WorldWideScience

Sample records for national clinical target

  1. 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.

  2. National Ignition Facility Target Chamber

    International Nuclear Information System (INIS)

    Wavrik, R W; Cox, J R; Fleming, P J

    2000-01-01

    On June 11, 1999 the Department of Energy dedicated the single largest piece of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) in Livermore, California. The ten (10) meter diameter aluminum target high vacuum chamber will serve as the working end of the largest laser in the world. The output of 192 laser beams will converge at the precise center of the chamber. The laser beams will enter the chamber in two by two arrays to illuminate 10 millimeter long gold cylinders called hohlraums enclosing 2 millimeter capsule containing deuterium, tritium and isotopes of hydrogen. The two isotopes will fuse, thereby creating temperatures and pressures resembling those found only inside stars and in detonated nuclear weapons, but on a minute scale. The NIF Project will serve as an essential facility to insure safety and reliability of our nation's nuclear arsenal as well as demonstrating inertial fusion's contribution to creating electrical power. The paper will discuss the requirements that had to be addressed during the design, fabrication and testing of the target chamber. A team from Sandia National Laboratories (SNL) and LLNL with input from industry performed the configuration and basic design of the target chamber. The method of fabrication and construction of the aluminum target chamber was devised by Pitt-Des Moines, Inc. (PDM). PDM also participated in the design of the chamber in areas such as the Target Chamber Realignment and Adjustment System, which would allow realignment of the sphere laser beams in the event of earth settlement or movement from a seismic event. During the fabrication of the target chamber the sphericity tolerances had to be addressed for the individual plates. Procedures were developed for forming, edge preparation and welding of individual plates. Construction plans were developed to allow the field construction of the target chamber to occur parallel to other NIF construction activities. This was

  3. Targets development at Sandia National Laboratories

    International Nuclear Information System (INIS)

    Smith, M.L.; Hebron, D.; Derzon, M.; Olson, R.; Alberts, T.

    1997-01-01

    For many years, Sandia National Laboratories under contract to the Department of Energy has produced targets designed to understand complex ion beam and z-pinch plasma physics. This poster focuses on the features of target designs that make them suitable for Z-pinch plasma physics applications. Precision diagnostic targets will prove critical in understanding the plasma physics model needed for future ion beam and z-pinch design. Targets are designed to meet specific physics needs; in this case the authors have fabricated targets to maximize information about the end-on versus side-on x-ray emission and z-pinch hohlraum development. In this poster, they describe the fabrication and characterization techniques. They include discussion of current targets under development as well as target fabrication capabilities. Advanced target designs are fabricated by Sandia National Laboratories in cooperation with General Atomics of San Diego, CA and W.J. Schafer Associates, Inc. of Livermore, CA

  4. Target Visualization at the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Potter, Daniel Abraham [Univ. of California, Davis, CA (United States)

    2011-01-01

    As the National Ignition Facility continues its campaign to achieve ignition, new methods and tools will be required to measure the quality of the targets used to achieve this goal. Techniques have been developed to measure target surface features using a phase-shifting diffraction interferometer and Leica Microsystems confocal microscope. Using these techniques we are able to produce a detailed view of the shell surface, which in turn allows us to refine target manufacturing and cleaning processes. However, the volume of data produced limits the methods by which this data can be effectively viewed by a user. This paper introduces an image-based visualization system for data exploration of target shells at the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. It aims to combine multiple image sets into a single visualization to provide a method of navigating the data in ways that are not possible with existing tools.

  5. NCI National Clinical Trials Network Structure

    Science.gov (United States)

    Learn about how the National Clinical Trials Network (NCTN) is structured. The NCTN is a program of the National Cancer Institute that gives funds and other support to cancer research organizations to conduct cancer clinical trials.

  6. 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.

  7. [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.

  8. 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

  9. 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.

  10. Resource implications of a national health target

    DEFF Research Database (Denmark)

    Jones, Peter; Sopina, Liza Elizaveta; Ashton, Toni

    2014-01-01

    Background The Shorter Stays in Emergency Departments health target was introduced in New Zealand in 2009. District Health Boards (DHBs) are expected to meet the target with no additional funding or incentives. The costs of implementing such targets have not previously been studied. Method A survey.......03), whereas expenditure in the hospital was not (r = 0.08, P = 0.75). Conclusion The fact that estimated expenditure on the target was over $50 million without additional funding suggests that DHBs were able to make savings through improved efficiencies and/or that funds were reallocated from other services...

  11. The National Spallation Neutron Source Target Station.

    Science.gov (United States)

    Gabriel, T. A.

    1997-05-01

    The technologies that are being utilized to design and build a state-of-the-art high powered (>= 1 MW), short pulsed (storage ring. Many scientific and technical disciplines are required to produce a successful target station. These disciplines include engineering, remote handling, neutronics, materials, thermal hydraulics, shock analysis, etc. In the areas of engineering and remote handling special emphasis is being given to rapid and efficient assembly and disassembly of critical parts of the target station. In the neutronics area, emphasis is being given to neutron yield and pulse optimization from the moderators, and heating and activation rates throughout the station. Development of structural materials to withstand aggressive radiation environments and that are compatible with other materials is also an important area. Thermal hydraulics and shock analysis are being closely studied since large amounts of energy are being deposited in small volumes in relatively short time periods (< 1 μsec). These areas will be expanded upon in the paper.

  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. Radioactive target and source development at Argonne National Laboratory

    International Nuclear Information System (INIS)

    Greene, J.P.; Ahmad, I.; Thomas, G.E.

    1992-01-01

    An increased demand for low-level radioactive targets has created the need for a laboratory dedicated to the production of these foils. A description is given of the radioactive target produced as well as source development work being performed at the Physics Division target facility of Argonne National Laboratory (ANL). Highlights include equipment used and the techniques employed. In addition, some examples of recent source preparation are given as well as work currently in progress

  14. National environmental targets and international emission reduction instruments

    International Nuclear Information System (INIS)

    Morthorst, P.E.

    2003-01-01

    According to the agreed burden sharing within the European Union the overall EU emission reduction target as agreed by in the Kyoto protocol is converted into national greenhouse gas reduction-targets for each of the member states. In parallel with national emission reduction initiatives common EU policies for emission reductions are considered. Currently discussed is the introduction of a market for tradable permits for CO 2 -emissions to achieve emission reductions within the power industry and other energy intensive industries. In parallel with this markets for green certificates to deploy renewable energy technologies seem to be appearing in a number of countries, among these Denmark, Italy, Sweden, Belgium (Flanders), England and Australia. Although these national initiatives for a green certificate market are fairly different, they could be a starting point for establishing a common EU certificate market. But interactions between national targets for greenhouse gas emissions and these international instruments for emission reduction are not a trivial matter, especially not seen in relation to the possible contributions of these instruments in achieving national GHG-reduction targets. The paper is split into three parts all taking a liberalised power market as starting point: The first part discusses the consequences of a general deployment of renewable energy technologies, using planning initiatives or national promotion schemes (feed-in tariffs). In the second part an international green certificate market is introduced into the liberalised power market context, substituting other national promotion schemes. Finally, in the third part a combination of an international green certificate market (TGC) and an international emission-trading scheme for CO 2 is analysed within the liberalised international power market set-up. The main conclusion is that neither the use of national renewable support schemes nor the introduction of a TGC-market into a liberalised

  15. Design of the target area for the National Ignition Facility

    International Nuclear Information System (INIS)

    Foley, R.J.; Karpenko, V.P.; Adams, C.H.

    1997-01-01

    The preliminary design of the target area for the National Ignition Facility has been completed. The target area is required to meet a challenging set of engineering system design requirements and user needs. The target area must provide the appropriate conditions before, during, and after each shot. The repeated introduction of large amounts of laser energy into the chamber and subsequent target emissions represent new design challenges for ICF facility design. Prior to each shot, the target area must provide the required target illumination, target chamber vacuum, diagnostics, and optically stable structures. During the shot, the impact of the target emissions on the target chamber, diagnostics, and optical elements is minimized and the workers and public are protected from excessive prompt radiation doses. After the shot, residual radioactivation is managed to allow the required accessibility. Diagnostic data is retrieved, operations and maintenance activities are conducted, and the facility is ready for the next shot. The target area subsystems include the target chamber, target positioner, structural systems, target diagnostics, environmental systems, and the final optics assembly. The engineering design of the major elements of the target area requires a unique combination of precision engineering, structural analysis, opto-mechanical design, random vibration suppression, thermal stability, materials engineering, robotics, and optical cleanliness. The facility has been designed to conduct both x- ray driven targets and to be converted at a later date for direct drive experiments. The NIF has been configured to provide a wide range of experimental environments for the anticipated user groups of the facility. The design status of the major elements of the target area is described

  16. The Ignition Target for the National Ignition Facility

    International Nuclear Information System (INIS)

    Atherton, L J; Moses, E I; Carlisle, K; Kilkenny, J

    2007-01-01

    The National Ignition Facility (NIF) is a 192 beam Nd-glass laser facility presently under construction at Lawrence Livermore National Laboratory (LLNL) for performing inertial confinement fusion (ICF) and experiments studying high energy density (HED) science. When completed in 2009, NIF will be able to produce 1.8 MJ, 500 TW of ultraviolet light for target experiments that will create conditions of extreme temperatures (>10 8 K), pressures (10-GBar) and matter densities (> 100 g/cm 3 ). A detailed program called the National Ignition Campaign (NIC) has been developed to enable ignition experiments in 2010, with the goal of producing fusion ignition and burn of a deuterium-tritium (DT) fuel mixture in millimeter-scale target capsules. The first of the target experiments leading up to these ignition shots will begin in 2008. Targets for the National Ignition Campaign are both complex and precise, and are extraordinarily demanding in materials fabrication, machining, assembly, cryogenics and characterization. An overview of the campaign for ignition will be presented, along with technologies for target fabrication, assembly and metrology and advances in growth and x-ray imaging of DT ice layers. The sum of these efforts represents a quantum leap in target precision, characterization, manufacturing rate and flexibility over current state-of-the-art

  17. 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

  18. Design of ignition targets for the National Ignition Facility

    International Nuclear Information System (INIS)

    Haan, S.W.; Dittrich, T.R.; Marinak, M.M.; Hinkel, D.E.

    1999-01-01

    This is a brief update on the work being done to design ignition targets for the National Ignition Facility. Updates are presented on three areas of current activity : improvements in modeling, work on a variety of targets spanning the parameter space of possible ignition targets ; and the setting of specifications for target fabrication and diagnostics. Highlights of recent activity include : a simulation of the Rayleigh-Taylor instability growth on an imploding capsule, done in 3D on a 72degree by 72degree wedge, with enough zones to resolve modes out to 100 ; and designs of targets at 250eV and 350eV, as well as the baseline 300 eV ; and variation of the central DT gas density, which influences both the Rayleigh-Taylor growth and the smoothness of the DT ice layer

  19. Recent developments in the target facilities at Argonne National Laboratory

    International Nuclear Information System (INIS)

    Greene, J.P.; Thomas, G.E.

    1989-01-01

    A description is given of recent developments in the target facility at Argonne National Laboratory (ANL). Highlights include equipment upgrades which enable us to provide enhanced capabilities for support of the Argonne Heavy-Ion ATLAS Accelerator Project. Also, future plans and additional equipment acquisitions will be discussed. (orig.)

  20. Burglar Target Selection: A Cross-National Comparison

    NARCIS (Netherlands)

    Townsley, M.; Birks, D.; Bernasco, W.; Johnson, S.D.; Ruiter, S.; White, G.

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both

  1. Burglar Target Selection : A Cross-national Comparison

    NARCIS (Netherlands)

    Townsley, Michael; Birks, Daniel; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both

  2. Recent developments in the target facilities at Argonne National Laboratory

    International Nuclear Information System (INIS)

    Greene, J.P.; Thomas, G.E.

    1988-01-01

    A description is given of recent developments in the target facility at Argonne National Laboratory. Highlights include equipment upgrades which enables us to provide enhanced capabilities for support of the Argonne Heavy-Ion ATLAS Accelerator Project. Also future plans and additional equipment acquisitions will be discussed. 3 refs., 3 tabs

  3. Hydrodynamic instabilities in beryllium targets for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Yi, S. A., E-mail: austinyi@lanl.gov; Simakov, A. N.; Wilson, D. C.; Olson, R. E.; Kline, J. L.; Batha, S. H. [Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, New Mexico 87545 (United States); Clark, D. S.; Hammel, B. A.; Milovich, J. L.; Salmonson, J. D.; Kozioziemski, B. J. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94551 (United States)

    2014-09-15

    Beryllium ablators offer higher ablation velocity, rate, and pressure than their carbon-based counterparts, with the potential to increase the probability of achieving ignition at the National Ignition Facility (NIF) [E. I. Moses et al., Phys. Plasmas 16, 041006 (2009)]. We present here a detailed hydrodynamic stability analysis of low (NIF Revision 6.1) and high adiabat NIF beryllium target designs. Our targets are optimized to fully utilize the advantages of beryllium in order to suppress the growth of hydrodynamic instabilities. This results in an implosion that resists breakup of the capsule, and simultaneously minimizes the amount of ablator material mixed into the fuel. We quantify the improvement in stability of beryllium targets relative to plastic ones, and show that a low adiabat beryllium capsule can be at least as stable at the ablation front as a high adiabat plastic target.

  4. 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

  5. Tritium and ignition target management at the National Ignition Facility.

    Science.gov (United States)

    Draggoo, Vaughn

    2013-06-01

    Isotopic mixtures of hydrogen constitute the basic fuel for fusion targets of the National Ignition Facility (NIF). A typical NIF fusion target shot requires approximately 0.5 mmoles of hydrogen gas and as much as 750 GBq (20 Ci) of 3H. Isotopic mix ratios are specified according to the experimental shot/test plan and the associated test objectives. The hydrogen isotopic concentrations, absolute amounts, gas purity, configuration of the target, and the physical configuration of the NIF facility are all parameters and conditions that must be managed to ensure the quality and safety of operations. An essential and key step in the preparation of an ignition target is the formation of a ~60 μm thick hydrogen "ice" layer on the inner surface of the target capsule. The Cryogenic Target Positioning System (Cryo-Tarpos) provides gas handling, cyro-cooling, x-ray imaging systems, and related instrumentation to control the volumes and temperatures of the multiphase (solid, liquid, and gas) hydrogen as the gas is condensed to liquid, admitted to the capsule, and frozen as a single spherical crystal of hydrogen in the capsule. The hydrogen fuel gas is prepared in discrete 1.7 cc aliquots in the LLNL Tritium Facility for each ignition shot. Post-shot hydrogen gas is recovered in the NIF Tritium Processing System (TPS). Gas handling systems, instrumentation and analytic equipment, material accounting information systems, and the shot planning systems must work together to ensure that operational and safety requirements are met.

  6. 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.

  7. Target designs for energetics experiments on the National Ignition Facility

    International Nuclear Information System (INIS)

    Meezan, N B; Glenzer, S H; Suter, L J

    2008-01-01

    The goal of the first hohlraum energetics experiments on the National Ignition Facility (NIF) [G. H. Miller et al, Optical Eng. 43, 2841 (2004)] is to select the hohlraum design for the first ignition experiments. Sub-scale hohlraums heated by 96 of the 192 laser beams on the NIF are used to emulate the laser-plasma interaction behavior of ignition hohlraums. These 'plasma emulator' targets are 70% scale versions of the 1.05 MJ, 300 eV ignition hohlraum and have the same energy-density as the full-scale ignition designs. Radiation-hydrodynamics simulations show that the sub-scale target is a good emulator of plasma conditions inside the ignition hohlraum, reproducing density n e within 10% and temperature T e within 15% along a laser beam path. Linear backscatter gain analysis shows the backscatter risk to be comparable to that of the ignition target. A successful energetics campaign will allow the National Ignition Campaign to focus its efforts on optimizing ignition hohlraums with efficient laser coupling

  8. Unprecedented climate events: Historical changes, aspirational targets, and national commitments

    Science.gov (United States)

    Diffenbaugh, Noah S.; Singh, Deepti; Mankin, Justin S.

    2018-01-01

    The United Nations Paris Agreement creates a specific need to compare consequences of cumulative emissions for pledged national commitments and aspirational targets of 1.5° to 2°C global warming. We find that humans have already increased the probability of historically unprecedented hot, warm, wet, and dry extremes, including over 50 to 90% of North America, Europe, and East Asia. Emissions consistent with national commitments are likely to cause substantial and widespread additional increases, including more than fivefold for warmest night over ~50% of Europe and >25% of East Asia and more than threefold for wettest days over >35% of North America, Europe, and East Asia. In contrast, meeting aspirational targets to keep global warming below 2°C reduces the area experiencing more than threefold increases to 90% of North America, Europe, East Asia, and much of the tropics—still exhibit sizable increases in the probability of record-setting hot, wet, and/or dry events. PMID:29457133

  9. 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.

  10. Impacts of National Decarbonization Targets for Subnational Societal Priorities

    Science.gov (United States)

    Peng, W.; Iyer, G.

    2017-12-01

    Carbon mitigation has well-recognized linkages with other environmental and socioeconomic priorities, such as air pollution, economic development, employment, etc. While climate change is a global issue, many other societal priorities are local concerns. Since local efforts form the pillars of achieving co-benefits and avoiding dis-benefits at the national level, it is critical to go beyond national-level analyses and focus on the synergies and tradeoffs at the subnational level. Here we use the United States as an example to evaluate the impacts of mid-century national-level deep decarbonization target for state-level societal priorities. Based on the Global Change Assessment Model with state-level details for the US (GCAM-USA), we design two mid-century scenarios: A Reference scenario that assumes the U.S. undertakes no additional climate mitigation policy, and a Deep Decarbonization Scenario that assumes the U.S. achieves the NDC goal through 2025 (26-28% reduction relative to 2005 levels) and then follows a straight-line trajectory to 80% reductions in economy-wide GHG emissions by 2050 relative to 2005. We then compare these two scenarios for a variety of metrics of carbon mitigation and other societal priorities in 2050. We highlight two findings. First, the synergies and tradeoffs of carbon mitigation with other societal goals at the subnational level can be quite different from the national level. For example, while deep decarbonization could improve national energy security by reducing the overall dependence on energy imports, it may exacerbate energy independence goals for some states by increasing inter-state electricity imports. Second, achieving national-level decarbonization target could result in unequal regional impacts across states. We find uneven geographic impacts for air pollution (more co-reductions occur in the eastern states), economic costs (energy prices increase more in the northeastern states) and employment (jobs increase in the western

  11. 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...

  12. Target diagnostic system for the National Ignition Facility (NIF)

    International Nuclear Information System (INIS)

    Leeper, R.J.; Chandler, G.A.; Cooper, G.W.; Derzon, M.S.

    1996-01-01

    A review of recent progress on the design of a diagnostic system proposed for ignition target experiments on the National Ignition Facility (NIF) will be presented. This diagnostic package contains an extensive suite of optical, x-ray, gamma-ray, and neutron diagnostics that enable measurements of the performance of both direct and indirect driven NIF targets. The philosophy used in designing all of the diagnostics in the set has emphasized redundant and independent measurement of fundamental physical quantities relevant to the operation of the NIF target. A unique feature of these diagnostics is that they are being designed to be capable of operating, in the high radiation, EMP, and debris backgrounds expected on the NIF facility. The diagnostic system proposed can be categorized into three broad areas: laser characterization, hohlraum characterization, and capsule performance diagnostics. The operating principles of a representative instrument from each class of diagnostic employed in this package will be summarized and illustrated with data obtained in recent prototype diagnostic tests

  13. Materials considerations for the National Spallation Neutron Source target

    International Nuclear Information System (INIS)

    Mansur, L.K.; DiStefano, J.R.; Farrell, K.; Lee, E.H.; Pawel, S.J.; Wechsler, M.S.

    1997-08-01

    The National Spallation Neutron Source (NSNS), in which neutrons are generated by bombarding a liquid mercury target with 1 GeV protons, will place extraordinary demands on materials performance. The target structural material will operate in an aggressive environment, subject to intense fluxes of high energy protons, neutrons, and other particles, while exposed to liquid mercury and to water. Components that require special consideration include the Hg liquid target container and protective shroud, beam windows, support structures, moderator containers, and beam tubes. In response to these demands a materials R and D program has been developed for the NSNS that includes: selection of materials; calculations of radiation damage; irradiations, post irradiation testing, and characterization; compatibility testing and characterization; design and implementation of a plan for monitoring of materials performance in service; and materials engineering and technical support to the project. Irradiations are being carried out in actual and simulated spallation environments. Compatibility experiments in Hg are underway to ascertain whether the phenomena of liquid metal embrittlement and temperature gradient mass transfer will be significant. Results available to date are assessed in terms of the design and operational performance of the facility

  14. National Ignition Facility Cryogenic Target Systems Interim Management Plan

    International Nuclear Information System (INIS)

    Warner, B

    2002-01-01

    Restricted availability of funding has had an adverse impact, unforeseen at the time of the original decision to projectize the National Ignition Facility (NIF) Cryogenic Target Handling Systems (NCTS) Program, on the planning and initiation of these efforts. The purpose of this document is to provide an interim project management plan describing the organizational structure and management processes currently in place for NCTS. Preparation of a Program Execution Plan (PEP) for NCTS has been initiated, and a current draft is provided as Attachment 1 to this document. The National Ignition Facility is a multi-megajoule laser facility being constructed at Lawrence Livermore National Laboratory (LLNL) by the National Nuclear Security Administration (NNSA) in the Department of Energy (DOE). Its primary mission is to support the Stockpile Stewardship Program (SSP) by performing experiments studying weapons physics, including fusion ignition. NIF also supports the missions of weapons effects, inertial fusion energy, and basic science in high-energy-density physics. NIF will be operated by LLNL under contract to the University of California (UC) as a national user facility. NIF is a low-hazard, radiological facility, and its operation will meet all applicable federal, state, and local Environmental Safety and Health (ES and H) requirements. The NCTS Interim Management Plan provides a summary of primary design criteria and functional requirements, current organizational structure, tracking and reporting procedures, and current planning estimates of project scope, cost, and schedule. The NIF Director controls the NIF Cryogenic Target Systems Interim Management Plan. Overall scope content and execution schedules for the High Energy Density Physics Campaign (SSP Campaign 10) are currently undergoing rebaselining and will be brought into alignment with resources expected to be available throughout the NNSA Future Years National Security Plan (FYNSP). The revised schedule for

  15. 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.

  16. 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...

  17. 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...

  18. Visualization of target inspection data at the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Potter, Daniel, E-mail: potter15@llnl.gov [Lawrence Livermore National Laboratory (United States); Antipa, Nick, E-mail: antipa1@llnl.gov [Lawrence Livermore National Laboratory (United States)

    2012-12-15

    Highlights: Black-Right-Pointing-Pointer Target surfaces are measured using a phase-shifting diffraction interferometer. Black-Right-Pointing-Pointer Datasets are several gigabytes that consist of tens to hundreds of files. Black-Right-Pointing-Pointer Software tools that provide a high-level overview of the entire dataset. Black-Right-Pointing-Pointer Single datasets loaded into the visualization session can be individually rotated. Black-Right-Pointing-Pointer Multiple datasets with common features are found then datasets can be aligned. - Abstract: As the National Ignition Facility continues its campaign to achieve ignition, new methods and tools will be required to measure the quality of the target capsules used to achieve this goal. Techniques have been developed to measure capsule surface features using a phase-shifting diffraction interferometer and Leica Microsystems confocal microscope. These instruments produce multi-gigabyte datasets which consist of tens to hundreds of files. Existing software can handle viewing a small subset of an entire dataset, but none can view a dataset in its entirety. Additionally, without an established mode of transport that keeps the target capsules properly aligned throughout the assembly process, a means of aligning the two dataset coordinate systems is needed. The goal of this project is to develop web based software utilizing WebGL which will provide high level overview visualization of an entire dataset, with the capability to retrieve finer details on demand, in addition to facilitating alignment of multiple datasets with one another based on common features that have been visually identified by users of the system.

  19. 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)

  20. 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.

  1. The first target experiments on the National Ignition Facility

    International Nuclear Information System (INIS)

    Landen, O.L.; Glenzer, S.H.; Froula, D.H.; Dewald, E.L.; Suter, L.J.; Schneider, M.B.; Hinkel, D.E.; Fernandez, J.C.; Kline, J.L.; Goldman, S.R.; Braun, D.G.; Celliers, P.M.; Moon, S.J.; Robey, H.S.; Lanier, N.E.; Glendinning, S.G.; Blue, B.E.; Wilde, B.H.; Jones, O.S.; Schein, J.; Divol, L.; Kalantar, D.H.; Campbell, K.M.; Holder, J.P.; McDonald, J.W.; Niemann, C.; Mackinnon, A.J.; Collins, G.W.; Bradley, D.K.; Eggert, J.H.; Hicks, D.G.; Gregori, G.; Kirkwood, R.K.; Young, B.K.; Foster, J.M.; Hansen, J.F.; Perry, T.S.; Munro, D.H.; Baldis, H.A.; Grim, G.P.; Heeter, R.F.; Hegelich, M.B.; Montgomery, D.S.; Rochau, G.A.; Olson, R.E.; Turner, R.E.; Workman, J.B.; Berger, R.L.; Cohen, B.I.; Kruer, W.L.; Langdon, A.B.; Langer, S.H.; Meezan, N.B.; Rose, H.A.; Still, C.H.; Williams, E.A.; Dodd, E.A.; Edwards, M.J.; Monteil, M.C.; Stevenson, R.M.; Thomas, B.R.; Coker, R.F.; Magelssen, G.R.; Rosen, P.A.; Stry, P.E.; Woods, D.; Weber, S.V.; Young, P.E.; Alvarez, S.; Armstrong, G.; Bahr, R.; Bourgade, G.L.; Bower, D.; Celeste, J.; Chrisp, M.; Compton, S.; Cox, J.; Constantin, C.; Costa, R.; Duncan, J.; Ellis, A.; Emig, J.; Gautier, C.; Greenwood, A.; Griffith, R.; Holdner, F.; Holtmeier, G.; Hargrove, D.; James, T.; Kamperschroer, J.; Kimbrough, J.; Landon, M.; Lee, F.D.; Malone, R.; May, M.; Montelongo, S.; Moody, J.; Ng, E.; Nikitin, A.; Pellinen, D.; Piston, K.; Poole, M.; Rekow, V.; Rhodes, M.; Shepherd, R.; Shiromizu, S.; Voloshin, D.; Warrick, A.; Watts, P.; Weber, F.; Young, P.; Arnold, P.

    2007-01-01

    A first set of shock timing, laser-plasma interaction, hohlraum energetics and hydrodynamic experiments have been performed using the first 4 beams of the National Ignition Facility (NIF), in support of indirect drive Inertial Confinement Fusion (ICF) and High Energy Density Physics (HEDP). In parallel, a robust set of optical and X-ray spectrometers, interferometer, calorimeters and imagers have been activated. The experiments have been undertaken with laser powers and energies of up to 8 TW and 17 kJ in flattop and shaped 1-9 ns pulses focused with various beam smoothing options. The experiments have demonstrated excellent agreement between measured and predicted laser-target coupling in foils and hohlraums, even when extended to a longer pulse regime unattainable at previous laser facilities, validated the predicted effects of beam smoothing on intense laser beam propagation in long scale-length plasmas and begun to test 3-dimensional codes by extending the study of laser driven hydrodynamic jets to 3-dimensional geometries. (authors)

  2. The first target experiments on the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Landen, O.L.; Glenzer, S.H.; Froula, D.H.; Dewald, E.L.; Suter, L.J.; Schneider, M.B.; Hinkel, D.E.; Fernandez, J.C.; Kline, J.L.; Goldman, S.R.; Braun, D.G.; Celliers, P.M.; Moon, S.J.; Robey, H.S.; Lanier, N.E.; Glendinning, S.G.; Blue, B.E.; Wilde, B.H.; Jones, O.S.; Schein, J.; Divol, L.; Kalantar, D.H.; Campbell, K.M.; Holder, J.P.; McDonald, J.W.; Niemann, C.; Mackinnon, A.J.; Collins, G.W.; Bradley, D.K.; Eggert, J.H.; Hicks, D.G.; Gregori, G.; Kirkwood, R.K.; Young, B.K.; Foster, J.M.; Hansen, J.F.; Perry, T.S.; Munro, D.H.; Baldis, H.A.; Grim, G.P.; Heeter, R.F.; Hegelich, M.B.; Montgomery, D.S.; Rochau, G.A.; Olson, R.E.; Turner, R.E.; Workman, J.B.; Berger, R.L.; Cohen, B.I.; Kruer, W.L.; Langdon, A.B.; Langer, S.H.; Meezan, N.B.; Rose, H.A.; Still, C.H.; Williams, E.A.; Dodd, E.A.; Edwards, M.J.; Monteil, M.C.; Stevenson, R.M.; Thomas, B.R.; Coker, R.F.; Magelssen, G.R.; Rosen, P.A.; Stry, P.E.; Woods, D.; Weber, S.V.; Young, P.E.; Alvarez, S.; Armstrong, G.; Bahr, R.; Bourgade, G.L.; Bower, D.; Celeste, J.; Chrisp, M.; Compton, S.; Cox, J.; Constantin, C.; Costa, R.; Duncan, J.; Ellis, A.; Emig, J.; Gautier, C.; Greenwood, A.; Griffith, R.; Holdner, F.; Holtmeier, G.; Hargrove, D.; James, T.; Kamperschroer, J.; Kimbrough, J.; Landon, M.; Lee, F.D.; Malone, R.; May, M.; Montelongo, S.; Moody, J.; Ng, E.; Nikitin, A.; Pellinen, D.; Piston, K.; Poole, M.; Rekow, V.; Rhodes, M.; Shepherd, R.; Shiromizu, S.; Voloshin, D.; Warrick, A.; Watts, P.; Weber, F.; Young, P.; Arnold, P

    2007-08-15

    A first set of shock timing, laser-plasma interaction, hohlraum energetics and hydrodynamic experiments have been performed using the first 4 beams of the National Ignition Facility (NIF), in support of indirect drive Inertial Confinement Fusion (ICF) and High Energy Density Physics (HEDP). In parallel, a robust set of optical and X-ray spectrometers, interferometer, calorimeters and imagers have been activated. The experiments have been undertaken with laser powers and energies of up to 8 TW and 17 kJ in flattop and shaped 1-9 ns pulses focused with various beam smoothing options. The experiments have demonstrated excellent agreement between measured and predicted laser-target coupling in foils and hohlraums, even when extended to a longer pulse regime unattainable at previous laser facilities, validated the predicted effects of beam smoothing on intense laser beam propagation in long scale-length plasmas and begun to test 3-dimensional codes by extending the study of laser driven hydrodynamic jets to 3-dimensional geometries. (authors)

  3. 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

  4. 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...

  5. [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.

  6. 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

  7. 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.)

  8. 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.

  9. National Database for Clinical Trials Related to Mental Illness (NDCT)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Database for Clinical Trials Related to Mental Illness (NDCT) is an extensible informatics platform for relevant data at all levels of biological and...

  10. The National Institute of Dental Research Clinical Dental Staff Fellowship.

    Science.gov (United States)

    Baum, Bruce J.; And Others

    1988-01-01

    A program in one of the National Institutes of Health offers clinical training fellowships as a means of training potential dental school faculty by providing both unique clinical skills and high-quality research experience. The program was developed in response to a perceived need for change in academic dentistry. (MSE)

  11. CPTAC Collaborates with Molecular & Cellular Proteomics to Address Reproducibility in Targeted Assay Development | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The journal Molecular & Cellular Proteomics (MCP), in collaboration with the Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announce new guidelines and requirements for papers describing the development and application of targeted mass spectrometry measurements of peptides, modified peptides and proteins (Mol Cell Proteomics 2017; PMID: 28183812).  NCI’s participation is part of NIH’s overall effort to address the r

  12. Research on the decomposition model for China’s National Renewable Energy total target

    International Nuclear Information System (INIS)

    Liu, Zhen; Shi, Yuren; Yan, Jianming; Ou, Xunmin; Lieu, Jenny

    2012-01-01

    It is crucial that China’s renewable energy national target in 2020 is effectively decomposed into respective period targets at the provincial level. In order to resolve problems arising from combining the national and local renewable energy development plan, a total target and period target decomposition model of renewable energy is proposed which considers the resource distribution and energy consumption of different provinces as well as the development characteristics of various renewable energy industries. In the model, the total proposed target is comprised of three shares: basic share, fixed share and floating share target. The target distributed for each province is then determined by the preference relation. That is, when total renewable energy target is distributed, the central government is more concerned about resources potential or energy consumption. Additionally, the growth models for various renewable energy industries are presented, and the period targets of renewable energy in various provinces are proposed in line with regional economic development targets. In order to verify whether the energy target can be achieved, only wind power, solar power, and hydropower are considered in this study. To convenient to assess the performance of local government, the two year period is chosen as an evaluation cycle in the paper. The renewable energy targets per two-year period for each province are calculated based on the overall national renewable energy target, energy requirements and resources distribution. Setting provincial period targets will help policy makers to better implement and supervise the overall renewable energy plan. - Highlights: It is very importance that the national target of renewable energy in 2020 can be effectively decomposed into the stages target of various province. In order to resolve the relation the plan between the national and local renewable energy development planning, a total target and phase target decomposition model

  13. 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.

  14. National Target for South Asia Specialists. A Report.

    Science.gov (United States)

    National Council on Foreign Language and International Studies, New York, NY.

    The South Asia Panel of the National Council on Foreign Languages and International Studies reports on the need for specialists in the languages and cultures of Afghanistan, Bangladesh, India, Nepal, Pakistan, Sri Lanka, Bhutan, and the Maldives. Two categories of specialists are discussed: (1) individuals in government, mission, etc., in…

  15. 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

  16. 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,

  17. Target Diagnostic Control System Implementation for the National Ignition Facility

    International Nuclear Information System (INIS)

    Shelton, R.T.; Kamperschroer, J.H.; Lagin, L.J.; Nelson, J.R.; O'Brien, D.W.

    2010-01-01

    The extreme physics of targets shocked by NIF's 192-beam laser are observed by a diverse suite of diagnostics. Many diagnostics are being developed by collaborators at other sites, but ad hoc controls could lead to unreliable and costly operations. A Diagnostic Control System (DCS) framework for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost Windows XP processor and Java application. Each instrument is aggregated with others as needed in the supervisory system to form an integrated diagnostic. The Java framework provides data management, control services and operator GUI generation. DCS instruments are reusable by replication with reconfiguration for specific diagnostics in XML. Advantages include minimal application code, easy testing, and high reliability. Collaborators save costs by assembling diagnostics with existing DCS instruments. This talk discusses target diagnostic instrumentation used on NIF and presents the DCS architecture and framework.

  18. Analysis of quality data based on national clinical databases

    DEFF Research Database (Denmark)

    Utzon, Jan; Petri, A.L.; Christophersen, S.

    2009-01-01

    There is little agreement on the philosophy of measuring clinical quality in health care. How data should be analyzed and transformed to healthcare information is an ongoing discussion. To accept a difference in quality between health departments as a real difference, one should consider to which...... extent the selection of patients, random variation, confounding and inconsistency may have influenced results. The aim of this article is to summarize aspects of clinical healthcare data analyses provided from the national clinical quality databases and to show how data may be presented in a way which...... is understandable to readers without specialised knowledge of statistics Udgivelsesdato: 2009/9/14...

  19. Analysis of quality data based on national clinical databases

    DEFF Research Database (Denmark)

    Utzon, Jan; Petri, A.L.; Christophersen, S.

    2009-01-01

    extent the selection of patients, random variation, confounding and inconsistency may have influenced results. The aim of this article is to summarize aspects of clinical healthcare data analyses provided from the national clinical quality databases and to show how data may be presented in a way which......There is little agreement on the philosophy of measuring clinical quality in health care. How data should be analyzed and transformed to healthcare information is an ongoing discussion. To accept a difference in quality between health departments as a real difference, one should consider to which...

  20. 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?

  1. 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...

  2. Credentialism, National Targets, and the Learning Society: Perspectives on Educational Attainment in the UK Steel Industry.

    Science.gov (United States)

    Fuller, Alison; Unwin, Lorna

    1999-01-01

    The UK's National Learning Targets for Education and Training, embracing 11- to 21-year-olds, adults, and employers, promote a credentialist approach to economic and social development. This article shows how the steel industry measures up. Using qualifications-based targets as a proxy for adult workforce capability is misguided. (Contains 40…

  3. Targeted Modification of Neutron Energy Spectra for National Security Applications

    Science.gov (United States)

    Bevins, James Edward

    At its core, research represents an attempt to break from the "this is the way we have always done it" paradigm. This idea is evidenced from the start in this research effort by the problem formulation to develop a new way to generate synthetic debris that mimics the samples that would be collected for forensics purposes following a nuclear weapon attack on the U.S. or its allies. The philosophy is also demonstrated by the design methodology used to solve the synthetic debris problem, using methods not commonly applied to nuclear engineering problems. Through this research, the bounds of what is deemed possible in neutron spectral shaping are moved ever so slightly. A capability for the production of synthetic debris and fission products was developed for the National Ignition Facility (NIF). Synthetic debris has historically been made in a limited fashion using sample doping techniques since the cessation of nuclear weapons testing, but a more robust alternative approach using neutron spectral shaping was proposed and developed by the University of California-Berkeley and Lawrence Livermore National Laboratory (LLNL). Using NIF as a starting source spectrum, the energy tuning assembly (ETA) developed in this work can irradiate samples with a combined thermonuclear and prompt fission neutron spectrum (TN+PFNS). When used with fissile foils, this irradiation will produce a synthetic fission product distribution that is realistic across all mass chains. To design the ETA, traditional parametric point design approaches were discarded in favor of formal optimization techniques. Finding a lack of suitable algorithms in the literature, a metaheuristic-based optimization algorithm, Gnowee, was developed for rapid convergence to nearly globally optimum solutions for complex, constrained engineering problems with mixed-integer and combinatorial design vectors and high-cost, noisy, discontinuous, black box objective function evaluations. Comparisons between Gnowee and

  4. Targeting poverty : lessons from monitoring Ireland's National Anti-Poverty Strategy

    OpenAIRE

    Layte, Richard; Nolan, Brian; Whelan, Christopher T.

    2000-01-01

    In 1997 the Irish government adopted the National Anti-Poverty Strategy (NAPS), a global target for the reduction of poverty which illuminates a range of issues relating to official poverty targets. The Irish target is framed in terms of a relative poverty measure incorporating both relative income and direct measures of deprivation based on data on the extent of poverty from 1994. Since 1994 Ireland has experienced an unprecedented period of economic growth that makes it particularly importa...

  5. National survey of pain clinics in Croatia: Organization and services

    Directory of Open Access Journals (Sweden)

    Mahir Fidahić

    2015-05-01

    Full Text Available Objective. To analyze organization and therapeutic procedures administered in tertiary outpatient pain clinics in Croatia. Methods. Data about organization of pain clinics, its personnel, equipment, continuing medical education, therapeutic procedures, research activities and relations with pharmaceutical industry were collected using questionnaires. Results. Twenty-two Croatian pain clinics were included in the study. Most of the pain clinics employ exclusively anesthesiologists and nurses. The most frequently prescribed therapeutic procedures in pain clinics were pharmacotherapy, transcutaneous electrical nerve stimulation, acupuncture and trigger point injections. Almost all pain clinics provide educational material for patients. Most of the pain clinics have regular interactions with pharmaceutical companies. Prescribing decisions were based mostly on information from scientific meetings, research articles and consultations with colleagues. Information sources which are considered to be the gold standard – the systematic reviews of The Cochrane Collaboration – were used less frequently (n=12; 57% than advertising materials from pharmaceutical companies (n=16; 76%. Few physicians and other pain clinics staff had scientific degrees or academic titles or were involved in a research project. Conclusion. The national study about pain clinics in Croatia pointed out that there is room for improvement of their organization and services. Pain clinics should employ health-care professionals with diverse backgrounds. They should offer treatments backed by the highest-level of scientific evidence. Since pain is a major public health issue, pain clinic staff should engage more in research to contribute to the growing field of pain research, to enhance capacities for pain research in Croatia, to incorporate scientific evidence into their daily decision-making and to enable evidence-based practice.

  6. National survey of pain clinics in Croatia: Organization and services.

    Science.gov (United States)

    Fidahić, Mahir; Dogan, Katarina; Sapunar, Damir; Puljak, Livia

    2015-01-01

    To analyze organization and therapeutic procedures administered in tertiary outpatient pain clinics in Croatia. Data about organization of pain clinics, its personnel, equipment, continuing medical education, therapeutic procedures, research activities and relations with pharmaceutical industry were collected using questionnaires. Twenty-two Croatian pain clinics were included in the study. Most of the pain clinics employ exclusively anesthesiologists and nurses. The most frequently prescribed therapeutic procedures in pain clinics were pharmacotherapy, transcutaneous electrical nerve stimulation, acupuncture and trigger point injections. Almost all pain clinics provide educational material for patients. Most of the pain clinics have regular interactions with pharmaceutical companies. Prescribing decisions were based mostly on information from scientific meetings, research articles and consultations with colleagues. Information sources which are considered to be the gold standard--the systematic reviews of The Cochrane Collaboration--were used less frequently (n=12; 57%) than advertising materials from pharmaceutical companies (n=16; 76%). Few physicians and other pain clinics staff had scientific degrees or academic titles or were involved in a research project. The national study about pain clinics in Croatia pointed out that there is room for improvement of their organization and services. Pain clinics should employ health-care professionals with diverse backgrounds. They should offer treatments backed by the highest-level of scientific evidence. Since pain is a major public health issue, pain clinic staff should engage more in research to contribute to the growing field of pain research, to enhance capacities for pain research in Croatia, to incorporate scientific evidence into their daily decision-making and to enable evidence-based practice. Copyright © 2015 by Academy of Sciences and Arts of Bosnia and Herzegovina.

  7. 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

  8. Target experimental area and systems of the Us national ignition facility

    International Nuclear Information System (INIS)

    Tobin, M.; Van Wonterghem, B.; MacGowan, B.J.; Hibbard, W.; Kalantar, D.; Lee, F.D.; Pittenger, L.; Wong, K.

    2000-01-01

    One of the major goals of the US National Ignition Facility is the demonstration of laser driven fusion ignition and burn of targets by inertial confinement and provide capability for a wide variety of high energy density physics experiments. The NIF target area houses the optical systems required to focus the 192 beamlets to a target precisely positioned at the center of the 10 meter diameter, 10-cm thick aluminum target chamber. The chamber serves as mounting surface for the 48 final optics assemblies, the target alignment and positioning equipment, and the target diagnostics. The internal surfaces of the chamber are protected by louvered steel beam dumps. The target area also provides the necessary shielding against target emission and environmental protection equipment. Despite its complexity, the design provides the flexibility to accommodate the needs of the various NIF user groups, such as direct and indirect drive irradiation geometries, modular final optics design, capability to handle cryogenic targets, and easily re-configurable diagnostic instruments. Efficient target area operations are ensured by using line-replaceable designs for systems requiring frequent inspection, maintenance and reconfiguration, such as the final optics, debris shields, phase plates and the diagnostic instruments. A precision diagnostic instrument manipulator (DIMS) allows fast removal and precise repositioning of diagnostic instruments. In addition we will describe several activities to enhance the target chamber availability, such as the target debris mitigation, the use of standard experimental configurations and the development of smart shot operations planning tools. (authors)

  9. Target experimental area and systems of the U.S. National Ignition Facility

    International Nuclear Information System (INIS)

    Tobin, M; Van Wonterghem, B; MacGowan, B J; Hibbard, W; Kalantar, D; Lee, F D; Pittenger, L; Wong, K

    1999-01-01

    One of the major goals of the US National Ignition Facility is the demonstration of laser driven fusion ignition and burn of targets by inertial confinement and provide capability for a wide variety of high energy density physics experiments. The NIF target area houses the optical systems required to focus the 192 beamlets to a target precisely positioned at the center of the 10 meter diameter, 10-cm thick aluminum target chamber. The chamber serves as mounting surface for the 48 final optics assemblies, the target alignment and positioning equipment, and the target diagnostics. The internal surfaces of the chamber are protected by louvered steel beam dumps. The target area also provides the necessary shielding against target emission and environmental protection equipment. Despite its complexity, the design provides the flexibility to accommodate the needs of the various NIF user groups, such as direct and indirect drive irradiation geometries, modular final optics design, capability to handle cryogenic targets, and easily re-configurable diagnostic instruments. Efficient target area operations are ensured by using line-replaceable designs for systems requiring frequent inspection, maintenance and reconfiguration, such as the final optics, debris shields, phase plates and the diagnostic instruments. A precision diagnostic instrument manipulator (DIMS) allows fast removal and precise repositioning of diagnostic instruments. In addition the authors describe several activities to enhance the target chamber availability, such as the target debris mitigation, the use of standard experimental configurations and the development of smart shot operations planning tools

  10. 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...

  11. An Overview of the Target Fabrication Operations at Lawrence Livermore National Laboratory

    International Nuclear Information System (INIS)

    Hibbard, R L; Bono, M J

    2005-01-01

    The Target Engineering team at Lawrence Livermore National Laboratory (LLNL) builds precision laser targets for the National Ignition Facility (NIF) and the Omega Laser in Rochester, NY, and other experimental facilities. The physics requirements demand precision in these targets, which creates a constant need for innovative manufacturing processes. As experimental diagnostics improve, there is greater demand for precision in fabrication, assembly, metrology, and documentation of as-built targets. The team specializes in meso-scale fabrication with core competencies in diamond turning, assembly, and metrology. Figure 1 shows a typical diamond turning center. The team builds over 200 laser targets per year in batches of five to fifteen targets. Thus, all are small-lot custom builds, and most are novel designs requiring engineering and process development. Component materials are metals, polymers and low density aerogel foams. Custom fixturing is used to locate parts on the Diamond Turning Machines (DTM) and assembly stations. This ensures parts can be repeatably located during manufacturing operations. Most target builds involve a series of fabricating one surface with features and then relocating the components on another fixture to finish the opposite side of the component. These components are then assembled to complete multiple-component targets. These targets are typically built one at a time. Cost and efficiency are issues with production of targets, and the team is developing batch processing techniques to meet precision target specifications and cost goals. Three example target builds will highlight some of the fabrication and material issues faced at LLNL. A low temperature Rayleigh Taylor target shows how multiple precision targets can be fabricated out of a single large disk. The ignition double shell targets highlight the required manufacturing complexity. A low density aerogel target highlights some material handling and assembly issues. The metrology

  12. X-ray emission from National Ignition Facility indirect drive targets

    International Nuclear Information System (INIS)

    Anderson, A.T.; Managan, R.A.; Tobin, M.T.; Peterson, P.F.

    1996-01-01

    We have performed a series of 1-D numerical simulations of the x-ray emission from National Ignition Facility (NIF) targets. Results are presented in terms of total x-ray energy, pulse length, and spectrum. Scaling of x-ray emissions is presented for variations in both target yield and hohlraum thickness. Experiments conducted on the Nova facility provide some validation of the computational tools and methods

  13. 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

  14. National Climate Policies: Aiming at the Factor 4 Target by 2050?

    International Nuclear Information System (INIS)

    Godard, Olivier

    2016-01-01

    The paper considers how the governments of midsize developed countries could define national strategies to control greenhouse gas emissions, assuming that such strategies are the product of cognitive and ethical choices relating to global climate scenarios and the rule for allocating shares of expected global climate damage to individual States. After evaluating the carbon value linked to each cognitive-ethical configuration, I identify the configurations that justify the target of dividing national emissions by 4 between 1990 and 2050 - a goal known as 'Factor 4'. Lastly, I examine the resulting constraints on the shape of the control trajectory leading to that target

  15. 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.

  16. 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.

  17. Inertial confinement fusion target insertion concepts for the National Ignition Facility

    International Nuclear Information System (INIS)

    Laughon, G.J.; Schultz, K.R.

    1996-01-01

    The National Ignition Facility (NIF) will be used to demonstrate fusion ignition in a laboratory environment in order to support development of inertial fusion as a potential fusion energy source for civilian use. However, target insertion must first be addressed before inertial fusion can become a practical energy source. Since target insertion systems currently utilized are not suitable for multiple shots in quick succession, insertion concepts involving free-falling and artificially accelerated targets are developed and evaluated against a set of predetermined guidelines. It is shown that a system involving a fast retraction positioner would be suitable. 5 refs., 4 figs

  18. A National Strategy to Develop Pragmatic Clinical Trials Infrastructure

    Science.gov (United States)

    Guise, Jeanne‐Marie; Dolor, Rowena J.; Meissner, Paul; Tunis, Sean; Krishnan, Jerry A.; Pace, Wilson D.; Saltz, Joel; Hersh, William R.; Michener, Lloyd; Carey, Timothy S.

    2014-01-01

    Abstract An important challenge in comparative effectiveness research is the lack of infrastructure to support pragmatic clinical trials, which compare interventions in usual practice settings and subjects. These trials present challenges that differ from those of classical efficacy trials, which are conducted under ideal circumstances, in patients selected for their suitability, and with highly controlled protocols. In 2012, we launched a 1‐year learning network to identify high‐priority pragmatic clinical trials and to deploy research infrastructure through the NIH Clinical and Translational Science Awards Consortium that could be used to launch and sustain them. The network and infrastructure were initiated as a learning ground and shared resource for investigators and communities interested in developing pragmatic clinical trials. We followed a three‐stage process of developing the network, prioritizing proposed trials, and implementing learning exercises that culminated in a 1‐day network meeting at the end of the year. The year‐long project resulted in five recommendations related to developing the network, enhancing community engagement, addressing regulatory challenges, advancing information technology, and developing research methods. The recommendations can be implemented within 24 months and are designed to lead toward a sustained national infrastructure for pragmatic trials. PMID:24472114

  19. Reengineering the National Clinical and Translational Research Enterprise: The Strategic Plan of the National Clinical and Translational Science Awards Consortium

    Science.gov (United States)

    Reis, Steven E.; Berglund, Lars; Bernard, Gordon R.; Califf, Robert M.; FitzGerald, Garret A.; Johnson, Peter C.

