WorldWideScience

Sample records for clinical performance targets

  1. Comprehensive evaluation and validation of targeted next-generation sequencing performance in two clinical laboratories.

    Science.gov (United States)

    Mendez, Pedro; Dang, Jennifer; Kim, James Wansoo; Lee, Sharon; Yoon, Jun-Hee; Kim, Thomas; Sailey, Charles J; Jablons, David M; Kim, Il-Jin

    2016-07-01

    Next-generation sequencing (NGS) has led to breakthroughs for genetic and genomic analyses and personalized medicine approaches for many diseases. More and more clinical laboratories are using NGS as a genetic screening tool for providing mutation information that is used to select the best treatment regimens for cancer patients. However, several obstacles prevent the routine implementation of NGS technology into the clinical molecular diagnosis setting: the sophisticated sample preparation process, high cost, time-consuming data analyses, as well as the reproducibility and accuracy of interpretation. To systematically evaluate the performance and quality of targeted NGS cancer panel analyses in clinical laboratories, we performed three different tests: i) laboratory-to-laboratory accuracy test, ii) intra-laboratory precision validation, and iii) limit of detection test, using formalin-fixed, paraffin-embedded cancer tissue specimens, cell lines and mutation positive DNA. A laboratory-to-laboratory accuracy test performed using 51 samples showed 100% sensitivity and 99.97% specificity. For the intra-laboratory precision test, 100% reproducibility was observed. For the limit of detection test, KRAS mutations from samples diluted from 70 to 2% of mutant allele frequencies were detected correctly. We believe that the present study demonstrated the feasibility of clinical implementation of a targeted NGS cancer panel analysis for personalized medicine. PMID:27121194

  2. 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

  3. The performance of a target-controlled infusion of propofol in combination with remifentanil : A clinical investigation with two propofol formulations

    NARCIS (Netherlands)

    Wietasch, JKG; Scholz, M; Zinserling, J; Kiefer, N; Frenkel, C; Knufermann, P; Brauer, U; Hoeft, A

    2006-01-01

    Target-controlled infusion (TCI) incorporates the pharmacokinetic variables of an IV drug to facilitate safe and reliable administration. In this clinical study we investigated the performance of propofol TCI in combination with remifentanil. Fifty-four adult patients scheduled for general surgery l

  4. Clinical Biomarkers for Hypoxia Targeting

    OpenAIRE

    Le, Quynh-Thu; Courter, Don

    2008-01-01

    Tumor hypoxia or a reduction of the tissue oxygen tension is a key microenvironmental factor for tumor progression and treatment resistance in solid tumors. Because hypoxic tumor cells have been demonstrated to be more resistant to ionizing radiation, hypoxia has been a focus of laboratory and clinical research in radiation therapy for many decades. It is believed that proper detection of hypoxic regions would guide treatment options and ultimately improve tumor response. To date, most clinic...

  5. Performance Targets and External Benchmarking

    DEFF Research Database (Denmark)

    Friis, Ivar; Hansen, Allan; Vámosi, Tamás S.

    Research on relative performance measures, transfer pricing, beyond budgeting initiatives, target costing, piece rates systems and value based management has for decades underlined the importance of external benchmarking in performance management. Research conceptualises external benchmarking...... of the ‘inside’ costs of the sub-component, technical specifications of the product, opportunistic behavior from the suppliers and cognitive limitation. These are all aspects that easily can dismantle the market mechanism and make it counter-productive in the organization. Thus, by directing more attention...... as a market mechanism that can be brought inside the firm to provide incentives for continuous improvement and the development of competitive advances. However, whereas extant research primarily has focused on the importance and effects of using external benchmarks, less attention has been directed towards...

  6. High performance inertial fusion targets

    International Nuclear Information System (INIS)

    Inertial confinement fusion (ICF) target designs are considered which may have very high gains (approximately 1000) and low power requirements (< 100 TW) for input energies of approximately one megajoule. These include targets having very low density shells, ultra thin shells, central ignitors, magnetic insulation, and non-ablative acceleration

  7. 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.

  8. Performance Simulations of Moving Target Search Algorithms

    Directory of Open Access Journals (Sweden)

    Peter K. K. Loh

    2009-01-01

    Full Text Available The design of appropriate moving target search (MTS algorithms for computer-generated bots poses serious challenges as they have to satisfy stringent requirements that include computation and execution efficiency. In this paper, we investigate the performance and behaviour of existing moving target search algorithms when applied to search-and-capture gaming scenarios. As part of the investigation, we also introduce a novel algorithm known as abstraction MTS. We conduct performance simulations with a game bot and moving target within randomly generated mazes of increasing sizes and reveal that abstraction MTS exhibits competitive performance even with large problem spaces.

  9. Performance Targets and External Market Prices

    DEFF Research Database (Denmark)

    Hansen, Allan; Friis, Ivar; Vámosi, Tamás S.

    the implementation of external market information in target setting – well known in transfer pricing, relative performance evaluation, beyond budgeting, target costing, piece rates systems and value based management – relate to challenging motivation and information problem. The analysis and discussion of those......In this paper we explore the processes of ‘bringing the market inside the firm’ to set performance targets and benchmark production workers productivity. We analyze attempts to use external suppliers’ bids in target setting in a Danish manufacturing company. The case study illustrates how...... problems, in particular those related to accounting for the internal performance (that are going to be compared with the external target), calculating the ‘inside’ costs and defining controllability, contributes to the management accounting as well as the piece-rate literature....

  10. Targeting inflammation in pancreatic cancer: Clinical translation.

    Science.gov (United States)

    Steele, Colin William; Kaur Gill, Nina Angharad; Jamieson, Nigel Balfour; Carter, Christopher Ross

    2016-04-15

    Preclinical modelling studies are beginning to aid development of therapies targeted against key regulators of pancreatic cancer progression. Pancreatic cancer is an aggressive, stromally-rich tumor, from which few people survive. Within the tumor microenvironment cellular and extracellular components exist, shielding tumor cells from immune cell clearance, and chemotherapy, enhancing progression of the disease. The cellular component of this microenvironment consists mainly of stellate cells and inflammatory cells. New findings suggest that manipulation of the cellular component of the tumor microenvironment is possible to promote immune cell killing of tumor cells. Here we explore possible immunogenic therapeutic strategies. Additionally extracellular stromal elements play a key role in protecting tumor cells from chemotherapies targeted at the pancreas. We describe the experimental findings and the pitfalls associated with translation of stromally targeted therapies to clinical trial. Finally, we discuss the key inflammatory signal transducers activated subsequent to driver mutations in oncogenic Kras in pancreatic cancer. We present the preclinical findings that have led to successful early trials of STAT3 inhibitors in pancreatic adenocarcinoma. PMID:27096033

  11. Texture metric that predicts target detection performance

    Science.gov (United States)

    Culpepper, Joanne B.

    2015-12-01

    Two texture metrics based on gray level co-occurrence error (GLCE) are used to predict probability of detection and mean search time. The two texture metrics are local clutter metrics and are based on the statistics of GLCE probability distributions. The degree of correlation between various clutter metrics and the target detection performance of the nine military vehicles in complex natural scenes found in the Search_2 dataset are presented. Comparison is also made between four other common clutter metrics found in the literature: root sum of squares, Doyle, statistical variance, and target structure similarity. The experimental results show that the GLCE energy metric is a better predictor of target detection performance when searching for targets in natural scenes than the other clutter metrics studied.

  12. Disclosure of investigators' recruitment performance in multicenter clinical trials

    DEFF Research Database (Denmark)

    Dal-Ré, Rafael; Moher, David; Gluud, Christian;

    2011-01-01

    Rafael Dal-Ré and colleagues argue that the recruitment targets and performance of all site investigators in multi-centre clinical trials should be disclosed in trial registration sites before a trial starts, and when it ends.......Rafael Dal-Ré and colleagues argue that the recruitment targets and performance of all site investigators in multi-centre clinical trials should be disclosed in trial registration sites before a trial starts, and when it ends....

  13. SNS second target station moderator performance update

    International Nuclear Information System (INIS)

    In its first years of operations of its first target station, the Spallation Neutron Source (SNS) is working towards a facility upgrade by a megawatt-class second target station operated at 20 Hz repetition rate, which is intended to complement the existing ORNL neutron sources, the first SNS target station and the HFIR reactor, with high-intensity cold neutron beams.The first round of optimization calculations converged on larger-volume cylindrical para-hydrogen moderators placed in wing configuration on top and bottom of a flat mercury target, premoderated by layers of ambient water and surrounded by beryllium reflector. The metric of these optimization calculations was time-averaged and energy-integrated neutron brightness below 5 meV with the requirement to be able to serve 20 ports with neutrons. A summary of these calculations will be given including lessons learned from the variety of simulated configurations and detailed neutron performance characteristics like spectral intensities, emission time distributions, local variations of moderator brightness at the viewed areas, and sensitivity of the optimization metric to optimized parameters for the most promising configuration.

  14. 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...... clinical trials evaluating the effect of targeted treatments in MM....

  15. TARGET POPULATION FOR CLINICAL TRIALS ON SARCOPENIA

    OpenAIRE

    Cesari, Matteo; Pahor, Marco

    2008-01-01

    The term “sarcopenia” describes the progressive decline of muscle mass, strength and function occurring with aging. It is not considered a disease, but the direct consequence of the aging process on the skeletal muscle. Multiple demographic (e.g. gender, race), biological (e.g. inflammatory status) and clinical (e.g. diabetes, metabolic syndrome, congestive heart failure, medications) factors are able to influence (positively or negatively) the skeletal muscle quality and quantity. The extrem...

  16. Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system.

    Science.gov (United States)

    Yuzawa, Sayaka; Nishihara, Hiroshi; Yamaguchi, Shigeru; Mohri, Hiromi; Wang, Lei; Kimura, Taichi; Tsuda, Masumi; Tanino, Mishie; Kobayashi, Hiroyuki; Terasaka, Shunsuke; Houkin, Kiyohiro; Sato, Norihiro; Tanaka, Shinya

    2016-07-01

    Recent genetic analyses using next-generation sequencers have revealed numerous genetic alterations in various tumors including meningioma, which is the most common primary brain tumor. However, their use as routine laboratory examinations in clinical applications for tumor genotyping is not cost effective. To establish a clinical sequencing system for meningioma and investigate the clinical significance of genotype, we retrospectively performed targeted amplicon sequencing on 103 meningiomas and evaluated the association with clinicopathological features. We designed amplicon-sequencing panels targeting eight genes including NF2 (neurofibromin 2), TRAF7, KLF4, AKT1, and SMO. Libraries prepared with genomic DNA extracted from PAXgene-fixed paraffin-embedded tissues of 103 meningioma specimens were sequenced using the Illumina MiSeq. NF2 loss in some cases was also confirmed by interphase-fluorescent in situ hybridization. We identified NF2 loss and/or at least one mutation in NF2, TRAF7, KLF4, AKT1, and SMO in 81 out of 103 cases (79%) by targeted amplicon sequencing. On the basis of genetic status, we categorized meningiomas into three genotype groups: NF2 type, TRAKLS type harboring mutation in TRAF7, AKT1, KLF4, and/or SMO, and 'not otherwise classified' type. Genotype significantly correlated with tumor volume, tumor location, and magnetic resonance imaging findings such as adjacent bone change and heterogeneous gadolinium enhancement, as well as histopathological subtypes. In addition, multivariate analysis revealed that genotype was independently associated with risk of recurrence. In conclusion, we established a rapid clinical sequencing system that enables final confirmation of meningioma genotype within 7 days turnaround time. Our method will bring multiple benefits to neuropathologists and neurosurgeons for accurate diagnosis and appropriate postoperative management. PMID:27102344

  17. BRVAAF and performance analysis for target detection

    Institute of Scientific and Technical Information of China (English)

    ZHANG Nan; TAO Ran; WANG Yue

    2009-01-01

    A bistatic range-velocity-acceleration ambiguity function (BRVAAF) is proposed. The model of radar measurements of an accelerating target involving the time delay, Doppler frequency and Doppler rate is given. The relationships between these measurements and the parameters of the bistatic geometry,target position, velocity and acceleration are derived. Moreover, the effects of the bistatic geometry factors on these measurements are analyzed. Besides, the two relationships of the bistatic integration loss and the bistatic optimum integration time with these factors are built and their change trends are described respectively. This research is helpful to analyze the influences of the bistatic geometry factors on the target detection and signal processing.

  18. BRVAAF and performance analysis for target detection

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    A bistatic range-velocity-acceleration ambiguity function (BRVAAF) is proposed. The model of radar measurements of an accelerating target involving the time delay, Doppler frequency and Doppler rate is given. The relationships between these measurements and the parameters of the bistatic geometry, target position, velocity and acceleration are derived. Moreover, the effects of the bistatic geometry factors on these measurements are analyzed. Besides, the two relationships of the bistatic integration loss and the bistatic optimum integration time with these factors are built and their change trends are described respectively. This research is helpful to analyze the influences of the bistatic geometry factors on the target detection and signal processing.

  19. On detection performance of MIMO radar for Rician target

    Institute of Scientific and Technical Information of China (English)

    TANG Jun; WU Yong; PENG YingNing; WANG XiuTan

    2009-01-01

    By using spatial dlversity, multiple-input-multiple-output (MIMO) radar can improve detection performance for fluctuating targets. In this paper, we propose a spatial fluctuation target model for MIMO radar, where targets are classified as non-fluctuating target, Rayleigh target and Rician target. Based on Stein's lemma, we use relative entropy to study detection performance of optimum detector for Riclan target. It is found that in low signal noise ratio (SNR) region, the performance improvement of MIMO radar for detecting Rician target depends on array gain, which is related to the number of receivers. In high SNR region, the improvement of performance depends on diversity gain, which is related to the product of the number of receivers and the number of transmitters. The conclusions of this paper are Important for designing MIMO radar system.

  20. [Clinical to planning target volume margins in prostate cancer radiotherapy].

    Science.gov (United States)

    Ramiandrisoa, F; Duvergé, L; Castelli, J; Nguyen, T D; Servagi-Vernat, S; de Crevoisier, R

    2016-10-01

    The knowledge of inter- and intrafraction motion and deformations of the intrapelvic target volumes (prostate, seminal vesicles, prostatectomy bed and lymph nodes) as well as the main organs at risk (bladder and rectum) allow to define rational clinical to planning target volume margins, depending on the different radiotherapy techniques and their uncertainties. In case of image-guided radiotherapy, prostate margins and seminal vesicles margins can be between 5 and 10mm. The margins around the prostatectomy bed vary from 10 to 15mm and those around the lymph node clinical target volume between 7 and 10mm. Stereotactic body radiotherapy allows lower margins, which are 3 to 5mm around the prostate. Image-guided and stereotactic body radiotherapy with adequate margins allow finally moderate or extreme hypofractionation. PMID:27614515

  1. Targeting cancer epigenetics: Linking basic biology to clinical medicine.

    Science.gov (United States)

    Shinjo, Keiko; Kondo, Yutaka

    2015-12-01

    Recent studies provide compelling evidence that epigenetic dysregulation is involved in almost every step of tumor development and progression. Differences in tumor behavior, which ultimately reflects clinical outcome, can be explained by variations in gene expression patterns generated by epigenetic mechanisms, such as DNA methylation. Therefore, epigenetic abnormalities are considered potential biomarkers and therapeutic targets. DNA methylation is stable at certain specific loci in cancer cells and predominantly reflects the characteristic clinicopathological features. Thus, it is an ideal biomarker for cancer screening, classification and prognostic purposes. Epigenetic treatment for cancers is based on the pharmacologic targeting of various core transcriptional programs that sustains cancer cell identity. Therefore, targeting aberrant epigenetic modifiers may be effective for multiple processes compared with using a selective inhibitor of aberrant single signaling pathway. This review provides an overview of the epigenetic alterations in human cancers and discusses about novel therapeutic strategies targeting epigenetic alterations.

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

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2010-01-01

    Background and Aim: Disease control is not achieved in a substantial proportion of patients with asthma. Recent advances in aerosol formulations and delivery devices may offer more effective therapy. This review will focus on the importance and potential clinical benefit of targeting the lung per...... treatment with ultrafine formulations of ICS will change the natural history of asthma and prevent airway remodelling in both the large and small airways.......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...... periphery in adult asthma by means of ultrafine aerosols. Results: Ultrafine formulations of inhaled corticosteroids have improved lung deposition up to at least 50 %, primarily in the peripheral airways. Ultrafine formulations of ICS provide equivalent asthma control to non-ultrafine ICS at approximately...

  3. Standard target sets for field sensor performance measurements

    Science.gov (United States)

    O'Connor, John D.; O'Shea, Patrick; Palmer, John E.; Deaver, Dawne M.

    2006-05-01

    The US Army Night Vision and Electronic Sensors Directorate (NVESD) Modeling and Simulation Division develops sensors models (FLIR 92, NV Therm, NV Therm IP) that predict the comparative performance of electro-optical sensors. The NVESD modeling branch developed a 12-vehicle, 12-aspect target signature set in 1998 with a known cycle criteria. It will be referred to as the 12-target set. This 12-target set has and will continue to be the modeling "gold standard" for laboratory human perception experiments supporting sensor performance modeling, and has been employed in dozens of published experiments. The 12-target set is, however, too costly for most acquisition field tests and evaluations. The authors developed an 8-vehicle 3-aspect target set, referred to as the 8- target set, and measured its discrimination task difficulty, (N50 and V50). Target identification (ID) range performance predictions for several sensors were made based on those V50/N50 values. A field collection of the 8-target set using those sensors provided imagery for a human perception study. The human perception study found excellent agreement between predicted and measured range performance. The goal of this development is to create a "silver standard" target set that is as dependable in measuring sensor performance as the "gold standard", and is affordable for Milestone A and other field trials.

  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...... advantage of targeted NGS is that multiple disease-specific genes can easily be sequenced simultaneously, which is favorable in genetic heterogeneous diseases. Prior to implementation in our diagnostic setting, we aimed to assess the sensitivity and specificity of targeted NGS by sequencing a collection......, 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. Update on clinical trials: genetic targets in breast cancer.

    Science.gov (United States)

    Lim, Bora; Cream, Leah V; Harvey, Harold A

    2013-01-01

    Breast cancer is the most commonly diagnosed cancer in women in United States. From data of American Cancer Society from 2007 reported total of 178,480 women diagnosed with breast cancer. The death rate from breast cancer has decreased in North America over time, but still accounts for second highest cancer death, following lung cancer. Breast cancer is staged based on tumor size, nodal involvement, and distant metastasis like any other solid tumors. However clinical staging is not the only important factor in management of breast cancer. Various molecular features divides breast cancer into many subgroups - that act differently, and respond differently from therapy. Thus the focus of breast cancer treatment has evolved focusing on specific targets. The most important biologic markers in subtyping of breast cancer so far are hormone receptor positivity and HER2/neu protein expression. Five molecular subtypes using intrinsic gene set include Basal mRNA, HER2 + mRNA, Luminal AmRNA, Luminal B mRNA, and Normal-like mRNA. In addition, better understanding of genetic target of breast cancer has given us arsenal of personalized, and more effective treatment approach.This review will focus on examples that highlight several mechanism of tumorigenesis, giving us not just understanding of gene pathways and the molecular biology, that could lead us to therapeutic target. Several important molecular targets have been investigated in preclinical and clinical trials, others are yet to be explored. We will also describe genetic mechanisms discovery related to overcoming resistance to current targeted therapies in breast cancer, including hormone receptor expression and HER 2- neu amplification. We will also review other exciting developments in understanding of breast cancer, the tumor microenvironment and cancer stem cells, and targeting agents in that area. PMID:23288634

  6. Modeling the effects of contrast enhancement on target acquisition performance

    Science.gov (United States)

    Du Bosq, Todd W.; Fanning, Jonathan D.

    2008-04-01

    Contrast enhancement and dynamic range compression are currently being used to improve the performance of infrared imagers by increasing the contrast between the target and the scene content, by better utilizing the available gray levels either globally or locally. This paper assesses the range-performance effects of various contrast enhancement algorithms for target identification with well contrasted vehicles. Human perception experiments were performed to determine field performance using contrast enhancement on the U.S. Army RDECOM CERDEC NVESD standard military eight target set using an un-cooled LWIR camera. The experiments compare the identification performance of observers viewing linearly scaled images and various contrast enhancement processed images. Contrast enhancement is modeled in the US Army thermal target acquisition model (NVThermIP) by changing the scene contrast temperature. The model predicts improved performance based on any improved target contrast, regardless of feature saturation or enhancement. To account for the equivalent blur associated with each contrast enhancement algorithm, an additional effective MTF was calculated and added to the model. The measured results are compared with the predicted performance based on the target task difficulty metric used in NVThermIP.

  7. Assessing Students – Clinical Competence Versus Performance

    Directory of Open Access Journals (Sweden)

    John Ruedy

    2007-06-01

    Full Text Available The recent elaboration of the range of physiciancompetencies upon which the quality of health care isdependent has fostered the development of a variety ofmethods of assessing medical student competencies andperformance. Such assessments are essential inproviding feedback to students to guide their learningand to faculty on the success of the curriculum inachieving competency outcomes. In addition theyprovide evidence that students have achieved minimumrequirements for progressing. Well-designed ObservedStructured Clinical Examinations (OSCEs, MiniClinical Examinations (Mini-CEXs and some forms ofMulti-Source Feedback (MSF can meet acceptablestandards of validity and reliability and are feasible.Competency assessments are limited in predicting howa student will actually act in the work situationparticularly in humanistic skills. More emphasis needsto be placed on student performance, in suchcompetencies as communication and professionalism, ina variety of settings by a number of observers.

  8. 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 pe...... treatment with ultrafine formulations of ICS will change the natural history of asthma and prevent airway remodelling in both the large and small airways.......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...... periphery in adult asthma by means of ultrafine aerosols. Results:  Ultrafine formulations of inhaled corticosteroids have improved lung deposition up to at least 50 %, primarily in the peripheral airways. Ultrafine formulations of ICS provide equivalent asthma control to non-ultrafine ICS at approximately...

  9. Targeting bone metastases in prostate cancer: improving clinical outcome.

    Science.gov (United States)

    Body, Jean-Jacques; Casimiro, Sandra; Costa, Luís

    2015-06-01

    Bone metastases develop in most patients with metastatic castration-resistant prostate cancer (mCRPC). They affect the structural integrity of bone, manifesting as pain and skeletal-related events (SREs), and are the primary cause of patient disability, reduced quality of life (QOL) and death. Understanding the pathophysiology of bone metastases resulted in the development of agents that improve clinical outcome, suggesting that managing both the systemic disease and associated bone events is important. Historically, the treatment of CRPC bone metastases with early radiopharmaceuticals and external beam radiation therapy was largely supportive; however, now, zoledronic acid and denosumab are integral to the therapeutic strategy for mCRPC. These agents substantially reduce skeletal morbidity and improve patient QOL. Radium-223 dichloride is the first bone-targeting agent to show improved survival and reduced pain and symptomatic skeletal events in patients with mCRPC without visceral disease. Five other systemic agents are currently approved for use in mCRPC based on their ability to improve survival. These include the cytotoxic drugs docetaxel and cabazitaxel, the hormone-based therapies, abiraterone and enzalutamide, and the immunotherapeutic vaccine sipuleucel-T. Abiraterone and enzalutamide are able to reduce SREs and improve survival in this setting. Novel agents targeting tumour and bone cells are under clinical development. PMID:26119830

  10. A wavelet contrast metric for the targeting task performance metric

    Science.gov (United States)

    Preece, Bradley L.; Flug, Eric A.

    2016-05-01

    Target acquisition performance depends strongly on the contrast of the target. The Targeting Task Performance (TTP) metric, within the Night Vision Integrated Performance Model (NV-IPM), uses a combination of resolution, signal-to-noise ratio (SNR), and contrast to predict and model system performance. While the dependence on resolution and SNR are well defined and understood, defining a robust and versatile contrast metric for a wide variety of acquisition tasks is more difficult. In this correspondence, a wavelet contrast metric (WCM) is developed under the assumption that the human eye processes spatial differences in a manner similar to a wavelet transform. The amount of perceivable information, or useful wavelet coefficients, is used to predict the total viewable contrast to the human eye. The WCM is intended to better match the measured performance of the human vision system for high-contrast, low-contrast, and low-observable targets. After further validation, the new contrast metric can be incorporated using a modified TTP metric into the latest Army target acquisition software suite, the NV-IPM.

  11. Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations.

    Science.gov (United States)

    Arout, Caroline A; Edens, Ellen; Petrakis, Ismene L; Sofuoglu, Mehmet

    2015-06-01

    Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and γ-aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain.

  12. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation.

    Science.gov (United States)

    Kamaly, Nazila; Xiao, Zeyu; Valencia, Pedro M; Radovic-Moreno, Aleksandar F; Farokhzad, Omid C

    2012-04-01

    Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development

  13. Clinically meaningful performance benchmarks in MS

    Science.gov (United States)

    Motl, Robert W.; Scagnelli, John; Pula, John H.; Sosnoff, Jacob J.; Cadavid, Diego

    2013-01-01

    Objective: Identify and validate clinically meaningful Timed 25-Foot Walk (T25FW) performance benchmarks in individuals living with multiple sclerosis (MS). Methods: Cross-sectional study of 159 MS patients first identified candidate T25FW benchmarks. To characterize the clinical meaningfulness of T25FW benchmarks, we ascertained their relationships to real-life anchors, functional independence, and physiologic measurements of gait and disease progression. Candidate T25FW benchmarks were then prospectively validated in 95 subjects using 13 measures of ambulation and cognition, patient-reported outcomes, and optical coherence tomography. Results: T25FW of 6 to 7.99 seconds was associated with a change in occupation due to MS, occupational disability, walking with a cane, and needing “some help” with instrumental activities of daily living; T25FW ≥8 seconds was associated with collecting Supplemental Security Income and government health care, walking with a walker, and inability to do instrumental activities of daily living. During prospective benchmark validation, we trichotomized data by T25FW benchmarks (10 seconds) ranges of performance. PMID:24174581

  14. A Lightweight Approach to Performance Portability with targetDP

    CERN Document Server

    Gray, Alan

    2016-01-01

    Leading HPC systems achieve their status through use of highly parallel devices such as NVIDIA GPUs or Intel Xeon Phi many-core CPUs. The concept of performance portability across such architectures, as well as traditional CPUs, is vital for the application programmer. In this paper we describe targetDP, a lightweight abstraction layer which allows grid-based applications to target data parallel hardware in a platform agnostic manner. We demonstrate the effectiveness of our pragmatic approach by presenting performance results for a complex fluid application (with which the model was co-designed), plus a separate lattice QCD particle physics code. For each application, a single source code base is seen to achieve portable performance, as assessed within the context of the Roofline model. TargetDP can be combined with MPI to allow use on systems containing multiple nodes: we demonstrate this through provision of scaling results on traditional and GPU-accelerated large scale supercomputers.

  15. Emmetropic eyes: objective performance and clinical reference

    Science.gov (United States)

    Tepichín-Rodríguez, Eduardo; Cruz Felix, Angel S.; López-Olazagasti, Estela; Balderas-Mata, Sandra

    2013-11-01

    The application of the wavefront sensors to measuring the monochromatic aberrations of the normal human eyes has given a new insight in the objective understanding of its performance. The resultant wavefront aberration function can be applied to evaluate the image quality on the retina, which includes the analysis of the higher-order aberrations. Among others, and due to their well-known mathematical properties for circular apertures, the wavefront aberration function is most commonly represented in terms of the Zernike polynomials. The main idea is to have a clinical reference of the objective performance of a set of normal human eyes. However, the high-order aberrations in normal human eyes are different for each persoņ that can be interpreted as that there are many possible solutions for the objective performance of emmetropic eyes. When dealing with the Zernike coefficients and excluding the spherical aberration, higher-order aberrations have a tendency to have a zero mean value. Different proposals have been suggested in the literature to deal with this feature. Moreover, it has been also shown that there is an ethnic dependency in the magnitude of the aberrations. We present in this work the objective performance of a set of uncorrected Mexican eyes, and compare them with other ethnic results published in the literature.

  16. Performance evaluation of correlation filters for target tracking

    Science.gov (United States)

    Gaxiola, Leopoldo N.; Diaz-Ramirez, Victor H.; Tapia, Juan J.; García-Martínez, Pascuala; Cuevas, Andres

    2015-09-01

    A performance evaluation of several state-of-the-art correlation filters within the context of target tracking is presented. The filters are tested using an introduced algorithm that is adapted online using information of current and past scene frames of the scene. The algorithm achieves a high-rate operation by focusing signal processing on a small fragment of the scene in each frame. The correlation filters are tested using several video test sequences that contain geometric modifications of the target, partial occlusions and clutter. The performance of the tested filters is characterized in terms of detection efficiency, tracking accuracy, and computational complexity using objective metrics.

  17. The design and performance of an improved target for MICE

    CERN Document Server

    Booth, C N; Langlands, J; Overton, E; Robinson, M; Smith, P J; Barber, G; Long, K R; Shepherd, B; Capocci, E; MacWaters, C; Tarrant, J

    2016-01-01

    The linear motor driving the target for the Muon Ionisation Cooling Experiment has been redesigned to improve its reliability and performance. A new coil-winding technique is described which produces better magnetic alignment and improves heat transport out of the windings. Improved field-mapping has allowed the more precise construction to be demonstrated, and an enhanced controller exploits the full features of the hardware, enabling increased acceleration and precision. The new user interface is described and analysis of performance data to monitor friction is shown to allow quality control of bearings and a measure of the ageing of targets during use.

  18. The design and performance of an improved target for MICE

    Science.gov (United States)

    Booth, C. N.; Hodgson, P.; Langlands, J.; Overton, E.; Robinson, M.; Smith, P. J.; Barber, G.; Long, K. R.; Shepherd, B.; Capocci, E.; MacWaters, C.; Tarrant, J.

    2016-05-01

    The linear motor driving the target for the Muon Ionisation Cooling Experiment has been redesigned to improve its reliability and performance. A new coil-winding technique is described which produces better magnetic alignment and improves heat transport out of the windings. Improved field-mapping has allowed the more precise construction to be demonstrated, and an enhanced controller exploits the full features of the hardware, enabling increased acceleration and precision. The new user interface is described and analysis of performance data to monitor friction is shown to allow quality control of bearings and a measure of the ageing of targets during use.

  19. 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.

