors (KOR, MOR, and DOR) identified not only the activity of library members expected to mimic the opioid receptor peptide ligands but also additional side-chain combinations that provided enhanced receptor binding selectivities (>100-fold) and affinities (as low as K(i) = 80 nM for KOR). A key insight to emerge from

  17. Development and validation of receptor occupancy pharmacodynamic assays used in the clinical development of the monoclonal antibody vedolizumab.

    Science.gov (United States)

    Wyant, Tim; Estevam, Jose; Yang, Lili; Rosario, Maria

    2016-03-01

    Vedolizumab is a monoclonal antibody approved for use in ulcerative colitis and Crohn's disease. By specifically binding to α4 β7 integrin, vedolizumab prevents trafficking of lymphocytes to the gut, thereby interfering with disease pathology. During the clinical development program, the pharmacodynamic effect of vedolizumab was evaluated by 2 flow cytometry receptor occupancy assays: act-1 (ACT-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Here we describe the development and validation of these assays. The ACT-1 assay is a receptor occupancy free-site assay that uses a monoclonal antibody with the same binding epitope as vedolizumab to detect free (unbound) sites on α4 β7 integrin. The MAdCAM-1 assay used a soluble version of the natural ligand for α4 β7 integrin to detect free sites. The assays were validated using a fit-for-purpose approach throughout the clinical development of vedolizumab. Both the ACT-1 assay and the MAdCAM-1 assay demonstrated acceptable reproducibility and repeatability. The assays were sufficiently stable to allow for clinical use. During clinical testing the assays demonstrated that vedolizumab was able to saturate peripheral cells at all doses tested. Two pharmacodynamic receptor occupancy assays were developed and validated to assess the effect of vedolizumab on peripheral blood cells. The results of these assays demonstrated the practical use of flow cytometry to examine pharmacodynamic response in clinical trials. © 2015 International Clinical Cytometry Society.

  18. Assessment of postprandial triglycerides in clinical practice: validation in a general population and coronary heart disease patients

    Science.gov (United States)

    BACKGROUND: Previous studies have suggested that for clinical purposes, subjects with fasting triglycerides (TGs) between 89-180 mg/dl (1-2 mmol/l) would benefit from postprandial TGs testing. OBJECTIVE: To determine the postprandial TG response in 2 independent studies and validate who should benef...

  19. Incremental Criterion Validity of the WJ-III COG Clinical Clusters: Marginal Predictive Effects beyond the General Factor

    Science.gov (United States)

    McGill, Ryan J.

    2015-01-01

    The current study examined the incremental validity of the clinical clusters from the Woodcock-Johnson III Tests of Cognitive Abilities (WJ-III COG) for predicting scores on the Woodcock-Johnson III Tests of Achievement (WJ-III ACH). All participants were children and adolescents (N = 4,722) drawn from the nationally representative WJ-III…

  20. Validation of the "United Registries for Clinical Assessment and Research" (UR-CARE), a European online registry for clinical care and research in Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Burisch, Johan; Gisbert, Javier P; Siegmund, Britta

    2018-01-01

    Background: The "United Registries for Clinical Assessment and Research" (UR-CARE) database is an initiative of the European Crohn's and Colitis Organisation (ECCO) to facilitate daily patient care and research studies in inflammatory bowel disease (IBD). Herein, we sought to validate the database......-99%); Case 5: 91% (87-93%)]. These numbers did not differ significantly from those found 6 weeks later (NcNemar's test p>0.05). Conclusion: The UR-CARE database appears to be feasible, valid and reliable as a tool and easy to use regardless of prior user experience and level of clinical IBD experience. UR......-CARE has the potential to enhance future European collaborations regarding clinical research in IBD....

  1. Development and validation of a simple model for cellular and cell cluster dosimetry with practical application in targeted radionuclide therapy

    International Nuclear Information System (INIS)

    Bardies, M.; Myers, M.J.

    1992-01-01

    The authors have developed an analytical technique for calculating the mean absorbed dose to the cell nucleus from a variety of spatial distributions of cells and activities and a wide range of emitted energies and radionuclides. The dose to the nucleus has been calculated using this method from activity distributed (1) on the cell surface (2) throughout the cytoplasm (3) throughout a cluster of cells (micrometastasis) and (4) on the surface of the cluster of cells. The derived absorption factors have been based on the latest point kernels of Berger and have been validated against published estimates. They show good agreement and the model has the advantage of being easily adapted for revisions and extensions of available low energy data. Data sets may be derived with the absorbed fractions or the absorbed dose per emission as a function of the radial extent of the activity, and either the individual energies of the emissions or the totality of the emissions from a particular radio-nuclide. The practical applications of the model have included: (a) calculation of the absorbed dose to radioimmuno-targeted micrometastasis in the peritoneum; (b) calculations of doses to cells labelled on the surface with some novel emitters such as 67 Cu, 177 Lu, 153 Sm, 111 Ag, 186 Re, 188 Re as well as 131 I, 125 I and 90 Y; (c) comparison of doses to the cell nucleus from MIBG labelled with 125 I and 131 I and distributed in the cytoplasm of the cell; and (d) estimates of the absorbed dose to the cell nucleus from alpha emitters distributed on the surface of the cell

  2. The Metacognitive Anger Processing (MAP) Scale - Validation in a Mixed Clinical and a Forensic In-Patient Sample

    DEFF Research Database (Denmark)

    Moeller, Stine Bjerrum; Bech, Per

    2018-01-01

    BACKGROUND: The metacognitive approach by Wells and colleagues has gained empirical support with a broad range of symptoms. The Metacognitive Anger Processing (MAP) scale was developed to provide a metacognitive measure on anger (Moeller, 2016). In the preliminary validation, three components were...... identified (positive beliefs, negative beliefs and rumination) to be positively correlated with the anger. AIMS: To validate the MAP in a sample of mixed clinical patients (n = 88) and a sample of male forensic patients (n = 54). METHOD: The MAP was administered together with measures of metacognition, anger......, rumination, anxiety and depressive symptoms. RESULTS: The MAP showed acceptable scalability and excellent reliability. Convergent validity was evidenced using the general metacognitive measure (MCQ-30), and concurrent validity was supported using two different anger measures (STAXI-2 and NAS). CONCLUSIONS...

  3. Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

    Science.gov (United States)

    Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

    2018-01-01

    Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

  4. [Basic and clinical studies of the gene product-targeting therapy based on leukemogenesis--editorial].

    Science.gov (United States)

    Chen, Sai-Juan; Chen, Li-Juan; Zhou, Guang-Biao

    2005-02-01

    In the last twenty years, using all-trans retinoic acid (ATRA) as a differentiation inducer, Shanghai Institute of Hematology has achieved an important breakthrough in the treatment of acute promyelocytic leukemia (APL), which realized the theory of reversing phenotype of cells and provided a successful model of differentiation therapy in cancers. Our group first discovered in the world the variant chromosome translocation t(11;17)(q23;q21) of APL, and cloned the PML-RAR alpha, PLZF-RAR alpha and NPM-RAR alpha fusion genes corresponding to the characterized chromosome translocations t(15;17); t(11;17) and t(5;17) in APL. Moreover, establishment of transgenic mice model of APL proved their effects on leukemogenesis. The ability of ATRA to modify the recruitment of nuclear receptor co-repressor with PML-RAR alpha but not PLZF-RAR alpha caused by the variant chromosome translocation elucidated the therapeutic mechanism of ATRA from the molecular level and provides new insight into transcription-modulating therapy. Since 1994, our group has successfully applied arsenic trioxide (As(2)O(3)) in treating relapsed APL patients, with the complete remission rate of 70% - 80%. The molecular mechanism study revealed that As(2)O(3) exerts a dose-dependent dual effect on APL. Low-dose As(2)O(3) induced partial differentiation of APL cells, while the higher dose induced apoptosis. As(2)O(3) binds ubiquitin like SUMO-1 through the lysine 160 of PML, resulting in the degradation of PML-RAR alpha. Taken together, ATRA and As(2)O(3) target the transcription factor PML-RAR alpha, the former by retinoic acid receptor and the latter by PML sumolization, both induce PML-RAR alpha degradation and APL cells differentiation and apoptosis. Because of the different acting pathways, ATRA and As(2)O(3) have no cross-resistance and can be used as combination therapy. Clinical trial in newly diagnosed APL patients showed that ATRA/As(2)O(3) in combination yields a longer disease-free survival

  5. Variation of clinical target volume definition in three-dimensional conformal radiation therapy for prostate cancer

    International Nuclear Information System (INIS)

    Valicenti, Richard K.; Sweet, John W.; Hauck, Walter W.; Hudes, Richard S.; Lee, Tony; Dicker, Adam P.; Waterman, Frank M.; Anne, Pramila R.; Corn, Benjamin W.; Galvin, James M.

    1999-01-01

    Purpose: Currently, three-dimensional conformal radiation therapy (3D-CRT) planning relies on the interpretation of computed tomography (CT) axial images for defining the clinical target volume (CTV). This study investigates the variation among multiple observers to define the CTV used in 3D-CRT for prostate cancer. Methods and Materials: Seven observers independently delineated the CTVs (prostate ± seminal vesicles [SV]) from the CT simulation data of 10 prostate cancer patients undergoing 3D-CRT. Six patients underwent CT simulation without the use of contrast material and serve as a control group. The other 4 had urethral and bladder opacification with contrast medium. To determine interobserver variation, we evaluated the derived volume, the maximum dimensions, and the isocenter for each examination of CTV. We assessed the reliability in the CTVs among the observers by correlating the variation for each class of measurements. This was estimated by intraclass correlation coefficient (ICC), with 1.00 defining absolute correlation. Results: For the prostate volumes, the ICC was 0.80 (95% confidence interval [CI]: 0.56-0.96). This changed to 0.92 (95% CI: 0.75-0.99) with the use of contrast material. Similarly, the maximal prostatic dimensions were reliable and improved. There was poor agreement in defining the SV. For this structure, the ICC never exceeded 0.28. The reliability of the isocenter was excellent, with the ICC exceeding 0.83 and 0.90 for the prostate ± SV, respectively. Conclusions: In 3D-CRT for prostate cancer, there was excellent agreement among multiple observers to define the prostate target volume but poor agreement to define the SV. The use of urethral and bladder contrast improved the reliability of localizing the prostate. For all CTVs, the isocenter was very reliable and should be used to compare the variation in 3D dosimetry among multiple observers

  6. Preclinical studies and clinical trial of targeted alpha therapy for cancer

    International Nuclear Information System (INIS)

    Allen, B.J.