    2009-01-01

    Advances in human health require the efficient and rapid translation of scientific discoveries into effective clinical treatments; this process in turn depends upon observational data gathered from patients, communities, and public-health research that can be used to guide basic scientific investigation. Such bidirectional translational science, however, faces unprecedented challenges due to the rapid pace of scientific and technological development, as well as the difficulties of negotiating increasingly complex regulatory and commercial environments that overlap the research domain. Further, numerous barriers to translational science have emerged among the nation’s academic research centers, including basic structural and cultural impediments to innovation and collaboration, shortages of trained investigators, and inadequate funding. To address these serious and systemic problems, in 2006, the National Institutes of Health created the Clinical and Translational Science Awards (CTSA) program, which aims to catalyze the transformation of biomedical research at a national level, speeding the discovery and development of therapies, fostering collaboration, engaging communities, and training succeeding generations of clinical and translational researchers. The authors report in detail on the planning process, begun in 2008, that was used to engage stakeholders and to identify, refine, and ultimately implement the CTSA program’s overarching strategic goals. They also discuss the implications and likely impact of this strategic planning process as it is applied among the nation’s academic health centers. PMID:20182119

  20. Initiated chemical vapor deposited nanoadhesive for bonding National Ignition Facility's targets

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Tom [Univ. of California, Berkeley, CA (United States)

    2016-05-19

    Currently, the target fabrication scientists in National Ignition Facility Directorate at Lawrence Livermore National Laboratory (LLNL) is studying the propagation force resulted from laser impulses impacting a target. To best study this, they would like the adhesive used to glue the target substrates to be as thin as possible. The main objective of this research project is to create adhesive glue bonds for NIF’s targets that are ≤ 1 μm thick. Polyglycidylmethacrylate (PGMA) thin films were coated on various substrates using initiated chemical vapor deposition (iCVD). Film quality studies using white light interferometry reveal that the iCVD PGMA films were smooth. The coated substrates were bonded at 150 °C under vacuum, with low inflow of Nitrogen. Success in bonding most of NIF’s mock targets at thicknesses ≤ 1 μm indicates that our process is feasible in bonding the real targets. Key parameters that are required for successful bonding were concluded from the bonding results. They include inert bonding atmosphere, sufficient contact between the PGMA films, and smooth substrates. Average bond strength of 0.60 MPa was obtained from mechanical shearing tests. The bonding failure mode of the sheared interfaces was observed to be cohesive. Future work on this project will include reattempt to bond silica aerogel to iCVD PGMA coated substrates, stabilize carbon nanotube forests with iCVD PGMA coating, and kinetics study of PGMA thermal crosslinking.

  1. CFD analysis of a liquid mercury target for the National Spallation Neutron Source

    International Nuclear Information System (INIS)

    Wendel, M.W.; Tov, M.S.

    1997-01-01

    Computational fluid dynamics (CFD) is being used to analyze the design of the National Spallation Neutron Source (NSNS) target. The target is subjected to the neutronic (internal) heat generation that results from the proton collisions with the mercury nuclei. The liquid mercury simultaneously serves as the neutronic target medium, transports away the heat generated within itself, and cools the metallic target structure. Recirculation and stagnation zones within the target are of particular concern because of the likelihood that they will result in local hot spots. These zones exist because the most feasible target designs include a complete U-turn flow redirection. Although the primary concern is that the target is adequately cooled, the pressure drop from inlet to outlet must also be considered because pressure drop directly affects structural loading and required pumping power. Various design options have been considered in an effort to satisfy these design criteria. Significant improvements to the design have been recommended based on the results. Detailed results are presented for the current target design including a comparison with published pressure-drop data. Comparisons are also made with forced convection heat transfer data for liquid mercury flow in circular tubes

  2. Implementation of the Polarized HD target at the Thomas Jefferson National Accelerator Facility

    International Nuclear Information System (INIS)

    Chaden Djalali; David Tedeschi

    2007-01-01

    The original goal of this proposal was to study frozen spin polarized targets (HD target and other technologies) and produce a conceptual design report for the implementation of such a target in the HALL B detector of the Thomas Jefferson National Accelerator Facility (JLab). During the first two years of the proposal, we came to the conclusion that the best suited target for JLab was a frozen spin target and helped with the design of such a target. We have not only achieved our original goal but have exceeded it by being involved in the actual building and testing of parts the target. The main reason for this success has been the hiring of a senior research associate, Dr. Oleksandr Dzyubak, who had more than 10 years of experience in the field of frozen spin polarized targets. The current grant has allowed the USC nuclear physics group to strengthen its role in the JLab collaboration and make important contribution to both the detector development and the scientific program

  3. 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.

  4. 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

  5. Design of a deuterium and tritium-ablator shock ignition target for the National Ignition Facility

    International Nuclear Information System (INIS)

    Terry, Matthew R.; Perkins, L. John; Sepke, Scott M.

    2012-01-01

    Shock ignition presents a viable path to ignition and high gain on the National Ignition Facility (NIF). In this paper, we describe the development of the 1D design of 0.5 MJ class, all-deuterium and tritium (fuel and ablator) shock ignition target that should be reasonably robust to Rayleigh-Taylor fluid instabilities, mistiming, and hot electron preheat. The target assumes “day one” NIF hardware and produces a yield of 31 MJ with reasonable allowances for laser backscatter, absorption efficiency, and polar drive power variation. The energetics of polar drive laser absorption require a beam configuration with half of the NIF quads dedicated to launching the ignitor shock, while the remaining quads drive the target compression. Hydrodynamic scaling of the target suggests that gains of 75 and yields 70 MJ may be possible.

  6. The physics basis for ignition using indirect-drive targets on the National Ignition Facility

    International Nuclear Information System (INIS)

    Lindl, John D.; Amendt, Peter; Berger, Richard L.; Glendinning, S. Gail; Glenzer, Siegfried H.; Haan, Steven W.; Kauffman, Robert L.; Landen, Otto L.; Suter, Laurence J.

    2004-01-01

    The 1990 National Academy of Science final report of its review of the Inertial Confinement Fusion Program recommended completion of a series of target physics objectives on the 10-beam Nova laser at the Lawrence Livermore National Laboratory as the highest-priority prerequisite for proceeding with construction of an ignition-scale laser facility, now called the National Ignition Facility (NIF). These objectives were chosen to demonstrate that there was sufficient understanding of the physics of ignition targets that the laser requirements for laboratory ignition could be accurately specified. This research on Nova, as well as additional research on the Omega laser at the University of Rochester, is the subject of this review. The objectives of the U.S. indirect-drive target physics program have been to experimentally demonstrate and predictively model hohlraum characteristics, as well as capsule performance in targets that have been scaled in key physics variables from NIF targets. To address the hohlraum and hydrodynamic constraints on indirect-drive ignition, the target physics program was divided into the Hohlraum and Laser-Plasma Physics (HLP) program and the Hydrodynamically Equivalent Physics (HEP) program. The HLP program addresses laser-plasma coupling, x-ray generation and transport, and the development of energy-efficient hohlraums that provide the appropriate spectral, temporal, and spatial x-ray drive. The HEP experiments address the issues of hydrodynamic instability and mix, as well as the effects of flux asymmetry on capsules that are scaled as closely as possible to ignition capsules (hydrodynamic equivalence). The HEP program also addresses other capsule physics issues associated with ignition, such as energy gain and energy loss to the fuel during implosion in the absence of alpha-particle deposition. The results from the Nova and Omega experiments approach the NIF requirements for most of the important ignition capsule parameters, including

  7. Impact of the national targeted Hepatitis A immunisation program in Australia: 2000-2014.

    Science.gov (United States)

    Thompson, Craig; Dey, Aditi; Fearnley, Emily; Polkinghorne, Benjamin; Beard, Frank

    2017-01-03

    In November 2005, hepatitis A vaccine was funded under the Australian National Immunisation Program for Aboriginal and Torres Strait Islander (Indigenous) children aged 12-24months in the targeted jurisdictions of Queensland, South Australia, Western Australia and the Northern Territory. We reviewed the epidemiology of hepatitis A from 2000 to 2014 using data from the Australian National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and Australian Bureau of Statistics causes-of-death data. The impact of the national hepatitis A immunisation program was assessed by comparison of pre-vaccine (2000-2005) and post-vaccine time periods (2006-2014), by age group, Indigenous status and jurisdiction using incidence rate ratios (IRR) per 100,000 population and 95% confidence intervals (CI). The national pre-vaccine notification rate in Indigenous people was four times higher than the non-Indigenous rate, and declined from 8.41 per 100,000 (95% CI 5.03-11.79) pre-vaccine to 0.85 per 100,000 (95% CI 0.00-1.99) post-vaccine, becoming similar to the non-Indigenous rate. Notification and hospitalisation rates in Indigenous children aged <5years from targeted jurisdictions declined in the post-vaccine period when compared to the pre-vaccine period (notifications: IRR=0.07; 95% CI 0.04-0.13; hospitalisations: IRR=0.04; 95% CI 0.01-0.16). As did notification rates in Indigenous people aged 5-19 (IRR=0.08; 95% CI 0.05-0.13) and 20-49years (IRR=0.06; 95% CI 0.02-0.15) in targeted jurisdictions. For non-Indigenous people from targeted jurisdictions, notification rates decreased significantly in children aged <5years (IRR 0.47; 95% CI 0.31-0.71), and significantly more overall (IRR=0.43; 95% CI 0.39-0.47) compared to non-Indigenous people from non-targeted jurisdictions (IRR=0.60; 95% CI 0.56-0.64). The national hepatitis A immunisation program has had a significant impact in the targeted population with relatively modest vaccine coverage, with

  8. 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 (...

  9. Targets and criteria for the effective participation of national industry in a domestic nuclear power programme

    International Nuclear Information System (INIS)

    Py, J.P.

    1986-01-01

    The interest in maximum use of national resource is common to all countries, the highly industrialized as well as the developing ones. Although benefits can be expected from national participation in a domestic nuclear power programme and may not be limited to this programme, such national participation is restricted by constraining factors: economic, financial, technical and political. Considering the various natures of activities - design, procurement, manufacturing, erection -, their technical difficulties, their potential spin-off effects on the overall industrial development of a country, the paper reviews the materials and components of a nuclear power plants which can be selected as targets for domestic production. The paper also reviews criteria which must be considered in setting these Target materials and components in order to overcome restricting factors to national participation such as cost of national products, financing, investment capability, adequate market size, availability of qualified manpower, industrial capability and quality standards, availability of technology and know-how, conflicts of interests. Some concrete examples drawn from previous experience will illustrate France efforts to overcome these limiting factors [fr

  10. 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

  11. Evaluation of Australian soup manufacturer compliance with national sodium reduction targets.

    Science.gov (United States)

    Levi, Rebecca; Probst, Yasmine; Crino, Michelle; Dunford, Elizabeth

    2018-04-01

    Packaged foods dominate Australia's food supply and are important contributors to nutrition-related disease. To help address this problem, the Food and Health Dialogue (FHD) was launched in 2009, setting voluntary sodium reduction targets for various categories of packaged foods. The aim of this study was to examine the food industry's progress and compliance with the FHD sodium reduction targets for soup products. Nutritional information was collected from product labels of all soup products available from four major Australian supermarkets annually between 2011 and 2014. Products were assigned to categories in line with those in the FHD. The proportion of soup products meeting sodium reduction targets was examined by (i) soup category; (ii) FHD participant status; and (iii) manufacturer. A 6% reduction in sodium levels in soups overall was found from 2011 to 2014 (P = 0.002). Significant reductions were observed for FHD participants (P < 0.05 for all) but not for non-participants. In 2014, 67% dry soups and 76% of wet soups met national sodium reduction targets. Despite the majority of soup products meeting the sodium reduction targets specified by the FHD, re-evaluation of the targets may be required to further reduce sodium levels in soups. Manufacturers participating in the FHD are likely to be driving sodium reductions in the Australian soup market, further highlighting the need for continued government leadership in this area to ensure all manufacturers are actively involved in the process. © 2017 Dietitians Association of Australia.

  12. Characterization of third-harmonic target plan irradiance on the National Ignition Facility Beamlet demonstration project

    International Nuclear Information System (INIS)

    Wegner, P.J.; Van Wonterghem, B.M.; Dixit, S.N.; Henesian, M.A.; Barker, C.E.; Thompson, C.E.; Seppala, L.G.; Caird, J.A.

    1997-01-01

    The Beamlet laser is a single-aperture prototype for the National Ignition Facility (NIF). We have recently installed and activated a 55 m 3 vacuum vessel and associated diagnostic package at the output of the Beamlet that we are using to characterize target plane irradiance at high power. Measurements obtained both with and without a kinoform diffractive optic are reported. Dependences on critical laser parameters including output power, spatial filtering, and wavefront correction are discussed and compared with simulations

  13. Los Alamos contribution to target diagnostics on the National Ignition Facility

    International Nuclear Information System (INIS)

    Mack, J.M.; Baker, D.A.; Caldwell, S.E.

    1994-01-01

    The National Ignition Facility (NIF) will have a large suite of sophisticated target diagnostics. This will allow thoroughly diagnosed experiments to be performed both at the ignition and pre-ignition levels. As part of the national effort Los Alamos National Laboratory will design, construct and implement a number of diagnostics for the NIF. This paper describes Los Alamos contributions to the ''phase I diagnostics.'' Phase I represents the most fundamental and basic measurement systems that will form the core for most work on the NIF. The Los Alamos effort falls into four categories: moderate to hard X-ray (time resolved imaging neutron spectroscopy- primarily with neutron time of flight devices; burn diagnostics utilizing gamma ray measurements; testing measurement concepts on the TRIDENT laser system at Los Alamos. Because of the high blast, debris and radiation environment, the design of high resolution X-ray imaging systems present significant challenges. Systems with close target proximity require special protection and methods for such protection is described. The system design specifications based on expected target performance parameters is also described. Diagnosis of nuclear yield and burn will be crucial to the NIF operation. Nuclear reaction diagnosis utilizing both neutron and gamma ray detection is discussed. The Los Alamos TRIDENT laser system will be used extensively for the development of new measurement concepts and diagnostic instrumentation. Some its potential roles in the development of diagnostics for NIF are given

  14. Los Alamos contribution to target diagnostics on the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Mack, J.M.; Baker, D.A.; Caldwell, S.E. [and others

    1994-07-01

    The National Ignition Facility (NIF) will have a large suite of sophisticated target diagnostics. This will allow thoroughly diagnosed experiments to be performed both at the ignition and pre-ignition levels. As part of the national effort Los Alamos National Laboratory will design, construct and implement a number of diagnostics for the NIF. This paper describes Los Alamos contributions to the ``phase I diagnostics.`` Phase I represents the most fundamental and basic measurement systems that will form the core for most work on the NIF. The Los Alamos effort falls into four categories: moderate to hard X-ray (time resolved imaging neutron spectroscopy- primarily with neutron time of flight devices; burn diagnostics utilizing gamma ray measurements; testing measurement concepts on the TRIDENT laser system at Los Alamos. Because of the high blast, debris and radiation environment, the design of high resolution X-ray imaging systems present significant challenges. Systems with close target proximity require special protection and methods for such protection is described. The system design specifications based on expected target performance parameters is also described. Diagnosis of nuclear yield and burn will be crucial to the NIF operation. Nuclear reaction diagnosis utilizing both neutron and gamma ray detection is discussed. The Los Alamos TRIDENT laser system will be used extensively for the development of new measurement concepts and diagnostic instrumentation. Some its potential roles in the development of diagnostics for NIF are given.

  15. 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.

  16. 7 CFR 3402.4 - Food and agricultural sciences areas targeted for National Needs Graduate and Postdoctoral...

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Food and agricultural sciences areas targeted for..., AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS... sciences areas targeted for National Needs Graduate and Postdoctoral Fellowship Grants Program support...

  17. 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.

  18. Raising Public Awareness of Clinical Trials: Development of Messages for a National Health Communication Campaign.

    Science.gov (United States)

    Massett, Holly A; Dilts, David M; Bailey, Robert; Berktold, Jennifer; Ledsky, Rebecca; Atkinson, Nancy L; Mishkin, Grace; Denicoff, Andrea; Padberg, Rose Mary; Allen, Marin P; Silver, Karen; Carrington, Kelli; Johnson, Lenora E

    2017-05-01

    Clinical trials are essential for developing new and effective treatments and improving patient quality of life; however, many trials cannot answer their primary research questions because they fall short of their recruitment goals. This article reports the results of formative research conducted in two populations, the public and primary care physicians, to identify messages that may raise awareness and increase interest in clinical trials and be used in a national communication campaign. Results suggested that participants were primarily motivated to participate in clinical trials out of a self-interest to help themselves first. Messages illustrated that current treatments were tested via clinical trials, helped normalize trials as routine practices, and reduced concerns over trying something new first. Participants wanted messages that portray trials as state-of-the-art choices that offer some hope, show people like themselves, and are described in a clear, concise manner with actionable steps for them to take. The study revealed some differences in message salience, with healthy audiences exhibiting lower levels of interest. Our results suggest that targeted messages are needed, and that communication with primary health-care providers is an important and necessary component in raising patient awareness of the importance of clinical trials.

  19. 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

  20. 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

  1. 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.

  2. A Criticality Safety Study on Storing Unirradiated Cintichem-Type Targets at Sandia National Laboratories

    International Nuclear Information System (INIS)

    Romero, D.J.; Parma, E.J.; Busch, R.D.

    1999-01-01

    This criticality safety analysis is performed to determine the effective multiplication factor (k eff ) for a storage cabinet filled with unirradiated Cintichem-type targets. These targets will be used to produce 99 Mo at Sandia National Laboratories and will be stored on-site prior to irradiation in the Annular Core Research Reactor. The analysis consisted of using the Monte Carlo code MCNP (Version 4A) to model and predict the k eff for the proposed dry storage configuration under credible loss of geometry and moderator control. Effects of target pitch, non-uniform loading, and target internal/external flooding are evaluated. Further studies were done with deterministic methods to verify the results obtained from MCNP and to obtain a clearer understanding of the parameters affecting system criticality. The diffusion accelerated neutral particle transport code ONEDANT was used to model the target in a one-dimensional, infinite half-slab geometry and determine the critical slab thickness. Hand calculations were also completed to determine the critical slab thickness with modified one-group, and one-group, two region approximations. Results obtained from ONEDANT and the hand calculations were compared to applicable cases in a commonly used criticality safety analysis handbook. Overall, the critical slab thicknesses obtained in the deterministic analysis were much larger than the dimensions of the cabinet and further support the predictions by MCNP that a critical system cannot be attained for the base case or in conditions where loss of geometry and moderation control occur

  3. 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...

  4. 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.

  5. 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.

  6. Reducing US cardiovascular disease burden and disparities through national and targeted dietary policies: A modelling study.

    Directory of Open Access Journals (Sweden)

    Jonathan Pearson-Stuttard

    2017-06-01

    Full Text Available Large socio-economic disparities exist in US dietary habits and cardiovascular disease (CVD mortality. While economic incentives have demonstrated success in improving dietary choices, the quantitative impact of different dietary policies on CVD disparities is not well established. We aimed to quantify and compare the potential effects on total CVD mortality and disparities of specific dietary policies to increase fruit and vegetable (F&V consumption and reduce sugar-sweetened beverage (SSB consumption in the US.Using the US IMPACT Food Policy Model and probabilistic sensitivity analyses, we estimated and compared the reductions in CVD mortality and socio-economic disparities in the US population potentially achievable from 2015 to 2030 with specific dietary policy scenarios: (a a national mass media campaign (MMC aimed to increase consumption of F&Vs and reduce consumption of SSBs, (b a national fiscal policy to tax SSBs to increase prices by 10%, (c a national fiscal policy to subsidise F&Vs to reduce prices by 10%, and (d a targeted policy to subsidise F&Vs to reduce prices by 30% among Supplemental Nutrition Assistance Program (SNAP participants only. We also evaluated a combined policy approach, combining all of the above policies. Data sources included the Surveillance, Epidemiology, and End Results Program, National Vital Statistics System, National Health and Nutrition Examination Survey, and published meta-analyses. Among the individual policy scenarios, a national 10% F&V subsidy was projected to be most beneficial, potentially resulting in approximately 150,500 (95% uncertainty interval [UI] 141,400-158,500 CVD deaths prevented or postponed (DPPs by 2030 in the US. This far exceeds the approximately 35,100 (95% UI 31,700-37,500 DPPs potentially attributable to a 30% F&V subsidy targeting SNAP participants, the approximately 25,800 (95% UI 24,300-28,500 DPPs for a 1-y MMC, or the approximately 31,000 (95% UI 26,800-35,300 DPPs for a 10

  7. 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.

  8. 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.

  9. Developing clinical practice guidelines: target audiences, identifying topics for guidelines, guideline group composition and functioning and conflicts of interest.

    Science.gov (United States)

    Eccles, Martin P; Grimshaw, Jeremy M; Shekelle, Paul; Schünemann, Holger J; Woolf, Steven

    2012-07-04

    Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the target audience(s) for guidelines and their use of guidelines; identifying topics for guidelines; guideline group composition (including consumer involvement) and the processes by which guideline groups function and the important procedural issue of managing conflicts of interest in guideline development.

  10. Perception survey on the introduction of clinical performance examination as part of the national nursing licensing examination in Korea

    Directory of Open Access Journals (Sweden)

    Su Jin Shin

    2017-10-01

    Full Text Available Purpose The purpose of this study was to analyze opinions about the action plan for implementation of clinical performance exam as part of the national nursing licensing examination and presents the expected effects of the performance exam and aspects to consider regarding its implementation. Methods This study used a mixed-methods design. Quantitative data were collected by a questionnaire survey, while qualitative data were collected by focus group interviews with experts. The survey targeted 200 nursing professors and clinical nurses with more than 5 years of work experience, and the focus group interviews were conducted with 28 of professors, clinical instructors, and nurses at hospitals. Results First, nursing professors and clinical specialists agreed that the current written tests have limitations in evaluating examinees’ ability, and that the introduction of a clinical performance exam will yield positive results. Clinical performance exam is necessary to evaluate and improve nurses’ work ability, which means that the implementation of a performance exam is advisable if its credibility and validity can be verified. Second, most respondents chose direct performance exams using simulators or standardized patients as the most suitable format of the test. Conclusion In conclusion, the current national nursing licensing exam is somewhat limited in its ability to identify competent nurses. Thus, the time has come for us to seriously consider the introduction of a performance exam. The prerequisites for successfully implementing clinical performance exam as part of the national nursing licensing exam are a professional training process and forming a consortium to standardize practical training.

  11. An evaluation on the impact of national cancer wait targets on a (UK) radiotherapy department

    International Nuclear Information System (INIS)

    Roberts, Neill

    2012-01-01

    The radiotherapy department in this evaluation has been working towards full compliance with national cancer wait targets (CWT) since their implementation. 31 and 62 day targets set a maximum time frame for cancer patients to commence treatment. This evaluation explored the impact of these targets on staff and patients within the radiotherapy department and their overall impact on the radiotherapy service. Methods: This evaluation followed a mixed method approach of sequential triangulation. Qualitative data collection and analysis dominate findings but existing quantitative data, available within the department, was used to support the overall findings. Staff and patient interviews were used to establish attitudes to and experiences of the CWT initiative in relation to radiotherapy treatment. Quantitative data was taken from the local Cancer Centre CWT database that tracks patients referred for radiotherapy. Findings and Conclusion: Qualitative data analysis identified four main themes: pressure, appropriateness of target lengths, quality of treatment provided and efficiency of working practices within the department. Responses within these themes were both positive and negative with patients mainly the former and staff the latter. Quantitative evaluation found an increased monitoring and management burden from the CWT initiative, primarily for administrative, clerical and managerial staff. The main impact of the CWT initiative was an increase in pressure on staff due to reduced time to prepare and deliver treatment. Patients felt the initiative had not impacted negatively on their care and experienced a reduction in anxiety due to a reduction in waiting time.

  12. Conceptual design of low activation target chamber and components for the National Ignition Facility

    International Nuclear Information System (INIS)

    Streckert, H.H.; Schultz, K.R.; Sager, G.T.; Kantner, R.D.

    1996-01-01

    The baseline design for the target chamber and chamber components for the National Ignition Facility (NIF) consists of aluminum alloy structural material. Low activation composite chamber and components have important advantages including enhanced environmental and safety characteristics and improved accessibility due to reduced neutron-induced radioactivity. A low activation chamber can be fabricated from carbon fiber reinforced epoxy using thick wall laminate technology similar to submarine bow dome fabrication for the U.S. Navy. A risk assessment analysis indicates that a composite chamber has a reasonably high probability of success, but that an aluminum alloy chamber represents a lower risk. Use of low activation composite materials for several chamber components such as the final optics assemblies, the target positioner and inserter, the diagnostics manipulator tubes, and the optics beam tubes would offer an opportunity to make significant reductions in post-shot radiation dose rate with smaller, less immediate impact on the NIF design. 7 refs., 3 figs

  13. Subsidies to target specialist outreach services into more remote locations: a national cross-sectional study.

    Science.gov (United States)

    O'Sullivan, Belinda G; McGrail, Matthew R; Stoelwinder, Johannes U

    2017-07-01

    Objective Targeting rural outreach services to areas of highest relative need is challenging because of the higher costs it imposes on health workers to travel longer distances. This paper studied whether subsidies have the potential to support the provision of specialist outreach services into more remote locations. Methods National data about subsidies for medical specialist outreach providers as part of the Wave 7 Medicine in Australia: Balancing Employment and Life (MABEL) Survey in 2014. Results Nearly half received subsidies: 19% (n=110) from a formal policy, namely the Australian Government Rural Health Outreach Fund (RHOF), and 27% (n=154) from other sources. Subsidised specialists travelled for longer and visited more remote locations relative to the non-subsidised group. In addition, compared with non-subsidised specialists, RHOF-subsidised specialists worked in priority areas and provided equally regular services they intended to continue, despite visiting more remote locations. Conclusion This suggests the RHOF, although limited to one in five specialist outreach providers, is important to increase targeted and stable outreach services in areas of highest relative need. Other subsidies also play a role in facilitating remote service distribution, but may need to be more structured to promote regular, sustained outreach practice. What is known about this topic? There are no studies describing subsidies for specialist doctors to undertake rural outreach work and whether subsidies, including formal and structured subsidies via the Australian Government RHOF, support targeted outreach services compared with no financial support. What does this paper add? Using national data from Australia, we describe subsidisation among specialist outreach providers and show that specialists subsidised via the RHOF or another source are more likely to provide remote outreach services. What are the implications for practitioners? Subsidised specialist outreach providers are

  14. 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.

  15. 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

  16. 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:

  17. Why providers participate in clinical trials: considering the National Cancer Institute's Community Clinical Oncology Program.

    Science.gov (United States)

    McAlearney, Ann Scheck; Song, Paula H; Reiter, Kristin L

    2012-11-01

    The translation of research evidence into practice is facilitated by clinical trials such as those sponsored by the National Cancer Institute's Community Clinical Oncology Program (CCOP) that help disseminate cancer care innovations to community-based physicians and provider organizations. However, CCOP participation involves unsubsidized costs and organizational challenges that raise concerns about sustained provider participation in clinical trials. This study was designed to improve our understanding of why providers participate in the CCOP in order to inform the decision-making process of administrators, clinicians, organizations, and policy-makers considering CCOP participation. We conducted a multi-site qualitative study of five provider organizations engaged with the CCOP. We interviewed 41 administrative and clinician key informants, asking about what motivated CCOP participation, and what benefits they associated with involvement. We deductively and inductively analyzed verbatim interview transcripts, and explored themes that emerged. Interviewees expressed both "altruistic" and "self-interested" motives for CCOP participation. Altruistic reasons included a desire to increase access to clinical trials and feeling an obligation to patients. Self-interested reasons included the desire to enhance reputation, and a need to integrate disparate cancer care activities. Perceived benefits largely matched expressed motives for CCOP participation, and included internal and external benefits to the organization, and quality of care benefits for both patients and participating physicians. The motives and benefits providers attributed to CCOP participation are consistent with translational research goals, offering evidence that participation can contribute value to providers by expanding access to innovative medical care for patients in need. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. National Institutes of Health Clinical Alerts and Advisories

    Science.gov (United States)

    ... 22, 2004 NHLBI Stops Study Testing How Long Children with Sickle Cell Anemia Should Have Blood Transfusions to Prevent Stroke National ... 8, 2000 Periodic Transfusions Lower Stroke Risk in Children with Sickle Cell Anemia National Heart, Lung, and Blood Institute (NHLBI) September ...

  19. 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

  20. Comprehensive target populations for current active safety systems using national crash databases.

    Science.gov (United States)

    Kusano, Kristofer D; Gabler, Hampton C

    2014-01-01

    The objective of active safety systems is to prevent or mitigate collisions. A critical component in the design of active safety systems is the identification of the target population for a proposed system. The target population for an active safety system is that set of crashes that a proposed system could prevent or mitigate. Target crashes have scenarios in which the sensors and algorithms would likely activate. For example, the rear-end crash scenario, where the front of one vehicle contacts another vehicle traveling in the same direction and in the same lane as the striking vehicle, is one scenario for which forward collision warning (FCW) would be most effective in mitigating or preventing. This article presents a novel set of precrash scenarios based on coded variables from NHTSA's nationally representative crash databases in the United States. Using 4 databases (National Automotive Sampling System-General Estimates System [NASS-GES], NASS Crashworthiness Data System [NASS-CDS], Fatality Analysis Reporting System [FARS], and National Motor Vehicle Crash Causation Survey [NMVCCS]) the scenarios developed in this study can be used to quantify the number of police-reported crashes, seriously injured occupants, and fatalities that are applicable to proposed active safety systems. In this article, we use the precrash scenarios to identify the target populations for FCW, pedestrian crash avoidance systems (PCAS), lane departure warning (LDW), and vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) systems. Crash scenarios were derived using precrash variables (critical event, accident type, precrash movement) present in all 4 data sources. This study found that these active safety systems could potentially mitigate approximately 1 in 5 of all severity and serious injury crashes in the United States and 26 percent of fatal crashes. Annually, this corresponds to 1.2 million all severity, 14,353 serious injury (MAIS 3+), and 7412 fatal crashes. In addition

  1. A survey of differentiation methods for national greenhouse gas reduction targets

    Energy Technology Data Exchange (ETDEWEB)

    Torvanger, Asbjoern; Godal, Odd

    1999-11-01

    The aim of the report is to contribute to exploring the potential differentiation methods for national greenhouse gas reduction targets. The Kyoto Protocol to the United Nations Framework Convention on Climate Change (UNFCCC) from 1997 established differentiation of targets among countries. A more systematic approach to differentiation would facilitate future negotiations. Three sources of methods or proposals are employed. The first are proposals from the Ad Hoc Group on the Berlin Mandate (AGBM) process from 1995 until the Kyoto Protocol was adopted in December 1997, in all 17 proposals were selected. The second source is the EU`s Triptique approach for differentiation of targets among its member states. The third source is recent academic literature where 8 contributions from the period 1992 to 1998 were included. The proposals are presented in a catalogue style. Based on 4 criteria on the usefulness of proposals or methods for future negotiations we have chosen 5 proposals, a Japanese, French, Norwegian, Brazilian in addition to the EU`s Triptique approach. Some numerical illustrations for the Baltic Sea region are presented. Given the joint Kyoto Protocol reduction target for the region we compare the burden sharing consequences for the proposals. For illustrations we employ the following fairness principles as differentiation methods: 1) The Sovereignty principle. 2) The Egalitarian principle. 3) The Ability to Pay principle. With the aim to evaluate the political feasibility of the various differentiation methods we compare the results across the countries in the Baltic Sea region and divide them into OECD and EIT countries. The outcome of the Kyoto Protocol is interpreted as an example of a politically feasible differentiation scheme. On the basis of the observations we find principles 1) and 2) less interesting. A ranking of the differentiation methods according to political feasibility is made and discussed. Among the countries in the Baltic Sea region

  2. [Clinical governance and patient safety culture in clinical laboratories in the Spanish National Health System].

    Science.gov (United States)

    Giménez-Marín, Á; Rivas-Ruiz, F

    To conduct a situational analysis of patient safety culture in public laboratories in the Spanish National Health System and to determine the clinical governance variables that most strongly influence patient safety. A descriptive cross-sectional study was carried out, in which a Survey of Patient Safety in Clinical Laboratories was addressed to workers in 26 participating laboratories. In this survey, which consisted of 45 items grouped into 6 areas, scores were assigned on a scale from 0 to 100 (where 0 is the lowest perception of patient safety). Laboratory managers were asked specific questions about quality management systems and technology. The mean scores for the 26 participating hospitals were evaluated, and the following results observed: in 4of the 6areas, the mean score was higher than 70 points. In the third area (equipment and resources) and the fourth area (working conditions), the scores were lower than 60 points. Every hospital had a digital medical record system. This 100% level of provision was followed by that of an electronic request management system, which was implemented in 82.6% of the hospitals. The results obtained show that the culture of security is homogeneous and of high quality in health service laboratories, probably due to the steady improvement observed. However, in terms of clinical governance, there is still some way to go, as shown by the presence of weaknesses in crucial dimensions of safety culture, together with variable levels of implementation of fail-safe technologies and quality management systems. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Optimized beryllium target design for indirectly driven inertial confinement fusion experiments on the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Simakov, Andrei N., E-mail: simakov@lanl.gov; Wilson, Douglas C.; Yi, Sunghwan A.; Kline, John L.; Batha, Steven H. [Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, New Mexico 87545 (United States); Clark, Daniel S.; Milovich, Jose L.; Salmonson, Jay D. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94551 (United States)

    2014-02-15

    For indirect drive inertial confinement fusion, Beryllium (Be) ablators offer a number of important advantages as compared with other ablator materials, e.g., plastic and high density carbon. In particular, the low opacity and relatively high density of Be lead to higher rocket efficiencies giving a higher fuel implosion velocity for a given X-ray drive; and to higher ablation velocities providing more ablative stabilization and reducing the effect of hydrodynamic instabilities on the implosion performance. Be ablator advantages provide a larger target design optimization space and can significantly improve the National Ignition Facility (NIF) [J. D. Lindl et al., Phys. Plasmas 11, 339 (2004)] ignition margin. Herein, we summarize the Be advantages, briefly review NIF Be target history, and present a modern, optimized, low adiabat, Revision 6 NIF Be target design. This design takes advantage of knowledge gained from recent NIF experiments, including more realistic levels of laser-plasma energy backscatter, degraded hohlraum-capsule coupling, and the presence of cross-beam energy transfer.

  4. 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

  5. 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.

  6. Polyimide capsules may hold high pressure DT fuel without cryogenic support for the National Ignition Facility indirect-drive targets

    International Nuclear Information System (INIS)

    Sanchez, J.J.; Letts, S.A.

    1997-01-01

    New target designs for the Omega upgrade laser and ignition targets in the National Ignition Facility (NIF) require thick (80 - 100 microm) cryogenic fuel layers. The Omega upgrade target will require cryogenic handling after initial fill because of the high fill pressures and the thin capsule walls. For the NIF indirectly driven targets, a larger capsule size and new materials offer hope that they can be built, filled and stored in a manner similar to the targets used in the Nova facility without requiring cryogenic handling

  7. The National Health Insurance, the decentralised clinical training ...

    African Journals Online (AJOL)

    studies, particularly those from Australia, Canada, and SA.[1-6] ... Gluckman's principles; therefore it is imperative to keep these in the forefront .... Digby A. Evidence, encounters and effects of South Africa's reforming Gluckman National Health.

  8. Automated alignment of the Advanced Radiographic Capability (ARC) target area at the National Ignition Facility

    Science.gov (United States)

    Roberts, Randy S.; Awwal, Abdul A. S.; Bliss, Erlan S.; Heebner, John E.; Leach, Richard R.; Orth, Charles D.; Rushford, Michael C.; Lowe-Webb, Roger R.; Wilhelmsen, Karl C.

    2015-09-01

    The Advanced Radiographic Capability (ARC) at the National Ignition Facility (NIF) is a petawatt-class, short-pulse laser system designed to provide x-ray backlighting of NIF targets. ARC uses four NIF beamlines to produce eight beamlets to create a sequence of eight images of an imploding fuel capsule using backlighting targets and diagnostic instrumentation. ARC employs a front end that produces two pulses, chirps the pulses out to 2 ns, and then injects the pulses into the two halves of each of four NIF beamlines. These pulses are amplified by NIF pre- and main amplifiers and transported to compressor vessels located in the NIF target area. The pulses are then compressed and pointed into the NIF target chamber where they impinge upon an array of backlighters. The interaction of the ARC laser pulses and the backlighting material produces bursts of high-energy x-rays that illuminate an imploding fuel capsule. The transmitted x-rays are imaged by diagnostic instrumentation to produce a sequence of radiograph images. A key component of the success of ARC is the automatic alignment system that accomplishes the precise alignment of the beamlets to avoid damaging equipment and to ensure that the beamlets are directed onto the tens-of-microns scale backlighters. In this paper, we describe the ARC automatic alignment system, with emphasis on control loops used to align the beampaths. We also provide a detailed discussion of the alignment image processing, because it plays a critical role in providing beam centering and pointing information for the control loops.

  9. The "Conveyor Belt Effect": A Re-Assessment of the Impact of National Targets for Lifelong Learning.

    Science.gov (United States)

    Gorard, Stephen; Selwyn, Neil; Rees, Gareth

    Although the National Targets for Education and Training in England and Wales include indicators for lifelong learning, and the progress towards the targets set for these indicators has been lauded by politicians and other observers, much of this apparent progress is actually accounted for by changes in these same indicators. However, once the…

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. Z-pinch driven inertial confinement fusion target physics research at Sandia National Laboratories

    International Nuclear Information System (INIS)

    Leeper, R.J.; Alberts, T.E.; Asay, J.R.

    2001-01-01

    Three hohlraum concepts are being pursued at Sandia National Laboratories (SNL) to investigate the possibility of using pulsed power driven magnetic implosions (z-pinches) to drive high gain targets capable of yields in the range of 200-1000 MJ. This research is being conducted on SNL's Z facility that is capable of driving peak currents of 20 MA in z-pinch loads producing implosion velocities as high as 7.5x10 7 cm/s, x-ray energies approaching 2 MJ, and x-ray powers exceeding 200 TW. This paper will discuss each of these hohlraum concepts and will overview the experiments that have been conducted on these systems to date. (author)

  16. 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.

  17. Radiation effects on active camera electronics in the target chamber at the National Ignition Facility

    Science.gov (United States)

    Dayton, M.; Datte, P.; Carpenter, A.; Eckart, M.; Manuel, A.; Khater, H.; Hargrove, D.; Bell, P.

    2017-08-01

    The National Ignition Facility's (NIF) harsh radiation environment can cause electronics to malfunction during high-yield DT shots. Until now there has been little experience fielding electronic-based cameras in the target chamber under these conditions; hence, the performance of electronic components in NIF's radiation environment was unknown. It is possible to purchase radiation tolerant devices, however, they are usually qualified for radiation environments different to NIF, such as space flight or nuclear reactors. This paper presents the results from a series of online experiments that used two different prototype camera systems built from non-radiation hardened components and one commercially available camera that permanently failed at relatively low total integrated dose. The custom design built in Livermore endured a 5 × 1015 neutron shot without upset, while the other custom design upset at 2 × 1014 neutrons. These results agreed with offline testing done with a flash x-ray source and a 14 MeV neutron source, which suggested a methodology for developing and qualifying electronic systems for NIF. Further work will likely lead to the use of embedded electronic systems in the target chamber during high-yield shots.

  18. Isotope materials availability and services for target production at the Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    Ratledge, J.E.; Dahl, T.L.; Ottinger, C.L.; Aaron, W.S.; Adair, H.L.

    1987-01-01

    Materials available through the Isotope Distribution Program include separated stable isotopes, byproduct radioisotopes, and research quantities of source and special nuclear materials. Isotope products are routinely available in the forms listed in the product description section of the Isotopes Products and Services Catalog distributed by the Oak Ridge National Laboratory (ORNL). Different forms can be provided in some cases, usually at additional cost. Routinely available services include cyclotron target irradiations, fabrication of special physical forms, source encapsulation, ion implantation, and special purifications. Materials and services that are not offered as part of the routine distribution program may be made available from commercial sources in the United States. Specific forms of isotopic research materials include thin films and foils for use as accelerator targets, metal or other compounds in the form of bars or wires, and metal foils. Methods of fabrication include evaporation, sputtering, rolling, electrolytic deposition, pressing, sintering, and casting. High-purity metal forms of plutonium, americium, and curium are prepared by vacuum reduction/distillation. Both fissionable and nonfissionable neutron dosimeters are prepared for determining the neutron energy spectra, flux, and fluence at various locations within a reactor. Details on what materials are available and how the materials and related services can be obtained from ORNL are described. (orig.)

  19. 2010 national progress report on R and D on LEU fuel and target technology in Argentina

    International Nuclear Information System (INIS)

    Balart, S.; Blaumann, H.; Cristini, P.; Gonzalez, A.G.; Gonzalez, R.; Hermida, J.D.; Lopez, M.; Mirandou, M.; Taboada, H.

    2010-01-01

    Since last RRFM meeting, CNEA has deployed several related tasks. The RA-6 MTR type reactor, converted its core from HEU to a new LEU silicide one is scaling up the power, according to a protocol requested by the national regulatory body, ARN. CNEA is deploying an intense R and D activity to fabricate both dispersed U-Mo (Al-Si matrix and Al cladding) and monolithic (Zry-4 cladding) miniplates to develop possible solutions to VHD dispersed and monolithic fuels technical problems. Some monolithic 58% enrichment U8%Mo and U10%Mo are being delivered to INL-DoE to be irradiated in ATR reactor core. A conscientious study on compound interphase formation in both cases is being carried out. CNEA, a worldwide leader on LEU technology for fission radioisotope production is providing Brazil with these radiopharmaceutical products and Egypt and Australia with the technology through INVAP SE. CNEA is also committed to improve the diffusion of LEU target and radiochemical technology for radioisotope production and target and process optimization. Future plans include: 1) Fabrication of a LEU dispersed U-Mo fuel prototype following the recommendations of the IAEA's Good Practices document, to be irradiated in a high flux reactor in the frame of the ARG/4/092 IAEA's Technical Cooperation project. 2) Development of LEU very high density monolithic and dispersed U-Mo fuel plates with Zry-4 or Al cladding as a part of the RERTR program. 3) Optimization of LEU target and radiochemical techniques for radioisotope production. (author)

  20. 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

  1. National responses to global health targets: exploring policy transfer in the context of the UNAIDS '90-90-90' treatment targets in Ghana and Uganda.

    Science.gov (United States)

    McRobie, Ellen; Matovu, Fred; Nanyiti, Aisha; Nonvignon, Justice; Abankwah, Daniel Nana Yaw; Case, Kelsey K; Hallett, Timothy B; Hanefeld, Johanna; Conteh, Lesong

    2018-01-01

    Global health organizations frequently set disease-specific targets with the goal of eliciting adoption at the national-level; consideration of the influence of target setting on national policies, programme and health budgets is of benefit to those setting targets and those intended to respond. In 2014, the Joint United Nations Programme on HIV/AIDS set 'ambitious' treatment targets for country adoption: 90% of HIV-positive persons should know their status; 90% of those on treatment; 90% of those achieving viral suppression. Using case studies from Ghana and Uganda, we explore how the target and its associated policy content have been adopted at the national level. That is whether adoption is in rhetoric only or supported by programme, policy or budgetary changes. We review 23 (14 from Ghana, 9 from Uganda) national policy, operational and strategic documents for the HIV response and assess commitments to '90-90-90'. In-person semi-structured interviews were conducted with purposively sampled key informants (17 in Ghana, 20 in Uganda) involved in programme-planning and resource allocation within HIV to gain insight into factors facilitating adoption of 90-90-90. Interviews were transcribed and analysed thematically, inductively and deductively, guided by pre-existing policy theories, including Dolowitz and Marsh's policy transfer framework to describe features of the transfer and the Global Health Advocacy and Policy Project framework to explain observations. Regardless of notable resource constraints, transfer of the 90-90-90 targets was evident beyond rhetoric with substantial shifts in policy and programme activities. In both countries, there was evidence of attempts to minimize resource constraints by seeking programme efficiencies, prioritization of programme activities and devising domestic financing mechanisms; however, significant resource gaps persist. An effective health network, comprised of global and local actors, mediated the adoption and adaptation

  2. Radiometric system for clinical applications in the National Health System

    International Nuclear Information System (INIS)

    Mesa Perez, G.; Arteche Diaz, R.; Camejo Batista, A.; Fonfria Bragado, C.

    2013-01-01

    In this paper it is presented the radiometric detection system SRNIC-02, manufactured at CEADEN. The system has three major components: a well-type Nal(TI) scintillator detector with its collimator, a measurement module, and the application software, which allows fixing the working parameters of the system, as well as the acquisition and processing of data. The system has two main applications in the National Health System, one for the quality control in Radiopharmacy, and in RIA/IRMA blood tests. There are 16 systems installed, in 13 provinces of the country up to this date. (Author)

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Robustness studies of ignition targets for the National Ignition Facility in two dimensions

    International Nuclear Information System (INIS)

    Clark, Daniel S.; Haan, Steven W.; Salmonson, Jay D.

    2008-01-01

    Inertial confinement fusion capsules are critically dependent on the integrity of their hot spots to ignite. At the time of ignition, only a certain fractional perturbation of the nominally spherical hot spot boundary can be tolerated and the capsule still achieve ignition. The degree to which the expected hot spot perturbation in any given capsule design is less than this maximum tolerable perturbation is a measure of the ignition margin or robustness of that design. Moreover, since there will inevitably be uncertainties in the initial character and implosion dynamics of any given capsule, all of which can contribute to the eventual hot spot perturbation, quantifying the robustness of that capsule against a range of parameter variations is an important consideration in the capsule design. Here, the robustness of the 300 eV indirect drive target design for the National Ignition Facility [Lindl et al., Phys. Plasmas 11, 339 (2004)] is studied in the parameter space of inner ice roughness, implosion velocity, and capsule scale. A suite of 2000 two-dimensional simulations, run with the radiation hydrodynamics code LASNEX, is used as the data base for the study. For each scale, an ignition region in the two remaining variables is identified and the ignition cliff is mapped. In accordance with the theoretical arguments of Levedahl and Lindl [Nucl. Fusion 37, 165 (1997)] and Kishony and Shvarts [Phys. Plasmas 8, 4925 (2001)], the location of this cliff is fitted to a power law of the capsule implosion velocity and scale. It is found that the cliff can be quite well represented in this power law form, and, using this scaling law, an assessment of the overall (one- and two-dimensional) ignition margin of the design can be made. The effect on the ignition margin of an increase or decrease in the density of the target fill gas is also assessed

  8. Laser-Plasma Interactions in Drive Campaign targets on the National Ignition Facility

    International Nuclear Information System (INIS)

    Hinkel, D E; Callahan, D A; Moody, J D; Amendt, P A; Lasinski, B F; MacGowan, B J; Meeker, D; Michel, P A; Ralph, J; Rosen, M D; Ross, J S; Schneider, M B; Storm, E; Strozzi, D J; Williams, E A

    2016-01-01

    The Drive campaign [D A Callahan et al., this conference] on the National Ignition Facility (NIF) laser [E. I. Moses, R. N. Boyd, B. A. Remington, C. J. Keane, R. Al-Ayat, Phys. Plasmas 16, 041006 (2009)] has the focused goal of understanding and optimizing the hohlraum for ignition. Both the temperature and symmetry of the radiation drive depend on laser and hohlraum characteristics. The drive temperature depends on the coupling of laser energy to the hohlraum, and the symmetry of the drive depends on beam-to-beam interactions that result in energy transfer [P. A. Michel, S. H. Glenzer, L. Divol, et al, Phys. Plasmas 17, 056305 (2010).] within the hohlraum. To this end, hohlraums are being fielded where shape (rugby vs. cylindrical hohlraums), gas fill composition (neopentane at room temperature vs. cryogenic helium), and gas fill density (increase of ∼ 150%) are independently changed. Cylindrical hohlraums with higher gas fill density show improved inner beam propagation, as should rugby hohlraums, because of the larger radius over the capsule (7 mm vs. 5.75 mm in a cylindrical hohlraum). Energy coupling improves in room temperature neopentane targets, as well as in hohlraums at higher gas fill density. In addition cross-beam energy transfer is being addressed directly by using targets that mock up one end of a hohlraum, but allow observation of the laser beam uniformity after energy transfer. Ideas such as splitting quads into “doublets” by re-pointing the right and left half of quads are also being pursued. LPI results of the Drive campaign will be summarized, and analyses of future directions presented. (paper)

  9. 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

  10. Clinical images evaluation of mammograms: a national survey

    International Nuclear Information System (INIS)

    Moon, Woo Kyung; Kim, Tae Jung; Cha, Joo Hee

    2003-01-01

    The goal of this study was to survey the overall quality of mammographic images in Korea. A total of 598 mammographic images collected from 257 hospitals nationwide were reviewed in terms of eight images quality categories, namely positioning, compression, contrast, exposure, sharpness, noise, artifacts, and examination identification, and rated on a five-point scale: (1=severe deficiency, 2=major deficiency, 3=minor deficiency, 4=good, 5=best). Failure was defined as the occurrence of more than four major deficiencies or one severe deficiency (score of 1 or 2). The results were compared among hospitals of varying kinds, and common problems in clinical images quality were identified. Two hundred and seventeen mammographic images (36.3%) failed the evaluation. Poor images were found in descending order of frequency, at The Society for Medical Examination (33/69, 47.8%), non-radiologyclinics (42/88, 47.7%), general hospitals (92/216, 42.6%), radiology clinics (39/102, 38.2%), and university hospitals (11/123, 8.9%) (p<0.01, Chi-square test). Among the 598 images, serious problems which occurred were related to positioning in 23.7% of instances (n=142) (p<0.01, Chi-square test), examination identification in 5.7% (n=34), exposure in 5.4% (n=32), contrast in 4.2% (n=25), sharpness in 2.7% (n=16), compression in 2.5% (n=15), artifacts in 2.5% (n=15), and noise in 0.3% (n=2). This study showed that in Korea, 36.3% of the mammograms examined in this sampling had important image-related defects that might have led to serious errors in patient management. The failure rate was significantly higher in non-radiology clinics and at The Society for Medical Examination than at university hospitals

  11. Bedside Teaching in Australian Clinical Schools: A National Study

    Directory of Open Access Journals (Sweden)

    Praveen L. Indraratna

    2013-01-01

    Full Text Available Purpose. Bedside teaching (BST of medical students has become less common in recent years; however, there have been strong recommendations made in the literature to continue this teaching modality for the valued benefits it provides. The purpose of the present study is to explore the perceptions and opinions of bedside teaching among senior Australian medical students. Methods. Medical students at Australian universities were surveyed by means of an electronic questionnaire. The results were collected and analysed. Results. A total of 517 responses were received from students at 15 universities and 94 different clinical sites. The percentage of students who identified BST as very important ranged from 62.5% in psychiatry to 90.4% in internal medicine. The optimal class size was nominated as 3-4 students, and students favoured a style where one individual performs a complete examination, with the remainder allowed to elicit the key sign afterwards. Students felt 3-4 hours of BST per week to be ideal. Advantages identified to BST included provision of feedback and elicitation of clinical signs. Disadvantages included time constraints and excessive class sizes. Conclusions. The unique benefits of BST result in its high demand by students, regardless of the discipline being taught.

  12. 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.

  13. Use of the target diagnostic control system in the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, R; Lagin, L; Nelson, J

    2011-07-25

    The extreme physics of targets shocked by NIF's 192-beam laser are observed by a diverse suite of diagnostics including optical backscatter, time-integrated, time resolved and gated X-ray sensors, laser velocity interferometry, and neutron time of flight. Diagnostics to diagnose fusion ignition implosion and neutron emissions have been developed. A Diagnostic Control System (DCS) for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost Window XP processor and Java application. Instruments are aggregated as needed in the supervisory system to form an integrated diagnostic. The Java framework provides data management, control services and operator GUI generation. During the past several years, over thirty-six diagnostics have been deployed using this architecture in support of the National Ignition Campaign (NIC). The DCS architecture facilitates the expected additions and upgrades to diagnostics as more experiments are performed. This paper presents the DCS architecture, framework and our experiences in using it during the NIC to operate, upgrade and maintain a large set of diagnostic instruments.