  20. The new rosetta targets observations, simulations and instrument performances

    CERN Document Server

    Epifani, Elena; Palumbo, Pasquale

    2004-01-01

    The Rosetta mission was successfully launched on March 2nd, 2004 for a rendezvous with the short period comet 67PChuryumov-Gerasimenko in 2014 The new baseline mission foresees also a double fly-by with asteroids 21 Lutetia and 2867 Steins, on the way towards the primary target This volume collects papers presented at the workshop on "The NEW Rosetta targets Observations, simulations and instrument performances", held in Capri on October 13-15, 2003 The papers cover the fields of observations of the new Rosetta targets, laboratory experiments and theoretical simulation of cometary processes, and the expected performances of Rosetta experiments Until real operations around 67PChuryumov-Gerasimenko will start in 10 years from now, new astronomical observations, laboratory experiments and theoretical models are required The goals are to increase knowledge about physics and chemistry of comets and to prepare to exploit at best Rosetta data

  1. Operational Performance Improvements to BRIght Target Explorer Constellation

    Science.gov (United States)

    Choi, Seung Yun

    The BRIght Target Explorer (BRITE)-Constellation is composed of six nano-satellites funded by Austria, Canada, and Poland, and each of them is equipped with an optical telescope that observes stars with visual magnitude +3.5 or brighter. BRITE-Constellation has provided numerous images of bright stars from Low Earth Orbit, which will eventually lead to investigation of origin of the Universe. This thesis presents the contribution of the author to BRITE mission, especially in BRITE Operations. The author performed antenna steering experiments on UniBRITE and BRITE-Toronto, to improve data downlink. To improve scientific data collection from BRITE satellites, the author computed available observation time for multiple targets every orbit, which resulted in collection of twice the amount of scientific data. Also, the author increased the available observation time for each target from 32 minutes to 48 minutes by improving the performance of the star tracker on-board BRITE-Toronto.

  2. Inflation targeting and inflation performance : a comparative analysis

    NARCIS (Netherlands)

    Samarina, Anna; De Haan, Jakob; Terpstra, M.

    2014-01-01

    This article examines how the impact of inflation targeting on inflation performance depends on the choice of country samples, adoption dates, time periods and methodological approaches. We apply two different estimation methods - difference-in-differences and propensity score matching - for our sam

  3. LANSCE (Los Alamos Neutron Scattering Center) target system performance

    International Nuclear Information System (INIS)

    The authors measured neutron beam fluxes at LANSCE using gold foil activation techniques. They did an extensive computer simulation of the as-built LANSCE Target/Moderator/Reflector/Shield geometry. They used this mockup in a Monte Carlo calculation to predict LANSCE neutronic performance for comparison with measured results. For neutron beam fluxes at 1 eV, the ratio of measured data to calculated varies from ∼0.6-0.9. The computed 1 eV neutron leakage at the moderator surface is 3.9 x 1010 n/eV-sr-s-μA for LANSCE high-intensity water moderators. The corresponding values for the LANSCE high-resolution water moderator and the liquid hydrogen moderator are 3.3 and 2.9 x 1010, respectively. LANSCE predicted moderator intensities (per proton) for a tungsten target are essentially the same as ISIS predicted moderator intensities for a depleted uranium target. The calculated LANSCE steady state unperturbed thermal (E 13 n/cm2-s. The unique LANSCE split-target/flux-trap-moderator system is performing exceedingly well. The system has operated without a target or moderator change for over three years at nominal proton currents of 25 μA of 800-MeV protons. 17 refs., 8 figs., 3 tabs

  4. Towards combinatorial targeted therapy in melanoma: from pre-clinical evidence to clinical application (review).

    Science.gov (United States)

    Grazia, Giulia; Penna, Ilaria; Perotti, Valentina; Anichini, Andrea; Tassi, Elena

    2014-09-01

    Over the last few years, clinical trials with BRAF and mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors have shown significant clinical activity in melanoma, but only a fraction of patients respond to these therapies, and development of resistance is frequent. This has prompted a large set of preclinical studies looking at several new combinatorial approaches of pathway- or target-specific inhibitors. At least five main drug association strategies have been verified in vitro and in preclinical models. The most promising include: i) vertical targeting of either MEK or phosphoinositide-3 kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways, or their combined blockade; ii) association of receptor tyrosine kinases (RTKs) inhibitors with other pro-apoptotic strategies; iii) engagement of death receptors in combination with MEK-, mTOR/PI3K-, histone deacetylase (HDAC)-inhibitors, or with anti-apoptotic molecules modulators; iv) strategies aimed at blocking anti-apoptotic proteins belonging to B-cell lymphoma (Bcl-2) or inhibitors of apoptosis (IAP) families associated with MEK/BRAF/p38 inhibition; v) co-inhibition of other molecules important for survival [proteasome, HDAC and Signal transducers and activators of transcription (Stat)3] and the major pathways activated in melanoma; vi) simultaneous targeting of multiple anti-apoptotic molecules. Here we review the anti-melanoma efficacy and mechanism of action of the above-mentioned combinatorial strategies, together with the potential clinical application of the most promising studies that may eventually lead to therapeutic benefit.

  5. Target acquisition performance : Effects of target aspect angle, dynamic imaging and signal processing

    NARCIS (Netherlands)

    Beintema, J.A.; Bijl, P.; Hogervorst, M.A.; Dijk, J.

    2008-01-01

    In an extensive Target Acquisition (TA) performance study, we recorded static and dynamic imagery of a set of military and civilian two-handheld objects at a range of distances and aspect angles with an under-sampled uncooled thermal imager. Next, we applied signal processing techniques including DS

  6. Cosmic Origins Spectrograph: On-Orbit Performance of Target Acquisitions

    Science.gov (United States)

    Penton, Steven V.

    2010-07-01

    COS is a slit-less spectrograph with a very small aperture (R=1.2500). To achieve the desired wavelength accuracies, HST+COS must center the target to within 0.100 of the center of the aperture for the FUV channel, and 0.0400 for NUV. During SMOV and early Cycle 17 we fine-tuned the COS target acquisition (TA) procedures to exceed this accuracy for all three COS TA modes; NUV imaging, NUV spectroscopic, and FUV spectroscopic. In Cycle 17, we also adjusted the COSto- FGS offsets in the SIAF file. This allows us to recommend skipping the time consuming ACQ/SEARCH in cases where the target coordinates are well known. Here we will compare the on-orbit performance of all COS TA modes in terms of centering accuracy, efficiency, and required signal-to-noise (S/N).

  7. 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

  8. The effect of target and non-target similarity on neural classification performance: a boost from confidence.

    Science.gov (United States)

    Marathe, Amar R; Ries, Anthony J; Lawhern, Vernon J; Lance, Brent J; Touryan, Jonathan; McDowell, Kaleb; Cecotti, Hubert

    2015-01-01

    Brain computer interaction (BCI) technologies have proven effective in utilizing single-trial classification algorithms to detect target images in rapid serial visualization presentation tasks. While many factors contribute to the accuracy of these algorithms, a critical aspect that is often overlooked concerns the feature similarity between target and non-target images. In most real-world environments there are likely to be many shared features between targets and non-targets resulting in similar neural activity between the two classes. It is unknown how current neural-based target classification algorithms perform when qualitatively similar target and non-target images are presented. This study address this question by comparing behavioral and neural classification performance across two conditions: first, when targets were the only infrequent stimulus presented amongst frequent background distracters; and second when targets were presented together with infrequent non-targets containing similar visual features to the targets. The resulting findings show that behavior is slower and less accurate when targets are presented together with similar non-targets; moreover, single-trial classification yielded high levels of misclassification when infrequent non-targets are included. Furthermore, we present an approach to mitigate the image misclassification. We use confidence measures to assess the quality of single-trial classification, and demonstrate that a system in which low confidence trials are reclassified through a secondary process can result in improved performance.

  9. How do Performance Targets Affect Future Performance by Students and Schools?

    OpenAIRE

    M. Sartarelli; Tampieri, A

    2011-01-01

    The paper examines whether meeting performance targets in tests at school has an effeect on students' subsequent achievement in education and the take-up by schools of financial support from the government for students. We build a theoretical model to describe the channels through which students' belief of their ability, as proxied by previous performance in tests, affect their current effort in preparing for a test, and how previous performance affects the effort in teaching by a school. We ...

  10. Ethnic disparities in undergraduate pre-clinical and clinical performance

    NARCIS (Netherlands)

    Stegers-Jager, Karen M.; Steyerberg, Ewout W.; Cohen-Schotanus, Janke; Themmen, Axel P. N.

    2012-01-01

    Medical Education 2012: 46:575585 Context Research from numerous medical schools has shown that students from ethnic minorities underperform compared with those from the ethnic majority. However, little is known about why this underperformance occurs and whether there are performance differences amo

  11. Treatment targets in systemic lupus erythematosus: biology and clinical perspective

    OpenAIRE

    Marian, Valentin; Anolik, Jennifer H.

    2012-01-01

    Systemic lupus erythematosus (SLE) is a complex disease characterized by numerous autoantibodies and clinical involvement in multiple organ systems. The immunological events triggering the onset and progression of clinical manifestations are also complex and multi-step, including breach of tolerance in the adaptive immune system, amplification of autoimmunity through innate and adaptive immune system dysregulation, and end-organ damage. Studies of murine genetic manipulations and human risk v...

  12. Nursing students’ perceived stress and influences in clinical performance

    OpenAIRE

    Laila Akhu-Zaheya; Insaf Shaban; Wejdan Khater

    2015-01-01

    Background: It is known that stress related to clinical training among nursing students could contribute to many physical and mental problems. However, little empirical evidence about the influence of stress in nurse students’ clinical performance Objective: The objective of this study was to assess the association between perceived stresses, stress related factors, and students’ clinical performance. Method: Using the perceived stress scale, 539 Jordanian nursing students from 2 publ...

  13. 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...

  14. Carbapenem susceptibility breakpoints, clinical implications with the moving target.

    Science.gov (United States)

    O'Donnell, J Nicholas; Miglis, Cristina M; Lee, Jane Y; Tuvell, Merika; Lertharakul, Tina; Scheetz, Marc H

    2016-01-01

    Carbapenems are primary agents used to treat a variety of Gram-negative multi-drug resistant infections. In parallel with increasing use, increasing resistance to carbapenem agents has manifested as increased minimum inhibitory concentrations (MICs). To attempt to improve clinical outcomes with carbapenems, the Clinical Laboratory Standards Institute and the Food Drug Administration decreased susceptibility breakpoints. The European equivalent expert committee, the European Committee on Antimicrobial Susceptibility Testing, also utilizes lower MIC susceptibility breakpoints. This review focuses on the rationale for recent breakpoint changes and the associated clinical outcomes for patients treated with carbapenems for infections with varying MICs proximal to the breakpoint. Supporting pharmacokinetics and pharmacodynamics that underpin the breakpoints are also reviewed. PMID:26918486

  15. Validation of the propagation, target echo and sonar performance model ALMOST with near field target echo measurements

    NARCIS (Netherlands)

    Schippers, P.

    2005-01-01

    Since the late eighties the sonar performance model ALMOST of TNO Defence, Security and Safety is under development. For active detection performance first a point target with one Target Strength (TS) value dependent on aspect angle was used, based on measurements or other sources. Within the Torped

  16. Targeting hedgehog signaling in cancer: research and clinical developments

    Directory of Open Access Journals (Sweden)

    Xie J

    2013-10-01

    Full Text Available Jingwu Xie, Christopher M Bartels, Scott W Barton, Dongsheng GuWells Center for Pediatric Research, Division of Hematology and Oncology, Department of Pediatrics, Indiana University Simon Cancer Center, Indiana University, Indianapolis, IN, USAAbstract: Since its first description in Drosophila by Drs Nusslein-Volhard and Wieschaus in 1980, hedgehog (Hh signaling has been implicated in regulation of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of Gorlin syndrome in 1996 by two independent teams. Later, it was shown that Hh signaling may be involved in many types of cancer, including skin, leukemia, lung, brain, and gastrointestinal cancers. In early 2012, the US Food and Drug Administration approved the clinical use of Hh inhibitor Erivedge/vismodegib for treatment of locally advanced and metastatic basal cell carcinomas. With further investigation, it is possible to see more clinical applications of Hh signaling inhibitors. In this review, we will summarize major advances in the last 3 years in our understanding of Hh signaling activation in human cancer, and recent developments in preclinical and clinical studies using Hh signaling inhibitors.Keywords: hedgehog, smoothened, PTCH1, cancer, signal transduction, clinical trials, animal model

  17. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation†

    OpenAIRE

    Kamaly, Nazila; Xiao, Zeyu; Valencia, Pedro M.; Radovic-Moreno, Aleksandar F.; Farokhzad, Omid C.

    2012-01-01

    Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newe...

  18. Melanin Targeted Pre-clinical PET Imaging of Melanoma Metastasis

    OpenAIRE

    Ren, Gang; Miao, Zheng; Liu, Hongguang; Jiang, Lei; Limpa-Amara, Naengnoi; Mahmood, Ashfaq; Gambhir, Sanjiv S.; Cheng, Zhen

    2009-01-01

    Dialkylamino-alkyl-benzamide possess affinities for melanin, suggesting that such 18F-labeled benzamides could potentially be used as melanin targeted positron emission tomography (PET) probes to identify melanotic melanoma metastases in vivo with high sensitivity and specificity. In this report, we describe the synthesis, in vitro and in vivo evaluation of 18F-N-[2-(diethylamino)ethyl]-4-fluoro-Benzamide (18F-FBZA) in mouse tumor models.

  19. Designing block copolymer architectures for targeted membrane performance

    KAUST Repository

    Dorin, Rachel Mika

    2014-01-01

    Using a combination of block copolymer self-assembly and non-solvent induced phase separation, isoporous ultrafiltration membranes were fabricated from four poly(isoprene-b-styrene-b-4-vinylpyridine) triblock terpolymers with similar block volume fractions but varying in total molar mass from 43 kg/mol to 115 kg/mol to systematically study the effect of polymer size on membrane structure. Small-angle X-ray scattering was used to probe terpolymer solution structure in the dope. All four triblocks displayed solution scattering patterns consistent with a body-centered cubic morphology. After membrane formation, structures were characterized using a combination of scanning electron microscopy and filtration performance tests. Membrane pore densities that ranged from 4.53 × 1014 to 1.48 × 1015 pores/m 2 were observed, which are the highest pore densities yet reported for membranes using self-assembly and non-solvent induced phase separation. Hydraulic permeabilities ranging from 24 to 850 L m-2 h-1 bar-1 and pore diameters ranging from 7 to 36 nm were determined from permeation and rejection experiments. Both the hydraulic permeability and pore size increased with increasing molar mass of the parent terpolymer. The combination of polymer characterization and membrane transport tests described here demonstrates the ability to rationally design macromolecular structures to target specific performance characteristics in block copolymer derived ultrafiltration membranes. © 2013 Elsevier Ltd. All rights reserved.

  20. Memory for found targets interferes with subsequent performance in multiple-target visual search.

    Science.gov (United States)

    Cain, Matthew S; Mitroff, Stephen R

    2013-10-01

    Multiple-target visual searches--when more than 1 target can appear in a given search display--are commonplace in radiology, airport security screening, and the military. Whereas 1 target is often found accurately, additional targets are more likely to be missed in multiple-target searches. To better understand this decrement in 2nd-target detection, here we examined 2 potential forms of interference that can arise from finding a 1st target: interference from the perceptual salience of the 1st target (a now highly relevant distractor in a known location) and interference from a newly created memory representation for the 1st target. Here, we found that removing found targets from the display or making them salient and easily segregated color singletons improved subsequent search accuracy. However, replacing found targets with random distractor items did not improve subsequent search accuracy. Removing and highlighting found targets likely reduced both a target's visual salience and its memory load, whereas replacing a target removed its visual salience but not its representation in memory. Collectively, the current experiments suggest that the working memory load of a found target has a larger effect on subsequent search accuracy than does its perceptual salience.

  1. The Prediction of Academic and Clinical Performance in Medical School

    Science.gov (United States)

    Gough, Harrison G.; Hall, Wallace B.

    1975-01-01

    A study of medical student performance showed the clinical performance factor more or less unpredictable from aptitude and premedical academic achievement indices while the academic performance factor was forecast with acceptable accuracy by equations based on the Medical College Admissions Test and premedical grade point average. (JT)

  2. Predictors of Successful Clinical Performance in Associate Degree Nursing Students.

    Science.gov (United States)

    Rice, Eileen

    2015-01-01

    The purpose of this study was to explore self-efficacy and emotional intelligence (EI) as predictors for successful clinical performance in nursing students. Students (n = 56) from 5 associate degree in nursing (ADN) schools in 2 Northeastern states participated in the study. Findings demonstrated significant relationships among EI, self-efficacy, and student-rated clinical competence. The findings from this study support the importance of fostering clinical self-efficacy and building EI abilities in ADN students. PMID:25628244

  3. Feedback-giving behaviour in performance evaluations during clinical clerkships

    NARCIS (Netherlands)

    Bok, Harold G J; Jaarsma, Debbie A D C; Spruijt, Annemarie; Van Beukelen, Peter; Van Der Vleuten, Cees P M; Teunissen, Pim W

    2015-01-01

    CONTEXT: Narrative feedback documented in performance evaluations by the teacher, i.e. the clinical supervisor, is generally accepted to be essential for workplace learning. Many studies have examined factors of influence on the usage of mini-clinical evaluation exercise (mini-CEX) instruments and p

  4. Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases.

    Science.gov (United States)

    Lange, Rogier; Ter Heine, Rob; Knapp, Russ Ff; de Klerk, John M H; Bloemendal, Haiko J; Hendrikse, N Harry

    2016-10-01

    Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha and conversion electron emitting radioisotopes have been investigated for the targeted treatment of painful bone metastases for >35years. We performed a systematic literature search and focused on the pharmaceutical development, preclinical research and early human studies of these radiopharmaceuticals. The characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are presented and compliance with these criteria by the compounds discussed is verified. The importance of both composition and preparation conditions for the stability and biodistribution of several agents is discussed. Very few studies have described the characterization of these products, although knowledge on the molecular structure is important with respect to in vivo behavior. This review discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of which only six agents have progressed to clinical use. Extensive clinical studies have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of these, (153)Sm-EDTMP represents the only compound with worldwide marketing authorization. (177)Lu-EDTMP has recently received approval for clinical use in India. This review illustrates that a thorough understanding of the radiochemistry of these agents is required to design simple and robust preparation and quality control methods, which are needed to fully exploit the potential benefits of these theranostic radiopharmaceuticals. Extensive biodistribution and dosimetry studies are indispensable to provide the portfolios that are required for assessment before human administration is possible. Use of the existing knowledge collected in this review should guide future research efforts and may lead to the approval of new promising agents. PMID:27496068

  5. The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

    International Nuclear Information System (INIS)

    Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such

  6. Platelet P2 receptors: from curiosity to clinical targets.

    Science.gov (United States)

    Cusack, N J; Hourani, S M

    2000-07-01

    Adenosine 5'-diphosphate (ADP) is a paracrine mediator that activates human blood platelets, causing them to become adhesive and thereby contributing to their role in hemostasis. The actions of ADP were initially thought to be mediated by a unique ADP receptor termed P2(T) found only on platelets and antagonized by ATP, but it appears that at least two P2Y receptor subtypes are involved, a P2Y(1) receptor linked in some way to control of intracellular-free calcium levels and another P2Y receptor linked via an inhibitory G protein to adenylate cyclase. In addition, the presence of excitatory P2X(1) receptors that mediate the influx of monovalent and divalent cations in response to both ADP and ATP has been demonstrated. The precise contribution that each of these P2 receptors make to the overall phenomena associated with platelet aggregation, adhesion and hemostasis is yet to be defined. Antithrombotic agents that interfere with the actions of ADP are marketed, and P2 receptor antagonists are entering clinical trials for acute treatments of thrombosis. This review seeks to summarize the present state of knowledge of platelet P2 receptor pharmacology and therapeutics.

  7. Inflation targeting and economic performance: The case of Mexico

    Directory of Open Access Journals (Sweden)

    Carrasco Carlos A.

    2011-01-01

    Full Text Available In the paper we analyze the impact of Inflation Targeting (IT in Mexico. The objective is to evaluate the impact of the implementation of inflation targeting and full-fledged inflation targeting (FFIT on the level and the variability of the inflation and the output in the Mexican economy. We conclude that inflation rates had been reduced in Mexico before the introduction of IT and FFIT. In our opinion, the structural reforms, including the Banxico reforms, are the main determinants of the decrease in inflation and its variability. The main impact of IT would have been the lock-in of inflation expectations around a low rate of inflation.

  8. EGFR-Targeting as a Biological Therapy: Understanding Nimotuzumab's Clinical Effects

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Rolando, E-mail: rolando@cim.sld.cu; Moreno, Ernesto; Garrido, Greta; Crombet, Tania [Center of Molecular Immunology, P.O. Box 16040, Havana 11600 (Cuba)

    2011-04-18

    Current clinical trials of epidermal growth factor receptor (EGFR)-targeted therapies are mostly guided by a classical approach coming from the cytotoxic paradigm. The predominant view is that the efficacy of EGFR antagonists correlates with skin rash toxicity and induction of objective clinical response. Clinical benefit from EGFR-targeted therapies is well documented; however, chronic use in advanced cancer patients has been limited due to cumulative and chemotherapy-enhanced toxicity. Here we analyze different pieces of data from mechanistic and clinical studies with the anti-EGFR monoclonal antibody Nimotuzumab, which provides several clues to understand how this antibody may induce a biological control of tumor growth while keeping a low toxicity profile. Based on these results and the current state of the art on EGFR-targeted therapies, we discuss the need to evaluate new therapeutic approaches using anti-EGFR agents, which would have the potential of transforming advanced cancer into a long-term controlled chronic disease.

  9. [Gross tumor volume (GTV) and clinical target volume (CTV) in adult gliomas].

    Science.gov (United States)

    Kantor, G; Loiseau, H; Vital, A; Mazeron, J J

    2001-10-01

    Glioblastoma multiform and astrocytoma are the most frequent primary cancer of the central nervous system of adult. Definitions of gross tumor volume (GTV) and clinical target volume (CTV) are based on the confrontation of clinical presentation (age, performance status, neurologic symptoms...), histological type and imaging aspects. For glioblastoma multiform, the GTV can be defined by the area of contrast enhancement observed on the CT scan or MRI. Definition of the CTV can be more difficult and have to take into account the risk of presence of isolated malignant cells in the oedema surrounding the tumor or in the adjacent brain structures. The classical concept of GTV plus a safety margin of 2 cm around is discussed with a CTV containing at least all the oedematous area and eventually adjacent brain structures (nuclei, corpus callosum or other long associative fibers...). For low grade astrocytoma, the definition of GTV can be difficult if the tumoral infiltration is diffuse without nodular visible tumor. CTV corresponds to at least T2 MRI hypersignal area when visible. For postoperative tumor, technical considerations are important for the detection of residual tumor. A safety margin around the resected area is designed according to the risk of presence of isolated cells or involvement of adjacent brain structures. PMID:11715309

  10. Emotional intelligence and clinical performance/retention of nursing students

    Directory of Open Access Journals (Sweden)

    Chelsea Marvos

    2015-01-01

    Full Text Available Objective: This exploratory, quantitative, descriptive study was undertaken to explore the relationship between clinical performance and anticipated retention in nursing students. Methods: After approval by the university′s Human Subjects Committee, a sample of 104 nursing students were recruited for this study, which involved testing with a valid and reliable emotional intelligence (EI instrument and a self-report survey of clinical competencies. Results: Statistical analysis revealed that although the group average for total EI score and the 6 score subsets were in the average range, approximately 30% of the individual total EI scores and 30% of two branch scores, identifying emotions correctly and understanding emotions, fell in the less than average range. This data, as well as the analysis of correlation with clinical self-report scores, suggest recommendations applicable to educators of clinical nursing students. Conclusions: Registered nurses make-up the largest segment of the ever-growing healthcare workforce. Yet, retention of new graduates has historically been a challenge for the profession. Given the projected employment growth in nursing, it is important to identify factors which correlate with high levels of performance and job retention among nurses. There is preliminary evidence that EI "a nontraditional intelligence measure" relates positively not only with retention of clinical staff nurses, but with overall clinical performance as well.

  11. Clinical guidance on the perioperative use of targeted agents in solid tumor oncology.

    Science.gov (United States)

    Mellor, James D; Cassumbhoy, Michelle; Jefford, Michael

    2011-06-01

    The use of targeted anti-cancer agents is increasing. It is common to utilize a multi-modal treatment approach towards solid tumors, often including surgical resection, and it has become apparent that some targeted agents can impair wound healing or cause an increased risk of perioperative complications. This article reviews targeted agents used in solid tumor oncology with an emphasis on clinically relevant details. Overall, the evidence of targeted agents causing surgical complications is limited. The greatest amount of evidence exists for bevacizumab causing perioperative complications, possibly due to its extended half-life. There are limited data for cetuximab, sorafenib and sunitinib and very little for other solid tumor targeted agents. Our findings suggest that there should be heightened pharmacovigilence around targeted agents with respect to perioperative complications and increased post-surgical support for patients to aid early detection of postoperative complications until definitive data become available. PMID:21585689

  12. 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.

  13. Comparison of the cancer gene targeting and biochemical selectivities of all targeted kinase inhibitors approved for clinical use.

    Directory of Open Access Journals (Sweden)

    Joost C M Uitdehaag

    Full Text Available The anti-proliferative activities of all twenty-five targeted kinase inhibitor drugs that are in clinical use were measured in two large assay panels: (1 a panel of proliferation assays of forty-four human cancer cell lines from diverse tumour tissue origins; and (2 a panel of more than 300 kinase enzyme activity assays. This study provides a head-on comparison of all kinase inhibitor drugs in use (status Nov. 2013, and for six of these drugs, the first kinome profiling data in the public domain. Correlation of drug activities with cancer gene mutations revealed novel drug sensitivity markers, suggesting that cancers dependent on mutant CTNNB1 will respond to trametinib and other MEK inhibitors, and cancers dependent on SMAD4 to small molecule EGFR inhibitor drugs. Comparison of cellular targeting efficacies reveals the most targeted inhibitors for EGFR, ABL1 and BRAF(V600E-driven cell growth, and demonstrates that the best targeted agents combine high biochemical potency with good selectivity. For ABL1 inhibitors, we computationally deduce optimized kinase profiles for use in a next generation of drugs. Our study shows the power of combining biochemical and cellular profiling data in the evaluation of kinase inhibitor drug action.

  14. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date.

    Science.gov (United States)

    Park, Jae H; Geyer, Mark B; Brentjens, Renier J

    2016-06-30

    Adoptive transfer of T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 has produced impressive results in treating patients with B-cell malignancies. Although these CAR-modified T cells target the same antigen, the designs of CARs vary as well as several key aspects of the clinical trials in which these CARs have been studied. It is unclear whether these differences have any impact on clinical outcome and treatment-related toxicities. Herein, we review clinical results reflecting the investigational use of CD19-targeted CAR T-cell therapeutics in patients with B-cell hematologic malignancies, in light of differences in CAR design and production, and outline the limitations inherent in comparing outcomes between studies. PMID:27207800

  15. Digital breast tomosynthesis versus digital mammography: a clinical performance study

    Energy Technology Data Exchange (ETDEWEB)

    Gennaro, Gisella; Baldan, Enrica; Bezzon, Elisabetta; Polico, Ilaria; Proietti, Alessandro; Toffoli, Aida [Venetian Oncological Institute (IOV), IRCCS, Department of Radiology, Padua (Italy); Toledano, Alicia [Statistics Collaborative Inc., Washington, DC (United States); Di Maggio, Cosimo [Padua University, Department of Oncological and Surgical Sciences, Padua (Italy); La Grassa, Manuela [Aviano Oncological Reference Center (CRO), IRCCS, Department of Radiology, Aviano (Pordenone) (Italy); Pescarini, Luigi [Venetian Oncological Institute (IOV), IRCCS, Department of Radiology, Padua (Italy); Padua University, Department of Oncological and Surgical Sciences, Padua (Italy); Muzzio, Pier Carlo [Venetian Oncological Institute (IOV), IRCCS, Department of Radiology, Padua (Italy); Padua University, Department of Medical Diagnostic Sciences, Padua (Italy)

    2010-07-15

    To compare the clinical performance of digital breast tomosynthesis (DBT) with that of full-field digital mammography (FFDM) in a diagnostic population. The study enrolled 200 consenting women who had at least one breast lesion discovered by mammography and/or ultrasound classified as doubtful or suspicious or probably malignant. They underwent tomosynthesis in one view [mediolateral oblique (MLO)] of both breasts at a dose comparable to that of standard screen-film mammography in two views [craniocaudal (CC) and MLO]. Images were rated by six breast radiologists using the BIRADS score. Ratings were compared with the truth established according to the standard of care and a multiple-reader multiple-case (MRMC) receiver-operating characteristic (ROC) analysis was performed. Clinical performance of DBT compared with that of FFDM was evaluated in terms of the difference between areas under ROC curves (AUCs) for BIRADS scores. Overall clinical performance with DBT and FFDM for malignant versus all other cases was not significantly different (AUCs 0.851 vs 0.836, p = 0.645). The lower limit of the 95% CI or the difference between DBT and FFDM AUCs was -4.9%. Clinical performance of tomosynthesis in one view at the same total dose as standard screen-film mammography is not inferior to digital mammography in two views. (orig.)

  16. 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.

  17. Comparison of FDA Approved Kinase Targets to Clinical Trial Ones: Insights from Their System Profiles and Drug-Target Interaction Networks

    Directory of Open Access Journals (Sweden)

    Jingyu Xu

    2016-01-01

    Full Text Available Kinase is one of the most productive classes of established targets, but the majority of approved drugs against kinase were developed only for cancer. Intensive efforts were therefore exerted for releasing its therapeutic potential by discovering new therapeutic area. Kinases in clinical trial could provide great opportunities for treating various diseases. However, no systematic comparison between system profiles of established targets and those of clinical trial ones was conducted. The reveal of probable difference or shift of trend would help to identify key factors defining druggability of established targets. In this study, a comparative analysis of system profiles of both types of targets was conducted. Consequently, the systems profiles of the majority of clinical trial kinases were identified to be very similar to those of established ones, but percentages of established targets obeying the system profiles appeared to be slightly but consistently higher than those of clinical trial targets. Moreover, a shift of trend in the system profiles from the clinical trial to the established targets was identified, and popular kinase targets were discovered. In sum, this comparative study may help to facilitate the identification of the druggability of established drug targets by their system profiles and drug-target interaction networks.

  18. Numerical Simulation of High Performance Shaped Charge Penetrating Concrete Targets

    Institute of Scientific and Technical Information of China (English)

    JIANG Jian-wei; WANG Li-ying; MEN Jian-bing

    2005-01-01

    Tandem warhead systems consist of a precursor shaped charge and a following kinetic energy projectile containing high explosive filling. This paper presents a numerical simulation analysis of the penetration forming and the process in which the shaped charge penetrated into concrete targets by using AUTODYN software. The shaped charge is consist of different materials, different standoff, different liner curvature and thickness. Parameters for the liner structure which can detemine ideal aperture and penetration depth are acquired. The simulation results are in agreement with them of the experiment.