    2002-01-01

    Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukemia, colorectal, breast and prostate cancers. Materials and Methods: The alpha-emitting radioisotope is Bi-213, which is produced by the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (eg plasmmogen activator inhibitor PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukemia (WM60 mab), colorectal (C30.6 mab), breast (PAI2) and prostate (PAI2, J591 mab) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Results: In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than nonspecific ACs, specific beta emitting conjugates or free isotope. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can also completely regress advanced sc melanomas but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Conclusions: These results point to the application of local and systemic TAT in the management of secondary cancer. A phase 1 and 2 clinical trial of TAT of subcutaneous, secondary melanoma has commenced at St George Hospital, and 10/30 subjects have been treated by intralesional injection

  7. Reexamining the validity and reliability of the clinical version of the Iowa gambling task: Evidence from a normal subject group

    Directory of Open Access Journals (Sweden)

    Ching-Hung eLin

    2013-05-01

    Full Text Available Over past decade, the Iowa gambling task (IGT has been utilized to test various decision deficits induced by neurological damage or psychiatric disorders. The IGT has recently been standardized for identifying 13 different neuropsychological disorders. Neuropsychological patients choose bad decks frequently, and normal subjects prefer good EV decks. However, the IGT has several validity and reliability problems. Some research groups have pointed out that the validity of IGT is influenced by the personality and emotional state of subjects. Additionally, several other studies have proposed that the prominent deck B phenomenon (PDB phenomenon – that is, normal subjects preferring bad deck B – may be the most serious problem confronting IGT validity. Specifically, deck B offers a high frequency of gains but negative EV. In the standard IGT administration, choice behavior can be understood with reference to gain-loss frequency (GLF rather than inferred future consequences (EV, the basic assumption of IGT. Furthermore, using two different criteria (basic assumption vs. professional norm results in significantly different classification results. Therefore, we recruited 72 normal subjects to test the validity and reliability of IGT. Each subject performed three runs of the computer-based clinical IGT version. The PDB phenomenon has been observed to a significant degree in the first and second stages of the clinical IGT version. Obviously, validity, reliability and the practice effect were unstable between two given stages. The present form of the clinical IGT version has only one stage, so its use should be reconsidered for examining normal decision makers; results from patient groups must also be interpreted with great care. GLF could be the main factor to be considered in establishing the constructional validity and reliability of the clinical IGT version.

  8. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Science.gov (United States)

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

    2017-05-01

    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  9. Clinicopathologic Analysis of Microscopic Extension in Lung Adenocarcinoma: Defining Clinical Target Volume for Radiotherapy

    International Nuclear Information System (INIS)

    Grills, Inga S.; Fitch, Dwight L.; Goldstein, Neal S.; Yan Di; Chmielewski, Gary W.; Welsh, Robert J.; Kestin, Larry L.

    2007-01-01

    Purpose: To determine the gross tumor volume (GTV) to clinical target volume margin for non-small-cell lung cancer treatment planning. Methods: A total of 35 patients with Stage T1N0 adenocarcinoma underwent wedge resection plus immediate lobectomy. The gross tumor size and microscopic extension distance beyond the gross tumor were measured. The nuclear grade and percentage of bronchoalveolar features were analyzed for association with microscopic extension. The gross tumor dimensions were measured on a computed tomography (CT) scan (lung and mediastinal windows) and compared with the pathologic dimensions. The potential coverage of microscopic extension for two different lung stereotactic radiotherapy regimens was evaluated. Results: The mean microscopic extension distance beyond the gross tumor was 7.2 mm and varied according to grade (10.1, 7.0, and 3.5 mm for Grade 1 to 3, respectively, p < 0.01). The 90th percentile for microscopic extension was 12.0 mm (13.0, 9.7, and 4.4 mm for Grade 1 to 3, respectively). The CT lung windows correlated better with the pathologic size than did the mediastinal windows (gross pathologic size overestimated by a mean of 5.8 mm; composite size [gross plus microscopic extension] underestimated by a mean of 1.2 mm). For a GTV contoured on the CT lung windows, the margin required to cover microscopic extension for 90% of the cases would be 9 mm (9, 7, and 4 mm for Grade 1 to 3, respectively). The potential microscopic extension dosimetric coverage (55 Gy) varied substantially between the stereotactic radiotherapy schedules. Conclusion: For lung adenocarcinomas, the GTV should be contoured using CT lung windows. Although a GTV based on the CT lung windows would underestimate the gross tumor size plus microscopic extension by only 1.2 mm for the average case, the clinical target volume expansion required to cover the microscopic extension in 90% of cases could be as large as 9 mm, although considerably smaller for high-grade tumors

  10. Auto-segmentation of low-risk clinical target volume for head and neck radiation therapy.

    Science.gov (United States)

    Yang, Jinzhong; Beadle, Beth M; Garden, Adam S; Gunn, Brandon; Rosenthal, David; Ang, Kian; Frank, Steven; Williamson, Ryan; Balter, Peter; Court, Laurence; Dong, Lei

    2014-01-01

    To investigate atlas-based auto-segmentation methods to improve the quality of the delineation of low-risk clinical target volumes (CTVs) of unilateral tonsil cancers. Sixteen patients received intensity modulated radiation therapy for left tonsil tumors. These patients were treated by a total of 8 oncologists, who delineated all contours manually on the planning CT image. We chose 6 of the patients as atlas cases and used atlas-based auto-segmentation to map each the atlas CTV to the other 10 patients (test patients). For each test patient, the final contour was produced by combining the 6 individual segmentations from the atlases using the simultaneous truth and performance level estimation algorithm. In addition, for each test patient, we identified a single atlas that produced deformed contours best matching the physician's manual contours. The auto-segmented contours were compared with the physician's manual contours using the slice-wise Hausdorff distance (HD), the slice-wise Dice similarity coefficient (DSC), and a total volume overlap index. No single atlas consistently produced good results for all 10 test cases. The multiatlas segmentation achieved a good agreement between auto-segmented contours and manual contours, with a median slice-wise HD of 7.4 ± 1.0 mm, median slice-wise DSC of 80.2% ± 5.9%, and total volume overlap of 77.8% ± 3.3% over the 10 test cases. For radiation oncologists who contoured both the test case and one of the atlas cases, the best atlas for a test case had almost always been contoured by the oncologist who had contoured that test case, indicating that individual physician's practice dominated in target delineation and was an important factor in optimal atlas selection. Multiatlas segmentation may improve the quality of CTV delineation in clinical practice for unilateral tonsil cancers. We also showed that individual physician's practice was an important factor in selecting the optimal atlas for atlas-based auto

  11. Clinical Validity of the ADI-R in a US-Based Latino Population

    Science.gov (United States)

    Vanegas, Sandra B.; Magaña, Sandra; Morales, Miguel; McNamara, Ellyn

    2016-01-01

    The Autism Diagnostic Interview-Revised (ADI-R) has been validated as a tool to aid in the diagnosis of Autism; however, given the growing diversity in the United States, the ADI-R must be validated for different languages and cultures. This study evaluates the validity of the ADI-R in a US-based Latino, Spanish-speaking population of 50 children…

  12. Concurrent Validation of the Clinical Opiate Withdrawal Scale (COWS) and Single-Item Indices against the Clinical Institute Narcotic Assessment (CINA) Opioid Withdrawal Instrument

    Science.gov (United States)

    Tompkins, D. Andrew; Bigelow, George E.; Harrison, Joseph A.; Johnson, Rolley E.; Fudala, Paul J.; Strain, Eric C.

    2009-01-01

    Introduction The Clinical Opiate Withdrawal Scale (COWS) is an 11-item clinician-administered scale assessing opioid withdrawal. Though commonly used in clinical practice, it has not been systematically validated. The present study validated the COWS in comparison to the validated Clinical Institute Narcotic Assessment (CINA) scale. Method Opioid-dependent volunteers were enrolled in a residential trial and stabilized on morphine 30 mg given subcutaneously four times daily. Subjects then underwent double-blind, randomized challenges of intramuscularly administered placebo and naloxone (0.4 mg) on separate days, during which the COWS, CINA, and visual analog scale (VAS) assessments were concurrently obtained. Subjects completing both challenges were included (N=46). Correlations between mean peak COWS and CINA scores as well as self-report VAS questions were calculated. Results Mean peak COWS and CINA scores of 7.6 and 24.4, respectively, occurred on average 30 minutes post-injection of naloxone. Mean COWS and CINA scores 30 minutes after placebo injection were 1.3 and 18.9, respectively. The Pearson correlation coefficient for peak COWS and CINA scores during the naloxone challenge session was 0.85 (p<0.001). Peak COWS scores also correlated well with peak VAS self-report scores of bad drug effect (r=0.57, p<0.001) and feeling sick (r=0.57, p<0.001), providing additional evidence of concurrent validity. Placebo was not associated with any significant elevation of COWS, CINA, or VAS scores, indicating discriminant validity. Cronbach’s alpha for the COWS was 0.78, indicating good internal consistency (reliability). Discussion COWS, CINA, and certain VAS items are all valid measurement tools for acute opiate withdrawal. PMID:19647958

  13. Simplified clinical prediction scores to target viral load testing in adults with suspected first line treatment failure in Phnom Penh, Cambodia.

    Directory of Open Access Journals (Sweden)

    Johan van Griensven

    Full Text Available BACKGROUND: For settings with limited laboratory capacity, 2013 World Health Organization (WHO guidelines recommend targeted HIV-1 viral load (VL testing to identify virological failure. We previously developed and validated a clinical prediction score (CPS for targeted VL testing, relying on clinical, adherence and laboratory data. While outperforming the WHO failure criteria, it required substantial calculation and review of all previous laboratory tests. In response, we developed four simplified, less error-prone and broadly applicable CPS versions that can be done 'on the spot'. METHODOLOGY/PRINCIPAL: Findings From May 2010 to June 2011, we validated the original CPS in a non-governmental hospital in Phnom Penh, Cambodia applying the CPS to adults on first-line treatment >1 year. Virological failure was defined as a single VL >1000 copies/ml. The four CPSs included CPS1 with 'current CD4 count' instead of %-decline-from-peak CD4; CPS2 with hemoglobin measurements removed; CPS3 having 'decrease in CD4 count below baseline value' removed; CPS4 was purely clinical. Score development relied on the Spiegelhalter/Knill-Jones method. Variables independently associated with virological failure with a likelihood ratio ≥ 1.5 or ≤ 0.67 were retained. CPS performance was evaluated based on the area-under-the-ROC-curve (AUROC and 95% confidence intervals (CI. The CPSs were validated in an independent dataset. A total of 1490 individuals (56.6% female, median age: 38 years (interquartile range (IQR 33-44; median baseline CD4 count: 94 cells/µL (IQR 28-205, median time on antiretroviral therapy 3.6 years (IQR 2.1-5.1, were included. Forty-five 45 (3.0% individuals had virological failure. CPS1 yielded an AUROC of 0.69 (95% CI: 0.62-0.75 in validation, CPS2 an AUROC of 0.68 (95% CI: 0.62-0.74, and CPS3, an AUROC of 0.67 (95% CI: 0.61-0.73. The purely clinical CPS4 performed poorly (AUROC-0.59; 95% CI: 0.53-0.65. CONCLUSIONS: Simplified CPSs retained

  14. Microinvasion of liver metastases from colorectal cancer: predictive factors and application for determining clinical target volume

    International Nuclear Information System (INIS)