  14. Use of the target diagnostic control system in the National Ignition Facility

    International Nuclear Information System (INIS)

    Shelton, R.; Lagin, L.; Nelson, J.

    2011-01-01

    The extreme physics of targets shocked by NIF's 192-beam laser are observed by a diverse suite of diagnostics including optical backscatter, time-integrated, time resolved and gated X-ray sensors, laser velocity interferometry, and neutron time of flight. Diagnostics to diagnose fusion ignition implosion and neutron emissions have been developed. A Diagnostic Control System (DCS) for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost Window XP processor and Java application. Instruments are aggregated as needed in the supervisory system to form an integrated diagnostic. The Java framework provides data management, control services and operator GUI generation. During the past several years, over thirty-six diagnostics have been deployed using this architecture in support of the National Ignition Campaign (NIC). The DCS architecture facilitates the expected additions and upgrades to diagnostics as more experiments are performed. This paper presents the DCS architecture, framework and our experiences in using it during the NIC to operate, upgrade and maintain a large set of diagnostic instruments.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. How Public Health Nurses Identify and Intervene in Child Maltreatment Based on the National Clinical Guideline

    Directory of Open Access Journals (Sweden)

    Paavilainen Eija

    2014-01-01

    Full Text Available Objectives. To describe how Finnish public health nurses identify and intervene in child maltreatment and how they implement the National Clinical Guideline in their work. Design and Sample. Cross-sectional survey of 367 public health nurses in Finland. Measures. A web-based questionnaire developed based on the content areas of the guideline: identifying, intervening, and implementing. Results. The respondents reported they identify child maltreatment moderately (mean 3.38, intervene in it better (4.15, and implement the guideline moderately (3.43, scale between 1 and 6. Those with experience of working with maltreated children reported they identify them better P<0.001, intervene better P<0.001, and implement the guideline better P<0.001 than those with no experience. This difference was also found for those who were aware of the guideline, had read it, and participated in training on child maltreatment, as compared to those who were not aware of the guideline, had not read it, or had not participated in such training. Conclusions. The public health nurses worked quite well with children who had experienced maltreatment and families. However, the results point out several developmental targets for increasing training on child maltreatment, for devising recommendations for child maltreatment, and for applying these recommendations systematically in practice.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. Clinical Research Nursing: A Critical Resource in the National Research Enterprise

    Science.gov (United States)

    Hastings, Clare E.; Fisher, Cheryl A.; McCabe, Margaret A.

    2012-01-01

    Translational clinical research has emerged as an important priority for the national research enterprise, with a clearly stated mandate to deliver prevention strategies, treatments and cures based on scientific innovations faster to the public. Within this national effort, a lack of consensus persists concerning the need for clinical nurses with expertise and specialized training in study implementation and the delivery of care to research participants. This paper reviews efforts to define and document the role of practicing nurses in implementing studies and coordinating clinical research in a variety of clinical settings and differentiates this clinical role from the role of nurses as scientists and principal investigators. We propose an agenda for building evidence that having nurses provide and coordinate study treatments and procedures can potentially improve research efficiency, participant safety, and the quality of research data. We also provide recommendations for the development of the emerging specialty of clinical research nursing. PMID:22172370

  5. 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.

  6. National Ignition Facility subsystem design requirements target positioning subsystem SSDR 1.8.2

    International Nuclear Information System (INIS)

    Pittenger, L.

    1996-01-01

    This Subsystem Design Requirement document is a development specification that establishes the performance, design, development and test requirements for the target positioner subsystem (WBS 1.8.2) of the NIF Target Experimental System (WBS 1.8)

  7. National Ignition Facility subsystem design requirements target diagnostics subsystem SSDR 1.8.3

    International Nuclear Information System (INIS)

    Lee, D.

    1996-01-01

    This SSDR establishes the performance, design, development and test requirements for the Target Experimental System's Diagnostic, WBS 1.8. 3. This includes the individual diagnostic components, the Target Diagnostic Data Acquisition System (Target DAS), the diagnostic vacuum system, the timing/fiducial system, and the EMI protection system

  8. 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.

  9. 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...

  10. The contribution of sectoral climate change mitigation options to national targets: a quantitative assessment of dairy production in Kenya

    Science.gov (United States)

    Brandt, Patric; Herold, Martin; Rufino, Mariana C.

    2018-03-01

    Reducing greenhouse gas (GHG) emissions from agriculture has become a critical target in national climate change policies. More than 80% of the countries in Sub-Saharan Africa (SSA) refer to the reduction of agricultural emissions, including livestock, in their nationally determined contribution (NDC) to mitigate climate change. The livestock sector in Kenya contributes largely to the gross domestic product and to GHG emissions from the land use sector. The government has recently pledged in its NDC to curb total GHG emissions by 30% by 2030. Quantifying and linking the mitigation potential of farm practices to national targets is required to support realistically the implementation of NDCs. Improvements in feed and manure management represent promising mitigation options for dairy production. This study aimed (i) to assess mitigation and food production benefits of feed and manure management scenarios, including land use changes covering Kenya’s entire dairy production region and (ii) to analyse the contribution of these practices to national targets on milk production and mitigation, and their biophysical feasibility given the availability of arable land. The results indicate that improving forage quality by increasing the use of Napier grass and supplementing dairy concentrates supports Kenya’s NDC target, reduces emission intensities by 26%-31%, partially achieves the national milk productivity target for 2030 by 38%-41%, and shows high feasibility given the availability of arable land. Covering manure heaps may reduce emissions from manure management by 68%. In contrast, including maize silage in cattle diets would not reduce emission intensities due to the risk of ten-fold higher emissions from the conversion of land required to grow additional maize. The shortage of arable land may render the implementation of these improved feed practices largely infeasible. This assessment provides the first quantitative estimates of the potential of feed

  11. 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.

  12. Target designs for the Brookhaven National Laboratory 5-MW pulsed spallation neutron source

    International Nuclear Information System (INIS)

    Ludewig, H.; Todosow, M.; Powell, J.R.

    1996-01-01

    A feasibility study of a compact high power density target for a spallation neutron source was under-taken. The target arrangement consists primarily of heavy metal, with appropriate cooling passages. A high intensity proton beam of intermediate energy is directed at the target, where it interacts with the heavy metal nuclei. The subsequent spallation reactions produce several neutrons per proton resulting in an intense neutron source. The proton beam is assumed to havean energy of 5 MW, and to be cyclic with a repetition rate of 10Hz and 50Hz. The study was divided into two broad sections. First, an analysis of preliminary target designs was undertaken to ensure the overall feasibility of the concepts involved in the design and eventual construction of such a high power density target. Second, two proposed target designs, based on the first set of analyses, are investigated in more detail. Special care is taken to ensure that the neutron fluxes in the moderator are at the desired level no material compatibility problems exist,and the target is able to operate in a reliable and safe manner. Several target materials, coolant types, and target arrangements are investigated in the first section. The second section concentrates on a single target material and geometric arrangement. However, several structural material choices continue to be investigated with the aim of minimizing the effects of structural heating, and associated thermally induced stresses. In the final section the conclusions of this preliminary study are summarized

  13. National Ignition Facility subsystem design requirements target area auxiliary subsystem SSDR 1.8.6

    International Nuclear Information System (INIS)

    Reitz, T.

    1996-01-01

    This Subsystem Design Requirement (SSDR) establishes the performance, design, development, and test requirements for the Target Area Auxiliary Subsystems (WBS 1.8.6), which is part of the NIF Target Experimental System (WBS 1.8). This document responds directly to the requirements detailed in NIF Target Experimental System SDR 003 document. Key elements of the Target Area Auxiliary Subsystems include: WBS 1.8.6.1 Local Utility Services; WBS 1.8.6.2 Cable Trays; WBS 1.8.6.3 Personnel, Safety, and Occupational Access; WBS 1.8.6.4 Assembly, Installation, and Maintenance Equipment; WBS 1.8.6.4.1 Target Chamber Service System; WBS 1.8.6.4.2 Target Bay Service Systems

  14. 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)

  15. 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.

  16. Clinical roles in clinical biochemistry: a national survey of practice in the UK.

    Science.gov (United States)

    Choudhury, Sirazum M; Williams, Emma L; Barnes, Sophie C; Alaghband-Zadeh, Jamshid; Tan, Tricia M; Cegla, Jaimini

    2017-05-01

    Background Using an online survey, we collected data to present a picture of how clinical authorization is performed in the UK. Methods A 21-question survey was uploaded to www.surveymonkey.com , and responses were invited via the mail base of the Association for Clinical Biochemistry and Laboratory Medicine. The questionnaire examined the intensity and function of the duty biochemist role and how different types of authorization are used to handle and release results. Results Of 70 responses received, 60 were suitable for analysis. Responses were received from every region of the UK. A typical duty biochemist shift started on average at 8:50, and finished at 17:25. The mean duration was 8 h 58 min. Clinical scientists are the most abundantly represented group on duty biochemist rotas. Higher banded clinical scientists and chemical pathologists covered out-of-hours shifts. Results were handled differently depending on the level of abnormality and the requesting area. Normal results tended to be released either directly from the analyser or after technical then autoauthorization (90%). A greater preference for clinical authorization was seen for abnormal and critical results originating from outpatients (49% and 69%, respectively) or general practice (51% and 71%) than for inpatients (33% and 53%) or A&E (25% and 37%). Conclusions The handling and authorization of biochemistry results varies greatly between laboratories. The role is clearly heterogeneous in the UK. Guidance from the Association for Clinical Biochemistry and Royal College of Pathologists may help to clarify the essential roles of the duty biochemist.

  17. 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.

  18. 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.

  19. 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.

  20. How is feedback from national clinical audits used? Views from English National Health Service trust audit leads.

    Science.gov (United States)

    Taylor, Angelina; Neuburger, Jenny; Walker, Kate; Cromwell, David; Groene, Oliver

    2016-04-01

    To explore how the output of national clinical audits in England is used by professionals and whether and how their impact could be enhanced. A mixed-methods study with the primary recipients of four national clinical audits of cancer care of 607 local audit leads, 274 (45%) completed a questionnaire and 32 participated in an interview. Our questions focused on how the audits were used and whether barriers existed to using the audits for local service improvement. We described variation in questionnaire responses between the audits using chi-squared tests. Results are reported as percentages with their 95% confidence intervals. Qualitative data were analysed using Framework analysis. More than 90% of survey respondents believed that the audit findings were relevant to their clinical work, and interviewees described how they used the audits for a range of purposes. Forty-two percent of survey respondents said they had changed their clinical practice, and 56% had implemented service improvements in response to the audits. The degree of change differed between the four audits, evident in both the questionnaire and the interview data. In the interviews, two recurring barriers emerged: (1) the importance of data quality, which, in turn, influenced the perceived relevance and validity of the audit data and therefore the ability to make changes based on it and (2) the need for clear presentation of benchmarked local performance data. The perceived authority and credibility of the professional bodies supporting the audits was a key factor underpinning the use of the audit findings. National cancer audit and feedback is used to improve services, but their impact could be enhanced by improving the data quality and relevance of feedback. © The Author(s) 2016.

  1. 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.

  2. 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.

  3. Feasibility of using ultra-high field (7 T MRI for clinical surgical targeting.

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    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.

  4. 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

  5. Assessing sample representativeness in randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network.

    Science.gov (United States)

    Susukida, Ryoko; Crum, Rosa M; Stuart, Elizabeth A; Ebnesajjad, Cyrus; Mojtabai, Ramin

    2016-07-01

    To compare the characteristics of individuals participating in randomized controlled trials (RCTs) of treatments of substance use disorder (SUD) with individuals receiving treatment in usual care settings, and to provide a summary quantitative measure of differences between characteristics of these two groups of individuals using propensity score methods. Design Analyses using data from RCT samples from the National Institute of Drug Abuse Clinical Trials Network (CTN) and target populations of patients drawn from the Treatment Episodes Data Set-Admissions (TEDS-A). Settings Multiple clinical trial sites and nation-wide usual SUD treatment settings in the United States. A total of 3592 individuals from 10 CTN samples and 1 602 226 individuals selected from TEDS-A between 2001 and 2009. Measurements The propensity scores for enrolling in the RCTs were computed based on the following nine observable characteristics: sex, race/ethnicity, age, education, employment status, marital status, admission to treatment through criminal justice, intravenous drug use and the number of prior treatments. Findings The proportion of those with ≥ 12 years of education and the proportion of those who had full-time jobs were significantly higher among RCT samples than among target populations (in seven and nine trials, respectively, at P difference in the mean propensity scores between the RCTs and the target population was 1.54 standard deviations and was statistically significant at P different from individuals receiving treatment in usual care settings. Notably, RCT participants tend to have more years of education and a greater likelihood of full-time work compared with people receiving care in usual care settings. © 2016 Society for the Study of Addiction.

  6. Status and methodology of publicly available national HIV care continua and 90-90-90 targets: A systematic review.

    Directory of Open Access Journals (Sweden)

    Reuben Granich

    2017-04-01

    Full Text Available In 2014, the Joint United Nations Program on HIV/AIDS (UNAIDS issued treatment goals for human immunodeficiency virus (HIV. The 90-90-90 target specifies that by 2020, 90% of individuals living with HIV will know their HIV status, 90% of people with diagnosed HIV infection will receive antiretroviral treatment (ART, and 90% of those taking ART will be virally suppressed. Consistent methods and routine reporting in the public domain will be necessary for tracking progress towards the 90-90-90 target.For the period 2010-2016, we searched PubMed, UNAIDS country progress reports, World Health Organization (WHO, UNAIDS reports, national surveillance and program reports, United States President's Emergency Plan for AIDS Relief (PEPFAR Country Operational Plans, and conference presentations and/or abstracts for the latest available national HIV care continuum in the public domain. Continua of care included the number and proportion of people living with HIV (PLHIV who are diagnosed, on ART, and virally suppressed out of the estimated number of PLHIV. We ranked the described methods for indicators to derive high-, medium-, and low-quality continuum. For 2010-2016, we identified 53 national care continua with viral suppression estimates representing 19.7 million (54% of the 2015 global estimate of PLHIV. Of the 53, 6 (with 2% of global burden were high quality, using standard surveillance methods to derive an overall denominator and program data from national cohorts for estimating steps in the continuum. Only nine countries in sub-Saharan Africa had care continua with viral suppression estimates. Of the 53 countries, the average proportion of the aggregate of PLHIV from all countries on ART was 48%, and the proportion of PLHIV who were virally suppressed was 40%. Seven countries (Sweden, Cambodia, United Kingdom, Switzerland, Denmark, Rwanda, and Namibia were within 12% and 10% of achieving the 90-90-90 target for "on ART" and for "viral suppression

  7. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice

    DEFF Research Database (Denmark)

    Sturgeon, Catharine M; Hoffman, Barry R; Chan, Daniel W

    2008-01-01

    BACKGROUND: This report presents updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines summarizing quality requirements for the use of tumor markers. METHODS: One subcommittee developed guidelines for analytical quality relevant to serum and tissue-based tumor...... questions to ensure selection of the appropriate test, adherence to good clinical and laboratory practices (e.g., minimization of the risk of incorrect patient and/or specimen identification, tube type, or timing), use of internationally standardized and well-characterized methods, careful adherence...... records. Also mandatory is extensive validation encompassing all stages of analysis before introduction of new technologies such as microarrays and mass spectrometry. Provision of high-quality tumor marker services is facilitated by dialogue involving researchers, diagnostic companies, clinical...

  8. Clinical reasoning of Filipino physical therapists: Experiences in a developing nation.

    Science.gov (United States)

    Rotor, Esmerita R; Capio, Catherine M

    2018-03-01

    Clinical reasoning is essential for physical therapists to engage in the process of client care, and has been known to contribute to professional development. The literature on clinical reasoning and experiences have been based on studies from Western and developed nations, from which multiple influencing factors have been found. A developing nation, the Philippines, has distinct social, economic, political, and cultural circumstances. Using a phenomenological approach, this study explored experiences of Filipino physical therapists on clinical reasoning. Ten therapists working in three settings: 1) hospital; 2) outpatient clinic; and 3) home health were interviewed. Major findings were: a prescription-based referral system limited clinical reasoning; procedural reasoning was a commonly experienced strategy while diagnostic and predictive reasoning were limited; factors that influenced clinical reasoning included practice setting and the professional relationship with the referring physician. Physical therapists' responses suggested a lack of autonomy in practice that appeared to stifle clinical reasoning. Based on our findings, we recommend that the current regulations governing PT practice in the Philippines may be updated, and encourage educators to strengthen teaching approaches and strategies that support clinical reasoning. These recommendations are consistent with the global trend toward autonomous practice.

  9. Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets- An Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

    Science.gov (United States)

    Ilekis, John V.; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M.; Soares, Michael J.; Cross, James C.; Zamudio, Stacy; Illsley, Nicholas P.; Myatt, Leslie; Colvis, Christine; Costantine, Maged M.; Haas, David M.; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-01-01

    Although much progress is being made in understanding the molecular pathways in the placenta involved in the pathophysiology of pregnancy related disorders, a significant gap exists in utilizing this information for developing new drug therapies to improve pregnancy outcome. On March 5–6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a two day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given in the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of this workshop. A broad number of topics were covered ranging from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and non-infectious agents. Research findings in these areas will be critical for formulating developing future treatments and developing therapies for the prevention of a number of pregnancy disorders of placental origin including preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented summarizing ongoing clinical efforts in the U.S. and in Europe testing novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy using virally-delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by enhancing nutrient transport to the fetus by modulating their placental transporters, as well as targeting placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles

  10. Enrollment Trends and Disparity Among Patients With Lung Cancer in National Clinical Trials, 1990 to 2012

    Science.gov (United States)

    Pang, Herbert H.; Stinchcombe, Thomas E.; Wong, Melisa L.; Cheng, Perry; Ganti, Apar Kishor; Sargent, Daniel J.; Zhang, Ying; Hu, Chen; Mandrekar, Sumithra J.; Redman, Mary W.; Manola, Judith B.; Schilsky, Richard L.; Cohen, Harvey J.; Bradley, Jeffrey D.; Adjei, Alex A.; Gandara, David; Ramalingam, Suresh S.; Vokes, Everett E.

    2016-01-01

    Purpose Under-representation of elderly, women, and racial/ethnic minority patients with cancer in clinical trials is of national concern. The goal of this study was to characterize enrollment trends and disparities by age, sex, and race/ethnicity in lung cancer trials. Methods We analyzed data for 23,006 National Cancer Institute cooperative group lung cancer trial participants and 578,476 patients with lung cancer from the SEER registry from 1990 to 2012. The enrollment disparity difference (EDD) and enrollment disparity ratio (EDR) were calculated on the basis of the proportion of each subgroup in the trial population and the US lung cancer population. Annual percentage changes (APCs) in the subgroup proportions in each population were compared over time. Results Enrollment disparity for patients ≥ 70 years of age with non–small-cell lung cancer improved from 1990 to 2012 (test of parallelism, P = .020), with a remaining EDD of 0.22 (95% CI, 0.19 to 0.25) and EDR of 1.65 (95% CI, 1.51 to 1.82) in 2010 to 2012. No improvement was seen for elderly patients with small-cell lung cancer (SCLC), with an APC of 0.20 (P = .714) among trial participants, despite a rising proportion of elderly patients with SCLC in the US population (APC, 0.32; P = .020). Enrollment disparity for women with lung cancer improved overall, with the gap closing by 2012 (EDD, 0.03 [95% CI, 0.00 to 0.06]; EDR, 1.07 [95% CI, 1.00 to 1.16]). Enrollment disparities persisted without significant improvement for elderly women, blacks, Asians/Pacific Islanders, and Hispanics. Conclusion Under-representation in lung cancer trials improved significantly from 1990 to 2012 for elderly patients with non–small-cell lung cancer and for women, but ongoing efforts to improve the enrollment of elderly patients with SCLC and minorities are needed. Our study highlights the importance of addressing enrollment disparities by demographic and disease subgroups to better target under-represented groups of

  11. [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

  12. 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

  13. 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

  14. A national clinical quality program for Veterans Affairs catheterization laboratories (from the Veterans Affairs clinical assessment, reporting, and tracking program).

    Science.gov (United States)

    Maddox, Thomas M; Plomondon, Mary E; Petrich, Megan; Tsai, Thomas T; Gethoffer, Hans; Noonan, Gregory; Gillespie, Brian; Box, Tamara; Fihn, Stephen D; Jesse, Robert L; Rumsfeld, John S

    2014-12-01

    A "learning health care system", as outlined in a recent Institute of Medicine report, harnesses real-time clinical data to continuously measure and improve clinical care. However, most current efforts to understand and improve the quality of care rely on retrospective chart abstractions complied long after the provision of clinical care. To align more closely with the goals of a learning health care system, we present the novel design and initial results of the Veterans Affairs (VA) Clinical Assessment, Reporting, and Tracking (CART) program-a national clinical quality program for VA cardiac catheterization laboratories that harnesses real-time clinical data to support clinical care and quality-monitoring efforts. Integrated within the VA electronic health record, the CART program uses a specialized software platform to collect real-time patient and procedural data for all VA patients undergoing coronary procedures in VA catheterization laboratories. The program began in 2005 and currently contains data on 434,967 catheterization laboratory procedures, including 272,097 coronary angiograms and 86,481 percutaneous coronary interventions, performed by 801 clinicians on 246,967 patients. We present the initial data from the CART program and describe 3 quality-monitoring programs that use its unique characteristics-procedural and complications feedback to individual labs, coronary device surveillance, and major adverse event peer review. The VA CART program is a novel approach to electronic health record design that supports clinical care, quality, and safety in VA catheterization laboratories. Its approach holds promise in achieving the goals of a learning health care system. Published by Elsevier Inc.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. [Contribution of Chilean research to the formulation of national clinical guidelines].

    Science.gov (United States)

    Núñez, Paulina F; Torres, Adrián C; Armas, Rodolfo M

    2014-12-01

    In Chile, 80 diseases were included in a health care system called Health Care Guarantees (GES) and clinical guidelines were elaborated for their management. To assess the scientific background of guidelines and if they were based on research financed by the Chilean National Commission for Science and Technology. The references of the 82 guidelines developed for 80 diseases were reviewed, registering their number, authors, country of origin and funding source. The guidelines had a total of 6,604 references. Of these, only 185 were Chilean (2.8%) and five (0.08%) originated from research financed by the National Commission for Science and Technology. The contribution of research funded by national agencies to the formulation of clinical guidelines is minimal.

  1. The National Hip Fracture Database (NHFD) - Using a national clinical audit to raise standards of nursing care.

    Science.gov (United States)

    Johansen, Antony; Boulton, Christopher; Hertz, Karen; Ellis, Michael; Burgon, Vivienne; Rai, Sunil; Wakeman, Rob

    2017-08-01

    The National Hip Fracture Database (NHFD) is a key clinical governance programme for staff working in trauma wards across England, Wales and Northern Ireland. It uses prospectively collected information about the 65,000 people who present with hip fracture each year, and links these with information about the quality of care and outcome for each individual. The NHFD can, therefore, provide a picture of the care offered to frail older people with this injury - people who, between them, occupy nearly half of inpatient trauma beds. The NHFD uses its website (www.nhfd.co.uk) to feed back live information to each of the countries' 180 trauma units - allowing them to bench mark their performance against national standards, and against that in other hospitals. This helps to develop a consensus over the best care for frail older people in areas where national guidance is not yet available. This article shows how the NHFD is contributing to four key aspects of patient safety and nursing care: the prevention of pressure ulcers and post-operative delirium, the monitoring of falls incidence across hospitals and nutritional assessment of patients with hip fracture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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)

  7. 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

  8. Assessing Multiple Pathways for Achieving China’s National Emissions Reduction Target

    Directory of Open Access Journals (Sweden)

    Mingyue Wang

    2018-06-01

    Full Text Available In order to achieve China’s target of carbon intensity emissions reduction in 2030, there is a need to identify a scientific pathway and feasible strategies. In this study, we used stochastic frontier analysis method of energy efficiency, incorporating energy structure, economic structure, human capital, capital stock and potential energy efficiency to identify an efficient pathway for achieving emissions reduction target. We set up 96 scenarios including single factor scenarios and multi-factors combination scenarios for the simulation. The effects of each scenario on achieving the carbon intensity reduction target are then evaluated. It is found that: (1 Potential energy efficiency has the greatest contribution to the carbon intensity emissions reduction target; (2 they are unlikely to reach the 2030 carbon intensity reduction target of 60% by only optimizing a single factor; (3 in order to achieve the 2030 target, several aspects have to be adjusted: the fossil fuel ratio must be lower than 80%, and its average growth rate must be decreased by 2.2%; the service sector ratio in GDP must be higher than 58.3%, while the growth rate of non-service sectors must be lowered by 2.4%; and both human capital and capital stock must achieve and maintain a stable growth rate and a 1% increase annually in energy efficiency. Finally, the specific recommendations of this research were discussed, including constantly improved energy efficiency; the upgrading of China’s industrial structure must be accelerated; emissions reduction must be done at the root of energy sources; multi-level input mechanisms in overall levels of education and training to cultivate the human capital stock must be established; investment in emerging equipment and accelerate the closure of backward production capacity to accumulate capital stock.

  9. On the Fielding of a High Gain, Shock-Ignited Target on the National Ignitiion Facility in the Near Term

    International Nuclear Information System (INIS)

    Perkins, L.J.; Betti, R.; Schurtz, G.P.; Craxton, R.S.; Dunne, A.M.; LaFortune, K.N.; Schmitt, A.J.; McKenty, P.W.; Bailey, D.S.; Lambert, M.A.; Ribeyre, X.; Theobald, W.R.; Strozzi, D.J.; Harding, D.R.; Casner, A.; Atzemi, S.; Erbert, G.V.; Andersen, K.S.; Murakami, M.; Comley, A.J.; Cook, R.C.; Stephens, R.B.

    2010-01-01

    Shock ignition, a new concept for igniting thermonuclear fuel, offers the possibility for a near-term (∼3-4 years) test of high gain inertial confinement fusion on the National Ignition Facility at less than 1MJ drive energy and without the need for new laser hardware. In shock ignition, compressed fusion fuel is separately ignited by a strong spherically converging shock and, because capsule implosion velocities are significantly lower than those required for conventional hotpot ignition, fusion energy gains of ∼60 may be achievable on NIF at laser drive energies around ∼0.5MJ. Because of the simple all-DT target design, its in-flight robustness, the potential need for only 1D SSD beam smoothing, minimal early time LPI preheat, and use of present (indirect drive) laser hardware, this target may be easier to field on NIF than a conventional (polar) direct drive hotspot ignition target. Like fast ignition, shock ignition has the potential for high fusion yields at low drive energy, but requires only a single laser with less demanding timing and spatial focusing requirements. Of course, conventional symmetry and stability constraints still apply. In this paper we present initial target performance simulations, delineate the critical issues and describe the immediate-term R and D program that must be performed in order to test the potential of a high gain shock ignition target on NIF in the near term.

  10. 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.

  11. National Practice Patterns for Clinical T1N0 Nasopharyngeal Cancer in the Elderly: A National Cancer Data Base Analysis.

    Science.gov (United States)

    Post, Carl M; Lin, Chi; Adeberg, Sebastian; Gupta, Mrigank; Zhen, Weining; Verma, Vivek

    2018-03-01

    The standard of care for T1N0 nasopharyngeal cancer (NPC) is definitive radiation therapy (RT). However, practice patterns in the elderly may not necessarily follow national guidelines. Herein, we investigated national practice patterns for T1N0 NPC. The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) in patients ≥70 years old. Patient, tumor, and treatment parameters were extracted. Kaplan-Meier analysis was used to compare overall survival (OS) between patients receiving RT versus those under observation. Logistic regression was used to examine variables associated with receipt of RT. Cox proportional hazards modeling determined variables associated with OS. Landmark analysis of patients surviving 1 year or more was performed to assess survival differences between groups. In total, data of 147 patients were analyzed. RT was delivered to 89 patients (61%), whereas 58 (39%) patients underwent observation. On multivariable analysis, older patients were less likely to receive RT (p=0.003), but there were no differences between groups in terms of Charlson-Deyo comorbidity index. Median and 5-year OS in patients receiving RT versus those under observation were 71 and 33 months, and 59% and 48% (p=0.011), respectively. For patients surviving 1 year or more (n=96), there was a strong trend showing that receipt of RT was associated with better median and 5-year OS. This National Data Base analysis shows that observation is relatively common for T1N0 NPC in the elderly, but is associated with poorer survival. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. 77 FR 13656 - Call for Papers: National Symposium on Moving Target Research

    Science.gov (United States)

    2012-03-07

    ... a dynamic attack surface to an adversary, increasing the work factor necessary to successfully attack and exploit a cyber target. Throughout the federal government, research related to MT has been... improvement in the defense of cyber systems (a game changer),'' including how to develop better measures of...

  13. Target Diagnostic Instrument-Based Controls Framework for the National Ignition Facility

    International Nuclear Information System (INIS)

    Shelton, R; O'Brien, D; Nelson, J; Kamperschroer, J

    2007-01-01

    NIF target diagnostics are being developed to observe and measure the extreme physics of targets irradiated by the 192-beam laser. The response time of target materials can be on the order of 100ps--the time it takes light to travel 3 cm--temperatures more than 100 times hotter than the surface of the sun, and pressures that exceed 109 atmospheres. Optical and x-ray diagnostics were developed and fielded to observe and record the results of the first 4-beam experiments at NIF. Hard and soft x-ray spectra were measured, and time-integrated and gated x-ray images of hydrodynamics experiments were recorded. Optical diagnostics recorded backscatter from the target, and VISAR laser velocimetry measurements were taken of laser-shocked target surfaces. Additional diagnostics are being developed and commissioned to observe and diagnose ignition implosions, including various neutron and activation diagnostics. NIF's diagnostics are being developed at LLNL and with collaborators at other sites. To accommodate the growing number of target diagnostics, an Instrument-Based Controls hardware-software framework has been developed to facilitate development and ease integration into the NIF Integrated Computer Control System (ICCS). Individual WindowsXP PC controllers for each digitizer, power supply and camera (i.e., instruments) execute controls software unique to each instrument model. Each hardware-software controller manages a single instrument, in contrast to the complexity of combining all the controls software needed for a diagnostic into a single controller. Because of this simplification, controllers can be more easily tested on the actual hardware, evaluating all normal and off-normal conditions. Each target diagnostic is then supported by a number of instruments, each with its own hardware-software instrument-based controller. Advantages of the instrument-based control architecture and framework include reusability, testability, and improved reliability of the deployed

  14. Target Diagnostic Instrument-Based Controls Framework for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, R; O' Brien, D; Nelson, J; Kamperschroer, J

    2007-05-07

    NIF target diagnostics are being developed to observe and measure the extreme physics of targets irradiated by the 192-beam laser. The response time of target materials can be on the order of 100ps--the time it takes light to travel 3 cm--temperatures more than 100 times hotter than the surface of the sun, and pressures that exceed 109 atmospheres. Optical and x-ray diagnostics were developed and fielded to observe and record the results of the first 4-beam experiments at NIF. Hard and soft x-ray spectra were measured, and time-integrated and gated x-ray images of hydrodynamics experiments were recorded. Optical diagnostics recorded backscatter from the target, and VISAR laser velocimetry measurements were taken of laser-shocked target surfaces. Additional diagnostics are being developed and commissioned to observe and diagnose ignition implosions, including various neutron and activation diagnostics. NIF's diagnostics are being developed at LLNL and with collaborators at other sites. To accommodate the growing number of target diagnostics, an Instrument-Based Controls hardware-software framework has been developed to facilitate development and ease integration into the NIF Integrated Computer Control System (ICCS). Individual WindowsXP PC controllers for each digitizer, power supply and camera (i.e., instruments) execute controls software unique to each instrument model. Each hardware-software controller manages a single instrument, in contrast to the complexity of combining all the controls software needed for a diagnostic into a single controller. Because of this simplification, controllers can be more easily tested on the actual hardware, evaluating all normal and off-normal conditions. Each target diagnostic is then supported by a number of instruments, each with its own hardware-software instrument-based controller. Advantages of the instrument-based control architecture and framework include reusability, testability, and improved reliability of the

  15. Emergency recompression: clinical audit of service delivery at a national level.

    Science.gov (United States)

    Ross, John As; Sayer, Martin Dj

    2009-03-01

    Clinical audit is an essential element to the maintenance or improvement of delivery of any medical service. During the development phase of a National Recompression Registration Service for Scotland, clinical audit was initiated to provide a standardised tool to monitor the quality of outcome with respect to the severity of presentation. A functional audit process was an essential consideration for planned future measurement of treatment efficacy at local (single hyperbaric unit) and national (multiple hyperbaric units) scales. The audit process was designed to be undemanding, robust and informative, irrespective of the experience of treatment centre and of the clinician in charge of treatment. The clinical records from 104 cases of divers with decompression illness were used to derive and evaluate measures of severity and clinical outcome that could be used for audit and quality assurance. The various measures of disease severity were examined against clinical outcome and days spent in care after admission to a hyperbaric unit. An initial version of the clinical audit format that was developed from this process is presented.

  16. Factors Influencing Support for National Health Insurance among Patients Attending Specialist Clinics in Malaysia

    Science.gov (United States)

    Almualm, Yasmin; Alkaff, Sharifa Ezat; Aljunid, Syed; Alsagoff, Syed Sagoff

    2013-01-01

    This study was carried out to determine the level of support towards the proposed National Health Insurance scheme among Malaysian patients attending specialist clinics at the National University of Malaysia Medical centre and its influencing factors. The cross sectional study was carried out from July-October 2012. 260 patients were selected using multistage sampling method. 71.2% of respondents supported the proposed National Health insurance scheme. 61.4% of respondents are willing to pay up to RM240 per year to join the National Health Insurance and 76.6% of respondents are of the view that enrolment in NHI should be made compulsory. Knowledge had a positive influence on respondent's support towards National Health Insurance. National Health Insurance when implemented in Malaysia can be used to raise funds for health care financing, increase access to health services and achieve the desired health status. More efforts should be taken to promote the scheme and educate the public in order to achieve higher support towards the proposed National Health Insurance. The cost to enroll in NHI as well as services to be included under the scheme should be duly considered. PMID:23985101

  17. 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

  18. Overview of Self-Management Resources Used by Canadian Chronic Kidney Disease Clinics: A National Survey.

    Science.gov (United States)

    Donald, Maoliosa; Gil, Sarah; Kahlon, Bhavneet; Beanlands, Heather; Straus, Sharon; Herrington, Gwen; Manns, Braden; Hemmelgarn, Brenda R

    2018-01-01

    Chronic kidney disease (CKD) clinics across Canada provide tailored care for patients with CKD with an aim to slow progression and prevent complications. These clinics provide CKD self-management resources; however, there is limited information about what resources are being used by clinics. We undertook a survey of CKD clinics across Canada to identify self-management resources for adults aged 18 years and over with CKD categories 1 to 5 and not requiring dialysis or transplant. To identify and collate self-management resources (eg, strategies, tools, educational materials) used by CKD clinics across Canada for adults with CKD (categories 1 to 5, not requiring kidney replacement therapy). Self-administered, semistructured electronic survey. Canadian CKD clinics with previously identified contact information. We contacted 57 CKD English-speaking clinics and invited them to complete an online survey. The survey was available from October 2016 to January 2017 and consisted of 17 questions regarding the use and attributes of self-management resources including topic, delivery format, provider, target population, where the intervention was provided, and resource languages. Forty-four clinics (77%) completed the survey. The most common topic was modality education provided in print format, by nurses. The most frequently used resource was the Kidney Foundation of Canada (KFOC) Living With Kidney Disease manual. We also identified that the majority of resources were available in English, targeting both patients and caregivers in the outpatient setting. Our survey included Canadian adult CKD clinics, which may not be generalizability to other settings, such as care of people with CKD in primary care. Adult CKD clinics across Canada provide some similar resources, but also provide many different self-management resources. Even though some of the same resources were used by multiple clinics, the way they were provided them (ie, provider, location, delivery format) varied by

  19. Overview of the national spallation neutron source with emphasis on the target station

    International Nuclear Information System (INIS)

    Gabriel, T.A.; Barnes, J.N.; Charlton, L.A.

    1997-01-01

    The technologies that are being utilized to design and build a state-of-the-art neutron spallation source, the National Spallation Neutron Source (NSNS), are discussed. Emphasis is given to the technology issues that present the greatest scientific challenges. The present facility configuration, ongoing analysis and the planned hardware research and development program are also described

  20. National Mesothelioma Virtual Bank: A standard based biospecimen and clinical data resource to enhance translational research

    Directory of Open Access Journals (Sweden)

    Valdivieso Federico A

    2008-08-01

    Full Text Available Abstract Background Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. Methods The National Mesothelioma Virtual Bank architecture is based on three major components: (a common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards, (b clinical and epidemiologic data annotation, and (c data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid™ (caBIG™, see http://cabig.nci.nih.gov. This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. Result The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. Conclusion The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational

  1. Nighttime assaults: using a national emergency department monitoring system to predict occurrence, target prevention and plan services

    Directory of Open Access Journals (Sweden)

    Bellis Mark A

    2012-09-01

    Full Text Available Abstract Background Emergency department (ED data have the potential to provide critical intelligence on when violence is most likely to occur and the characteristics of those who suffer the greatest health impacts. We use a national experimental ED monitoring system to examine how it could target violence prevention interventions towards at risk communities and optimise acute responses to calendar, holiday and other celebration-related changes in nighttime assaults. Methods A cross-sectional examination of nighttime assault presentations (6.01 pm to 6.00 am; n = 330,172 over a three-year period (31st March 2008 to 30th March 2011 to English EDs analysing changes by weekday, month, holidays, major sporting events, and demographics of those presenting. Results Males are at greater risk of assault presentation (adjusted odds ratio [AOR] 3.14, 95% confidence intervals [CIs] 3.11-3.16; P 2 = 0.918; P  Conclusions To date, the role of ED data has focused on helping target nightlife police activity. Its utility is much greater; capable of targeting and evaluating multi-agency life course approaches to violence prevention and optimising frontline resources. National ED data are critical for fully engaging health services in the prevention of violence.

  2. 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

  3. 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.

  4. Management of unconverted light for the National Ignition Facility target chamber

    International Nuclear Information System (INIS)

    Anderson, A. T.; Bletzer, K.; Burnham, A. K.; Dixit, S.; Genin, F. Y.; Hibbard, W.; Norton, J.; Scott, J. M.; Whitman, P. K.

    1998-01-01

    The NIF target chamber beam dumps must survive high x-ray, laser, ion, and shrapnel exposures without excessive generation of vapors or particulate that will contaminate the final optics debris shields, thereby making the debris shields susceptible to subsequent laser damage. The beam dumps also must be compatible with attaining and maintaining the required target chamber vacuum and must not activate significantly under high neutron fluxes. Finally, they must be developed, fabricated, and maintained for a reasonable cost. The primary challenge for the beam dump is to survive up to 20 J/cm 2 of lpm light and 1 - 2 J/cm 2 of nominally 200 - 350 eV blackbody temperature x rays. Additional threats include target shrapnel, and other contamination issues. Designs which have been evaluated include louvered hot-pressed boron carbide (B 4 C) or stainless steel (SS) panels, in some cases covered with transparent Teflon film, and various combinations of inexpensive low thermal expansion glasses backed by inexpensive absorbing glass. Louvered designs can recondense a significant amount of ablated material that would otherwise escape into the target chamber. Transparent Teflon was evaluated as an alternative way to capture ablated material. The thin Teflon sheet would need to be replaced after each shot since it exhibits both laser damage and considerable x- ray ablation with each shot. Uncontaminated B 4 C, SS, and low thermal expansion glasses have reasonably small x-ray and laser ablation rates, although the glasses begin to fail catastrophically after 100 high fluence shots. Commercially available absorbing glasses require a pre-shield of either Teflon or low thermal expansion glass to prevent serious degradation by the x-ray fluence. Advantages of the hot-pressed B 4 C and SS over glass are their performance against microshrapnel, their relative indifference to contamination, and their ability to be refurbished by aggressive cleaning using CO 2 pellets, glass beads, high

  5. National survey on sports injuries in the Netherlands: target populations for sports injury prevention programs.

    Science.gov (United States)

    Schmikli, Sandor L; Backx, Frank J G; Kemler, Helena J; van Mechelen, Willem

    2009-03-01

    To define target populations for sports injury prevention programs. A computer-assisted telephone survey on sports injuries and sports participation during 2000-2005 using a 3-month recall period. Data obtained from a representative sample of Dutch citizens. Fifty-eight thousand four hundred five Dutch citizens aged older than 3 years. Age, gender, and type of sports were used to distinguish subgroups with a substantial contribution to sports injuries. The absolute number of sports injuries, the incidence of sports injuries per 10,000 hours, the severity, and costs of sports injuries. Sports participation was associated with 1.5 million injuries per year and 10 injuries per 10,000 hours; of these, 50% had to be treated medically. Two-thirds of all medically treated sports injuries were associated with 9 sports (representing 18 subpopulations, all younger than 55 years): outdoor soccer (males 4-54 years and females 4-17 years), indoor soccer (males 18-34 years), tennis (males/females 35-54 years), volleyball (females 18-54 years), field hockey (males 18-34 years and females 4-17 years), running/jogging (males/females 35-54 years), gymnastics (males/females 4-17 years), skiing/snowboarding (males 4-17 years and females 18-34 years), and equestrian sports (females 18-34 years). These groups showed more than average injury rates and covered two-thirds of all direct and indirect costs (euro 400 million). The survey identified the most important (sports-, age-, and gender-specific) target populations for injury prevention programs in the Netherlands. Sports participants aged older than 55 years were excluded from these target groups because of their limited contribution to the total sports injury problem.

  6. Target area acquisition and control system survivability for the National Ignition Facility

    International Nuclear Information System (INIS)

    Hagans, K.; Stathis, P.; Wiedwald, J.; Campbell, D.

    1994-06-01

    The hardening of instruments to survive NIF target emission environments presents a significant challenge. Neutron flux is predicted to be as much as six orders of magnitude greater than the highest achieved neutron flux on NOVA. Not withstanding the high prompt radiation fields, the specifications for the instruments are demanding; requiring high resolution imaging and sub nanosecond transient measurements. We present an analysis of the sensitivity of the proposed NIF instrumentation design to EMP, X-rays, gamma rays, and neutrons. Major components assessed include fiber optic cable transport, high bandwidth cable and charge coupled detector (CCD) imaging systems

  7. Priority of domestic biomass resources for energy: Importance of national environmental targets in a climate perspective

    DEFF Research Database (Denmark)

    Tonini, Davide; Vadenbo, Carl; Astrup, Thomas Fruergaard

    2017-01-01

    ) for electricity/heat is generally preferred, as long as coal/oil is still used within the energy system. Yet, to fulfill environmental targets for renewable energy in the transport sector, the diversion of a significant share of biogas (and/or other biofuels) from these more beneficial uses is necessary...... that utilizing the energy potential of manure and straw represents the primary opportunity for further global warming mitigation. For this purpose, co-digestion (for manure) and combustion with heat-and-power production (for straw) appear as the most promising technologies. The utilization of biomass (or biogas...

  8. Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan

    OpenAIRE

    Ono, Yosuke; Ono, Sachiko; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Tanaka, Yuji

    2017-01-01

    Background: Myxedema coma is a life-threatening and emergency presentation of hypothyroidism. However, the clinical features and outcomes of this condition have been poorly defined because of its rarity. Methods: We conducted a retrospective observational study of patients diagnosed with myxedema coma from July 2010 through March 2013 using a national inpatient database in Japan. We investigated characteristics, comorbidities, treatments, and in-hospital mortality of patients with myxedem...

  9. Clinical Case Registries: Simultaneous Local and National Disease Registries for Population Quality Management

    Science.gov (United States)

    Backus, Lisa I.; Gavrilov, Sergey; Loomis, Timothy P.; Halloran, James P.; Phillips, Barbara R.; Belperio, Pamela S.; Mole, Larry A.

    2009-01-01

    The Department of Veterans Affairs (VA) has a system-wide, patient-centric electronic medical record system (EMR) within which the authors developed the Clinical Case Registries (CCR) to support population-centric delivery and evaluation of VA medical care. To date, the authors have applied the CCR to populations with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Local components use diagnosis codes and laboratory test results to identify patients who may have HIV or HCV and support queries on local care delivery with customizable reports. For each patient in a local registry, key EMR data are transferred via HL7 messaging to a single national registry. From 128 local registry systems, over 60,000 and 320,000 veterans in VA care have been identified as having HIV and HCV, respectively, and entered in the national database. Local and national reports covering demographics, resource usage, quality of care metrics and medication safety issues have been generated. PMID:19717794

  10. A national survey of clinical pharmacy services in county hospitals in China.

    Science.gov (United States)

    Yao, Dongning; Xi, Xiaoyu; Huang, Yuankai; Hu, Hao; Hu, Yuanjia; Wang, Yitao; Yao, Wenbing

    2017-01-01

    Clinical pharmacy is not only a medical science but also an elaborate public health care system firmly related to its subsystems of education, training, qualification authentication, scientific research, management, and human resources. China is a developing country with a tremendous need for improvements in the public health system, including the clinical pharmacy service system. The aim of this research was to evaluate the infrastructure and personnel qualities of clinical pharmacy services in China. Public county hospitals in China. A national survey of clinical pharmacists in county hospitals was conducted. It was sampled through a stratified sampling strategy. Responses were analyzed using descriptive and inferential statistics. The main outcome measures include the coverage of clinical pharmacy services, the overall staffing of clinical pharmacists, the software and hardware of clinical pharmacy services, the charge mode of clinical pharmacy services, and the educational background, professional training acquisition, practical experience, and entry path of clinical pharmacists. The overall coverage of clinical pharmacy services on both the department scale (median = 18.25%) and the patient scale (median = 15.38%) does not meet the 100% coverage that is required by the government. In 57.73% of the sample hospitals, the staffing does not meet the requirement, and the size of the clinical pharmacist group is smaller in larger hospitals. In addition, 23.4% of the sample hospitals do not have management rules for the clinical pharmacists, and 43.1% do not have rational drug use software, both of which are required by the government. In terms of fees, 89.9% of the sample hospitals do not charge for the services. With regard to education, 8.5% of respondents are with unqualified degree, and among respondents with qualified degree, 37.31% are unqualified in the major; 43% of respondents lack the clinical pharmacist training required by the government. Most

  11. A national survey of memory clinics in the Republic of Ireland.

    Science.gov (United States)

    Cahill, Suzanne; Pierce, Maria; Moore, Vanessa

    2014-04-01

    This national survey investigates the location, resourcing, staff composition, treatments, waiting time, and numbers of patients attending memory clinics (MCs) in the Republic of Ireland. It also explores Directors' attitudes to future service development including their views about the advantages and disadvantages of quality standards for MCs. An audio-taped telephone interview was conducted with the Directors. A total of 14 MCs were identified across the Republic of Ireland, ten of which are hospital-based and most of which offer diagnostic services and are located in Dublin. Nine MCs are medical consultant led and operate under the direction of either Old Age Psychiatrists or Geriatricians. Results show wide variation regarding the location, team size, service availability, and numbers of patients attending. The average number of patients attending in 2011 was 126. Only six clinics employ dedicated Allied Health Professionals. Less than half of the clinics are research active. Whilst most Directors welcomed the availability of national standards, several expressed concern that standards might, in the absence of funding, result in the closure of the most poorly resourced services. This survey provides valuable data on the main characteristics of all of the 14 MCs delivering services in the Republic of Ireland and raises critical and fundamental questions about the goals and outcomes of MC services. The survey data collected can be used by other countries for cross-national comparison.

  12. Target diagnostic control system implementation for the National Ignition Facility (invited)

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, R. T.; Kamperschroer, J. H.; Lagin, L. J.; Nelson, J. R.; O' Brien, D. W. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States)

    2010-10-15

    The extreme physics of targets shocked by NIF's 192-beam laser is observed by a diverse suite of diagnostics. Many diagnostics are being developed by collaborators at other sites, but ad hoc controls could lead to unreliable and costly operations. A diagnostic control system (DCS) framework for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost WINDOWS XP processor and JAVA application. Each instrument is aggregated with others as needed in the supervisory system to form an integrated diagnostic. The JAVA framework provides data management, control services, and operator graphical user interface generation. DCS instruments are reusable by replication with reconfiguration for specific diagnostics in extensible markup language. Advantages include minimal application code, easy testing, and high reliability. Collaborators save costs by assembling diagnostics with existing DCS instruments. This talk discusses target diagnostic instrumentation used on NIF and presents the DCS architecture and framework.

  13. Target diagnostic control system implementation for the National Ignition Facility (invited)

    International Nuclear Information System (INIS)

    Shelton, R. T.; Kamperschroer, J. H.; Lagin, L. J.; Nelson, J. R.; O'Brien, D. W.

    2010-01-01

    The extreme physics of targets shocked by NIF's 192-beam laser is observed by a diverse suite of diagnostics. Many diagnostics are being developed by collaborators at other sites, but ad hoc controls could lead to unreliable and costly operations. A diagnostic control system (DCS) framework for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost WINDOWS XP processor and JAVA application. Each instrument is aggregated with others as needed in the supervisory system to form an integrated diagnostic. The JAVA framework provides data management, control services, and operator graphical user interface generation. DCS instruments are reusable by replication with reconfiguration for specific diagnostics in extensible markup language. Advantages include minimal application code, easy testing, and high reliability. Collaborators save costs by assembling diagnostics with existing DCS instruments. This talk discusses target diagnostic instrumentation used on NIF and presents the DCS architecture and framework.

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

    NARCIS (Netherlands)

    Zachiu, Cornel; Ries, Mario G; Ramaekers, Pascal; Guey, Jean-Luc; Moonen, Chrit T W; de Senneville, Baudouin Denis

    2017-01-01

    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

  15. National survey of clinical communication assessment in medical education in the United Kingdom (UK).

    Science.gov (United States)

    Laidlaw, Anita; Salisbury, Helen; Doherty, Eva M; Wiskin, Connie

    2014-01-13

    All medical schools in the UK are required to be able to provide evidence of competence in clinical communication in their graduates. This is usually provided by summative assessment of clinical communication, but there is considerable variation in how this is carried out. This study aimed to gain insight into the current assessment of clinical communication in UK medical schools. The survey was sent via e-mail to communication leads who then were asked to consult with all staff within their medical school involved in the assessment of communication. Results were obtained from 27 out of 33 schools (response rate 82%) and a total of 34 courses. The average number of assessments per year was 2.4 (minimum 0, maximum 10). The Objective Structured Clinical Exam (OSCE) was the most commonly used method of assessment (53%). Other assessments included MCQ and workplace based assessments. Only nine courses used a single method of assessment. Issues raised included, logistics and costs of assessing mainly by OSCE, the robustness and reliability of such exams and integration with other clinical skills. It is encouraging that a variety of assessment methods are being used within UK medical schools and that these methods target different components of clinical communication skills acquisition.