  19. Documenting clinical performance problems among medical students: feedback for learner remediation and curriculum enhancement

    Directory of Open Access Journals (Sweden)

    Brian E. Mavis

    2013-07-01

    Full Text Available Introduction: We operationalized the taxonomy developed by Hauer and colleagues describing common clinical performance problems. Faculty raters pilot tested the resulting worksheet by observing recordings of problematic simulated clinical encounters involving third-year medical students. This approach provided a framework for structured feedback to guide learner improvement and curricular enhancement. Methods: Eighty-two problematic clinical encounters from M3 students who failed their clinical competency examination were independently rated by paired clinical faculty members to identify common problems related to the medical interview, physical examination, and professionalism. Results: Eleven out of 26 target performance problems were present in 25% or more encounters. Overall, 37% had unsatisfactory medical interviews, with ‘inadequate history to rule out other diagnoses’ most prevalent (60%. Seventy percent failed because of physical examination deficiencies, with missing elements (69% and inadequate data gathering (69% most common. One-third of the students did not introduce themselves to their patients. Among students failing based on standardized patient (SP ratings, 93% also failed to demonstrate competency based on the faculty ratings. Conclusions: Our review form allowed clinical faculty to validate pass/fail decisions based on standardized patient ratings. Detailed information about performance problems contributes to learner feedback and curricular enhancement to guide remediation planning and faculty development.

  20. Establishing proof of mechanism: Assessing target modulation in early-phase clinical trials.

    Science.gov (United States)

    Kummar, Shivaani; Do, Khanh; Coyne, Geraldine O'Sullivan; Chen, Alice; Ji, Jiuping; Rubinstein, Larry; Doroshow, James H

    2016-08-01

    Since modulation of the putative target and the observed anti-tumor effects form the basis for the clinical development of a molecularly targeted therapy, early-phase clinical trials should be designed to demonstrate proof-of-mechanism in tissues of interest. In addition to establishing safety and the maximum tolerated dose, first-in-human clinical trials should be designed to demonstrate target modulation, define the proposed mechanism of action, and evaluate pharmacokinetic-pharmacodynamic relationships of a new anti-cancer agent. Assessing target modulation in paired tumor biopsies in patients with solid tumors presents multiple challenges, including procedural issues such as patient safety, ethical considerations, and logistics of sample handling and processing. In addition, the availability of qualified biomarker assay technologies, resources to conduct such studies, and real-time analysis of samples to detect inter-species differences that may affect the determination of optimal sampling time points must be taken into account. This article provides a discussion of the challenges that confront the practical application of pharmacodynamic studies in early-phase clinical trials of anti-cancer agents. PMID:27663476

  1. Targeted next-generation sequencing can replace Sanger sequencing in clinical diagnostics

    NARCIS (Netherlands)

    Sikkema-Raddatz, B.; Johansson, L.F.; de Boer, E.N.; Almomani, R.; Boven, L.G.; van den Berg, M.P.; van Spaendonck-Zwarts, K.Y.; van Tintelen, J.P.; Sijmons, R.H.; Jongbloed, J.D.H.; Sinke, R.J.

    2013-01-01

    Mutation detection through exome sequencing allows simultaneous analysis of all coding sequences of genes. However, it cannot yet replace Sanger sequencing (SS) in diagnostics because of incomplete representation and coverage of exons leading to missing clinically relevant mutations. Targeted next-g

  2. Clinical laboratory as an economic model for business performance analysis

    Science.gov (United States)

    Buljanović, Vikica; Patajac, Hrvoje; Petrovečki, Mladen

    2011-01-01

    Aim To perform SWOT (strengths, weaknesses, opportunities, and threats) analysis of a clinical laboratory as an economic model that may be used to improve business performance of laboratories by removing weaknesses, minimizing threats, and using external opportunities and internal strengths. Methods Impact of possible threats to and weaknesses of the Clinical Laboratory at Našice General County Hospital business performance and use of strengths and opportunities to improve operating profit were simulated using models created on the basis of SWOT analysis results. The operating profit as a measure of profitability of the clinical laboratory was defined as total revenue minus total expenses and presented using a profit and loss account. Changes in the input parameters in the profit and loss account for 2008 were determined using opportunities and potential threats, and economic sensitivity analysis was made by using changes in the key parameters. The profit and loss account and economic sensitivity analysis were tools for quantifying the impact of changes in the revenues and expenses on the business operations of clinical laboratory. Results Results of simulation models showed that operational profit of €470 723 in 2008 could be reduced to only €21 542 if all possible threats became a reality and current weaknesses remained the same. Also, operational gain could be increased to €535 804 if laboratory strengths and opportunities were utilized. If both the opportunities and threats became a reality, the operational profit would decrease by €384 465. Conclusion The operational profit of the clinical laboratory could be significantly reduced if all threats became a reality and the current weaknesses remained the same. The operational profit could be increased by utilizing strengths and opportunities as much as possible. This type of modeling may be used to monitor business operations of any clinical laboratory and improve its financial situation by

  3. Clinical task performance and imaging task performance compared for two different commercial electronic portal imaging systems

    International Nuclear Information System (INIS)

    Full text: This paper reports on the investigation and comparison of performance of a Varian Portal Vision system and a Siemens Beamview Plus system using the framework outlined by ICRU Report 54. Radiation Therapy EPI (Electronic Portal Imaging) systems are one of the main applications of digital imaging technology in a radiation therapy department. Radiation Therapy EPI systems may produce images of a lesser quality than the diagnostic radiology equivalent. It is therefore important to optimise the system to obtain the best performance possible. Contrasting opinion on the performance of EPI by clinicians, radiation therapists, medical physicists and engineers often exists, even when the same system and even the same image are being evaluated. Differing opinion occurs because of differences in task end points and task assessment methods of two broad groups of individuals, the human-observer group and the technical-measurement group. Each group uses different task criteria and methodology for assessing performance. The human-observer group is primarily interested in system performance that assures a high level clinical-task performance while the technical-measurement group is concerned with system performance that assures a high level of imaging-task performance. The technical-measurement group tends to be closely associated with imaging system technology, testing, adjustment and optimisation tasks which are couched in terms imaging-task criteria. The human-observer group is usually attempting to optimise performance using clinical-task criteria. The challenge is to provide a balanced evaluation using complementary imaging-task performance and clinical-task performance assessments. Comparison of the systems is on the basis of imaging-task performance i.e. technical-measurement through physical performance assessments such as spatial resolution and noise level, and clinical-task performance i.e. human-observer measurements through the application of psychophysical

  4. 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.

  5. All-ceramic systems: laboratory and clinical performance.

    Science.gov (United States)

    Guess, Petra C; Schultheis, Stefan; Bonfante, Estevam A; Coelho, Paulo G; Ferencz, Jonathan L; Silva, Nelson R F A

    2011-04-01

    Several all-ceramic systems have been developed in dentistry to meet the increased expectations of patients and dentists for highly aesthetic, biocompatible, and long-lasting restorations. However, early bulk fractures or chippings have led the research community to investigate the mechanical performance of the all-ceramic systems. This overview explores the current knowledge of monolithic and bilayer dental all-ceramic systems, addressing composition and processing mechanisms, laboratory and clinical performance, and possible future trends for all-ceramic materials. PMID:21473997

  6. Disease-specific target gene expression profiling of molecular imaging probes: database development and clinical validation.

    Science.gov (United States)

    Chan, Lawrence Wing-Chi; Ngo, Connie Hiu-Ching; Wang, Fengfeng; Zhao, Moss Y; Zhao, Mengying; Law, Helen Ka-Wai; Wong, Sze Chuen Cesar; Yung, Benjamin Yat-Ming

    2014-01-01

    Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD) provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP) database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET) study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2-deoxy-2-d-glucose (FDG), respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/. PMID:25022454

  7. Clinical Significance of Auditory Target P300 Subcomponents in Psychosis: Differential Diagnosis, Symptom Profiles, and Course

    Science.gov (United States)

    Perlman, Greg; Foti, Dan; Jackson, Felicia; Kotov, Roman; Constantino, Eduardo; Hajcak, Greg

    2015-01-01

    Background Reduced auditory target P300 amplitude is a leading biomarker for psychotic disorders, although its relevance for differential diagnosis and link to specific clinical features (symptom profiles, functional impairment, and course) is unclear. This study aims to clarify the clinical significance of auditory target P300 using concurrent and retrospective clinical data from a longitudinal cohort with psychosis. Methods 92 cases from an epidemiological study of first-admission psychosis were assessed using an auditory oddball paradigm at 15-year follow-up along with 44 never-psychotic adults. Subcomponents of auditory target P300 amplitude (i.e., a central positive P3a, a parietal positive P3b, and a frontal negative slow wave) were isolated using temporal-spatial principal components analysis. Results P3a amplitude was blunted across psychotic disorders relative to non-psychotic adults. P3b amplitude was reduced in schizophrenia specifically, including cases initially misclassified at baseline. The frontal negative slow wave did not distinguish among groups. P3b amplitude reduction was associated with several clinical features at the concurrent assessment, as well as previous time points, including recovery from psychosis even 5 years earlier and functioning even 15 years earlier. Conclusions Auditory target P300 amplitude yields both a schizophrenia-specific component (i.e., P3b) and a transdiagnostic psychosis component (i.e., P3a). The P3b component may also shed light on prognosis, real-world functioning, and course, as well as help to reduce misdiagnosis of psychotic disorders. Prospective studies are needed to test whether P3b tracks or predicts clinical status. PMID:25934167

  8. Toward prediction of hyperspectral target detection performance after lossy image compression

    Science.gov (United States)

    Kaufman, Jason R.; Vongsy, Karmon M.; Dill, Jeffrey C.

    2016-05-01

    Hyperspectral imagery (HSI) offers numerous advantages over traditional sensing modalities with its high spectral content that allows for classification, anomaly detection, target discrimination, and change detection. However, this imaging modality produces a huge amount of data, which requires transmission, processing, and storage resources; hyperspectral compression is a viable solution to these challenges. It is well known that lossy compression of hyperspectral imagery can impact hyperspectral target detection. Here we examine lossy compressed hyperspectral imagery from data-centric and target-centric perspectives. The compression ratio (CR), root mean square error (RMSE), the signal to noise ratio (SNR), and the correlation coefficient are computed directly from the imagery and provide insight to how the imagery has been affected by the lossy compression process. With targets present in the imagery, we perform target detection with the spectral angle mapper (SAM) and adaptive coherence estimator (ACE) and evaluate the change in target detection performance by examining receiver operating characteristic (ROC) curves and the target signal-to-clutter ratio (SCR). Finally, we observe relationships between the data- and target-centric metrics for selected visible/near-infrared to shortwave infrared (VNIR/SWIR) HSI data, targets, and backgrounds that motivate potential prediction of change in target detection performance as a function of compression ratio.

  9. Challenges in the design of clinically useful brain-targeted drug nanocarriers.

    Science.gov (United States)

    Costantino, L; Boraschi, D; Eaton, M

    2014-01-01

    Nowadays, the delivery of drugs by means of intravenously administered nanosized drug carriers - polymerdrug conjugates, liposomes and micelles, is technically possible. These delivery systems are mainly designed for tumour therapy, and accumulate passively into tumours by means of the well known EPR effect. Targeted nanocarriers, that additionally contain ligands for receptors expressed on cell surfaces, are also widely studied but products of this kind are not marketed, and only a few are in clinical trial. Polymeric nanoparticles (Np) able to deliver drugs to the CNS were pioneered in 1995; a number of papers have been published dealing with brain-targeted drug delivery using polymeric Np able to cross the BBB, mainly for the treatment of brain tumours. At present, however, the translation potential of these Np seems to have been exceeded by targeted liposomes, a platform based on a proven technology. This drug delivery system entered clinical trials soon after its discovery, while the challenges in formulation, characterization and manufacturing of brain-targeted polymeric Np and the cost/benefit ratio could be the factors that have prevented their development. A key issue is that it is virtually impossible to define the in vivo fate of polymers, especially in the brain, which is a regulatory requirement; perhaps this is why no progress has been made. The most advanced Np for brain tumours treatment will be compared here with the published data available for those in clinical trial for tumours outside the CNS, to highlight the knowledge gaps that still penalise these delivery systems. At present, new approaches for brain tumours are emerging, such as lipid Np or the use of monoclonal antibody (mAb)-drug conjugates, which avoid polymers. The success or failure in the approval of the polymeric Np currently in clinical trials will certainly affect the field. At present, the chances of their approval appear to be very low.

  10. Clinical Evaluation of Targeting Accuracy of Gamma Knife Radiosurgery in Trigeminal Neuralgia

    International Nuclear Information System (INIS)

    Purpose: The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgical treatment with the Leksell Gamma Knife for trigeminal neuralgia. We also studied the applied radiation dose within the area of focal contrast enhancement on the trigeminal nerve root following radiosurgery. Methods and Materials: From an initial group of 78 patients with trigeminal neuralgia treated with gamma knife radiosurgery using a 90-Gy dose, we analyzed a subgroup of 65 patients for whom 6-month follow-up MRI showed focal contrast enhancement of the trigeminal nerve. Follow-up MRI was spatially coregistered to the radiosurgical planning MRI. Target accuracy was assessed from deviation of the coordinates of the intended target compared with the center of enhancement on postoperative 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 0.91 mm in Euclidean space. The radiation doses fitting within the borders of the contrast enhancement of the trigeminal nerve root ranged from 49 to 85 Gy (median value, 77 ± 8.7 Gy). Conclusions: The median deviation found in clinical assessment of gamma knife treatment for trigeminal neuralgia is low and compatible with its high rate of efficiency. Focal enhancement of the trigeminal nerve after radiosurgery occurred in 83% of our patients and was not associated with clinical outcome. Focal enhancement borders along the nerve root fit with a median dose of 77 ± 8.7 Gy

  11. Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative

    Science.gov (United States)

    Lim, Sun Min; Kim, Eun Young; Kim, Hye Ryun; Ali, Siraj M.; Greenbowe, Joel R.; Shim, Hyo Sup; Chang, Hyun; Lim, Seungtaek; Paik, Soonmyung; Cho, Byoung Chul

    2016-01-01

    Background: Identification of clinically relevant oncogenic drivers in advanced cancer is critical in selecting appropriate targeted therapy. Using next-generation sequencing (NGS)-based clinical cancer gene assay, we performed comprehensive genomic profiling (CGP) of advanced cases of lung adenocarcinoma. Methods: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer. Results: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GAs). GAs per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50% (80/190) non-synonymous base substitutions, 15% (29/190) insertions or deletion, and 3% (5/190) splice site mutation. TP53 mutation was the most common GAs (15%, n=29/190), followed by CDKN2A homozygous loss (5%, n=10/190), KRAS mutation (4%, n=8/190), EGFR mutation (4%, n=8/190) and MDM2 amplification (2%, n=5/190). As per NCCN guidelines, targetable GAs were identified in 16 patients (31%) (BRAF mutation [n=1], EGFR mutation [n=8], ERBB2 mutation [n=4], MET amplification [n=1], KIF5B-RET rearrangement [n=2], CCDC6-RET rearrangement [n=1], CD74-ROS1 rearrangement [n=1], EZR-ROS1 rearrangement [n=5], and SLC34A2-ROS1 rearrangement [n=1]). Conclusion: Fifty eight percent of patients wild type by standard testing for EGFR/KRAS/ALK have GAs identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative can reveal additional avenues of benefit from targeted therapy. PMID:26992220

  12. Modelling the performance of USV manoeuvring and target tracking: an approach using frequency modulated continuous wave radar rotary system.

    Science.gov (United States)

    Onunka, Chiemela; Nnadozie, Remigius Chidozie

    2013-12-01

    The performance of frequency modulated continuous wave (FMCW) radar in tracking targets is presented and analysed. Obstacle detection, target tracking and radar target tracking performance models are developed and were used to investigate and to propose ways of improving the autonomous motion of unmanned surface vehicle (USV). Possible factors affecting the performance of FMCW radar in tracking targets are discussed and analysed. PMID:23853743

  13. Clinical performance feedback and quality improvement opportunities for perioperative physicians

    Directory of Open Access Journals (Sweden)

    Kaye AD

    2014-05-01

    Full Text Available Alan David Kaye,1 Olutoyin J Okanlawon,2 Richard D Urman21Department of Anesthesiology, Louisiana State University School of Medicine, New Orleans, LA, 2Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston MA, USAAbstract: Clinical performance feedback is an important component of the ongoing development and education of health care practitioners. For physicians, feedback about their clinical practice and outcomes is central to developing both confidence and competence at all stages of their medical careers. Cultural and financial infrastructures need to be in place, and the concept of feedback needs to be readily embraced and encouraged by clinical leadership and other stakeholders. The "buy-in" includes the expectation and view that feedback occurs on a routine basis, and those engaged in the process are both encouraged to participate and held accountable. Feedback must be part of an overarching quality improvement and physician education agenda; it is not meant to be an isolated, fragmented initiative that is typically undermined by lack of resources or systemic barriers to gaining improvement within programs. Effective feedback should be an integral part of clinical practice. Anesthesiologists and other perioperative physicians are identifying specialty-specific indicators that can be used when creating a broader quality improvement agenda. Placing a more immediate formal feedback strategy that focuses on goal-oriented behavior is rapidly becoming a mainstay. Physicians may use their individual feedback reports for reflection and designing personal development plans as lifelong learners and leaders in improving patient care.Keywords: physician education, outcomes measurement, performance improvement, anesthesiology

  14. From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage.

    Science.gov (United States)

    Mastellos, Dimitrios C; Reis, Edimara S; Yancopoulou, Despina; Hajishengallis, George; Ricklin, Daniel; Lambris, John D

    2016-10-01

    Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably stirred the field of complement therapeutic design, providing new insights into complement's contribution to disease pathogenesis and also helping to leverage a more personalized, comprehensive approach to patient management. In this regard, a rapidly expanding toolbox of complement therapeutics is being developed to address unmet clinical needs in several immune-mediated and inflammatory diseases. Elegant approaches employing both surface-directed and fluid-phase inhibitors have exploited diverse components of the complement cascade as putative points of therapeutic intervention. Targeting C3, the central hub of the system, has proven to be a promising strategy for developing biologics as well as small-molecule inhibitors with clinical potential. Complement modulation at the level of C3 has recently shown promise in preclinical primate models, opening up new avenues for therapeutic intervention in both acute and chronic indications fueled by uncontrolled C3 turnover. This review highlights recent developments in the field of complement therapeutics, focusing on C3-directed inhibitors and alternative pathway (AP) regulator-based approaches. Translational perspectives and considerations are discussed, particularly with regard to the structure-guided drug optimization and clinical advancement of a new generation of C3-targeted peptidic inhibitors. PMID:27353192

  15. 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

  16. Challenges of clinical trial design for targeted agents against pediatric leukemias

    Directory of Open Access Journals (Sweden)

    Francis Jay Mussai

    2015-01-01

    Full Text Available The past 40 years have seen significant improvements in both event-free and overall survival for children with acute lymphoblastic or acute myeloid leukemia (ALL or AML respectively. Serial national and international clinical trials have optimised the use of conventional chemotherapeutic drugs and, along with improvements in supportive care that have enabled the delivery of more intensive regimens, have been responsible for the major improvements in patient outcome seen over the past few decades,. The benefits of dose intensification, however, have likely now been maximised, and over the same period, the identification of new cytotoxic drugs has been limited.As the biology of leukemogenesis has become better understood, key molecules and intracellular pathways have been identified that offer the possibility of targeting directly the leukemia cells whilst sparing normal cells. Consequently, there is now a drive to develop novel leukemia-specific or ‘targeted’ therapies. These new classes of drugs will have mechanisms of action, toxicities and therapeutic indices quite different from conventional cytotoxic drugs previously encountered, thus rendering current clinical trial methodologies inappropriate; clinical trial methods will need to be adapted to accommodate these features of these new classes of drugs. This review will address the challenges and some of the techniques for developing clinical trials for targeted therapies.

  17. Targeting FAK in human cancer: from finding to first clinical trials.

    Science.gov (United States)

    Golubovskaya, Vita M

    2014-01-01

    It is twenty years since Focal Adhesion Kinase (FAK) was found to be overexpressed in many types of human cancer. FAK plays an important role in adhesion, spreading, motility, invasion, metastasis, survival, angiogenesis, and recently has been found to play an important role as well in epithelial to mesenchymal transition (EMT), cancer stem cells and tumor microenvironment. FAK has kinase-dependent and kinase independent scaffolding, cytoplasmic and nuclear functions. Several years ago FAK was proposed as a potential therapeutic target; the first clinical trials were just reported, and they supported further studies of FAK as a promising therapeutic target. This review discusses the main functions of FAK in cancer, and specifically focuses on recent novel findings on the role of FAK in cancer stem cells, microenvironment, epithelial-to-mesenchymal transition, invasion, metastasis, and also highlight new approaches of targeting FAK and critically discuss challenges that lie ahead for its targeted therapeutics. The review provides a summary of translational approaches of FAK-targeted and combination therapies and outline perspectives and future directions of FAK research. PMID:24389213

  18. The UK clinical aptitude test and clinical course performance at Nottingham: a prospective cohort study

    OpenAIRE

    Yates, Janet; James, David

    2013-01-01

    Background The UK Clinical Aptitude Test (UKCAT) was introduced in 2006 as an additional tool for the selection of medical students. It tests mental ability in four distinct domains (Verbal Reasoning, Quantitative Reasoning, Abstract Reasoning, and Decision Analysis), and the results are available to students and admission panels in advance of the selection process. Our first study showed little evidence of any predictive validity for performance in the first two years of the Nottingham un...

  19. Design choices made by target users for a pay-for-performance program in primary care: an action research approach

    Directory of Open Access Journals (Sweden)

    Kirschner Kirsten

    2012-03-01

    Full Text Available Abstract Background International interest in pay-for-performance (P4P initiatives to improve quality of health care is growing. Current programs vary in the methods of performance measurement, appraisal and reimbursement. One may assume that involvement of health care professionals in the goal setting and methods of quality measurement and subsequent payment schemes may enhance their commitment to and motivation for P4P programs and therefore the impact of these programs. We developed a P4P program in which the target users were involved in decisions about the P4P methods. Methods For the development of the P4P program a framework was used which distinguished three main components: performance measurement, appraisal and reimbursement. Based on this framework design choices were discussed in two panels of target users using an adapted Delphi procedure. The target users were 65 general practices and two health insurance companies in the South of the Netherlands. Results Performance measurement was linked to the Dutch accreditation program based on three domains (clinical care, practice management and patient experience. The general practice was chosen as unit of assessment. Relative standards were set at the 25th percentile of group performance. The incentive for clinical care was set twice as high as the one for practice management and patient experience. Quality scores were to be calculated separately for all three domains, and for both the quality level and the improvement of performance. The incentive for quality level was set thrice as high as the one for the improvement of performance. For reimbursement, quality scores were divided into seven levels. A practice with a quality score in the lowest group was not supposed to receive a bonus. The additional payment grew proportionally for each extra group. The bonus aimed at was on average 5% to 10% of the practice income. Conclusions Designing a P4P program for primary care with involvement of

  20. Effects of Target and Distractor Saturations on the Cognitive Performance of an Integrated Display Interface

    Institute of Scientific and Technical Information of China (English)

    XUE Chengqi; LI Jing; WANG Haiyan; NIU Yafeng

    2015-01-01

    Color coding is often used to enhance decision quality in complex man-machine interfaces of integrated display systems. However, people are easily distracted by irrelevant colors and by the numerous data points and complex structures in the interface. Although an increasing number of studies are seriously focusing on the problem of achieving efficient color coding, few are able to determine the effects of target and distractor saturations on cognitive performance. To study the performances of target colors among distractors, a systematic experiment is conducted to assess the influence of high and low saturated targets on cognitive performance, and the affecting extent of different saturated distractors of homogeneous colors on targets. According to the analysis of the reaction time through the non-parametric statistical method, a calculation method of the cognitive performance of each color is proposed. Based on the calculation of the color differences and the accumulation of the reaction times, it is shown that with the different saturated distractors of homogeneous colors, the high saturated yellow targets perform better than the low saturated ones, and the green and blue targets have moderate performances. When searching for a singleton target placed on a black background, the color difference between the target and the distractor should be more than 20ΔE*ab units in the yellow saturation coding, whereas the color difference should be more than 40ΔE*ab units in the blue and green saturation coding. In addition, as regards saturation coding, the influence of the color difference between the target and the background on cognitive performance is greater than that of the color difference between the target and the distractor. Seemingly, the hue attribute determines whether the saturation difference between the target and the distractor affects the cognitive performance. Based on the experimental results, the simulation design of the instrument dials in a flight

  1. Bridging academic science and clinical research in the search for novel targeted anti-cancer agents

    Institute of Scientific and Technical Information of China (English)

    Alex Matter

    2015-01-01

    This review starts with a brief history of drug discovery&development, and the place of Asia in this worldwide effort discussed. hTe conditions and constraints of a successful translational R&D involving academic basic research and clinical research are discussed and the Singapore model for pursuit of open R&D described. hTe importance of well-characterized, validated drug targets for the search for novel targeted anti-cancer agents is emphasized, as well as a structured, high quality translational R&D. Furthermore, the characteristics of an attractive preclinical development drug candidate are discussed laying the foundation of a successful preclinical development. hTe most frequent sources of failures are described and risk management at every stage is highly recommended. Organizational factors are also considered to play an important role. hTe factors to consider before starting a new drug discovery&development project are described, and an example is given of a successful clinical project that has had its roots in local universities and was carried through preclinical development into phase I clinical trials.

  2. Bridging academic science and clinical research in the search for novel targeted anti-cancer agents.

    Science.gov (United States)

    Matter, Alex

    2015-12-01

    This review starts with a brief history of drug discovery & development, and the place of Asia in this worldwide effort discussed. The conditions and constraints of a successful translational R&D involving academic basic research and clinical research are discussed and the Singapore model for pursuit of open R&D described. The importance of well-characterized, validated drug targets for the search for novel targeted anti-cancer agents is emphasized, as well as a structured, high quality translational R&D. Furthermore, the characteristics of an attractive preclinical development drug candidate are discussed laying the foundation of a successful preclinical development. The most frequent sources of failures are described and risk management at every stage is highly recommended. Organizational factors are also considered to play an important role. The factors to consider before starting a new drug discovery & development project are described, and an example is given of a successful clinical project that has had its roots in local universities and was carried through preclinical development into phase I clinical trials. PMID:26779369

  3. Relationship between oral clinical conditions and daily performances

    Directory of Open Access Journals (Sweden)

    Andréa Silveira Gomes

    2009-03-01

    Full Text Available The aim of this study was to assess the impact of oral status on the daily performances of civil servants from the Public Works and Waste Management Department of the city of Porto Alegre, located in Southern Brazil. A cross-sectional study was conducted on a representative sample composed of 276 civil servants with ages ranging from 35 to 44 years. The Oral Impacts on Daily Performances index developed was employed to measure impacts caused by oral clinical conditions. Oral examinations were performed after the interviews. Multinomial Logistic Regression Analysis was used. After adjusting for sex and educational level, the results showed that the subjects with high DMFT scores were 5.8 times (95% CI = 2.1-16.1 more likely to have high impacts on their everyday life than those with low DMFT scores. Subjects that presented some coronal caries were 4.3 times (95% CI = 1.9-9.8 more likely to have high impacts on their everyday life than those with no coronal caries. Dental status assessed through the DMFT index and coronal caries are important indicators of impacts on the everyday life of the studied population.

  4. The mTOR pathway in obesity driven gastrointestinal cancers: Potential targets and clinical trials.

    Science.gov (United States)

    Malley, Cian O; Pidgeon, Graham P

    2016-06-01

    The mechanistic target of rapamycin (mTOR) is a crucial point of convergence between growth factor signalling, metabolism, nutrient status and cellular proliferation. The mTOR pathway is heavily implicated in the progression of many cancers and is emerging as an important driver of gastrointestinal (GI) malignancies. Due to its central role in adapting metabolism to environmental conditions, mTOR signalling is also believed to be critical in the development of obesity. Recent research has delineated that excessive nutrient intake can promote signalling through the mTOR pathway and possibly evoke changes to cellular metabolism that could accelerate obesity related cancers. Acting through its two effector complexes mTORC1 and mTORC2, mTOR dictates the transcription of genes important in glycolysis, lipogenesis, protein translation and synthesis and has recently been defined as a central mediator of the Warburg effect in cancer cells. Activation of the mTOR pathway is involved in both the pathogenesis of GI malignancies and development of resistance to conventional chemotherapy and radiotherapy. The use of mTOR inhibitors is a promising therapeutic option in many GI malignancies, with greatest clinical efficacy seen in combination regimens. Recent research has also provided insight into crosstalk between mTOR and other pathways which could potentially expand the list of therapeutic targets in the mTOR pathway. Here we review the available strategies for targeting the mTOR pathway in GI cancers. We discuss current clinical trials of both established and novel mTOR inhibitors, with particular focus on combinations of these drugs with conventional chemotherapy, radiotherapy and targeted therapies.

  5. Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer.

    Science.gov (United States)

    Scheiermann, Julia; Klinman, Dennis M

    2014-11-12

    Synthetic oligonucleotides (ODN) that express unmethylated "CpG motifs" trigger cells that express Toll-like receptor 9. In humans this includes plasmacytoid dendritic cells and B cells. CpG ODN induce an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. Their utility as vaccine adjuvants was evaluated in a number of clinical trials. Results indicate that CpG ODN improve antigen presentation and the generation of vaccine-specific cellular and humoral responses. This work provides an up-to-date overview of the utility of CpG ODN as adjuvants for vaccines targeting infectious agents and cancer. PMID:24975812

  6. PERFORMANCE COMPARISON OF ECG COMPRESSIONALGORITHMS BASED ON CLINICAL DIAGNOSIS

    Institute of Scientific and Technical Information of China (English)

    李顺山; 李高平; 乐园; 庄天戈

    2001-01-01

    This paper reviewed the recent progress in the field of electrocardiogram (ECG) compression and compared the efficiency of some compression algorithms. By experimenting on the 500 cases of ECG signals from the ECG database of China, it obtained the numeral indexes for each algorithm. Then by using the automatic diagnostic program developed by Shanghai Zhongshan Hospital, it also got the parameters of the reconstructed signals from linear approximation distance threshold (LADT), wavelet transform (WT), differential pulse code modulation (DPCM) and discrete cosine transform (DCT) algorithm. The results show that when the index of percent of root-mean-square difference(PRD) is less than 2.5%, the diagnostic agreement ratio is more than 90%; the index of PRD cannot completely show the damage of significant clinical information; the performance of wavelet algorithm exceeds other methods in the same compression ratio (CR). For the statistical result of the parameters of various methods and the clinical diagnostic results, it is of certain value and originality in the field of ECG compression research.