    Qian, Yang; Zeng, Zhao-Chong; Ji, Yuan; Xiao, Yin-Ping

    2015-01-01

    This study evaluates the microscopic characteristics of liver metastases from colorectal cancer (LMCRC) invasion and provides a reference for expansion from gross tumor volume (GTV) to clinical targeting volume (CTV). Data from 129 LMCRC patients treated by surgical resection at our hospital between January 2008 and September 2009 were collected for study. Tissue sections used for pathology and clinical data were reviewed. Patient information used for the study included gender, age, original tumor site, number of tumors, tumor size, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199), synchronous or metachronous liver metastases, and whether patients received chemotherapy. The distance of liver microinvasion from the tumor boundary was measured microscopically by two senior pathologists. Of 129 patients evaluated, 81 (62.8 %) presented microinvasion distances from the tumor boundary ranging between 1.0 − 7.0 mm. A GTV-to-CTV expansion of 5, 6.7, or 7.0 mm was required to provide a 95, 99, or 100 % probability, respectively, of obtaining clear resection margins by microscopic observation. The extent of invasion was not related to gender, age, synchronous or metachronous liver metastases, tumor size, CA199 level, or chemotherapy. The extent of invasion was related to original tumor site, CEA level, and number of tumors. A scoring system was established based on the latter three positive predictors. Using this system, an invasion distance less than 3 mm was measured in 93.4 % of patients with a score of ≤1 point, but in only 85.7 % of patients with a score of ≤2 points. The extent of tumor invasion in our LMCRC patient cohort correlated with original tumor site, CEA level, and number of tumors. These positive predictors may potentially be used as a scoring system for determining GTV-to-CTV expansion

  15. Deriving a clinical prediction rule to target sexual healthcare to women attending British General Practices.

    Science.gov (United States)

    Edelman, N L; Cassell, J A; Mercer, C H; Bremner, S A; Jones, C I; Gersten, A; deVisser, R O

    2018-07-01

    Some women attending General Practices (GPs) are at higher risk of unintended pregnancy (RUIP) and sexually transmitted infections (STI) than others. A clinical prediction rule (CPR) may help target resources using psychosocial questions as an acceptable, effective means of assessment. The aim was to derive a CPR that discriminates women who would benefit from sexual health discussion and intervention. Participants were recruited to a cross-sectional survey from six GPs in a city in South-East England in 2016. On arrival, female patients aged 16-44 years were invited to complete a questionnaire that addressed psychosocial factors, and the following self-reported outcomes: 2+ sexual partners in the last year (2PP) and RUIP. For each sexual risk, psychosocial questions were retained from logistic regression modelling which best discriminated women at risk using the C-statistic. Sensitivity and specificity were established in consultation with GP staff. The final sample comprised N = 1238 women. 2PP was predicted by 11 questions including age, binge-drinking weekly, ever having a partner who insulted you often, current smoking, and not cohabiting (C-statistic = 0.83, sensitivity = 73% and specificity = 77%). RUIP was predicted by 5 questions including sexual debut years, and emergency contraception use in the last 6 months (C-statistic = 0.70, sensitivity = 69% and specificity = 57%). 2PP was better discriminated than RUIP but neither to a clinically-useful degree. The finding that different psychosocial factors predicted each outcome has implications for prevention strategies. Further research should investigate causal links between psychosocial factors and sexual risk. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Phase-II Clinical Validation of a Powered Exoskeleton for the Treatment of Elbow Spasticity.

    Science.gov (United States)

    Crea, Simona; Cempini, Marco; Mazzoleni, Stefano; Carrozza, Maria Chiara; Posteraro, Federico; Vitiello, Nicola

    2017-01-01

    Introduction: Spasticity is a typical motor disorder in patients affected by stroke. Typically post-stroke rehabilitation consists of repetition of mobilization exercises on impaired limbs, aimed to reduce muscle hypertonia and mitigate spastic reflexes. It is currently strongly debated if the treatment's effectiveness improves with the timeliness of its adoption; in particular, starting intensive rehabilitation as close as possible to the stroke event may counteract the growth and postpone the onset of spasticity. In this paper we present a phase-II clinical validation of a robotic exoskeleton in treating subacute post-stroke patients. Methods: Seventeen post-stroke patients participated in 10 daily rehabilitation sessions using the NEUROExos Elbow Module exoskeleton, each one lasting 45 min: the exercises consisted of isokinetic passive mobilization of the elbow, with torque threshold to detect excessive user's resistance to the movement. We investigated the safety by reporting possible adverse events, such as mechanical, electrical or software failures of the device or injuries or pain experienced by the patient. As regards the efficacy , the Modified Ashworth Scale, was identified as primary outcome measure and the NEEM metrics describing elbow joint resistance to passive extension (i.e., maximum extension torque and zero-torque angle) as secondary outcomes. Results: During the entire duration of the treatments no failures or adverse events for the patients were reported. No statistically significant differences were found in the Modified Ashworth Scale scores, between pre-treatment and post-treatment and between post-treatment and follow-up sessions, indicating the absence of spasticity increase throughout (14 days) and after (3-4 months follow-up) the treatment. Exoskeleton metrics confirmed the absence of significant difference in between pre- and post-treatment data, whereas intra-session data highlighted significant differences in the secondary outcomes

  17. Phase-II Clinical Validation of a Powered Exoskeleton for the Treatment of Elbow Spasticity

    Directory of Open Access Journals (Sweden)

    Simona Crea

    2017-05-01

    Full Text Available Introduction: Spasticity is a typical motor disorder in patients affected by stroke. Typically post-stroke rehabilitation consists of repetition of mobilization exercises on impaired limbs, aimed to reduce muscle hypertonia and mitigate spastic reflexes. It is currently strongly debated if the treatment's effectiveness improves with the timeliness of its adoption; in particular, starting intensive rehabilitation as close as possible to the stroke event may counteract the growth and postpone the onset of spasticity. In this paper we present a phase-II clinical validation of a robotic exoskeleton in treating subacute post-stroke patients.Methods: Seventeen post-stroke patients participated in 10 daily rehabilitation sessions using the NEUROExos Elbow Module exoskeleton, each one lasting 45 min: the exercises consisted of isokinetic passive mobilization of the elbow, with torque threshold to detect excessive user's resistance to the movement. We investigated the safety by reporting possible adverse events, such as mechanical, electrical or software failures of the device or injuries or pain experienced by the patient. As regards the efficacy, the Modified Ashworth Scale, was identified as primary outcome measure and the NEEM metrics describing elbow joint resistance to passive extension (i.e., maximum extension torque and zero-torque angle as secondary outcomes.Results: During the entire duration of the treatments no failures or adverse events for the patients were reported. No statistically significant differences were found in the Modified Ashworth Scale scores, between pre-treatment and post-treatment and between post-treatment and follow-up sessions, indicating the absence of spasticity increase throughout (14 days and after (3–4 months follow-up the treatment. Exoskeleton metrics confirmed the absence of significant difference in between pre- and post-treatment data, whereas intra-session data highlighted significant differences in the

  18. Validation of co-registration of clinical lung ventilation and perfusion SPECT

    International Nuclear Information System (INIS)

    Marsh, S.H.; O'Keeffe, D.S.; Barnden, L.R.

    2010-01-01

    Full text: This talk will present results from a recent validation study of coregistration of computed tomography ventilation and perfusion (SPECT V/Q) images. The coregistration algorithm was incorporated in Qonsub, a program to coregister, normalise and subtract the SPECT (V/Q) images. Ventilation and perfusion image data were acquired from 23 patients undergoing a routine clinical SPECT V/Q study. The only change to normal patient management was the placement of three Tc 9 9 m filled fiducial markers adhered to the skin on the patient's torso. To quantify coregistration accuracy, image data were modified (within software) to remove the markers and Qonsub determined a parameter set of six values fully describing the six degree rigid transformation. The accuracy with which the six parameters coregister the images was then quantified by applying the same transformation parameters to the ventilation markers and determining how well they locate to the perfusion marker positions. Results show that for 65% of patients surveyed co-registration accuracy was to within I pixel, 30% were co-registered with an accuracy between 1 and 2 pixels and 5% were co-registered with an accuracy of between 2 and 3 pixels. Because patient placement between scans resulted in a misregistration of at most five pixels, a more rigorous test of the algorithm was required. Ethics approval had not been sought to intentionally misregister patient images, so the algorithm had to be further tested by synthetically misregistering the images. For these images Qonsub generally co-registered with the same accuracy as the original image. (author)

  19. Validation of the Six Sigma Z-score for the quality assessment of clinical laboratory timeliness.

    Science.gov (United States)

    Ialongo, Cristiano; Bernardini, Sergio

    2018-03-28

    The International Federation of Clinical Chemistry and Laboratory Medicine has introduced in recent times the turnaround time (TAT) as mandatory quality indicator for the postanalytical phase. Classic TAT indicators, namely, average, median, 90th percentile and proportion of acceptable test (PAT), are in use since almost 40 years and to date represent the mainstay for gauging the laboratory timeliness. In this study, we investigated the performance of the Six Sigma Z-score, which was previously introduced as a device for the quantitative assessment of timeliness. A numerical simulation was obtained modeling the actual TAT data set using the log-logistic probability density function. Five thousand replicates for each size of the artificial TAT random sample (n=20, 50, 250 and 1000) were generated, and different laboratory conditions were simulated manipulating the PDF in order to generate more or less variable data. The Z-score and the classic TAT indicators were assessed for precision (%CV), robustness toward right-tailing (precision at different sample variability), sensitivity and specificity. Z-score showed sensitivity and specificity comparable to PAT (≈80% with n≥250), but superior precision that ranged within 20% by moderately small sized samples (n≥50); furthermore, Z-score was less affected by the value of the cutoff used for setting the acceptable TAT, as well as by the sample variability that reflected into the magnitude of right-tailing. The Z-score was a valid indicator of laboratory timeliness and a suitable device to improve as well as to maintain the achieved quality level.

  20. Anatomical masking of pressure footprints based on the Oxford Foot Model: validation and clinical relevance.

    Science.gov (United States)

    Giacomozzi, Claudia; Stebbins, Julie A

    2017-03-01

    Plantar pressure analysis is widely used in the assessment of foot function. In order to assess regional loading, a mask is applied to the footprint to sub-divide it into regions of interest (ROIs). The most common masking method is based on geometric features of the footprint (GM). Footprint masking based on anatomical landmarks of the foot has been implemented more recently, and involves the integration of a 3D motion capture system, plantar pressure measurement device, and a multi-segment foot model. However, thorough validation of anatomical masking (AM) using pathological footprints has not yet been presented. In the present study, an AM method based on the Oxford Foot Model (OFM) was compared to an equivalent GM. Pressure footprints from 20 young healthy subjects (HG) and 20 patients with clubfoot (CF) were anatomically divided into 5 ROIs using a subset of the OFM markers. The same foot regions were also identified by using a standard GM method. Comparisons of intra-subject coefficient of variation (CV) showed that the OFM-based AM was at least as reliable as the GM for all investigated pressure parameters in all foot regions. Clinical relevance of AM was investigated by comparing footprints from HG and CF groups. Contact time, maximum force, force-time integral and contact area proved to be sensitive parameters that were able to distinguish HG and CF groups, using both AM and GM methods However, the AM method revealed statistically significant differences between groups in 75% of measured variables, compared to 62% using a standard GM method, indicating that the AM method is more sensitive for revealing differences between groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. European Randomized Study of Screening for Prostate Cancer Risk Calculator: External Validation, Variability, and Clinical Significance.