  16. HIV/AIDS National Strategic Plans of Sub-Saharan African countries: an analysis for gender equality and sex-disaggregated HIV targets

    Science.gov (United States)

    Sherwood, Jennifer; Sharp, Alana; Cooper, Bergen; Roose-Snyder, Beirne; Blumenthal, Susan

    2017-01-01

    Abstract National Strategic Plans (NSPs) for HIV/AIDS are country planning documents that set priorities for programmes and services, including a set of targets to quantify progress toward national and international goals. The inclusion of sex-disaggregated targets and targets to combat gender inequality is important given the high disease burden among young women and adolescent girls in Sub-Saharan Africa, yet no comprehensive gender-focused analysis of NSP targets has been performed. This analysis quantitatively evaluates national HIV targets, included in NSPs from eighteen Sub-Saharan African countries, for sex-disaggregation. Additionally, NSP targets aimed at reducing gender-based inequality in health outcomes are compiled and inductively coded to report common themes. On average, in the eighteen countries included in this analysis, 31% of NSP targets include sex-disaggregation (range 0–92%). Three countries disaggregated a majority (>50%) of their targets by sex. Sex-disaggregation in data reporting was more common for targets related to the early phases of the HIV care continuum: 83% of countries included any sex-disaggregated targets for HIV prevention, 56% for testing and linkage to care, 22% for improving antiretroviral treatment coverage, and 11% for retention in treatment. The most common target to reduce gender inequality was to prevent gender-based violence (present in 50% of countries). Other commonly incorporated target areas related to improving women’s access to family planning, human and legal rights, and decision-making power. The inclusion of sex-disaggregated targets in national planning is vital to ensure that programmes make progress for all population groups. Improving the availability and quality of indicators to measure gender inequality, as well as evaluating programme outcomes by sex, is critical to tracking this progress. This analysis reveals an urgent need to set specific and separate targets for men and women in order to achieve

  17. Why Providers Participate in Clinical Trials: Considering the National Cancer Institute’s Community Clinical Oncology Program

    Science.gov (United States)

    McAlearney, Ann Scheck; Song, Paula H.; Reiter, Kristin L.

    2012-01-01

    Background The translation of research evidence into practice is facilitated by clinical trials such as those sponsored by the National Cancer Institute’s Community Clinical Oncology Program (CCOP) that help disseminate cancer care innovations to community-based physicians and provider organizations. However, CCOP participation involves unsubsidized costs and organizational challenges that raise concerns about sustained provider participation in clinical trials. Objectives This study was designed to improve our understanding of why providers participate in the CCOP in order to inform the decision-making process of administrators, clinicians, organizations, and policy-makers considering CCOP participation. Research Methods We conducted a multi-site qualitative study of five provider organizations engaged with the CCOP. We interviewed 41 administrative and clinician key informants, asking about what motivated CCOP participation, and what benefits they associated with involvement. We deductively and inductively analyzed verbatim interview transcripts, and explored themes that emerged. Results Interviewees expressed both “altruistic” and “self-interested” motives for CCOP participation. Altruistic reasons included a desire to increase access to clinical trials and feeling an obligation to patients. Self-interested reasons included the desire to enhance reputation, and a need to integrate disparate cancer care activities. Perceived benefits largely matched expressed motives for CCOP participation, and included internal and external benefits to the organization, and quality of care benefits for both patients and participating physicians. Conclusion The motives and benefits providers attributed to CCOP participation are consistent with translational research goals, offering evidence that participation can contribute value to providers by expanding access to innovative medical care for patients in need. PMID:22925970

  18. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute's genomic medicine portfolio.

    Science.gov (United States)

    Manolio, Teri A

    2016-10-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual's genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of "Genomic Medicine Meetings," under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and difficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI's genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. Published by Elsevier Ireland Ltd.

  19. Characteristics of adults with anxiety or depression treated at an internet clinic: comparison with a national survey and an outpatient clinic.

    Science.gov (United States)

    Titov, Nickolai; Andrews, Gavin; Kemp, Alice; Robinson, Emma

    2010-05-28

    There is concern that people seeking treatment over the Internet for anxiety or depressive disorders may not resemble the general population or have less severe disorders than patients attending outpatient clinics or cases identified in community surveys. Thus the response to treatment in Internet based trials might not generalize. We reviewed the characteristics of applicants to an Australian Internet-based treatment clinic for anxiety and depression, and compared this sample with people from a national epidemiological survey and a sample of patients at a specialist outpatient anxiety and depression clinic. Participants included 774 volunteers to an Internet clinic, 454 patients at a specialist anxiety disorders outpatient clinic, and 627 cases identified in a national epidemiological survey. Main measures included demographic characteristics, and severity of symptoms as measured by the Kessler 10-Item scale (K-10), the 12-item World Health Organisation Disability Assessment Schedule second edition (WHODAS-II), the Penn State Worry Questionnaire (PSWQ), the Body Sensations Questionnaire (BSQ), the Automatic Cognitions Questionnaire (ACQ), the Social Interaction Anxiety Scale (SIAS) and the Social Phobia Scale (SPS). The severity of symptoms of participants attending the two clinics was similar, and both clinic samples were more severe than cases in the epidemiological survey. The Internet clinic and national samples were older and comprised more females than those attending the outpatient clinic. The Internet clinic sample were more likely to be married than the other samples. The Internet clinic and outpatient clinic samples had higher levels of educational qualifications than the national sample, but employment status was similar across groups. The Internet clinic sample have disorders as severe as those attending an outpatient clinic, but with demographic characteristics more consistent with the national sample. These data indicate that the benefits of Internet

  20. Characteristics of adults with anxiety or depression treated at an internet clinic: comparison with a national survey and an outpatient clinic.

    Directory of Open Access Journals (Sweden)

    Nickolai Titov

    2010-05-01

    Full Text Available There is concern that people seeking treatment over the Internet for anxiety or depressive disorders may not resemble the general population or have less severe disorders than patients attending outpatient clinics or cases identified in community surveys. Thus the response to treatment in Internet based trials might not generalize.We reviewed the characteristics of applicants to an Australian Internet-based treatment clinic for anxiety and depression, and compared this sample with people from a national epidemiological survey and a sample of patients at a specialist outpatient anxiety and depression clinic. Participants included 774 volunteers to an Internet clinic, 454 patients at a specialist anxiety disorders outpatient clinic, and 627 cases identified in a national epidemiological survey. Main measures included demographic characteristics, and severity of symptoms as measured by the Kessler 10-Item scale (K-10, the 12-item World Health Organisation Disability Assessment Schedule second edition (WHODAS-II, the Penn State Worry Questionnaire (PSWQ, the Body Sensations Questionnaire (BSQ, the Automatic Cognitions Questionnaire (ACQ, the Social Interaction Anxiety Scale (SIAS and the Social Phobia Scale (SPS.The severity of symptoms of participants attending the two clinics was similar, and both clinic samples were more severe than cases in the epidemiological survey. The Internet clinic and national samples were older and comprised more females than those attending the outpatient clinic. The Internet clinic sample were more likely to be married than the other samples. The Internet clinic and outpatient clinic samples had higher levels of educational qualifications than the national sample, but employment status was similar across groups.The Internet clinic sample have disorders as severe as those attending an outpatient clinic, but with demographic characteristics more consistent with the national sample. These data indicate that the benefits

  1. Individual-level outcomes from a national clinical leadership development programme.

    Science.gov (United States)

    Patton, Declan; Fealy, Gerard; McNamara, Martin; Casey, Mary; Connor, Tom O; Doyle, Louise; Quinlan, Christina

    2013-08-01

    A national clinical leadership development programme was instituted for Irish nurses and midwives in 2010. Incorporating a development framework and leadership pathway and a range of bespoke interventions for leadership development, including workshops, action-learning sets, mentoring and coaching, the programme was introduced at seven pilot sites in the second half of 2011. The programme pilot was evaluated with reference to structure, process and outcomes elements, including individual-level programme outcomes. Evaluation data were generated through focus groups and group interviews, individual interviews and written submissions. The data provided evidence of nurses' and midwives' clinical leadership development through self and observer-reported behaviours and dispositions including accounts of how the programme participants developed and displayed particular clinical leadership competencies. A key strength of the new programme was that it involved interventions that focussed on specific leadership competencies to be developed within the practice context.

  2. Mentoring, coaching and action learning: interventions in a national clinical leadership development programme.

    Science.gov (United States)

    McNamara, Martin S; Fealy, Gerard M; Casey, Mary; O'Connor, Tom; Patton, Declan; Doyle, Louise; Quinlan, Christina

    2014-09-01

    To evaluate mentoring, coaching and action learning interventions used to develop nurses' and midwives' clinical leadership competencies and to describe the programme participants' experiences of the interventions. Mentoring, coaching and action learning are effective interventions in clinical leadership development and were used in a new national clinical leadership development programme, introduced in Ireland in 2011. An evaluation of the programme focused on how participants experienced the interventions. A qualitative design, using multiple data sources and multiple data collection methods. Methods used to generate data on participant experiences of individual interventions included focus groups, individual interviews and nonparticipant observation. Seventy participants, including 50 programme participants and those providing the interventions, contributed to the data collection. Mentoring, coaching and action learning were positively experienced by participants and contributed to the development of clinical leadership competencies, as attested to by the programme participants and intervention facilitators. The use of interventions that are action-oriented and focused on service development, such as mentoring, coaching and action learning, should be supported in clinical leadership development programmes. Being quite different to short attendance courses, these interventions require longer-term commitment on the part of both individuals and their organisations. In using mentoring, coaching and action learning interventions, the focus should be on each participant's current role and everyday practice and on helping the participant to develop and demonstrate clinical leadership skills in these contexts. © 2014 John Wiley & Sons Ltd.

  3. SANDS: a service-oriented architecture for clinical decision support in a National Health Information Network.

    Science.gov (United States)

    Wright, Adam; Sittig, Dean F

    2008-12-01

    In this paper, we describe and evaluate a new distributed architecture for clinical decision support called SANDS (Service-oriented Architecture for NHIN Decision Support), which leverages current health information exchange efforts and is based on the principles of a service-oriented architecture. The architecture allows disparate clinical information systems and clinical decision support systems to be seamlessly integrated over a network according to a set of interfaces and protocols described in this paper. The architecture described is fully defined and developed, and six use cases have been developed and tested using a prototype electronic health record which links to one of the existing prototype National Health Information Networks (NHIN): drug interaction checking, syndromic surveillance, diagnostic decision support, inappropriate prescribing in older adults, information at the point of care and a simple personal health record. Some of these use cases utilize existing decision support systems, which are either commercially or freely available at present, and developed outside of the SANDS project, while other use cases are based on decision support systems developed specifically for the project. Open source code for many of these components is available, and an open source reference parser is also available for comparison and testing of other clinical information systems and clinical decision support systems that wish to implement the SANDS architecture. The SANDS architecture for decision support has several significant advantages over other architectures for clinical decision support. The most salient of these are:

  4. Service impact of a national clinical leadership development programme: findings from a qualitative study.

    Science.gov (United States)

    Fealy, Gerard M; McNamara, Martin S; Casey, Mary; O'Connor, Tom; Patton, Declan; Doyle, Louise; Quinlan, Christina

    2015-04-01

    The study reported here was part of a larger study, which evaluated a national clinical leadership development programme with reference to resources, participant experiences, participant outcomes and service impact. The aim of the present study was to evaluate the programme's service impact. Clinical leadership development develops competencies that are expressed in context. The outcomes of clinical leadership development occur at individual, departmental and organisational levels. The methods used to evaluate the service impact were focus groups, group interviews and individual interviews. Seventy participants provided data in 18 separate qualitative data collection events. The data contained numerous accounts of service development activities, initiated by programme participants, which improved service and/or improved the culture of the work setting. Clinical leadership development programmes that incorporate a deliberate service impact element can result in identifiable positive service outcomes. The nuanced relationship between leader development and service development warrants further investigation. This study demonstrates that clinical leadership development can impact on service in distinct and identifiable ways. Clinical leadership development programmes should focus on the setting in which the leadership competencies will be demonstrated. © 2013 John Wiley & Sons Ltd.

  5. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer.

    Science.gov (United States)

    van Driel, Pieter B A A; Boonstra, Martin C; Slooter, Maxime D; Heukers, Raimond; Stammes, Marieke A; Snoeks, Thomas J A; de Bruijn, Henriette S; van Diest, Paul J; Vahrmeijer, Alexander L; van Bergen En Henegouwen, Paul M P; van de Velde, Cornelis J H; Löwik, Clemens W G M; Robinson, Dominic J; Oliveira, Sabrina

    2016-05-10

    Photodynamic therapy (PDT) induces cell death through local light activation of a photosensitizer (PS) and has been used to treat head and neck cancers. Yet, common PS lack tumor specificity, which leads to collateral damage to normal tissues. Targeted delivery of PS via antibodies has pre-clinically improved tumor selectivity. However, antibodies have long half-lives and relatively poor tissue penetration, which could limit therapeutic efficacy and lead to long photosensitivity. Here, in this feasibility study, we evaluate at the pre-clinical level a recently introduced format of targeted PDT, which employs nanobodies as targeting agents and a water-soluble PS (IRDye700DX) that is traceable through optical imaging. In vitro, the PS solely binds to cells and induces phototoxicity on cells overexpressing the epidermal growth factor receptor (EGFR), when conjugated to the EGFR targeted nanobodies. To investigate whether this new format of targeted PDT is capable of inducing selective tumor cell death in vivo, PDT was applied on an orthotopic mouse tumor model with illumination at 1h post-injection of the nanobody-PS conjugates, as selected from quantitative fluorescence spectroscopy measurements. In parallel, and as a reference, PDT was applied with an antibody-PS conjugate, with illumination performed 24h post-injection. Importantly, EGFR targeted nanobody-PS conjugates led to extensive tumor necrosis (approx. 90%) and almost no toxicity in healthy tissues, as observed through histology 24h after PDT. Overall, results show that these EGFR targeted nanobody-PS conjugates are selective and able to induce tumor cell death in vivo. Additional studies are now needed to assess the full potential of this approach to improving PDT. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. NCI Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 11, 2014.

  7. NCI Requests Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 9, 2012.

  8. Indirect-drive noncryogenic double-shell ignition targets for the National Ignition Facility: Design and analysis

    International Nuclear Information System (INIS)

    Amendt, Peter; Colvin, J.D.; Tipton, R.E.; Hinkel, D.E.; Edwards, M.J.; Landen, O.L.; Ramshaw, J.D.; Suter, L.J.; Varnum, W.S.; Watt, R.G.

    2002-01-01

    Analysis and design of indirect-drive National Ignition Facility double-shell targets with hohlraum temperatures of 200 eV and 250 eV are presented. The analysis of these targets includes the assessment of two-dimensional radiation asymmetry and nonlinear mix. Two-dimensional integrated hohlraum simulations indicate that the x-ray illumination can be adjusted to provide adequate symmetry control in hohlraums specially designed to have high laser-coupling efficiency [Suter et al., Phys. Plasmas 7, 2092 (2000)]. These simulations also reveal the need to diagnose and control localized 10-15 keV x-ray emission from the high-Z hohlraum wall because of strong absorption by the high-Z inner shell. Preliminary estimates of the degree of laser backscatter from an assortment of laser-plasma interactions suggest comparatively benign hohlraum conditions. The application of a variety of nonlinear mix models and phenomenological tools, including buoyancy-drag models, multimode simulations and fall-line optimization, indicates a possibility of achieving ignition, i.e., fusion yields greater than 1 MJ. Planned experiments on the Omega laser will test current understanding of high-energy radiation flux asymmetry and mix-induced yield degradation in double-shell targets

  9. Target salt 2025: a global overview of national programs to encourage the food industry to reduce salt in foods.

    Science.gov (United States)

    Webster, Jacqui; Trieu, Kathy; Dunford, Elizabeth; Hawkes, Corinna

    2014-08-21

    Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce salt. A systematic review of the literature was supplemented by key informant questionnaires to inform categorization of the initiatives. Fifty nine food industry salt reduction programs were identified. Thirty eight countries had targets for salt levels in foods and nine countries had introduced legislation for some products. South Africa and Argentina have both introduced legislation limiting salt levels across a broad range of foods. Seventeen countries reported reductions in salt levels in foods-the majority in bread. While these trends represent progress, many countries have yet to initiate work in this area, others are at early stages of implementation and further monitoring is required to assess progress towards achieving the global target.

  10. Targeted Nanoparticles for Image-guided Treatment of Triple Negative Breast Cancer: Clinical Significance and Technological Advances

    Science.gov (United States)

    Miller-Kleinhenz, Jasmine M.; Bozeman, Erica N.

    2015-01-01

    Effective treatment of triple negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and non-invasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise towards the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug-resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention (EPR) effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor associated endothelial cells, stromal fibroblasts and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as others and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. PMID:25966677

  11. Targeted nanoparticles for image-guided treatment of triple-negative breast cancer: clinical significance and technological advances.

    Science.gov (United States)

    Miller-Kleinhenz, Jasmine M; Bozeman, Erica N; Yang, Lily

    2015-01-01

    Effective treatment of triple-negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and noninvasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise toward the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle-based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor-associated endothelial cells, stromal fibroblasts, and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in-depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as by others, and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. © 2015 Wiley Periodicals, Inc.

  12. 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.

  13. Use of national clinical databases for informing and for evaluating health care policies.

    Science.gov (United States)

    Black, Nick; Tan, Stefanie

    2013-02-01

    Policy-makers and analysts could make use of national clinical databases either to inform or to evaluate meso-level (organisation and delivery of health care) and macro-level (national) policies. Reviewing the use of 15 of the best established databases in England, we identify and describe four published examples of each use. These show that policy-makers can either make use of the data itself or of research based on the database. For evaluating policies, the major advantages are the huge sample sizes available, the generalisability of the data, its immediate availability and historic information. The principal methodological challenges involve the need for risk adjustment and time-series analysis. Given their usefulness in the policy arena, there are several reasons why national clinical databases have not been used more, some due to a lack of 'push' by their custodians and some to the lack of 'pull' by policy-makers. Greater exploitation of these valuable resources would be facilitated by policy-makers' and custodians' increased awareness, minimisation of legal restrictions on data use, improvements in the quality of databases and a library of examples of applications to policy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Canadian Chronic Kidney Disease Clinics: A National Survey of Structure, Function and Models of Care

    Directory of Open Access Journals (Sweden)

    Adeera Levin

    2014-11-01

    Full Text Available Background: The goals of care for patients with chronic kidney disease (CKD are to delay progression to end stage renal disease, reduce complications, and to ensure timely transition to dialysis or transplantation, while optimizing independence. Recent guidelines recommend that multidisciplinary team based care should be available to patients with CKD. While most provinces fund CKD care, the specific models by which these outcomes are achieved are not known. Funding for clinics is hospital or program based. Objectives: To describe the structure and function of clinics in order to understand the current models of care, inform best practice and potentially standardize models of care. Design: Prospective cross sectional observational survey study. Setting, Patients/Participants: Canadian nephrology programs in all provinces. Methods and Measurements: Using an open-ended semi-structured questionnaire, we surveyed 71 of 84 multidisciplinary adult CKD clinics across Canada, by telephone and with written semi-structured questionnaires; (June 2012 to November 2013. Standardized introductory scripts were used, in both English and French. Results: CKD clinic structure and models of care vary significantly across Canada. Large variation exists in staffing ratios (Nephrologist, dieticians, pharmacists and nurses to patients, and in referral criteria. Dialysis initiation decisions were usually made by MDs. The majority of clinics (57% had a consistent model of care (the same Nephrologist and nurse per patient, while others had patients seeing a different nephrologist and nurses at each clinic visit. Targets for various modality choices varied, as did access to those modalities. No patient or provider educational tools describing the optimal time to start dialysis exist in any of the clinics. Limitations: The surveys rely on self reporting without validation from independent sources, and there was limited involvement of Quebec clinics. These are relative

  15. Year-End Clinic Handoffs: A National Survey of Academic Internal Medicine Programs.

    Science.gov (United States)

    Phillips, Erica; Harris, Christina; Lee, Wei Wei; Pincavage, Amber T; Ouchida, Karin; Miller, Rachel K; Chaudhry, Saima; Arora, Vineet M

    2017-06-01

    While there has been increasing emphasis and innovation nationwide in training residents in inpatient handoffs, very little is known about the practice and preparation for year-end clinic handoffs of residency outpatient continuity practices. Thus, the latter remains an identified, yet nationally unaddressed, patient safety concern. The 2014 annual Association of Program Directors in Internal Medicine (APDIM) survey included seven items for assessing the current year-end clinic handoff practices of internal medicine residency programs throughout the country. Nationwide survey. All internal medicine program directors registered with APDIM. Descriptive statistics of programs and tools used to formulate a year-end handoff in the ambulatory setting, methods for evaluating the process, patient safety and quality measures incorporated within the process, and barriers to conducting year-end handoffs. Of the 361 APDIM member programs, 214 (59%) completed the Transitions of Care Year-End Clinic Handoffs section of the survey. Only 34% of respondent programs reported having a year-end ambulatory handoff system, and 4% reported assessing residents for competency in this area. The top three barriers to developing a year-end handoff system were insufficient overlap between graduating and incoming residents, inability to schedule patients with new residents in advance, and time constraints for residents, attendings, and support staff. Most internal medicine programs do not have a year-end clinic handoff system in place. Greater attention to clinic handoffs and resident assessment of this care transition is needed.

  16. XML-based clinical data standardisation in the National Health Service Scotland

    Directory of Open Access Journals (Sweden)

    Raluca Bunduchi

    2006-12-01

    Full Text Available The objective of this paper is to clarify the role that socio-economic factors played in shaping the development of XML-based clinical data standards in the National Health Service in Scotland from 2000 to 2004. The paper discusses the NHS Scotland approach to clinical data standardisation, emphasising the actors involved, their choices during the standard development process and the factors that have shaped these choices. The case suggests that the NHS Scotland approach to clinical data standardisation is shaped by strong political pressures for fast development of an integrated electronic patient care system, economic pressures for high efficiency and cost reductions, and organisational requirements for strong clinical support. Such economic, political and organisational pressures explain the informal approach to standard development, the emphasis on fast system development and strong clinical involvement. At the same time, market factors explain the low commitment of the IT vendors, which might have otherwise put significant pressure onNHSScotland to pursue a more formalised standardisation approach within an internationally recognised standard-setting body.

  17. National turnaround time survey: professional consensus standards for optimal performance and thresholds considered to compromise efficient and effective clinical management.

    Science.gov (United States)

    McKillop, Derek J; Auld, Peter

    2017-01-01

    Background Turnaround time can be defined as the time from receipt of a sample by the laboratory to the validation of the result. The Royal College of Pathologists recommends that a number of performance indicators for turnaround time should be agreed with stakeholders. The difficulty is in arriving at a goal which has some evidence base to support it other than what may simply be currently achievable technically. This survey sought to establish a professional consensus on the goals and meaning of targets for laboratory turnaround time. Methods A questionnaire was circulated by the National Audit Committee to 173 lead consultants for biochemistry in the UK. The survey asked each participant to state their current target turnaround time for core investigations in a broad group of clinical settings. Each participant was also asked to provide a professional opinion on what turnaround time would pose an unacceptable risk to patient safety for each departmental category. A super majority (2/3) was selected as the threshold for consensus. Results The overall response rate was 58% ( n = 100) with a range of 49-72% across the individual Association for Clinical Biochemistry and Laboratory Medicine regions. The consensus optimal turnaround time for the emergency department was 2 h considered unacceptable. The times for general practice and outpatient department were 48 h and for Wards 12 h, respectively. Conclusions We consider that the figures provide a useful benchmark of current opinion, but clearly more empirical standards will have to develop alongside other aspects of healthcare delivery.

  18. Projected national impact of colorectal cancer screening on clinical and economic outcomes and health services demand.

    Science.gov (United States)

    Ladabaum, Uri; Song, Kenneth

    2005-10-01

    Colorectal cancer (CRC) screening is effective and cost-effective, but the potential national impact of widespread screening is uncertain. It is controversial whether screening colonoscopy can be offered widely and how emerging tests may impact health services demand. Our aim was to produce integrated, comprehensive estimates of the impact of widespread screening on national clinical and economic outcomes and health services demand. We used a Markov model and census data to estimate the national consequences of screening 75% of the US population with conventional and emerging strategies. Screening decreased CRC incidence by 17%-54% to as few as 66,000 cases per year and CRC mortality by 28%-60% to as few as 23,000 deaths per year. With no screening, total annual national CRC-related expenditures were 8.4 US billion dollars. With screening, expenditures for CRC care decreased by 1.5-4.4 US billion dollars but total expenditures increased to 9.2-15.4 US billion dollars. Screening colonoscopy every 10 years required 8.1 million colonoscopies per year including surveillance, with other strategies requiring 17%-58% as many colonoscopies. With improved screening uptake, total colonoscopy demand increased in general, even assuming substantial use of virtual colonoscopy. Despite savings in CRC care, widespread screening is unlikely to be cost saving and may increase national expenditures by 0.8-2.8 US billion dollars per year with conventional tests. The current national endoscopic capacity, as recently estimated, may be adequate to support widespread use of screening colonoscopy in the steady state. The impact of emerging tests on colonoscopy demand will depend on the extent to which they replace screening colonoscopy or increase screening uptake in the population.

  19. Target volume definition for external beam partial breast radiotherapy: Clinical, pathological and technical studies informing current approaches

    International Nuclear Information System (INIS)

    Kirby, Anna M.; Coles, Charlotte E.; Yarnold, John R.

    2010-01-01

    Partial breast irradiation (PBI) is currently under investigation in several phase III trials and, following a recent consensus statement, its use off-study may increase despite ongoing uncertainty regarding optimal target volume definition. We review the clinical, pathological and technical evidence for target volume definition in external beam partial breast irradiation (EB-PBI). The optimal method of tumour bed (TB) delineation requires X-ray CT imaging of implanted excision cavity wall markers. The definition of clinical target volume (CTV) as TB plus concentric 15 mm margins is based on the anatomical distribution of multifocal and multicentric disease around the primary tumour in mastectomy specimens, and the clinical locations of local tumour relapse (LR) after breast conservation surgery. If the majority of LR originate from foci of residual invasive and/or intraduct disease in the vicinity of the TB after complete microscopic resection, CTV margin logically takes account of the position of primary tumour within the surgical resection specimen. The uncertain significance of independent primary tumours as sources of preventable LR, and of wound healing responses in stimulating LR, increases the difficulties in defining optimal CTV. These uncertainties may resolve after long-term follow-up of current PBI trials. By contrast, a commonly used 10 mm clinical to planning target volume (PTV) margin has a stronger evidence base, although departmental set-up errors need to be confirmed locally. A CTV-PTV margin >10 mm may be required in women with larger breasts and/or large seromas, whilst the role of image-guided radiotherapy with or without TB markers in reducing CTV-PTV margins needs to be explored.

  20. A centralized informatics infrastructure for the National Institute on Drug Abuse Clinical Trials Network

    Science.gov (United States)

    Pan, Jeng-Jong; Nahm, Meredith; Wakim, Paul; Cushing, Carol; Poole, Lori; Tai, Betty; Pieper, Carl F.

    2009-01-01

    Background Clinical trial networks were created to provide a sustaining infrastructure for the conduct of multisite clinical trials. As such, they must withstand changes in membership. Centralization of infrastructure including knowledge management, portfolio management, information management, process automation, work policies, and procedures in clinical research networks facilitates consistency and ultimately research. Purpose In 2005, the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) transitioned from a distributed data management model to a centralized informatics infrastructure to support the network’s trial activities and administration. We describe the centralized informatics infrastructure and discuss our challenges to inform others considering such an endeavor. Methods During the migration of a clinical trial network from a decentralized to a centralized data center model, descriptive data were captured and are presented here to assess the impact of centralization. Results We present the framework for the informatics infrastructure and evaluative metrics. The network has decreased the time from last patient-last visit to database lock from an average of 7.6 months to 2.8 months. The average database error rate decreased from 0.8% to 0.2%, with a corresponding decrease in the interquartile range from 0.04%–1.0% before centralization to 0.01%–0.27% after centralization. Centralization has provided the CTN with integrated trial status reporting and the first standards-based public data share. A preliminary cost-benefit analysis showed a 50% reduction in data management cost per study participant over the life of a trial. Limitations A single clinical trial network comprising addiction researchers and community treatment programs was assessed. The findings may not be applicable to other research settings. Conclusions The identified informatics components provide the information and infrastructure needed for our clinical trial

  1. Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications.

    Science.gov (United States)

    Li, Junjie; Oyen, Raymond; Verbruggen, Alfons; Ni, Yicheng

    2013-01-01

    Hitting the evasive tumor cells proves challenging in targeted cancer therapies. A general and unconventional anticancer approach namely small molecule sequential dual-targeting theragnostic strategy (SMSDTTS) has recently been introduced with the aims to target and debulk the tumor mass, wipe out the residual tumor cells, and meanwhile enable cancer detectability. This dual targeting approach works in two steps for systemic delivery of two naturally derived drugs. First, an anti-tubulin vascular disrupting agent, e.g., combretastatin A4 phosphate (CA4P), is injected to selectively cut off tumor blood supply and to cause massive necrosis, which nevertheless always leaves peripheral tumor residues. Secondly, a necrosis-avid radiopharmaceutical, namely (131)I-hypericin ((131)I-Hyp), is administered the next day, which accumulates in intratumoral necrosis and irradiates the residual cancer cells with beta particles. Theoretically, this complementary targeted approach may biologically and radioactively ablate solid tumors and reduce the risk of local recurrence, remote metastases, and thus cancer mortality. Meanwhile, the emitted gamma rays facilitate radio-scintigraphy to detect tumors and follow up the therapy, hence a simultaneous theragnostic approach. SMSDTTS has now shown promise from multicenter animal experiments and may demonstrate unique anticancer efficacy in upcoming preliminary clinical trials. In this short review article, information about the two involved agents, the rationale of SMSDTTS, its preclinical antitumor efficacy, multifocal targetability, simultaneous theragnostic property, and toxicities of the dose regimens are summarized. Meanwhile, possible drawbacks, practical challenges and future improvement with SMSDTTS are discussed, which hopefully may help to push forward this strategy from preclinical experiments towards possible clinical applications.

  2. Anticipated Ethics and Regulatory Challenges in PCORnet: The National Patient-Centered Clinical Research Network.

    Science.gov (United States)

    Ali, Joseph; Califf, Robert; Sugarman, Jeremy

    2016-01-01

    PCORnet, the National Patient-Centered Clinical Research Network, seeks to establish a robust national health data network for patient-centered comparative effectiveness research. This article reports the results of a PCORnet survey designed to identify the ethics and regulatory challenges anticipated in network implementation. A 12-item online survey was developed by leadership of the PCORnet Ethics and Regulatory Task Force; responses were collected from the 29 PCORnet networks. The most pressing ethics issues identified related to informed consent, patient engagement, privacy and confidentiality, and data sharing. High priority regulatory issues included IRB coordination, privacy and confidentiality, informed consent, and data sharing. Over 150 IRBs and five different approaches to managing multisite IRB review were identified within PCORnet. Further empirical and scholarly work, as well as practical and policy guidance, is essential if important initiatives that rely on comparative effectiveness research are to move forward.

  3. Clinical applications of perfluorocarbon nanoparticles for molecular imaging and targeted therapeutics.

    Science.gov (United States)

    Tran, Trung D; Caruthers, Shelton D; Hughes, Michael; Marsh, John N; Cyrus, Tillmann; Winter, Patrick M; Neubauer, Anne M; Wickline, Samuel A; Lanza, Gregory M

    2007-01-01

    Molecular imaging is a novel tool that has allowed non-invasive diagnostic imaging to transition from gross anatomical description to identification of specific tissue epitopes and observation of biological processes at the cellular level. This technique has been confined to the field of nuclear imaging; however, recent advances in nanotechnology have extended this research to include ultrasound (US) and magnetic resonance (MR) imaging. The exploitation of nanotechnology for MR and US molecular imaging has generated several candidate contrast agents. One multimodality platform, targeted perfluorocarbon (PFC) nanoparticles, is useful for noninvasive detection with US and MR, targeted drug delivery, and quantification.

  4. National comparison of {sup 131}I measurement among nuclear medicine clinics of eight countries

    Energy Technology Data Exchange (ETDEWEB)

    Olsovcova, Veronika, E-mail: volsovcova@cmi.c [Czech Metrology Institute, Radiova 1, Praha 10, 102 00 (Czech Republic); Iwahara, Akira [Laboratorio Nacional de Metrologia das Radiacoes Ionizantes, Instituto de Radioprotecao e Dosimetria, Av. Salvador Allende, s/no. Recreio, Rio de Janeiro, CEP 22780-160 Brazil (Brazil); Oropesa, Pilar [Centro de Isotopos, Ave. Monumental y Carretera La Rada, Km 31/2, Guanabacoa, Ciudad Habana (Cuba); Joseph, Leena; Ravindra, Anuradha [Bhabha Atomic Research Centre, Radiation Safety Systems Division, Trombay, Mumbai-400 085 (India); Ghafoori, Mostafa [SSDL, Agricultural, Medical and Industrial Research School (AMIRS). Nuclear Science and Technology Research Institute, AEOI, Karaj (Iran, Islamic Republic of); Son, Hye-Kyung [Radiation Safety Division, National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, 194 Tongilro, Eunpyung-Gu, Seoul, 122-704 (Korea, Republic of); Sahagia, Maria [Horia Hulubei National Institute of R and D for Physics and Engineering, POB MG-6, 077125 Bucharest (Romania); Tastan, Selma [Ankara University Medical Faculty, Department of Nuclear Medicine, Cebeci 06100, Ankara (Turkey); Zimmerman, Brian [Dosimetry and Medical Radiation Physics Section, International Atomic Energy Agency, P.O. Box 100, A-1400 Vienna (Austria); Ionizing Radiation Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8462 (United States)

    2010-07-15

    A generally applicable protocol for organizing comparisons among nuclear medicine clinics created within the IAEA project CRP E2.10.05 was tested in Brazil, Cuba, Czech Republic, India, Iran, Republic of Korea, Romania and Turkey in 2007. Comparisons of measurement of {sup 131}I were organized by local pilot laboratories with different backgrounds and levels of experience in this field. The results and experiences gained were compared and analyzed. A majority of results in each national comparison were within 10% of the reference value.

  5. Treatment of adult patients with schizophrenia and complex mental health needs - A national clinical guideline

    DEFF Research Database (Denmark)

    Baandrup, Lone; Østrup Rasmussen, Jesper; Klokker, Louise

    2016-01-01

    BACKGROUND AND AIM: The Danish Health and Medicines Authority assembled a group of experts to develop a national clinical guideline for patients with schizophrenia and complex mental health needs. Within this context, ten explicit review questions were formulated, covering several identified key...... therapy for persistent positive and/or negative symptoms, and the combination of cognitive behavioural therapy and motivational interviewing for cannabis and/or central stimulant abuse. SSRI or SNRI add-on treatment for persistent negative symptoms should be used only cautiously. Where no evidence...

  6. Clinical, Bacteriologic, and Geographic Stratification of Melioidosis Emerges from the Sri Lankan National Surveillance Program.

    Science.gov (United States)

    Sathkumara, Harindra D; Merritt, Adam J; Corea, Enoka M; Krishnananthasivam, Shivankari; Natesan, Mohan; Inglis, Timothy J J; De Silva, Aruna Dharshan

    2018-02-01

    Melioidosis, a potentially fatal tropical infection, is said to be underdiagnosed in low-income countries. An increase in melioidosis cases in Sri Lanka allowed us to analyze the relationship among clinical outcome, bacteriology, epidemiology, and geography in the first 108 laboratory-confirmed cases of melioidosis from a nationwide surveillance program. The additional 76 cases of laboratory-confirmed melioidosis confirmed further associations between Burkholderia pseudomallei multilocus sequence typing (MLST) and infection phenotype; ST1137/unifocal bacteremic infection (χ 2 = 3.86, P national genotyping-supported melioidosis registry will improve melioidosis diagnosis, treatment, and prevention where underdiagnosis and mortality rates remain high.

  7. Targeted hepatic sonography during clinic visits for detection of fatty liver in overweight children: a pilot study.

    Science.gov (United States)

    Perito, Emily R; Tsai, Patrika M; Hawley, Sarah; Lustig, Robert H; Feldstein, Vickie A

    2013-04-01

    The purpose of this study was to assess the feasibility and utility of targeted hepatic sonography to evaluate for hepatic steatosis during a subspecialty clinic visit. In this pilot study, we performed targeted hepatic sonography on 25 overweight children aged 7 to 17 years consecutively seen in a pediatric obesity clinic. Long-axis images of the right lobe of the liver and a split-screen image of liver and spleen were taken. Images were interpreted in real time by the radiologist and shown to the family. Demographics, clinical measurements, and laboratory parameters were also collected from the specialty clinic visit on the same day. Sonography required a median of 4 minutes during the visit (interquartile range, 3-5 minutes). All consented patients completed the study. The median alanine aminotransferase (ALT) level was 23 U/L in those with no steatosis (n = 14), 26 U/L with mild steatosis (n = 6), and 41 U/L with moderate/marked steatosis (n = 5). Children with ALT levels of 25 to 50 U/L had very variable sonographic measures of hepatic steatosis. When the participants were categorized by the overall degree of fatty liver, hepatic steatosis was significantly associated with the aspartate aminotransferase level (P = .028), ALT level (P = .003), and diastolic blood pressure (P = .05) but did not correlate with age, sex, Latino race, or insulin resistance. Targeted hepatic sonography added information not apparent from routine ALT screening and provided immediate feedback to clinicians and families about the effect of obesity on end organs. This examination could be a feasible, informative addition to screening for children at high risk for nonalcoholic fatty liver disease who are seen in clinics that specialize in obesity.

  8. Possible version of the compression degradation of the thermonuclear indirect-irradiation targets at the national ignition facility and a reason for the failure of ignition

    Energy Technology Data Exchange (ETDEWEB)

    Rozanov, V. B., E-mail: rozanov@sci.lebedev.ru; Vergunova, G. A., E-mail: verg@sci.lebedev.ru [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation)

    2017-01-15

    The main parameters of compression of a target and tendencies at change in the irradiation conditions are determined by analyzing the published results of experiments at the megajoule National Ignition Facility (NIF) on the compression of capsules in indirect-irradiation targets by means of the one-dimensional RADIAN program in the spherical geometry. A possible version of the “failure of ignition” of an indirect-irradiation target under the NIF conditions is attributed to radiation transfer. The application of onedimensional model to analyze the National Ignition Campaign (NIC) experiments allows identifying conditions corresponding to the future ignition regime and distinguishing them from conditions under which ignition does not occur.

  9. Socioeconomic inequalities in prognostic markers of non-Hodgkin lymphoma: analysis of a national clinical database

    DEFF Research Database (Denmark)

    Frederiksen, Birgitte Lidegaard; Brown, Peter de Nully; Dalton, Susanne Oksbjerg

    2011-01-01

    in histological subgroups reflecting aggressiveness of disease among the social groups. One of the most likely mechanisms of the social difference is longer delay in those with low socioeconomic position. The findings of social inequality in prognostic markers in non-Hodgkin lymphoma (NHL) patients could already......The survival of non-Hodgkin lymphoma patients strongly depends on a range of prognostic factors. This registry-based clinical cohort study investigates the relation between socioeconomic position and prognostic markers in 6234 persons included in a national clinical database in 2000-2008, Denmark....... Several measures of individual socioeconomic position were achieved from Statistics Denmark. The risk of being diagnosed with advanced disease, as expressed by the six prognostic markers (Ann Arbor stage III or IV, more than one extranodal lesion, elevated serum lactate dehydrogenase (LDH), performance...

  10. Reagent Target Request for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    NCI's Antibody Characterization Program provides reagents and other critical resources to support protein/peptide measurements and analysis. In an effort to produce and distribute well-characterized monoclonal antibodies to the scientific community, the program is seeking cancer related protein targets for antibody production and characterization for distribution to the research community. Submission Period: May 20, 2011 - July 1, 2011.

  11. The co registration of initial PET on the CT-radiotherapy reduces significantly the variabilities of anatomo-clinical target volume in the child hodgkin disease

    International Nuclear Information System (INIS)

    Metwally, H.; Blouet, A.; David, I.; Rives, M.; Izar, F.; Courbon, F.; Filleron, T.; Laprie, A.; Plat, G.; Vial, J.

    2009-01-01

    It exists a great interobserver variability for the anatomo-clinical target volume (C.T.V.) definition in children suffering of Hodgkin disease. In this study, the co-registration of the PET with F.D.G. on the planning computed tomography has significantly lead to a greater coherence in the clinical target volume definition. (N.C.)

  12. Survey and visual detection of Zaire ebolavirus in clinical samples targeting the nucleoprotein gene in Sierra Leone

    Directory of Open Access Journals (Sweden)

    Jing Yuan

    2015-12-01

    Full Text Available Ebola virus (EBOV can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP method to detect Zaire ebolavirus using the nucleoprotein gene (NP as a target sequence. Two different techniques were used, a calcein/Mn2+ complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR. Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.

  13. Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Francesco Panza

    2016-01-01

    Full Text Available The failure of several Phase II/III clinical trials in Alzheimer’s disease (AD with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI is methylthioninium (MT, a drug existing in equilibrium between a reduced (leuco-methylthioninium and oxidized form (MT+. MT chloride (methylene blue was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid.

  14. Multi-MW accelerator target material properties under proton irradiation at Brookhaven National Laboratory linear isotope producer

    Science.gov (United States)

    Simos, N.; Ludewig, H.; Kirk, H.; Dooryhee, E.; Ghose, S.; Zhong, Z.; Zhong, H.; Makimura, S.; Yoshimura, K.; Bennett, J. R. J.; Kotsinas, G.; Kotsina, Z.; McDonald, K. T.

    2018-05-01

    The effects of proton beams irradiating materials considered for targets in high-power accelerator experiments have been studied using the Brookhaven National Laboratory's (BNL) 200 MeV proton linac. A wide array of materials and alloys covering a wide range of the atomic number (Z) are being scoped by the high-power accelerator community prompting the BNL studies to focus on materials representing each distinct range, i.e. low-Z, mid-Z and high-Z. The low range includes materials such as beryllium and graphite, the midrange alloys such as Ti-6Al-4V, gum metal and super-Invar and finally the high-Z range pure tungsten and tantalum. Of interest in assessing proton irradiation effects are (a) changes in physiomechanical properties which are important in maintaining high-power target functionality, (b) identification of possible limits of proton flux or fluence above which certain materials cease to maintain integrity, (c) the role of material operating temperature in inducing or maintaining radiation damage reversal, and (d) phase stability and microstructural changes. The paper presents excerpt results deduced from macroscopic and microscopic post-irradiation evaluation (PIE) following several irradiation campaigns conducted at the BNL 200 MeV linac and specifically at the isotope producer beam-line/target station. The microscopic PIE relied on high energy x-ray diffraction at the BNL NSLS X17B1 and NSLS II XPD beam lines. The studies reveal the dramatic effects of irradiation on phase stability in several of the materials, changes in physical properties and ductility loss as well as thermally induced radiation damage reversal in graphite and alloys such as super-Invar.

  15. The experimental plan for cryogenic layered target implosions on the National Ignition Facility - The inertial confinement approach to fusion

    International Nuclear Information System (INIS)

    Edwards, M. J.; Lindl, J. D.; Spears, B. K.; Weber, S. V.; Atherton, L. J.; Bleuel, D. L.; Bradley, D. K.; Callahan, D. A.; Cerjan, C. J.; Clark, D; Collins, G. W.; Fair, J. E.; Fortner, R. J.; Glenzer, S. H.; Haan, S. W.; Hammel, B. A.; Hamza, A. V.; Hatchett, S. P.; Izumi, N.; Jacoby, B.

    2011-01-01

    Ignition requires precisely controlled, high convergence implosions to assemble a dense shell of deuterium-tritium (DT) fuel with ρR>∼1 g/cm 2 surrounding a 10 keV hot spot with ρR ∼ 0.3 g/cm 2 . A working definition of ignition has been a yield of ∼1 MJ. At this yield the α-particle energy deposited in the fuel would have been ∼200 kJ, which is already ∼10 x more than the kinetic energy of a typical implosion. The National Ignition Campaign includes low yield implosions with dudded fuel layers to study and optimize the hydrodynamic assembly of the fuel in a diagnostics rich environment. The fuel is a mixture of tritium-hydrogen-deuterium (THD) with a density equivalent to DT. The fraction of D can be adjusted to control the neutron yield. Yields of ∼10 14-15 14 MeV (primary) neutrons are adequate to diagnose the hot spot as well as the dense fuel properties via down scattering of the primary neutrons. X-ray imaging diagnostics can function in this low yield environment providing additional information about the assembled fuel either by imaging the photons emitted by the hot central plasma, or by active probing of the dense shell by a separate high energy short pulse flash. The planned use of these targets and diagnostics to assess and optimize the assembly of the fuel and how this relates to the predicted performance of DT targets is described. It is found that a good predictor of DT target performance is the THD measurable parameter, Experimental Ignition Threshold Factor, ITFX ∼ Y x dsf 2.3 , where Y is the measured neutron yield between 13 and 15 MeV, and dsf is the down scattered neutron fraction defined as the ratio of neutrons between 10 and 12 MeV and those between 13 and 15 MeV.

  16. National questionnaire study on clinical ICT systems proofs: physicians suffer from poor usability.

    Science.gov (United States)

    Viitanen, Johanna; Hyppönen, Hannele; Lääveri, Tinja; Vänskä, Jukka; Reponen, Jarmo; Winblad, Ilkka

    2011-10-01

    In the health informatics field, usability studies typically focus on evaluating a single information system and involve a rather small group of end-users. However, little is known about the usability of clinical information and communication technology (ICT) environment in which healthcare professionals work daily. This paper aims at contributing to usability research and user-oriented development of healthcare technologies with three objectives: inform researchers and practitioners about the current state of usability of clinical ICT systems, increase the understanding of usability aspects specific for clinical context, and encourage a more holistic approach on studying usability issues in health informatics field. A national web questionnaire study was conducted in Finland in spring 2010 with 3929 physicians actively working in patient care. For the purposes of the study, we described three dimensions of clinical ICT system usability that reflect the physicians' viewpoint on system usage: (1) compatibility between clinical ICT systems and physicians' tasks, (2) ICT support for information exchange, communication and collaboration in clinical work, and (3) interoperability and reliability. The dimensions derive from the definitions of usability and clinical context of use analysis, and reflect the ability of ICT systems to have a positive impact on patient care by supporting physicians in achieving their goals with a pleasant user experience. The research data incorporated 32 statements with a five-point Likert-scale on physicians' experiences on usability of their currently used ICT systems and a summative question about school grade given to electronic health record (EHR) systems. Physicians' estimates of their EHR systems were very critical. With the rating scale from 4 or fail to 10 or excellent, the average of the grades varied from 6.1 to 8.4 dependent on the kind of facility the physician is working. Questionnaire results indicated several usability

  17. Image-aided Suicide Gene Therapy Utilizing Multifunctional hTERT-targeting Adenovirus for Clinical Translation in Hepatocellular Carcinoma.

    Science.gov (United States)

    Kim, Yun-Hee; Kim, Kyung Tae; Lee, Sang-Jin; Hong, Seung-Hee; Moon, Ju Young; Yoon, Eun Kyung; Kim, Sukyoung; Kim, Eun Ok; Kang, Se Hun; Kim, Seok Ki; Choi, Sun Il; Goh, Sung Ho; Kim, Daehong; Lee, Seong-Wook; Ju, Mi Ha; Jeong, Jin Sook; Kim, In-Hoo

    2016-01-01

    Trans-splicing ribozyme enables to sense and reprogram target RNA into therapeutic transgene and thereby becomes a good sensing device for detection of cancer cells, judging from transgene expression. Previously we proposed PEPCK-Rz-HSVtk (PRT), hTERT targeting trans-splicing ribozyme (Rz) driven by liver-specific promoter phosphoenolpyruvate carboxykinase (PEPCK) with downstream suicide gene, herpes simplex virus thymidine kinase (HSVtk) for hepatocellular carcinoma (HCC) gene therapy. Here, we describe success of a re-engineered adenoviral vector harboring PRT in obtaining greater antitumor activity with less off-target effect for clinical application as a theranostics. We introduced liver-selective apolipoprotein E (ApoE) enhancer to the distal region of PRT unit to augment activity and liver selectivity of PEPCK promoter, and achieved better transduction into liver cancer cells by replacement of serotype 35 fiber knob on additional E4orf1-4 deletion of E1&E3-deleted serotype 5 back bone. We demonstrated that our refined adenovirus harboring PEPCK/ApoE-Rz-HSVtk (Ad-PRT-E) achieved great anti-tumor efficacy and improved ability to specifically target HCC without damaging normal hepatocytes. We also showed noninvasive imaging modalities were successfully employed to monitor both how well a therapeutic gene (HSVtk) was expressed inside tumor and how effectively a gene therapy took an action in terms of tumor growth. Collectively, this study suggests that the advanced therapeutic adenoviruses Ad-PRT-E and its image-aided evaluation system may lead to the powerful strategy for successful clinical translation and the development of clinical protocols for HCC therapy.

  18. Psychosocial impact of participation in the National Veterans Wheelchair Games and Winter Sports Clinic.

    Science.gov (United States)

    Sporner, Michelle L; Fitzgerald, Shirley G; Dicianno, Brad E; Collins, Diane; Teodorski, Emily; Pasquina, Paul F; Cooper, Rory A

    2009-01-01

    The purpose of this study was to determine the characteristics of individuals who participate in the National Veterans Wheelchair Games (NVWG) and the Winter Sports Clinic (WSC) for veterans with disabilities. In addition, it was of interest to determine how these events had impacted their lives. Participants were recruited at the 20th Winter Sports Clinic, held in Snowmass Colorado and the 26th National Veterans Wheelchair Games held in Anchorage, Alaska. Data of interest included demographic, sport participation information, community integration, self-esteem, and quality of life. A secondary data analysis was completed to determine how comparable individuals who attended the NVWG/WSC were to individuals who did not participate in these events. The 132 participants were a mean age of 47.4 + 13.4 and lived with a disability for an average of 13.4 + 12.1. Participants felt that the NVWG/WSC increased their knowledge of sports equipment (92%), learning sports (89%), mobility skills (84%), and acceptance of disability (84%). The majority of participants stated that the NVWG/WSC improved their life. Of those who participated at the NVWG/WSC, they tended to be more mobile, but have increased physical and cognitive limitations as measured by the CHART when compared to the non-attendees. Recommending veterans participate in events such as the NVWG and WSC can provide psychosocial benefits to veterans with disabilities.