  7. Prosthetic heart valves: Objective Performance Criteria versus randomized clinical trial.

    Science.gov (United States)

    Grunkemeier, Gary L; Jin, Ruyun; Starr, Albert

    2006-09-01

    The current Food and Drug Administration (FDA) heart valve guidance document uses an objective performance criteria (OPC) methodology to evaluate the clinical performance of prosthetic heart valves. OPC are essentially historical controls, but they have turned out to be an adequate, and perhaps optimal, study design in this situation. Heart valves have a simple open-and-close mechanism, device effectiveness is easy to document, and the common complications (thromboembolism, thrombosis, bleeding, leak, and infection) are well known and easily detected. Thus, randomized clinical trials (RCTs) have not been deemed necessary for the regulatory approval of prosthetic heart valves. The OPC are derived from the average complication rates of all approved heart valves. Studies based on OPC have been shown to work well; many different valve models have gained FDA market approval based on this methodology. Although heart valve RCTs are not required by the FDA, they have been done to compare valves or treatment regimens after approval. Recently, the Artificial Valve Endocarditis Reduction Trial (AVERT) was designed to compare a new Silzone sewing ring, designed to reduce infection, with the Standard sewing ring on a St. Jude Medical heart valve. This was the largest heart valve RCT ever proposed (4,400 valve patients, followed for as long as 4 years), but it was stopped prematurely because of a high leak rate associated with the Silzone valve. Examining the results showed that a much smaller, OPC-based study with 800 patient-years would have been sufficient to disclose this complication of the Silzone valve. PMID:16928482

  8. Online virtual isocenter based radiation field targeting for high performance small animal microirradiation

    Science.gov (United States)

    Stewart, James M. P.; Ansell, Steve; Lindsay, Patricia E.; Jaffray, David A.

    2015-12-01

    Advances in precision microirradiators for small animal radiation oncology studies have provided the framework for novel translational radiobiological studies. Such systems target radiation fields at the scale required for small animal investigations, typically through a combination of on-board computed tomography image guidance and fixed, interchangeable collimators. Robust targeting accuracy of these radiation fields remains challenging, particularly at the millimetre scale field sizes achievable by the majority of microirradiators. Consistent and reproducible targeting accuracy is further hindered as collimators are removed and inserted during a typical experimental workflow. This investigation quantified this targeting uncertainty and developed an online method based on a virtual treatment isocenter to actively ensure high performance targeting accuracy for all radiation field sizes. The results indicated that the two-dimensional field placement uncertainty was as high as 1.16 mm at isocenter, with simulations suggesting this error could be reduced to 0.20 mm using the online correction method. End-to-end targeting analysis of a ball bearing target on radiochromic film sections showed an improved targeting accuracy with the three-dimensional vector targeting error across six different collimators reduced from 0.56+/- 0.05 mm (mean  ±  SD) to 0.05+/- 0.05 mm for an isotropic imaging voxel size of 0.1 mm.

  9. The PCSK9 Inhibitors: A Novel Therapeutic Target Enters Clinical Practice

    Science.gov (United States)

    Lepor, Norman E.; Kereiakes, Dean J.

    2015-01-01

    There is a critical need for alternative, potent agents that can reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with heterozygous familial hyperlipidemia and statin intolerance and those not reaching lipid-lowering treatment goals who are at high risk for cardiovascular (CV) events. The first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was approved in July 2015 by the US Food and Drug Administration as an adjunct to diet and maximally tolerated statin therapy for treatment of adults with heterozygous familial hyperlipidemia or clinical atherosclerotic CV disease, who require additional lowering of LDL-C levels. In clinical trials, PCSK9 inhibitors have been shown to reduce LDL-C levels by as much as 60% to 70% when administered as monotherapy or as an add-on treatment to statins and other lipid-lowering therapies. In studies of PCSK9 genetic mutations, loss of function in the PCSK9 allele was associated with a relative decrease of 88% in the risk for atherosclerotic CV events during 15 years of patient follow-up. The use of PCSK9 inhibitors may eventually support the LDL-C hypothesis that the lower the LDL-C level, the lower the CV risk. Although some recent clinical practice guidelines have deemphasized the importance of numeric LDL-C targets, many clinicians are reluctant to discard them, and this position is supported by recent clinical evidence. We eagerly await the results of the ODYSSEY, FOURIER, and SPIRE clinical outcome trials, which we anticipate will provide further validation that “lower is better” with respect to reducing LDL-C levels and improving clinical outcomes. PMID:26834934

  10. 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. PMID:26689598

  11. Effects of localized auditory information on visual target detection performance using a helmet-mounted display.

    Science.gov (United States)

    Nelson, W T; Hettinger, L J; Cunningham, J A; Brickman, B J; Haas, M W; McKinley, R L

    1998-09-01

    An experiment was conducted to evaluate the effects of localized auditory information on visual target detection performance. Visual targets were presented on either a wide field-of-view dome display or a helmet-mounted display and were accompanied by either localized, nonlocalized, or no auditory information. The addition of localized auditory information resulted in significant increases in target detection performance and significant reductions in workload ratings as compared with conditions in which auditory information was either nonlocalized or absent. Qualitative and quantitative analyses of participants' head motions revealed that the addition of localized auditory information resulted in extremely efficient and consistent search strategies. Implications for the development and design of multisensory virtual environments are discussed. Actual or potential applications of this research include the use of spatial auditory displays to augment visual information presented in helmet-mounted displays, thereby leading to increases in performance efficiency, reductions in physical and mental workload, and enhanced spatial awareness of objects in the environment.

  12. targetDP: an Abstraction of Lattice Based Parallelism with Portable Performance

    CERN Document Server

    Gray, Alan

    2014-01-01

    To achieve high performance on modern computers, it is vital to map algorithmic parallelism to that inherent in the hardware. From an application developer's perspective, it is also important that code can be maintained in a portable manner across a range of hardware. Here we present targetDP, a lightweight programming layer that allows the abstraction of data parallelism for applications that employ structured grids. A single source code may be used to target both thread level parallelism (TLP) and instruction level parallelism (ILP) on either SIMD multi-core CPUs or GPU-accelerated platforms. targetDP is implemented via standard C preprocessor macros and library functions, can be added to existing applications incrementally, and can be combined with higher-level paradigms such as MPI. We present CPU and GPU performance results for a benchmark taken from the lattice Boltzmann application that motivated this work. These demonstrate not only performance portability, but also the improved optimisation resulting...

  13. Quantitative performance targets by using balanced scorecard system: application to waste management and public administration.

    Science.gov (United States)

    Mendes, Paula; Nunes, Luis Miguel; Teixeira, Margarida Ribau

    2014-09-01

    This article demonstrates how decision-makers can be guided in the process of defining performance target values in the balanced scorecard system. We apply a method based on sensitivity analysis with Monte Carlo simulation to the municipal solid waste management system in Loulé Municipality (Portugal). The method includes two steps: sensitivity analysis of performance indicators to identify those performance indicators with the highest impact on the balanced scorecard model outcomes; and sensitivity analysis of the target values for the previously identified performance indicators. Sensitivity analysis shows that four strategic objectives (IPP1: Comply with the national waste strategy; IPP4: Reduce nonrenewable resources and greenhouse gases; IPP5: Optimize the life-cycle of waste; and FP1: Meet and optimize the budget) alone contribute 99.7% of the variability in overall balanced scorecard value. Thus, these strategic objectives had a much stronger impact on the estimated balanced scorecard outcome than did others, with the IPP1 and the IPP4 accounting for over 55% and 22% of the variance in overall balanced scorecard value, respectively. The remaining performance indicators contribute only marginally. In addition, a change in the value of a single indicator's target value made the overall balanced scorecard value change by as much as 18%. This may lead to involuntarily biased decisions by organizations regarding performance target-setting, if not prevented with the help of methods such as that proposed and applied in this study. PMID:25023987

  14. Quantitative performance targets by using balanced scorecard system: application to waste management and public administration.

    Science.gov (United States)

    Mendes, Paula; Nunes, Luis Miguel; Teixeira, Margarida Ribau

    2014-09-01

    This article demonstrates how decision-makers can be guided in the process of defining performance target values in the balanced scorecard system. We apply a method based on sensitivity analysis with Monte Carlo simulation to the municipal solid waste management system in Loulé Municipality (Portugal). The method includes two steps: sensitivity analysis of performance indicators to identify those performance indicators with the highest impact on the balanced scorecard model outcomes; and sensitivity analysis of the target values for the previously identified performance indicators. Sensitivity analysis shows that four strategic objectives (IPP1: Comply with the national waste strategy; IPP4: Reduce nonrenewable resources and greenhouse gases; IPP5: Optimize the life-cycle of waste; and FP1: Meet and optimize the budget) alone contribute 99.7% of the variability in overall balanced scorecard value. Thus, these strategic objectives had a much stronger impact on the estimated balanced scorecard outcome than did others, with the IPP1 and the IPP4 accounting for over 55% and 22% of the variance in overall balanced scorecard value, respectively. The remaining performance indicators contribute only marginally. In addition, a change in the value of a single indicator's target value made the overall balanced scorecard value change by as much as 18%. This may lead to involuntarily biased decisions by organizations regarding performance target-setting, if not prevented with the help of methods such as that proposed and applied in this study.

  15. Quiet eye training: the acquisition, refinement and resilient performance of targeting skills.

    Science.gov (United States)

    Vine, Samuel J; Moore, Lee J; Wilson, Mark R

    2014-01-01

    How we learn and refine motor skills in the most effective manner and how we prevent performance breakdown in pressurised or demanding circumstances are among the most important questions within the sport psychology and skill acquisition literature. The quiet eye (QE) has emerged as a characteristic of highly skilled perceptual and motor performance in visually guided motor tasks. Defined as the final fixation that occurs prior to a critical movement, over 70 articles have been published in the last 15 years probing the role that the QE plays in underpinning skilled performance. The aim of this review is to integrate research findings from studies examining the QE as a measure of visuomotor control in the specific domain of targeting skills; motor skills requiring an object to be propelled to a distant target. Previous reviews have focused primarily on the differences in QE between highly skilled performers and their less skilled counterparts. The current review aims to discuss contemporary findings relating to 1. The benefits of QE training for the acquisition and refinement of targeting skills; 2. The effects of anxiety upon the QE and subsequent targeting skill performance and 3. The benefits of QE training in supporting resilient performance under elevated anxiety. Finally, potential processes through which QE training proffers this advantage, including improved attentional control, response programming and external focus, will be discussed and directions for future research proposed.

  16. A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial

    Science.gov (United States)

    Goldfien, Robert; Pressman, Alice; Jacobson, Alice; Ng, Michele; Avins, Andrew

    2016-01-01

    Context: Relatively few patients with gout receive appropriate treatment. Objective: To determine whether a pharmacist-staffed gout management program is more effective than usual care in achieving target serum uric acid (sUA) levels in gout patients. Design: A parallel-group, randomized controlled trial of a pharmacist-staffed, telephone-based program for managing hyperuricemia vs usual care. Trial duration was 26 weeks. Main Outcome Measures: Primary outcome measure was achieving sUA levels at or below 6 mg/dL at the 26-week visit. Secondary outcome was mean change in sUA levels in the control and intervention groups. Participants were adults with recurrent gout and sUA levels above 6.0 mg/dL. Participants were randomly assigned to management by a clinical pharmacist following protocol or to monitoring of sUA levels but management of their gout by their usual treating physician. Results: Of 102 patients who met eligibility criteria, 77 subjects obtained a baseline sUA measurement and were entered into the trial. Among 37 participants in the intervention group, 13 (35%) had sUA levels at or below 6.0 mg/dL at 26 weeks, compared with 5 (13%) of 40 participants in the control group (risk ratio = 2.8, 95% confidence interval [CI] = 1.1 to 7.1, p = 0.03). The mean change in sUA levels among controls was +0.1 mg/dL compared with −1.5 mg/dL in the intervention group (sUA difference = −1.6, 95% CI = −0.9 to −2.4, p pharmacist-staffed program was more effective than usual care for achieving target sUA levels. These results suggest a structured program could greatly improve gout management. PMID:27352414

  17. Molecular profiling of patients with colorectal cancer and matched targeted therapy in phase I clinical trials.

    Science.gov (United States)

    Dienstmann, Rodrigo; Serpico, Danila; Rodon, Jordi; Saura, Cristina; Macarulla, Teresa; Elez, Elena; Alsina, Maria; Capdevila, Jaume; Perez-Garcia, Jose; Sánchez-Ollé, Gessamí; Aura, Claudia; Prudkin, Ludmila; Landolfi, Stefania; Hernández-Losa, Javier; Vivancos, Ana; Tabernero, Josep

    2012-09-01

    Clinical experience increasingly suggests that molecular prescreening and biomarker enrichment strategies in phase I trials with targeted therapies will improve the outcomes of patients with cancer. In keeping with the exigencies of a personalized oncology program, tumors from patients with advanced chemorefractory colorectal cancer were analyzed for specific aberrations (KRAS/BRAF/PIK3CA mutations, PTEN and pMET expression). Patients were subsequently offered phase I trials with matched targeted agents (MTA) directed at the identified anomalies. During 2010 and 2011, tumor molecular analysis was conducted in 254 patients: KRAS mutations (80 of 254, 31.5%), BRAF mutations (24 of 196, 12.2%), PIK3CA mutations (15 of 114, 13.2%), KRAS and PIK3CA mutations (9 of 114, 7.9%), low PTEN expression (97 of 183, 53.0%), and high pMET expression (38 of 64, 59.4%). In total, 68 patients received 82 different MTAs: phosphoinositide 3-kinase (PI3K) pathway inhibitor (if PIK3CA mutation, n = 10; or low PTEN, n = 32), PI3K pathway inhibitor plus MEK inhibitor (if KRAS mutation, n = 10; or BRAF mutation, n = 1), second-generation anti-EGF receptor monoclonal antibodies (if wild-type KRAS, n = 11), anti-hepatocyte growth factor monoclonal antibody (if high pMET, n = 10), mTOR inhibitor plus anti-insulin-like growth factor-1 receptor monoclonal antibody (if low PTEN, n = 5), and BRAF inhibitor (if BRAF mutation, n = 3). Median time-to-treatment failure on MTA was 7.9 versus 16.3 weeks for their prior systemic antitumor therapy (P 16 weeks in 10 cases (12.2%). These results suggest that matching chemorefractory patients with colorectal cancer with targeted agents in phase I trials based on the current molecular profile does not confer a significant clinical benefit.

  18. Importance/performance analysis: a tool for service quality control by clinical laboratories.

    Science.gov (United States)

    Scammon, D L; Weiss, R

    1991-01-01

    A study of customer satisfaction with clinical laboratory service is used as the basis for identifying potential improvements in service and more effectively targeting marketing activities to enhance customer satisfaction. Data on customer satisfaction are used to determine the aspects of service most critical to customers, how well the organization is doing in delivery of service, and how consistent service delivery is. Importance-performance analysis is used to highlight areas for future resource reallocation and strategic emphasis. Suggestions include the establishment of performance guidelines for customer contact personnel, the enhancement of timely delivery of reports via electronic transmission (computer and fax), and the development of standardized graphics for request and report forms to facilitate identification of appropriate request forms and guide clients to key items of information on reports.

  19. Survey and Rapid detection of Bordetella pertussis in clinical samples targeting the BP485 in China

    Directory of Open Access Journals (Sweden)

    Wei eLiu

    2015-03-01

    Full Text Available Bordetella pertussis is an important human respiratory pathogen. Here, we describe a loop-mediated isothermal amplification (LAMP method for the rapid detection of B. pertussis in clinical samples based on a visual test. The LAMP assay detected the BP485 target sequence within 60 min with a detection limit of 1.3 pg/µl, a 10-fold increase in sensitivity compared with conventional PCR. All 31 non-pertussis respiratory pathogens tested were negative for LAMP detection, indicating the high specificity of the primers for B. pertussis. To evaluate the application of the LAMP assay to clinical diagnosis, of 105 sputum and nasopharyngeal samples collected from the patients with suspected respiratory infections in China, a total of 12 Bordetella pertussis isolates were identified from 33 positive samples detected by LAMP-based surveillance targeting BP485. Strikingly, a 4.5 months old baby and her mother were found to be infected with B. pertussis at the same time. All isolates belonged to different B. pertussis multilocus sequence typing (MLST groups with different alleles of the virulence-related genes including 4 alleles of ptxA, 6 of prn, 4 of tcfA, 2 of fim2 and 3 of fim3. The diversity of B. pertussis carrying toxin genes in clinical strains indicates a rapid and continuing evolution of B. pertussis. This combined with its high prevalence will make it difficult to control. In conclusion, we have developed a visual detection LAMP assay, which could be a useful tool for rapid B. pertussis detection, especially in situations where resources are poor and in point-of-care tests.

  20. Target detection performance in helmet-mounted and conventional dome displays.

    Science.gov (United States)

    Hettinger, L J; Nelson, W T; Haas, M W

    1996-01-01

    An experiment was conducted to assess visual target detection performance using a helmet-mounted display (HMD) and a conventional flight simulation dome display. Measures of workload and mood were also obtained. Participants in both viewing conditions scanned an area 120 degrees vertical by 240 degrees horizontal while attempting to locate targets that appeared to be approaching them from one of a possible 18 locations. Results indicated significantly superior performance in the conventional dome display. Workload and mood measures also showed a significant advantage for the dome display. Results are discussed in terms of their implications for the design and use of HMD systems as components of airborne virtual environment interfaces.

  1. The effect of target and non-target similarity on neural classification performance: a boost from confidence

    OpenAIRE

    Marathe, Amar R.; Ries, Anthony J.; Vernon J Lawhern; Lance, Brent J.; Touryan, Jonathan; McDowell, Kaleb; Cecotti, Hubert

    2015-01-01

    Brain computer interaction (BCI) technologies have proven effective in utilizing single-trial classification algorithms to detect target images in rapid serial visualization presentation tasks. While many factors contribute to the accuracy of these algorithms, a critical aspect that is often overlooked concerns the feature similarity between target and non-target images. In most real-world environments there are likely to be many shared features between targets and non-targets resulting in si...

  2. Physician judgment in clinical settings: methodological influences and cognitive performance.

    Science.gov (United States)

    Dawson, N V

    1993-07-01

    Understanding the quality of physicians' intuitive judgments is essential in determining the appropriate use of their judgments in medical decision-making (vis-a-vis analytical or actuarial approaches). As part of this process, the quality of physicians' predictions must be assessed because prediction is fundamental to common clinical tasks: determining diagnosis, prognosis, and therapy; establishing monitoring intervals; performing screening and preventive maneuvers. Critical evaluation of predictive capabilities requires an assessment of the components of the prediction process: the data available for prediction, the method used for prediction, and the accuracy of prediction. Although variation in and uncertainty about the underlying data elements are often acknowledged as a source of inaccurate predictions, prediction also can be confounded by both methodological and cognitive limitations. During the past two decades, numerous factors have been recognized that may bias test characteristics (sensitivity and specificity). These same factors may also produce bias in intuitive judgments. The use of cognitive processes to simplify judgment tasks (e.g., the availability and representativeness heuristics) and the presence of certain biases in the judgment process (e.g., ego, regret) may present obstacles to accurate estimation of probabilities by physicians. Limitations on the intuitive use of information (cognitive biases) have been demonstrated in both medical and nonmedical decision-making settings. Recent studies have led to a deepening understanding of the advantages and disadvantages of intuitive and analytical approaches to decision making. Here, many aspects of the basis for this understanding are reviewed.

  3. Experimental investigation of penetration performance of shaped charge into concrete targets

    Institute of Scientific and Technical Information of China (English)

    Cheng Wang; Tianbao Ma; Jianguo Ning

    2008-01-01

    In order to develop a tandem warhead that can effectively destroy concrete targets, this paper explores the penetration performance of shaped charges with different cone angles and liner materials into concrete targets by means of experiments. The penetration process and the destruction mechanism of concrete targets by shaped charges and kinetic energy projectiles are analyzed and compared. Experimental results suggest that both kinetic energetic projectile and shaped charge are capable of destroying concrete targets, but the magnitudes of damage are different. Compared with a kinetic energy projectile, a shaped charge has more significant effect of penetration into the target, and causes very large spalling area. Hence, a shaped charge is quite suitable for first-stage charge of tandem warhead. It is also found that, with the increase of shaped charge liner cone angle, the depth of penetration decreases gradually while the hole diameter becomes larger. Penetration depth with copper liner is larger than of aluminum liner but hole diameter is relatively smaller, and the shaped charge with steel liner is between the above two cases. The shaped charge with a cone angle of 100° can form a jet projectile charge (JPC). With JPC, a hole with optimum depth and diameter on concrete targets can be formed, which guarantees that the second-stage warhead smoothly penetrates into the hole and explodes at the optimum depth to achieve the desired level of destruction in concrete targets.

  4. Experimental investigation of penetration performance of shaped charge into concrete targets

    Science.gov (United States)

    Wang, Cheng; Ma, Tianbao; Ning, Jianguo

    2008-06-01

    In order to develop a tandem warhead that can effectively destroy concrete targets, this paper explores the penetration performance of shaped charges with different cone angles and liner materials into concrete targets by means of experiments. The penetration process and the destruction mechanism of concrete targets by shaped charges and kinetic energy projectiles are analyzed and compared. Experimental results suggest that both kinetic energetic projectile and shaped charge are capable of destroying concrete targets, but the magnitudes of damage are different. Compared with a kinetic energy projectile, a shaped charge has more significant effect of penetration into the target, and causes very large spalling area. Hence, a shaped charge is quite suitable for first-stage charge of tandem warhead. It is also found that, with the increase of shaped charge liner cone angle, the depth of penetration decreases gradually while the hole diameter becomes larger. Penetration depth with copper liner is larger than of aluminum liner but hole diameter is relatively smaller, and the shaped charge with steel liner is between the above two cases. The shaped charge with a cone angle of 100° can form a jet projectile charge (JPC). With JPC, a hole with optimum depth and diameter on concrete targets can be formed, which guarantees that the second-stage warhead smoothly penetrates into the hole and explodes at the optimum depth to achieve the desired level of destruction in concrete targets.

  5. Analytical performance specifications: relating laboratory performance to quality required for intended clinical use.

    Science.gov (United States)

    Dalenberg, Daniel A; Schryver, Patricia G; Klee, George G

    2013-03-01

    This article proposes analytic performance goals for five quality indicators: precision, trueness, linearity, detection limits, and consistency across instruments and time. We defined our goals using methods linked to clinical practice data. Goals for desirable precision and trueness are based on biological variation. Linearity goals are related to total error recommendations. Detection limit goals are derived from 0.1 percentile of patient values. Goals for consistency are derived from the variability of distributions of patient test values. Data were collected and evaluated for each of these quality indicators for 46 chemistry tests measured on the Roche cobas 8000 analyzer.

  6. Research on target information optics communications transmission characteristic and performance in multi-screens testing system

    Science.gov (United States)

    Li, Hanshan

    2016-04-01

    To enhance the stability and reliability of multi-screens testing system, this paper studies multi-screens target optical information transmission link properties and performance in long-distance, sets up the discrete multi-tone modulation transmission model based on geometric model of laser multi-screens testing system and visible light information communication principle; analyzes the electro-optic and photoelectric conversion function of sender and receiver in target optical information communication system; researches target information transmission performance and transfer function of the generalized visible-light communication channel; found optical information communication transmission link light intensity space distribution model and distribution function; derives the SNR model of information transmission communication system. Through the calculation and experiment analysis, the results show that the transmission error rate increases with the increment of transmission rate in a certain channel modulation depth; when selecting the appropriate transmission rate, the bit error rate reach 0.01.

  7. Sustained Attention to Local and Global Target Features Is Different: Performance and Tympanic Membrane Temperature

    Science.gov (United States)

    Helton, William S.; Hayrynen, Lauren; Schaeffer, David

    2009-01-01

    Vision researchers have investigated the differences between global and local feature perception. No one has, however, examined the role of global and local feature discrimination in sustained attention tasks. In this experiment participants performed a sustained attention task requiring either global or local letter target discriminations or…

  8. Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy.

    Science.gov (United States)

    Morera, Ludovica; Lübbert, Michael; Jung, Manfred

    2016-01-01

    The term epigenetics is defined as heritable changes in gene expression that are not due to alterations of the DNA sequence. In the last years, it has become more and more evident that dysregulated epigenetic regulatory processes have a central role in cancer onset and progression. In contrast to DNA mutations, epigenetic modifications are reversible and, hence, suitable for pharmacological interventions. Reversible histone methylation is an important process within epigenetic regulation, and the investigation of its role in cancer has led to the identification of lysine methyltransferases and demethylases as promising targets for new anticancer drugs. In this review, we describe those enzymes and their inhibitors that have already reached the first stages of clinical trials in cancer therapy, namely the histone methyltransferases DOT1L and EZH2 as well as the demethylase LSD1. PMID:27222667

  9. SGLT 2 Inhibitors: A New Therapeutic Target And Its Role In Current Clinical Practice

    Directory of Open Access Journals (Sweden)

    PV Shiji

    2015-10-01

    Full Text Available Diabetes, one of the major life style diseases, is associated with high morbidity and mortality owing to its microvascular and macrovascular complications. The chance of development of various complications can be effectively prevented by tight glycemic control. We have various groups of drugs like Biguanides, Sulfonyl ureas, Glitazones, Alpha-glucosidase inhibitors, Incretin based therapy, Insulin and Insulin analogues in the armamentarium to treat diabetes. But still, the number of patients attaining glycemic targets are relatively low and various adverse effect limit the use of some of these drugs, especially in special groups. Hence there is ongoing research to develop newer and newer drugs which provide sustained blood glucose reduction with minimal adverse effects. SGLT-2 inhibitors are a new group of drugs recently approved by FDA to treat Diabetes. In this review we discuss about mechanism of action, various adverse effects and the clinical role of various SGLT-2 Inhibitors.

  10. Developing Performance Cost Index Targets for ASHRAE Standard 90.1 Appendix G – Performance Rating Method - Rev.1

    Energy Technology Data Exchange (ETDEWEB)

    Rosenberg, Michael I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hart, Philip R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-03-01

    Appendix G, the Performance Rating Method in ASHRAE Standard 90.1 has been updated to make two significant changes for the 2016 edition, to be published in October of 2016. First, it allows Appendix G to be used as a third path for compliance with the standard in addition to rating beyond code building performance. This prevents modelers from having to develop separate building models for code compliance and beyond code programs. Using this new version of Appendix G to show compliance with the 2016 edition of the standard, the proposed building design needs to have a performance cost index (PCI) less than targets shown in a new table based on building type and climate zone. The second change is that the baseline design is now fixed at a stable level of performance set approximately equal to the 2004 code. Rather than changing the stringency of the baseline with each subsequent edition of the standard, compliance with new editions will simply require a reduced PCI (a PCI of zero is a net-zero building). Using this approach, buildings of any era can be rated using the same method. The intent is that any building energy code or beyond code program can use this methodology and merely set the appropriate PCI target for their needs. This report discusses the process used to set performance criteria for compliance with ASHRAE Standard 90.1-2016 and suggests a method for demonstrating compliance with other codes and beyond code programs.

  11. Developing Performance Cost Index Targets for ASHRAE Standard 90.1 Appendix G – Performance Rating Method

    Energy Technology Data Exchange (ETDEWEB)

    Rosenberg, Michael I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hart, Philip R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-02-16

    Appendix G, the Performance Rating Method in ASHRAE Standard 90.1 has been updated to make two significant changes for the 2016 edition, to be published in October of 2016. First, it allows Appendix G to be used as a third path for compliance with the standard in addition to rating beyond code building performance. This prevents modelers from having to develop separate building models for code compliance and beyond code programs. Using this new version of Appendix G to show compliance with the 2016 edition of the standard, the proposed building design needs to have a performance cost index (PCI) less than targets shown in a new table based on building type and climate zone. The second change is that the baseline design is now fixed at a stable level of performance set approximately equal to the 2004 code. Rather than changing the stringency of the baseline with each subsequent edition of the standard, compliance with new editions will simply require a reduced PCI (a PCI of zero is a net-zero building). Using this approach, buildings of any era can be rated using the same method. The intent is that any building energy code or beyond code program can use this methodology and merely set the appropriate PCI target for their needs. This report discusses the process used to set performance criteria for compliance with ASHRAE Standard 90.1-2016 and suggests a method for demonstrating compliance with other codes and beyond code programs.

  12. Radial displacement of clinical target volume in node negative head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Wan; Wu, Hong Gyun; Song, Sang Hyuk; Kim, Jung In [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    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.

  13. PI3K and Akt as molecular targets for cancer therapy: current clinical outcomes

    Institute of Scientific and Technical Information of China (English)

    Ipsita PAL; Mahitosh MANDAL

    2012-01-01

    The PI3K-Akt pathway is a vital regulator of cell proliferation and survival.Alterations in the PIK3CA gene that lead to enhanced PI3K kinase activity have been reported in many human cancer types,including cancers of the colon,breast,brain,liver,stomach and lung.Deregulation of PI3K causes aberrant Akt activity.Therefore targeting this pathway could have implications for cancer treatment.The first generation PI3K-Akt inhibitors were proven to be highly effective with a low IC50,but later,they were shown to have toxic side effects and poor pharmacological properties and selectivity.Thus,these inhibitors were only effective in preclinical models.However,derivatives of these first generation inhibitors are much more selective and are quite effective in targeting the PI3K-Akt pathway,either alone or in combination.These second-generation inhibitors are essentially a specific chemical moiety that helps to form a strong hydrogen bond interaction with the PI3K/Akt molecule.The goal of this review is to delineate the current efforts that have been undertaken to inhibit the various components of the PI3K and Akt pathway in different types of cancer both in vitro and in vivo.Our focus here is on these novel therapies and their inhibitory effects that depend upon their chemical nature,as well as their development towards clinical trials.

  14. Optimal marker-strategy clinical trial design to detect predictive markers for targeted therapy.

    Science.gov (United States)

    Zang, Yong; Liu, Suyu; Yuan, Ying

    2016-07-01

    In developing targeted therapy, the marker-strategy design (MSD) provides an important approach to evaluate the predictive marker effect. This design first randomizes patients into non-marker-based or marker-based strategies. Patients allocated to the non-marker-based strategy are then further randomized to receive either the standard or targeted treatments, while patients allocated to the marker-based strategy receive treatments based on their marker statuses. Little research has been done on the statistical properties of the MSD, which has led to some widespread misconceptions and placed clinical researchers at high risk of using inefficient designs. In this article, we show that the commonly used between-strategy comparison has low power to detect the predictive effect and is valid only under a restrictive condition that the randomization ratio within the non-marker-based strategy matches the marker prevalence. We propose a Wald test that is generally valid and also uniformly more powerful than the between-strategy comparison. Based on that, we derive an optimal MSD that maximizes the power to detect the predictive marker effect by choosing the optimal randomization ratios between the two strategies and treatments. Our numerical study shows that using the proposed optimal designs can substantially improve the power of the MSD to detect the predictive marker effect. We use a lung cancer trial to illustrate the proposed optimal designs.

  15. 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.

  16. Performance of resonant radar target identification algorithms using intra-class weighting functions

    Science.gov (United States)

    Mustafa, A.

    The use of calibrated resonant-region radar cross section (RCS) measurements of targets for the classification of large aircraft is discussed. Errors in the RCS estimate of full scale aircraft flying over an ocean, introduced by the ionospheric variability and the sea conditions were studied. The Weighted Target Representative (WTR) classification algorithm was developed, implemented, tested and compared with the nearest neighbor (NN) algorithm. The WTR-algorithm has a low sensitivity to the uncertainty in the aspect angle of the unknown target returns. In addition, this algorithm was based on the development of a new catalog of representative data which reduces the storage requirements and increases the computational efficiency of the classification system compared to the NN-algorithm. Experiments were designed to study and evaluate the characteristics of the WTR- and the NN-algorithms, investigate the classifiability of targets and study the relative behavior of the number of misclassifications as a function of the target backscatter features. The classification results and statistics were shown in the form of performance curves, performance tables and confusion tables.