    Science.gov (United States)

    Gómez-Gómez, Enrique; Carrasco-Valiente, Julia; Blanca-Pedregosa, Ana; Barco-Sánchez, Beatriz; Fernandez-Rueda, Jose Luis; Molina-Abril, Helena; Valero-Rosa, Jose; Font-Ugalde, Pilar; Requena-Tapia, Maria José

    2017-04-01

    To externally validate the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) and to evaluate its variability between 2 consecutive prostate-specific antigen (PSA) values. We prospectively catalogued 1021 consecutive patients before prostate biopsy for suspicion of prostate cancer (PCa). The risk of PCa and significant PCa (Gleason score ≥7) from 749 patients was calculated according to ERSPC-RC (digital rectal examination-based version 3 of 4) for 2 consecutive PSA tests per patient. The calculators' predictions were analyzed using calibration plots and the area under the receiver operating characteristic curve (area under the curve). Cohen kappa coefficient was used to compare the ability and variability. Of 749 patients, PCa was detected in 251 (33.5%) and significant PCa was detected in 133 (17.8%). Calibration plots showed an acceptable parallelism and similar discrimination ability for both PSA levels with an area under the curve of 0.69 for PCa and 0.74 for significant PCa. The ERSPC showed 226 (30.2%) unnecessary biopsies with the loss of 10 significant PCa. The variability of the RC was 16% for PCa and 20% for significant PCa, and a higher variability was associated with a reduced risk of significant PCa. We can conclude that the performance of the ERSPC-RC in the present cohort shows a high similitude between the 2 PSA levels; however, the RC variability value is associated with a decreased risk of significant PCa. The use of the ERSPC in our cohort detects a high number of unnecessary biopsies. Thus, the incorporation of ERSPC-RC could help the clinical decision to carry out a prostate biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Validation of an arterial tortuosity measure with application to hypertension collection of clinical hypertensive patients.

    Science.gov (United States)

    Diedrich, Karl T; Roberts, John A; Schmidt, Richard H; Kang, Chang-Ki; Cho, Zang-Hee; Parker, Dennis L

    2011-10-18

    Hypertension may increase tortuosity or twistedness of arteries. We applied a centerline extraction algorithm and tortuosity metric to magnetic resonance angiography (MRA) brain images to quantitatively measure the tortuosity of arterial vessel centerlines. The most commonly used arterial tortuosity measure is the distance factor metric (DFM). This study tested a DFM based measurement's ability to detect increases in arterial tortuosity of hypertensives using existing images. Existing images presented challenges such as different resolutions which may affect the tortuosity measurement, different depths of the area imaged, and different artifacts of imaging that require filtering. The stability and accuracy of alternative centerline algorithms was validated in numerically generated models and test brain MRA data. Existing images were gathered from previous studies and clinical medical systems by manually reading electronic medical records to identify hypertensives and negatives. Images of different resolutions were interpolated to similar resolutions. Arterial tortuosity in MRA images was measured from a DFM curve and tested on numerically generated models as well as MRA images from two hypertensive and three negative control populations. Comparisons were made between different resolutions, different filters, hypertensives versus negatives, and different negative controls. In tests using numerical models of a simple helix, the measured tortuosity increased as expected with more tightly coiled helices. Interpolation reduced resolution-dependent differences in measured tortuosity. The Korean hypertensive population had significantly higher arterial tortuosity than its corresponding negative control population across multiple arteries. In addition one negative control population of different ethnicity had significantly less arterial tortuosity than the other two. Tortuosity can be compared between images of different resolutions by interpolating from lower to higher

  3. Validity and clinical feasibility of the ADHD rating scale (ADHD-RS) A Danish Nationwide Multicenter Study

    DEFF Research Database (Denmark)

    Szomlaiski, N; Dyrborg, J; Rasmussen, H

    2008-01-01

    Aim: To establish the validity of a Danish version of the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS), secondly to present national norm scores compared to that of United States and other European data and thirdly to evaluate ADHD-RS when used for monitoring treatment...... effectiveness. Methods: A Danish translation of the ADHD-RS was used on a normative sample of 837 children. Two clinical samples, 138 hyperkinetic disorder (HKD) cases and 110 clinical controls were recruited from eleven Danish Child and Adolescent Mental Health (CAMH) centres and assessed according to usual...... clinical standards. The HKD children were rated by parents and teachers at baseline and at follow-up 3 months later. Results: Internal validity of ADHD-RS was high and the factor structure supported the diagnostic classification system ICD-10. The questionnaire discriminated HKD patients in a mixed...

  4. Design of a Competency Evaluation Model for Clinical Nursing Practicum, Based on Standardized Language Systems: Psychometric Validation Study.

    Science.gov (United States)

    Iglesias-Parra, Maria Rosa; García-Guerrero, Alfonso; García-Mayor, Silvia; Kaknani-Uttumchandani, Shakira; León-Campos, Álvaro; Morales-Asencio, José Miguel

    2015-07-01

    To develop an evaluation system of clinical competencies for the practicum of nursing students based on the Nursing Interventions Classification (NIC). Psychometric validation study: the first two phases addressed definition and content validation, and the third phase consisted of a cross-sectional study for analyzing reliability. The study population was undergraduate nursing students and clinical tutors. Through the Delphi technique, 26 competencies and 91 interventions were isolated. Cronbach's α was 0.96. Factor analysis yielded 18 factors that explained 68.82% of the variance. Overall inter-item correlation was 0.26, and total-item correlation ranged between 0.66 and 0.19. A competency system for the nursing practicum, structured on the NIC, is a reliable method for assessing and evaluating clinical competencies. Further evaluations in other contexts are needed. The availability of standardized language systems in the nursing discipline supposes an ideal framework to develop the nursing curricula. © 2015 Sigma Theta Tau International.

  5. A randomized clinical trial to compare the immediate effects of seated thoracic manipulation and targeted supine thoracic manipulation on cervical spine flexion range of motion and pain.

    Science.gov (United States)

    Karas, Steve; Olson Hunt, Megan J

    2014-05-01

    Randomized clinical trial. To determine the effectiveness of seated thoracic manipulation versus targeted supine thoracic manipulation on cervical spine pain and flexion range of motion (ROM). There is evidence that thoracic spine manipulation is an effective treatment for patients with cervical spine pain. This evidence includes a variety of techniques to manipulate the thoracic spine. Although each of them is effective, no research has compared techniques to determine which produces the best outcomes. A total of 39 patients with cervical spine pain were randomly assigned to either a seated thoracic manipulation or targeted supine thoracic manipulation group. Pain and flexion ROM measures were taken before and after the intervention. Pain reduction (post-treatment-pre-treatment) was significantly greater in those patients receiving the targeted supine thoracic manipulation compared to the seated thoracic manipulation (Pmanipulation group. The results of this study indicate that a targeted supine thoracic manipulation may be more effective in reducing cervical spine pain and improving cervical flexion ROM than a seated thoracic manipulation. Future studies should include a variety of patients and physical therapists (PTs) to validate our findings.

  6. New pricing approaches for bundled payments: Leveraging clinical standards and regional variations to target avoidable utilization.

    Science.gov (United States)

    Hellsten, Erik; Chu, Scally; Crump, R Trafford; Yu, Kevin; Sutherland, Jason M

    2016-03-01

    Develop pricing models for bundled payments that draw inputs from clinician-defined best practice standards and benchmarks set from regional variations in utilization. Health care utilization and claims data for a cohort of incident Ontario ischemic and hemorrhagic stroke episodes. Episodes of care are created by linking incident stroke hospitalizations with subsequent health service utilization across multiple datasets. Costs are estimated for episodes of care and constituent service components using setting-specific case mix methodologies and provincial fee schedules. Costs are estimated for five areas of potentially avoidable utilization, derived from best practice standards set by an expert panel of stroke clinicians. Alternative approaches for setting normative prices for stroke episodes are developed using measures of potentially avoidable utilization and benchmarks established by the best performing regions. There are wide regional variations in the utilization of different health services within episodes of stroke care. Reconciling the best practice standards with regional utilization identifies significant amounts of potentially avoidable utilization. Normative pricing models for stroke episodes result in increasingly aggressive redistributions of funding. Bundled payment pilots to date have been based on the costs of historical service patterns, which effectively 'bake in' unwarranted and inefficient variations in utilization. This study demonstrates the feasibility of novel clinically informed episode pricing approaches that leverage these variations to target reductions in potentially avoidable utilization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Clinically targeted screening for congenital CMV - potential for integration into the National Hearing Screening Programme.

    Science.gov (United States)

    Kadambari, S; Luck, S; Davis, A; Williams, Ej; Berrington, J; Griffiths, Pd; Sharland, M

    2013-10-01

    Screening for a condition should only be undertaken if certain strict criteria are met. Congenital CMV (cCMV) is a leading cause of sensorineuronal hearing loss (SNHL) and meets many of these criteria, but is not currently screened for in the UK. Ganciclovir reduces CMV-induced progressive SNHL if treatment is begun in the first month of life. The Newborn Hearing Screening Programme (NHSP) has been shown to identify SNHL at the earliest possible age. The potential of integrating screening for cCMV into the NHSP is discussed to consolidate the link between screening, early diagnosis and management. The early diagnosis and treatment of cCMV may prevent a small proportion of late SNHL. In the absence of any screening programme, we provide evidence that clinically targeted screening through the NHSP is a potential option in the UK, enhancing the diagnostic pathway and enabling appropriate early treatment to reduce long-term morbidity. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  8. Clinical investigation of TROP-2 as an independent biomarker and potential therapeutic target in colon cancer.

    Science.gov (United States)

    Zhao, Peng; Yu, Hai-Zheng; Cai, Jian-Hui

    2015-09-01

    Colon cancer is associated with a severe demographic and economic burden worldwide. The pathogenesis of colon cancer is highly complex and involves sequential genetic and epigenetic mechanisms. Despite extensive investigation, the pathogenesis of colon cancer remains to be elucidated. As the third most common type of cancer worldwide, the treatment options for colon cancer are currently limited. Human trophoblast cell‑surface marker (TROP‑2), is a cell‑surface transmembrane glycoprotein overexpressed by several types of epithelial carcinoma. In addition, TROP‑2 has been demonstrated to be associated with tumorigenesis and invasiveness in solid types of tumor. The aim of the present study was to investigate the protein expression of TROP‑2 in colon cancer tissues, and further explore the association between the expression of TROP‑2 and clinicopathological features of patients with colon cancer. The expression and localization of the TROP‑2 protein was examined using western blot analysis and immunofluorescence staining. Finally, the expression of TROP‑2 expression was correlated to conventional clinicopathological features of colon cancer using a χ2 test. The results revealed that TROP‑2 protein was expressed at high levels in the colon cancer tissues, which was associated with the development and pathological process of colon cancer. Therefore, TROP‑2 may be used as a biomarker to determine the clinical prognosis, and as a potential therapeutic target in colon cancer.

  9. Role of Bioreactor Technology in Tissue Engineering for Clinical Use and Therapeutic Target Design

    Directory of Open Access Journals (Sweden)

    Clare Selden

    2018-04-01

    Full Text Available Micro and small bioreactors are well described for use in bioprocess development in pre-production manufacture, using ultra-scale down and microfluidic methodology. However, the use of bioreactors to understand normal and pathophysiology by definition must be very different, and the constraints of the physiological environment influence such bioreactor design. This review considers the key elements necessary to enable bioreactors to address three main areas associated with biological systems. All entail recreation of the in vivo cell niche as faithfully as possible, so that they may be used to study molecular and cellular changes in normal physiology, with a view to creating tissue-engineered grafts for clinical use; understanding the pathophysiology of disease at the molecular level; defining possible therapeutic targets; and enabling appropriate pharmaceutical testing on a truly representative organoid, thus enabling better drug design, and simultaneously creating the potential to reduce the numbers of animals in research. The premise explored is that not only cellular signalling cues, but also mechano-transduction from mechanical cues, play an important role.