  19. Federated queries of clinical data repositories: Scaling to a national network.

    Science.gov (United States)

    Weber, Griffin M

    2015-06-01

    Federated networks of clinical research data repositories are rapidly growing in size from a handful of sites to true national networks with more than 100 hospitals. This study creates a conceptual framework for predicting how various properties of these systems will scale as they continue to expand. Starting with actual data from Harvard's four-site Shared Health Research Information Network (SHRINE), the framework is used to imagine a future 4000 site network, representing the majority of hospitals in the United States. From this it becomes clear that several common assumptions of small networks fail to scale to a national level, such as all sites being online at all times or containing data from the same date range. On the other hand, a large network enables researchers to select subsets of sites that are most appropriate for particular research questions. Developers of federated clinical data networks should be aware of how the properties of these networks change at different scales and design their software accordingly. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Obstacles to the implementation of the treat-to-target strategy for rheumatoid arthritis in clinical practice in Japan.

    Science.gov (United States)

    Kaneko, Yuko; Koike, Takao; Oda, Hiromi; Yamamoto, Kazuhiko; Miyasaka, Nobuyuki; Harigai, Masayoshi; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Takeuchi, Tsutomu

    2015-01-01

    To clarify the obstacles preventing the implementation of the treat-to-target (T2T) strategy for rheumatoid arthritis (RA) in clinical practice. A total of 301 rheumatologists in Japan completed a questionnaire. In the first section, participants were indirectly questioned on the implementation of basic components of T2T, and in the second section, participants were directly questioned on their level of agreement and application. Although nearly all participants set treatment targets for the majority of RA patients with moderate to high disease activity, the proportion who set clinical remission as their target was 59%, with only 45% of these using composite measures. The proportion of participants who monitored X-rays and Health Assessment Questionnaires for all their patients was 44% and 14%, respectively. The proportion of participants who did not discuss treatment strategies was 44%, with approximately half of these reasoning that this was due to a proportion of patients having a lack of understanding of the treatment strategy or inability to make decisions. When participants were directly questioned, there was a high level of agreement with the T2T recommendations. Although there was a high level of agreement with the T2T recommendations, major obstacles preventing its full implementation still remain.

  1. Headache after traumatic brain injury: a national survey of clinical practices and treatment approaches.

    Science.gov (United States)

    Brown, Allen W; Watanabe, Thomas K; Hoffman, Jeanne M; Bell, Kathleen R; Lucas, Sylvia; Dikmen, Sureyya

    2015-01-01

    Individuals with headache after traumatic brain injury (TBI) receive care in a wide variety of clinical locations by physicians trained in multiple specialties. To understand current practice patterns and perceptions of treatment issues among clinicians managing headache after TBI. National survey of current clinical practice using a 20-item questionnaire developed by the authors. Survey respondents were members of the Central Nervous System Council list survey of the American Academy of Physical Medicine and Rehabilitation (N = 1782) and the American Headache Society membership (N = 1260). The survey was sent electronically to potential participants and was followed by 2 biweekly reminders. The survey queried the physicians' clinical setting; their use of headache classification systems, headache diaries, checklists, and diagnostic procedures; the pharmacologic and nonpharmacologic treatments prescribed; and headache chronicity and associated symptoms and disorders among their patients with TBI. Completed surveys were received from 193 respondents. The use of standardized classification systems and checklists was commonly reported. Respondents used nonpharmacologic and pharmacologic treatment approaches with similar frequency and modest perceived success rates. A high frequency of headache-associated new sleep and mood disorders was reported. When response differences occurred between practice settings, they reflected a focus on headache diagnosis, classification, and pharmacologic treatment among neurology and specialty headache clinics, whereas a nonpharmacologic approach to management among TBI specialty and general rehabilitation clinicians was more commonly reported. Management strategies for treating headache after TBI vary widely among general and specialty clinical practices. This suggests that additional research is needed that would lead to an increase in the use of established headache classification and the development of standardized management

  2. SU-E-P-03: The Australian Clinical Dosimetry Service, a Bespoke National Solution

    International Nuclear Information System (INIS)

    Williams, I; Lye, J; Alves, A; Lehmann, J; Kenny, J; Dunn, L; Kron, T

    2015-01-01

    Purpose: The Australian Clinical Dosimetry Service, (ACDS) was a pilot program to enable the Australian Government to determine whether a locally designed audit program was suitable for mitigating dosimetric error risk to radiotherapy patients within Australia. The outcomes from four years of operations will be presented and discussed with a focus why and how the pilot requirements were met. The consequnces of success will be considered, the lessons learnt from the pilot program and how they are impacting the future ACDS design, operation and engagement with stakeholders. Methods: The ACDS was designed over 2010/11 by experts drawn from the three professions in consultation with the national Department of Health. The list of outcomes required over a three year pilot was expressed in a Memorandum of Understanding, (MoU) between Health and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) which hosted the ACDS. Results: The ACDS has achieved all the MoU requirements. This paper describes how the staff within the ACDS engaged with the professional clinical workforce and provided a successful and functioning audit service. It identifies the strengths and weaknesses within the MoU and the ACDS structure and how the ACDS resolved a number of conflicting issues. It identifies the successes within the ACDS and how these were achieved. It provides details to assist and advise those seeking to design or modify national or regional auditing programs. Finally the paper reviews potential futures for the ACDS. Conclusion: The raw number of audits and outcomes indicate that the ACDS has met the MoU auditing requirements. The reasons for the ACDS’ success are highly dependent on: attracting quality staff who can respond with agility to changing situations, a high level of communication with the professional community, a high level of engagement by the community and an interested and engaged Federal Department. The Australian Clinical Dosimetry Service is a

  3. SU-E-P-03: The Australian Clinical Dosimetry Service, a Bespoke National Solution

    Energy Technology Data Exchange (ETDEWEB)

    Williams, I; Lye, J; Alves, A [Australian Clinical Dosimetry Service, Yallambie, Vic (Australia); Lehmann, J [University of Sydney, Sydney (Australia); Kenny, J [Epworth HealthCare, Richmond, VIC (Australia); Dunn, L [Royal Melbourne Institute of Technology, Melbourne (Australia); Kron, T [Peter MacCallum Cancer Instit., Melbourne (Australia)

    2015-06-15

    Purpose: The Australian Clinical Dosimetry Service, (ACDS) was a pilot program to enable the Australian Government to determine whether a locally designed audit program was suitable for mitigating dosimetric error risk to radiotherapy patients within Australia. The outcomes from four years of operations will be presented and discussed with a focus why and how the pilot requirements were met. The consequnces of success will be considered, the lessons learnt from the pilot program and how they are impacting the future ACDS design, operation and engagement with stakeholders. Methods: The ACDS was designed over 2010/11 by experts drawn from the three professions in consultation with the national Department of Health. The list of outcomes required over a three year pilot was expressed in a Memorandum of Understanding, (MoU) between Health and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) which hosted the ACDS. Results: The ACDS has achieved all the MoU requirements. This paper describes how the staff within the ACDS engaged with the professional clinical workforce and provided a successful and functioning audit service. It identifies the strengths and weaknesses within the MoU and the ACDS structure and how the ACDS resolved a number of conflicting issues. It identifies the successes within the ACDS and how these were achieved. It provides details to assist and advise those seeking to design or modify national or regional auditing programs. Finally the paper reviews potential futures for the ACDS. Conclusion: The raw number of audits and outcomes indicate that the ACDS has met the MoU auditing requirements. The reasons for the ACDS’ success are highly dependent on: attracting quality staff who can respond with agility to changing situations, a high level of communication with the professional community, a high level of engagement by the community and an interested and engaged Federal Department. The Australian Clinical Dosimetry Service is a

  4. Are data from national quality registries used in quality improvement at Swedish hospital clinics?

    Science.gov (United States)

    Fredriksson, Mio; Halford, Christina; Eldh, Ann Catrine; Dahlström, Tobias; Vengberg, Sofie; Wallin, Lars; Winblad, Ulrika

    2017-11-01

    To investigate the use of data from national quality registries (NQRs) in local quality improvement as well as purported key factors for effective clinical use in Sweden. Comparative descriptive: a web survey of all Swedish hospitals participating in three NQRs with different levels of development (certification level). Heads of the clinics and physician(s) at clinics participating in the Swedish Stroke Register (Riksstroke), the Swedish National Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) and the Swedish Lung Cancer Registry (NLCR). Individual and unit level use of NQRs in local quality improvement, and perceptions on data quality, organizational conditions and user motivation. Riksstroke data were reported as most extensively used at individual and unit levels (x̅ 17.97 of 24 and x̅ 27.06 of 35). Data quality and usefulness was considered high for the two most developed NQRs (x̅ 19.86 for Riksstroke and x̅ 19.89 for GallRiks of 25). Organizational conditions were estimated at the same level for Riksstroke and GallRiks (x̅ 12.90 and x̅ 13.28 of 20) while the least developed registry, the NLCR, had lower estimates (x̅ 10.32). In Riksstroke, the managers requested registry data more often (x̅ 15.17 of 20). While there were significant differences between registries in key factors such as management interest, use of NQR data in local quality improvement seems rather prevalent, at least for Riksstroke. The link between the registry's level of development and factors important for routinization of innovations such as NQRs needs investigation. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  5. Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sheikhbahaei, Sara; Solnes, Lilja B.; Javadi, Mehrbod S.; Pomper, Martin G.; Rowe, Steven P. [Johns Hopkins University School of Medicine, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Afshar-Oromieh, Ali; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Eiber, Matthias [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Technical University of Munich, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Ross, Ashley E.; Pienta, Kenneth J.; Allaf, Mohamad E.; Gorin, Michael A. [Johns Hopkins University School of Medicine, The James Buchanan Brady Urological Institute and Department of Urology, Baltimore, MD (United States)

    2017-11-15

    The rapidly expanding clinical adaptation of prostate-specific membrane antigen (PSMA)-targeted PET imaging in the evaluation of patients with prostate cancer has placed an increasing onus on understanding both the potential pearls of interpretation as well as limitations of this new technique. As with any new molecular imaging modality, accurate characterization of abnormalities on PSMA-targeted PET imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants of radiotracer uptake, and potential sources of false-positive and false-negative imaging findings. In recent years, a growing number of reports have come to light describing incidental non-prostatic benign or malignant pathologies with high uptake on PSMA-targeted PET imaging. In this review, we have summarized the published literature regarding the potential pearls and technical and interpretive pitfalls of this imaging modality. Knowledge of these limitations can increase the confidence of interpreting physicians and thus improve patient care. As PSMA-targeted PET is expected to be evaluated in larger prospective trials, the dissemination of potential diagnostic pitfalls and the biologic underpinning of those findings will be of increased importance. (orig.)

  6. Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging

    International Nuclear Information System (INIS)

    Sheikhbahaei, Sara; Solnes, Lilja B.; Javadi, Mehrbod S.; Pomper, Martin G.; Rowe, Steven P.; Afshar-Oromieh, Ali; Haberkorn, Uwe; Eiber, Matthias; Ross, Ashley E.; Pienta, Kenneth J.; Allaf, Mohamad E.; Gorin, Michael A.

    2017-01-01

    The rapidly expanding clinical adaptation of prostate-specific membrane antigen (PSMA)-targeted PET imaging in the evaluation of patients with prostate cancer has placed an increasing onus on understanding both the potential pearls of interpretation as well as limitations of this new technique. As with any new molecular imaging modality, accurate characterization of abnormalities on PSMA-targeted PET imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants of radiotracer uptake, and potential sources of false-positive and false-negative imaging findings. In recent years, a growing number of reports have come to light describing incidental non-prostatic benign or malignant pathologies with high uptake on PSMA-targeted PET imaging. In this review, we have summarized the published literature regarding the potential pearls and technical and interpretive pitfalls of this imaging modality. Knowledge of these limitations can increase the confidence of interpreting physicians and thus improve patient care. As PSMA-targeted PET is expected to be evaluated in larger prospective trials, the dissemination of potential diagnostic pitfalls and the biologic underpinning of those findings will be of increased importance. (orig.)

  7. Assessment of patient safety culture in clinical laboratories in the Spanish National Health System.

    Science.gov (United States)

    Giménez-Marín, Angeles; Rivas-Ruiz, Francisco; García-Raja, Ana M; Venta-Obaya, Rafael; Fusté-Ventosa, Margarita; Caballé-Martín, Inmaculada; Benítez-Estevez, Alfonso; Quinteiro-García, Ana I; Bedini, José Luis; León-Justel, Antonio; Torra-Puig, Montserrat

    2015-01-01

    There is increasing awareness of the importance of transforming organisational culture in order to raise safety standards. This paper describes the results obtained from an evaluation of patient safety culture in a sample of clinical laboratories in public hospitals in the Spanish National Health System. A descriptive cross-sectional study was conducted among health workers employed in the clinical laboratories of 27 public hospitals in 2012. The participants were recruited by the heads of service at each of the participating centers. Stratified analyses were performed to assess the mean score, standardized to a base of 100, of the six survey factors, together with the overall patient safety score. 740 completed questionnaires were received (88% of the 840 issued). The highest standardized scores were obtained in Area 1 (individual, social and cultural) with a mean value of 77 (95%CI: 76-78), and the lowest ones, in Area 3 (equipment and resources), with a mean value of 58 (95%CI: 57-59). In all areas, a greater perception of patient safety was reported by the heads of service than by other staff. We present the first multicentre study to evaluate the culture of clinical safety in public hospital laboratories in Spain. The results obtained evidence a culture in which high regard is paid to safety, probably due to the pattern of continuous quality improvement. Nevertheless, much remains to be done, as reflected by the weaknesses detected, which identify areas and strategies for improvement.

  8. Using an International Clinical Registry of Regional Anesthesia to Identify Targets for Quality Improvement

    Science.gov (United States)

    Sites, Brian D.; Barrington, Michael J.; Davis, Matthew

    2014-01-01

    Background Despite the widespread use of regional anesthesia, limited information on clinical performance exists. Institutions, therefore, have little knowledge of how they are performing in regards to both safety and effectiveness. In this study, we demonstrate how a medical institution (or physician/physician group) may use data from a multi-center clinical registry of regional anesthesia to inform quality improvement strategies. Methods We analyzed data from the International Registry of Regional Anesthesia that includes prospective data on peripheral regional anesthesia procedures from 19 centers located around the world. Using data from the clinical registry, we present summary statistics of the overall safety and effectiveness of regional anesthesia. Furthermore, we demonstrate, using a variety of performance measures, how these data can be used by hospitals to identify areas for quality improvement. To do so, we compare the performance of one member institution (a United States medical center in New Hampshire) to that of the other 18 member institutions of the clinical registry. Results The clinical registry contained information on 23,271 blocks that were performed between June 1, 2011, and May 1, 2014, on 16,725 patients. The overall success rate was 96.7%, immediate complication rate was 2.2%, and the all-cause 60-day rate of neurological sequelae was 8.3 (95% CI, 7.2–9.7) per 10,000. Registry wide major hospital events included 7 wrong site blocks, 3 seizures, 1 complete heart block, 1 retroperitoneal hematoma, and 3 pneumothoraces. For our reference medical center, we identified areas meriting quality improvement. Specifically, after accounting for differences in the age, sex, and health status of patient populations, the reference medical center appeared to rely more heavily on opioids for post procedure management, had higher patient pain scores, and experienced delayed discharge when compared with other member institutions. Conclusions To our

  9. 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.

  10. Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials.

    Science.gov (United States)

    Eckel, Florian; Schmid, Roland M

    2014-01-01

    In biliary tract cancer, gemcitabine platinum (GP) doublet palliative chemotherapy is the current standard treatment. The aim of this study was to analyze recent trials, even those small and nonrandomized, and identify superior new regimens. Trials published in English between January 2000 and January 2014 were analyzed, as well as ASCO abstracts from 2010 to 2013. In total, 161 trials comprising 6,337 patients were analyzed. The pooled results of standard therapy GP (no fluoropyrimidine, F, or other drug) were as follows: the median response rate (RR), tumor control rate (TCR), time to tumor progression (TTP) and overall survival (OS) were 25.9 and 63.5%, and 5.3 and 9.5 months, respectively. GFP triplets as well as G-based chemotherapy plus targeted therapy were significantly superior to GP concerning tumor control (TCR, TTP) and OS, with no difference in RR. Triplet combinations of GFP as well as G-based chemotherapy with (predominantly EGFR) targeted therapy are most effective concerning tumor control and survival.

  11. Targeted NGS meets expert clinical characterization: Efficient diagnosis of spastic paraplegia type 11

    Directory of Open Access Journals (Sweden)

    Cristina Castro-Fernández

    2015-06-01

    Full Text Available Next generation sequencing (NGS is transforming the diagnostic approach for neurological disorders, since it allows simultaneous analysis of hundreds of genes, even based on just a broad, syndromic patient categorization. However, such an approach bears a high risk of incidental and uncertain genetic findings. We report a patient with spastic paraplegia whose comprehensive neurological and imaging examination raised a high clinical suspicion of SPG11. Thus, although our NGS pipeline for this group of disorders includes gene panel and exome sequencing, in this sample only the spatacsin gene region was captured and subsequently searched for mutations. Two probably pathogenic variants were quickly and clearly identified, confirming the diagnosis of SPG11. This case illustrates how combination of expert clinical characterization with highly oriented NGS protocols leads to a fast, cost-efficient diagnosis, minimizing the risk of findings with unclear significance.

  12. Recurrence pattern of squamous cell carcinoma in the midthoracic esophagus: implications for the clinical target volume design of postoperative radiotherapy

    Directory of Open Access Journals (Sweden)

    Wang X

    2016-10-01

    stations 2, 4, 5, and 7 LNs should be delineated as clinical target volume of postoperative prophylactic irradiation, and upper abdominal LNs should be excluded. While for midthoracic ESCC with three or more positive nodes, upper abdominal LNs should also be included. The length of tumor and histological differentiation should be considered comprehensively to design the clinical target volume for radiotherapy. Keywords: esophagus cancer, radiotherapy, recurrence and metastasis, clinical target volume

  13. HIV/AIDS National Strategic Plans of Sub-Saharan African countries: an analysis for gender equality and sex-disaggregated HIV targets.

    Science.gov (United States)

    Sherwood, Jennifer; Sharp, Alana; Cooper, Bergen; Roose-Snyder, Beirne; Blumenthal, Susan

    2017-12-01

    National Strategic Plans (NSPs) for HIV/AIDS are country planning documents that set priorities for programmes and services, including a set of targets to quantify progress toward national and international goals. The inclusion of sex-disaggregated targets and targets to combat gender inequality is important given the high disease burden among young women and adolescent girls in Sub-Saharan Africa, yet no comprehensive gender-focused analysis of NSP targets has been performed. This analysis quantitatively evaluates national HIV targets, included in NSPs from eighteen Sub-Saharan African countries, for sex-disaggregation. Additionally, NSP targets aimed at reducing gender-based inequality in health outcomes are compiled and inductively coded to report common themes. On average, in the eighteen countries included in this analysis, 31% of NSP targets include sex-disaggregation (range 0-92%). Three countries disaggregated a majority (>50%) of their targets by sex. Sex-disaggregation in data reporting was more common for targets related to the early phases of the HIV care continuum: 83% of countries included any sex-disaggregated targets for HIV prevention, 56% for testing and linkage to care, 22% for improving antiretroviral treatment coverage, and 11% for retention in treatment. The most common target to reduce gender inequality was to prevent gender-based violence (present in 50% of countries). Other commonly incorporated target areas related to improving women's access to family planning, human and legal rights, and decision-making power. The inclusion of sex-disaggregated targets in national planning is vital to ensure that programmes make progress for all population groups. Improving the availability and quality of indicators to measure gender inequality, as well as evaluating programme outcomes by sex, is critical to tracking this progress. This analysis reveals an urgent need to set specific and separate targets for men and women in order to achieve an equitable

  14. A national survey on pediatric critical values used in clinical laboratories across Canada.

    Science.gov (United States)

    Gong, Yanping; Adeli, Khosrow

    2009-11-01

    Notification of critical values to clinical staff is an important post-analytical process in all acute care clinical laboratories. No data are available however on how laboratories obtain or establish critical values, particularly in pediatric settings. This study was designed to examine and compare critical values used for pediatric patients in biochemistry laboratories in Canada and assess potential interlaboratory variability. Fourteen clinical laboratories, including two in pediatric hospitals and twelve in hospitals caring for both children and adults, participated in a survey that included 14 pre-selected STAT chemistry tests and 19 pre-selected therapeutic drug monitoring (TDM) tests. Among fourteen chemistry tests, good agreement was observed for critical values used for sodium and pH at both low and high levels within 14 participant laboratories. Significant interlaboratory variability existed for glucose critical values at the high end, magnesium at high end, and PO2 at the low end. For 19 TDM tests, the majority of laboratories did not have alert values to report values over the therapeutic level but not toxic. For critical values greater than the toxic range, significant variability existed at both trough and peak levels among laboratories surveyed. When asked to provide the source for critical values established at each site, only a limited number of laboratories identified their sources as either internal decision or published references. Although all laboratories have established and routinely use critical values to alert clinical staff, considerable variability exists in both the critical limits reported as well as the source of such values. There is a clear need for new national efforts to standardize pediatric critical value reporting and establish evidence-based critical limits for all medical laboratories across Canada.

  15. Decline in new psychoactive substance use disorders following legislation targeting headshops: Evidence from national addiction treatment data.

    Science.gov (United States)

    Smyth, Bobby P; Lyons, Suzi; Cullen, Walter

    2017-09-01

    New psychoactive substances (NPS) have hedonic effects that may lead to dependence. Headshops selling NPS increased in number in Ireland from late 2009. Legislation was enacted in May and August of 2010 that caused their closure. It is unknown whether such events impact the rate of NPS use disorders. We conducted a population-based study using the Irish national database of episodes of addiction treatment between 2009 and 2012. We examined trends in the rate of NPS-related treatment episodes among young adults. Joinpoint trend analysis software was used to identify significant changes in trend. Of the 31 284 episodes of addiction treatment commenced by adults aged 18 to 34 years, 756 (2.4%) were NPS related. In 2012, the 12-month moving average rate had fallen 48% from its peak in 2010, from 9.0/100 000 to 4.7/100 000. Joinpoint analysis indicated that the rate of NPS related episodes increased by 218% (95% confidence interval 86 to 445, P = 0.001) every 4 months until the first third of 2010. From that point, the rate declined by 9.8% (95% confidence interval -14.1 to -5.4, P = 0.001) per 4-month period. There was no significant trend change in the rate of non-NPS related treatment episodes. Over the 2 years after the enactment of prohibition-styled legislation targeting NPS and headshops, the rate of NPS related addiction treatment episodes among young adults declined progressively and substantially. We found no coinciding trend change in the rate of episodes linked to other drug groups. [Smyth BP, Lyons S, Cullen W. Decline in new psychoactive substance use disorders following legislation targeting headshops: Evidence fromnational addiction treatment data. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  16. "Mind the gap!" Evaluation of the performance gap attributable to exception reporting and target thresholds in the new GMS contract: National database analysis

    Directory of Open Access Journals (Sweden)

    Cookson Richard

    2008-06-01

    Full Text Available Abstract Background The 2003 revision of the UK GMS contract rewards general practices for performance against clinical quality indicators. Practices can exempt patients from treatment, and can receive maximum payment for less than full coverage of eligible patients. This paper aims to estimate the gap between the percentage of maximum incentive gained and the percentage of patients receiving indicated care (the pay-performance gap, and to estimate how much of the gap is attributable respectively to thresholds and to exception reporting. Methods Analysis of Quality Outcomes Framework data in the National Primary Care Database and exception reporting data from the Information Centre from 8407 practices in England in 2005 – 6. The main outcome measures were the gap between the percentage of maximum incentive gained and the percentage of patients receiving indicated care at the practice level, both for individual indicators and a combined composite score. An additional outcome was the percentage of that gap attributable respectively to exception reporting and maximum threshold targets set at less than 100%. Results The mean pay-performance gap for the 65 aggregated clinical indicators was 13.3% (range 2.9% to 48%. 52% of this gap (6.9% of eligible patients is attributable to thresholds being set at less than 100%, and 48% to patients being exception reported. The gap was greater than 25% in 9 indicators: beta blockers and cholesterol control in heart disease; cholesterol control in stroke; influenza immunization in asthma; blood pressure, sugar and cholesterol control in diabetes; seizures in epilepsy and treatment of hypertension. Conclusion Threshold targets and exception reporting introduce an incentive ceiling, which substantially reduces the percentage of eligible patients that UK practices need to treat in order to receive maximum incentive payments for delivering that care. There are good clinical reasons for exception reporting, but after

  17. Which Target Blood Pressure in Year 2018? Evidence from Recent Clinical Trials.

    Science.gov (United States)

    Heimark, Sondre; Mariampillai, Julian E; Narkiewicz, Krzysztof; Nilsson, Peter M; Kjeldsen, Sverre E

    2018-04-16

    The Systolic Blood Pressure Intervention Trial (SPRINT) suggested a favourable effect of lowering blood pressure to Blood Pressure (ACCORD) study, the International Verapamil-Trandolapril Study (INVEST), the Telmisartan, Ramipril or Both in Patients at High Risk for Vascular Events trial (ONTARGET)/the Telmisartan Randomised AssessmenNt Study in aCE iNtolerant participants with cardiovascular Disease (TRANSCEND) study and The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. These studies confirm a positive effect on cardiovascular protection with blood pressure lowering treatment to between 120-140 mmHg in patients with and without diabetes, but no additional effect of lowering blood pressure to blood pressure < 130/80 mmHg appears appropriate in most high-risk hypertensive patients. Additionally, early and sustained BP control below this target is required for optimal cardiovascular protection.

  18. Auto-Targeted Neurostimulation Is Not Superior to Placebo in Chronic Low Back Pain: A Fourfold Blind Randomized Clinical Trial.

    Science.gov (United States)

    Aguilar Ferrándiz, Maria Encarnación; Nijs, Jo; Gidron, Yori; Roussel, Nathalie; Vanderstraeten, Rob; Van Dyck, Dries; Huysmans, Eva; De Kooning, Margot

    2016-07-01

    Myofascial trigger points (MTrPs) are common in people with musculoskeletal pain and may play a role in chronic nonspecific low back pain (CLBP). One of the potential treatments of MTrPs is the Nervomatrix Soleve® auto-targeted neurostimulation device, providing targeted transcutaneous electrical nerve stimulation (TENS) to MTrPs in the lower back muscles. To date, no controlled studies have evaluated the effectiveness of this device for the pain management of this population. To examine whether the Nervomatrix Soleve® auto-targeted neurostimulation device is superior over placebo for the treatment of CLBP. A fourfold-blind randomized controlled trial was conducted. Brussels University Hospital, health care centers and pharmacies around Belgium. Participants with CLBP for at least 3 months were randomly assigned to the experimental (the Nervomatrix Soleve® auto-targeted neurostimulation device providing TENS-stimulation and mechanical pressure) or placebo group (the Nervomatrix Soleve® auto-targeted neurostimulation device providing mechanical pressure alone without current). The treatment protocol in both groups consisted of 6 treatment sessions per patient. Participants were evaluated at baseline prior to the intervention, immediately following treatment, and at one month follow-up. Pain and pain behavior (steps climbed) were assessed as primary outcome measures. Secondary outcome measures were pain functioning, health beliefs, symptoms of central sensitization, pain catastrophizing, and kinesiophobia. In total, 39 participants were included in the study. Participants in both groups improved significantly for pain and functioning, but no significant differences were observed between groups. These improvements were not clinically meaningful for any of the reported measures. The health beliefs changed significantly in both groups (P pain, pain behavior, functioning, central sensitization, pain catastrophizing, and health beliefs.

  19. Key principles for a national clinical decision support knowledge sharing framework: synthesis of insights from leading subject matter experts.

    Science.gov (United States)

    Kawamoto, Kensaku; Hongsermeier, Tonya; Wright, Adam; Lewis, Janet; Bell, Douglas S; Middleton, Blackford

    2013-01-01

    To identify key principles for establishing a national clinical decision support (CDS) knowledge sharing framework. As part of an initiative by the US Office of the National Coordinator for Health IT (ONC) to establish a framework for national CDS knowledge sharing, key stakeholders were identified. Stakeholders' viewpoints were obtained through surveys and in-depth interviews, and findings and relevant insights were summarized. Based on these insights, key principles were formulated for establishing a national CDS knowledge sharing framework. Nineteen key stakeholders were recruited, including six executives from electronic health record system vendors, seven executives from knowledge content producers, three executives from healthcare provider organizations, and three additional experts in clinical informatics. Based on these stakeholders' insights, five key principles were identified for effectively sharing CDS knowledge nationally. These principles are (1) prioritize and support the creation and maintenance of a national CDS knowledge sharing framework; (2) facilitate the development of high-value content and tooling, preferably in an open-source manner; (3) accelerate the development or licensing of required, pragmatic standards; (4) acknowledge and address medicolegal liability concerns; and (5) establish a self-sustaining business model. Based on the principles identified, a roadmap for national CDS knowledge sharing was developed through the ONC's Advancing CDS initiative. The study findings may serve as a useful guide for ongoing activities by the ONC and others to establish a national framework for sharing CDS knowledge and improving clinical care.

  20. Olfactory Function and Associated Clinical Correlates in Former National Football League Players

    Science.gov (United States)

    Alosco, Michael L.; Jarnagin, Johnny; Tripodis, Yorghos; Platt, Michael; Martin, Brett; Chaisson, Christine E.; Baugh, Christine M.; Fritts, Nathan G.; Cantu, Robert C.

    2017-01-01

    Abstract Professional American football players incur thousands of repetitive head impacts (RHIs) throughout their lifetime. The long-term consequences of RHI are not well characterized, but may include olfactory dysfunction. RHI has been associated with changes to brain regions involved in olfaction, and olfactory impairment is common after traumatic brain injury. Olfactory dysfunction is a frequent early sequelae of neurodegenerative diseases (e.g., Alzheimer's disease), and RHI is associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). We examined olfaction, and its association with clinical measures, in former National Football League (NFL) players. Ninety-five former NFL players (ages 40–69) and 28 same-age controls completed a neuropsychological and neuropsychiatric evaluation as part of a National Institutes of Health–funded study. The Brief Smell Identification Test (B-SIT) assessed olfaction. Principal component analysis generated a four-factor structure of the clinical measures: behavioral/mood, psychomotor speed/executive function, and verbal and visual memory. Former NFL players had worse B-SIT scores relative to controls (p = 0.0096). A B-SIT cutoff of 11 had the greatest accuracy (c-statistic = 0.61) and specificity (79%) for discriminating former NFL players from controls. In the former NFL players, lower B-SIT scores correlated with greater behavioral/mood impairment (p = 0.0254) and worse psychomotor speed/executive functioning (p = 0.0464) after controlling for age and education. Former NFL players exhibited lower olfactory test scores relative to controls, and poorer olfactory test performance was associated with worse neuropsychological and neuropsychiatric functioning. Future work that uses more-comprehensive tests of olfaction and structural and functioning neuroimaging may improve understanding on the association between RHI and olfaction. PMID:27430424

  1. Olfactory Function and Associated Clinical Correlates in Former National Football League Players.

    Science.gov (United States)

    Alosco, Michael L; Jarnagin, Johnny; Tripodis, Yorghos; Platt, Michael; Martin, Brett; Chaisson, Christine E; Baugh, Christine M; Fritts, Nathan G; Cantu, Robert C; Stern, Robert A

    2017-02-15

    Professional American football players incur thousands of repetitive head impacts (RHIs) throughout their lifetime. The long-term consequences of RHI are not well characterized, but may include olfactory dysfunction. RHI has been associated with changes to brain regions involved in olfaction, and olfactory impairment is common after traumatic brain injury. Olfactory dysfunction is a frequent early sequelae of neurodegenerative diseases (e.g., Alzheimer's disease), and RHI is associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). We examined olfaction, and its association with clinical measures, in former National Football League (NFL) players. Ninety-five former NFL players (ages 40-69) and 28 same-age controls completed a neuropsychological and neuropsychiatric evaluation as part of a National Institutes of Health-funded study. The Brief Smell Identification Test (B-SIT) assessed olfaction. Principal component analysis generated a four-factor structure of the clinical measures: behavioral/mood, psychomotor speed/executive function, and verbal and visual memory. Former NFL players had worse B-SIT scores relative to controls (p = 0.0096). A B-SIT cutoff of 11 had the greatest accuracy (c-statistic = 0.61) and specificity (79%) for discriminating former NFL players from controls. In the former NFL players, lower B-SIT scores correlated with greater behavioral/mood impairment (p = 0.0254) and worse psychomotor speed/executive functioning (p = 0.0464) after controlling for age and education. Former NFL players exhibited lower olfactory test scores relative to controls, and poorer olfactory test performance was associated with worse neuropsychological and neuropsychiatric functioning. Future work that uses more-comprehensive tests of olfaction and structural and functioning neuroimaging may improve understanding on the association between RHI and olfaction.

  2. External audit of clinical practice and medical decision making in a new Asian oncology center: Results and implications for both developing and developed nations

    International Nuclear Information System (INIS)

    Shakespeare, Thomas P.; Back, Michael F.; Lu, Jiade J.; Lee, Khai Mun; Mukherjee, Rahul K.

    2006-01-01

    Purpose: The external audit of oncologist clinical practice is increasingly important because of the incorporation of audits into national maintenance of certification (MOC) programs. However, there are few reports of external audits of oncology practice or decision making. Our institution (The Cancer Institute, Singapore) was asked to externally audit an oncology department in a developing Asian nation, providing a unique opportunity to explore the feasibility of such a process. Methods and Materials: We audited 100 randomly selected patients simulated for radiotherapy in 2003, using a previously reported audit instrument assessing clinical documentation/quality assurance and medical decision making. Results: Clinical documentation/quality assurance, decision making, and overall performance criteria were adequate 74.4%, 88.3%, and 80.2% of the time, respectively. Overall 52.0% of cases received suboptimal management. Multivariate analysis revealed palliative intent was associated with improved documentation/clinical quality assurance (p = 0.07), decision making (p 0.007), overall performance (p = 0.003), and optimal treatment rates (p 0.07); non-small-cell lung cancer or central nervous system primary sites were associated with better decision making (p = 0.001), overall performance (p = 0.03), and optimal treatment rates (p = 0.002). Conclusions: Despite the poor results, the external audit had several benefits. It identified learning needs for future targeting, and the auditor provided facilitating feedback to address systematic errors identified. Our experience was also helpful in refining our national revalidation audit instrument. The feasibility of the external audit supports the consideration of including audit in national MOC programs

  3. A national study of the provision of oncology sperm banking services among Canadian fertility clinics.

    Science.gov (United States)

    Yee, S; Buckett, W; Campbell, S; Yanofsky, R A; Barr, R D

    2013-07-01

    The purpose of this study was to survey the current state of oncology sperm banking services provided by fertility clinics across Canada. A total of 78 Canadian fertility facilities were invited to complete a questionnaire related to the availability, accessibility, affordability and utilisation of sperm banking services for cancer patients. The total response rate was 59%, with 20 (69%) in vitro fertilisation clinics and 26 (53%) other fertility centres returning the survey. A total of 24 responding facilities accepted oncology sperm banking referrals. The time frame to book the first banking appointment for 19 (79%) facilities was within 2 days. Inconsistent practice was found regarding the consent process for cancer patients who are of minority age. Eight (33%) facilities did not provide any subsidy and charged a standard banking fee regardless of patients' financial situations. Overall, the utilisation of oncology sperm banking services was low despite its availability and established efficacy, suggesting that Canadian cancer patients are notably underserved. The study has highlighted some important issues for further consideration in improving access to sperm banking services for cancer patients, especially for adolescents. Better collaboration between oncology and reproductive medicine to target healthcare providers would help to improve sperm banking rates. © 2013 John Wiley & Sons Ltd.

  4. Lab Plays Central Role in Groundbreaking National Clinical Trial in Precision Medicine | Frederick National Laboratory for Cancer Research

    Science.gov (United States)

    The Molecular Characterization Laboratory at the Frederick National Laboratory for Cancer Research lies at the heart of an ambitious new approach for testing cancer drugs that will use the newest tools of precision medicine to select the best treatme

  5. Characteristics of substance abuse treatment programs providing services for HIV/AIDS, hepatitis C virus infection, and sexually transmitted infections: the National Drug Abuse Treatment Clinical Trials Network.

    Science.gov (United States)

    Brown, Lawrence S; Kritz, Steven Allan; Goldsmith, R Jeffrey; Bini, Edmund J; Rotrosen, John; Baker, Sherryl; Robinson, Jim; McAuliffe, Patrick

    2006-06-01

    Illicit drug users sustain the epidemics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), hepatitis C (HCV), and sexually transmitted infections (STIs). Substance abuse treatment programs present a major intervention point in stemming these epidemics. As a part of the "Infections and Substance Abuse" study, established by the National Drug Abuse Treatment Clinical Trials Network, sponsored by National Institute on Drug Abuse, three surveys were developed; for treatment program administrators, for clinicians, and for state and District of Columbia health and substance abuse department administrators, capturing service availability, government mandates, funding, and other key elements related to the three infection groups. Treatment programs varied in corporate structure, source of revenue, patient census, and medical and non-medical staffing; medical services, counseling services, and staff education targeted HIV/AIDS more often than HCV or STIs. The results from this study have the potential to generate hypotheses for further health services research to inform public policy.

  6. [Effectiveness of Varenicline with counseling programs on smoking cessation in a targeted clinical setting in China].

    Science.gov (United States)

    Jiang, Bin; He, Yao; Zuo, Fang; Wu, Lei; Liu, Qinghui; Zhang, Li; Zhou, Changxi; Cheng, Kk; Chan, Sc; Lam, Th

    2014-12-01

    To evaluate the effectiveness of Varenicline for smoking cessation in a community-based smoking-cessation-clinic (SCC) in Chinese smokers. A prospective observational study was conducted in Beijing, China. 799 smokers (762 men and 37 women) were assessed on data gathered from structured questionnaires at baseline and follow up programs at 1, 3 and 6 months. Trained physician counselors provided free individual counseling and follow-up interviews with brief counseling for all the subjects. 272 subjects were additionally prescribed Varenicline according to their own choice and reported data were compared to those without Varenicline. Outcomes were self-reported, regarding the 7-day point prevalence on abstinence rate and continuous abstinence rates at 1, 3 and 6 month follow-up periods. At 6-month and by intention-to-treat, the 7-day point prevalence on abstinence rate with Varenicline and counseling, was significantly higher than the group with counseling only (34.6% versus 23.1%; OR = 1.75, 95% CI: 1.27-2.42;P group with Varenicline(31.3% versus 18.2% ;OR = 2.04, 95% CI:1.46-2.86;P < 0.001). Varenicline also showed better outcomes at 1 and 3 month follow-up. Varenicline prescription in the smoking cessation clinic appeared to be effective that doubled the rates of quitting among Chinese smokers in the practice at a community-based SCC.

  7. First test of the prompt gamma ray timing method with heterogeneous targets at a clinical proton therapy facility

    International Nuclear Information System (INIS)

    Hueso-González, Fernando; Enghardt, Wolfgang; Golnik, Christian; Petzoldt, Johannes; Pausch, Guntram; Fiedler, Fine; Priegnitz, Marlen; Römer, Katja E; Wagner, Andreas; Janssens, Guillaume; Prieels, Damien; Smeets, Julien; Vander Stappen, François

    2015-01-01

    Ion beam therapy promises enhanced tumour coverage compared to conventional radiotherapy, but particle range uncertainties significantly blunt the achievable precision. Experimental tools for range verification in real-time are not yet available in clinical routine. The prompt gamma ray timing method has been recently proposed as an alternative to collimated imaging systems. The detection times of prompt gamma rays encode essential information about the depth-dose profile thanks to the measurable transit time of ions through matter. In a collaboration between OncoRay, Helmholtz-Zentrum Dresden-Rossendorf and IBA, the first test at a clinical proton accelerator (Westdeutsches Protonentherapiezentrum Essen, Germany) with several detectors and phantoms is performed. The robustness of the method against background and stability of the beam bunch time profile is explored, and the bunch time spread is characterized for different proton energies. For a beam spot with a hundred million protons and a single detector, range differences of 5 mm in defined heterogeneous targets are identified by numerical comparison of the spectrum shape. For higher statistics, range shifts down to 2 mm are detectable. A proton bunch monitor, higher detector throughput and quantitative range retrieval are the upcoming steps towards a clinically applicable prototype. In conclusion, the experimental results highlight the prospects of this straightforward verification method at a clinical pencil beam and settle this novel approach as a promising alternative in the field of in vivo dosimetry. (paper)

  8. Design risk analysis comparison between low-activation composite and aluminum alloy target chamber for the National Ignition Facility

    International Nuclear Information System (INIS)

    Streckert, H.H.; Schleicher, R.W.

    1997-01-01

    The baseline design for the target chamber for the National Ignition Facility (NIF) consists of an aluminum alloy spherical shell. A low-activation composite chamber (e.g., carbon fiber/epoxy) has important advantages such as enhanced environmental and safety characteristics, improved chamber accessibility due to reduced neutron-induced radioactivity, and elimination of the concrete shield. However, it is critical to determine the design and manufacturing risk for the first application. The replacement of such a critical component requires a detailed development risk assessment. A semiquantitative approach to risk assessment has been applied to this problem based on failure modes, effects, and criticality analysis. This analysis consists of a systematic method for organizing the collective judgment of the designers to identify failure modes, estimate probabilities, judge the severity of the consequence, and illustrate risk in a matrix representation. The results of the analyses indicate that the composite chamber has a reasonably high probability of success in the NIF application. The aluminum alloy chamber, however, represents a lower risk, partially based on a more mature technology. 8 refs., 4 figs., 5 tabs

  9. A comprehensive review of everolimus clinical reports: a new mammalian target of rapamycin inhibitor.

    Science.gov (United States)

    Gurk-Turner, Cheryle; Manitpisitkul, Wana; Cooper, Matthew

    2012-10-15

    As new immunosuppressive agents are introduced to the market, clinicians are faced with the daunting task of sifting through the published literature to decide the value that the agent will add to their own practice. We often must extrapolate information provided through study in other solid-organ transplantation populations than our specific area of interest as we interpret the results and outcomes. With these challenges in mind, this compilation of published work for the newest mammalian target of rapamycin inhibitor everolimus (Certican; Novartis Pharmaceuticals, Hanover, NJ) (Zortress; Novartis Pharmaceuticals, Basel, Switzerland) is intended to provide a concise but thorough presentation of available literature so that the reader who may be unfamiliar with the agent can make their own judgment. Both Ovid and PubMed search engines were queried with a particular focus on high-impact articles noted in the Web of Science or Citation Index. Work described solely in abstract or case report form was excluded, as well as meta-analyses or those that were editorial or commentary in nature. Included were publications presented using the English language that described adult human subjects who received a heart, lung, kidney, or liver allograft. The goal of this strategy was to allow for the inclusion of pertinent literature in an unbiased fashion. Tables are provided that outline trial specific information, leaving a discussion of major outcomes to the text of the review.

  10. Impact of the nursing consultation in the External Fixatives Clinic of National Children Hospital

    Directory of Open Access Journals (Sweden)

    Virginia Salas Cerdas

    2013-04-01

    Full Text Available This article presents the results of a study which analyzed 10 cases (8 female and 2 male aged betweentwo and 17 years, with a number of bone defects, and conducted over a period of three months in the externalfixator Clinic National Children's Hospital. Aimed to provide a clear vision about the need of this pediatricpopulation to have a consultation with Clinical Nursing. The exploratory study was conducted using anobservation guide and interviews with users, parents and interdisciplinary team, and implemented the nursingsegmented into three stages: pre-consultation, consultation and post-consultation, evaluating each the problemsand needs of each user (a, as well as the achievements of the children in this research and the role played by thenurse in the consultations. The results show specifically the educational aspects in physical and emotional healthnurse that gave the users and their families and at-hospital benefits through the implementation of the nursing. Weconclude that children participating in the study achieve proper assimilation and implementation of healtheducation regarding: skin healing fixer, signs and symptoms of infection, operation keys, administration ofantibiotics, plaster care and healthy food choices. In addition, awareness was achieved in children and theirparents in monitoring medical indications allowing satisfactory results in treatment.

  11. Hurdles in clinical implementation of academic advanced therapy medicinal products: A national evaluation.

    Science.gov (United States)

    de Wilde, Sofieke; Veltrop-Duits, Louise; Hoozemans-Strik, Merel; Ras, Thirza; Blom-Veenman, Janine; Guchelaar, Henk-Jan; Zandvliet, Maarten; Meij, Pauline

    2016-06-01

    Since the implementation of the European Union (EU) regulation for advanced therapy medicinal products (ATMPs) in 2009, only six ATMPs achieved marketing authorization approval in the EU. Recognizing the major developments in the ATMP field, starting mostly in academic institutions, we investigated which hurdles were experienced in the whole pathway of ATMP development towards clinical care. Quality interviews were executed with different stakeholders in The Netherlands involved in the ATMP development field, e.g. academic research groups, national authorities and patient organizations. Based on the hurdles mentioned in the interviews, questionnaires were subsequently sent to the academic principal investigators (PIs) and ATMP good manufacturing practice (GMP) facility managers to quantify these hurdles. Besides the familiar regulatory routes of marketing authorization (MA) and hospital exemption (HE), a part of the academic PIs perceived that ATMPs should become available by the Tissues and Cells Directive or did not anticipate on the next development steps towards implementation of their ATMP towards regular clinical care. The main hurdles identified were: inadequate financial support, rapidly evolving field, study-related problems, lacking regulatory knowledge, lack of collaborations and responsibility issues. Creating an academic environment stimulating and planning ATMP development and licensing as well as investing in expanding the relevant regulatory knowledge in academic institutions seems a prerequisite to develop ATMPs from bench to patient. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  12. Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan

    Directory of Open Access Journals (Sweden)

    Yosuke Ono

    2017-04-01

    Full Text Available Background: Myxedema coma is a life-threatening and emergency presentation of hypothyroidism. However, the clinical features and outcomes of this condition have been poorly defined because of its rarity. Methods: We conducted a retrospective observational study of patients diagnosed with myxedema coma from July 2010 through March 2013 using a national inpatient database in Japan. We investigated characteristics, comorbidities, treatments, and in-hospital mortality of patients with myxedema coma. Results: We identified 149 patients diagnosed with myxedema coma out of approximately 19 million inpatients in the database. The mean (standard deviation age was 77 (12 years, and two-thirds of the patients were female. The overall proportion of in-hospital mortality among cases was 29.5%. The number of patients was highest in the winter season. Patients treated with steroids, catecholamines, or mechanical ventilation showed higher in-hospital mortality than those without. Variations in type and dosage of thyroid hormone replacement were not associated with in-hospital mortality. The most common comorbidity was cardiovascular diseases (40.3%. The estimated incidence of myxedema coma was 1.08 per million people per year in Japan. Multivariable logistic regression analysis revealed that higher age and use of catecholamines (with or without steroids were significantly associated with higher in-hospital mortality. Conclusions: The present study identified the clinical characteristics and outcomes of patients with myxedema coma using a large-scale database. Myxedema coma mortality was independently associated with age and severe conditions requiring treatment with catecholamines.

  13. IL-8 as antibody therapeutic target in inflammatory diseases: Reduction of clinical activity in palmoplantar pustulosis

    DEFF Research Database (Denmark)

    Skov, L.; Beurskens, F.J.; Reitamo, S.

    2008-01-01

    IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependent...... human neutrophil activation and migration. We investigated whether interference in the cytokine network by HuMab 10F8 might benefit patients suffering from palmoplantar pustulosis, a chronic inflammatory skin disease. Treatment of patients with HuMab 10F8 was well tolerated and significantly reduced...... clinical disease activity at all five endpoints, which included a >= 50% reduction in the formation of fresh pustules. IL-8 neutralization was monitored at the site of inflammation by assessing exudates of palmoplantar pustulosis lesions. HuMab 10F8 sequestered IL-8 in situ, as observed by rapid dose...

  14. Improving email strategies to target stress and productivity in clinical practice.

    Science.gov (United States)

    Armstrong, Melissa J

    2017-12-01

    Physician burnout is gaining increased attention in medicine and neurology and often relates to hours worked and insufficient time. One component of this is administrative burden, which relates to regulatory requirements and electronic health record tasks but may also involve increased time spent processing emails. Research in academic medical centers demonstrates that physicians face increasing inbox sizes related to mass distribution emails from various sources on top of emails required for patient care, research, and teaching. This commentary highlights the contribution of administrative tasks to physician burnout, research to date on email in medical contexts, and corporate strategies for reducing email burden that are applicable to neurology clinical practice. Increased productivity and decreased stress can be achieved by limiting the amount one accesses email, managing inbox size, and utilizing good email etiquette. Department and practice physician leaders have roles in decreasing email volume and modeling good practice.

  15. Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice

    Directory of Open Access Journals (Sweden)

    Donald R. Love

    2013-03-01

    Full Text Available The role of gene deletion and duplication in the aetiology of disease has become increasingly evident over the last decade. In addition to the classical deletion/duplication disorders diagnosed using molecular techniques, such as Duchenne Muscular Dystrophy and Charcot-Marie-Tooth Neuropathy Type 1A, the significance of partial or whole gene deletions in the pathogenesis of a large number single-gene disorders is becoming more apparent. A variety of dosage analysis methods are available to the diagnostic laboratory but the widespread application of many of these techniques is limited by the expense of the kits/reagents and restrictive targeting to a particular gene or portion of a gene. These limitations are particularly important in the context of a small diagnostic laboratory with modest sample throughput. We have developed a gene-targeted, custom-designed comparative genomic hybridisation (CGH array that allows twelve clinical samples to be interrogated simultaneously for exonic deletions/duplications within any gene (or panel of genes on the array. We report here on the use of the array in the analysis of a series of clinical samples processed by our laboratory over a twelve-month period. The array has proven itself to be robust, flexible and highly suited to the diagnostic environment.

  16. Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.

    Science.gov (United States)

    Wallace, Lindsay M; Saad, Nizar Y; Pyne, Nettie K; Fowler, Allison M; Eidahl, Jocelyn O; Domire, Jacqueline S; Griffin, Danielle A; Herman, Adam C; Sahenk, Zarife; Rodino-Klapac, Louise R; Harper, Scott Q

    2018-03-16

    RNAi emerged as a prospective molecular therapy nearly 15 years ago. Since then, two major RNAi platforms have been under development: oligonucleotides and gene therapy. Oligonucleotide-based approaches have seen more advancement, with some promising therapies that may soon reach market. In contrast, vector-based approaches for RNAi therapy have remained largely in the pre-clinical realm, with limited clinical safety and efficacy data to date. We are developing a gene therapy approach to treat the autosomal-dominant disorder facioscapulohumeral muscular dystrophy. Our strategy involves silencing the myotoxic gene DUX4 using adeno-associated viral vectors to deliver targeted microRNA expression cassettes (miDUX4s). We previously demonstrated proof of concept for this approach in mice, and we are now taking additional steps here to assess safety issues related to miDUX4 overexpression and sequence-specific off-target silencing. In this study, we describe improvements in vector design and expansion of our miDUX4 sequence repertoire and report differential toxicity elicited by two miDUX4 sequences, of which one was toxic and the other was not. This study provides important data to help advance our goal of translating RNAi gene therapy for facioscapulohumeral muscular dystrophy.