  17. Cool-down performance of the new apparatus for fuel layering demonstrations of FIREX targets

    Science.gov (United States)

    Iwamoto, A.; Norimatsu, T.; Nakai, M.; Sakagami, H.; Shiraga, H.; Azechi, H.

    2016-03-01

    FIREX targets have been developed under two layering strategies: foam shell and cone guide laser heating methods. Basic studies have been conducted by the collaboration research between ILE and NIFS. Then the next stage requires the characterization of a layered solid fuel. The present system is at the disadvantage of optical observations. Therefore, a new apparatus is designed to solve it. Glass windows with a wide aperture are installed for an interferometer and a microscope. To isolate the vibration from a cryocooler, active vibration control units are equipped, and flexible thermal conductive links are utilized. Furthermore, a quick target exchange mechanism is applied to deal with different types of FIREX targets. A target holder is detachable from a main vacuum chamber. A metal gasket with not fixing bolts but a load of ∼ thousand newtons on ensures GHe leak tightness for target cooling. Eventually, the design temperature of 10.00 K at a target container has been achieved. The cool-down performance indecates that the new apparatus provides a cryogenic environment for fuel layering demonstrations.

  18. Non-target adjacent stimuli classification improves performance of classical ERP-based brain computer interface

    Science.gov (United States)

    Ceballos, G. A.; Hernández, L. F.

    2015-04-01

    Objective. The classical ERP-based speller, or P300 Speller, is one of the most commonly used paradigms in the field of Brain Computer Interfaces (BCI). Several alterations to the visual stimuli presentation system have been developed to avoid unfavorable effects elicited by adjacent stimuli. However, there has been little, if any, regard to useful information contained in responses to adjacent stimuli about spatial location of target symbols. This paper aims to demonstrate that combining the classification of non-target adjacent stimuli with standard classification (target versus non-target) significantly improves classical ERP-based speller efficiency. Approach. Four SWLDA classifiers were trained and combined with the standard classifier: the lower row, upper row, right column and left column classifiers. This new feature extraction procedure and the classification method were carried out on three open databases: the UAM P300 database (Universidad Autonoma Metropolitana, Mexico), BCI competition II (dataset IIb) and BCI competition III (dataset II). Main results. The inclusion of the classification of non-target adjacent stimuli improves target classification in the classical row/column paradigm. A gain in mean single trial classification of 9.6% and an overall improvement of 25% in simulated spelling speed was achieved. Significance. We have provided further evidence that the ERPs produced by adjacent stimuli present discriminable features, which could provide additional information about the spatial location of intended symbols. This work promotes the searching of information on the peripheral stimulation responses to improve the performance of emerging visual ERP-based spellers.

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

    Directory of Open Access Journals (Sweden)

    Yuval Duchin

    Full Text Available The advantages of ultra-high magnetic field (7 Tesla MRI for basic science research and neuroscience applications have proven invaluable. Structural and functional MR images of the human brain acquired at 7 T exhibit rich information content with potential utility for clinical applications. However, (1 substantial increases in susceptibility artifacts, and (2 geometrical distortions at 7 T would be detrimental for stereotactic surgeries such as deep brain stimulation (DBS, which typically use 1.5 T images for surgical planning. Here, we explore whether these issues can be addressed, making feasible the use of 7 T MRI to guide surgical planning. Twelve patients with Parkinson's disease, candidates for DBS, were scanned on a standard clinical 1.5 T MRI and a 7 T MRI scanner. Qualitative and quantitative assessments of global and regional distortion were evaluated based on anatomical landmarks and transformation matrix values. Our analyses show that distances between identical landmarks on 1.5 T vs. 7 T, in the mid-brain region, were less than one voxel, indicating a successful co-registration between the 1.5 T and 7 T images under these specific imaging parameter sets. On regional analysis, the central part of the brain showed minimal distortion, while inferior and frontal areas exhibited larger distortion due to proximity to air-filled cavities. We conclude that 7 T MR images of the central brain regions have comparable distortions to that observed on a 1.5 T MRI, and that clinical applications targeting structures such as the STN, are feasible with information-rich 7 T imaging.

  20. Performance of passive target tracking using bearing-frequency and bearings of multiple arrays

    Institute of Scientific and Technical Information of China (English)

    DU Xuanmin; YAO Lan

    2002-01-01

    Two target motion analysis (TMA) methods using multi-dimension information are studied, one is TMA with bearing-frequency and the other is TMA with multiple arrays. The optimization algorithm combining Gauss-Newton (G-N) method with Levenberg-Marquardt(LM) method is applied to analyze the performance of target tracking with maximum likelihood estimation(MLE), and Monte Carlo experiments are presented. The results show that although the TMA with multi-dimension information have eliminated the maneuvers needed by conventional bearing-only TMA, but the application are not of universality.

  1. Comparison of monostatic and bistatic bearing estimation performance for low RCS targets

    Science.gov (United States)

    Boyle, Robert J.; Wasylkiwskyj, Wasyl

    1994-07-01

    Bistatic radars, specifically forward-scatter radars, are proposed as an alternative to standard monostatic radars against targets whose radar cross sections (RCS) have been reduced by passive means. Forward-scatter radars operate by detecting echoes from a targets forward-scatter RCS, which is insensitive to effects of passive RCS reduction techniques. However, the performance of the forward-scatter radar is compromised when the angular separation between the interference, which propagates directly from the transmitter to the receiver, and the target return is less than the Rayleigh resolution limit of the receiving antenna. This research presents the results of a parametric study of the ability of a forward-scatter radar to detect and measure the bearing of a large target, whose RCS is reduced via passive means. Super-resolution array processing techniques, particularly root-MUSIC (multiple signal classification), are used to overcome the traditional limitations resulting from the Rayleigh resolution limit of the antenna. The study compares the received power and the bearing measurement accuracy of the forward-scatter radar to that of an 'equivalent' monostatic radar system. The results indicate that forward-scatter radars enjoy advantages in detection and bearing measurement when the backscatter RCS of the target has been reduced and when the target is close to the baseline. The results also indicate that, through the use of super-resolution array processing, the capability of the forward-scatter radar to accurately measure the bearing of the target is dependent upon the amount of interference from the direct wave (i.e., the wave which propagates from the transmitter directly to the receiver) and the correlation between the direct wave and the target echo. Good bearing estimates can be achieved if the correlation coefficient is less than 0.95. Bearing measurements may be improved by suppressing the direct wave by either sidelobe control or null steering

  2. Target identification and navigation performance modeling of a passive millimeter wave imager.

    Science.gov (United States)

    Jacobs, Eddie L; Furxhi, Orges

    2010-07-01

    Human task performance using a passive interferometric millimeter wave imaging sensor is modeled using a task performance modeling approach developed by the U.S. Army Night Vision and Electronic Sensors Directorate. The techniques used are illustrated for an imaging system composed of an interferometric antenna array, optical upconversion, and image formation using a shortwave infrared focal plane array. Two tasks, target identification and pilotage, are modeled. The effects of sparse antenna arrays on task performance are considered. Applications of this model include system trade studies for concealed weapon identification, navigation in fog, and brownout conditions. PMID:20648126

  3. Application of 212Pb for Targeted α-particle Therapy (TAT: Pre-clinical and Mechanistic Understanding through to Clinical Translation

    Directory of Open Access Journals (Sweden)

    Kwon Yong

    2015-08-01

    Full Text Available Targeted α-particle therapy (TAT, in which an α-particle emitting radionuclide is specifically directed to a biological target, is gaining more attention to treat cancers as new targets are validated. Bio-vectors such as monoclonal antibodies are able to selectively transport α-particles to destroy targeted cancer cells. TAT has the potential for an improved therapeutic ratio over β-particle targeted conjugate therapy. The short path length and the intense ionization path generated render α-emitters suitable for treatment and management of minimal disease such as micrometastases or residual tumor after surgical debulking. 212Pb is the longer-lived parent radionuclide of 212Bi and serves as an in vivo generator of 212Bi. 212Pb has demonstrated significant utility in both in vitro and in vivo models. Recent evaluation of 212Pb-TCMC-trastuzumab in a Phase I clinical trial has demonstrated the feasibility of 212Pb in TAT for the treatment of ovarian cancer patients. This review highlights progress in radionuclide production, radiolabeling chemistry, molecular mechanisms, and application of 212Pb to targeted pre-clinical and clinical radiation therapy for the management and treatment of cancer.

  4. A method of calculating a lung clinical target volume DVH for IMRT with intrafractional motion.

    Science.gov (United States)

    Kung, J H; Zygmanski, P; Choi, N; Chen, G T Y

    2003-06-01

    The motion of lung tumors from respiration has been reported in the literature to be as large as 1-2 cm. This motion requires an additional margin between the Clinical Target Volume (CTV) and the Planning Target Volume (PTV). In Intensity Modulated Radiotherapy (IMRT), while such a margin is necessary, the margin may not be sufficient to avoid unintended high and low dose regions to the interior on moving CTV. Gated treatment has been proposed to improve normal tissues sparing as well as to ensure accurate dose coverage of the tumor volume. The following questions have not been addressed in the literature: (a) what is the dose error to a target volume without a gated IMRT treatment? (b) What is an acceptable gating window for such a treatment. In this study, we address these questions by proposing a novel technique for calculating the three-dimensional (3-D) dose error that would result if a lung IMRT plan were delivered without a gated linac beam. The method is also generalized for gated treatment with an arbitrary triggering window. IMRT plans for three patients with lung tumors were studied. The treatment plans were generated with HELIOS for delivery with 6 MV on a CL2100 Varian linear accelerator with a 26 pair MLC. A CTV to PTV margin of 1 cm was used. An IMRT planning system searches for an optimized fluence map phi(x,y) for each port, which is then converted into a dynamic MLC file (DMLC). The DMLC file contains information about MLC subfield shapes and the fractional Monitor Units (MUs) to be delivered for each subfield. With a lung tumor, a CTV that executes a quasiperiodic motion z(t) does not receive phi(x,y), but rather an Effective Incident Fluence EIF(x,y). We numerically evaluate the EIF(x,y) from a given DMLC file by a coordinate transformation to the Target's Eye View (TEV). In the TEV coordinate system, the CTV itself is stationary, and the MLC is seen to execute a motion -z(t) that is superimposed on the DMLC motion. The resulting EIF(x,y) is

  5. A method of calculating a lung clinical target volume DVH for IMRT with intrafractional motion

    International Nuclear Information System (INIS)

    The motion of lung tumors from respiration has been reported in the literature to be as large as 1-2 cm. This motion requires an additional margin between the Clinical Target Volume (CTV) and the Planning Target Volume (PTV). In Intensity Modulated Radiotherapy (IMRT), while such a margin is necessary, the margin may not be sufficient to avoid unintended high and low dose regions to the interior on moving CTV. Gated treatment has been proposed to improve normal tissues sparing as well as to ensure accurate dose coverage of the tumor volume. The following questions have not been addressed in the literature: (a) what is the dose error to a target volume without a gated IMRT treatment? (b) What is an acceptable gating window for such a treatment. In this study, we address these questions by proposing a novel technique for calculating the three-dimensional (3-D) dose error that would result if a lung IMRT plan were delivered without a gated linac beam. The method is also generalized for gated treatment with an arbitrary triggering window. IMRT plans for three patients with lung tumors were studied. The treatment plans were generated with HELIOS for delivery with 6 MV on a CL2100 Varian linear accelerator with a 26 pair MLC. A CTV to PTV margin of 1 cm was used. An IMRT planning system searches for an optimized fluence map Φ(x,y) for each port, which is then converted into a dynamic MLC file (DMLC). The DMLC file contains information about MLC subfield shapes and the fractional Monitor Units (MUs) to be delivered for each subfield. With a lung tumor, a CTV that executes a quasiperiodic motion z(t) does not receive Φ(x,y), but rather an Effective Incident Fluence EIF(x,y). We numerically evaluate the EIF(x,y) from a given DMLC file by a coordinate transformation to the Target's Eye View (TEV). In the TEV coordinate system, the CTV itself is stationary, and the MLC is seen to execute a motion -z(t) that is superimposed on the DMLC motion. The resulting EIF(x,y) is input

  6. 42 CFR 493.1453 - Condition: Laboratories performing high complexity testing; clinical consultant.

    Science.gov (United States)

    2010-10-01

    ... Condition: Laboratories performing high complexity testing; clinical consultant. The laboratory must have a... testing; clinical consultant. 493.1453 Section 493.1453 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION...

  7. Technology transfer from biomedical research to clinical practice: measuring innovation performance.

    Science.gov (United States)

    Balas, E Andrew; Elkin, Peter L

    2013-12-01

    Studies documented 17 years of transfer time from clinical trials to practice of care. Launched in 2002, the National Institutes of Health (NIH) translational research initiative needs to develop metrics for impact assessment. A recent White House report highlighted that research and development productivity is declining as a result of increased research spending while the new drugs output is flat. The goal of this study was to develop an expanded model of research-based innovation and performance thresholds of transfer from research to practice. Models for transfer of research to practice have been collected and reviewed. Subsequently, innovation pathways have been specified based on common characteristics. An integrated, intellectual property transfer model is described. The central but often disregarded role of research innovation disclosure is highlighted. Measures of research transfer and milestones of progress have been identified based on the Association of University Technology Managers 2012 performance reports. Numeric milestones of technology transfer are recommended at threshold (top 50%), target (top 25%), and stretch goal (top 10%) performance levels. Transfer measures and corresponding target levels include research spending to disclosure (0.81), patents to start-up (>0.1), patents to licenses (>2.25), and average per license income (>$48,000). Several limitations of measurement are described. Academic institutions should take strategic steps to bring innovation to the center of scholarly discussions. Research on research, particularly on pathways to disclosures, is needed to improve R&D productivity. Researchers should be informed about the technology transfer performance of their institution and regulations should better support innovators.

  8. Performance Analysis of a Noncontact Plastic Fiber Optical Fiber Displacement Sensor with Compensation of Target Reflectivity

    Directory of Open Access Journals (Sweden)

    Daniele Tosi

    2013-01-01

    Full Text Available An inexpensive fiber-based noncontact distance sensor specific for monitoring short-range displacements in micromachining applications is presented. To keep the overall costs low, the sensor uses plastic optical fibers and an intensiometric approach based on the received light intensity after the reflection from the target whose displacement has to be measured. A suitable target reflectivity compensation technique is implemented to mitigate the effects due to target surface nonuniformity or ageing. The performances of the sensor are first evaluated for different fiber configurations and target reflectivity profiles and positions using a numerical method based on Monte Carlo simulations. Then, experimental validations on a configuration designed to work up to 1.5 mm have been conducted. The results have confirmed the validity of the proposed sensor architecture, which demonstrated excellent compensation capabilities, with errors below 0.04 mm in the (0-1 mm range regardless the color and misalignment of the target.

  9. A clinically attainable dose of L-asparaginase targets glutamine addiction in lymphoid cell lines.

    Science.gov (United States)

    Sugimoto, Koichi; Suzuki, Hiroshi I; Fujimura, Tsutomu; Ono, Asami; Kaga, Naoko; Isobe, Yasushi; Sasaki, Makoto; Taka, Hikari; Miyazono, Kohei; Komatsu, Norio

    2015-11-01

    L-asparaginase (L-ASNase) is an important branch of chemotherapy for acute lymphoblastic leukemia (ALL) and some types of non-Hodgkin's lymphoma, including natural killer (NK)-cell lymphoma. Although it mediates hydrolysis of asparagine (Asn) and glutamine (Gln), which are variably required for cancer cell survival, the relative contribution of Asn and Gln depletion to the anti-tumor activity in therapeutic doses is unclear in ALL and malignant lymphoma. Here we demonstrate that L-ASNase exerts cytotoxicity through targeting the Gln addiction phenotype in lymphoid cell lines. A clinically attainable intermediate dose of L-ASNase induced massive apoptosis in ALL Jurkat and mantle cell lymphoma Jeko cell lines, while a low dose of L-ASNase effectively killed NK-cell lymphoma cells. In the lymphoid cell lines Jurkat and Jeco, deprivation of Gln but not Asn specifically suppressed cell growth and survival, and phenocopied the action of L-ASNase. L-ASNase treatment and Gln deprivation dramatically disrupted the refilling of the tricarboxylic acid (TCA) cycle by intracellular glutamate (Glu) and disturbed the mitochondrial integrity, which were alleviated by various anaplerotic TCA cycle intermediates, suggesting a direct contribution of glutaminase activity of L-ASNase. The action of L-ASNase differs between Jurkat cells and NK-cell lymphoma cells, according to their dependence on Gln and Asn. Furthermore, we observed that high expression of glutaminase GLS1 is associated with increased sensivity to L-ASNase in pediatric B lineage ALL. Our results redefine L-ASNase as a therapeutic agent targeting Gln addiction in certain lymphoid cells and offer an additional basis for predicting L-ASNase sensitivity and engineering selective L-ASNase derivatives for leukemia and lymphoma.

  10. Average Minimum Transmit Power to achieve SINR Targets: Performance Comparison of Various User Selection Algorithms

    CERN Document Server

    Salim, Umer

    2010-01-01

    In multi-user communication from one base station (BS) to multiple users, the problem of minimizing the transmit power to achieve some target guaranteed performance (rates) at users has been well investigated in the literature. Similarly various user selection algorithms have been proposed and analyzed when the BS has to transmit to a subset of the users in the system, mostly for the objective of the sum rate maximization. We study the joint problem of minimizing the transmit power at the BS to achieve specific signal-to-interference-and-noise ratio (SINR) targets at users in conjunction with user scheduling. The general analytical results for the average transmit power required to meet guaranteed performance at the users' side are difficult to obtain even without user selection due to joint optimization required over beamforming vectors and power allocation scalars. We study the transmit power minimization problem with various user selection algorithms, namely semi-orthogonal user selection (SUS), norm-based...

  11. Targeted Remedial Education for Under-Performing Teenagers: Costs and Benefits

    OpenAIRE

    Victor Lavy; Analia Schlosser

    2004-01-01

    There is renewed interest in ways to enhance secondary education, especially among disadvantaged students. This study evaluates the short-term effects of a remedial-education program that provided additional instruction to under-performing high-school students in Israel. The program targeted 10th twelfth graders who needed additional help to pass the matriculation exams. Using a comparison group of schools that enrolled in the program later and implementing a differences-in-differences estima...

  12. The Effects of Texas's Targeted Pre-Kindergarten Program on Academic Performance

    OpenAIRE

    Rodney J. Andrews; Paul Jargowsky; Kristin Kuhne

    2012-01-01

    There has been a resurgence in research that investigates the efficacy of early investments as a means of reducing gaps in academic performance. However, the strongest evidence for these effects comes from experimental evaluations of small, highly enriched programs. We add to this literature by assessing the extent to which a large-scale public program, Texas's targeted pre-Kindergarten (pre-K), affects scores on math and reading achievement tests, the likelihood of being retained in grade, a...

  13. Pharmacological targeting of dopamine D3 receptors: Possible clinical applications of selective drugs.

    Science.gov (United States)

    Pich, Emilio Merlo; Collo, Ginetta

    2015-09-01

    Dopamine D3 receptors have been pharmacologically engaged in humans since the development of the first antipsychotics and ergot-derivative dopamine (DA) agonists, even without knowing it. These agents were generally non-selective, developed primarily to target D2 receptors. In the last 10 years the understanding of the clinical implication of D3 receptors has been progressing also due to the identification of D3 gene polymorphisms, the use of more selective PET ligands such as [(11)C]-(+)-PHNO and the learning regarding the clinical use of the D3-preferential D2/D3 agonists ropinirole and pramipexole. A new specific neuroplasticity role of D3 receptor regarding dendrite arborisation outgrowth in dopaminergic neurons was also proposed to support, at least in part, the slowing of disease observed in subjects with Parkinson׳s Disease treated with DA agonists. Similar mechanisms could be at the basis of the antidepressant-like effects observed with DA agonists when co-administered with standard of care. Severe adverse event occurring with the use of anti-parkinsonian DA agonists in predisposed subjects, i.e., impulse control disorders, are now suggested to be putatively related to overactive D3 receptors. Not surprisingly, blockade of D3 receptors was proposed as treatment for addictive disorders, a goal that could be potentially achieved by repositioning buspirone, an anxiolytic drug with D3-preferential antagonistic features, or with novel selective D3 antagonists or partial agonists currently in development for schizophrenia. At the moment ABT-925 is the only selective D3 antagonist tested in schizophrenic patients in Phase II, showing an intriguing cognitive enhancing effects supported by preclinical data. Finally, exploratory pharmacogenetic analysis suggested that ABT-925 could be effective in a subpopulation of patients with a polymorphism on the D3 receptor, opening to a possible personalised medicine approach. PMID:26298833

  14. Microinvasion of liver metastases from colorectal cancer: predictive factors and application for determining clinical target volume

    International Nuclear Information System (INIS)

    This study evaluates the microscopic characteristics of liver metastases from colorectal cancer (LMCRC) invasion and provides a reference for expansion from gross tumor volume (GTV) to clinical targeting volume (CTV). Data from 129 LMCRC patients treated by surgical resection at our hospital between January 2008 and September 2009 were collected for study. Tissue sections used for pathology and clinical data were reviewed. Patient information used for the study included gender, age, original tumor site, number of tumors, tumor size, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199), synchronous or metachronous liver metastases, and whether patients received chemotherapy. The distance of liver microinvasion from the tumor boundary was measured microscopically by two senior pathologists. Of 129 patients evaluated, 81 (62.8 %) presented microinvasion distances from the tumor boundary ranging between 1.0 − 7.0 mm. A GTV-to-CTV expansion of 5, 6.7, or 7.0 mm was required to provide a 95, 99, or 100 % probability, respectively, of obtaining clear resection margins by microscopic observation. The extent of invasion was not related to gender, age, synchronous or metachronous liver metastases, tumor size, CA199 level, or chemotherapy. The extent of invasion was related to original tumor site, CEA level, and number of tumors. A scoring system was established based on the latter three positive predictors. Using this system, an invasion distance less than 3 mm was measured in 93.4 % of patients with a score of ≤1 point, but in only 85.7 % of patients with a score of ≤2 points. The extent of tumor invasion in our LMCRC patient cohort correlated with original tumor site, CEA level, and number of tumors. These positive predictors may potentially be used as a scoring system for determining GTV-to-CTV expansion

  15. Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology

    Science.gov (United States)

    Gao, Li; Wang, Xiao-dong; Niu, Yang-yang; Duan, Dan-dan; Yang, Xue; Hao, Jian; Zhu, Cui-hong; Chen, Dan; Wang, Ke-xin; Qin, Xue-mei; Wu, Xiong-zhi

    2016-01-01

    Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan–Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc. PMID:27143508

  16. Performance of long-pulse source reference target-moderator-reflector configurations

    International Nuclear Information System (INIS)

    We have calculated the performance of five similar target-moderator-reflector geometries that are reasonably well optimized for long-pulse source applications. For all cases, the moderators are fully coupled; that is, no poisons, decouplers, or liner are used. For each case, the energy- and time-dependent characteristics of the moderator source brightness have been parameterized using empirical functions. These parameterizations have been made available to users of the Monte Carlo neutron scattering instrument design code MCLIB for use in evaluating the performance of neutron scattering instruments on a long-pulse source. (author) 7 figs., 2 tabs., 5 refs

  17. A target detection model predicting field observer performance in maritime scenes

    Science.gov (United States)

    Culpepper, Joanne B.; Wheaton, Vivienne C.

    2014-10-01

    The U.S. Army's target acquisition models, the ACQUIRE and Target Task Performance (TTP) models, have been employed for many years to assess the performance of thermal infrared sensors. In recent years, ACQUIRE and the TTP models have been adapted to assess the performance of visible sensors. These adaptations have been primarily focused on the performance of an observer viewing a display device. This paper describes an implementation of the TTP model to predict field observer performance in maritime scenes. Predictions of the TTP model implementation were compared to observations of a small watercraft taken in a field trial. In this field trial 11 Australian Navy observers viewed a small watercraft in an open ocean scene. Comparisons of the observed probability of detection to predictions of the TTP model implementation showed the normalised RSS metric overestimated the probability of detection. The normalised Pixel Contrast using a literature value for V50 yielded a correlation of 0.58 between the predicted and observed probability of detection. With a measured value of N50 or V50 for the small watercraft used in this investigation, this implementation of the TTP model may yield stronger correlation with observed probability of detection.

  18. Performance Enhancement of Underwater Target Tracking by Fusing Data of Array of Global Positioning System Sonobuoys

    Directory of Open Access Journals (Sweden)

    Ahmed El-Shafie

    2009-01-01

    Full Text Available Problem statement: An accurate knowledge of geographic positions of sonobuoys is critical for the conduct of antisubmarine warfare operations and detected target localization. Deployed from an airborne platform or a surface vessel, arrays of sonobuoys could be used to efficiently track and localize submarines. Lastly, some sonobuoys were being equipped with GPS for improving system accuracy and potentially allowing networked Sonobuoy positioning. However, the computation of the range using the propagation loss profile and the data of one sonobuoy usually leads to inaccurate target localization due to several effects and uncertainties. It was, alternatively, reported that if the target is within the detection rage of two or more sonobuoys, greatly improved target localization can be achieved. Approach: Aim of this research was to investigate the feasibility of fusing data from a distributed field of GPS sonobuoys to create an Artificial Intelligence (AI based model for the error of the range computation in case of the target being detected by only one sonobuoy. Proposed module was designed utilizing Adaptive Neuron-Fuzzy Inference Systems (ANFIS to estimate the range error associated with the computation using the propagation loss profile when the target is within the detection range of only one sonobuoy. The architecture of the proposed ANFIS system had two unique features. First was the real-time cross-validation applied during the update (training procedure of the ANFIS-based module while the target was detected by two sonobuoys and the range was computed. Second feature was the use of non-overlapping and moving window for the real-time implementation of the ANFIS-based data fusion module. Results: Performance of the proposed system was examined with simulation data considering different scenarios for both the array of GPS sonobuoys and the target. Results showed that the corrected positioning by one sonobuoy is completely following the

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

    OpenAIRE

    Steven M Yip; Heng, Daniel Y. C.; Tang, Patricia A.

    2016-01-01

    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 dat...

  20. Performance of clinical mammography: a nationwide study from Denmark

    DEFF Research Database (Denmark)

    Jensen, Allan; Vejborg, Ilse; Severinsen, Niels;

    2006-01-01

    in Denmark in the year 2000 were collected and linked to cancer outcome. Use of the National Institute of Radiation Hygiene register for identification of radiology clinics ensured comprehensive nationwide registration. We used the final mammographic assessment at the end of the imaging work-up to determine...

  1. Ovarian cancer: Ion channel and aquaporin expression as novel targets of clinical potential.

    Science.gov (United States)

    Frede, Julia; Fraser, Scott P; Oskay-Özcelik, Gülten; Hong, Yeosun; Ioana Braicu, E; Sehouli, Jalid; Gabra, Hani; Djamgoz, Mustafa B A

    2013-07-01

    Ovarian cancer is associated with limited overall survival, due to problems in early detection and therapy. Membrane ion channels have been proposed to play a significant, concerted role in the cancer process, from initial proliferation to metastasis, and promise to be early, functional biomarkers. We review the evidence for ion channel and aquaporin expression and functioning in human ovarian cancer cells and tissues. In vitro, K(+) channels, mainly voltage-gated, including Ca(2+)-activated channels, have been found to control the cell cycle, as in other cancers. Voltage-gated, volume-regulated and intracellular Cl(-) channels have been detected in vitro and in vivo and shown to be involved in proliferation, adhesion and invasion. Evidence for 'transient receptor potential', voltage-gated sodium and calcium channels, which have been shown to contribute to pathogenesis of other carcinomas, is also emerging in ovarian cancer. Aquaporins may be involved in cell growth, migration and formation of ascites via increased water permeability of micro-vessels. It is concluded that functional expression of ion channels and their regulation by steroid hormones and growth factors are an integral part of ovarian cancer development and progression. Furthermore, ion channels may be involved in multidrug resistance, commonly associated with treatment of ovarian cancer. We propose that ion channel studies can facilitate our understanding of the pathobiology of ovarian cancer and, ultimately, can serve as viable novel targets for its clinical management. PMID:23683551

  2. [Gross tumor volume (GTV) and clinical target volume (CTV) in radiotherapy of benign skull base tumors].

    Science.gov (United States)

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

    2001-10-01

    Skull base tumours represent about 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-dimentional 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. PMID:11715310

  3. 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.

  4. Real world clinical performance of the zotarolimus eluting coronary stent system in Chinese patients: a prospective,multicenter registry study

    Institute of Scientific and Technical Information of China (English)

    HAN Ya-ling; XU Kai; WANG Wei-min; HUO Yong; CHEN Ji-yan; XU Bo; YAN Hong-bing; WANG Le-feng; LI Wei-min; CONG Hong-liang; JING Quan-min; WANG Shou-li

    2011-01-01

    Background Early clinical trials with the Endeavor zotarolimus eluting stent (ZES) in western populations demonstrated low rates of target lesion revascularization with a favorable safety profile including low late stent thrombosis with up to 5 years of follow-up.The aim of this clinical registry study was to evaluate real world clinical performance of the ZES coronary system in Chinese patients.Methods The China Endeavor Registry is a prospective,multicenter registry assessing the safety of the ZES system in a real world patient population.It was conducted at 46 centers in China in routine treatment of patients with coronary artery stenosis,including patients with clinical characteristics or lesion types that are often excluded from randomized controlled trials.The registry included 2210 adult patients who underwent single-vessel or multi-vessel percutaneous coronary intervention.The primary end point was the rate of major adverse cardiac events (MACE) at 12 months.Results The 12-month rate of MACE for all patients in the registry was 3.03%.Cardiac death or myocardial infarction rate was 1.28% and target lesion revascularization rate was 1.66%,non-target lesion target vessel revascularization (TVR) was 0.52%,TVR was 2.18%,and target vessel failure was 3.22%.There was only one case of emergent cardiac bypass surgery.The 12-month overall incidence of all Academic Research Consortium (ARC)-defined stent thrombosis was 0.43%.Conclusion Mid-term results from the real-world China Endeavor Registry suggest that Endeavor ZES was safe and effective in Chinese patients.