  10. Postoperative radiotherapy for glioma: improved delineation of the clinical target volume using the geodesic distance calculation.

    Directory of Open Access Journals (Sweden)

    DanFang Yan

    Full Text Available OBJECTS: To introduce a new method for generating the clinical target volume (CTV from gross tumor volume (GTV using the geodesic distance calculation for glioma. METHODS: One glioblastoma patient was enrolled. The GTV and natural barriers were contoured on each slice of the computer tomography (CT simulation images. Then, a graphic processing unit based on a parallel Euclidean distance transform was used to generate the CTV considering natural barriers. Three-dimensional (3D visualization technique was applied to show the delineation results. Speed of operation and precision were compared between this new delineation method and the traditional method. RESULTS: In considering spatial barriers, the shortest distance from the point sheltered from these barriers equals the sum of the distance along the shortest path between the two points; this consists of several segments and evades the spatial barriers, rather than being the direct Euclidean distance between two points. The CTV was generated irregularly rather than as a spherical shape. The time required to generate the CTV was greatly reduced. Moreover, this new method improved inter- and intra-observer variability in defining the CTV. CONCLUSIONS: Compared with the traditional CTV delineation, this new method using geodesic distance calculation not only greatly shortens the time to modify the CTV, but also has better reproducibility.

  11. Variation of gross tumor volume and clinical target volume definition for lung cancer

    International Nuclear Information System (INIS)

    Liang Jun; Li Minghui; Chen Dongdu

    2011-01-01

    Objective: To study the variation of gross tumor volume (GTV) and clinical target volume (CTV) definition for lung cancer between different doctors. Methods: Ten lung cancer patients with PET-CT simulation were selected from January 2008 to December 2009.GTV and CTV of these patients were defined by four professors or associate professors of radiotherapy independently. Results: The mean ratios of largest to smallest GTV and CTV were 1.66 and 1.65, respectively. The mean coefficients of variation for GTV and CTV were 0.20 and 0.17, respectively. System errors of CTV definition in three dimension were less than 5 mm, which was the largest in inferior and superior (0.48 cm, 0.37 cm, 0.32 cm; F=0.40, 0.60, 0.15, P=0.755, 0.618, 0.928). Conclusions: The variation of GTV and CTV definition for lung cancer between different doctors exist. The mean ratios of largest to smallest GTV and CTV were less than 1.7. The variation was in hilar and mediastinum lymphanode regions. System error of CTV definition was the largest (<5 mm) in cranio-caudal direction. (authors)

  12. Targeted genomic biomarkers for diagnosis and therapy: from basic research to clinical perspective

    International Nuclear Information System (INIS)

    Thakur, Mathew L.

    2014-01-01

    In 2010, more than 30,000 men succumbed to prostate cancer (PC) and more than 240,000 new PC cases were identified in the USA. Digital rectal examination, MRI, and a blood test for prostate specific antigen (PSA) determination play a significant role in detecting advanced PC. However, they are not considered reliable tools for early warning of PC, to detect recurrent cancer or to determine metastatic status of the disease. Unreliable diagnosis results in undertreatment or overtreatment of patients with minimal benefit, enormous morbidity, incontinence, and/or impotence. Histology remains the mainstay of PC confirmation. However, out of >750,000 biopsies performed each year in the USA, >65% show benign pathology, causing patient morbidity and costing hundreds of millions of healthcare dollars. Biological fluids, including urine, represent a promising source of biomarkers for detection and prediction of PC prognosis. Because urine is available non-invasively and readily, numerous studies targeting DNA, RNA, protein and metabolite based biomarkers have been performed. However, none have yet reached the clinic. Even FDA approved PCA3 test has low sensitivity and limitations in predicting aggressive PC

  13. Validity and clinical utility of the simplified Wells rule for assessing clinical probability for the exclusion of pulmonary embolism

    NARCIS (Netherlands)

    Douma, Renée A.; Gibson, Nadine S.; Gerdes, Victor E. A.; Büller, Harry R.; Wells, Philip S.; Perrier, Arnaud; Le Gal, Grégoire

    2009-01-01

    The recently introduced simplified Wells rule for the exclusion of pulmonary embolism (PE) assigns only one point to the seven variables of the original Wells rule. This study was performed to independently validate the simplified Wells rule for the exclusion of PE. We retrospectively calculated the

  14. Quality assurance of the clinical learning environment in Austria: Construct validity of the Clinical Learning Environment, Supervision and Nurse Teacher Scale (CLES+T scale).

    Science.gov (United States)

    Mueller, Gerhard; Mylonas, Demetrius; Schumacher, Petra

    2018-04-21

    Within nursing education, the clinical learning environment is of a high importance in regards to the development of competencies and abilities. The organization, atmosphere, and supervision in the clinical learning environment are only a few factors that influence this development. In Austria there is currently no valid instrument available for the evaluation of influencing factors. The aim of the study was to test the construct validity with principal component analysis as well as the internal consistency of the German Clinical Learning Environment, Supervision and Teacher Scale (CLES+T scale) in Austria. The present validation study has a descriptive-quantitative cross-sectional design. The sample consisted of 385 nursing students from thirteen training institutions in Austria. The data collection was carried out online between March and April 2016. Starting with a polychoric correlation matrix, a parallel analysis with principal component extraction and promax rotation was carried out due to the ordinal data. The exploratory ordinal factor analysis supported a four-component solution and explained 73% of the total variance. The internal consistency of all 25 items reached a Cronbach's α of 0.95 and the four components ranged between 0.83 and 0.95. The German version of the CLES+T scale seems to be a useful instrument for identifying potential areas of improvement in clinical practice in order to derive specific quality measures for the practical learning environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Validation of the Andon KD595 for clinical use and self-measurement according to the European Society of Hypertension International Protocol.

    Science.gov (United States)

    Wu, Ning; Zhang, Xuezhong; Wang, Wen; Zhang, Hongye

    2016-04-01

    This study aimed to evaluate the accuracy of the automated oscillometric upper arm blood pressure monitor Andon KD595 for home blood pressure monitoring according to the European Society of Hypertension International Protocol revision 2010. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were sequentially measured in 33 participants using the standard mercury sphygmomanometer and the Andon KD595 device. Ninety-nine pairs of comparisons were obtained from 33 participants for analysis. The KD595 device achieved the targets in part 1 of the validation study. The number of absolute differences between the device and the observers within a range of 5, 10, and 15 mmHg was 72/99, 93/99, and 96/99, respectively, for SBP and 72/99, 96/99, and 99/99, respectively, for DBP. The device also achieved the targets in part 2 of the validation study. A total of 28 and 25 participants had at least two of the three device-observer differences within 5 mmHg (required≥24) for SBP and DBP, respectively. The number of participants without device-observer difference within 5 mmHg was two for SBP and two for DBP (required≤3). The Andon upper arm blood pressure monitor KD595 has passed the International Protocol requirements and it can be recommended for clinical use and self-measurement in adults.

  16. Validation of the Andon KD5031 for clinical use and self-measurement according to the European Society of Hypertension International Protocol.

    Science.gov (United States)

    Wu, Ning; Zhang, Xuezhong; Wang, Wen; Zhang, Hongye

    2016-10-01

    This study aimed to evaluate the accuracy of the automated oscillometric upper arm blood pressure (BP) monitor Andon KD5031 for home BP monitoring according to the European Society of Hypertension International Protocol revision 2010. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were sequentially measured in 33 participants using the standard mercury sphygmomanometer and the Andon KD5031 device. Ninety-nine pairs of comparisons were obtained from 33 participants for analysis. The KD5031 device achieved the targets in part 1 of the validation study. The number of absolute differences between the device and the observers within a range of 5, 10, and 15 mmHg was 66/99, 93/99, and 98/99, respectively, for SBP and 72/99, 94/99, and 99/99, respectively, for DBP. The device also achieved the targets in part 2 of the validation study. Twenty-six participants for both SBP and DBP had at least two of the three device-observer differences within 5 mmHg (required ≥24). The number of participants without a device-observer difference within 5 mmHg was one for SBP and three for DBP (required ≤3). The Andon upper arm BP monitor KD5031 has passed the International Protocol requirements, and it can be recommended for clinical use and self-measurement in adults.

  17. Validation of the Prague C&M classification of Barrett's esophagus in clinical practice

    NARCIS (Netherlands)

    Alvarez Herrero, Lorenza; Curvers, Wouter L.; van Vilsteren, Frederike G. I.; Wolfsen, Herbert; Ragunath, Krish; Wong Kee Song, Louis-Michel; Mallant-Hent, Rosalie C.; van Oijen, Arnoud; Scholten, Pieter; Schoon, Erik J.; Schenk, Ed B. E.; Weusten, Bas L. A. M.; Bergman, Jacques G. H. M.

    2013-01-01

    Background and study aims: The Prague C&M classification for Barrett's esophagus has found widespread acceptance but has only been validated by Barrett's experts scoring video sequences. To date, validation has been lacking for its application in routine practice during real-time endoscopy. The aim

  18. Feasibility, reliability, and clinical validity of the Test of Attentional Performance for Children (KiTAP in Fragile X syndrome (FXS

    Directory of Open Access Journals (Sweden)

    Knox Andrew

    2012-02-01

    Full Text Available Abstract Background Attention and inhibition are core executive-function deficits in FRagile X syndrome (FXS. This pilot study evaluated the feasibility, reproducibility, and clinical relevance of the KiTAP, a computer-based pictorial measure of attention and inhibition with an enchanted-castle theme, in an FXS cohort. Methods The 8-subtest KiTAP battery (as many subtests as each could perform was given to 36 subjects with FXS, of variable age and cognitive/behavioral functioning, and 29 were retested, with an interval of 2 to 4 weeks between sessions. Subjects were rated by parents on the Aberrant Behavior Checklist-Community Edition (ABC-C and Behavior Assessment System for Children, Second Edition (BASC-2. Feasibility, ceiling and basal effects, and data range and distribution analyses were used to eliminate outliers and invalid data points. Reproducibility of scores was analyzed using intraclass correlation coefficients (ICCs and validity/clinical relevance was assessed by correlating KiTAP scores with ABC-C and BASC-2 scores. Results Most of the participants with FXS were able to complete the Alertness, Distractibility, Flexibility, and Go/NoGo subtests.About 50 to 60% completed the Visual Scanning and Vigilance subtests, and 20 to 25% completed the Sustained Attention and Divided Attention subtests. A panel of seven scores from four subtests were identified as feasible for most subjects, lacked excessive ceiling, basal, or learning effects, exhibited an acceptable range and distribution of scores, had good reproducibility (ICC > 0.7, and correlated with behavioral ratings for hyperactivity or attention (P Conclusions The KiTAP can be administered to cohorts with FXS over a wide range of function with valid reproducible scores. With additional validation, it could represent a useful outcome measure for assessment of attention/executive-function abilities in clinical trials targeted to these core deficits in FXS.

  19. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

    Directory of Open Access Journals (Sweden)

    Kaichun Li

    2016-01-01

    Full Text Available Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2, can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab, VEGF targeting monoclonal antibodies (bevacizumab, mTOR inhibitor (everolimus, or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.