  17. Improved Dose Targeting for a Clinical Epithermal Neutron Capture Beam Using Optional 6Li Filtration

    International Nuclear Information System (INIS)

    Binns, Peter J.; Riley, Kent J.; Ostrovsky, Yakov; Gao Wei; Albritton, J. Raymond; Kiger, W.S.; Harling, Otto K.

    2007-01-01

    Purpose: The aim of this study was to construct a 6 Li filter and to improve penetration of thermal neutrons produced by the fission converter-based epithermal neutron beam (FCB) for brain irradiation during boron neutron capture therapy (BNCT). Methods and Materials: Design of the 6 Li filter was evaluated using Monte Carlo simulations of the existing beam line and radiation transport through an ellipsoidal water phantom. Changes in beam performance were determined using three figures of merit: (1) advantage depth (AD), the depth at which the total biologically weighted dose to tumor equals the maximum weighted dose to normal tissue; (2) advantage ratio (AR), the ratio of the integral tumor dose to that of normal tissue averaged from the surface to the AD; and (3) advantage depth dose rate (ADDR), the therapeutic dose rate at the AD. Dosimetry performed with the new filter installed provided calibration data for treatment planning. Past treatment plans were recalculated to illustrate the clinical potential of the filter. Results: The 8-mm-thick Li filter is more effective for smaller field sizes, increasing the AD from 9.3 to 9.9 cm, leaving the AR unchanged at 5.7 but decreasing the ADDR from 114 to 55 cGy min -1 for the 12 cm diameter aperture. Using the filter increases the minimum deliverable dose to deep seated tumors by up to 9% for the same maximum dose to normal tissue. Conclusions: Optional 6 Li filtration provides an incremental improvement in clinical beam performance of the FCB that could help to establish a therapeutic window in the future treatment of deep-seated tumors

  18. 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.

  19. Nation

    DEFF Research Database (Denmark)

    Østergaard, Uffe

    2014-01-01

    Nation er et gammelt begreb, som kommer af det latinske ord for fødsel, natio. Nationalisme bygger på forestillingen om, at mennesker har én og kun én national identitet og har ret til deres egen nationalstat. Ordet og forestillingen er kun godt 200 år gammel, og i 1900-tallet har ideologien bredt...

  20. University psychiatry in Italy: organisation and integration of university clinics and the National Health Service

    Directory of Open Access Journals (Sweden)

    Pier Maria Furlan

    2013-09-01

    Full Text Available INTRODUCTION: In the Italian psychiatric system, community-based care has become increasingly important and widespread since the national reform of 1978. This report aims to provide an overview of the involvement of university medical schools in this process, considering their responsibility for teaching and training specialist practitioners and professionals. METHODS: The study was carried out between early 2010 and February 2011. An 18-items, self-administered, questionnaire was designed to investigate the number of faculty members that are responsible both for running a clinical ward and for providing community-based healthcare. RESULTS: Nine out of 53 faculty members (17% manage a Mental Health Department, 9 (17% manage a University Department, and 2 (3.8% manage both types of department. Less than half of the teachers have full responsibility (hospital and community; however the percentage reaches 73.2% if we include the hospital wards open to the community emergencies. The remaining 26.8% have no responsibility for community psychiatry. Moreover there were undoubtedly still too many universities with specialisation schools that are without an appropriate network of facilities enabling them to offer complex psychiatric training. DISCUSSION: As expected, there were several types of healthcare management that were not uniformly distributed throughout Italy and there were also marked differences between mental health care provision in the North, Centre, and South of Italy. The university involvement in clinical responsibility was great, but at the management level there was a lack of equality in terms of clinical care, which risks being reflected also on the institutional functions of teaching and research.

  1. Proton therapy of iris melanoma with 50 CGE. Influence of target volume on clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Riechardt, Aline I.; Joussen, Antonia M. [Charite University of Medicine, Department of Ophthalmology, Berlin (Germany); Karle, Bettina [Helios Klinikum Emil-von-Behring, Department of Radiation Oncology, Berlin (Germany); Cordini, Dino; Heufelder, Jens [Charite University of Medicine, Department of Ophthalmology, Berlin (Germany); Helmholtz-Zentrum Berlin, Lise-Meitner-Campus, Berlin-Protonen, Berlin (Germany); Budach, Volker [Charite University of Medicine, Department of Radiation Oncology, Berlin (Germany); Gollrad, Johannes [Helmholtz-Zentrum Berlin, Lise-Meitner-Campus, Berlin-Protonen, Berlin (Germany); Charite University of Medicine, Department of Radiation Oncology, Berlin (Germany)

    2017-11-15

    The aim of this study was to evaluate local tumour control, incidence of radiation-induced glaucoma and associated interventions of sector-based and whole anterior segment proton beam therapy (PBT) for the treatment of iris melanoma. We retrospectively analysed the data of 77 patients with iris melanoma who underwent PBT applied as 50 CGE in four daily fractions. Of the patients, 47 received PBT with a circular-shaped collimator and 30 with a conformal sector-shaped target volume. Local control, eye preservation and secondary glaucoma were evaluated. Median follow-up time was 54.9 months. Local tumour control was 100% in patients receiving whole anterior segment irradiation. Two patients developed pigment dispersion in the non-irradiated area after sector-based PBT and received whole anterior segment salvage PBT. The mean volume of ciliary body irradiated was 89.0% and 34.9% for whole anterior segment and lesion-based irradiation, respectively. At the end of follow-up, secondary glaucoma was found in 74.3% of the patients with whole anterior segment irradiation and in 19.2% with sector-based irradiation. Patients with sector-based PBT had a stable visual acuity of logMAR 0.1, while it declined from logMAR 0.1 to 0.4 after whole anterior segment irradiation. We found a significant reduction in radiation-induced secondary glaucoma and glaucoma-associated surgical interventions and stable visual acuity after sector-based irradiation compared with whole anterior segment irradiation. Sector-based irradiation revealed a higher risk for local recurrence, but selected patients with well-circumscribed iris melanoma benefit from applying a lesion-based target volume when treated with sector-based PBT. (orig.) [German] Ziel der Arbeit war es, nach Irismelanomtherapie durch sektorielle oder Ganzfeldbestrahlung mittels Protonentherapie mit 50 CGE (Cobalt-Gray-Aequivalent) Tumorkontrolle, Inzidenz des strahleninduzierten Glaukoms und damit assoziierte Interventionen auszuwerten

  2. Adolescent survivors: a secondary analysis of a clinical trial targeting behavior change.

    Science.gov (United States)

    Cox, Cheryl L; McLaughlin, Rosemary A; Rai, Shesh N; Steen, Brenda D; Hudson, Melissa M

    2005-08-01

    The late effects of radiation and chemotherapy increase childhood cancer survivors' risk of chronic health problems. Survivors' behavior is important in modifying this risk, yet adolescent and young adult survivors fail to engage in important health-promoting behaviors and frequently practice high-risk behaviors. This secondary analysis re-evaluated a multi-component behavior-change intervention that had previously demonstrated no impact in adolescent survivors of childhood cancer. The parent trial compared 132 adolescent survivors in the intervention arm with 135 in the standard-care arm at baseline and at 1 year for disease and treatment knowledge, perception of late effects risk, and the frequency of health-risk and health-protective behaviors (combined as a single summative measure). In contrast, the secondary analysis examined each of the 14 behaviors separately. Additionally, an analysis of covariance (ANCOVA) was conducted to examine the change in health behaviors while statistically controlling for age, gender, and the wide variation in baseline behaviors. Knowledge (P = 0.038), breast self-examination (BSE) (P junk food consumption decreased (P = 0.052) and smoking abstinence was maintained (P = 0.088). Significant interactions between gender and treatment group were demonstrated. Health-risk and health-protective behaviors cannot be effectively combined in a one-dimensional measure. Gender and age influence the impact of interventions targeting health behavior in survivors. Future trials should include observation of the patient-clinician encounter, more complex sampling methods, and pre-trial knowledge of the distribution of the study behaviors.

  3. Reaching national consensus on the core clinical skill outcomes for family medicine postgraduate training programmes in South Africa.

    Science.gov (United States)

    Akoojee, Yusuf; Mash, Robert

    2017-05-26

    Family physicians play a significant role in the district health system and need to be equipped with a broad range of clinical skills in order to meet the needs and expectations of the communities they serve. A previous study in 2007 reached national consensus on the clinical skills that should be taught in postgraduate family medicine training prior to the introduction of the new speciality. Since then, family physicians have been trained, employed and have gained experience of working in the district health services. The national Education and Training Committee of the South African Academy of Family Physicians, therefore, requested a review of the national consensus on clinical skills for family medicine training. A Delphi technique was used to reach national consensus in a panel of 17 experts: family physicians responsible for training, experienced family physicians in practice and managers responsible for employing family physicians. Consensus was reached on 242 skills from which the panel decided on 211 core skills, 28 elective skills and 3 skills to be deleted from the previous list. The panel was unable to reach consensus on 11 skills. The findings will guide training programmes on the skills to be addressed and ensure consistency across training programmes nationally. The consensus will also guide formative assessment as documented in the national portfolio of learning and summative assessment in the national exit examination. The consensus will be of interest to other countries in the region where training programmes in family medicine are developing.

  4. What margins should be added to the clinical target volume in radiotherapy treatment planning of lung cancer?

    International Nuclear Information System (INIS)

    Ekberg, L.; Wittgren, L.; Holmberg, O.

    1995-01-01

    When defining the planning target volume (PTV) in radiotherapy treatment planning, it is vital to add geometrical margins of normal tissue around the clinical target volume (CTV). This is to ensure that the whole CTV will receive the planned absorbed dose taking into account both set-up deviations and target movements as well as other geometrical variations in the treatment chain. The problem is our limited knowledge of how large these margins should be. To assess the size of needed margins around the CTV in conformal radiotherapy of lung cancer, electronic portal imaging was employed in 232 irradiation field set-ups of 14 patients. This was done in order to quantify the uncertainty in the execution of treatment considering patient movement and set-up displacements. For an estimation of the added geometrical variation from target movement during irradiation, fluoroscopy was used at the simulation of the irradiation fields. The set-up study showed an average systematic deviation for all individual fields of 3.1 mm and an average maximal systematic deviation (in either transversal or craniocaudal direction) of 4.8 mm. The random errors can be described by an average standard deviation of 2.8 mm for all fields in either direction. Major gradual displacements as a function of time was also detected in one of the patients. CTV-movements of several millimetres during respiration could be observed. It was also seen that heartbeats could add to CTV-movements during irradiation with an equal magnitude. The combined effect of these factors are considered when making an overall estimation of margins that should be added to the CTV

  5. An intensive nurse-led, multi-interventional clinic is more successful in achieving vascular risk reduction targets than standard diabetes care.

    LENUS (Irish Health Repository)

    MacMahon Tone, J

    2009-06-01

    The aim of this research was to determine whether an intensive, nurse-led clinic could achieve recommended vascular risk reduction targets in patients with type 2 diabetes as compared to standard diabetes management.

  6. Energy performance certificates and 3-dimensional city models as a means to reach national targets – A case study of the city of Kiruna

    International Nuclear Information System (INIS)

    Johansson, Tim; Vesterlund, Mattias; Olofsson, Thomas; Dahl, Jan

    2016-01-01

    Highlights: • Visualization of energy use is a useful tool for energy advisors. • Feature Manipulation Engine can be used for visualization of data from energy certificates. • Multi data visualization from the energy certificates can be preformed. • Future scenarios can be calculated and analyzed. • The case study shows that the national levels for energy reduction will be hard to fulfill. - Abstract: Enhanced dissemination of information regarding energy saving and climate change targeted toward property owners is considered to be an important strategy in order to reach the Swedish national target of energy efficiency in the building sector by 2050. Here the municipality energy advisors and the national register for energy performance certificates can facilitate the mitigation of energy use in the building stock. So far few studies have focused on the practical road map to the national target of energy use on the city/district level and to the communication aspects with stakeholders in the creation of energy city models. In this paper a city energy model is developed based on the requests and need for visualization from a group of energy advisors. Six different scenarios are studied in order to analyze the possibility of reaching the energy targets specified by the government in the town of Kiruna. The results show that: (1) it is possible to automatically create city energy models using extract, transform and load tools based on spatial and non-spatial data from national registers and databases; (2) city energy models improve the understanding of energy use in buildings and can therefore be a valuable tool for energy advisors, real estate companies and urban planners. The case study of Kiruna showed that the proposed energy saving measures in the energy performance certificates need to be implemented and new buildings in the urban transformation must be of high energy standard in order to reach the national target in Kiruna.

  7. Performance scores in general practice: a comparison between the clinical versus medication-based approach to identify target populations.

    Directory of Open Access Journals (Sweden)

    Olivier Saint-Lary

    Full Text Available CONTEXT: From one country to another, the pay-for-performance mechanisms differ on one significant point: the identification of target populations, that is, populations which serve as a basis for calculating the indicators. The aim of this study was to compare clinical versus medication-based identification of populations of patients with diabetes and hypertension over the age of 50 (for men or 60 (for women, and any consequences this may have on the calculation of P4P indicators. METHODS: A comparative, retrospective, observational study was carried out with clinical and prescription data from a panel of general practitioners (GPs, the Observatory of General Medicine (OMG for the year 2007. Two indicators regarding the prescription for statins and aspirin in these populations were calculated. RESULTS: We analyzed data from 21.690 patients collected by 61 GPs via electronic medical files. Following the clinical-based approach, 2.278 patients were diabetic, 8,271 had hypertension and 1.539 had both against respectively 1.730, 8.511 and 1.304 following the medication-based approach (% agreement = 96%, kappa = 0.69. The main reasons for these differences were: forgetting to code the morbidities in the clinical approach, not taking into account the population of patients who were given life style and diet rules only or taking into account patients for whom morbidities other than hypertension could justify the use of antihypertensive drugs in the medication-based approach. The mean (confidence interval per doctor was 33.7% (31.5-35.9 for statin indicator and 38.4% (35.4-41.4 for aspirin indicator when the target populations were identified on the basis of clinical criteria whereas they were 37.9% (36.3-39.4 and 43.8% (41.4-46.3 on the basis of treatment criteria. CONCLUSION: The two approaches yield very "similar" scores but these scores cover different realities and offer food for thought on the possible usage of these indicators in the

  8. Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

    International Nuclear Information System (INIS)

    Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Shirai, Toshiyuki; Noda, Koji; Kanai, Tatsuaki; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

    2015-01-01

    At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with α r = 0.764 Gy −1 and β = 0.0615 Gy −2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

  9. Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

    Science.gov (United States)

    Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

    2015-04-01

    At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

  10. Implementation of a Targeted Screening Program to Detect Airflow Obstruction Suggestive of Chronic Obstructive Pulmonary Disease within a Presurgical Screening Clinic

    Directory of Open Access Journals (Sweden)

    Chantal Robitaille

    2015-01-01

    Full Text Available BACKGROUND: Targeted spirometry screening for chronic obstructive pulmonary disease (COPD has been studied in primary care and community settings. Limitations regarding availability and quality of testing remain. A targeted spirometry screening program was implemented within a presurgical screening (PSS clinic to detect undiagnosed airways disease and identify patients with COPD/asthma in need of treatment optimization.

  11. 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

  12. 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.

  13. Effects of Popular Diets without Specific Calorie Targets on Weight Loss Outcomes: Systematic Review of Findings from Clinical Trials

    Directory of Open Access Journals (Sweden)

    Stephen D. Anton

    2017-07-01

    Full Text Available The present review examined the evidence base for current popular diets, as listed in the 2016 U.S. News & World Report, on short-term (≤six months and long-term (≥one year weight loss outcomes in overweight and obese adults. For the present review, all diets in the 2016 U.S. News & World Report Rankings for “Best Weight-Loss Diets”, which did not involve specific calorie targets, meal replacements, supplementation with commercial products, and/or were not categorized as “low-calorie” diets were examined. Of the 38 popular diets listed in the U.S. News & World Report, 20 met our pre-defined criteria. Literature searches were conducted through PubMed, Cochrane Library, and Web of Science using preset key terms to identify all relevant clinical trials for these 20 diets. A total of 16 articles were identified which reported findings of clinical trials for seven of these 20 diets: (1 Atkins; (2 Dietary Approaches to Stop Hypertension (DASH; (3 Glycemic-Index; (4 Mediterranean; (5 Ornish; (6 Paleolithic; and (7 Zone. Of the diets evaluated, the Atkins Diet showed the most evidence in producing clinically meaningful short-term (≤six months and long-term (≥one-year weight loss. Other popular diets may be equally or even more effective at producing weight loss, but this is unknown at the present time since there is a paucity of studies on these diets.

  14. National Beef Quality Audit-2011: Harvest-floor assessments of targeted characteristics that affect quality and value of cattle, carcasses, and byproducts

    Science.gov (United States)

    The National Beef Quality Audit-2011(NBQA-2011) was conducted to assess targeted characteristics on the harvest floor that affect the quality and value of cattle, carcasses, and byproducts. Survey teams evaluated approximately 18,000 cattle/carcasses between May and November 2011 in 8 beef processin...

  15. Impact of Targeted Preoperative Optimization on Clinical Outcome in Emergency Abdominal Surgeries: A Prospective Randomized Trial.

    Science.gov (United States)

    Sethi, Ashish; Debbarma, Miltan; Narang, Neeraj; Saxena, Anudeep; Mahobia, Mamta; Tomar, Gaurav Singh

    2018-01-01

    Perforation peritonitis continues to be one of the most common surgical emergencies that need a surgical intervention most of the times. Anesthesiologists are invariably involved in managing such cases efficiently in perioperative period. The assessment and evaluation of Acute Physiology and Chronic Health Evaluation II (APACHE II) score at presentation and 24 h after goal-directed optimization, administration of empirical broad-spectrum antibiotics, and definitive source control postoperatively. Outcome assessment in terms of duration of hospital stay and mortality in with or without optimization was also measured. It is a prospective, randomized, double-blind controlled study in hospital setting. One hundred and one patients aged ≥18 years, of the American Society of Anesthesiologists physical Status I and II (E) with clinical diagnosis of perforation peritonitis posted for surgery were enrolled. Enrolled patients were randomly divided into two groups. Group A is optimized by goal-directed optimization protocol in the preoperative holding room by anesthesiology residents whereas in Group S, managed by surgery residents in the surgical wards without any fixed algorithm. The assessment of APACHE II score was done as a first step on admission and 24 h postoperatively. Duration of hospital stay and mortality in both the groups were also measured and compared. Categorical data are presented as frequency counts (percent) and compared using the Chi-square or Fisher's exact test. The statistical significance for categorical variables was determined by Chi-square analysis. For continuous variables, a two-sample t -test was applied. The mean APACHE II score on admission in case and control groups was comparable. Significant lowering of serial scores in case group was observed as compared to control group ( P = 0.02). There was a significant lowering of mean duration of hospital stay seen in case group (9.8 ± 1.7 days) as compared to control group ( P = 0

  16. Framework for the analysis of the low-carbon scenario 2020 to achieve the national carbon Emissions reduction target: Focused on educational facilities

    International Nuclear Information System (INIS)

    Koo, Choongwan; Kim, Hyunjoong; Hong, Taehoon

    2014-01-01

    Since the increase in greenhouse gas emissions has increased the global warming potential, an international agreement on carbon emissions reduction target (CERT) has been formulated in Kyoto Protocol (1997). This study aimed to develop a framework for the analysis of the low-carbon scenario 2020 to achieve the national CERT. To verify the feasibility of the proposed framework, educational facilities were used for a case study. This study was conducted in six steps: (i) selection of the target school; (ii) establishment of the reference model for the target school; (iii) energy consumption pattern analysis by target school; (iv) establishment of the energy retrofit model for the target school; (v) economic and environmental assessment through the life cycle cost and life cycle CO 2 analysis; and (vi) establishment of the low-carbon scenario in 2020 to achieve the national CERT. This study can help facility managers or policymakers establish the optimal retrofit strategy within the limited budget from a short-term perspective and the low-carbon scenario 2020 to achieve the national CERT from the long-term perspective. The proposed framework could be also applied to any other building type or country in the global environment

  17. When Are Circular Lesions Square? A National Clinical Education Skin Lesion Audit and Study

    Directory of Open Access Journals (Sweden)

    Benjamin H Miranda

    2014-09-01

    Full Text Available BackgroundSkin cancer is the most prevalent cancer by organ type and referral accuracy is vital for diagnosis and management. The British Association of Dermatologists (BAD and literature highlight the importance of accurate skin lesion examination, diagnosis and educationally-relevant studies.MethodsWe undertook a review of the relevant literature, a national audit of skin lesion description standards and a study of speciality training influences on these descriptions. Questionnaires (n=200, with pictures of a circular and an oval lesion, were distributed to UK dermatology/plastic surgery consultants and speciality trainees (ST, general practitioners (GP, and medical students (MS. The following variables were analysed against a pre-defined 95% inclusion accuracy standard: site, shape, size, skin/colour, and presence of associated scars.ResultsThere were 250 lesion descriptions provided by 125 consultants, STs, GPs, and MSs. Inclusion accuracy was greatest for consultants over STs (80% vs. 68%; P<0.001, GPs (57% and MSs (46% (P<0.0001, for STs over GPs (P<0.010 and MSs (P<0.0001 and for GPs over MSs (P<0.010, all falling below audit standard. Size description accuracy sub-analysis according to circular/oval dimensions was as follows: consultants (94%, GPs (80%, STs (73%, MSs (37%, with the most common error implying a quadrilateral shape (66%. Addressing BAD guidelines and published requirements for more empirical performance data to improve teaching methods, we performed a national audit and studied skin lesion descriptions. To improve diagnostic and referral accuracy for patients, healthcare professionals must strive towards accuracy (a circle is not a square.ConclusionsWe provide supportive evidence that increased speciality training improves this process and propose that greater focus is placed on such training early on during medical training, and maintained throughout clinical practice.

  18. Clinical transfusion practice update: haemovigilance, complications, patient blood management and national standards.

    Science.gov (United States)

    Engelbrecht, Sunelle; Wood, Erica M; Cole-Sinclair, Merrole F

    2013-09-16

    Blood transfusion is not without risk. Although the risks of HIV and hepatitis transmission have diminished, haemovigilance programs highlight that other significant transfusion hazards remain. Sepsis from bacterial contamination is the most common residual infectious hazard in developed countries, and events due to clerical error are problematic. Unnecessary transfusions should be avoided. New national guidelines on patient blood management (PBM) emphasise holistic approaches, including strategies to reduce transfusion requirements. Perioperative PBM should incorporate preoperative haemoglobin and medication optimisation, intraoperative blood conservation, and consideration of restrictive postoperative transfusion and cell-salvage techniques. When massive transfusion is required, hospitals should implement massive transfusion protocols. These protocols reduce mortality, improve communication and facilitate adequate provision of blood products. They should include multidisciplinary team involvement and guidelines for use of blood components and adjunctive agents. Although fresh frozen plasma to red blood cell and platelet to red blood cell ratios of ≥ 1 : 2 appear to reduce mortality in trauma patients who receive massive transfusion, there is insufficient evidence to recommend specific ratios. Systematic reviews have found no significant benefit of recombinant activated factor VII in critical bleeding, and an increase in thromboembolic events; specialist haematology advice is therefore recommended when considering use of this agent. The National Safety and Quality Health Service Standards address use of blood and blood products, and provide important transfusion principles for adoption by all clinicians. Storage of red cells in additive solution results in changes, known as the "storage lesion", and studies to determine the clinical effect of the age of blood at transfusion are ongoing.

  19. Who Is Food Insecure? Implications for Targeted Recruitment and Outreach, National Health and Nutrition Examination Survey, 2005–2010

    Science.gov (United States)

    Leonard, Tammy; Xuan, Lei; Amory, Richard; Higashi, Robin T.; Nguyen, Oanh Kieu; Pezzia, Carla; Swales, Stephanie

    2016-01-01

    Introduction Food insecurity is negatively associated with health; however, health needs may differ among people participating in food assistance programs. Our objectives were to characterize differences in health among people receiving different types of food assistance and summarize strategies for targeted recruitment and outreach of various food insecure populations. Methods We examined health status, behaviors, and health care access associated with food insecurity and receipt of food assistance among US adults aged 20 years or older using data from participants (N = 16,934) of the National Health and Nutrition Examination Survey from 2005 through 2010. Results Food insecurity affected 19.3% of US adults (95% confidence interval, 17.9%–20.7%). People who were food insecure reported poorer health and less health care access than those who were food secure (P food insecure, 58.0% received no assistance, 20.3% received only Supplemental Nutrition Assistance Program (SNAP) benefits, 9.7% received only food bank assistance, and 12.0% received both SNAP and food bank assistance. We observed an inverse relationship between receipt of food assistance and health and health behaviors among the food insecure. Receipt of both (SNAP and food bank assistance) was associated with the poorest health; receiving no assistance was associated with the best health. For example, functional limitations were twice as prevalent among people receiving both types of food assistance than among those receiving none. Conclusion Receipt of food assistance is an overlooked factor associated with health and has the potential to shape future chronic disease prevention efforts among the food insecure. PMID:27736055

  20. The relation between societal factors and different forms of prejudice: A cross-national approach on target-specific and generalized prejudice.

    Science.gov (United States)

    Meeusen, Cecil; Kern, Anna

    2016-01-01

    The goal of this paper was to investigate the generalizability of prejudice across contexts by analyzing associations between different types of prejudice in a cross-national perspective and by investigating the relation between country-specific contextual factors and target-specific prejudices. Relying on the European Social Survey (2008), results indicated that prejudices were indeed positively associated, confirming the existence of a generalized prejudice component. Next to substantial cross-national differences in associational strength, also within country variance in target-specific associations was observed. This suggested that the motivations for prejudice largely vary according to the intergroup context. Two aspects of the intergroup context - economic conditions and cultural values - showed to be related to generalized and target-specific components of prejudice. Future research on prejudice and context should take an integrative approach that considers both the idea of generalized and specific prejudice simultaneously. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A consensus-based guideline defining clinical target volume for primary disease in external beam radiotherapy for intact uterine cervical cancer

    International Nuclear Information System (INIS)

    Toita, Takafumi; Ohno, Tatsuya; Kaneyasu, Yuko

    2011-01-01

    The objective of this study was to develop a consensus-based guideline to define clinical target volume for primary disease (clinical target volume primary) in external beam radiotherapy for intact uterine cervical cancer. The working subgroup of the Japan Clinical Oncology Group (JCOG) Radiation Therapy Study Group began developing a guideline for primary clinical target volume in November 2009. The group consisted of 10 radiation oncologists and 2 gynecologic oncologists. The process started with comparing the contouring on computed tomographic images of actual cervical cancer cases among the members. This was followed by a comprehensive literature review that included primary research articles and textbooks as well as information on surgical procedures. Extensive discussion occurred in face-to-face meetings (three occasions) and frequent e-mail communications until a consensus was reached. The working subgroup reached a consensus on the definition for the clinical target volume primary. The clinical target volume primary consists of the gross tumor volume, uterine cervix, uterine corpus, parametrium, vagina and ovaries. Definitions for these component structures were determined. Anatomical boundaries in all directions were defined for the parametrium. Examples delineating these boundaries were prepared for the posterior border of the parametrium for various clinical situations (id est (i.e.) central tumor bulk, degree of parametrial involvement). A consensus-based guideline defining the clinical target volume primary was developed for external beam radiotherapy for intact uterine cervical cancer. This guideline will serve as a template for radiotherapy protocols in future clinical trials. It may also be used in actual clinical practice in the setting of highly precise external beam radiotherapy, including intensity-modulated radiotherapy. (author)

  2. Clinical trials of boron neutron capture therapy [in humans] [at Beth Israel Deaconess Medical Center][at Brookhaven National Laboratory

    International Nuclear Information System (INIS)

    Wallace, Christine

    2001-01-01

    Assessment of research records of Boron Neutron Capture Therapy was conducted at Brookhaven National Laboratory and Beth Israel Deaconess Medical Center using the Code of Federal Regulations, FDA Regulations and Good Clinical Practice Guidelines. Clinical data were collected FR-om subjects' research charts, and differences in conduct of studies at both centers were examined. Records maintained at Brookhaven National Laboratory were not in compliance with regulatory standards. Beth Israel's records followed federal regulations. Deficiencies discovered at both sites are discussed in the reports

  3. Profiling cancer gene mutations in clinical formalin-fixed, paraffin-embedded colorectal tumor specimens using targeted next-generation sequencing.

    Science.gov (United States)

    Zhang, Liangxuan; Chen, Liangjing; Sah, Sachin; Latham, Gary J; Patel, Rajesh; Song, Qinghua; Koeppen, Hartmut; Tam, Rachel; Schleifman, Erica; Mashhedi, Haider; Chalasani, Sreedevi; Fu, Ling; Sumiyoshi, Teiko; Raja, Rajiv; Forrest, William; Hampton, Garret M; Lackner, Mark R; Hegde, Priti; Jia, Shidong

    2014-04-01

    The success of precision oncology relies on accurate and sensitive molecular profiling. The Ion AmpliSeq Cancer Panel, a targeted enrichment method for next-generation sequencing (NGS) using the Ion Torrent platform, provides a fast, easy, and cost-effective sequencing workflow for detecting genomic "hotspot" regions that are frequently mutated in human cancer genes. Most recently, the U.K. has launched the AmpliSeq sequencing test in its National Health Service. This study aimed to evaluate the clinical application of the AmpliSeq methodology. We used 10 ng of genomic DNA from formalin-fixed, paraffin-embedded human colorectal cancer (CRC) tumor specimens to sequence 46 cancer genes using the AmpliSeq platform. In a validation study, we developed an orthogonal NGS-based resequencing approach (SimpliSeq) to assess the AmpliSeq variant calls. Validated mutational analyses revealed that AmpliSeq was effective in profiling gene mutations, and that the method correctly pinpointed "true-positive" gene mutations with variant frequency >5% and demonstrated high-level molecular heterogeneity in CRC. However, AmpliSeq enrichment and NGS also produced several recurrent "false-positive" calls in clinically druggable oncogenes such as PIK3CA. AmpliSeq provided highly sensitive and quantitative mutation detection for most of the genes on its cancer panel using limited DNA quantities from formalin-fixed, paraffin-embedded samples. For those genes with recurrent "false-positive" variant calls, caution should be used in data interpretation, and orthogonal verification of mutations is recommended for clinical decision making.

  4. Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan.

    Science.gov (United States)

    Ono, Yosuke; Ono, Sachiko; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Tanaka, Yuji

    2017-03-01

    Myxedema coma is a life-threatening and emergency presentation of hypothyroidism. However, the clinical features and outcomes of this condition have been poorly defined because of its rarity. We conducted a retrospective observational study of patients diagnosed with myxedema coma from July 2010 through March 2013 using a national inpatient database in Japan. We investigated characteristics, comorbidities, treatments, and in-hospital mortality of patients with myxedema coma. We identified 149 patients diagnosed with myxedema coma out of approximately 19 million inpatients in the database. The mean (standard deviation) age was 77 (12) years, and two-thirds of the patients were female. The overall proportion of in-hospital mortality among cases was 29.5%. The number of patients was highest in the winter season. Patients treated with steroids, catecholamines, or mechanical ventilation showed higher in-hospital mortality than those without. Variations in type and dosage of thyroid hormone replacement were not associated with in-hospital mortality. The most common comorbidity was cardiovascular diseases (40.3%). The estimated incidence of myxedema coma was 1.08 per million people per year in Japan. Multivariable logistic regression analysis revealed that higher age and use of catecholamines (with or without steroids) were significantly associated with higher in-hospital mortality. The present study identified the clinical characteristics and outcomes of patients with myxedema coma using a large-scale database. Myxedema coma mortality was independently associated with age and severe conditions requiring treatment with catecholamines. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  5. Cost evaluation of clinical laboratory in Taiwan's National Health System by using activity-based costing.

    Science.gov (United States)

    Su, Bin-Guang; Chen, Shao-Fen; Yeh, Shu-Hsing; Shih, Po-Wen; Lin, Ching-Chiang

    2016-11-01

    To cope with the government's policies to reduce medical costs, Taiwan's healthcare service providers are striving to survive by pursuing profit maximization through cost control. This article aimed to present the results of cost evaluation using activity-based costing performed in the laboratory in order to throw light on the differences between costs and the payment system of National Health Insurance (NHI). This study analyzed the data of costs and income of the clinical laboratory. Direct costs belong to their respective sections of the department. The department's shared costs, including public expenses and administrative assigned costs, were allocated to the department's respective sections. A simple regression equation was created to predict profit and loss, and evaluate the department's break-even point, fixed cost, and contribution margin ratio. In clinical chemistry and seroimmunology sections, the cost per test was lower than the NHI payment and their major laboratory tests had revenues with the profitability ratio of 8.7%, while the other sections had a higher cost per test than the NHI payment and their major tests were in deficit. The study found a simple linear regression model as follows: "Balance=-84,995+0.543×income (R2=0.544)". In order to avoid deficit, laboratories are suggested to increase test volumes, enhance laboratory test specialization, and become marginal scale. A hospital could integrate with regional medical institutions through alliances or OEM methods to increase volumes to reach marginal scale and reduce laboratory costs, enhancing the level and quality of laboratory medicine.

  6. Prevalence and genetic diversity of Trichomonas vaginalis clinical isolates in a targeted population in Xinxiang City, Henan Province, China.

    Science.gov (United States)

    Zhang, Zhenchao; Kang, Lixia; Wang, Weijuan; Zhao, Xin; Li, Yuhua; Xie, Qing; Wang, Shuai; He, Tong; Li, Han; Xiao, Tingwei; Chen, Yunchao; Zuo, Suqiong; Kong, Lingmin; Li, Pengju; Li, Xiangrui

    2018-03-02

    Trichomonas vaginalis (TV) is a protozoan parasite that causes trichomoniasis, a sexually transmitted disease, worldwide. In this study, we investigated the prevalence and genetic characterization of T. vaginalis and contrasted the most prevalent strains of T. vaginalis isolated from Xinxiang City, Henan Province, China. In Xinxiang from September 2015 to September 2017, a total of 267 (1.64%, 95% confidence interval, CI: 1.45-1.85) clinical T. vaginalis-positive samples from vaginal secretions were observed by wet mount microscopy from 16,294 women with some clinical symptoms of trichomoniasis. We found that trichomoniasis frequently occurred in the 21- to 40-year-old age group and in winter. After the 267 clinical T. vaginalis positive samples were cultured, 68 isolates of T. vaginalis were harvested and identified as genotype E (58.82%), H (17.65%), mixed 1 (17.65%) and mixed 2 (5.88%) using a sensitive and reliable polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) typing method on the actin gene. The phylogenetic diversity analysis showed that the genotype E samples fell within a separate clade compared to the other T. vaginalis isolates, while the samples of the genotype H separated into two clades. Our results demonstrate a notable gene polymorphism of clinical isolates from the targeted population and provide insight into the performance of these genetic markers in the molecular epidemiology of trichomoniasis. However, further studies are needed to clarify the association between a certain genotype and the pathogenicity of T. vaginalis.

  7. Associating Drugs, Targets and Clinical Outcomes into an Integrated Network Affords a New Platform for Computer-Aided Drug Repurposing

    DEFF Research Database (Denmark)

    Oprea, Tudor; Nielsen, Sonny Kim; Ursu, Oleg

    2011-01-01

    benefit from an integrated, semantic-web compliant computer-aided drug repurposing (CADR) effort, one that would enable deep data mining of associations between approved drugs (D), targets (T), clinical outcomes (CO) and SE. We report preliminary results from text mining and multivariate statistics, based...... on 7684 approved drug labels, ADL (Dailymed) via text mining. From the ADL corresponding to 988 unique drugs, the "adverse reactions" section was mapped onto 174 SE, then clustered via principal component analysis into a 5 x 5 self-organizing map that was integrated into a Cytoscape network of SE......Finding new uses for old drugs is a strategy embraced by the pharmaceutical industry, with increasing participation from the academic sector. Drug repurposing efforts focus on identifying novel modes of action, but not in a systematic manner. With intensive data mining and curation, we aim to apply...

  8. Interobserver variability of clinical target volume delineation in supra-diaphragmatic Hodgkin's disease. A multi-institutional experience

    International Nuclear Information System (INIS)

    Genovesi, Domenico; Cefaro, Giampiero Ausili; Vinciguerra, Annamaria

    2011-01-01

    To determine interobserver variability in clinical target volume (CTV) of supra-diaphragmatic Hodgkin's lymphoma. At the 2008 AIRO (Italian Society of Radiation Oncology) Meeting, the Radiation Oncology Department of Chieti proposed a multi-institutional contouring dummy-run of two cases of early stage supra-diaphragmatic Hodgkin's lymphoma after chemotherapy. Clinical history, diagnostics, and planning CT imaging were available on Chieti's radiotherapy website (www.radioterapia.unich.it). Participating centers were requested to delineate the CTV and submit it to the coordinating center. To quantify interobserver variability of CTV delineations, the total volume, craniocaudal, laterolateral, and anteroposterior diameters were calculated. A total of 18 institutions for case A and 15 institutions for case B submitted the targets. Case A presented significant variability in total volume (range: 74.1-1,157.1 cc), craniocaudal (range: 6.5-22.5 cm; median: 16.25 cm), anteroposterior (range: 5.04-14.82 cm; median: 10.28 cm), and laterolateral diameters (range: 8.23-22.88 cm; median: 15.5 cm). Mean CTV was 464.8 cc (standard deviation: 280.5 cc). Case B presented significant variability in total volume (range: 341.8-1,662 cc), cranio-caudal (range: 8.0-28.5 cm; median: 23 cm), anteroposterior (range: 7.9-1.8 cm; median: 11.1 cm), and laterolateral diameters (range: 12.9-24.0 cm; median: 18.8 cm). Mean CTV was 926.0 cc (standard deviation: 445.7 cc). This significant variability confirms the need to apply specific guidelines to improve contouring uniformity in Hodgkin's lymphoma. (orig.)

  9. Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer.

    Science.gov (United States)

    Voutila, Jon; Reebye, Vikash; Roberts, Thomas C; Protopapa, Pantelitsa; Andrikakou, Pinelopi; Blakey, David C; Habib, Robert; Huber, Hans; Saetrom, Pal; Rossi, John J; Habib, Nagy A

    2017-12-06

    Small activating RNAs (saRNAs) are short double-stranded oligonucleotides that selectively increase gene transcription. Here, we describe the development of an saRNA that upregulates the transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode of action, and describe its development into a clinical candidate. A bioinformatically directed nucleotide walk around the CEBPA gene identified an saRNA sequence that upregulates CEBPA mRNA 2.5-fold in human hepatocellular carcinoma cells. A nuclear run-on assay confirmed that this upregulation is a transcriptionally driven process. Mechanistic experiments demonstrate that Argonaute-2 (Ago2) is required for saRNA activity, with the guide strand of the saRNA shown to be associated with Ago2 and localized at the CEBPA genomic locus using RNA chromatin immunoprecipitation (ChIP) assays. The data support a sequence-specific on-target saRNA activity that leads to enhanced CEBPA mRNA transcription. Chemical modifications were introduced in the saRNA duplex to prevent activation of the innate immunity. This modified saRNA retains activation of CEBPA mRNA and downstream targets and inhibits growth of liver cancer cell lines in vitro. This novel drug has been encapsulated in a liposomal formulation for liver delivery, is currently in a phase I clinical trial for patients with liver cancer, and represents the first human study of an saRNA therapeutic. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Cigarette Smoking During Substance Use Disorder Treatment: Secondary Outcomes from a National Drug Abuse Treatment Clinical Trials Network study.

    Science.gov (United States)

    McClure, Erin A; Campbell, Aimee N C; Pavlicova, Martina; Hu, Meichen; Winhusen, Theresa; Vandrey, Ryan G; Ruglass, Lesia M; Covey, Lirio S; Stitzer, Maxine L; Kyle, Tiffany L; Nunes, Edward V

    2015-06-01

    The majority of patients enrolled in treatment for substance use disorders (SUDs) also use tobacco. Many will continue to use tobacco even during abstinence from other drugs and alcohol, often leading to smoking-related illnesses. Despite this, little research has been conducted to assess the influence of being a smoker on SUD treatment outcomes and changes in smoking during a treatment episode. In this secondary analysis, cigarette smoking was evaluated in participants completing outpatient SUD treatment as part of a multi-site study conducted by the National Drug Abuse Treatment Clinical Trials Network. Analyses included the assessment of changes in smoking and nicotine dependence via the Fagerström Test for Nicotine Dependence during the 12-week study among all smokers (aim #1), specifically among those in the experimental treatment group (aim #2), and the moderating effect of being a smoker on treatment outcomes (aim #3). Participants generally did not reduce or quit smoking throughout the course of the study. Among a sub-set of participants with higher baseline nicotine dependence scores randomized to the control arm, scores at the end of treatment were lower compared to the experimental arm, though measures of smoking quantity did not appear to decrease. Further, being a smoker was associated with poorer treatment outcomes compared to non-smokers enrolled in the trial. This study provides evidence that patients enrolled in community-based SUD treatment continue to smoke, even when abstaining from drugs and alcohol. These results add to the growing literature encouraging the implementation of targeted, evidence-based interventions to promote abstinence from tobacco among SUD treatment patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. MAAGs (Medical Audit Advisory Groups): the Eli Lilly National Clinical Audit Centre.

    Science.gov (United States)

    Baker, R; Fraser, R

    1993-01-01

    Outlines the framework for promoting audit in general practice, created as one part of the health service reforms. Medical Audit Advisory Groups (MAAGs) were set up in each district with the aim of participation in audit of all general practitioners by April 1992. The activities undertaken have included those recommended by the Department of Health; the most significant of these being the appointment of lay facilitators who are able to assist general practitioners and primary care teams co-operate over efforts to improve the quality of care, and may offer one means of introducing some of the methods of total quality management into general practice. Discusses the problems which remain: audit is not yet sufficiently systematic, interface audit with secondary care is at a very early stage, the ways to involve managers and patients in audit remain to be clarified, and there is little evidence of the consequences of audit in terms of improved care. The Eli Lilly National Clinical Audit Centre has been set up within the Department of General Practice, University of Leicester, in order to address these issues.

  12. Molecular breast imaging: First results from Italian-National-Institute-of-Health clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Cusanno, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy)]. E-mail: francesco.cusanno@iss.infn.it; Cisbani, E. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Colilli, S. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Fratoni, R. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Garibaldi, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Giuliani, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Gricia, M. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Lucentini, M. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Magliozzi, M.L. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Santanvenere, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Torrioli, S. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Cinti, M.N. [University La Sapienza, Rome (Italy); Pani, R. [University La Sapienza, Rome (Italy); Pellegrini, R. [University La Sapienza, Rome (Italy); Simonetti, G. [University Tor Vergata, Rome (Italy); Schillaci, O. [University Tor Vergata, Rome (Italy); Del Vecchio, S. [CNR Napoli, Naples (Italy); Salvatore, M. [CNR Napoli, Naples (Italy); Majewski, S. [Jefferson Lab, Newport News (United States); De Vincentis, G. [University La Sapienza, Rome (Italy); Scopinaro, F. [University La Sapienza, Rome (Italy)

    2007-02-01

    Dedicated high resolution detectors are needed for detection of small tumors by molecular imaging with radionuclides. Absorptive collimation are typically used for imaging single photon emitters, but it results in a strong reduction in efficiency. Systems based on electronic collimation offer higher efficiency but they are complex and expensive. In case of scintimammography, dual-head detectors increase sensitivity and cancel out the dependence of the lesion depth. In the system presented here, pixellated scintillator arrays (NaI:Tl) were coupled to arrays of PSPMT's, HPK H8500 Flat Panel. A dual-head detector having field of view of 100x100 mm{sup 2} and 150x200 mm{sup 2} were designed and built. The electronic system allows readout of all the anode pad signals. First clinical trials, performed in the framework of the Scintimammography project of Italian National Institute of Health and University of Tor Vergata in Rome, and University of Naples, are presented.

  13. Elective Clinical Target Volumes for Conformal Therapy in Anorectal Cancer: A Radiation Therapy Oncology Group Consensus Panel Contouring Atlas

    International Nuclear Information System (INIS)

    Myerson, Robert J.; Garofalo, Michael C.; El Naqa, Issam; Abrams, Ross A.; Apte, Aditya; Bosch, Walter R.; Das, Prajnan; Gunderson, Leonard L.; Hong, Theodore S.; Kim, J.J. John; Willett, Christopher G.; Kachnic, Lisa A.

    2009-01-01

    Purpose: To develop a Radiation Therapy Oncology Group (RTOG) atlas of the elective clinical target volume (CTV) definitions to be used for planning pelvic intensity-modulated radiotherapy (IMRT) for anal and rectal cancers. Methods and Materials: The Gastrointestinal Committee of the RTOG established a task group (the nine physician co-authors) to develop this atlas. They responded to a questionnaire concerning three elective CTVs (CTVA: internal iliac, presacral, and perirectal nodal regions for both anal and rectal case planning; CTVB: external iliac nodal region for anal case planning and for selected rectal cases; CTVC: inguinal nodal region for anal case planning and for select rectal cases), and to outline these areas on individual computed tomographic images. The imaging files were shared via the Advanced Technology Consortium. A program developed by one of the co-authors (I.E.N.) used binomial maximum-likelihood estimates to generate a 95% group consensus contour. The computer-estimated consensus contours were then reviewed by the group and modified to provide a final contouring consensus atlas. Results: The panel achieved consensus CTV definitions to be used as guidelines for the adjuvant therapy of rectal cancer and definitive therapy for anal cancer. The most important difference from similar atlases for gynecologic or genitourinary cancer is mesorectal coverage. Detailed target volume contouring guidelines and images are discussed. Conclusion: This report serves as a template for the definition of the elective CTVs to be used in IMRT planning for anal and rectal cancers, as part of prospective RTOG trials.

  14. THE NATIONAL ONCOLOGICAL PROGRAM IMPLEMENTATION – EXPERIENCE IN THE VLADIMIR REGION (TO THE 70TH ANNIVERSARY OF THE REGIONAL CLINICAL ONCOLOGICAL DISPENSARY

    Directory of Open Access Journals (Sweden)

    A. G. Zirin

    2017-01-01

    Full Text Available By 2010, on the background of the steady increase in the incidence of malignant tumors in the Vladimir area, primary oncological care level worked inefficiently.Condition of material and technical base of the Vladimir Regional Clinical Oncological Dispensary was also unsatisfactory. All these problems required solution in the form of the National Oncology Program realization in the region. The National Oncological Program has begun to work in the Vladimir region since 2011. Target indicators of the oncological program implementation by 2015 were established. They are: Increase of 5-year survival value of patients with malignant tumors after diagnosis date to 51.4%; Increase the number of malignant tumors early detection cases at the I–II stages up to 51%; Decrease the mortality rate of working age population to 99 per 100 000; Decrease of mortality within one year from the first time of cancer diagnosis to 27%. The following main objectives such as radically improved the material and technical base of oncology dispensary; modern methods of prevention, diagnosis and patients treatment improvement and introduction; the system providing population cancer care focused on the cancer early detection and the specialized combined antitumor treatment provision are realized in order to achieve these goals. The implementation of the tasks allowed to achieve positive dynamics of Vladimir region population cancer care indicators. All the main targets of the National Oncology Program for the Vladimir region were achieved successfully. Implementation of the National Oncology Program has had an extremely positive effect on the cancer services development of, as well as for the health of the entire population of the Vladimir region.

  15. National Level Co-Control Study of the Targets for Energy Intensity and Sulfur Dioxide in China

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Nan; Price, Lynn; Zheng, Nina; Ke, Jing; Hasanbeigi, Ali

    2011-10-15

    Since 2006, China has set goals of reducing energy intensity, emissions, and pollutants in multiple guidelines and in the Five Year Plans. Various strategies and measures have then been taken to improve the energy efficiency in all sectors and to reduce pollutants. Since controlling energy, CO{sub 2} emissions, and pollutants falls under the jurisdiction of different government agencies in China, many strategies are being implemented to fulfill only one of these objectives. Co-controls or integrated measures could simultaneously reduce greenhouse gas (GHG) emissions and criteria air pollutant emissions. The targets could be met in a more cost effective manner if the integrated measures can be identified and prioritized. This report provides analysis and insights regarding how these targets could be met via co-control measures focusing on both CO{sub 2} and SO{sub 2} emissions in the cement, iron &steel, and power sectors to 2030 in China. An integrated national energy and emission model was developed in order to establish a baseline scenario that was used to assess the impact of actions already taken by the Chinese government as well as planned and expected actions. In addition, CO{sub 2} mitigation scenarios and SO{sub 2} control scenarios were also established to evaluate the impact of each of the measures and the combined effects. In the power sector, although the end of pipe SO{sub 2} control technology such as flue gas desulfurization (FGD) has the largest reduction potential for SO{sub 2} emissions, other CO{sub 2} control options have important co-benefits in reducing SO{sub 2} emissions of 52.6 Mt of SO{sub 2} accumulatively. Coal efficiency improvements along with hydropower, renewable and nuclear capacity expansion will result in more than half of the SO{sub 2} emission reductions as the SO{sub 2} control technology through 2016. In comparison, the reduction from carbon capture and sequestration (CCS) is much less and has negative SO{sub 2} reductions

  16. Common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project

    NARCIS (Netherlands)

    Karaa, A.; Rahman, S.; Lombes, A.; Yu-Wai-Man, P.; Sheikh, M.K.; Alai-Hansen, S.; Cohen, B.H.; Dimmock, D.; Emrick, L.; Falk, M.J.; McCormack, S.; Mirsky, D.; Moore, T.; Parikh, S.; Shoffner, J.; Taivassalo, T.; Tarnopolsky, M.; Tein, I.; Odenkirchen, J.C.; Goldstein, A.; Koene, S.; Smeitink, J.A.M.; et al.,

    2017-01-01

    OBJECTIVES: The common data elements (CDE) project was developed by the National Institute of Neurological Disorders and Stroke (NINDS) to provide clinical researchers with tools to improve data quality and allow for harmonization of data collected in different research studies. CDEs have been

  17. Predictors of Academic Success for the National Board Dental Hygiene Examination and the Southern Regional Testing Agency Clinical Exam

    Science.gov (United States)

    Efurd, Melissa G.