  5. Distinct effects of positive and negative music on older adults' auditory target identification performances.

    Science.gov (United States)

    Vieillard, Sandrine; Bigand, Emmanuel

    2014-01-01

    Older adults, compared to younger adults, are more likely to attend to pleasant situations and avoid unpleasant ones. Yet, it is unclear whether such a phenomenon may be generalized to musical emotions. In this study, we investigated whether there is an age-related difference in how musical emotions are experienced and how positive and negative music influences attention performances in a target identification task. Thirty-one young and twenty-eight older adults were presented with 40 musical excerpts conveying happiness, peacefulness, sadness, and threat. While listening to music, participants were asked to rate their feelings and monitor each excerpt for the occurrence of an auditory target. Compared to younger adults, older adults reported experiencing weaker emotional activation when listening to threatening music and showed higher level of liking for happy music. Correct reaction times (RTs) for target identification were longer for threatening than for happy music in older adults but not in younger adults. This suggests that older adults benefit from a positive musical context and can regulate emotion elicited by negative music by decreasing attention towards it (and therefore towards the auditory target).

  6. PERFORMANCE EVALUATION OF THE DOUBLE-THRESHOLD CFAR DETECTOR IN MULTIPLE-TARGET SITUATIONS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In radar systems of automatic detection, an estimate of background clutter power is used to set thedetection threshold. An interference saturated environment is frequently encountered in these systems (multi-ple target situations). Therefore, the detection of signals in such an environment becomes one of the most im-portant problems to be solved. The double-threshold algorithm is one of the more interesting detectors used inthese situations. While the first threshold operation ensures that the calculation of the detection (second)threshold is based on a set of samples which is free of strong interferers and is therefore much more represen-tative of the noise level, the second threshold is used to declare the presence or the absence of the radar target.The object of the present paper is to analyze the performance of such type of CFAR schemes when the radarreceiver contains a noncoherent integrator amongst its basic elements. It is found that the processor detectabil-ity loss is very low and the performance degradation, caused by interferers is quite small even if the number ofoutlying targets is large, given that the first threshold is properly chosen.

  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...

  8. Transition to clinical training : influence of pre-clinical knowledge and skills, and consequences for clinical performance

    NARCIS (Netherlands)

    van Hell, Elisabeth A.; Kuks, Jan B. M.; Schonrock-Adema, Johanna; van Lohuizen, Mirjam T.; Cohen-Schotanus, Janke

    2008-01-01

    CONTEXT Many students experience a tough transition from pre-clinical to clinical training and previous studies suggest that this may constrict students' progress. However, clear empirical evidence of this is lacking. The aim of this study was to determine: whether the perceived difficulty of transi

  9. 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.

  10. The Effect of Noise on Human Performance: A Clinical Trial

    Directory of Open Access Journals (Sweden)

    K Azam

    2013-04-01

    Full Text Available Background: Noise is defined as unwanted or meaningless sound that apart from auditory adverse health effects may distract attention from cues that are important for task performance. Human performance is influenced by many job-related factors and workplace conditions including noise level.Objective: To study the effect of noise on human performance.Methods: The participants included 40 healthy male university students. The experimental design consisted of 3 (sound pressure level x 3 (noise schedule x 2 (noise type factors. To investigate occupational skill performance, some specific test batteries were used: 1 steadiness test, 2 Minnesota manual dexterity test, 3 hand tool dexterity test, and 4 two-arm coordination test. Time duration of test completion was measured as speed response; to determine error response, the time taken during committing an error by participants while performing a task was measured.Results: Speed response obtained from the 4 tests in combined conditions of noise schedule, harmonic index, and sound pressure level was highest for (intermittent, treble, 95 dB, (continuous, treble, 95 dB, (continuous, treble, 85 dB and (intermittent, treble, 95 dB, respectively.Conclusion: Treble noise was found significant in reducing human performance; also, intermittent noise, especially at high pressure levels, was responsible for worsening environmental conditions during performing a task.

  11. 3D modeling and simulation of the thermal performance of solid cyclotron targets

    Energy Technology Data Exchange (ETDEWEB)

    Avila-Rodriguez, M.A.; Sader, J.A.; McQuarrie, S.A. [Alberta Univ., Edmonton PET Centre, Cross Cancer Institute, AB (Canada); McQuarrie, S.A. [Alberta Univ., Faculty of Medicine and Dentistry, Div. of Oncologic Imaging, Edmonton, AB (Canada)

    2007-07-01

    COMSOL Multiphysics was used to model and simulate the thermal performance of solid targets irradiated with charged particles. Parametric solutions for beam power densities in the range from 1.5 10{sup 5} to 1.5 10{sup 6} W/m{sup 2} and cooling water flow velocities from 0.2 to 4.0 m/s were obtained for different plate materials. Results showed that materials with a high thermal conductivity to heat capacity ratio behave better in cooling dynamic systems requiring fast dissipation of heat. Results also showed that water flow rates greater than 2.6 L/min do not noticeably improve the heat dissipation of solid targets irradiated with charged particles. (authors)

  12. The 727 airplane target thrust reverser static performance model test for refanned JT8D engines

    Science.gov (United States)

    Chow, C. T. P.; Atkey, E. N.

    1974-01-01

    The results of a scale model static performance test of target thrust reverser configurations for the Pratt and Whitney Aircraft JT8D-100 series engine are presented. The objective of the test was to select a series of suitable candidate reverser configurations for the subsequent airplane model wind tunnel ingestion and flight controls tests. Test results indicate that adequate reverse thrust performance with compatible engine airflow match is achievable for the selected configurations. Tapering of the lips results in loss of performance and only minimal flow directivity. Door pressure surveys were conducted on a selected number of lip and fence configurations to obtain data to support the design of the thrust reverser system.

  13. Performance limits for exo-clutter Ground Moving Target Indicator (GMTI) radar.

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2010-09-01

    The performance of a Ground Moving Target Indicator (GMTI) radar system depends on a variety of factors, many which are interdependent in some manner. It is often difficult to 'get your arms around' the problem of ascertaining achievable performance limits, and yet those limits exist and are dictated by physics. This report identifies and explores those limits, and how they depend on hardware system parameters and environmental conditions. Ultimately, this leads to a characterization of parameters that offer optimum performance for the overall GMTI radar system. While the information herein is not new to the literature, its collection into a single report hopes to offer some value in reducing the 'seek time'.

  14. Clinical effects of pranayama on performance of rifle shooters

    Directory of Open Access Journals (Sweden)

    Amte Snehal Shekhar, Mistry Hetal M

    2014-07-01

    Full Text Available Background: Yoga has an enormous scientifically proven effect on man’s physical and psychological functioning. Pranayama constitute the most vital aspects of yoga. Various methods of pranayama have a sound scientific basis and are traditionally believed to produce equilibrium between psychic and somatic aspects of bodily functions. The link between body and mind is obligatory for the better performance of sports persons. Aim: The aim of the study is to find out the effect of pranayama on the performance of Rifle shooters by measuring the parameters like-breath holding time, lung functional capacity and shooting performance. Method: 52 state level shooters subjects were chosen from 2 centres between the age group of 15-30years. Out of them, 26 shooters were given training in the techniques of pranayama for 3weeks.The other 26 subjects served as control i.e. with out Pranayama training. Variables like shooting performance, breath holding time (BHT, peak expiratory flow rate (PEFR, respiratory rate (RR and pulse rate (PR were measured in both the groups. Results: The study showed highly significant improvement in all the five variables shooting performance (in mm, BHT, PEFR, RR and PR with p value of 3.62E-05, 2.78E-07, 1.31E-09, 0.013, 3.40E-04respectively. Conclusion: So it can be concluded that pranayama is efficacious for better performance of Rifle shooters and should be included in their training practice.

  15. EFFECTS OF MERGERS AND ACQUISITIONS ON FINANCIAL PERFORMANCE OF THE TARGET COMPANY

    Directory of Open Access Journals (Sweden)

    ADRIANA DUŢESCU

    2013-05-01

    Full Text Available Many studies revealed the fact that mergers and acquisitions are a risky business. Disregarding the M&A advisers’ fees, evaluations show that most of the companies completing M&A transactions disappoint to deliver on promised financial performance. But, as many would say, it is an investment and the highest risks produce the highest results - whether they're good or bad. Within this paper, we were intending to analyse the rate of success of relevant M&A transactions that took place in 2007 in Romania, by comparing the financial statements of the target companies before and after the acquisition, in the current economic context. The main objective of this study is to generally determine the successfulness of the M&A transactions, starting from assessing changes induced by the M&A transaction to the target company, with the help of three important financial ratios: profit margin, ROE and receivable collection period. Even though the study may present some bias, we have tried to be as objective as possible and not influence its outcome: that 80% of 10 most important private Mergers and Acquisitions taking place in Romania in 2007 and that meet several conditions: o The target is part of the consumer goods and services market (mainly trade and tourism and is an important player in its industry o The target is a Romanian private company, and its shares are not listed on the stock exchange o The acquirer is majority shareholder after the transaction The target company remained as a sole entity and was not integrated into the mother company after the transaction were not successful.

  16. Targeting the poorest in a performance-based financing programme in northern Cameroon.

    Science.gov (United States)

    Flink, Ilse Je; Ziebe, Roland; Vagaï, Djebba; van de Looij, Frank; van 't Riet, Hilda; Houweling, Tanja Aj

    2016-07-01

    Performance-Based Financing (PBF) is a promising approach to improve health system performance in developing countries, but there are concerns that it may inadequately address inequalities in access to care. Incentives for reaching the poor may prove beneficial, but evidence remains limited. We evaluated a system of targeting the poorest of society ('indigents') in a PBF programme in Cameroon, examining (under)coverage, leakage and perceived positive and negative effects. We conducted a documentation review, 59 key informant interviews and 33 focus group discussions with community members (poor and vulnerable people-registered as indigents and those not registered as such). We found that community health workers were able to identify very poor and vulnerable people with a minimal chance of leakage to non-poor people. Nevertheless, the targeting system only reached a tiny proportion (≤1%) of the catchment population, and other poor and vulnerable people were missed. Low a priori set objectives and implementation problems-including a focus on easily identifiable groups (elderly, orphans), unclarity about pre-defined criteria, lack of transport for identification and insufficient motivation of community health workers-are likely to explain the low coverage. Registered indigents perceived improvements in access, quality and promptness of care, and improvements in economic status and less financial worries. However, lack of transport and insufficient knowledge about the targeting benefits, remained barriers for health care use. Negative effects of the system as experienced by indigents included negative reactions (e.g. jealousy) of community members. In conclusion, a system of targeting the poorest of society in PBF programmes may help reduce inequalities in health care use, but only when design and implementation problems leading to substantial under-coverage are addressed. Furthermore, remaining barriers to health care use (e.g. transport) and negative reactions

  17. The Use of Paired Comparisons for Developing Criteria for the Observation of Student Clinical Performance.

    Science.gov (United States)

    Rippey, Robert M.; Krutchkoff, David J.

    1984-01-01

    The method of paired comparisons was used to rank 42 dental students on their performance in emergency and screening clinic rotations. Results suggest this methodology may provide more internally consistent student assessments on more subtle aspects of clinical performance than those assessed by multiple-choice tests or written performance…

  18. Modified distal shoe appliance--fabrication and clinical performance.

    Science.gov (United States)

    Gujjar, Kumar Raghav; Indushekar, K R; Amith, H V; Sharma, Shefali Li

    2012-01-01

    When the primary second molar is prematurely lost, mesial movement and migration of the permanent first molar often occurs. This is one of the most difficult problems of the developing dentition confronted by pediatric dentists. Use of a space maintainer that will guide the permanent first molar into its normal position is indicated. In cases with bilateral premature loss of primary molars, the conventional design of distal shoe poses a variety of problems and, therefore, necessitates a customized design for the eruption guidance of permanent first molars. The purpose of this case report is to discuss an innovative design of a distal shoe appliance, which was used with good clinical results.

  19. Locoregional extension patterns of nasopharyngeal carcinoma and suggestions for clinical target volume delineation

    Institute of Scientific and Technical Information of China (English)

    Wen-Fei Li; Jun Ma; Ying Sun; Mo Chen; Ling-Long Tang; Li-Zhi Liu; Yan-Ping Mao; Lei Chen; Guan-Qun Zhou; Li Li

    2012-01-01

    Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection.This study aimed to define the Iocoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation.Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed.According to incidence rates of tumor invasion,the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%),medium-risk (5%-30%),and low-risk (<5%) groups.The lymph node (LN) level was determined according to the Radiation Therapy Oncology Group guidelines,which were further categorized into the upper neck (retropharyngeal region and level Ⅱ),middle neck (levels Ⅲ and Va),and lower neck (levels IV and Vb and the supraclavicular fossa).The high-risk anatomic sites were adjacent to the nasopharynx,whereas those at medium-or low-risk were separated from the nasopharynx.If the high-risk anatomic sites were involved,the rates of tumor invasion into the adjacent medium-risk sites increased; if not,the rates were significantly lower (P < 0.01).Among the 1920 (81.1%) patients with positive LN,the incidence rates of LN metastasis in the upper,middle,and lower neck were 99.6%,30.2%,and 7.2%,respectively,and skip metastasis happened in only 1.2% of patients.In the 929 patients who had unilateral upper neck involvement,the rates of contralateral middle neck and lower neck involvement were 1.8% and 0.4%,respectively.Thus,local disease spreads stepwise from proximal sites to distal sites,and LN metastasis spreads from the upper neck to the lower neck.Individualized CTV delineation for NPC may be feasible.

  20. Operational assessment of Target Acquisitions Weapons Software (TAWS) prediction performance at Nellis AFB, NV

    OpenAIRE

    Hernandez, Jerome H.

    2006-01-01

    Target Acquisition Weapons Software (TAWS) Version 3.4 is a joint Tactical Decision Aid (TDA) used to predict performance of electro-optic and electro-magnetic (EM/EO) munitions and navigation systems. TAWS is the USAF and USN mission-planning standard for laser-guided, infrared, and TV munitions and navigation systems TDAs. As TAWS continues to deploy through the mission planning community there is a need to establish a systematic approach to assessing TAWS accuracy. This study was an op...

  1. Reliable and Valid Assessment of Clinical Bronchoscopy Performance

    DEFF Research Database (Denmark)

    Konge, Lars; Larsen, Klaus Richter; Clementsen, Paul;

    2012-01-01

    : The interrater reliability was high, with Cronbach's a = 0.86. Assessment of 3 bronchoscopies by a single rater had a generalizability coefficient of 0.84. The correlation between experience and performance was good (Pearson correlation = 0.76). There were significant differences between the groups for all...

  2. Seeking value in Medicare: performance measurement for clinical professionals.

    Science.gov (United States)

    Sprague, Lisa

    2013-10-30

    The Medicare program, despite its reputation of being a bill payer with little regard to the worth of the services it buys, has begun to put in place a range of programs aimed at assessing quality and value, with more to come. Attention to resource use and cost is nascent. The issues are complex, and it is no surprise that there is a level of contention between providers and regulators, even though both profess commitment to improved quality. This paper summarizes the quality and value programs that apply to physicians and other clinical professionals, as well as programs designed to encourage the adoption of technology to support quality improvement. Participation in all is voluntary. However, a decision not to participate increasingly carries a financial penalty, as Congress (and, by extension, the U.S. Department of Health and Human Services, or HHS) tries to encourage behavior it cannot force.

  3. Seeking value in Medicare: performance measurement for clinical professionals.

    Science.gov (United States)

    Sprague, Lisa

    2013-10-30

    The Medicare program, despite its reputation of being a bill payer with little regard to the worth of the services it buys, has begun to put in place a range of programs aimed at assessing quality and value, with more to come. Attention to resource use and cost is nascent. The issues are complex, and it is no surprise that there is a level of contention between providers and regulators, even though both profess commitment to improved quality. This paper summarizes the quality and value programs that apply to physicians and other clinical professionals, as well as programs designed to encourage the adoption of technology to support quality improvement. Participation in all is voluntary. However, a decision not to participate increasingly carries a financial penalty, as Congress (and, by extension, the U.S. Department of Health and Human Services, or HHS) tries to encourage behavior it cannot force. PMID:24312987

  4. Optical ensemble analysis of intraocular lens performance through a simulated clinical trial with ZEMAX.

    Science.gov (United States)

    Zhao, Huawei

    2009-01-01

    A ZEMAX model was constructed to simulate a clinical trial of intraocular lenses (IOLs) based on a clinically oriented Monte Carlo ensemble analysis using postoperative ocular parameters. The purpose of this model is to test the feasibility of streamlining and optimizing both the design process and the clinical testing of IOLs. This optical ensemble analysis (OEA) is also validated. Simulated pseudophakic eyes were generated by using the tolerancing and programming features of ZEMAX optical design software. OEA methodology was verified by demonstrating that the results of clinical performance simulations were consistent with previously published clinical performance data using the same types of IOLs. From these results we conclude that the OEA method can objectively simulate the potential clinical trial performance of IOLs.

  5. Peri-operative warming devices: performance and clinical application.

    Science.gov (United States)

    John, M; Ford, J; Harper, M

    2014-06-01

    Since the adverse consequences of accidental peri-operative hypothermia have been recognised, there has been a rapid expansion in the development of new warming equipment designed to prevent it. This is a review of peri-operative warming devices and a critique of the evidence assessing their performance. Forced-air warming is a common and extensively tested warming modality that outperforms passive insulation and water mattresses, and is at least as effective as resistive heating. More recently developed devices include circulating water garments, which have shown promising results due to their ability to cover large surface areas, and negative pressure devices aimed at improving subcutaneous perfusion for warming. We also discuss the challenge of fluid warming, looking particularly at how devices' performance varies according to flow rate. Our ultimate aim is to provide a guide through the bewildering array of devices on the market so that clinicians can make informed and accurate choices for their particular hospital environment. PMID:24720346

  6. Sustained effect of simulation-based ultrasound training on clinical performance

    DEFF Research Database (Denmark)

    Tolsgaard, M G; Ringsted, C; Dreisler, E;

    2015-01-01

    OBJECTIVE: The objective was to study the effect of initial simulation-based transvaginal ultrasound training compared to only clinical training on the clinical performances of residents in Obstetrics and Gynecology (OB-GYN) measured at two months into the residency. METHODS: In a randomized study......, new residents in OB-GYN (N = 33) without prior ultrasound experience were included from three teaching hospitals. Participants were allocated to simulation-based training and subsequent clinical training (n = 18) or only clinical training (n = 15). The simulation-based training was performed on a...

  7. Developing and assessing initiatives designed to improve clinical teaching performance.

    Science.gov (United States)

    Khandelwal, Sorabh; Bernard, Aaron W; Wald, David A; Manthey, David E; Fisher, Jonathan; Ankel, Felix; Williams, Sarah R; Szyld, Demian; Riddle, Janet; Anders Ericsson, K

    2012-12-01

    To improve the teaching performance of emergency physicians, it is necessary to understand the attributes of expert teachers and the optimal methods to deliver faculty development. A working group of medical educators was formed to review the literature, summarize what is known on the topic, and provide recommendations for future research. This occurred as a track of the 2012 Academic Emergency Medicine (AEM) consensus conference "Education Research in Emergency Medicine: Opportunities, Challenges, and Strategies for Success." The group concluded that the current state of research on these topics is limited. Improvement in understanding will come through research focusing on Kirkpatrick's higher levels of evaluation (behavior and results). PMID:23216823

  8. Emotional intelligence and clinical interview performance of dental students.

    Science.gov (United States)

    Hannah, Annette; Lim, Bee T; Ayers, Kathryn M S

    2009-09-01

    One hundred and sixteen third-year dental students participating in a consultation skills course in Dunedin, New Zealand, completed a standardized psychometric Social Skills Inventory (SSI) and were assessed by tutors, simulated patients, and themselves. Students with higher social skills abilities obtained higher performance scores and demonstrated better interview structure. Patients reported being more likely to return to students for a dental consultation following the second interview, and students' consultation skills were rated (by tutors, patients, and students) higher at the end of the course than the beginning. Female students had higher global social skills abilities and were more emotionally expressive and sensitive than male students, while the latter had better emotional control. Female students performed better in the first interview than male students, but there was no significant gender difference in the second interview. Tutor and simulated patient ratings suggested that a consultation skills course can increase the ability of students in general, and English as a second language students in particular, to relate to their patients, manage anxiety, identify ethical issues, and recognize significant psychosocial issues that lead to more accurate diagnosis and treatment processes, ensuring the effective delivery of patient-centered dental education.

  9. The impact of selected contextual factors on experts' clinical reasoning performance (does context impact clinical reasoning performance in experts?).

    NARCIS (Netherlands)

    Durning, S.J.; Artino, A.R.; Boulet, J.R.; Dorrance, K.; Vleuten, C.P.M. van der; Schuwirth, L.

    2012-01-01

    Context specificity, or the variation in a participant's performance from one case, or situation, to the next, is a recognized problem in medical education. However, studies have not explored the potential reasons for context specificity in experts using the lens of situated cognition and cognitive

  10. The Impact of Selected Contextual Factors on Experts' Clinical Reasoning Performance (Does Context Impact Clinical Reasoning Performance in Experts?)

    Science.gov (United States)

    Durning, Steven J.; Artino, Anthony R.; Boulet, John R.; Dorrance, Kevin; van der Vleuten, Cees; Schuwirth, Lambert

    2012-01-01

    Context specificity, or the variation in a participant's performance from one case, or situation, to the next, is a recognized problem in medical education. However, studies have not explored the potential reasons for context specificity in experts using the lens of situated cognition and cognitive load theories (CLT). Using these theories, we…

  11. Current status on performance of CT colonography and clinical indications

    International Nuclear Information System (INIS)

    CT colonography (CTC) is a robust and reliable imaging test of the colon. Accuracy for the detection of colorectal cancer (CRC) is as high as conventional colonoscopy (CC). Identification of polyp is size dependent, with large lesions (≥10 mm) accurately detected and small lesions (6–9 mm) identified with moderate to good sensitivity. Recent studies show good sensitivity for the identification of nonpolypoid (flat) lesions as well. Current CTC indications include the evaluation of patients who had undergone a previous incomplete CC or those who are unfit for CC (elderly and frail individuals, patients with underlying severe clinical conditions, or with contraindication to sedation). CTC can also be efficiently used in the assessment of diverticular disease (excluding patients with acute diverticulitis, where the exam should be postponed), before laparoscopic surgery for CRC (to have an accurate localization of the lesion), in the evaluation of colonic involvement in the case of deep pelvic endometriosis (replacing barium enema). CTC is also a safe procedure in patients with colostomy. For CRC screening, CTC should be considered an opportunistic screening test (not available for population, or mass screening) to be offered to asymptomatic average-risk individuals, of both genders, starting at age 50. The use in individuals with positive family history should be discussed with the patient first. Absolute contraindication is to propose CTC for surveillance of genetic syndromes and chronic inflammatory bowel diseases (in particular, ulcerative colitis). The use of CTC in the follow-up after surgery for CRC is achieving interesting evidences despite the fact that literature data are still relatively weak in terms of numerosity of the studied populations. In patients who underwent previous polypectomy CTC cannot be recommended as first test because debate is still open. It is desirable that in the future CTC would be the first-line and only diagnostic test for

  12. Current status on performance of CT colonography and clinical indications

    Energy Technology Data Exchange (ETDEWEB)

    Laghi, Andrea, E-mail: andrea.laghi@uniroma1.it [Department of Radiological Sciences, Oncology and Pathology Sapienza – Università di Roma, Polo Pontino, I.C.O.T. Hospital, Via Franco Faggiana 43, 04100 Latina (Italy); Rengo, Marco [Department of Radiological Sciences, Oncology and Pathology Sapienza – Università di Roma, Polo Pontino, I.C.O.T. Hospital, Via Franco Faggiana 43, 04100 Latina (Italy); Graser, Anno [InstitutfürKlinische Radiologie, Klinikumder Ludwig-Maximilians-Universität München, Campus Großhadern, Marchioninistr. 15, 81377 München (Germany); Iafrate, Franco [Department of Radiological Sciences, Oncology and Pathology Sapienza – Università di Roma, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome (Italy)

    2013-08-15

    CT colonography (CTC) is a robust and reliable imaging test of the colon. Accuracy for the detection of colorectal cancer (CRC) is as high as conventional colonoscopy (CC). Identification of polyp is size dependent, with large lesions (≥10 mm) accurately detected and small lesions (6–9 mm) identified with moderate to good sensitivity. Recent studies show good sensitivity for the identification of nonpolypoid (flat) lesions as well. Current CTC indications include the evaluation of patients who had undergone a previous incomplete CC or those who are unfit for CC (elderly and frail individuals, patients with underlying severe clinical conditions, or with contraindication to sedation). CTC can also be efficiently used in the assessment of diverticular disease (excluding patients with acute diverticulitis, where the exam should be postponed), before laparoscopic surgery for CRC (to have an accurate localization of the lesion), in the evaluation of colonic involvement in the case of deep pelvic endometriosis (replacing barium enema). CTC is also a safe procedure in patients with colostomy. For CRC screening, CTC should be considered an opportunistic screening test (not available for population, or mass screening) to be offered to asymptomatic average-risk individuals, of both genders, starting at age 50. The use in individuals with positive family history should be discussed with the patient first. Absolute contraindication is to propose CTC for surveillance of genetic syndromes and chronic inflammatory bowel diseases (in particular, ulcerative colitis). The use of CTC in the follow-up after surgery for CRC is achieving interesting evidences despite the fact that literature data are still relatively weak in terms of numerosity of the studied populations. In patients who underwent previous polypectomy CTC cannot be recommended as first test because debate is still open. It is desirable that in the future CTC would be the first-line and only diagnostic test for

  13. Promising targets and current clinical trials in metastatic non-squamous NSCLC

    Directory of Open Access Journals (Sweden)

    Alona eZer

    2014-11-01

    Full Text Available Lung adenocarcinoma is the most rapidly increasing subtype of lung cancer today. With the discovery of EGFR mutations and ALK rearrangements and targeted therapy, personalized medicine has become a reality for patients with lung adenocarcinoma. Here we review potential additional targets and novel therapies of interest in lung adenocarcinoma including targets within the cell surface (receptor tyrosine kinases EGFR, HER2, RET, ROS1, MET, TRK, targets in intracellular pathways (ALK, RAS-RAF-MEK, PI3K-AKT-PTEN, WNT, nuclear targets such as PARP, HSP90 and histone deacetylase, and selected pathways in the tumour environment. With the evolving ability to identify specific molecular aberrations in patient tumours in routine practice, our ability to further personalize therapy in lung adenocarcinoma is rapidly expanding.

  14. Alternative performance metrics and target values for the CID2013 database

    Science.gov (United States)

    Virtanen, T.; Nuutinen, M.; Radun, J.; Leisti, T.; Häkkinen, J.

    2015-01-01

    An established way of validating and testing new image quality assessment (IQA) algorithms have been to compare how well they correlate with subjective data on various image databases. One of the most common measures is to calculate linear correlation coefficient (LCC) and Spearman's rank order correlation coefficient (SROCC) against the subjective mean opinion score (MOS). Recently, databases with multiply distorted images have emerged 1,2. However with multidimensional stimuli, there is more disagreement between observers as the task is more preferential than that of distortion detection. This reduces the statistical differences between image pairs. If the subjects cannot distinguish a difference between some of the image pairs, should we demand any better performance with IQA algorithms? This paper proposes alternative performance measures for the evaluation of IQA's for the CID2013 database. One proposed alternative performance measure is root-mean-square-error (RMSE) value for the subjective data as a function of the number of observers. The other alternative performance measure is the number of statistical differences between image pairs. This study shows that after 12 subjects the RMSE value saturates around the level of three, meaning that a target RMSE value for an IQA algorithm for CID2013 database should be three. In addition, this study shows that the state-of-the-art IQA algorithms found the better image from the image pairs with a probability of 0.85 when the image pairs with statistically significant differences were taken into account.

  15. Critical heat flux performance of hypervapotrons proposed for use in the ITER divertor vertical target

    Energy Technology Data Exchange (ETDEWEB)

    Youchison, D.L.; Marshall, T.D.; McDonald, J.M.; Lutz, T.J.; Watson, R.D. [Sandia National Labs., Albuquerque, NM (United States); Driemeyer, D.E. Kubik, D.L.; Slattery, K.T.; Hellwig, T.H. [McDonnell Douglas Aerospace, St. Louis, MO (United States)

    1997-09-01

    Task T-222 of the International Thermonuclear Experimental Reactor (ITER) program addresses the manufacturing and testing of permanent components for use in the ITER divertor. Thermalhydraulic and critical heat flux performance of the heat sinks proposed for use in the divertor vertical target are part of subtask T-222.4. As part of this effort, two single channel, medium scale, bare copper alloy, hypervapotron mockups were designed, fabricated, and tested using the EB-1200 electron beam system. The objectives of the effort were to develop the design and manufacturing procedures required for construction of robust high heat flux (HHF) components, verify thermalhydraulic, thermomechanical and critical heat flux (CHF) performance under ITER relevant conditions, and perform analyses of HHF data to identify design guidelines and failure criteria and possibly modify any applicable CHF correlations. The design, fabrication, and finite element modeling of two types of hypervapotrons are described; a common version already in use at the Joint European Torus (JET) and a new attached fin design. HHF test data on the attached fin hypervapotron will be used to compare the CHF performance under uniform heating profiles on long heated lengths with that of localized, highly peaked, off nominal profiles.

  16. A facilitative versus directive approach in training clinical skills? Investigating students’ clinical performance and perceptions

    OpenAIRE

    Berghmans, Inneke; Druine, Nathalie; Dochy, Filip; Struyven, Katrien

    2012-01-01

    Over the years, many medical school curricula have started implementing diverse student-centred teaching and learning methodologies. Previous studies, however, have indicated that students prefer more traditional and directive methodologies instead, raising questions on which training approach should be advocated. This study contrasts the effects of a student-centred (i.e. facilitative) training approach on students’ clinical skills learning with students’ perceptions. More specifically, a qu...

  17. Development of the Computerized Model of Performance-Based Measurement System to Measure Nurses' Clinical Competence.

    Science.gov (United States)

    Liou, Shwu-Ru; Liu, Hsiu-Chen; Tsai, Shu-Ling; Cheng, Ching-Yu; Yu, Wei-Chieh; Chu, Tsui-Ping

    2016-04-01

    Critical thinking skills and clinical competence are for providing quality patient care. The purpose of this study is to develop the Computerized Model of Performance-Based Measurement system based on the Clinical Reasoning Model. The system can evaluate and identify learning needs for clinical competency and be used as a learning tool to increase clinical competency by using computers. The system includes 10 high-risk, high-volume clinical case scenarios coupled with questions testing clinical reasoning, interpersonal, and technical skills. Questions were sequenced to reflect patients' changing condition and arranged by following the process of collecting and managing information, diagnosing and differentiating urgency of problems, and solving problems. The content validity and known-groups validity was established. The Kuder-Richardson Formula 20 was 0.90 and test-retest reliability was supported (r = 0.78). Nursing educators can use the system to understand students' needs for achieving clinical competence, and therefore, educational plans can be made to better prepare students and facilitate their smooth transition to a future clinical environment. Clinical nurses can use the system to evaluate their performance-based abilities and weakness in clinical reasoning. Appropriate training programs can be designed and implemented to practically promote nurses' clinical competence and quality of patient care. PMID:26829522

  18. 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.

  19. 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.