  20. Validation and Clinical Evaluation of a Novel Method To Measure Miltefosine in Leishmaniasis Patients Using Dried Blood Spot Sample Collection

    Science.gov (United States)

    Rosing, H.; Hillebrand, M. J. X.; Blesson, S.; Mengesha, B.; Diro, E.; Hailu, A.; Schellens, J. H. M.; Beijnen, J. H.

    2016-01-01

    To facilitate future pharmacokinetic studies of combination treatments against leishmaniasis in remote regions in which the disease is endemic, a simple cheap sampling method is required for miltefosine quantification. The aims of this study were to validate a liquid chromatography-tandem mass spectrometry method to quantify miltefosine in dried blood spot (DBS) samples and to validate its use with Ethiopian patients with visceral leishmaniasis (VL). Since hematocrit (Ht) levels are typically severely decreased in VL patients, returning to normal during treatment, the method was evaluated over a range of clinically relevant Ht values. Miltefosine was extracted from DBS samples using a simple method of pretreatment with methanol, resulting in >97% recovery. The method was validated over a calibration range of 10 to 2,000 ng/ml, and accuracy and precision were within ±11.2% and ≤7.0% (≤19.1% at the lower limit of quantification), respectively. The method was accurate and precise for blood spot volumes between 10 and 30 μl and for Ht levels of 20 to 35%, although a linear effect of Ht levels on miltefosine quantification was observed in the bioanalytical validation. DBS samples were stable for at least 162 days at 37°C. Clinical validation of the method using paired DBS and plasma samples from 16 VL patients showed a median observed DBS/plasma miltefosine concentration ratio of 0.99, with good correlation (Pearson's r = 0.946). Correcting for patient-specific Ht levels did not further improve the concordance between the sampling methods. This successfully validated method to quantify miltefosine in DBS samples was demonstrated to be a valid and practical alternative to venous blood sampling that can be applied in future miltefosine pharmacokinetic studies with leishmaniasis patients, without Ht correction. PMID:26787691

  1. SU-E-T-50: Automatic Validation of Megavoltage Beams Modeled for Clinical Use in Radiation Therapy

    International Nuclear Information System (INIS)

    Melchior, M; Salinas Aranda, F; Sciutto, S; Dodat, D; Larragueta, N

    2014-01-01

    Purpose: To automatically validate megavoltage beams modeled in XiO™ 4.50 (Elekta, Stockholm, Sweden) and Varian Eclipse™ Treatment Planning Systems (TPS) (Varian Associates, Palo Alto, CA, USA), reducing validation time before beam-on for clinical use. Methods: A software application that can automatically read and analyze DICOM RT Dose and W2CAD files was developed using MatLab integrated development environment.TPS calculated dose distributions, in DICOM RT Dose format, and dose values measured in different Varian Clinac beams, in W2CAD format, were compared. Experimental beam data used were those acquired for beam commissioning, collected on a water phantom with a 2D automatic beam scanning system.Two methods were chosen to evaluate dose distributions fitting: gamma analysis and point tests described in Appendix E of IAEA TECDOC-1583. Depth dose curves and beam profiles were evaluated for both open and wedged beams. Tolerance parameters chosen for gamma analysis are 3% and 3 mm dose and distance, respectively.Absolute dose was measured independently at points proposed in Appendix E of TECDOC-1583 to validate software results. Results: TPS calculated depth dose distributions agree with measured beam data under fixed precision values at all depths analyzed. Measured beam dose profiles match TPS calculated doses with high accuracy in both open and wedged beams. Depth and profile dose distributions fitting analysis show gamma values < 1. Relative errors at points proposed in Appendix E of TECDOC-1583 meet therein recommended tolerances.Independent absolute dose measurements at points proposed in Appendix E of TECDOC-1583 confirm software results. Conclusion: Automatic validation of megavoltage beams modeled for their use in the clinic was accomplished. The software tool developed proved efficient, giving users a convenient and reliable environment to decide whether to accept or not a beam model for clinical use. Validation time before beam-on for clinical use

  2. Clinical validation of a body-fixed 3D accelerometer and algorithm for activity monitoring in orthopaedic patients

    Directory of Open Access Journals (Sweden)

    Matthijs Lipperts

    2017-10-01

    Conclusion: Activity monitoring of orthopaedic patients by counting and timing a large set of relevant daily life events is feasible in a user- and patient-friendly way and at high clinical validity using a generic three-dimensional accelerometer and algorithms based on empirical and physical methods. The algorithms performed well for healthy individuals as well as patients recovering after total joint replacement in a challenging validation set-up. With such a simple and transparent method real-life activity parameters can be collected in orthopaedic practice for diagnostics, treatments, outcome assessment, or biofeedback.

  3. Behavioral Indicators on a Mobile Sensing Platform Predict Clinically Validated Psychiatric Symptoms of Mood and Anxiety Disorders.

    Science.gov (United States)

    Place, Skyler; Blanch-Hartigan, Danielle; Rubin, Channah; Gorrostieta, Cristina; Mead, Caroline; Kane, John; Marx, Brian P; Feast, Joshua; Deckersbach, Thilo; Pentland, Alex Sandy; Nierenberg, Andrew; Azarbayejani, Ali

    2017-03-16

    There is a critical need for real-time tracking of behavioral indicators of mental disorders. Mobile sensing platforms that objectively and noninvasively collect, store, and analyze behavioral indicators have not yet been clinically validated or scalable. The aim of our study was to report on models of clinical symptoms for post-traumatic stress disorder (PTSD) and depression derived from a scalable mobile sensing platform. A total of 73 participants (67% [49/73] male, 48% [35/73] non-Hispanic white, 33% [24/73] veteran status) who reported at least one symptom of PTSD or depression completed a 12-week field trial. Behavioral indicators were collected through the noninvasive mobile sensing platform on participants' mobile phones. Clinical symptoms were measured through validated clinical interviews with a licensed clinical social worker. A combination hypothesis and data-driven approach was used to derive key features for modeling symptoms, including the sum of outgoing calls, count of unique numbers texted, absolute distance traveled, dynamic variation of the voice, speaking rate, and voice quality. Participants also reported ease of use and data sharing concerns. Behavioral indicators predicted clinically assessed symptoms of depression and PTSD (cross-validated area under the curve [AUC] for depressed mood=.74, fatigue=.56, interest in activities=.75, and social connectedness=.83). Participants reported comfort sharing individual data with physicians (Mean 3.08, SD 1.22), mental health providers (Mean 3.25, SD 1.39), and medical researchers (Mean 3.03, SD 1.36). Behavioral indicators passively collected through a mobile sensing platform predicted symptoms of depression and PTSD. The use of mobile sensing platforms can provide clinically validated behavioral indicators in real time; however, further validation of these models and this platform in large clinical samples is needed. ©Skyler Place, Danielle Blanch-Hartigan, Channah Rubin, Cristina Gorrostieta

  4. Six-minute stepper test: a valid clinical exercise tolerance test for COPD patients

    Directory of Open Access Journals (Sweden)

    Grosbois JM

    2016-03-01

    .005. Performances on the 6MST and 6MWT were significantly improved after PR (570 vs 488 steps, P=0.001 and 448 vs 406 m, respectively; P<0.0001. Improvements of the 6MST and 6MWT after PR were significantly correlated (r=0.34; P=0.03.Conclusion: The results of this study show that the 6MST is a valid test to evaluate exercise tolerance in COPD patients. The use of this test in clinical practice appears to be particularly relevant for the assessment of patients managed by home PR. Keywords: 6-minute stepper test, 6-minute walk test, exercise tolerance, pulmonary rehabilitation, cardiopulmonary exercise testing, validity

  5. Clinical assessment of dysphagia in neurodegeneration (CADN): development, validity and reliability of a bedside tool for dysphagia assessment.

    Science.gov (United States)

    Vogel, Adam P; Rommel, Natalie; Sauer, Carina; Horger, Marius; Krumm, Patrick; Himmelbach, Marc; Synofzik, Matthis

    2017-06-01

    Screening assessments for dysphagia are essential in neurodegenerative disease. Yet there are no purpose-built tools to quantify swallowing deficits at bedside or in clinical trials. A quantifiable, brief, easy to administer assessment that measures the impact of dysphagia and predicts the presence or absence of aspiration is needed. The Clinical Assessment of Dysphagia in Neurodegeneration (CADN) was designed by a multidisciplinary team (neurology, neuropsychology, speech pathology) validated against strict methodological criteria in two neurodegenerative diseases, Parkinson's disease (PD) and degenerative ataxia (DA). CADN comprises two parts, an anamnesis (part one) and consumption (part two). Two-thirds of patients were assessed using reference tests, the SWAL-QOL symptoms subscale (part one) and videofluoroscopic assessment of swallowing (part two). CADN has 11 items and can be administered and scored in an average of 7 min. Test-retest reliability was established using correlation and Bland-Altman plots. 125 patients with a neurodegenerative disease were recruited; 60 PD and 65 DA. Validity was established using ROC graphs and correlations. CADN has sensitivity of 79 and 84% and specificity 71 and 69% for parts one and two, respectively. Significant correlations with disease severity were also observed (p dysphagia symptomatology and risk of aspiration. The CADN is a reliable, valid, brief, quantifiable, and easily deployed assessment of swallowing in neurodegenerative disease. It is thus ideally suited for both clinical bedside assessment and future multicentre clinical trials in neurodegenerative disease.

  6. Clinical target volume delineation in glioblastomas: pre-operative versus post-operative/pre-radiotherapy MRI

    Science.gov (United States)

    Farace, P; Giri, M G; Meliadò, G; Amelio, D; Widesott, L; Ricciardi, G K; Dall'Oglio, S; Rizzotti, A; Sbarbati, A; Beltramello, A; Maluta, S; Amichetti, M

    2011-01-01

    Objectives Delineation of clinical target volume (CTV) is still controversial in glioblastomas. In order to assess the differences in volume and shape of the radiotherapy target, the use of pre-operative vs post-operative/pre-radiotherapy T1 and T2 weighted MRI was compared. Methods 4 CTVs were delineated in 24 patients pre-operatively and post-operatively using T1 contrast-enhanced (T1PRECTV and T1POSTCTV) and T2 weighted images (T2PRECTV and T2POSTCTV). Pre-operative MRI examinations were performed the day before surgery, whereas post-operative examinations were acquired 1 month after surgery and before chemoradiation. A concordance index (CI) was defined as the ratio between the overlapping and composite volumes. Results The volumes of T1PRECTV and T1POSTCTV were not statistically different (248 ± 88 vs 254 ± 101), although volume differences >100 cm3 were observed in 6 out of 24 patients. A marked increase due to tumour progression was shown in three patients. Three patients showed a decrease because of a reduced mass effect. A significant reduction occurred between pre-operative and post-operative T2 volumes (139 ± 68 vs 78 ± 59). Lack of concordance was observed between T1PRECTV and T1POSTCTV (CI = 0.67 ± 0.09), T2PRECTV and T2POSTCTV (CI = 0.39 ± 0.20) and comparing the portion of the T1PRECTV and T1POSTCTV not covered by that defined on T2PRECTV images (CI = 0.45 ± 0.16 and 0.44 ± 0.17, respectively). Conclusion Using T2 MRI, huge variations can be observed in peritumoural oedema, which are probably due to steroid treatment. Using T1 MRI, brain shifts after surgery and possible progressive enhancing lesions produce substantial differences in CTVs. Our data support the use of post-operative/pre-radiotherapy T1 weighted MRI for planning purposes. PMID:21045069

  7. COSMID: A Web-based Tool for Identifying and Validating CRISPR/Cas Off-target Sites

    Directory of Open Access Journals (Sweden)

    Thomas J Cradick

    2014-01-01

    Full Text Available Precise genome editing using engineered nucleases can significantly facilitate biological studies and disease treatment. In particular, clustered regularly interspaced short palindromic repeats (CRISPR with CRISPR-associated (Cas proteins are a potentially powerful tool for modifying a genome by targeted cleavage of DNA sequences complementary to designed guide strand RNAs. Although CRISPR/Cas systems can have on-target cleavage rates close to the transfection rates, they may also have relatively high off-target cleavage at similar genomic sites that contain one or more base pair mismatches, and insertions or deletions relative to the guide strand. We have developed a bioinformatics-based tool, COSMID (CRISPR Off-target Sites with Mismatches, Insertions, and Deletions that searches genomes for potential off-target sites (http://crispr.bme.gatech.edu. Based on the user-supplied guide strand and input parameters, COSMID identifies potential off-target sites with the specified number of mismatched bases and insertions or deletions when compared with the guide strand. For each site, amplification primers optimal for the chosen application are also given as output. This ranked-list of potential off-target sites assists the choice and evaluation of intended target sites, thus helping the design of CRISPR/Cas systems with minimal off-target effects, as well as the identification and quantification of CRISPR/Cas induced off-target cleavage in cells.