    2012-01-01

    The purpose for conducting this study was to investigate and describe the relationship between applicant criteria for a dental hygiene program and subsequent outcomes on credentialing exams: the National Board Dental Hygiene Exam and the Southern Regional Testing Agency clinical exam. Because admission criteria play a crucial role in applicant…

  18. The National Clinical Skills Competition Promotes the Construction of a Comprehensive Training Program for Chinese Medical Students

    Science.gov (United States)

    Yang, Jing; Huang, Si-min; Lu, Chun-ting; Feng, Lie

    2018-01-01

    To explore an efficient training program based on an analysis in organizing seven sessions for the National Clinical Skills Competition in China. Each year, 6-12 excellent medical students of our university are selected as an observation team. Comparisons of the teaching characteristics were performed in this study. An optimal curriculum…

  19. A national stakeholder consensus study of challenges and priorities for clinical learning environments in postgraduate medical education

    NARCIS (Netherlands)

    Kilty, Caroline; Wiese, Anel; Bergin, Colm; Flood, Patrick; Fu, Na; Horgan, Mary; Higgins, Agnes; Maher, Bridget; O’Kane, Grainne; Prihodova, Lucia; Slattery, Dubhfeasa; Stoyanov, Slavi; Bennett, Deirdre

    2018-01-01

    Background: High quality clinical learning environments (CLE) are critical to postgraduate medical education (PGME). The understaffed and overcrowded environments in which many residents work present a significant challenge to learning. The purpose of this study was to develop a national expert

  20. National survey on turnaround time of clinical biochemistry tests in 738 laboratories in China.

    Science.gov (United States)

    Zhang, Xiaoyan; Fei, Yang; Wang, Wei; Zhao, Haijian; Wang, Minqi; Chen, Bingquan; Zhou, Jie; Wang, Zhiguo

    2018-02-01

    This survey was initiated to estimate the current status of turnaround time (TAT) monitoring of clinical biochemistry in China, provide baseline data for establishment of quality specifications and analyze the impact factors of TAT. 738 laboratories were included. Questionnaires involved general information and data of related indicators of TAT during 1 week were provided to participating laboratories. Nine quality indicators were covered, which were medians, 90th and outlier rates of pre-examination, examination, and post-examination TAT. The 25th percentile, median, and 75th percentile of TATs were calculated as optimum, desirable, and minimum quality specifications. Percentages and sigma values were used to describe the outlier rates. Mann-Whitney and Kruskal-Wallis tests were used to identify the potential impacts of TAT. Response rate of this survey was 46.44%. More than 50% of the laboratories indicated they had set up target TATs in three time intervals and monitored TATs generally. The post-examination TAT of most laboratories was 0min, while the pre-examination and examination TAT varied. Sigma values of outlier rates for 45%~60% of laboratories were above 4, while 15%~20% of labs whose sigma values were below 3. Group comparisons suggested nurse or mechanical pipeline transportation, link laboratory information system with hospital information system, and using computer reporting instead of printing report were related to shorter TATs. Despite of the remarkable progresses of TATs in China, there was also room to improve. Laboratories should strengthen the construction of information systems, identify reasons for TAT delay to improve the service quality continuously. © 2017 Wiley Periodicals, Inc.

  1. 10 years of Vertigo Clinic at National Hospital Abuja, Nigeria: what have we learned?

    Science.gov (United States)

    Olusesi, Abiodun D; Abubakar, J

    2016-11-01

    The clinician's major role in management of the dizzy patient involves determining what dizziness is vertigo, and what vertigo is of central or peripheral origin. These demand attention to details of history, otolaryngological workup including vestibular assessment, and often use of diagnostic and management algorithms. There is paucity of published reports of the management outcomes of peripheral vestibular diseases from Africa. Two tertiary care otologist-led dedicated vertigo clinics are located in Abuja, Nigeria. A prospective, non-randomized study of patients presenting with features of peripheral vestibular diseases attending the National Hospital Abuja Nigeria (between May 2005 and April 2014) and CSR Otologics Specialist Clinics (May 2010 to April 2014) was carried out. Both institutions adopted the same diagnostic and management protocols. Data extracted from anonymized databases created for this study include age, sex, vertigo duration (acute 12 weeks), dizziness handicap inventory score at presentation and at subsequent visits, otological and vestibular findings, ice-water caloric testing results, other investigation outcomes, treatments offered and outcomes. 561/575 (97.5 %) of the cases recorded had peripheral vestibular disease. The male-to-female ratio was 290:271. The mean age of the subjects was 44.7 years. Duration of vertigo at presentation was acute in 278 subjects and chronic in 283 subjects. Identifiable clinical diagnostic groups include BPPV (n = 200), Meniere's disease (n = 189), cervicogenic vertigo (n = 35), labyrinthitis (n = 32), Migraine-associated vertigo (MAV) (n = 32), cholesteatoma/perilymph Fistula (n = 10), climacteric vertigo (n = 8) and unclassified vertigo (n = 55). Migraine-associated vertigo recorded the highest DHI score (95 % CI 75 ± 4.3), followed by cholesteatoma/perilymph fistula (95 % CI 72 ± 6.1) and labyrinthitis (95 % CI 62 ± 1.9). Pure tone audiometry (95 % CI 67.3 ± 3

  2. Targeting adults who provide alcohol to underage youth: results from a national survey of local law enforcement agencies.

    Science.gov (United States)

    Jones-Webb, Rhonda; Toomey, Traci L; Lenk, Kathleen M; Nelson, Toben F; Erickson, Darin J

    2015-06-01

    We investigated what local enforcement agencies are doing to target adults who provide alcohol to underage youth; what types of enforcement activities are being conducted to target adult providers; and factors that encourage enforcement activities that target adult providers. We surveyed 1,056 local law enforcement agencies in the US and measured whether or not the agency conducted enforcement activities that target adults who provide alcohol to underage youth. We also measured whether certain agency and jurisdiction characteristics were associated with enforcement activities that target adults who provide alcohol to underage youth. Less than half (42%) of local enforcement agencies conducted enforcement efforts targeting adults who provide alcohol to underage youth. Agencies that conducted the enforcement activities targeting adult providers were significantly more likely to have a full time officer specific to alcohol enforcement, a division specific to alcohol enforcement, a social host law, and to perceive underage drinking was very common. Results suggest that targeting social providers (i.e., adults over 21 years of age) will require greater law enforcement resources, implementation of underage drinking laws (e.g., social host policies), and changing perceptions among law enforcement regarding underage drinking. Future studies are needed to identify the most effective enforcement efforts and to examine how enforcement efforts are prospectively linked to alcohol consumption.

  3. Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records.

    Directory of Open Access Journals (Sweden)

    Mar Pujades-Rodriguez

    Full Text Available To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design.Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997-2010, all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding.Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67-43.72], cardiac arrest or sudden cardiac death (6.33 [3.69-10.85], heart failure (4.31, [3.30-5.62], and atrial fibrillation (3.80 [3.04-4.75]. HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27-2.84] and coronary revascularisation (2.32 [1.46-3.69].The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding.Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases.

  4. Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records.

    Science.gov (United States)

    Pujades-Rodriguez, Mar; Guttmann, Oliver P; Gonzalez-Izquierdo, Arturo; Duyx, Bram; O'Mahony, Constantinos; Elliott, Perry; Hemingway, Harry

    2018-01-01

    To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997-2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67-43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69-10.85]), heart failure (4.31, [3.30-5.62]), and atrial fibrillation (3.80 [3.04-4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27-2.84]) and coronary revascularisation (2.32 [1.46-3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases.

  5. Visually directed vs. software-based targeted biopsy compared to transperineal template mapping biopsy in the detection of clinically significant prostate cancer.

    Science.gov (United States)

    Valerio, Massimo; McCartan, Neil; Freeman, Alex; Punwani, Shonit; Emberton, Mark; Ahmed, Hashim U

    2015-10-01

    Targeted biopsy based on cognitive or software magnetic resonance imaging (MRI) to transrectal ultrasound registration seems to increase the detection rate of clinically significant prostate cancer as compared with standard biopsy. However, these strategies have not been directly compared against an accurate test yet. The aim of this study was to obtain pilot data on the diagnostic ability of visually directed targeted biopsy vs. software-based targeted biopsy, considering transperineal template mapping (TPM) biopsy as the reference test. Prospective paired cohort study included 50 consecutive men undergoing TPM with one or more visible targets detected on preoperative multiparametric MRI. Targets were contoured on the Biojet software. Patients initially underwent software-based targeted biopsies, then visually directed targeted biopsies, and finally systematic TPM. The detection rate of clinically significant disease (Gleason score ≥3+4 and/or maximum cancer core length ≥4mm) of one strategy against another was compared by 3×3 contingency tables. Secondary analyses were performed using a less stringent threshold of significance (Gleason score ≥4+3 and/or maximum cancer core length ≥6mm). Median age was 68 (interquartile range: 63-73); median prostate-specific antigen level was 7.9ng/mL (6.4-10.2). A total of 79 targets were detected with a mean of 1.6 targets per patient. Of these, 27 (34%), 28 (35%), and 24 (31%) were scored 3, 4, and 5, respectively. At a patient level, the detection rate was 32 (64%), 34 (68%), and 38 (76%) for visually directed targeted, software-based biopsy, and TPM, respectively. Combining the 2 targeted strategies would have led to detection rate of 39 (78%). At a patient level and at a target level, software-based targeted biopsy found more clinically significant diseases than did visually directed targeted biopsy, although this was not statistically significant (22% vs. 14%, P = 0.48; 51.9% vs. 44.3%, P = 0.24). Secondary

  6. Variation in the Definition of Clinical Target Volumes for Pelvic Nodal Conformal Radiation Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Lawton, Colleen A.F.; Michalski, Jeff; El-Naqa, Issam; Kuban, Deborah; Lee, W. Robert; Rosenthal, Seth A.; Zietman, Anthony; Sandler, Howard; Shipley, William; Ritter, Mark; Valicenti, Richard; Catton, Charles; Roach, Mack; Pisansky, Thomas M.; Seider, Michael

    2009-01-01

    Purpose: We conducted a comparative study of clinical target volume (CTV) definition of pelvic lymph nodes by multiple genitourinary (GU) radiation oncologists looking at the levels of discrepancies amongst this group. Methods and Materials: Pelvic computed tomography (CT) scans from 2 men were distributed to 14 Radiation Therapy Oncology Group GU radiation oncologists with instructions to define CTVs for the iliac and presacral lymph nodes. The CT data with contours were then returned for analysis. In addition, a questionnaire was completed that described the physicians' method for target volume definition. Results: Significant variation in the definition of the iliac and presacral CTVs was seen among the physicians. The minimum, maximum, mean (SD) iliac volumes (mL) were 81.8, 876.6, 337.6 ± 203 for case 1 and 60.3, 627.7, 251.8 ± 159.3 for case 2. The volume of 100% agreement was 30.6 and 17.4 for case 1 and 2 and the volume of the union of all contours was 1,012.0 and 807.4 for case 1 and 2, respectively. The overall agreement was judged to be moderate in both cases (kappa = 0.53 (p < 0.0001) and kappa = 0.48 (p < 0.0001). There was no volume of 100% agreement for either of the two presacral volumes. These variations were confirmed in the responses to the associated questionnaire. Conclusions: Significant disagreement exists in the definition of the CTV for pelvic nodal radiation therapy among GU radiation oncology specialists. A consensus needs to be developed so as to accurately assess the merit and safety of such treatment.

  7. Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service.

    Directory of Open Access Journals (Sweden)

    Angela Hamblin

    2017-02-01

    Full Text Available Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS, mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing.We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351 of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays. At least one mutation was identified in 87% (296/342 of tumours. A locally

  8. Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis.

    Science.gov (United States)

    Cheng, Hui-Man; Wu, Yang-Chang; Wang, Qingmin; Song, Michael; Wu, Jackson; Chen, Dion; Li, Katherine; Wadman, Eric; Kao, Shung-Te; Li, Tsai-Chung; Leon, Francisco; Hayden, Karen; Brodmerkel, Carrie; Chris Huang, C

    2017-09-02

    Indigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways. A randomized, double-blind, placebo-controlled clinical study was conducted using Indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24). Patients were treated with Indigo naturalis ointment (n = 16) or matched placebo (n = 8) twice daily for 8 weeks, with 1 week of follow-up. At week 8, significant improvements in Psoriasis Area and Severity Index (PASI) scores from baseline were observed in Indigo naturalis-treated patients (56.3% had 75% improvement [PASI 75] response) compared with placebo (0.0%). A gene expression signature of moderate psoriasis was established from baseline skin biopsies, which included the up-regulation of the interleukin (IL)-17 pathway as a key component; Indigo naturalis treatment resulted in most of these signature genes returning toward normal, including down-regulation of the IL-17 pathway. Using an in vitro keratinocyte assay, an IL-17-inhibitory effect was observed for tryptanthrin, a component of Indigo naturalis. This study demonstrated the clinical efficacy of Indigo naturalis in moderate psoriasis, and exemplified a novel experimental medicine approach to understand TCM targeting mechanisms. NCT01901705 .

  9. Imaginary Worlds and the Institute for Clinical and Economic Review (ICER Evidence Report: Targeted Immune Modulators for Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Paul C Langley

    2017-05-01

    Full Text Available In April 2017, the Institute for Clinical and Economic Review (ICER issued its evidence report on the value of targeted immune modulators (TIMs in rheumatoid arthritis. The report made the case that for the TIMs to be accepted for formulary placement in the US, where notional willingness-to-pay thresholds are the ICER gateway criteria, manufacturers should be prepared to offer substantial unit price discounts. The purpose of this commentary is to make the case that the methodology underpinning the ICER claims for value assessment does not meet the required standards of normal science. None of the claims made for clinical and comparative cost-effectiveness are credible, evaluable and replicable. As such, formulary committees have no idea whether ICER recommendations are right or even if they are wrong. They are, in fact, immune to failure and should be rejected. Utilizing ICER claims generated by simulated projections, this review points out that it is entirely possible to justify the current WAC or net pricing structure of TIMS. The review concludes that if ICER is to contribute to the successful formulary placement of drugs and devices the methodology for pricing recommendation should be re-assessed. As it stands, questions must be raised regarding recommendations for, possibly unnecessary, price discounts. ICER needs to develop an assessment framework that focuses on developing claims for competing therapies that are robust, evaluable and replicable together with recommendations on how these claims are to be evaluated in a timeframe meaningful to health care decision makers.   Type: Commentary

  10. 75 FR 62543 - Proposed Collection; Comment Request; National Evaluation of the Clinical and Translational...

    Science.gov (United States)

    2010-10-12

    ... comment on proposed data collection projects, the National Center for Research Resources (NCRR), the National Institutes of Health (NIH) will publish periodic summaries of proposed projects to be submitted to... academic medical centers and their research partners, increasing the efficiency of the research process...

  11. Existing data sources for clinical epidemiology: the Danish National Pathology Registry and Data Bank

    DEFF Research Database (Denmark)

    Erichsen, Rune; Lash, Timothy L; Hamilton-Dutoit, Stephen J

    2010-01-01

    of epidemiological research. We describe two recent additions to these databases: the Danish National Pathology Registry (DNPR) and its underlying national online registration database, the Danish Pathology Data Bank (DPDB). The DNPR and the DPDB contain detailed nationwide records of all pathology specimens...

  12. Extension of Local Disease in Nasopharyngeal Carcinoma Detected by Magnetic Resonance Imaging: Improvement of Clinical Target Volume Delineation

    International Nuclear Information System (INIS)

    Liang Shaobo; Sun Ying; Liu Lizhi; Chen Yong; Chen Lei; Mao Yanping; Tang Linglong; Tian Li; Lin Aihua; Liu Mengzhong; Li Li; Ma Jun

    2009-01-01

    Purpose: To define by MRI the local extension patterns in patients presenting with nasopharyngeal carcinoma (NPC) and to improve clinical target volume delineation. Methods and Materials: Consecutive patients (N = 943) with newly diagnosed and untreated NPC were included in this study. All patients underwent MRI of the nasopharynx and neck, which was reviewed by two radiologists. Results: According to the incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were initially classified into three risk grades: high risk (≥ 35%), medium risk (≥ 5-35%), and low risk (< 5%). Incidence rates of tumor invasion into anatomic sites at medium risk were increased, reaching 55.2%, when adjacent high-risk anatomic sites were involved. However, the rates were substantially lower, mostly < 10%, when adjacent high-risk sites were not involved. The incidence rates of concurrent tumor invasion into bilateral sites were < 10%, except in the case of prevertebral muscle involvement (13.1%). Among the 178 incidences of cavernous sinus invasion, there were often two or more simultaneous infiltration routes (60.6%); when only one route was involved, the foramen ovale was the most common (26.4%). Conclusions: In patients presenting with NPC, local disease spreads stepwise from proximal sites to more distal sites. Tumors extend quickly through privileged pathways such as neural foramina. The anatomic sites surrounding the nasopharynx are at low risk of concurrent bilateral tumor invasion. Selective radiotherapy of the local disease in NPC may be feasible.

  13. Gross tumor volume (GTV) and clinical target volume (CTV) for radiation therapy of benign skull base tumours

    International Nuclear Information System (INIS)

    Maire, J.P.; Liguoro, D.; San Galli, F.

    2001-01-01

    Skull base tumours represent a out 35 to 40% of all intracranial tumours. There are now many reports in the literature confirming the fact that about 80 to 90% of such tumours are controlled with fractionated radiotherapy. Stereotactic and 3-dimensional treatment planning techniques increase local control and central nervous system tolerance. Definition of the gross tumor volume (GTV) is generally easy with currently available medical imaging systems and computers for 3-dimensional dosimetry. The definition of the clinical target volume (CTV) is more difficult to appreciate: it is defined from the CTV plus a margin, which depends on the histology and anterior therapeutic history of the tumour. It is important to take into account the visible tumour and its possible extension pathways (adjacent bone, holes at the base of skull) and/or an anatomic region (sella turcica + adjacent cavernous sinus). It is necessary to evaluate these volumes with CT Scan and MRI to appreciate tumor extension in a 3-dimensional approach, in order to reduce the risk of marginal recurrences. The aim of this paper is to discuss volume definition as a function of tumour site and tumour type to be irradiated. (authors)

  14. Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic

    International Nuclear Information System (INIS)

    Morrison, B. F.; Aiken, W.; Mayhew, R.; Gordon, Y.; Reid, M.

    2016-01-01

    Prostate cancer is highly prevalent in Jamaica and is the leading cause of cancer-related deaths. Our aim was to evaluate the patterns of screening in the largest organized screening clinic in Jamaica at the Jamaica Cancer Society. A retrospective analysis of all men presenting for screening at the Jamaica Cancer Society from 1995 to 2005 was done. All patients had digital rectal examinations (DRE) and prostate specific antigen (PSA) tests done. Results of prostate biopsies were noted. 1117 men of mean age 59.9 ± 8.2 years presented for screening. The median documented PSA was 1.6 ng/mL (maximum of 5170 ng/mL). Most patients presented for only 1 screen. There was a gradual reduction in the mean age of presentation for screening over the period. Prostate biopsies were requested on 11% of screening visits; however, only 59% of these were done. 5.6% of all persons screened were found to have cancer. Of the cancers diagnosed, Gleason 6 adenocarcinoma was the commonest grade and median PSA was 8.9 ng/mL (range 1.5-1059 ng/mL). Older men tend to screen for prostate cancer in Jamaica. However, compliance with regular maintenance visits and requests for confirmatory biopsies are poor. Screening needs intervention in the Jamaican population.

  15. Screening mammography. A missed clinical opportunity? Results of the NCI [National Cancer Institute] Breast Cancer Screening Consortium and national health interview survey studies

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Data from seven studies sponsored by the National Cancer Institute (NCI) were used to determine current rates of breast cancer screening and to identify the characteristics of and reasons for women not being screened. All seven studies were population-based surveys of women aged 50 to 74 years without breast cancer. While over 90% of non-Hispanic white respondents had regular sources of medical care, 46% to 76% had a clinical breast examination within the previous year, and only 25% to 41% had a mammogram. Less educated and poorer women had fewer mammograms. The two most common reasons women gave for never having had a mammogram were that they did not known they needed it and that their physician had not recommended it. Many physicians may have overlooked the opportunity to recommend mammography for older women when performing a clinical breast examination and to educate their patients about the benefit of screening mammography

  16. Clinical Reasoning Education at US Medical Schools: Results from a National Survey of Internal Medicine Clerkship Directors.

    Science.gov (United States)

    Rencic, Joseph; Trowbridge, Robert L; Fagan, Mark; Szauter, Karen; Durning, Steven

    2017-11-01

    Recent reports, including the Institute of Medicine's Improving Diagnosis in Health Care, highlight the pervasiveness and underappreciated harm of diagnostic error, and recommend enhancing health care professional education in diagnostic reasoning. However, little is known about clinical reasoning curricula at US medical schools. To describe clinical reasoning curricula at US medical schools and to determine the attitudes of internal medicine clerkship directors toward teaching of clinical reasoning. Cross-sectional multicenter study. US institutional members of the Clerkship Directors in Internal Medicine (CDIM). Examined responses to a survey that was emailed in May 2015 to CDIM institutional representatives, who reported on their medical school's clinical reasoning curriculum. The response rate was 74% (91/123). Most respondents reported that a structured curriculum in clinical reasoning should be taught in all phases of medical education, including the preclinical years (64/85; 75%), clinical clerkships (76/87; 87%), and the fourth year (75/88; 85%), and that more curricular time should be devoted to the topic. Respondents indicated that most students enter the clerkship with only poor (25/85; 29%) to fair (47/85; 55%) knowledge of key clinical reasoning concepts. Most institutions (52/91; 57%) surveyed lacked sessions dedicated to these topics. Lack of curricular time (59/67, 88%) and faculty expertise in teaching these concepts (53/76, 69%) were identified as barriers. Internal medicine clerkship directors believe that clinical reasoning should be taught throughout the 4 years of medical school, with the greatest emphasis in the clinical years. However, only a minority reported having teaching sessions devoted to clinical reasoning, citing a lack of curricular time and faculty expertise as the largest barriers. Our findings suggest that additional institutional and national resources should be dedicated to developing clinical reasoning curricula to improve

  17. The FORGE AHEAD clinical readiness consultation tool: a validated tool to assess clinical readiness for chronic disease care mobilization in Canada's First Nations.

    Science.gov (United States)

    Hayward, Mariam Naqshbandi; Mequanint, Selam; Paquette-Warren, Jann; Bailie, Ross; Chirila, Alexandra; Dyck, Roland; Green, Michael; Hanley, Anthony; Tompkins, Jordan; Harris, Stewart

    2017-03-23

    Given the astounding rates of diabetes and related complications, and the barriers to providing care present in Indigenous communities in Canada, intervention strategies that take into account contextual factors such as readiness to mobilize are needed to maximize improvements and increase the likelihood of success and sustainment. As part of the national FORGE AHEAD Program, we sought to develop, test and validate a clinical readiness consultation tool aimed at assessing the readiness of clinical teams working on-reserve in First Nations communities to participate in quality improvement (QI) to enhance diabetes care in Canada. A literature review was conducted to identify existing readiness tools. The ABCD - SAT was adapted using a consensus approach that emphasized a community-based participatory approach and prioritized the knowledge and wisdom held by community members. The tool was piloted with a group of 16 people from 7 provinces and 11 partnering communities to assess language use, clarity, relevance, format, and ease of completion using examples. Internal reliability analysis and convergence validity were conducted with data from 53 clinical team members from 11 First Nations communities (3-5 per community) who have participated in the FORGE AHEAD program. The 27-page Clinical Readiness Consultation Tool (CRCT) consists of five main components, 21 sub-components, and 74 items that are aligned with the Expanded Chronic Care Model. Five-point Likert scale feedback from the pilot ranged from 3.25 to 4.5. Length of the tool was reported as a drawback but respondents noted that all the items were needed to provide a comprehensive picture of the healthcare system. Results for internal consistency showed that all sub-components except for two were within acceptable ranges (0.77-0.93). The Team Structure and Function sub-component scale had a moderately significant positive correlation with the validated Team Climate Inventory, r = 0.45, p < 0.05. The

  18. A longitudinal study of organizational formation, innovation adoption, and dissemination activities within the National Drug Abuse Treatment Clinical Trials Network.

    Science.gov (United States)

    Roman, Paul M; Abraham, Amanda J; Rothrauff, Tanja C; Knudsen, Hannah K

    2010-06-01

    The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. This article focuses on three dimensions of CTN's organizational functioning. First, a longitudinal dataset is used to examine CTN's formation as a network of interorganizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered interorganizational interaction over time. Second, adoption of buprenorphine and motivational incentives among CTN's affiliated community treatment programs (CTPs) is examined over three waves of data. Although adoption is found to increase with CTPs' CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs' pursuit of the CTN's dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future.

  19. The national clinical audit of falls and bone health-secondary prevention of falls and fractures: a physiotherapy perspective.

    Science.gov (United States)

    Goodwin, Victoria; Martin, Finbarr C; Husk, Janet; Lowe, Derek; Grant, Robert; Potter, Jonathan

    2010-03-01

    To establish current physiotherapy practice in the secondary management of falls and fragility fractures compared with national guidance. Web-based national clinical audit. Acute trusts (n=157) and primary care trusts (n=146) in England, Wales and Northern Ireland. Data were collected on 5642 patients with non-hip fragility fractures and 3184 patients with a hip fracture. Those patients who were bedbound or who declined assessment or rehabilitation were excluded from the analysis. Results indicate that of those with non-hip fractures, 28% received a gait and balance assessment, 22% participated in an exercise programme, and 3% were shown how to get up from the floor. For those with a hip fracture, the results were 68%, 44% and 7%, respectively. Physiotherapists have a significant role to play in the secondary prevention of falls and fractures. However, along with managers and professional bodies, more must be done to ensure that clinical practice reflects the evidence base and professional standards.

  20. Simple model of the indirect compression of targets under conditions close to the national ignition facility at an energy of 1.5 MJ

    Energy Technology Data Exchange (ETDEWEB)

    Rozanov, V. B., E-mail: rozanov@sci.lebedev.ru; Vergunova, G. A., E-mail: verg@sci.lebedev.ru [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation)

    2015-11-15

    The possibility of the analysis and interpretation of the reported experiments with the megajoule National Ignition Facility (NIF) laser on the compression of capsules in indirect-irradiation targets by means of the one-dimensional RADIAN program in the spherical geometry has been studied. The problem of the energy balance in a target and the determination of the laser energy that should be used in the spherical model of the target has been considered. The results of action of pulses differing in energy and time profile (“low-foot” and “high-foot” regimes) have been analyzed. The parameters of the compression of targets with a high-density carbon ablator have been obtained. The results of the simulations are in satisfactory agreement with the measurements and correspond to the range of the observed parameters. The set of compared results can be expanded, in particular, for a more detailed determination of the parameters of a target near the maximum compression of the capsule. The physical foundation of the possibility of using the one-dimensional description is the necessity of the closeness of the last stage of the compression of the capsule to a one-dimensional process. The one-dimensional simulation of the compression of the capsule can be useful in establishing the boundary behind which two-dimensional and three-dimensional simulation should be used.

  1. SU-F-I-51: CT/MR Image Deformation: The Clinical Assessment QA in Target Delineation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, C; Chen, Y [Monmouth Medical Center, Long Branch, NJ (United States)

    2016-06-15

    Purpose: To study the deformation effects in CT/MR image registration of head and neck (HN) cancers. We present a clinical indication in guiding and simplifying registration procedures of this process while CT images possessed artifacts. Methods: CT/MR image fusion provides better soft tissue contrast in intracranial GTV definition with artifacts. However, whether the fusion process should include the deformation process is questionable and not recommended. We performed CT/MR image registration of a HN patient with tonsil GTV and nodes delineation on Varian Velocity™ system. Both rigid transformation and deformable registration of the same CT/MR imaging data were processed separately. Physician’s selection of target delineation was implemented to identify the variations. Transformation matrix was shown with visual identification, as well as the deformation QA numbers and figures were assessed. Results: The deformable CT/MR images were traced with the calculated matrix, both translation and rotational parameters were summarized. In deformable quality QA, the calculated Jacobian matrix was analyzed, which the min/mean/max of 0.73/0/99/1.37, respectively. Jacobian matrix of right neck node was 0.84/1.13/1.41, which present dis-similarity of the nodal area. If Jacobian = 1, the deformation is at the optimum situation. In this case, the deformation results have shown better target delineation for CT/MR deformation than rigid transformation. Though the root-mean-square vector difference is 1.48 mm, with similar rotational components, the cord and vertebrae position were aligned much better in the deformable MR images than the rigid transformation. Conclusion: CT/MR with/without image deformation presents similar image registration matrix; there were significant differentiate the anatomical structures in the region of interest by deformable process. Though vendor suggested only rigid transformation between CT/MR assuming the geometry remain similar, our findings

  2. Clinical findings confirm national guidelines regarding primary gastroscopy for upper gastrointestinal symptoms

    DEFF Research Database (Denmark)

    Rolff, Hans Christian; Simonsen, Louise Rolighed; Rosenberg, Jacob

    2011-01-01

    This study describes unsedated transnasal oesophagogastroduodenoscopy (UT-OGD) in the office setting. Evaluation of national guidelines regarding primary endoscopy for the investigation of upper gastrointestinal (GI) symptoms was also a focus of this study....

  3. Lab Plays Central Role in Groundbreaking National Clinical Trial in Precision Medicine | FNLCR Staging

    Science.gov (United States)

    The Molecular Characterization Laboratory at the Frederick National Laboratory for Cancer Research lies at the heart of an ambitious new approach for testing cancer drugs that will use the newest tools of precision medicine to select the best treatme

  4. Embedding Mental Health Support in Schools: Learning from the Targeted Mental Health in Schools (TaMHS) National Evaluation

    Science.gov (United States)

    Wolpert, Miranda; Humphrey, Neil; Belsky, Jay; Deighton, Jessica

    2013-01-01

    The Targeted Mental Health in Schools (TaMHS) programme was a nationwide initiative that funded mental health provision in schools for pupils at risk of or already experiencing mental health problems. The implementation, impact and experience of this programme was evaluated using quantitative and qualitative methodology involving three main…

  5. A consensus-based guideline defining the clinical target volume for pelvic lymph nodes in external beam radiotherapy for uterine cervical cancer

    International Nuclear Information System (INIS)

    Toita, Takafumi; Ohno, Tatsuya; Kaneyasu, Yuko

    2010-01-01

    The objective of this study was to develop a consensus-based guideline as well as an atlas defining pelvic nodal clinical target volumes in external beam radiotherapy for uterine cervical cancer. A working subgroup to establish the consensus-based guideline on clinical target volumes for uterine cervical cancer was formulated by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July 2008. The working subgroup consisted of seven radiation oncologists. The process resulting in the consensus included a comparison of contouring on CT images among the members, reviewing of published textbooks and the relevant literature and a distribution analysis of metastatic nodes on computed tomography/magnetic resonance imaging of actual patients. The working subgroup defined the pelvic nodal clinical target volumes for cervical cancer and developed an associated atlas. As a basic criterion, the lymph node clinical target volume was defined as the area encompassed by a 7 mm margin around the applicable pelvic vessels. Modifications were made in each nodal area to cover adjacent adipose tissues at risk of microscopic nodal metastases. Although the bones and muscles were excluded, the bowel was not routinely excluded in the definition. Each of the following pelvic node regions was defined: common iliac, external iliac, internal iliac, obturator and presacral. Anatomical structures bordering each lymph node region were defined for six directions; anterior, posterior, lateral, medial, cranial and caudal. Drafts of the definition and the atlas were reviewed by members of the JCOG Gynecologic Cancer Study Group (GCSG). We developed a consensus-based guideline defining the pelvic node clinical target volumes that included an atlas. The guideline will be continuously updated to reflect the ongoing changes in the field. (author)

  6. Contemporary analysis of erectile, voiding, and oncologic outcomes following primary targeted cryoablation of the prostate for clinically localized prostate cancer

    Directory of Open Access Journals (Sweden)

    Christopher J. Diblasio

    2008-08-01

    Full Text Available PURPOSE: To evaluate erectile function (EF and voiding function following primary targeted cryoablation of the prostate (TCAP for clinically localized prostate cancer (CaP in a contemporary cohort. MATERIALS AND METHODS: We retrospectively reviewed all patients treated between 2/2000-5/2006 with primary TCAP. Variables included age, Gleason sum, pre-TCAP prostate specific antigen (PSA, prostate volume, clinical stage, pre-TCAP hormonal ablation, pre-TCAP EF and American Urologic Association Symptom Score (AUASS. EF was recorded as follows: 1 = potent; 2 = sufficient for intercourse; 3 = partial/insufficient; 4 = minimal/insufficient; 5 = none. Voiding function was analyzed by comparing pre/post-TCAP AUASS. Statistical analysis utilized SAS software with p < 0.05 considered significant. RESULTS: After exclusions, 78 consecutive patients were analyzed with a mean age of 69.2 years and follow-up 39.8 months. Thirty-five (44.9% men reported pre-TCAP EF level of 1-2. Post-TCAP, 9 of 35 (25.7% regained EF of level 1-2 while 1 (2.9% achieved level 3 EF. Median pre-TCAP AUASS was 8.75 versus 7.50 postoperatively (p = 0.39. Six patients (7.7% experienced post-TCAP urinary incontinence. Lower pre-TCAP PSA (p = 0.008 and higher Gleason sum (p = 0.002 were associated with higher post-TCAP AUASS while prostate volume demonstrated a trend (p = 0.07. Post-TCAP EF and stable AUASS were not associated with increased disease-recurrence (p = 0.24 and p = 0.67, respectively. CONCLUSIONS: Stable voiding function was observed post-TCAP, with an overall incontinence rate of 7.7%. Further, though erectile dysfunction is common following TCAP, 25.7% of previously potent patients demonstrated erections suitable for intercourse. While long-term data is requisite, consideration should be made for prospective evaluation of penile rehabilitation following primary TCAP.

  7. Clinical variability of target volume description and treatment plans in conformal radiotherapy in muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Logue, John P; Sharrock, Carole L; Cowan, Richard A.; Read, Graham; Marrs, Julie; Mott, David

    1996-01-01

    Purpose/Objective: The delineation of tumor and the production of a treatment plan to encompass this is the prime step in radiotherapy planning. Conformal radiotherapy is developing rapidly and although plentiful research has addressed the implementation of the radiotherapy prescription, scant attention has been made to the fundamental step of production, by the clinician, of an appropriate target volume. As part of an ongoing randomized trial of conformal radiotherapy, in bladder cancer, we have therefore assessed the interphysician variability of radiologists and radiation oncologists (RO) in assessing Gross Tumor Volume(GTV) (ICRU 50) and the adherence of the radiation oncologists to the study protocol of producing a Planning Target Volume (PTV). Materials and Methods: Four patients with T3 carcinoma of bladder who had been entered into the trial were identified. The clinical details, MR scans and CT scans were made available. Eight RO and 3 dedicated diagnostic oncology radiologists were invited to directly outline the GTV onto CT images on a planning computer consul. The RO in addition created a PTV following the trial protocol of 15mm margin around the GTV. Three RO sub-specialized in Urological radiotherapy; all RO had completed training. Volumes were produced, for each clinician, and comparison of these volumes and their isocenters were analyzed. In addition the margins allowed were measured and compared. Results: There was a maximum variation ratio (largest to smallest volume outlined) of the GTV in the four cases of 1.74 among radiologists and 3.74 among oncologists. There was a significant difference (p=0.01) in mean GTV between RO and the radiologists. The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean difference of 13.4 cm 3 The between observer variance within speciality comprised only 9.9% of the total variance in the data having accounted for case and observers speciality. The variation ratio in PTV among oncologists

  8. Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical Phase I/II trials

    International Nuclear Information System (INIS)

    Chen Zhinan; Mi Li; Xu Jing

    2006-01-01

    Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ( 131 I) metuximab injection (Licartin), a novel 131 I-labeled HAb18G/CD147-specific monoclonal antibody F(ab') 2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p 131 I) metuximab injection is safe and active for HCC patients

  9. 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.

  10. Social assessment for the Wenatchee National Forest wildfires of 1994: targeted analysis for the Leavenworth, Entiat, and Chelan Ranger Districts.

    Science.gov (United States)

    Matthew S. Carroll; Angela J. Findley; Keith A. Blatner; Sandra Rodriguez Mendez; Steven E. Daniels; Gregg B. Walker

    2000-01-01

    A purposive social assessment across three communities explored reactions of local residents to wildfires in the Wenatchee National Forest in north-central Washington. Research concentrated on identifying the diversity of fundamental beliefs and values held by local residents about wildfire and forest management. Particular emphasis was given to investigating community...

  11. Consensus Guidelines for Delineation of Clinical Target Volume for Intensity-Modulated Pelvic Radiotherapy for the Definitive Treatment of Cervix Cancer

    International Nuclear Information System (INIS)

    Lim, Karen; Small, William; Portelance, Lorraine; Creutzberg, Carien; Juergenliemk-Schulz, Ina M.; Mundt, Arno; Mell, Loren K.; Mayr, Nina; Viswanathan, Akila; Jhingran, Anuja; Erickson, Beth; De Los Santos, Jennifer; Gaffney, David; Yashar, Catheryn; Beriwal, Sushil; Wolfson, Aaron

    2011-01-01

    Purpose: Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group. Methods and Materials: A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. Results: Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate. Conclusions: This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.

  12. Pharmacokinetics and tumor targeting of 131I-labeled F(ab')2 fragments of the chimeric monoclonal antibody G250: preclinical and clinical pilot studies.

    NARCIS (Netherlands)

    Brouwers, A.H.; Mulders, P.F.A.; Oosterwijk, E.; Buijs, W.C.A.M.; Corstens, F.H.M.; Boerman, O.C.; Oyen, W.J.G.

    2004-01-01

    INTRODUCTION: Clinical and animal studies of chimeric monoclonal antibody G250 (moAb cG250) for the targeting of clear-cell renal cell carcinoma (RCC), to date, have been with the intact IgG form. To determine whether F(ab')2 fragments are more suited for radioimmunotherapy (RIT) than intact IgG,

  13. Comparison of low-normal and high-normal IGF-1 target levels during growth hormone replacement therapy : A randomized clinical trial in adult growth hormone deficiency

    NARCIS (Netherlands)

    van Bunderen, Christa C; Lips, Paul; Kramer, Mark H H; Drent, Madeleine L

    BACKGROUND: Current guidelines state that the goals of growth hormone (GH) therapy in adults should be an appropriate clinical response, avoidance of side effects, and an IGF-1 value within the age-adjusted reference range. There are no published studies on the target level for IGF-1 that offer

  14. Managing conflicts of interest in the UK National Institute for Health and Care Excellence (NICE) clinical guidelines programme: qualitative study.

    Science.gov (United States)

    Graham, Tanya; Alderson, Phil; Stokes, Tim

    2015-01-01

    There is international concern that conflicts of interest (COI) may bias clinical guideline development and render it untrustworthy. Guideline COI policies exist with the aim of reducing this bias but it is not known how such policies are interpreted and used by guideline producing organisations. This study sought to determine how conflicts of interest (COIs) are disclosed and managed by a national clinical guideline developer (NICE: the UK National Institute for Health and Care Excellence). Qualitative study using semi-structured telephone interviews with 14 key informants: 8 senior staff of NICE's guideline development centres and 6 chairs of guideline development groups (GDGs). We conducted a thematic analysis. Participants regard the NICE COI policy as comprehensive leading to transparent and independent guidance. The application of the NICE COI policy is, however, not straightforward and clarity could be improved. Disclosure of COI relies on self reporting and guideline developers have to take "on trust" the information they receive, certain types of COI (non-financial) are difficult to categorise and manage and disclosed COI can impact on the ability to recruit clinical experts to GDGs. Participants considered it both disruptive and stressful to exclude members from GDG meetings when required by the COI policy. Nonetheless the impact of this disruption can be minimised with good group chairing skills. We consider that the successful implementation of a COI policy in clinical guideline development requires clear policies and procedures, appropriate training of GDG chairs and an evaluation of how the policy is used in practice.

  15. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute’s genomic medicine portfolio

    Science.gov (United States)

    Manolio, Teri A.

    2016-01-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual’s genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of “Genomic Medicine Meetings,” under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and diffficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI’s genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. PMID:27612677

  16. Precision Medicine in NCI’s National Clinical Trials Network: Progress and Lessons Learned

    Science.gov (United States)

    NCI’s Jeff Abrams, M.D., Acting Director for Clinical Research in the Division of Cancer Treatment and Diagnosis (DCTD) and Associate Director of the Cancer Therapy Evaluation Program (CTEP) and Nita Seibel, M.D., Head of the Pediatric Solid Tumor Therapeutics in the Clinical Investigations Branch of CTEP, DCTD will host a Google Hangout on Air. The discussion will be moderated by Andrea Denicoff, R.N., N.P, Head, NCTN Clinical Trials Operations in the Investigational Drug Branch of CTEP, DCTD.

  17. Quality of care at ART clinic in Shashamanne referral hospital, West Arsi zone, Oromina National Regional State, South Ethiopia

    Directory of Open Access Journals (Sweden)

    Melese Belayneh

    2017-01-01

    Full Text Available Background Low income nations like Ethiopia, which are heavily affected by HIV pandemic, health system needs to provide comprehensive services for escalating numbers of HIV positive patients. While demand is increasing, resources are not expanding at desirable rates to meet these demands. This leads to the risk of running poor quality antiretroviral therapy in resource limited health facilities. However, there is paucity of research based evidences on the quality of health services in the country in general, and on anti retroviral therapy in particular. Objective To assess quality of care at antiretroviral therapy clinic in Shashamanne Referral Hospital. Method A cross‐sectional study was conducted in Shashamanne Referral hospital from May 30 to June 30,2017.The study population were selected people living with HIV, antiretroviral therapy clinics and health care workers in antiretroviral therapy clinics during the study period. Stratified sampling method was used to identify study population. Interviewer administered questionnaire was employed among 204 patients to assess their satisfaction. Medical records review check list was used to get vital information from documents of 354 patients. Interview guide was also used to assess providers’ view on services. Data were entered by using SPSS version 20 and analyzed using descriptive, bivariate and multivariate techniques. Ethical clearance was obtained from Jimma University College of Public Health and Medical Sciences. Results Resources required for implementation of antiretroviral therapy wee available as per recommendation by the national Guideline. However, scarcity of some OIs and ARV drugs and absence of a few laboratory services seen in the hospital. HIV/AIDS care given in line with national guidelines but study revealed that only 42.7% of clients eligible for isoniazid preventive therapy actually taken it. Average mean satisfaction score of patients was 2.51 and significant

  18. Homozygous familiar hypercholesterolemia in China: Case series from the national lipid clinics and literature review

    Directory of Open Access Journals (Sweden)

    Cheng-Gang Zhu

    2017-03-01

    Conclusion: In a conclusion, we found a relatively common recruitment of this type of patients in our hospital, which might have an important clinical implication for the identification and management of the patients with FH in China.

  19. Management of rheumatoid arthritis in clinical practice using treat-to-target strategy: Where do we stand in the multi-ethnic Malaysia population?

    Science.gov (United States)

    Tan, Bee Eng; Lim, Ai Lee; Kan, Sow Lai; Lim, Chong Hong; Ng, Ying Fun; Tng, Serene Li Ching; Hassin, Nur Syakirah; Chandran, Losshenee; Hamid, Norshahida Abdul; Lee, Yvonne Yin Leng

    2017-06-01

    To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.

  20. SANDS: an architecture for clinical decision support in a National Health Information Network.

    Science.gov (United States)

    Wright, Adam; Sittig, Dean F

    2007-10-11

    A new architecture for clinical decision support called SANDS (Service-oriented Architecture for NHIN Decision Support) is introduced and its performance evaluated. The architecture provides a method for performing clinical decision support across a network, as in a health information exchange. Using the prototype we demonstrated that, first, a number of useful types of decision support can be carried out using our architecture; and, second, that the architecture exhibits desirable reliability and performance characteristics.

  1. Optical design of the National Ignition Facility main laser and switchyard/target area beam transport systems

    Science.gov (United States)

    Miller, John L.; English, R. Edward, Jr.; Korniski, Ronald J.; Rodgers, J. Michael

    1999-07-01

    The optical design of the main laser and transport mirror sections of the National Ignition Facility are described. For the main laser the configuration, layout constraints, multiple beam arrangement, pinhole layout and beam paths, clear aperture budget, ray trace models, alignment constraints, lens designs, wavefront performance, and pupil aberrations are discussed. For the transport mirror system the layout, alignment controls and clear aperture budget are described.

  2. Content and Target Aspects of the Relativism Concept of National Stereotypes in the Higher School Foreign Language Teaching

    Directory of Open Access Journals (Sweden)

    N. V. Sorokina

    2013-01-01

    Full Text Available The paper deals with the innovative educational concept of teaching the foreign languages to the senior university students. The research methodology is based on M. Bennett’s model of intercultural sensitivitydevelopment necessary for the gradual transformation of ethnocentrism into ethno-relativism. The development of students’ relativistic perception of national stereotypes is perceived by the author as an important factor of both the natural cognitive mechanism and intercultural communication. The author argues that relativistic perception of national stereotypes can be achieved by fostering the intercultural world outlook, and therefore recommends incorporating a relativistic world view component in educational content structure along with the traditional components of knowledge, skills, attitudes, motives, creative activity expertise, etc.The paper emphasizes three consequent educational modules of ethnodifferentiation, ethno-integration and ethno-relativity in the proposed methodological system. The gradual fulfillment of educational goals, relatedto the above modules, can ensure the transformation of students’ perception of national stereotypes at the cognitive, affective, and behavioral levels. The proposed educational concept, approbated in the GermanLanguage Department of Zabaykalsky State University in 2010 – 2013, along with the research data prove the effectiveness of the given method, and demonstrate a substantial development of students’ intercultural competence and a decline in the ethnocentrism level.

  3. National priorities for the assessment of clinical conditions and medical technologies: report of a pilot study

    National Research Council Canada - National Science Library

    Lara, María Elena; Goodman, Clifford

    1990-01-01

    ... and Medical Technologies Report of a Pilot Study Maria Elena Lara and Clifford Goodman, editors Priority-Setting Group Council on Health Care Technology Institute of Medicine NATIONAL ACADEMY PRESS WASHINGTON, D.C. 1990 i Copyrightoriginal retained, the be not from cannot book, paper original however, for version formatting, authoritative the typese...

  4. A National Survey of School Counselor Supervision Practices: Administrative, Clinical, Peer, and Technology Mediated Supervision

    Science.gov (United States)

    Perera-Diltz, Dilani M.; Mason, Kimberly L.

    2012-01-01

    Supervision is vital for personal and professional development of counselors. Practicing school counselors (n = 1557) across the nation were surveyed to explore current supervision practices. Results indicated that 41.1% of school counselors provide supervision. Although 89% receive some type of supervision, only 10.3% of school counselors receive…

  5. Facilitating the implementation of clinical technology in healthcare: what role does a national agency play?

    Science.gov (United States)

    Harvey, Gill; Llewellyn, Sue; Maniatopoulos, Greg; Boyd, Alan; Procter, Rob

    2018-05-10

    Accelerating the implementation of new technology in healthcare is typically complex and multi-faceted. One strategy is to charge a national agency with the responsibility for facilitating implementation. This study examines the role of such an agency in the English National Health Service. In particular, it compares two different facilitation strategies employed by the agency to support the implementation of insulin pump therapy. The research involved an empirical case study of four healthcare organisations receiving different levels of facilitation from the national agency: two received active hands-on facilitation; one was the intended recipient of a more passive, web-based facilitation strategy; the other implemented the technology without any external facilitation. The primary method of data collection was semi-structured qualitative interviews with key individuals involved in implementation. The integrated-PARIHS framework was applied as a conceptual lens to analyse the data. The two sites that received active facilitation from an Implementation Manager in the national agency made positive progress in implementing the technology. In both sites there was a high level of initial receptiveness to implementation. This was similar to a site that had successfully introduced insulin pump therapy without facilitation support from the national agency. By contrast, a site that did not have direct contact with the national agency made little progress with implementation, despite the availability of a web-based implementation resource. Clinicians expressed differences of opinion around the value and effectiveness of the technology and contextual barriers related to funding for implementation persisted. The national agency's intended roll out strategy using passive web-based facilitation appeared to have little impact. When favourable conditions exist, in terms of agreement around the value of the technology, clinician receptiveness and motivation to change, active

  6. Social franchising primary healthcare clinics--a model for South African National Health Insurance?

    Science.gov (United States)

    Robinson, Andrew Ken Lacey

    2015-09-21

    This article describes the first government social franchise initiative in the world to deliver a 'brand' of quality primary healthcare (PHC) clinic services. Quality and standards of care are not uniformly and reliably delivered across government PHC clinics in North West Province, South Africa, despite government support, numerous policies, guidelines and in-service training sessions provided to staff. Currently the strongest predictor of good-quality service is the skill and dedication of the facility manager. A project utilising the social franchising business model, harvesting best practices, has been implemented with the aim of developing a system to ensure reliably excellent healthcare service provision in every facility in North West. The services of social franchising consultants have been procured to develop the business model to drive this initiative. Best practices have been benchmarked, and policies, guidelines and clinic support systems have been reviewed, evaluated and assessed, and incorporated into the business plan. A pilot clinic has been selected to refine and develop a working social franchise model. This will then be replicated in one clinic to confirm proof of concept before further scale-up. The social franchise business model can provide solutions to a reliable and recognisable 'brand' of quality universal coverage of healthcare services.

  7. Embedding mental health support in schools: Learning from the Targeted Mental Health in Schools (TaMHS) national evaluation

    OpenAIRE

    Wolpert, M; Humphrey, N; Belsky, J; Deighton, J

    2013-01-01

    The Targeted Mental Health in Schools (TaMHS) programme was a nationwide initiative that funded mental health provision in schools for pupils at risk of or already experiencing mental health problems. The implementation, impact and experience of this programme was evaluated using quantitative and qualitative methodology involving three main studies: (1) a 1-year RCT involving 8658 8-10 year olds and 6583 11-13 year olds, (2) a 3-year longitudinal study involving 3346 8-10 year olds and 2647 1...

  8. Clinical practice guidelines in complementary and alternative medicine. An analysis of opportunities and obstacles. Practice and Policy Guidelines Panel, National Institutes of Health Office of Alternative Medicine.

    Science.gov (United States)

    1997-01-01

    An estimated 1 of 3 Americans uses some form of complementary and alternative medicine (CAM), such as acupuncture, homeopathy, or herbal medicine. In 1995, the National Institutes of Health Office of Alternative Medicine convened an expert panel to examine the role of clinical practice guidelines in CAM. The panel concluded that CAM practices currently are unsuitable for the development of evidence-based practice guidelines, in part because of the lack of relevant outcomes data from well-designed clinical trials. Moreover, the notions of standardization and appropriateness, inherent in guideline development, face challenging methodologic problems when applied to CAM, which considers many different treatment practices appropriate and encourages highly individualized care. Due to different belief systems and divergent theories about the nature of health and illness, CAM disciplines have fundamental differences in how they define target conditions, causes of disease, interventions, and outcome measures of effectiveness. These differences are even more striking when compared with those used by Western medicine. The panel made a series of recommendations on strategies to strengthen the evidence base for future guideline development in CAM and to meet better the current information needs of clinicians, patients, and guideline developers who seek information about CAM treatments.

  9. Long-term Mechanical Circulatory Support System reliability recommendation by the National Clinical Trial Initiative subcommittee.

    Science.gov (United States)

    Lee, James

    2009-01-01

    The Long-Term Mechanical Circulatory Support (MCS) System Reliability Recommendation was published in the American Society for Artificial Internal Organs (ASAIO) Journal and the Annals of Thoracic Surgery in 1998. At that time, it was stated that the document would be periodically reviewed to assess its timeliness and appropriateness within 5 years. Given the wealth of clinical experience in MCS systems, a new recommendation has been drafted by consensus of a group of representatives from the medical community, academia, industry, and government. The new recommendation describes a reliability test methodology and provides detailed reliability recommendations. In addition, the new recommendation provides additional information and clinical data in appendices that are intended to assist the reliability test engineer in the development of a reliability test that is expected to give improved predictions of clinical reliability compared with past test methods. The appendices are available for download at the ASAIO journal web site at www.asaiojournal.com.