  20. Performance of genotype-MTBDR test directly on clinical specimens

    Directory of Open Access Journals (Sweden)

    Gülden Yılmaz

    2012-12-01

    Full Text Available Objectives: Most important point for the control and effective treatment of multidrug resistant tuberculosis (MDR-TBis early diagnosis and rapid determination of the resistance. The aim of this study is to assess the performance of theGenotype-MTBDR assay applied directly on sputum samples and compare the results with those obtained by DNA sequencingand phenotypic susceptibility testing.Materials and methods: Between November 2005 and February 2006, 93 smear and culture positive sputum sampleswere included in the study. Drug susceptibility results for rifampin (RIF and isoniazid (INH, obtained by proportionmethod on L-J medium, Genotype-MTBDR and DNA sequencing were compared.Results: The rate of concordance between the results of the Genotype-MTBDR and DNA sequencing was 93.5% and96.7% for RIF and INH, respectively. Moreover, Genotype-MTBDR detected all the RIF (24 and INH (18 resistant strainsobtained by sequencing (100%. Compared to the DNA sequencing method; the sensitivity, specificity, positive predictiveand negative predictive value for RIF and INH were 100%, 91.3%, 80%, 100% and 100%, 96%, 85.7%, 100% respectively.Conclusion: Genotype-MTBDR, one of molecular assays, distinctly shortens the time for diagnosis and detection of resistanceto INH and RIF, essential for management of MDR-TB. The test appears to have good sensitivity and specificitywhen also used directly on sputum specimens. J Microbiol Infect Dis 2012; 2(4: 135-141Key words: Mycobacterium tuberculosis; drug resistance; genotype-MTBDR.

  1. Expression and its clinical significance of mammalian target of rapamycin and vascular endothelial growth factor in gastroenteropancreatic neuroendocrine neoplasm

    Institute of Scientific and Technical Information of China (English)

    陈洁

    2014-01-01

    Objective To explore the expression,correlation and clinical significance of mammalian target of rapamycin(mT OR)and vascular endothelial growth factor(VEGF)in gastroenteropancreatic neuroendocrine neoplasm(GEP-NEN).Methods From October 1995 to December 2012,the paraffin tissue specimens of 114 pathological diagnosed GEP-NEN were collected.The expressions of mT OR and VEGF at protein level were detected

  2. Quantitative performance of a quadrupole-orbitrap-MS in targeted LC-MS determinations of small molecules.

    Science.gov (United States)

    Grund, Baptiste; Marvin, Laure; Rochat, Bertrand

    2016-05-30

    High-resolution mass spectrometry (HRMS) has been associated with qualitative and research analysis and QQQ-MS with quantitative and routine analysis. This view is now challenged and for this reason, we have evaluated the quantitative LC-MS performance of a new high-resolution mass spectrometer (HRMS), a Q-orbitrap-MS, and compared the results obtained with a recent triple-quadrupole MS (QQQ-MS). High-resolution full-scan (HR-FS) and MS/MS acquisitions have been tested with real plasma extracts or pure standards. Limits of detection, dynamic range, mass accuracy and false positive or false negative detections have been determined or investigated with protease inhibitors, tyrosine kinase inhibitors, steroids and metanephrines. Our quantitative results show that today's available HRMS are reliable and sensitive quantitative instruments and comparable to QQQ-MS quantitative performance. Taking into account their versatility, user-friendliness and robustness, we believe that HRMS should be seen more and more as key instruments in quantitative LC-MS analyses. In this scenario, most targeted LC-HRMS analyses should be performed by HR-FS recording virtually "all" ions. In addition to absolute quantifications, HR-FS will allow the relative quantifications of hundreds of metabolites in plasma revealing individual's metabolome and exposome. This phenotyping of known metabolites should promote HRMS in clinical environment. A few other LC-HRMS analyses should be performed in single-ion-monitoring or MS/MS mode when increased sensitivity and/or detection selectivity will be necessary.

  3. Improved heart, lung and target dose with deep inspiration breath hold in a large clinical series of breast cancer patients

    International Nuclear Information System (INIS)

    Background and purpose: This study aims at evaluating the effect of deep-inspiration breath hold (DIBH) on target coverage and dose to organs at risk in a large series of breast cancer patients. Materials and methods: Clinical dose plans for 319 breast cancer patients were evaluated: 144 left-sided patients treated with DIBH and 175 free-breathing (FB) patients (83 left-sided and 92 right-sided). All patients received whole breast irradiation with tangential fields, based on a forward-planned intensity-modulated radiation therapy (IMRT) technique. Dose to heart, ipsi-lateral lung and ipsi-lateral breast were assessed and median values compared between patient groups. Results: Comparing group median values, DIBH plans show large reductions of dose to the heart compared with left-sided FB plans; V20Gy (relative volume receiving ⩾20 Gy) for the heart is reduced from 7.8% to 2.3% (−70%, p < 0.0001), V40Gy from 3.4% to 0.3% (−91%, p < 0.0001) and mean dose from 5.2 to 2.7 Gy (−48%, p < 0.0001). Lung dose also shows a small reduction in V20Gy (p < 0.04), while median target coverage is slightly improved (p = 0.0002). Conclusions: In a large series of clinical patients we find that implementation of DIBH in daily clinical practice results in reduced irradiation of heart and lung, without compromising target coverage

  4. Molecular targets for the treatment of pancreatic cancer: Clinical and experimental studies

    OpenAIRE

    Matsuoka, Tasuku; Yashiro, Masakazu

    2016-01-01

    Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients with pancreatic cancer remain unsatisfactory. Molecularly targeted cancer therapy has advanced in the past decade with the use of a number of pathways as candidates of therapeutic targets. This review summarizes the molecular features of this refractory disease while focusing on the...

  5. Targeted therapies in cancer - challenges and chances offered by newly developed techniques for protein analysis in clinical tissues.

    Science.gov (United States)

    Malinowsky, K; Wolff, C; Gündisch, S; Berg, D; Becker, Kf

    2010-12-19

    In recent years, new anticancer therapies have accompanied the classical approaches of surgery and radio- and chemotherapy. These new forms of treatment aim to inhibit specific molecular targets namely altered or deregulated proteins, which offer the possibility of individualized therapies.The specificity and efficiency of these new approaches, however, bring about a number of challenges. First of all, it is essential to specifically identify and quantify protein targets in tumor tissues for the reasonable use of such targeted therapies. Additionally, it has become even more obvious in recent years that the presence of a target protein is not always sufficient to predict the outcome of targeted therapies. The deregulation of downstream signaling molecules might also play an important role in the success of such therapeutic approaches. For these reasons, the analysis of tumor-specific protein expression profiles prior to therapy has been suggested as the most effective way to predict possible therapeutic results. To further elucidate signaling networks underlying cancer development and to identify new targets, it is necessary to implement tools that allow the rapid, precise, inexpensive and simultaneous analysis of many network components while requiring only a small amount of clinical material.Reverse phase protein microarray (RPPA) is a promising technology that meets these requirements while enabling the quantitative measurement of proteins. Together with recently developed protocols for the extraction of proteins from formalin-fixed, paraffin-embedded (FFPE) tissues, RPPA may provide the means to quantify therapeutic targets and diagnostic markers in the near future and reliably screen for new protein targets.With the possibility to quantitatively analyze DNA, RNA and protein from a single FFPE tissue sample, the methods are available for integrated patient profiling at all levels of gene expression, thus allowing optimal patient stratification for

  6. Targeted therapies in cancer - challenges and chances offered by newly developed techniques for protein analysis in clinical tissues

    Directory of Open Access Journals (Sweden)

    K Malinowsky, C Wolff, S Gündisch, D Berg, KF Becker

    2011-01-01

    Full Text Available In recent years, new anticancer therapies have accompanied the classical approaches of surgery and radio- and chemotherapy. These new forms of treatment aim to inhibit specific molecular targets namely altered or deregulated proteins, which offer the possibility of individualized therapies.The specificity and efficiency of these new approaches, however, bring about a number of challenges. First of all, it is essential to specifically identify and quantify protein targets in tumor tissues for the reasonable use of such targeted therapies. Additionally, it has become even more obvious in recent years that the presence of a target protein is not always sufficient to predict the outcome of targeted therapies. The deregulation of downstream signaling molecules might also play an important role in the success of such therapeutic approaches. For these reasons, the analysis of tumor-specific protein expression profiles prior to therapy has been suggested as the most effective way to predict possible therapeutic results. To further elucidate signaling networks underlying cancer development and to identify new targets, it is necessary to implement tools that allow the rapid, precise, inexpensive and simultaneous analysis of many network components while requiring only a small amount of clinical material.Reverse phase protein microarray (RPPA is a promising technology that meets these requirements while enabling the quantitative measurement of proteins. Together with recently developed protocols for the extraction of proteins from formalin-fixed, paraffin-embedded (FFPE tissues, RPPA may provide the means to quantify therapeutic targets and diagnostic markers in the near future and reliably screen for new protein targets.With the possibility to quantitatively analyze DNA, RNA and protein from a single FFPE tissue sample, the methods are available for integrated patient profiling at all levels of gene expression, thus allowing optimal patient stratification

  7. Performance Comparison of Hybrid GA-PSO Based Tuned IMMs for Maneuver Target Tracking

    Directory of Open Access Journals (Sweden)

    Ravi Kumar Jatoth

    2013-11-01

    Full Text Available Target tracking is very important field of research as it has wider applications in defense as well as civilian applications. Kalman filter is generally used for such applications. When the process and measurements are non linear extensions of Kalman filters like Extended Kalman Filter, Unscented Kalman Filters are widely used. UKF can give estimations up to second order characteristics of random process. The target is maneuvering and switching among different models like constant velocity (CV, constant acceleration (CA or constant turn (CT, Interactive Multiple Models (IMM are employed. Implementation of IMM filters for any application is difficult because of initialization of Kalman filter i,e, tuning of filter has to be performed before applying to real time situations. It demands prior estimations of Noise covariance matrices which are left for engineering intuitions. This paper presents the nonlinear state estimation using IMM and tuning of the filter is done using bio-inspired algorithms like PSO GA and Hybrid GA-PSO.

  8. 42 CFR 493.1415 - Condition: Laboratories performing moderate complexity testing; clinical consultant.

    Science.gov (United States)

    2010-10-01

    ... laboratory must have a clinical consultant who meets the qualification requirements of § 493.1417 of this... complexity testing; clinical consultant. 493.1415 Section 493.1415 Public Health CENTERS FOR MEDICARE... LABORATORY REQUIREMENTS Personnel for Nonwaived Testing Laboratories Performing Moderate Complexity...

  9. Clinical Observed Performance Evaluation: A Prospective Study in Final Year Students of Surgery

    Science.gov (United States)

    Markey, G. C.; Browne, K.; Hunter, K.; Hill, A. D.

    2011-01-01

    We report a prospective study of clinical observed performance evaluation (COPE) for 197 medical students in the pre-qualification year of clinical education. Psychometric quality was the main endpoint. Students were assessed in groups of 5 in 40-min patient encounters, with each student the focus of evaluation for 8 min. Each student had a series…

  10. Reviewing Residents' Competence : A Qualitative Study of the Role of Clinical Competency Committees in Performance Assessment

    NARCIS (Netherlands)

    Hauer, Karen E.; Chesluk, Benjamin; Iobst, William; Holmboe, Eric; Baron, Robert B.; Boscardin, Christy K.; ten Cate, Olle; O'Sullivan, Patricia S.

    2015-01-01

    Purpose Clinical competency committees (CCCs) are now required in graduate medical education. This study examined how residency programs understand and operationalize this mandate for resident performance review. Method In 2013, the investigators conducted semistructured interviews with 34 residency

  11. Clinical problems with the performance of euthanasia and physician-assisted suicide in The Netherlands

    NARCIS (Netherlands)

    J.H. Groenewoud (Hanny); A. van der Heide (Agnes); B.D. Onwuteaka-Philipsen (Bregje); D.L. Willems (Dick); P.J. van der Maas (Paul); G. van der Wal (Gerrit)

    2000-01-01

    textabstractBACKGROUND AND METHODS: The characteristics and frequency of clinical problems with the performance of euthanasia and physician-assisted suicide are uncertain. We analyzed data from two studies of euthanasia and physician-assisted suicide in The Netherlands

  12. Development and Psychometric Evaluation of the Nursing Instructors’ Clinical Teaching Performance Inventory

    OpenAIRE

    2014-01-01

    Evaluation of nursing instructors’ clinical teaching performance is a prerequisite to the quality assurance of nursing education. One of the most common procedures for this purpose is using student evaluations. This study was to develop and evaluate the psychometric properties of Nursing Instructors’ Clinical Teaching Performance Inventory (NICTPI). The primary items of the inventory were generated by reviewing the published literature and the existing questionnaires as well as consulting wit...

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

    Directory of Open Access Journals (Sweden)

    Jing eYuan

    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.

  14. Strengthening the Role of Ocular Pathology in Clinical Thinking Training Targeting for House Staff

    Institute of Scientific and Technical Information of China (English)

    Yungang Ding; Wenxin Zhang; Xiaohui Liu; Jianxian Lin; Jianliang Zheng; Yongping Li

    2011-01-01

    Ocular pathology serves as one vital branch subject of histopathology, and also as a basic ocular science analysing the pathogenesis of eye disease,the regular pattern of disease progress,and ocular morphology,tissue metabolism and functional changes noted during the onset of ocular diseases.The underlying purpose lies in revealing and investigating the mechanism of such diseases and the nature of lesions,providing essential theoretical evidence to diagnosis and treatment of eye diseases.ocular pathology acts as a bridge connecting basic and clinical medical science1.Clinical ophthalmologists,especially junior house staff,should attach importance to ocular pathology,understand,be familiar with,and master basic knowledge in ocular pathological subject to cultivate sound clinical thinking and analytical ability and to improve comprehensive diagnosis and treatment efficacy in clinical setting.

  15. Metaplastic breast cancer: clinical overview and molecular aberrations for potential targeted therapy.

    Science.gov (United States)

    Abouharb, Sausan; Moulder, Stacy

    2015-03-01

    Metaplastic breast cancer is a rare subtype of invasive mammary carcinoma, with an aggressive behavior and usually poor outcome. Responses to systemic chemotherapy are suboptimal compared to patients with standard invasive ductal carcinoma. Limited data are available in regards to best treatment modalities, including chemotherapy. This review gives an overview of metaplastic breast cancer and its clinical and pathologic characteristics, in addition to treatment strategies, clinical trials, and future directions.

  16. Performance of combined clinical mammography and needle biopsy: a nationwide study from Denmark

    DEFF Research Database (Denmark)

    Jensen, Allan; Rank, Fritz; Dyreborg, Uffe;

    2006-01-01

    Clinical mammography and needle biopsy are key tools for non-operative assessment of breast lesions. We evaluated the performance of all combined tests undertaken in Denmark in 2000. Clinical mammography and needle biopsy data were collected and linked to final cancer outcome, to determine...... sensitivity, specificity, and predictive values of clinical mammography, needle biopsy, and combined test. In 2000, 6709 combined tests were performed in 36 mammography clinics in Denmark. The combined test was consistently more sensitive than any single test, increasing the proportion of women correctly...... identified with breast cancer by 9% compared with clinical mammography alone. For concordant combined tests (i.e. either both benign or both malignant), specificity and positive predictive value were 100%, sensitivity was 99.1%, and positive predictive value was 99.6%. Therefore, Danish patients...

  17. Grading the performance of clinical skills: lessons to be learned from the performing arts.

    Science.gov (United States)

    Roberts, Deborah

    2011-08-01

    The drift towards competency based nurse interventions has seen a growth in concern regarding the most appropriate methods of assessment of such competencies. Nurse educators and practitioners alike are struggling with the concept of measuring the performance of nursing skills; due to an uneasy relationship between competence, capability, intuition and expertise. Different currencies of value may be ascribed to the assessment of nursing practice, resulting in the use of subjective judgements together with the development of assessment criteria which have different weightings, depending on the values of the assessor. Within the performing arts, students' practice performance is also assessed, with seemingly many similarities between applying value to performance in dance or theatre and nursing. Within performing arts assessment a balancing act is also being played out between academic education and professional training (where complex performances are notoriously hard to evaluate). This paper explores the nature of assessment within the performing arts and makes suggestions regarding their application within the context of nurse education. If nursing is indeed a blend of art and science, then it seems sensible to look to the performing arts to see if lessons could be learned.

  18. Concepts and targets in triple-negative breast cancer: recent results and clinical implications.

    Science.gov (United States)

    Saha, Poornima; Nanda, Rita

    2016-09-01

    Triple-negative breast cancer (TNBC) is a heterogeneous disease in which tumors are defined by lack of expression of the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) receptor. No targeted therapies are available for the treatment of TNBC, and chemotherapy remains the standard of care. Gene expression profiling has identified six distinct molecular subtypes of TNBC. The identification of novel targets, coupled with the development of therapies for different subsets of TNBC, holds great promise for the future treatment of this aggressive form of breast cancer. This review focuses on novel therapies in development for the treatment of TNBC.

  19. Regulative change targeting energy performance of buildings in Sweden. Key drivers and main implications

    Energy Technology Data Exchange (ETDEWEB)

    Fuglseth, Bente Beckstroem

    2009-02-15

    This report has explored changes in two regulations targeting energy performance of buildings in Sweden, energy requirements and certification of buildings. The objective has been to investigate the effect of the implementation of the EU directive on energy performance of buildings (EPBD) on these two regulations and to what degree the directive can explain the regulative changes. The analytical framework has also included domestic factors; the influence of the national government and the organizational field. The analysis revealed that whereas the EPBD has acted only as facilitator in connection with the changes in energy requirements, it has been the sole driver of some of the changes in Sweden's new certification system. Several of the changes during the period studied can however be traced to the national government and the organizational field. But the EPBD has also worked as a facilitator of the changes promoted by domestic actors. The directive has been used to legitimize radical changes that would have been difficult to implement in other ways. (Author). 40 refs., 2 tabs

  20. Effect of Target Configuration on the Neutronic Performance of the Gas-Cooled ADS

    CERN Document Server

    Biss, K; Shetty, N; Nabbi, R

    2013-01-01

    With the utilization of nuclear energy transuranic elements like Pu, Am and Cm are produced causing high, long term radioactivity and radio toxicity, respectively. To reduce the radiological impact on the environment and to the repository Partitioning and Transmutation is considered as an efficient way. In this respect comprehensive research works are performed at different research institutes worldwide. The results show that the transmutation of TRU is achieved with fast neutrons due to the higher fission probability. Based on Accelerator Driven Systems (ADS) those neutrons are used in a particular system, in which mainly liquid metal eutectic (lead bismuth) is used as coolant. The neutronic performance of an ADS system based on gas cooling was studied in this work by using the simulation tool MCNPX. The usage of the Monte-Carlo method in MCNPX allows the simulation of the physical processes in a 3D-model of the core. In dependence of the spallation target material and design several parameters like the mult...

  1. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation.

    Science.gov (United States)

    Rincon, Melvin Y; VandenDriessche, Thierry; Chuah, Marinee K

    2015-10-01

    Gene therapy is a promising modality for the treatment of inherited and acquired cardiovascular diseases. The identification of the molecular pathways involved in the pathophysiology of heart failure and other associated cardiac diseases led to encouraging preclinical gene therapy studies in small and large animal models. However, the initial clinical results yielded only modest or no improvement in clinical endpoints. The presence of neutralizing antibodies and cellular immune responses directed against the viral vector and/or the gene-modified cells, the insufficient gene expression levels, and the limited gene transduction efficiencies accounted for the overall limited clinical improvements. Nevertheless, further improvements of the gene delivery technology and a better understanding of the underlying biology fostered renewed interest in gene therapy for heart failure. In particular, improved vectors based on emerging cardiotropic serotypes of the adeno-associated viral vector (AAV) are particularly well suited to coax expression of therapeutic genes in the heart. This led to new clinical trials based on the delivery of the sarcoplasmic reticulum Ca(2+)-ATPase protein (SERCA2a). Though the first clinical results were encouraging, a recent Phase IIb trial did not confirm the beneficial clinical outcomes that were initially reported. New approaches based on S100A1 and adenylate cyclase 6 are also being considered for clinical applications. Emerging paradigms based on the use of miRNA regulation or CRISPR/Cas9-based genome engineering open new therapeutic perspectives for treating cardiovascular diseases by gene therapy. Nevertheless, the continuous improvement of cardiac gene delivery is needed to allow the use of safer and more effective vector doses, ultimately bringing gene therapy for heart failure one step closer to reality.

  2. The effect of image-guided radiation therapy on the margin between the clinical target volume and planning target volume in lung cancer

    International Nuclear Information System (INIS)

    Introduction: This study aimed to evaluate the effect of image-guided radiation therapy (IGRT) on the margin between the clinical target volume (CTV) and planning target volume (PTV) in lung cancer. Methods: The CTV and PTV margin were determined in three dimensions by four radiation oncologists using a standard method in 10 lung cancer patients, and compared to consensus values. Transfer error was measured using a rigid phantom containing gold markers. Systematic error and random error set up errors were calculated in three dimensions from pre-treatment and post-treatment cone beam CT scans. Finally, the margin between the CTV and PTV was corrected for set up error and calculated. Results: The margins between the CTV and PTV with IGRT (and without IGRT) were 0.88 cm (0.96 cm), 0.99 cm (1.08 cm) and 1.28 cm (1.82 cm) in the anterior and posterior (AP), left and right (LR) and superior and inferior (SI) directions, respectively. Images from two other patients verified the validity of the corrected margin. The target delineation errors of the radiation oncologists are considered to be the largest compared with the set up errors. The application of IGRT reduced the set up errors and the margins between CTV and PTV. Conclusions: The delineation errors of radiation oncologists are the most important factor to consider for the margin between CTV and PTV for lung cancer. IGRT can reduce the margins by reducing the set up errors, especially in the SI direction. Further research is required to assess whether the reduction in the margin is solely based on set up errors

  3. A review on pro- and anti-angiogenic factors as targets of clinical intervention

    NARCIS (Netherlands)

    Bouis, D; Kusumanto, Y; Meijer, C; Mulder, NH; Hospers, GAP

    2006-01-01

    Angiogenesis plays an important role in physiology and pathology. It is a tightly regulated process, influenced by the microenvironment and modulated by a multitude of pro- and anti-angiogenic factors. A thorough understanding of the angiogenic process may lead to novel therapies to target ischemic

  4. Attainment of multifactorial treatment targets among the elderly in a lipid clinic

    Institute of Scientific and Technical Information of China (English)

    Fotios Barkas; Evangelos Liberopoulos; Eleftherios Klouras; Angelos Liontos; Moses Elisaf

    2015-01-01

    Objective To examine target attainment of lipid-lowering, antihypertensive and antidiabetic treatment in the elderly in a specialist set-ting of a University Hospital in Greece. Methods This was a retrospective study including consecutive subjects≥65 years old (n=465) with a follow-up ≥ 3 years. Low-density lipoprotein cholesterol (LDL-C), blood pressure (BP) and glycated hemoglobin (HbA1c) goal achievement were recorded according to European Society of Cardiology/European Atherosclerosis Society (ESC/EAS), European Society of Hypertension (ESH)/ESC and European Association for the Study of Diabetes (EASD) guidelines. Results The LDL-C targets were attained by 27%, 48%and 62%of very high, high and moderate risk patients, respectively. Those receiving statin+ezetimibe achieved higher rates of LDL-C goal achievement compared with those receiving statin monotherapy (48%vs. 33%, P<0.05). Of the diabetic sub-jects, 71%had BP<140/85 mmHg, while 78%of those without diabetes had BP<140/90 mmHg. A higher proportion of the non-diabetic individuals (86%) had BP<150/90 mmHg. Also, a higher proportion of those with diabetes had HbA1c<8%rather than<7%(88%and 47%, respectively). Of note, almost one out of three non-diabetic individuals and one out of ten diabetic individuals had achieved all three treatment targets. Conclusions Even in a specialist setting of a University Hospital, a high proportion of the elderly remain at suboptimal LDL-C, BP and HbA1c levels. The use of drug combinations could improve multifactorial treatment target attainment, while less strict tar-gets could be more easily achieved in this population.

  5. The Relationship between Emotional Intelligence, Self-Efficacy, and Clinical Performance in Associate Degree Nursing Students

    Science.gov (United States)

    Rice, Eileen W.

    2013-01-01

    The purpose of this study was to explore self-efficacy, an individual's beliefs about his or her ability to perform a series of tasks, and emotional intelligence, an individual's ability to perceive, use, understand, and manage emotions, as predictors for successful clinical performance in nursing students. The participants were 49 female and 7…

  6. Comparison of Clinical Targeted Next-Generation Sequence Data from Formalin-Fixed and Fresh-Frozen Tissue Specimens

    OpenAIRE

    Spencer, David H.; Sehn, Jennifer K.; Abel, Haley J.; Watson, Mark A.; Pfeifer, John D; Duncavage, Eric J.

    2013-01-01

    Next-generation sequencing (NGS) has emerged as a powerful technique for the detection of genetic variants in the clinical laboratory. NGS can be performed using DNA from FFPE tissue, but it is unknown whether such specimens are truly equivalent to unfixed tissue for NGS applications. To address this question, we performed hybridization-capture enrichment and multiplexed Illumina NGS for 27 cancer-related genes using DNA from 16 paired fresh-frozen and routine FFPE lung adenocarcinoma specime...

  7. Impact of tDCS on Performance and Learning of Target Detection: Interaction with Stimulus Characteristics and Experimental Design

    Science.gov (United States)

    Coffman, B. A.; Trumbo, M. C.; Flores, R. A.; Garcia, C. M.; van der Merwe, A. J.; Wassermann, E. M.; Weisend, M. P.; Clark, V. P.

    2012-01-01

    We have previously found that transcranial direct current stimulation (tDCS) over right inferior frontal cortex (RIFC) enhances performance during learning of a difficult visual target detection task (Clark et al., 2012). In order to examine the cognitive mechanisms of tDCS that lead to enhanced performance, here we analyzed its differential…

  8. Natural antioxidants for non-alcoholic fatty liver disease: molecular targets and clinical perspectives.

    Science.gov (United States)

    Salomone, Federico; Godos, Justyna; Zelber-Sagi, Shira

    2016-01-01

    Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), is emerging as a main health problem in industrialized countries. Lifestyle modifications are effective in the treatment of NAFLD; however, the long-term compliance is low. Therefore, several pharmacological treatments have been proposed but none has shown significant efficacy or long-term safety. Natural polyphenols are a heterogeneous class of polyphenolic compounds contained in vegetables, which are being proposed for the treatment of different metabolic disorders. Although the beneficial effect of these compounds has traditionally related to their antioxidant properties, they also exert several beneficial effects on hepatic and extra-hepatic glucose and lipid homeostasis. Furthermore, natural polyphenols exert antifibrogenic and antitumoural effects in animal models, which appear relevant from a clinical point of view because of the association of NASH with cirrhosis and hepatocellular carcinoma. Several polyphenols, such anthocyanins, curcumin and resveratrol and those present in coffee, tea, soy are available in the diet and their consumption can be proposed as part of a healthy diet for the treatment of NAFLD. Other phenolic compounds, such as silymarin, are commonly consumed worldwide as nutraceuticals or food supplements. Natural antioxidants are reported to have beneficial effects in preclinical models of NAFLD and in pilot clinical trials, and thus need clinical evaluation. In this review, we summarize the existing evidence regarding the potential role of natural antioxidants in the treatment of NAFLD and examine possible future clinical applications. PMID:26436447

  9. From DNA to Targeted Therapeutics: Bringing Synthetic Biology to the Clinic

    OpenAIRE

    Chen, Yvonne Y; Smolke, Christina D.

    2011-01-01

    Synthetic biology aims to make biological engineering more scalable and predictable, lowering the cost and facilitating the translation of synthetic biological systems to practical applications. Increasingly sophisticated, rationally designed synthetic systems that are capable of complex functions pave the way to translational applications, including disease diagnostics and targeted therapeutics. Here, we provide an overview of recent developments in synthetic biology in the context of transl...

  10. Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic.

    Science.gov (United States)

    Imamura, Yusuke; Sadar, Marianne D

    2016-08-01

    The androgen receptor is a transcription factor and validated therapeutic target for prostate cancer. Androgen deprivation therapy remains the gold standard treatment, but it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer. There have been improvements in the therapeutic landscape with new agents approved, such as abiraterone acetate, enzalutamide, sipuleucel-T, cabazitaxel and Ra-223, in the past 5 years. New insight into the mechanisms of resistance to treatments in advanced disease is being and has been elucidated. All current androgen receptor-targeting therapies inhibit the growth of prostate cancer by blocking the ligand-binding domain, where androgen binds to activate the receptor. Persuasive evidence supports the concept that constitutively active androgen receptor splice variants lacking the ligand-binding domain are one of the resistant mechanisms underlying advanced disease. Transcriptional activity of the androgen receptor requires a functional AF-1 region in its N-terminal domain. Preclinical evidence proved that this domain is a druggable target to forecast a potential paradigm shift in the management of advanced prostate cancer. This review presents an overview of androgen receptor-related mechanisms of resistance as well as novel therapeutic agents to overcome resistance that is linked to the expression of androgen receptor splice variants in castration-resistant prostate cancer. PMID:27302572

  11. Clinical performance of a light-cured denture base material compared to polymethylmethacrylate--a randomized clinical study.

    Science.gov (United States)

    Gohlke-Wehrße, Hanna-Lena; Giese-Kraft, Katja; Wöstmann, Bernd

    2012-06-01

    The aim of this study was to evaluate the clinical long-term performance of a visible light-cured resin (VLCR) denture base material and to compare it to a well-established polymethylmethacrylate (PMMA)-based denture acrylic in a randomized split-mouth clinical long-term study. One hundred removable partial dentures in 90 patients, with at least two saddles each, were investigated. One saddle was made of VLCR, while the other was made of PMMA at random. Plaque adhesion, tissue reaction, and technical parameters of the dentures were assessed 6, 12, and 18 months after treatment. Statistical analysis was performed using the Wilcoxon rank-sum test. Though VLCR showed higher plaque adhesion than PMMA after 6, 12, and 18 months (p denture acrylic and metal and the boundary between denture acrylic and denture tooth PMMA was rated higher than VLCR. The surface quality of the upper side of the denture saddles showed no significant differences (p > 0.05). Neither VLCR nor PMMA showed discoloration at any point in time (p > 0.05). It can be concluded that VLCR is a viable alternative for the production of removable dentures. Especially in patients with hypersensitivities to PMMA, VLCR is particularly suitable for clinical use.

  12. Lognormal approximation for quantifying performance of Bayesian target classifier in presence of pose uncertainty

    Science.gov (United States)

    Irving, William W.; Washburn, Robert B.; Tenney, Robert R.