  8. SU-E-T-345: Validation of a Patient-Specific Monte Carlo Targeted Radionuclide Therapy Dosimetry Platform

    International Nuclear Information System (INIS)

    Besemer, A; Bednarz, B

    2014-01-01

    Purpose: There is a compelling need for personalized dosimetry in targeted radionuclide therapy given that conventional dose calculation methods fail to accurately predict dose response relationships. To address this need, we have developed a Geant4-based Monte Carlo patient-specific 3D dosimetry platform for TRT. This platform calculates patient-specific dose distributions based on serial CT/PET or CT/SPECT images acquired after injection of the TRT agent. In this work, S-values and specific absorbed fractions (SAFs) were calculated using this platform and benchmarked against reference values. Methods: S-values for 1, 10, 100, and 1000g spherical tumors with uniform activity distributions of I-124, I-125, I-131, F-18, and Ra-223 were calculated and compared to OLINDA/EXM reference values. SAFs for monoenergetic photons of 0.01, 0.1, and 1 MeV and S factors for monoenergetic electrons of 0.935 MeV were calculated for the liver, kidneys, lungs, pancreas, spleen, and adrenals in the Zubal Phantom and compared with previously published values. Sufficient particles were simulated to keep the voxel statistical uncertainty below 5%. Results: The calculated spherical S-values agreed within a few percent of reference data from OLINDA/EXM for each radionuclide and sphere size. The comparison of photon SAFs and electron S-values with previously published values showed good agreement with the previously published values. The S-values and SAFs of the source organs agreed within 1%. Conclusion: Our platform has been benchmarked against reference values for a variety of radionuclides and over a wide range of energies and tumor sizes. Therefore, this platform could be used to provide accurate patientspecific dosimetry for use in radiopharmaceutical clinical trials

  9. Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases.

    Science.gov (United States)

    Mallaret, Martial; Renaud, Mathilde; Redin, Claire; Drouot, Nathalie; Muller, Jean; Severac, Francois; Mandel, Jean Louis; Hamza, Wahiba; Benhassine, Traki; Ali-Pacha, Lamia; Tazir, Meriem; Durr, Alexandra; Monin, Marie-Lorraine; Mignot, Cyril; Charles, Perrine; Van Maldergem, Lionel; Chamard, Ludivine; Thauvin-Robinet, Christel; Laugel, Vincent; Burglen, Lydie; Calvas, Patrick; Fleury, Marie-Céline; Tranchant, Christine; Anheim, Mathieu; Koenig, Michel

    2016-07-01

    Establishing a molecular diagnosis of autosomal recessive cerebellar ataxias (ARCA) is challenging due to phenotype and genotype heterogeneity. We report the validation of a previously published clinical practice-based algorithm to diagnose ARCA. Two assessors performed a blind analysis to determine the most probable mutated gene based on comprehensive clinical and paraclinical data, without knowing the molecular diagnosis of 23 patients diagnosed by targeted capture of 57 ataxia genes and high-throughput sequencing coming from a 145 patients series. The correct gene was predicted in 61 and 78 % of the cases by the two assessors, respectively. There was a high inter-rater agreement [K = 0.85 (0.55-0.98) p < 0.001] confirming the algorithm's reproducibility. Phenotyping patients with proper clinical examination, imaging, biochemical investigations and nerve conduction studies remain crucial for the guidance of molecular analysis and to interpret next generation sequencing results. The proposed algorithm should be helpful for diagnosing ARCA in clinical practice.

  10. Clinical validity of a relocation stress scale for the families of patients transferred from intensive care units.

    Science.gov (United States)

    Oh, HyunSoo; Lee, Seul; Kim, JiSun; Lee, EunJu; Min, HyoNam; Cho, OkJa; Seo, WhaSook

    2015-07-01

    This study was conducted to develop a family relocation stress scale by modifying the Son's Relocation Stress Syndrome Scale, to examine its clinical validity and reliability and to confirm its suitability for measuring family relocation stress. The transfer of ICU patients to general wards is a significant anxiety-producing event for family members. However, no relocation stress scale has been developed specifically for families. A nonexperimental, correlation design was adopted. The study subjects were 95 family members of 95 ICU patients at a university hospital located in Incheon, South Korea. Face and construct validities of the devised family relocation stress scale were examined. Construct validity was examined using factor analysis and by using a nomological validity test. Reliability was also examined. Face and content validity of the scale were verified by confirming that its items adequately measured family relocation stress. Factor analysis yielded four components, and the total variance explained by these four components was 63·0%, which is acceptable. Nomological validity was well supported by significant relationships between relocation stress and degree of preparation for relocation, patient self-care ability, family burden and satisfaction with the relocation process. The devised scale was also found to have good reliability. The family relocation stress scale devised in this study was found to have good validity and reliability, and thus, is believed to offer a means of assessing family relocation stress. The findings of this study provide a reliable and valid assessment tool when nurses prepare families for patient transfer from an ICU to a ward setting, and may also provide useful information to those developing an intervention programme for family relocation stress management. © 2015 John Wiley & Sons Ltd.

  11. Feasibility of a semi-automated contrast-oriented algorithm for tumor segmentation in retrospectively gated PET images: phantom and clinical validation

    Science.gov (United States)

    Carles, Montserrat; Fechter, Tobias; Nemer, Ursula; Nanko, Norbert; Mix, Michael; Nestle, Ursula; Schaefer, Andrea

    2015-12-01

    PET/CT plays an important role in radiotherapy planning for lung tumors. Several segmentation algorithms have been proposed for PET tumor segmentation. However, most of them do not take into account respiratory motion and are not well validated. The aim of this work was to evaluate a semi-automated contrast-oriented algorithm (COA) for PET tumor segmentation adapted to retrospectively gated (4D) images. The evaluation involved a wide set of 4D-PET/CT acquisitions of dynamic experimental phantoms and lung cancer patients. In addition, segmentation accuracy of 4D-COA was compared with four other state-of-the-art algorithms. In phantom evaluation, the physical properties of the objects defined the gold standard. In clinical evaluation, the ground truth was estimated by the STAPLE (Simultaneous Truth and Performance Level Estimation) consensus of three manual PET contours by experts. Algorithm evaluation with phantoms resulted in: (i) no statistically significant diameter differences for different targets and movements (Δ φ =0.3+/- 1.6 mm); (ii) reproducibility for heterogeneous and irregular targets independent of user initial interaction and (iii) good segmentation agreement for irregular targets compared to manual CT delineation in terms of Dice Similarity Coefficient (DSC  =  0.66+/- 0.04 ), Positive Predictive Value (PPV  =  0.81+/- 0.06 ) and Sensitivity (Sen.  =  0.49+/- 0.05 ). In clinical evaluation, the segmented volume was in reasonable agreement with the consensus volume (difference in volume (%Vol)  =  40+/- 30 , DSC  =  0.71+/- 0.07 and PPV  =  0.90+/- 0.13 ). High accuracy in target tracking position (Δ ME) was obtained for experimental and clinical data (Δ ME{{}\\text{exp}}=0+/- 3 mm; Δ ME{{}\\text{clin}}=0.3+/- 1.4 mm). In the comparison with other lung segmentation methods, 4D-COA has shown the highest volume accuracy in both experimental and clinical data. In conclusion, the accuracy in volume

  12. Clinical validation of a dose reduction study in paediatric abdomen MSCT scanning

    International Nuclear Information System (INIS)

    Ciccarone, A.; Fonda, C.; Zatelli, Giovanna; Mazzocchi, S.

    2008-01-01

    Full text: In our previous work an individual dose adaptation in abdomen of paediatric patients has been showed at the Meyer children hospital of Florence. For each kV really feasible in our MSCT scanner, a table of mAs versus abdomen thickness and width ratio has been developed only on the basis of water cylinder phantoms. The choice of the water arise by the fact that in pediatric patient the quantity of water inside the body is major than that of adult. In this way a reduction dose has showed with respect to the ordinary paediatric scanning protocol in use before and the same image quality has been preserved in the case of an optimized CT scanning technique of a standard adult patient of height 175 cm and weight 70 kg. However these results were only theoretical because relied on water phantoms. Now this work concerns the clinical validation of our dose reduction study on phantoms. So 50 examinations were acquired with the dose reduction scanning technique and scored randomly, without knowing weight and height of patient by three radiologists. These scores were compared with that of other 50 abdomen examination before dose reduction study. The scores refers to the noise perceived by radiologist and to the diagnostic quality of radiograph. As last, a score on the low contrast tissue separation between muscle and fat and a score on visibility of structure therein have been asked to the radiologists. The same work has concerned the abdomen examinations with iodine contrast medium. In this study the score of each radiographs has been catalogued in four range of age, 0 - 1; 1 - 3; 3 - 8; 8 - 13 years. Aligned rank and Wilcoxon's signed rank tests were used for statistical analyses. The table of modulating mAs with respect to the size of patient obtained with only water phantom study has been revised so that none reduced detection in low-visibility structures like fat or muscle or liver was evident. Nevertheless a reduction in CTDI of 30 % has been reached in our new

  13. Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule

    NARCIS (Netherlands)

    Bendermacher, Bianca L. W.; Teijink, Joep A. W.; Willigendael, Edith M.; Bartelink, Marie-Louise; Büller, Harry R.; Peters, Ron J. G.; Boiten, Jelis; Langenberg, Machteld; Prins, Martin H.