  10. Monte-Carlo model development for evaluation of current clinical target volume definition for heterogeneous and hypoxic glioblastoma.

    Science.gov (United States)

    Moghaddasi, L; Bezak, E; Harriss-Phillips, W

    2016-05-07

    Clinical target volume (CTV) determination may be complex and subjective. In this work a microscopic-scale tumour model was developed to evaluate current CTV practices in glioblastoma multiforme (GBM) external radiotherapy. Previously, a Geant4 cell-based dosimetry model was developed to calculate the dose deposited in individual GBM cells. Microscopic extension probability (MEP) models were then developed using Matlab-2012a. The results of the cell-based dosimetry model and MEP models were combined to calculate survival fractions (SF) for CTV margins of 2.0 and 2.5 cm. In the current work, oxygenation and heterogeneous radiosensitivity profiles were incorporated into the GBM model. The genetic heterogeneity was modelled using a range of α/β values (linear-quadratic model parameters) associated with different GBM cell lines. These values were distributed among the cells randomly, taken from a Gaussian-weighted sample of α/β values. Cellular oxygen pressure was distributed randomly taken from a sample weighted to profiles obtained from literature. Three types of GBM models were analysed: homogeneous-normoxic, heterogeneous-normoxic, and heterogeneous-hypoxic. The SF in different regions of the tumour model and the effect of the CTV margin extension from 2.0-2.5 cm on SFs were investigated for three MEP models. The SF within the beam was increased by up to three and two orders of magnitude following incorporation of heterogeneous radiosensitivities and hypoxia, respectively, in the GBM model. However, the total SF was shown to be overdominated by the presence of tumour cells in the penumbra region and to a lesser extent by genetic heterogeneity and hypoxia. CTV extension by 0.5 cm reduced the SF by a maximum of 78.6  ±  3.3%, 78.5  ±  3.3%, and 77.7  ±  3.1% for homogeneous and heterogeneous-normoxic, and heterogeneous hypoxic GBMs, respectively. Monte-Carlo model was developed to quantitatively evaluate SF for genetically

  11. Targeted Genetic Screen in Amyotrophic Lateral Sclerosis Reveals Novel Genetic Variants with Synergistic Effect on Clinical Phenotype

    Directory of Open Access Journals (Sweden)

    Johnathan Cooper-Knock

    2017-11-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is underpinned by an oligogenic rare variant architecture. Identified genetic variants of ALS include RNA-binding proteins containing prion-like domains (PrLDs. We hypothesized that screening genes encoding additional similar proteins will yield novel genetic causes of ALS. The most common genetic variant of ALS patients is a G4C2-repeat expansion within C9ORF72. We have shown that G4C2-repeat RNA sequesters RNA-binding proteins. A logical consequence of this is that loss-of-function mutations in G4C2-binding partners might contribute to ALS pathogenesis independently of and/or synergistically with C9ORF72 expansions. Targeted sequencing of genomic DNA encoding either RNA-binding proteins or known ALS genes (n = 274 genes was performed in ALS patients to identify rare deleterious genetic variants and explore genotype-phenotype relationships. Genomic DNA was extracted from 103 ALS patients including 42 familial ALS patients and 61 young-onset (average age of onset 41 years sporadic ALS patients; patients were chosen to maximize the probability of identifying genetic causes of ALS. Thirteen patients carried a G4C2-repeat expansion of C9ORF72. We identified 42 patients with rare deleterious variants; 6 patients carried more than one variant. Twelve mutations were discovered in known ALS genes which served as a validation of our strategy. Rare deleterious variants in RNA-binding proteins were significantly enriched in ALS patients compared to control frequencies (p = 5.31E-18. Nineteen patients featured at least one variant in a RNA-binding protein containing a PrLD. The number of variants per patient correlated with rate of disease progression (t-test, p = 0.033. We identified eighteen patients with a single variant in a G4C2-repeat binding protein. Patients with a G4C2-binding protein variant in combination with a C9ORF72 expansion had a significantly faster disease course (t-test, p = 0.025. Our data are

  12. [Epidermolysis bullosa in peru: clinical and epidemiological study of patients treated in a national reference pediatric hospital, 1993-2015].

    Science.gov (United States)

    Torres-Iberico, Rosario; Palomo-Luck, Patricia; Torres-Ramos, Gilmer; Lipa-Chancolla, Roxana

    2017-01-01

    To describe the clinical and epidemiological characteristics of patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de Salud (INSN) in Lima, Peru; a National Reference Center for this disease. Observational, descriptive and transversal study. We reviewed the clinical histories and laboratory tests of patients diagnosed with EB treated in INSN from 1993 to 2015. 93 patients were registered. The average age was 7.9 ± 5.6 years; 53.8% (n = 50) were boys. Clinical forms corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%), union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The clinical form could not be identified in a case. A total of 48 cases (51.6%) came from Lima and Callao, and 45 cases (48.4%) from other provinces of the country. Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%), odontogenic (87.1%), and nutritional (79.6%) involvement, as well as pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%). 93 cases of EB were reported in INSN, the predominant clinical presentation was the dystrophic form.

  13. A parent-report Gender Identity Questionnaire for Children: A cross-national, cross-clinic comparative analysis.

    Science.gov (United States)

    Cohen-Kettenis, Peggy T; Wallien, Madeleine; Johnson, Laurel L; Owen-Anderson, Allison F H; Bradley, Susan J; Zucker, Kenneth J

    2006-07-01

    A one-factor, 14-item parent-report Gender Identity Questionnaire for Children (GIQC) was developed in a sample of 325 clinic-referred children with gender identity problems and 504 controls from Toronto, Canada (Johnson et al., 2004). In this study, we report a cross-national, cross-clinic comparative analysis of the GIQC on gender-referred children (N = 338) from Toronto and gender-referred children (N = 175) from Utrecht, The Netherlands. Across clinics, the results showed both similarities and differences. Gender-referred boys from Utrecht had a significantly higher total score (indicating more cross-gender behavior) than did gender-referred boys from Toronto, but there was no significant difference for girls. In the Toronto sample, the gender-referred girls had a significantly higher total score than the gender-referred boys, but there was no significant sex difference in the Utrecht sample. Across both clinics, gender-referred children who met the complete DSM criteria for gender identity disorder (GID) had a significantly higher cross-gender score than the gender-referred children who were subthreshold for GID (Cohen's d = 1.11). The results of this study provide the first empirical evidence of relative similarity in cross-gender behavior in a sample of gender-referred children from western Europe when compared to North American children. The results also provide some support for cross-clinic consistency in clinician-based diagnosis of GID.

  14. National Clinical Skills Competition: an effective simulation-based method to improve undergraduate medical education in China

    Directory of Open Access Journals (Sweden)

    Guanchao Jiang

    2016-02-01

    Full Text Available Background: The National Clinical Skills Competition has been held in China for 5 consecutive years since 2010 to promote undergraduate education reform and improve the teaching quality. The effects of the simulation-based competition will be analyzed in this study. Methods: Participation in the competitions and the compilation of the questions used in the competition finals are summarized, and the influence and guidance quality are further analyzed. Through the nationwide distribution of questionnaires in medical colleges, the effects of the simulation-based competition on promoting undergraduate medical education reform were evaluated. Results: The results show that approximately 450 students from more than 110 colleges (accounting for 81% of colleges providing undergraduate clinical medical education in China participated in the competition each year. The knowledge, skills, and attitudes were comprehensively evaluated by simulation-based assessment. Eight hundred and eighty copies of the questionnaires were distributed to 110 participating medical schools in 2015. In total, 752 valid responses were received across 95 schools. The majority of the interviewees agreed or strongly agreed that competition promoted the adoption of advanced educational principles (76.8%, updated the curriculum model and instructional methods (79.8%, strengthened faculty development (84.0%, improved educational resources (82.1%, and benefited all students (53.4%. Conclusions: The National Clinical Skills Competition is widely accepted in China. It has effectively promoted the reform and development of undergraduate medical education in China.

  15. National Clinical Skills Competition: an effective simulation-based method to improve undergraduate medical education in China.

    Science.gov (United States)

    Jiang, Guanchao; Chen, Hong; Wang, Qiming; Chi, Baorong; He, Qingnan; Xiao, Haipeng; Zhou, Qinghuan; Liu, Jing; Wang, Shan

    2016-01-01

    The National Clinical Skills Competition has been held in China for 5 consecutive years since 2010 to promote undergraduate education reform and improve the teaching quality. The effects of the simulation-based competition will be analyzed in this study. Participation in the competitions and the compilation of the questions used in the competition finals are summarized, and the influence and guidance quality are further analyzed. Through the nationwide distribution of questionnaires in medical colleges, the effects of the simulation-based competition on promoting undergraduate medical education reform were evaluated. The results show that approximately 450 students from more than 110 colleges (accounting for 81% of colleges providing undergraduate clinical medical education in China) participated in the competition each year. The knowledge, skills, and attitudes were comprehensively evaluated by simulation-based assessment. Eight hundred and eighty copies of the questionnaires were distributed to 110 participating medical schools in 2015. In total, 752 valid responses were received across 95 schools. The majority of the interviewees agreed or strongly agreed that competition promoted the adoption of advanced educational principles (76.8%), updated the curriculum model and instructional methods (79.8%), strengthened faculty development (84.0%), improved educational resources (82.1%), and benefited all students (53.4%). The National Clinical Skills Competition is widely accepted in China. It has effectively promoted the reform and development of undergraduate medical education in China.

  16. DOE FES FY2017 Joint Research Target Fourth Quarter Milestone Report for theNational Spherical Torus Experiment Upgrade.

    Energy Technology Data Exchange (ETDEWEB)

    Soukhanovskii, V. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-09-13

    A successful high-performance plasma operation with a radiative divertor has been demonstrated on many tokamak devices, however, significant uncertainty remains in accurately modeling detachment thresholds, and in how detachment depends on divertor geometry. Whereas it was originally planned to perform dedicated divertor experiments on the National Spherical Tokamak Upgrade to address critical detachment and divertor geometry questions for this milestone, the experiments were deferred due to technical difficulties. Instead, existing NSTX divertor data was summarized and re-analyzed where applicable, and additional simulations were performed.

  17. Impact of Clinical Factors on the Achievement of Target Blood Pressure in Hypertensive Patients from Ivanovo Region of Russia: Data of 2015.

    Science.gov (United States)

    Kiselev, A R; Posnenkova, O M; Belova, O A; Romanchuk, S V; Popova, Y V; Prokhorov, M D; Gridnev, V I

    2017-12-01

    In Russia, blood pressure (BP) control is below the optimal. The little is known about regional features and barriers to adequate BP control in Russian primary care. To evaluate the impact of clinical factors on achieving the target BP in hypertensive patients in one region of Russia. Retrospective medical data of 2015 on 11,129 patients (31.4% male) with hypertension (Htn) from Ivanovo region of Russia were examined. Achievement of target BP was assessed in all patients. We study association between BP control and clinical factors. 45.9% of studied patients with Htn had controlled BP. The frequency of achieving the target BP in subsets of hypertensive patients was 37.8% in patients with diabetes, 39.5% in patients with coronary artery disease, and 29.9% in patients with chronic heart failure. The main clinical factors associated with achieving the target BP in studied hypertensive patients were the advice on alcohol consumption, advice on smoking cessation, and advice on weight reduction. Therapy with main antihypertensive drugs (in particular, beta-blockers and thiazide diuretics) were also factors of optimal BP control in these patients. Comorbidities (chronic heart failure and cardiovascular diseases requiring the prescription of aspirin and statins) and family history of coronary artery disease were associated with inadequate BP control. A negative effect of some antihypertensive drugs (potassium sparing diuretics, ARBs, ACE-Is, and dihydropyridine CCBs) on BP control that was found out in our study requires further investigation. Other studied factors had no influence on BP control in patients with Htn from Ivanovo region. We identified regional factors of BP control in hypertensive patients from Ivanovo region of Russia. It is shown that individual medical education (in particular, medical advices) is the most important factor of optimal BP control. The intervention with antihypertensive therapy (beta-blockers and thiazide diuretics) facilitates the

  18. 75 FR 13550 - Office of Clinical and Preventive Services: National HIV Program

    Science.gov (United States)

    2010-03-22

    ... services, reducing stigma, and making testing routine. This open competition seeks to expand fiscal... physical and mental health of the American people. Dated: March 12, 2010. Yvette Roubideaux, Director... DEPARTMENT OF HEALTH AND HUMAN SERVICES Indian Health Service Office of Clinical and Preventive...

  19. Surfing the best practice guidelines: national clinical guideline clearinghouse in development.

    Science.gov (United States)

    1997-08-01

    The growth in development and usage of clinical guidelines during the last five years has been remarkable. Not only are health care practitioners reaching for what's deemed to be the best in protocols and practice, consumers, too, are looking toward standards and guidelines as they become more educated about the quality and quantity of health care services they should be receiving.

  20. Lung-MAP Launches: First Precision Medicine Trial From National Clinical Trials Network

    Science.gov (United States)

    A unique public-private collaboration today announced the initiation of the Lung Cancer Master Protocol (Lung-MAP) trial, a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinom

  1. Identification of Best Practices for Resident Aesthetic Clinics in Plastic Surgery Training: The ACAPS National Survey

    Directory of Open Access Journals (Sweden)

    C. Scott Hultman, MD, MBA, FACS

    2015-03-01

    Conclusions: RACs are an important component of plastic surgery education. Most clinics are financially viable but carry high malpractice risk and consume significant resources. Best practices, to maximize patient safety and optimize resident education, include use of accredited procedural rooms and direct faculty supervision of all components of care.

  2. Tumor Vessel Development and Expansion in Ewing's Sarcoma: A Review of the Vasculogenesis Process and Clinical Trials with Vascular-Targeting Agents

    Science.gov (United States)

    Stewart, Keri S.; Kleinerman, Eugenie S.

    2011-01-01

    Ewing's sarcoma accounts for a disproportionately high portion of the overall pediatric mortality rate compared to its rare incidence in the pediatric population. Little progress has been made since the introduction of traditional chemotherapies, and understanding the biology of the tumor is critical for developing new therapies. Ewing's sarcomas rely on a functional vascular supply, which is formed by a combination of angiogenesis and vasculogenesis. Recent insights into the molecular regulation of bone marrow (BM) cell participation in vascular development have identified VEGF, SDF-1α, and DLL4 as critical players in the vasculogenesis process. Clinical trials using vascular targeting agents, specifically targeting VEGF or DLL4, are underway. PMID:21785569

  3. National Ignition Facility subsystem design requirements laser and target area building (LTAB) SSDR 1.2.2.1

    International Nuclear Information System (INIS)

    Kempel, P.; Hands, J.

    1996-01-01

    This Subsystem Design Requirements (SSDR) document establishes the performance, design, and verification requirements for the conventional building systems and subsystems of the Laser and Target Area Building (LTAB), including those that house and support the operation of high-energy laser equipment and the operational flow of personnel and materials throughout the facility. This SSDR addresses the following subsystems associated with the LTAB: Building structural systems for the Target Bay, Switchyards, Diagnostic Building, Decontamination Area, Laser Bays, Capacitor Bays and Operations Support Area, and the necessary space associated with building-support equipment; Architectural building features associated with housing the space and with the operational cleanliness of the functional operation of the facilities; Heating, Ventilating, and Air Conditioning (HVAC) systems for maintaining a clean and thermally stable ambient environment within the facilities; Plumbing systems that provide potable water and sanitary facilities for the occupants, plus stormwater drainage for transporting rainwater; Fire Protection systems that guard against fire damage to the facilities and their contents; Material handling systems for transporting personnel and heavy materials within the building areas; Mechanical process piping systems for liquids and gases that provide cooling and other service to experimental laser equipment and components; Electrical power and grounding systems that provide service and standby power to building and experimental equipment, including lighting distribution and communications systems for the facilities; Instrumentation and control systems that ensure the safe operation of conventional facilities systems, such as those listed above. Detailed requirements for building subsystems that are not addressed in this document (such as specific sizes, locations, or capacities) are included in detail-level NIP Project Interface Control Documents (ICDS)

  4. Proposed Optimal Fluoroscopic Targets for Cooled Radiofrequency Neurotomy of the Sacral Lateral Branches to Improve Clinical Outcomes: An Anatomical Study.

    Science.gov (United States)

    Stout, Alison; Dreyfuss, Paul; Swain, Nathan; Roberts, Shannon; Loh, Eldon; Agur, Anne

    2017-11-23

    Current sacroiliac joint (SIJ) cooled radiofrequency (RF) is based on fluoroscopic anatomy of lateral branches (LBs) in three specimens. Recent studies confirm significant variation in LB positions. To determine if common fluoroscopic needle placements for cooled SIJ RF are adequate to lesion all S1-3 LBs. If not, would different targets improve lesion accuracy? The LBs of 20 cadavers were dissected bilaterally (40 SIJs), and 26 G radiopaque wires were sutured to the LBs. With a 10-mm radius ruler centered at each foramen, standard targets were assessed, as judged by a clockface on the right, for S1 and S2 at 2:30, 4:00, and 5:30 positions and at S3 at 2:30 and 4:00. Mirror image targets were assessed on the left. Assuming an 8-mm lesion diameter, the percentage of LBs that would not be ablated for each level was determined. Imaging through the superior end plate of S1 was compared against segment specific (SS) imaging. Nine point four percent of LBs would not be ablated at S1 vs 0.99% at S2 vs 35% at S3, and 60% of the 40 SIJs would be completely denervated using current targets. SS imaging did not improve results. Alternate target locations could improve the miss rate to 2.8% at S1 and 0% at S3 and would ablate all LBs in 95% of SIJs. Using a conservative 8-mm lesion measurement, contemporary cooled RF needle targets are inadequate to lesion all target LBs. Modifications to current targets are recommended to increase the effectiveness of the procedure. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  5. National clinical guidelines for management of the palatally ectopic maxillary canine.

    Science.gov (United States)

    Husain, J; Burden, D; McSherry, P; Morris, D; Allen, M

    2012-08-01

    This review summarises updated clinical guidelines produced by the Clinical Standards Committee of the Faculty of Dental Surgery, Royal College of Surgeons of England (FDSRCS). This guideline on the management of the palatally ectopic maxillary canine illustrates the information contained in the recently updated online version. The timely recognition of ectopic canines is important for the overall management of the dentition. This review illustrates five management strategies for ectopic permanent canines: interceptive treatment by extraction of the deciduous canine, surgical exposure and orthodontic alignment, surgical removal of the palatally ectopic permanent canine, auto-transplantation and no active treatment/leave and observe. The current available evidence for each of these management options has been evaluated and awarded a grade used by the Scottish Intercollegiate Guidelines Network.

  6. [Extrinsic allergic alveolitis. Clinical experience at the Instituto National de Enfermedades Respiratorias (INER)].

    Science.gov (United States)

    Chapela-Mendoza, R; Selman-Lama, M

    1999-01-01

    Extrinsic allergic alveolitis is an interstitial lung disease caused by exposure to a variety of inhaled antigens. In Mexico, the most frequent form is due to the inhalation of avian antigens, markedly pigeon proteins. Depending on type and time exposure, the disease presents different clinical forms usually characterized by progressive dyspnea, ground glass or reticulonodular images on chest x rays, a restrictive functional pattern, rest hypoxemia worsening with exercise, and increase of T lymphocytes in bronchoalveolar lavage with an inversion in the helper/suppressor ratio. In this paper, we discuss a 15-year experience with this pathological problem in Mexico, emphasizing the differences with this disorder in Caucasian populations. Generally, our patients display a chronic form of the disease, which evolves to fibrosis in about one-half of the patients. In this sense, the diagnostic, prognostic, and therapeutic focusing exhibit different elements, and thus the development of clinical and basic research is strongly required.

  7. Estimate of average glandular dose (AGD) in national clinics of mammography

    International Nuclear Information System (INIS)

    Mora, Patricia; Segura, Helena

    2004-01-01

    The breast cancer represents the second cause of death by cancer in the femme population of our country. The specialized equipment for the obtaining of the mammographic images is higher every day and its use increases daily. The quality of the radiographic study is linked to the dose that this tissue intrinsically sensible receives to the ionizing radiations. The present work makes the first national study to quantify the average glandular doses and to connect them with the diagnostic quality and the recommendations to international scale. (Author) [es

  8. Managing conflicts of interest in the UK National Institute for Health and Care Excellence (NICE clinical guidelines programme: qualitative study.

    Directory of Open Access Journals (Sweden)

    Tanya Graham

    Full Text Available There is international concern that conflicts of interest (COI may bias clinical guideline development and render it untrustworthy. Guideline COI policies exist with the aim of reducing this bias but it is not known how such policies are interpreted and used by guideline producing organisations. This study sought to determine how conflicts of interest (COIs are disclosed and managed by a national clinical guideline developer (NICE: the UK National Institute for Health and Care Excellence.Qualitative study using semi-structured telephone interviews with 14 key informants: 8 senior staff of NICE's guideline development centres and 6 chairs of guideline development groups (GDGs. We conducted a thematic analysis.Participants regard the NICE COI policy as comprehensive leading to transparent and independent guidance. The application of the NICE COI policy is, however, not straightforward and clarity could be improved. Disclosure of COI relies on self reporting and guideline developers have to take "on trust" the information they receive, certain types of COI (non-financial are difficult to categorise and manage and disclosed COI can impact on the ability to recruit clinical experts to GDGs. Participants considered it both disruptive and stressful to exclude members from GDG meetings when required by the COI policy. Nonetheless the impact of this disruption can be minimised with good group chairing skills.We consider that the successful implementation of a COI policy in clinical guideline development requires clear policies and procedures, appropriate training of GDG chairs and an evaluation of how the policy is used in practice.

  9. Pneumatic sample-transfer system for use with the Lawrence Livermore National Laboratory rotating target neutron source (RTNS-I)

    International Nuclear Information System (INIS)

    Williams, R.E.

    1981-07-01

    A pneumatic sample-transfer system is needed to be able to rapidly retrieve samples irradiated with 14-MeV neutrons at the Rotating Target Neutron Source (RTNS-I). The rabbit system, already in place for many years, has been refurbished with modern system components controlled by an LSI-11 minicomputer. Samples can now be counted three seconds after an irradiation. There are many uses for this expanded 14-MeV neutron activation capability. Several fission products difficult to isolate from mixed fission fragments can be produced instead through (n,p) or (n,α) reactions with stable isotopes. Mass-separated samples of Nd, Mo, and Se, for example, can be irradiated to produce Pr, Nb, and As radionuclides sufficient for decay scheme studies. The system may also be used for multielement fast-neutron activation analysis because the neutron flux is greater than 2 x 10 11 n/cm 2 -sec. Single element analyses of Si and O are also possible. Finally, measurements of fast-neutron cross sections producing short-lived activation products can be performed with this system. A description of the rabbit system and instructions for its use are presented in this report

  10. [Surgical History Taking and Clinical Examination: Establishing a Standardised System by Means of a Nation-Wide Academic Teaching Project].

    Science.gov (United States)

    von Bernstorff, W; Irmer, H; Menges, P; Peters, S; Heidecke, C-D; Busemann, A

    2017-02-01

    Background: History taking and systematic clinical examination are central techniques of physicians. Medicine in general and surgery in particular frequently require immediate decisions and start of therapies. So far, a standardised surgical system for history taking and clinical examination in teaching has been lacking at our faculty. A consensus of all medical faculties on a standardised system could be a tool to improve the medical teaching and education at our teaching institutions. Methods: The established Anglo-Saxonian system of history taking and clinical examination was adapted to our own clinical needs. Thereafter, this system was sent out to all chairmen of general and visceral surgery departments in German University Hospitals asking for evaluation and improvements. We adapted the system according to the chairmen's comments and suggestions. Since winter semester 2011 this system has been integrated into the clinical course of history taking and examination. It is compulsory for all 5th semester students (first clinical year/graduate course) at the Universitätsmedizin Greifswald. In addition, a video was produced demonstrating all major techniques of clinical examination. This video is available for all students on a password blocked site of the World Wide Web. Results: Altogether, 89 % of all contacted chairmen returned their comments and suggestions for improvements. After implementation of the new system, positive evaluations of students increased significantly from 63.5 to 77.0 % in general and abdominal surgery (p history taking and clinical examination applicable for students as well as qualified surgeons in daily routine work. It has been approved by the majority of the departments of surgery of all German university hospitals. Furthermore, it can be applied by other medical specialties, in particular, internal medicine. Furthermore, the standardisation of history taking and clinical examination can contribute to improve patients' safety as

  11. Identity fusion predicts endorsement of pro-group behaviours targeting nationality, religion, or football in Brazilian samples.

    Science.gov (United States)

    Bortolini, Tiago; Newson, Martha; Natividade, Jean Carlos; Vázquez, Alexandra; Gómez, Ángel

    2018-04-01

    A visceral feeling of oneness with a group - identity fusion - has proven to be a stronger predictor of pro-group behaviours than other measures of group bonding, such as group identification. However, the relationship between identity fusion, other group alignment measures and their different roles in predicting pro-group behaviour is still controversial. Here, we test whether identity fusion is related to, but different from, unidimensional and multidimensional measures of group identification. We also show that identity fusion explains further variance of the endorsement of pro-group behaviour than these alternative measures and examine the structural and discriminant properties of identity fusion and group identification measures in three different contexts: nationality, religion, and football fandom. Finally, we extend the fusion literature to a new culture: Brazil. To the best of our knowledge, this is the first research explicitly addressing a comparison between these two forms of group alignment, identity fusion and identification with a group, and their role in predicting pro-group behaviours. © 2018 The British Psychological Society.

  12. Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction

    DEFF Research Database (Denmark)

    Hørslev-Petersen, K; Hetland, M L; Ørnbjerg, L M

    2015-01-01

    OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease-modifying antirheuma......OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease.......12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04). CONCLUSIONS: An aggressive triamcinolone and synthetic DMARD treat-to-target strategy...... was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28>3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were...

  13. Changing epidemiology of AA amyloidosis: clinical observations over 25 years at a single national referral centre.

    Science.gov (United States)

    Lane, Thirusha; Pinney, Jennifer H; Gilbertson, Janet A; Hutt, David F; Rowczenio, Dorota M; Mahmood, Shameem; Sachchithanantham, Sajitha; Fontana, Marianna; Youngstein, Taryn; Quarta, Candida C; Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N; Lachmann, Helen J

    2017-09-01

    Systemic AA amyloidosis is a serious complication of chronic inflammation; however, there are relatively few published data on its incidence. We investigated the changing epidemiology of AA amyloidosis over a 25-year period at a single national referral centre. We conducted a retrospective study of all patients diagnosed with AA amyloidosis who had attended the centre between 1990 and 2014 inclusive. Six hundred and twenty-five patients were studied in three cohorts: C1: 1990-1997; C2: 1998-2006; C3: 2007-2014. Mean age at presentation increased from 46 in C1 to 56 in C3 (p AA amyloidosis over a quarter of a century, reflecting advances in therapeutics and overall management of complex chronic disease in an ageing population. AA amyloidosis of uncertain aetiology presents an emerging major problem. Newer techniques such as next-generation sequencing may aid diagnosis and effective treatment, thereby improving overall survival.

  14. Optical alignment techniques for line-imaging velocity interferometry and line-imaging self-emulsion of targets at the National Ignition Facility (NIF)

    International Nuclear Information System (INIS)

    Malone, Robert M.; Frogget, Brent C.; Kaufman, Morris I.; Tunnell, Thomas W.; Guyton, Robert L.; Reinbachs, Imants P.; Watts, Phillip W.

    2007-01-01

    The National Ignition Facility (NIF) requires optical diagnostics for measuring shock velocities in shock physics experiments. The Velocity Interferometer System for Any Reflector (VISAR) measures shock velocities, shock breakout times, and emission of 1- to 5-mm targets at a location remote to the NIF target chamber. Three optical systems using the same vacuum chamber port each have a total track of 69 feet. All optical lenses are on kinematic mounts or sliding rails, enabling pointing accuracy of the optical axis to be checked. Counter-propagating laser beams (orange and red) align these diagnostics to a listing of tolerances. The orange alignment laser is introduced at the entrance to the two-level interferometer table and passes forward through the optical systems to the recording streak cameras. The red alignment laser is introduced in front of the recording streak cameras and passes in the reverse direction through all optical elements, out of the interferometer table, eventually reaching the target chamber center. Red laser wavelength is selected to be at the 50 percent reflection point of a special beamsplitter used to separate emission light from the Doppler-shifted interferometer light. Movable aperture cards, placed before and after lens groups, show the spread of alignments spots created by the orange and red alignment lasers. Optical elements include 1- to 15-inch-diameter mirrors, lenses with up to 10.5-inch diameters, beamsplitters, etalons, dove prisms, filters, and pellicles. Alignment of more than 75 optical elements must be verified before each target shot. Archived images from eight alignment cameras prove proper alignment before each shot

  15. National survey on internal quality control for tumour markers in clinical laboratories in China.

    Science.gov (United States)

    Wang, Wei; Zhong, Kun; Yuan, Shuai; He, Falin; Du, Yuxuan; Hu, Zhehui; Wang, Zhiguo

    2018-06-15

    This survey was initiated to obtain knowledge on the current situation of internal quality control (IQC) practice for tumour markers (TMs) in China. Additionally, we tried to acquire the most appropriate quality specifications. This survey was a current status survey. The IQC information had been collected via online questionnaires. All of 1821 clinical laboratories which participated in the 2016 TMs external quality assessment (EQA) programme had been enrolled. The imprecision evaluation criteria were the minimal, desirable, and optimal allowable imprecisions based on biological variations, and 1/3 total allowable error (TEa) and 1/4 TEa. A total of 1628 laboratories answered the questionnaires (89%). The coefficients of variation (CVs) of the IQC of participant laboratories varied greatly from 1% (5 th percentile) to 13% (95 th percentile). More than 82% (82 - 91%) of participant laboratories two types of CVs met 1/3 TEa except for CA 19-9. The percentiles of current CVs were smaller than cumulative CVs. A number of 1240 laboratories (76%) reported their principles and systems used. The electrochemiluminescence was the most used principle (45%) and had the smallest CVs. The performance of laboratories for TMs IQC has yet to be improved. On the basis of the obtained results, 1/3 TEa would be realistic and attainable quality specification for TMs IQC for clinical laboratories in China.

  16. The use of ovarian reserve markers in IVF clinical practice: a national consensus.

    Science.gov (United States)

    La Marca, Antonio; Ferraretti, Anna Pia; Palermo, Roberto; Ubaldi, Filippo M

    2016-01-01

    Ovarian reserve markers have been documented to perform very well in the clinical practice. While this is widely recognized, still now there is no consensus on how to use new biomarkers in the clinical practice. This study was conducted among Italian IVF centres using the Delphi technique, a validated consensus-building process. Briefly three consecutive questionnaires were developed for clinicians in charge of IVF centres. In the first rounds, participants were asked to rate the importance of a list of statements regarding the categorization of ovarian response and the diagnostic role of biomarkers. In round 3, participants were asked to rate their agreement and consensus on the list of statements derived from the first two rounds. There were 120 respondents. Consensus was achieved for many points: (a) poor ovarian response is predicted on the basis of the following: AMH  3 ng/ml or AFC > 14; (c) day 3 FSH measurement should always be associated to estradiol; (d) AMH can be measured on a random basis; (e) the measurement of the AFC with the 2D technology may be considered adequate and (f) the AFC should be measured in the early follicular phase and consists in the total number of 2-9 mm follicles in both the ovaries. The present study suggests that extensive consensus on the importance and use of new ovarian reserve markers to improve IVF safety and performance is already present among clinicians.

  17. National Priority Setting of Clinical Practice Guidelines Development for Chronic Disease Management.

    Science.gov (United States)

    Jo, Heui-Sug; Kim, Dong Ik; Oh, Moo-Kyung

    2015-12-01

    By November 2013, a total of 125 clinical practice guidelines (CPGs) have been developed in Korea. However, despite the high burden of diseases and the clinical importance of CPGs, most chronic diseases do not have available CPGs. Merely 83 CPGs are related to chronic diseases, and only 40 guidelines had been developed in the last 5 yr. Considering the rate of the production of new evidence in medicine and the worsening burden from chronic diseases, the need for developing CPGs for more chronic diseases is becoming increasingly pressing. Since 2011, the Korean Academy of Medical Sciences and the Korea Centers for Disease Control and Prevention have been jointly developing CPGs for chronic diseases. However, priorities have to be set and resources need to be allocated within the constraint of a limited funding. This study identifies the chronic diseases that should be prioritized for the development of CPGs in Korea. Through an objective assessment by using the analytic hierarchy process and a subjective assessment with a survey of expert opinion, high priorities were placed on ischemic heart disease, cerebrovascular diseases, Alzheimer's disease and other dementias, osteoarthritis, neck pain, chronic kidney disease, and cirrhosis of the liver.

  18. Specialist perioperative allergy clinic services in the UK 2016: Results from the Royal College of Anaesthetists Sixth National Audit Project.

    Science.gov (United States)

    Egner, W; Cook, T; Harper, N; Garcez, T; Marinho, S; Kong, K L; Nasser, S; Thomas, M; Warner, A; Hitchman, J; Floss, K

    2017-10-01

    Guidelines for investigation of perioperative drug allergy exist, but the quality of services is unknown. Specialist perioperative anaphylaxis services were surveyed through the Royal College of Anaesthetists 6 th National Audit Project. We compare self-declared UK practice in specialist perioperative allergy services with national recommendations. A SurveyMonkey™ questionnaire was distributed to providers of allergy services in the UK. Responses were assessed for adherence to the best practice recommendations of the British Society for Allergy and Clinical Immunology (BSACI), the Association of Anaesthetists of Great Britain and Ireland and the National Institute for Health and Care Excellence (NICE) Guidance on Drug Allergy-CG183. Over 1200 patients were evaluated in 44 centres annually. Variation in workload, waiting times, access, staffing and diagnostic approach was noted. Paediatric centres had the longest routine waiting times (most wait >13 weeks) in contrast to adult centres (most wait specialist nurses and 18/44 (41%) an anaesthetist] and provision of information [18/44 (41%) gave immediate information in clinic and 5/44 (11%) sign-posted support groups]. Most centres were able to provide diagnostic challenges to antibiotics [40/44 (91%]) and local anaesthetics [41/44 (93%)]. Diagnostic testing is not harmonized, with marked variability in the NMBA panels used to identify safe alternatives. Chlorhexidine and latex are not part of routine testing in many centres. Poor access to services and patient information provision require attention. Harmonization of diagnostic approach is desirable, particularly with regard to a minimum NMBA panel for identification of safe alternatives. © 2017 John Wiley & Sons Ltd.

  19. Which Clinical and Patient Factors Influence the National Economic Burden of Hospital Readmissions After Total Joint Arthroplasty?

    Science.gov (United States)

    Kurtz, Steven M; Lau, Edmund C; Ong, Kevin L; Adler, Edward M; Kolisek, Frank R; Manley, Michael T

    2017-12-01

    The Affordable Care Act of 2010 advanced the economic model of bundled payments for total joint arthroplasty (TJA), in which hospitals will be financially responsible for readmissions, typically at 90 days after surgery. However, little is known about the financial burden of readmissions and what patient, clinical, and hospital factors drive readmission costs. (1) What is the incidence, payer mix, and demographics of THA and TKA readmissions in the United States? (2) What patient, clinical, and hospital factors are associated with the cost of 30- and 90-day readmissions after primary THA and TKA? (3) Are there any differences in the economic burden of THA and TKA readmissions between payers? (4) What types of THA and TKA readmissions are most costly to the US hospital system? The recently developed Nationwide Readmissions Database from the Healthcare Cost and Utilization Project (2006 hospitals from 21 states) was used to identify 719,394 primary TJAs and 62,493 90-day readmissions in the first 9 months of 2013 based on International Classification of Diseases, 9th Revision, Clinical Modification codes. We classified the reasons for readmissions as either procedure- or medical-related. Cost-to-charge ratios supplied with the Nationwide Readmissions Database were used to compute the individual per-patient cost of 90-day readmissions as a continuous variable in separate general linear models for THA and TKA. Payer, patient, clinical, and hospital factors were treated as covariates. We estimated the national burden of readmissions by payer and by the reason for readmission. The national rates of 30- and 90-day readmissions after THA were 4% (95% confidence interval [CI], 4.2%-4.5%) and 8% (95% CI, 7.5%-8.1%), respectively. The national rates of 30- and 90-day readmissions after primary TKA were 4% (95% CI, 3.8%-4.0%) and 7% (95% CI, 6.8%-7.2%), respectively. The five most important variables responsible for the cost of 90-day THA readmissions (in rank order, based

  20. Impact of National Institutes of Health Gastrointestinal PROMIS Measures in Clinical Practice: Results of a Multicenter Controlled Trial.

    Science.gov (United States)

    Almario, Christopher V; Chey, William D; Khanna, Dinesh; Mosadeghi, Sasan; Ahmed, Shahzad; Afghani, Elham; Whitman, Cynthia; Fuller, Garth; Reid, Mark; Bolus, Roger; Dennis, Buddy; Encarnacion, Rey; Martinez, Bibiana; Soares, Jennifer; Modi, Rushaba; Agarwal, Nikhil; Lee, Aaron; Kubomoto, Scott; Sharma, Gobind; Bolus, Sally; Spiegel, Brennan M R

    2016-11-01

    The National Institutes of Health (NIH) created the Patient Reported Outcomes Measurement Information System (PROMIS) to allow efficient, online measurement of patient-reported outcomes (PROs), but it remains untested whether PROMIS improves outcomes. Here, we aimed to compare the impact of gastrointestinal (GI) PROMIS measures vs. usual care on patient outcomes. We performed a pragmatic clinical trial with an off-on study design alternating weekly between intervention (GI PROMIS) and control arms at one Veterans Affairs and three university-affiliated specialty clinics. Adults with GI symptoms were eligible. Intervention patients completed GI PROMIS symptom questionnaires on an e-portal 1 week before their visit; PROs were available for review by patients and their providers before and during the clinic visit. Usual care patients were managed according to customary practices. Our primary outcome was patient satisfaction as determined by the Consumer Assessment of Healthcare Providers and Systems questionnaire. Secondary outcomes included provider interpersonal skills (Doctors' Interpersonal Skills Questionnaire (DISQ)) and shared decision-making (9-item Shared Decision Making Questionnaire (SDM-Q-9)). There were 217 and 154 patients in the GI PROMIS and control arms, respectively. Patient satisfaction was similar between groups (P>0.05). Intervention patients had similar assessments of their providers' interpersonal skills (DISQ 89.4±11.7 vs. 89.8±16.0, P=0.79) and shared decision-making (SDM-Q-9 79.3±12.4 vs. 79.0±22.0, P=0.85) vs. This is the first controlled trial examining the impact of NIH PROMIS in clinical practice. One-time use of GI PROMIS did not improve patient satisfaction or assessment of provider interpersonal skills and shared decision-making. Future studies examining how to optimize PROs in clinical practice are encouraged before widespread adoption.

  1. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer

    NARCIS (Netherlands)

    Van Driel, Pieter B A A; Boonstra, Martin C.; Slooter, Maxime D.; Heukers, Raimond; Stammes, Marieke A.; Snoeks, Thomas J A; De Bruijn, Henriette S.; Van Diest, Paul J.; Vahrmeijer, Alexander L.; Van Bergen En Henegouwen, Paul M P; Van De Velde, Cornelis J H; Löwik, Clemens W G M; Robinson, Dominic J.; Oliveira, Sabrina

    2016-01-01

    Photodynamic therapy (PDT) induces cell death through local light activation of a photosensitizer (PS) and has been used to treat head and neck cancers. Yet, common PS lack tumor specificity, which leads to collateral damage to normal tissues. Targeted delivery of PS via antibodies has

  2. The Business Case for Provider Participation in Clinical Trials Research: An Application to the National Cancer Institute's Community Clinical Oncology Program

    Science.gov (United States)

    Song, Paula H.; Reiter, Kristin L.; Weiner, Bryan J.; Minasian, Lori; McAlearney, Ann Scheck

    2012-01-01

    Background Provider-based research networks (PBRNs) make clinical trials available in community-based practice settings, where most people receive their care, but provider participation requires both financial and in-kind contributions. Purpose This study explores whether providers believe there is a business case for participating in PBRNs and what factors contribute to the business case. Methodology/Approach We use a multiple case study methodology approach to examine the National Cancer Institute's Community Clinical Oncology Program, a longstanding federally funded PBRN. Interviews with 41 key informants across five sites, selected on the basis of organizational maturity, were conducted using a semi-structured interview guide. We analyzed interview transcripts using an iterative, deductive process to identify themes and subthemes in the data. Findings We found that a business case for provider participation in PBRNs may exist if both direct and indirect financial benefits are identified and included in the analysis, and if the time horizon is long enough to allow those benefits to be realized. We identified specific direct and indirect financial benefits that were perceived as important contributors to the business case and the perceived length of time required for a positive return to accrue. Practice Implications As the lack of a business case may result in provider reluctance to participate in PBRNs, knowledge of the benefits we identified may be crucial to encouraging and sustaining participation, thereby preserving patient access to innovative community-based treatments. The results are also relevant to federally-funded PBRNs outside of oncology or to providers considering participation in any clinical trials research. PMID:23044836

  3. The business case for provider participation in clinical trials research: an application to the National Cancer Institute's community clinical oncology program.

    Science.gov (United States)

    Song, Paula H; Reiter, Kristin L; Weiner, Bryan J; Minasian, Lori; McAlearney, Ann Scheck

    2013-01-01

    Provider-based research networks (PBRNs) make clinical trials available in community-based practice settings, where most people receive their care, but provider participation requires both financial and in-kind contributions. The aim of this study was to explore whether providers believe there is a business case for participating in PBRNs and what factors contribute to the business case. We use a multiple case study methodology approach to examine the National Cancer Institute's community clinical oncology program, a long-standing federally funded PBRN. Interviews with 41 key informants across five sites, selected on the basis of organizational maturity, were conducted using a semistructured interview guide. We analyzed interview transcripts using an iterative, deductive process to identify themes and subthemes in the data. We found that a business case for provider participation in PBRNs may exist if both direct and indirect financial benefits are identified and included in the analysis and if the time horizon is long enough to allow those benefits to be realized. We identified specific direct and indirect financial benefits that were perceived as important contributors to the business case and the perceived length of time required for a positive return to accrue. As the lack of a business case may result in provider reluctance to participate in PBRNs, knowledge of the benefits we identified may be crucial to encouraging and sustaining participation, thereby preserving patient access to innovative community-based treatments. The results are also relevant to federally funded PBRNs outside of oncology or to providers considering participation in any clinical trials research.

  4. Mechanism of Action of Prostate Stem Cell Antigen Targeted Antibody Therapy and its Relevance to Clinical Application in Prostate Cancer

    National Research Council Canada - National Science Library

    Reiter, Robert; Tran, Chau

    2008-01-01

    .... A better understanding of PSCA function and its antibody activity will enable rational patient selection and trial design all of which are particularly relevant to subsequent clinical trials of PSCA antibody...

  5. Mechanism of Action of Prostate Stem Cell Antigen Targeted Antibody Therapy and Its Relevance to Clinical Application in Prostate Cancer

    National Research Council Canada - National Science Library

    Reiter, Robert; Tran, Chau

    2007-01-01

    .... A better understanding of PSCA function and its antibody activity will enable rational patient selection and trial design, all of which are particularly relevant to subsequent clinical trials of PSCA antibody...

  6. Lumbar spinal stenosis: comparison of surgical practice variation and clinical outcome in three national spine registries.

    Science.gov (United States)

    Lønne, Greger; Fritzell, Peter; Hägg, Olle; Nordvall, Dennis; Gerdhem, Paul; Lagerbäck, Tobias; Andersen, Mikkel; Eiskjaer, Søren; Gehrchen, Martin; Jacobs, Wilco; van Hooff, Miranda L; Solberg, Tore K

    2018-05-21

    Decompression surgery for lumbar spinal stenosis (LSS) is the most common spinal procedure in the elderly. To avoid persisting low back pain, adding arthrodesis has been recommended, especially if there is a coexisting degenerative spondylolisthesis. However, this strategy remains controversial, resulting in practice-based variation. The present study aimed to evaluate in a pragmatic study if surgical selection criteria and variation in use of arthrodesis in three Scandinavian countries can be linked to variation in treatment effectiveness. This is an observational study based on a combined cohort from the national spine registries of Norway, Sweden, and Denmark. Patients aged 50 and older operated during 2011-2013 for LSS were included. Patient-Reported Outcome Measures (PROMs): Oswestry Disability Index (ODI) (primary outcome), Numeric Rating Scale (NRS) for leg pain and back pain, and health-related quality of life (Euro-Qol-5D) were reported. Analysis included case-mix adjustment. In addition, we report differences in hospital stay. Analyses of baseline data were done by analysis of variance (ANOVA), chi-square, or logistic regression tests. The comparisons of the mean changes of PROMs at 1-year follow-up between the countries were done by ANOVA (crude) and analysis of covariance (case-mix adjustment). Out of 14,223 included patients, 10,890 (77%) responded at 1-year follow-up. Apart from fewer smokers in Sweden and higher comorbidity rate in Norway, baseline characteristics were similar. The rate of additional fusion surgery (patients without or with spondylolisthesis) was 11% (4%, 47%) in Norway, 21% (9%, 56%) in Sweden, and 28% (15%, 88%) in Denmark. At 1-year follow-up, the mean improvement for ODI (95% confidence interval) was 18 (17-18) in Norway, 17 (17-18) in Sweden, and 18 (17-19) in Denmark. Patients operated with arthrodesis had prolonged hospital stay. Real-life data from three national spine registers showed similar indications for decompression

  7. Clinical manifestation and aetiology of a genital associated disease in Olive baboons (Papio hamadryas anubis) at Lake Manyara National Park, Tanzania

    OpenAIRE

    Knauf, Sascha

    2011-01-01

    The aim of the study was to investigate a genitally associated disease and to describe its clinical manifestation and aetiology in baboons at Lake Manyara National Park in the United Republic of Tanzania. Lake Manyara National Park is located in the northern part of the country, 160 km northwest of the Mt. Kilimanjaro. It is among the smallest protected areas, but belongs to the extended ecosystem of the Serengeti, Ngorongoro Conservation Area, Lake Manyara and Tarangire National Park. The...

  8. Satisfaction Survey on Information Technology-Based Glucose Monitoring System Targeting Diabetes Mellitus in Private Local Clinics in Korea

    Directory of Open Access Journals (Sweden)

    Hun-Sung Kim

    2017-06-01

    Full Text Available BackgroundPrivate local clinics in Korea have little experience with information technology (IT-based glucose monitoring (ITGM. Our aim is to examine user satisfaction and the possibility of using ITGM service practically.MethodsPatients sent their blood glucose levels to physicians in local clinics. The physicians reviewed the blood glucose values online and provided personal consultations through text messaging or phone calls. Thereafter, a satisfaction survey on the ITGM service, the modified Morisky scale, and patient assessment of chronic illness care were administered.ResultsOne hundred and seventy patients from seven private local clinics used the ITGM. Overall satisfaction, including that about the ITGM service, the device, and its usefulness, was rated higher than “mostly satisfied” (score 4.2±0.8 out of 5.0 and even higher among the elderly. Satisfaction was positively associated with age, especially in those older than 60 years. The main reason for intent for future use of the service was the time/place flexibility. Highly motivated patients tended to answer positively regarding information satisfaction (P=0.0377.ConclusionOur study is the first to investigate ITGM satisfaction in private local clinics. The feasibility of users utilizing ITGM should be clarified, and future clinical research on the service's clinical effects and cost-benefit analysis is needed.

  9. Comparative evaluation of PCR amplification of RLEP, 16S rRNA, rpoT and Sod A gene targets for detection of M. leprae DNA from clinical and environmental samples

    Directory of Open Access Journals (Sweden)

    Ravindra P Turankar

    2015-01-01

    Conclusion: Amongst all the gene targets used in this study, PCR positivity using RLEP gene target was the highest in all the clinical and environmental samples. Further, the RLEP gene target was able to detect 53% of blood samples as positive in BI-negative leprosy cases indicating its future standardization and use for diagnostic purposes.

  10. Ambulatory-based education in internal medicine: current organization and implications for transformation. Results of a national survey of resident continuity clinic directors.

    Science.gov (United States)

    Nadkarni, Mohan; Reddy, Siddharta; Bates, Carol K; Fosburgh, Blair; Babbott, Stewart; Holmboe, Eric

    2011-01-01

    Many have called for ambulatory training redesign in internal medicine (IM) residencies to increase primary care career outcomes. Many believe dysfunctional, clinic environments are a key barrier to meaningful ambulatory education, but little is actually known about the educational milieu of continuity clinics nationwide. We wished to describe the infrastructure and educational milieu at resident continuity clinics and assess clinic readiness to meet new IM-RRC requirements. National survey of ACGME accredited IM training programs. Directors of academic and community-based continuity clinics. Two hundred and twenty-one out of 365 (62%) of clinic directors representing 49% of training programs responded. Wide variation amongst continuity clinics in size, structure and educational organization exist. Clinics below the 25th percentile of total clinic sessions would not meet RRC-IM requirements for total number of clinic sessions. Only two thirds of clinics provided a longitudinal mentor. Forty-three percent of directors reported their trainees felt stressed in the clinic environment and 25% of clinic directors felt overwhelmed. The survey used self reported data and was not anonymous. A slight predominance of larger clinics and university based clinics responded. Data may not reflect changes to programs made since 2008. This national survey demonstrates that the continuity clinic experience varies widely across IM programs, with many sites not yet meeting new ACGME requirements. The combination of disadvantaged and ill patients with inadequately resourced clinics, stressed residents, and clinic directors suggests that many sites need substantial reorganization and institutional commitment.New paradigms, encouraged by ACGME requirement changes such as increased separation of inpatient and outpatient duties are needed to improve the continuity clinic experience.

  11. Condutas usuais entre os reumatologistas brasileiros: levantamento nacional Routine clinical practices of Brazilian rheumatologists: national overview

    Directory of Open Access Journals (Sweden)

    Marta M. C. Medeiros

    2006-04-01

    ão-hormonais (AINHs (89,3%, relaxante muscular (72,9%, fisioterapia (33,3%. O repouso no leito foi orientado por 31,6% dos especialistas. Num caso de lombalgia crônica com raio X recente mostrando espondilolistese grau 1 e discoartrose, 39,6% dos reumatologistas não solicitavam nenhum exame adicional, enquanto 26,2% e 24,4% solicitavam tomografia computadorizada (TC e ressonância nuclear magnética (RNM, respectivamente. As condutas mais indicadas nesse caso foram: fisioterapia (75,1%, relaxante muscular (48,5%, RPG (45,6%, exercícios físicos (41%, AINH seletivo da Cox-2 (40,5%, amitriptilina (35,3%, analgésicos opióides (34,7%. Outros cenários de artrose de joelho e ombro doloroso foram apresentados. CONCLUSÕES: a baixa taxa de devolução dos questionários pode refletir uma prática aind