    2006-01-01

    BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To

  14. Definition and delineation of the clinical target volume for rectal cancer

    International Nuclear Information System (INIS)

    Roels, Sarah; Duthoy, Wim; Haustermans, Karin; Penninckx, Freddy; Vandecaveye, Vincent; Boterberg, Tom; Neve, Wilfried de

    2006-01-01

    Purpose: Optimization of radiation techniques to maximize local tumor control and to minimize small bowel toxicity in locally advanced rectal cancer requires proper definition and delineation guidelines for the clinical target volume (CTV). The purpose of this investigation was to analyze reported data on the predominant locations and frequency of local recurrences and lymph node involvement in rectal cancer, to propose a definition of the CTV for rectal cancer and guidelines for its delineation. Methods and Materials: Seven reports were analyzed to assess the incidence and predominant location of local recurrences in rectal cancer. The distribution of lymphatic spread was analyzed in another 10 reports to record the relative frequency and location of metastatic lymph nodes in rectal cancer, according to the stage and level of the primary tumor. Results: The mesorectal, posterior, and inferior pelvic subsites are most at risk for local recurrences, whereas lymphatic tumor spread occurs mainly in three directions: upward into the inferior mesenteric nodes; lateral into the internal iliac lymph nodes; and, in a few cases, downward into the external iliac and inguinal lymph nodes. The risk for recurrence or lymph node involvement is related to the stage and the level of the primary lesion. Conclusion: Based on a review of articles reporting on the incidence and predominant location of local recurrences and the distribution of lymphatic spread in rectal cancer, we defined guidelines for CTV delineation including the pelvic subsites and lymph node groups at risk for microscopic involvement. We propose to include the primary tumor, the mesorectal subsite, and the posterior pelvic subsite in the CTV in all patients. Moreover, the lateral lymph nodes are at high risk for microscopic involvement and should also be added in the CTV

  15. HaloPlex Targeted Resequencing for Mutation Detection in Clinical Formalin-Fixed, Paraffin-Embedded Tumor Samples.

    Science.gov (United States)

    Moens, Lotte N J; Falk-Sörqvist, Elin; Ljungström, Viktor; Mattsson, Johanna; Sundström, Magnus; La Fleur, Linnéa; Mathot, Lucy; Micke, Patrick; Nilsson, Mats; Botling, Johan

    2015-11-01

    In recent years, the advent of massively parallel next-generation sequencing technologies has enabled substantial advances in the study of human diseases. Combined with targeted DNA enrichment methods, high sequence coverage can be obtained for different genes simultaneously at a reduced cost per sample, creating unique opportunities for clinical cancer diagnostics. However, the formalin-fixed, paraffin-embedded (FFPE) process of tissue samples, routinely used in pathology departments, results in DNA fragmentation and nucleotide modifications that introduce a number of technical challenges for downstream biomolecular analyses. We evaluated the HaloPlex target enrichment system for somatic mutation detection in 80 tissue fractions derived from 20 clinical cancer cases with paired tumor and normal tissue available in both FFPE and fresh-frozen format. Several modifications to the standard method were introduced, including a reduced target fragment length and two strand capturing. We found that FFPE material can be used for HaloPlex-based target enrichment and next-generation sequencing, even when starting from small amounts of DNA. By specifically capturing both strands for each target fragment, we were able to reduce the number of false-positive errors caused by FFPE-induced artifacts and lower the detection limit for somatic mutations. We believe that the HaloPlex method presented here will be broadly applicable as a tool for somatic mutation detection in clinical cancer settings. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  16. Expanding the Nomological Net of the Pathological Narcissism Inventory: German Validation and Extension in a Clinical Inpatient Sample.

    Science.gov (United States)

    Morf, Carolyn C; Schürch, Eva; Küfner, Albrecht; Siegrist, Philip; Vater, Aline; Back, Mitja; Mestel, Robert; Schröder-Abé, Michela

    2017-06-01

    The Pathological Narcissism Inventory (PNI) is a multidimensional measure for assessing grandiose and vulnerable features in narcissistic pathology. The aim of the present research was to construct and validate a German translation of the PNI and to provide further information on the PNI's nomological net. Findings from a first study confirm the psychometric soundness of the PNI and replicate its seven-factor first-order structure. A second-order structure was also supported but with several equivalent models. A second study investigating associations with a broad range of measures ( DSM Axis I and II constructs, emotions, personality traits, interpersonal and dysfunctional behaviors, and well-being) supported the concurrent validity of the PNI. Discriminant validity with the Narcissistic Personality Inventory was also shown. Finally, in a third study an extension in a clinical inpatient sample provided further evidence that the PNI is a useful tool to assess the more pathological end of narcissism.

  17. Identification of selective inhibitors of RET and comparison with current clinical candidates through development and validation of a robust screening cascade [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Amanda J. Watson

    2016-05-01

    Full Text Available RET (REarranged during Transfection is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET is a mechanism of oncogenesis in medullary thyroid carcinomas where both germline and sporadic activating somatic mutations are prevalent.   At present, there are no known specific RET inhibitors in clinical development, although many potent inhibitors of RET have been opportunistically identified through selectivity profiling of compounds initially designed to target other tyrosine kinases. Vandetanib and cabozantinib, both multi-kinase inhibitors with RET activity, are approved for use in medullary thyroid carcinoma, but additional pharmacological activities, most notably inhibition of vascular endothelial growth factor - VEGFR2 (KDR, lead to dose-limiting toxicity. The recent identification of RET fusions present in ~1% of lung adenocarcinoma patients has renewed interest in the identification and development of more selective RET inhibitors lacking the toxicities associated with the current treatments.   In an earlier publication [Newton et al, 2016; 1] we reported the discovery of a series of 2-substituted phenol quinazolines as potent and selective RET kinase inhibitors. Here we describe the development of the robust screening cascade which allowed the identification and advancement of this chemical series.  Furthermore we have profiled a panel of RET-active clinical compounds both to validate the cascade and to confirm that none display a RET-selective target profile.

  18. A simplified approach to the pooled analysis of calibration of clinical prediction rules for systematic reviews of validation studies

    Directory of Open Access Journals (Sweden)

    Dimitrov BD

    2015-04-01

    Full Text Available Borislav D Dimitrov,1,2 Nicola Motterlini,2,† Tom Fahey2 1Academic Unit of Primary Care and Population Sciences, University of Southampton, Southampton, United Kingdom; 2HRB Centre for Primary Care Research, Department of General Medicine, Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland †Nicola Motterlini passed away on November 11, 2012 Objective: Estimating calibration performance of clinical prediction rules (CPRs in systematic reviews of validation studies is not possible when predicted values are neither published nor accessible or sufficient or no individual participant or patient data are available. Our aims were to describe a simplified approach for outcomes prediction and calibration assessment and evaluate its functionality and validity. Study design and methods: Methodological study of systematic reviews of validation studies of CPRs: a ABCD2 rule for prediction of 7 day stroke; and b CRB-65 rule for prediction of 30 day mortality. Predicted outcomes in a sample validation study were computed by CPR distribution patterns (“derivation model”. As confirmation, a logistic regression model (with derivation study coefficients was applied to CPR-based dummy variables in the validation study. Meta-analysis of validation studies provided pooled estimates of “predicted:observed” risk ratios (RRs, 95% confidence intervals (CIs, and indexes of heterogeneity (I2 on forest plots (fixed and random effects models, with and without adjustment of intercepts. The above approach was also applied to the CRB-65 rule. Results: Our simplified method, applied to ABCD2 rule in three risk strata (low, 0–3; intermediate, 4–5; high, 6–7 points, indicated that predictions are identical to those computed by univariate, CPR-based logistic regression model. Discrimination was good (c-statistics =0.61–0.82, however, calibration in some studies was low. In such cases with miscalibration, the under

  19. Validation of the Konsung QD217A for clinical use and self-measurement according to the European Society of Hypertension International Protocol.

    Science.gov (United States)

    Wu, Ning; Zhang, Xuezhong; Wang, Wen; Zhang, Hongye

    2015-08-01

    This study aimed to evaluate the accuracy of the automated oscillometric upper arm blood pressure (BP) monitor Konsung QD217A for home BP monitoring according to the European Society of Hypertension International Protocol revision 2010. Three trained observers validated the performance of these devices by comparing the measurements obtained from these devices with those taken using a standard mercury sphygmomanometer. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were sequentially measured in 33 participants using a standard mercury sphygmomanometer and the Konsung QD217A device. A total of 99 pairs of comparisons were obtained from 33 participants. The QD217A device achieved the targets in part 1 of the validation study. The number of absolute differences between the device and the observers within a range of 5, 10 and 15 mmHg was 70/99, 92/99 and 96/99, respectively, for SBP and 80/99, 94/99 and 99/99, respectively, for DBP. The device also achieved the targets in part 2 of the validation study. A total of 27 and 31 participants for SBP and DBP, respectively, showed at least two of the three device-observers differences within 5 mmHg (required≥24). The number of participants without device-observer difference within 5 mmHg was one for SBP and one for DBP (required≤3). The Konsung upper arm BP monitor QD217A has passed the International Protocol requirements and it can be recommended for clinical use and self-measurement in adults. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

  20. Measuring the statistical validity of summary meta‐analysis and meta‐regression results for use in clinical practice

    Science.gov (United States)

    Riley, Richard D.

    2017-01-01

    An important question for clinicians appraising a meta‐analysis is: are the findings likely to be valid in their own practice—does the reported effect accurately represent the effect that would occur in their own clinical population? To this end we advance the concept of statistical validity—where the parameter being estimated equals the corresponding parameter for a new independent study. Using a simple (‘leave‐one‐out’) cross‐validation technique, we demonstrate how we may test meta‐analysis estimates for statistical validity using a new validation statistic, Vn, and derive its distribution. We compare this with the usual approach of investigating heterogeneity in meta‐analyses and demonstrate the link between statistical validity and homogeneity. Using a simulation study, the properties of Vn and the Q statistic are compared for univariate random effects meta‐analysis and a tailored meta‐regression model, where information from the setting (included as model covariates) is used to calibrate the summary estimate to the setting of application. Their properties are found to be similar when there are 50 studies or more, but for fewer studies Vn has greater power but a higher type 1 error rate than Q. The power and type 1 error rate of Vn are also shown to depend on the within‐study variance, between‐study variance, study sample size, and the number of studies in the meta‐analysis. Finally, we apply Vn to two published meta‐analyses and conclude that it usefully augments standard methods when deciding upon the likely validity of summary meta‐analysis estimates in clinical practice. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:28620945

  1. Development and Validation of Simulated Virtual Patients to Impart Early Clinical Exposure in Endocrine Physiology

    Science.gov (United States)

    Gupta, Akriti; Singh, Satendra; Khaliq, Farah; Dhaliwal, Upreet; Madhu, S. V.

    2018-01-01

    In the country presently, preclinical medical students are not routinely exposed to real patients. Thus, when they start clinical postings, they are found to have poor clinical reasoning skills. Simulated virtual patients (SVPs) can improve clinical skills without endangering real patients. This pilot study describes the development of two SVPs in…

  2. The validity and reliability of value-added and target-setting procedures with special reference to Key Stage 3

    OpenAIRE

    Moody, Ian Robin

    2003-01-01

    The validity of value-added systems of measurement is crucially dependent upon there being a demonstrably unambiguous relationship between the so-called baseline, or intake measures, and any subsequent measure of performance at a later stage. The reliability of such procedures is dependent on the relationships between these two measures being relatively stable over time. A number of questions arise with regard to both the validity and reliability of value-added procedures at any level in educ...

  3. [Autism Spectrum Disorder in DSM-5 - concept, validity, and reliability, impact on clinical care and future research].

    Science.gov (United States)

    Freitag, Christine M

    2014-05-01

    Autism Spectrum Disorder (ASD) in DSM-5 comprises the former DSM-IV-TR diagnoses of Autistic Disorder, Asperger's Disorde