    1996-06-01

    We analyze a class of Bayesian, binary hypothesis-testing problems relevant to the classification of targets in the presence of pose uncertainty. When hypothesis H1 is true, we observe one of N1 possible complex-valued signal vectors, immersed in additive, white complex Gaussian noise; when hypothesis H2 occurs, we observe one of N2 other possible signal vectors, again immersed in noise. Given prior probabilities for H1 and H2, and also prior conditional probabilities for the presence of each of the signal vectors, the problem is to determine both a decision rule that minimizes the error probability and also the associated minimal problem is to determine both a decision rule that minimizes the error probability and also the associated minimal error probability. The optimal decision rule here is well-known to be a likelihood ratio test having a straightforward analytical form; however, the performance of this optimal test is intractable analytically, and thus approximations are required to calculate the probability of error. We devise an approximation based on the observation that both the numerator and denominator of the likelihood ratio test statistic consist of sums of lognormal random variables. Previous work has shown that such sums are well approximated as themselves having a lognormal distribution; we exploit this fact to obtain a simple, approximate error probability expression. For a specific problem, we then compare the resulting error probability numbers with ones obtained via Monte Carlo simulation, demonstrating good agreement between the two methods.

  13. 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

  14. The impact of patient support programs on adherence, clinical, humanistic, and economic patient outcomes: a targeted systematic review

    Directory of Open Access Journals (Sweden)

    Ganguli A

    2016-04-01

    Full Text Available Arijit Ganguli,1 Jerry Clewell,2 Alicia C Shillington3 1Department of Health Economics and Outcomes Research, 2Department of Medical Affairs, AbbVie, North Chicago, IL, USA; 3EPI-Q Inc., Oak Brook, IL, USA Background: Patient support programs (PSPs, including medication management and counseling, have the potential to improve care in chronic disease states with complex therapies. Little is known about the program’s effects on improving clinical, adherence, humanistic, and cost outcomes. Purpose: To conduct a targeted review describing medical conditions in which PSPs have been implemented; support delivery components (eg, face-to-face, phone, mail, and internet; and outcomes associated with implementation. Data sources: MEDLINE – 10 years through March 2015 with supplemental handsearching of reference lists. Study selection: English-language trials and observational studies of PSPs providing at minimum, counseling for medication management, measurement of ≥1 clinical outcome, and a 3-month follow-up period during which outcomes were measured. Data extraction: Program characteristics and related clinical, adherence, humanistic, and cost outcomes were abstracted. Study quality and the overall strength of evidence were reviewed using standard criteria. Data synthesis: Of 2,239 citations, 64 studies met inclusion criteria. All targeted chronic disease processes and the majority (48 [75%] of programs offered in-clinic, face-to-face support. All but 9 (14.1% were overseen by allied health care professionals (eg, nurses, pharmacists, paraprofessionals. Forty-one (64.1% reported at least one significantly positive clinical outcome. The most frequent clinical outcome impacted was adherence, where 27 of 41 (66% reported a positive outcome. Of 42 studies measuring humanistic outcomes (eg, quality of life, functional status, 27 (64% reported significantly positive outcomes. Only 15 (23.4% programs reported cost or utilization-related outcomes, and, of

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Eccles Martin P

    2012-07-01

    Full Text Available Abstract 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.

  17. CLINICAL EXPERIENCE WITH USTEKINUMAB IN THE TREATMENT OF EARLY PSORIATIC ARTHRITIS USING TREAT-TO-TARGET STRATEGY

    Directory of Open Access Journals (Sweden)

    E. Yu. Loginova

    2015-01-01

    Full Text Available The new Treat-to-Target (T2T strategy in the treatment of early psoriatic arthritis (PsA is aimed at achieving remission or low disease activity. As of now, the new biological agent ustekinumb (UST, anti-interleukin (IL 12/23 monoclonal antibodies, was used to treat psoriasis and PsA. The paper presents clinical observations of the efficacy of UST in early PsA treated according T2T strategy. The described clinical cases demonstrate that use of UST 45 mg both alone and in combination with methotrexate for early PsA with moderate and high activity reduced manifestations of peripheral arthritis and psoriasis, promoting rapid achievement of remission or minimal disease activity. Overall, UST is well tolerated by the patients.

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

    Science.gov (United States)

    Castro-Fernández, Cristina; Arias, Manuel; Blanco-Arias, Patricia; Santomé-Collazo, Luis; Amigo, Jorge; Carracedo, Ángel; Sobrido, Maria-Jesús

    2015-06-01

    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.

  19. 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.

  20. Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility.

    Science.gov (United States)

    Alvi, Muhammad A; McArt, Darragh G; Kelly, Paul; Fuchs, Marc-Aurel; Alderdice, Matthew; McCabe, Clare M; Bingham, Victoria; McGready, Claire; Tripathi, Shailesh; Emmert-Streib, Frank; Loughrey, Maurice B; McQuaid, Stephen; Maxwell, Perry; Hamilton, Peter W; Turkington, Richard; James, Jacqueline A; Wilson, Richard H; Salto-Tellez, Manuel

    2015-08-28

    Small bowel accounts for only 0.5% of cancer cases in the US but incidence rates have been rising at 2.4% per year over the past decade. One-third of these are adenocarcinomas but little is known about their molecular pathology and no molecular markers are available for clinical use. Using a retrospective 28 patient matched normal-tumor cohort, next-generation sequencing, gene expression arrays and CpG methylation arrays were used for molecular profiling. Next-generation sequencing identified novel mutations in IDH1, CDH1, KIT, FGFR2, FLT3, NPM1, PTEN, MET, AKT1, RET, NOTCH1 and ERBB4. Array data revealed 17% of CpGs and 5% of RNA transcripts assayed to be differentially methylated and expressed respectively (p clinically exploitable markers.

  1. Targeting Notch signaling pathway in cancer: Clinical development advances and challenges

    OpenAIRE

    Takebe, Naoko; Nguyen, Dat; Yang, Sherry X

    2013-01-01

    Notch signaling plays an important role in development and cell fate determination, and it is deregulated in human hematologic malignancies and solid tumors. This review includes a brief introduction of the relevant pathophysiology of Notch signaling pathway and primarily focuses on the clinical development of promising agents that either obstruct Notch receptor cleavages such as γ-secretase inhibitors (GSIs) or interfere with the Notch ligand–receptor interaction by monoclonal antibodies (mA...

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

    OpenAIRE

    Cristina Castro-Fernández; Manuel Arias; Patricia Blanco-Arias; Luis Santomé-Collazo; Jorge Amigo; Ángel Carracedo; Maria-Jesús Sobrido

    2015-01-01

    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...

  3. Review of novel therapeutic targets for improving heart failure treatment based on experimental and clinical studies

    OpenAIRE

    Bonsu KO; Owusu IK; Buabeng KO; Reidpath DD; Kadirvelu A

    2016-01-01

    Kwadwo Osei Bonsu,1,2 Isaac Kofi Owusu,3 Kwame Ohene Buabeng,4 Daniel Diamond Reidpath,1 Amudha Kadirvelu1 1School of Medicine and Health Sciences, Monash University Sunway Campus, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 2Accident and Emergency Directorate, Komfo Anokye Teaching Hospital, 3Department of Medicine, 4Department of Clinical and Social Pharmacy, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Abstra...

  4. Review of novel therapeutic targets for improving heart failure treatment based on experimental and clinical studies

    OpenAIRE

    Osei Bonsu, Kwadwo

    2016-01-01

    Kwadwo Osei Bonsu,1,2 Isaac Kofi Owusu,3 Kwame Ohene Buabeng,4 Daniel Diamond Reidpath,1 Amudha Kadirvelu1 1School of Medicine and Health Sciences, Monash University Sunway Campus, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 2Accident and Emergency Directorate, Komfo Anokye Teaching Hospital, 3Department of Medicine, 4Department of Clinical and Social Pharmacy, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Ab...

  5. Clinical Perspectives on Targeting of Myeloid Derived Suppressor Cells in the Treatment of Cancer

    Directory of Open Access Journals (Sweden)

    Yana George Najjar

    2013-03-01

    Full Text Available Tumors escape immune recognition by several mechanisms, and induction of myeloid derived suppressor cells (MDSC is thought to play a major role in tumor mediated immune evasion. MDSC arise from myeloid progenitor cells that do not differentiate into mature dendritic cells, granulocytes or macrophages, and are characterized by the ability to suppress T cell and natural killer (NK cell function. They are increased in patients with cancer including renal cell carcinoma (RCC, and their levels have been shown to correlate with prognosis and overall survival. Multiple methods of inhibiting MDSCs are currently under investigation. These can broadly be categorized into methods that a promote differentiation of MDSC into mature, non-suppressive cells (all trans retinoic acid, vitamin D, b decrease MDSC levels (sunitinib, gemcitabine, 5-FU, CDDO-Me, or c functionally inhibit MDSC (PDE-5 inhibitors, COX-2 inhibitors. Recently, several pre-clinical tumor models of combination therapy involving sunitinib plus vaccines and/or adoptive therapy have shown promise in MDSC inhibition and improved outcomes in the tumor bearing host. Current clinical trials are underway in RCC patients to assess not only the impact on clinical outcome, but how this combination can enhance anti-tumor immunity and reduce immune suppression. Decreasing immune suppression by MDSC in the cancer host may improve outcomes and prolong survival in this patient population.

  6. Effect of metabolic abnormalities on cognitive performance and clinical symptoms in schizophrenia

    OpenAIRE

    Wysokiński, Adam; Dzienniak, Małgorzata; Kłoszewska, Iwona

    2013-01-01

    Aim. The objective of this study is to determine whether and how metabolic abnormalities are associated with clinical symptoms and cognitive performance in schizophrenia. Methods. 46 adult patients with schizophrenia taking first- or second generation antipsychotics were included in the study. The following data were collected: BMI, abdominal circumference, lipid panel and blood glucose, blood pressure and treatment of comorbidities. Clinical symptoms were assessed using PANSS, CDSS, CGI a...

  7. Performances of 27 MEDLINE systems tested by searches with clinical questions.

    OpenAIRE

    Haynes, R B; Walker, C J; McKibbon, K. A.; Johnston, M. E.; Willan, A R

    1994-01-01

    OBJECTIVE: To compare the performances of online and compact-disc (CD-ROM) versions of the National Library of Medicine's (NLM) MEDLINE database. DESIGN: Analytic survey. INTERVENTION: Clinical questions were drawn from 18 searches originally conducted spontaneously by clinicians from wards and clinics who had used Grateful Med Version 4.0. Clinicians' search strategies were translated to meet the specific requirements of 13 online and 14 CD-ROM MEDLINE systems. A senior librarian and vendors...

  8. Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

    Science.gov (United States)

    Vici, P; Pizzuti, L; Mariani, L; Zampa, G; Santini, D; Di Lauro, L; Gamucci, T; Natoli, C; Marchetti, P; Barba, M; Maugeri-Saccà, M; Sergi, D; Tomao, F; Vizza, E; Di Filippo, S; Paolini, F; Curzio, G; Corrado, G; Michelotti, A; Sanguineti, G; Giordano, A; De Maria, R; Venuti, A

    2016-10-01

    Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

  9. Neuronal nicotinic receptors as novel targets for inflammation and neuroprotection:mechanistic considerations and clinical relevance

    Institute of Scientific and Technical Information of China (English)

    Merouane BENGHEKIF

    2009-01-01

    A number of studies have confirmed the potential for neuronal nicotinic acetylcholine receptor (NNR)-mediated neuro- protection and, more recently, its anti-inflammatory effects. The mechanistic overlap between these pathways and the ubiquitous effects observed following diverse insults suggest that NNRs modulate fundamental pathways involved in cell survival. These results have wide-reaching implications for the design of experimental therapeutics that regulate inflamma- tory and anti-apoptotic responses through NNRs and represent an initial step toward understanding the benefits of novel therapeutic strategies for the management of central nervous system disorders that target neuronal survival and associated inflammatory processes.

  10. Quality Research in Radiation Oncology Analysis of Clinical Performance Measures in the Management of Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Karyn A., E-mail: goodmank@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Khalid, Najma [Quality Research in Radiation Oncology, American College of Radiology Clinical Research Center, Philadelphia, Pennsylvania (United States); Kachnic, Lisa A. [Department of Radiation Oncology, Boston University Medical Center, Boston, Massachusetts (United States); Minsky, Bruce D. [Department of Radiation Oncology, University of Texas MD, Anderson Cancer Center, Houston, Texas (United States); Crozier, Cheryl; Owen, Jean B. [Quality Research in Radiation Oncology, American College of Radiology Clinical Research Center, Philadelphia, Pennsylvania (United States); Devlin, Phillip M. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Thomas, Charles R. [Department of Radiation Medicine, Knight Cancer Institute at the Oregon Health and Science University, Portland, Oregon (United States)

    2013-02-01

    Background: The specific aim was to determine national patterns of radiation therapy (RT) practice in patients treated for stage IB-IV (nonmetastatic) gastric cancer (GC). Methods and Materials: A national process survey of randomly selected US RT facilities was conducted which retrospectively assessed demographics, staging, geographic region, practice setting, and treatment by using on-site record review of eligible GC cases treated from 2005 to 2007. Three clinical performance measures (CPMs), (1) use of computed tomography (CT)-based treatment planning; (2) use of dose volume histograms (DVHs) to evaluate RT dose to the kidneys and liver; and (3) completion of RT within the prescribed time frame; and emerging quality indicators, (i) use of intensity modulated RT (IMRT); (ii) use of image-guided tools (IGRT) other than CT for RT target delineation; and (iii) use of preoperative RT, were assessed. Results: CPMs were computed for 250 eligible patients at 45 institutions (median age, 62 years; 66% male; 60% Caucasian). Using 2000 American Joint Committee on Cancer criteria, 13% of patients were stage I, 29% were stage II, 32% were stage IIIA, 10% were stage IIIB, and 12% were stage IV. Most patients (43%) were treated at academic centers, 32% were treated at large nonacademic centers, and 25% were treated at small to medium sized facilities. Almost all patients (99.5%) underwent CT-based planning, and 75% had DVHs to evaluate normal tissue doses to the kidneys and liver. Seventy percent of patients completed RT within the prescribed time frame. IMRT and IGRT were used in 22% and 17% of patients, respectively. IGRT techniques included positron emission tomography (n=20), magnetic resonance imaging (n=1), respiratory gating and 4-dimensional CT (n=22), and on-board imaging (n=10). Nineteen percent of patients received preoperative RT. Conclusions: This analysis of radiation practice patterns for treating nonmetastatic GC indicates widespread adoption of CT

  11. What is the relationship between emotional intelligence and dental student clinical performance?

    Science.gov (United States)

    Victoroff, Kristin Zakariasen; Boyatzis, Richard E

    2013-04-01

    Emotional intelligence has emerged as a key factor in differentiating average from outstanding performers in managerial and leadership positions across multiple business settings, but relatively few studies have examined the role of emotional intelligence in the health care professions. The purpose of this study was to examine the relationship between emotional intelligence (EI) and dental student clinical performance. All third- and fourth-year students at a single U.S. dental school were invited to participate. Participation rate was 74 percent (100/136). Dental students' EI was assessed using the Emotional Competence Inventory-University version (ECI-U), a seventy-two-item, 360-degree questionnaire completed by both self and other raters. The ECI-U measured twenty-two EI competencies grouped into four clusters (Self-Awareness, Self-Management, Social Awareness, and Relationship Management). Clinical performance was assessed using the mean grade assigned by clinical preceptors. This grade represents an overall assessment of a student's clinical performance including diagnostic and treatment planning skills, time utilization, preparation and organization, fundamental knowledge, technical skills, self-evaluation, professionalism, and patient management. Additional variables were didactic grade point average (GPA) in Years 1 and 2, preclinical GPA in Years 1 and 2, Dental Admission Test academic average and Perceptual Ability Test scores, year of study, age, and gender. Multiple linear regression analyses were conducted. The Self-Management cluster of competencies (b=0.448, p<0.05) and preclinical GPA (b=0.317, p<0.01) were significantly correlated with mean clinical grade. The Self-Management competencies were emotional self-control, achievement orientation, initiative, trustworthiness, conscientiousness, adaptability, and optimism. In this sample, dental students' EI competencies related to Self-Management were significant predictors of mean clinical grade

  12. Evaluation of a new clinical performance assessment tool : A reliability study

    Directory of Open Access Journals (Sweden)

    C. Joseph

    2012-12-01

    Full Text Available Clinical practice is an essential requirement of any graduatephysiotherapy programme. For this purpose, valid and reliable assessment toolsare paramount for the measurement of key competencies in the real-worldsetting. This study aims to determine the internal consistency and inter-raterreliability of a newly developed and validated clinical performance assessmentform. A cross-sectional quantitative research design was used, which includedpaired evaluations of 32 (17 treatment and 15 assessment student examinationsperformed by two independent clinical educators. Chronbachs alpha was computedto assess internal consistency and intraclass correlation coefficient (ICC’s withconfidence intervals of 95% were computed to determine the percentage agreement between paired examiners. Thedegree of internal consistency was substantial for all key performance areas of both examinations, except for timeand organisational management (0.21 and professionalism (0.42 in the treatment and evaluation examinationsrespectively. The overall internal consistency was 0.89 and 0.73 for both treatment and assessment examinations,indicating substantial agreement. With regard to agreement between raters, the ICC’s for the overall marks were0.90 and 0.97 for both treatment and assessment examinations. Clinical educators demonstrated a high level ofreliability in the assessment of students’ competence using the newly developed clinical performance assessment form.These findings greatly underscore the reliability of results obtained through observation of student examinations, andadd another tool to the basket of ensuring quality assurance in physiotherapy clinical practice assessment.

  13. Using a mesoscale ensemble to predict forecast error and perform targeted observation

    Institute of Scientific and Technical Information of China (English)

    DU Jun; YU Rucong; CUI Chunguang; LI Jun

    2014-01-01

    Using NCEP short range ensemble forecast (SREF) system, demonstrated two fundamental on-going evolu-tions in numerical weather prediction (NWP) are through ensemble methodology. One evolution is the shift from traditional single-value deterministic forecast to flow-dependent (not statistical) probabilistic forecast to address forecast uncertainty. Another is from a one-way observation-prediction system shifting to an in-teractive two-way observation-prediction system to increase predictability of a weather system. In the first part, how ensemble spread from NCEP SREF predicting ensemble-mean forecast error was evaluated over a period of about a month. The result shows that the current capability of predicting forecast error by the 21-member NCEP SREF has reached to a similar or even higher level than that of current state-of-the-art NWP models in predicting precipitation, e.g., the spatial correlation between ensemble spread and absolute fore-cast error has reached 0.5 or higher at 87 h (3.5 d) lead time on average for some meteorological variables. This demonstrates that the current operational ensemble system has already had preliminary capability of predicting the forecast error with usable skill, which is a remarkable achievement as of today. Given the good spread-skill relation, the probability derived from the ensemble was also statistically reliable, which is the most important feature a useful probabilistic forecast should have. The second part of this research tested an ensemble-based interactive targeting (E-BIT) method. Unlike other mathematically-calculated objec-tive approaches, this method is subjective or human interactive based on information from an ensemble of forecasts. A numerical simulation study was performed to eight real atmospheric cases with a 10-member, bred vector-based mesoscale ensemble using the NCEP regional spectral model (RSM, a sub-component of NCEP SREF) to prove the concept of this E-BIT method. The method seems to work most

  14. Students’ performance in the different clinical skills assessed in OSCE: what does it reveal?

    Directory of Open Access Journals (Sweden)

    Joong Hiong Sim

    2015-02-01

    Full Text Available Introduction: The purpose of this study was to compare students’ performance in the different clinical skills (CSs assessed in the objective structured clinical examination. Methods: Data for this study were obtained from final year medical students’ exit examination (n=185. Retrospective analysis of data was conducted using SPSS. Means for the six CSs assessed across the 16 stations were computed and compared. Results: Means for history taking, physical examination, communication skills, clinical reasoning skills (CRSs, procedural skills (PSs, and professionalism were 6.25±1.29, 6.39±1.36, 6.34±0.98, 5.86±0.99, 6.59±1.08, and 6.28±1.02, respectively. Repeated measures ANOVA showed there was a significant difference in the means of the six CSs assessed [F(2.980, 548.332=20.253, p<0.001]. Pairwise multiple comparisons revealed significant differences between the means of the eight pairs of CSs assessed, at p<0.05. Conclusions: CRSs appeared to be the weakest while PSs were the strongest, among the six CSs assessed. Students’ unsatisfactory performance in CRS needs to be addressed as CRS is one of the core competencies in medical education and a critical skill to be acquired by medical students before entering the workplace. Despite its challenges, students must learn the skills of clinical reasoning, while clinical teachers should facilitate the clinical reasoning process and guide students’ clinical reasoning development.

  15. Performances and stability of a 2.4 ton Gd organic liquid scintillator target for antineutrino detection

    CERN Document Server

    Barabanov, I R; Cattadori, C; Danilov, N A; Di Vacri, A; Krilov, Yu S; Ioannucci, L; Yanovich, E A; Aglietta, M; Bonardi, A; Bruno, G; Fulgione, W; Kemp, E; Malguin, A S; Porta, A; Selvi, M

    2008-01-01

    In this work we report the performances and the chemical and physical properties of a (2 x 1.2) ton organic liquid scintillator target doped with Gd up to ~0.1%, and the results of a 2 year long stability survey. In particular we have monitored the amount of both Gd and primary fluor actually in solution, the optical and fluorescent properties of the Gd-doped liquid scintillator (GdLS) and its performances as a neutron detector, namely neutron capture efficiency and average capture time. The experimental survey is ongoing, the target being continuously monitored. After two years from the doping time the performances of the Gd-doped liquid scintillator do not show any hint of degradation and instability; this conclusion comes both from the laboratory measurements and from the "in-tank" measurements. This is the largest stable Gd-doped organic liquid scintillator target ever produced and continuously operated for a long period.

  16. 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.

  17. Emotional Intelligence in Internal Medicine Residents: Educational Implications for Clinical Performance and Burnout.

    Science.gov (United States)

    Satterfield, Jason; Swenson, Sara; Rabow, Michael

    2009-01-01

    We measured emotional intelligence (EQ; the ability to perceive, understand, and manage emotions in the self and others) in a sample of 28 internal medicine residents at the beginning and end of an academic year. EQ scores increased significantly over the course of the year. Higher EQ scores at the end of the year were significantly related to higher ratings for overall clinical performance and medical interviewing. Higher EQ scores also correlated with lower levels of burnout. Results suggest that clinically significant changes in EQ can occur over the course of medical training. Further study should determine if and how educational interventions can affect EQ, EQ-related performance, and burnout.

  18. Catheter-based flow measurements in hemodialysis fistulas - Bench testing and clinical performance

    DEFF Research Database (Denmark)

    Heerwagen, Søren T; Lönn, Lars; Schroeder, Torben V;

    2012-01-01

    Purpose: The purpose of this study was to perform bench and clinical testing of a catheter-based intravascular system capable of measuring blood flow in hemodialysis vascular accesses during endovascular procedures. Methods: We tested the Transonic ReoCath Flow Catheter System which uses the ther......Purpose: The purpose of this study was to perform bench and clinical testing of a catheter-based intravascular system capable of measuring blood flow in hemodialysis vascular accesses during endovascular procedures. Methods: We tested the Transonic ReoCath Flow Catheter System which uses...

  19. 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.

  20. Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications.

    Science.gov (United States)

    Tortora, Giampaolo; Ciardiello, Fortunato; Gasparini, Giampietro

    2008-09-01

    Cellular heterogeneity, redundancy of molecular pathways and effects of the microenvironment contribute to the survival, motility and metastasis of cells in solid tumors. It is unlikely that tumors are entirely dependent on only one abnormally activated signaling pathway; consequently, treatment with an agent that interferes with a single target may be insufficient. Combined blockade of functionally linked and relevant multiple targets has become an attractive therapeutic strategy. The EGFR and ERBB2 (HER2) pathways and VEGF-dependent angiogenesis have a pivotal role in cancer pathogenesis and progression. Robust experimental evidence has shown that these pathways are functionally linked and has demonstrated a suggested role for VEGF in the acquired resistance to anti-ERBB drugs when these receptors are pharmacologically blocked. Combined inhibition of ERBB and VEGF signaling interferes with a molecular feedback loop responsible for acquired resistance to anti-ERBB agents and promotes apoptosis while ablating tumor-induced angiogenesis. To this aim, either two agents highly selective against VEGF and ERBB respectively, or, alternatively, a single multitargeted agent, can be used. Preclinical studies have proven the efficacy of both these approaches and early clinical studies have provided encouraging results. This Review discusses the experimental rationale for, preclinical studies of and clinical trials on combined blockade of ERBB and VEGF signaling.

  1. Targeting gut-liver axis for the treatment of nonalcoholic steatohepatitis: translational and clinical evidence.

    Science.gov (United States)

    Federico, Alessandro; Dallio, Marcello; Godos, Justyna; Loguercio, Carmela; Salomone, Federico

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is widely emerging as the most prevalent liver disorder and is associated with increased risk of liver-related and cardiovascular mortality. Recent experimental and clinical studies have revealed the pivotal role played by the alteration of gut-liver axis in the onset of fatty liver and related metabolic disturbances. Gut-liver cross talk is implicated not only in the impairment of lipid and glucose homeostasis leading to steatogenesis, but also in the initiation of inflammation and fibrogenesis, which characterize nonalcoholic steatohepatitis (NASH), the evolving form of NAFLD. The gut microbiota has been recognized as the key player in the gut-liver liaison and because of its complexity can act as a villain or a victim. Gut microbiota not only influences absorption and disposal of nutrients to the liver, but also conditions hepatic inflammation by supplying toll-like receptor ligands, which can stimulate liver cells to produce proinflammatory cytokines. Thus, the modification of intestinal bacterial flora by specific probiotics has been proposed as a therapeutic approach for the treatment of NASH. In this review, we summarized the evidence regarding the role of gut-liver axis in the pathogenesis of NASH and discussed the potential therapeutic role of gut microbiota modulation in the clinical setting. PMID:26318867

  2. CURRENT TARGET OF ANTIHYPERTENSIVE THERAPY. DATA FROM CLINICAL TRIALS. PART 2

    Directory of Open Access Journals (Sweden)

    V. V. Popov

    2012-01-01

    Full Text Available Arterial hypertension (HT takes leading position in the structure of morbidity and mortality among the cardiovascular diseases in the economically developed and developing countries of the world. Despite progress in treatment of this disease, a number of people with uncontrolled or resistant HT increases. There is a problem of inefficiency of therapy or lack of patients' adherence to treatment. Therefore, search for new approaches to treatment of HT continues. Current most effective agents for blood pressure control, and possible future antihypertensive agents, are related to groups of agents, which inhibit renin–angiotensin–aldosterone system (RAAS. Novel targets for antihypertensive therapy could include the angiotensin II type 2 and type 1 receptor , neutral endopeptidase, aldosterone synthase, renalase, endothelin receptors, (prorenin receptors, vaccine against RAAS components. Development of novel agents and approaches to HT therapy is discussed.

  3. CURRENT TARGET OF ANTIHYPERTENSIVE THERAPY. DATA FROM CLINICAL TRIALS. PART 1

    Directory of Open Access Journals (Sweden)

    V. V. Popov

    2012-01-01

    Full Text Available Arterial hypertension (HT takes leading position in the structure of morbidity and mortality among the cardiovascular diseases in the economically developed and developing countries of the world. Despite progress in treatment of this disease, a number of people with uncontrolled or resistant HT increases. There is a problem of inefficiency of therapy or lack of patients' adherence to treatment. Therefore, search for new approaches to treatment of HT continues. Current most effective agents for blood pressure control, and possible future antihypertensive agents, are related to groups of agents, which inhibit renin–angiotensin–aldosterone system (RAAS. Novel targets for antihypertensive therapy could include the angiotensin II type 2 and type 1 receptor , neutral endopeptidase, aldosterone synthase, renalase, endothelin receptors, (prorenin receptors, vaccine against RAAS components. Development of novel agents and approaches to HT therapy is discussed.

  4. FY2014 FES (Fusion Energy Sciences) Theory & Simulation Performance Target, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Guoyong [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Budny, Robert [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Gorelenkov, Nikolai [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Poli, Francesca [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Chen, Yang [Univ. of Colorado, Boulder, CO (United States); McClenaghan, Joseph [Univ. of California, Irvine, CA (United States); Lin, Zhihong [Univ. of California, Irvine, CA (United States); Spong, Don [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bass, Eric [Univ. of California, San Diego, CA (United States); Waltz, Ron [General Atomics, San Diego, CA (United States)

    2014-10-14

    We report here the work done for the FY14 OFES Theory Performance Target as given below: "Understanding alpha particle confinement in ITER, the world's first burning plasma experiment, is a key priority for the fusion program. In FY 2014, determine linear instability trends and thresholds of energetic particle-driven shear Alfven eigenmodes in ITER for a range of parameters and profiles using a set of complementary simulation models (gyrokinetic, hybrid, and gyrofluid). Carry out initial nonlinear simulations to assess the effects of the unstable modes on energetic particle transport". In the past year (FY14), a systematic study of the alpha-driven Alfven modes in ITER has been carried out jointly by researchers from six institutions involving seven codes including the transport simulation code TRANSP (r. Budny and F. Poli, PPPL), three gyrokinetic codes: GEM (Y. Chen, Univ. of Colorado), GTC (J. McClenaghan, Z. Lin, UCI), and GYRO (E. Bass, R. Waltz, UCSD/GA), the hybrid code M3D-K (G.Y. Fu, PPPL), the gyro-fluid code TAEFL (D. Spong, ORNL), and the linear kinetic stability code NOVA-K (N. Gorelenkov, PPPL). A range of ITER parameters and profiles are specified by TRANSP simulation of a hybrid scenario case and a steady state scenario case. Based on the specified ITER equilibria linear stability calculations are done to determine the stability boundary of alpha-driven high-n TAEs using the five initial value codes (GEM, GTC, GYRO, M3D-K, and TAEFL) and the kinetic stability code (NOVA-K). Both the effects of alpha particles and beam ions have been considered. Finally the effects of the unstable modes on energetic particle transport have been explored using GEM and M3D-K.

  5. FY2014 FES (Fusion Energy Sciences) Theory & Simulation Performance Target, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Guoyong [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Budny, Robert [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Gorelenkov, Nikolai [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Poli, Francesca [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Chen, Yang [Univ. of Colorado, Boulder, CO (United States); McClenaghan, Joseph [Univ. of California, Irvine, CA (United States); Lin, Zhihong [Univ. of California, Irvine, CA (United States); Spong, Don [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bass, Eric [Univ. of California, San Diego, CA (United States); Waltz, Ron [General Atomics, San Diego, CA (United States)

    2014-10-14

    We report here the work done for the FY14 OFES Theory Performance Target as given below: "Understanding alpha particle confinement in ITER, the world's first burning plasma experiment, is a key priority for the fusion program. In FY 2014, determine linear instability trends and thresholds of energetic particle-driven shear Alfven eigenmodes in ITER for a range of parameters and profiles using a set of complementary simulation models (gyrokinetic, hybrid, and gyrofluid). Carry out initial nonlinear simulations to assess the effects of the unstable modes on energetic particle transport". In the past year (FY14), a systematic study of the alpha-driven Alfven modes in ITER has been carried out jointly by researchers from six institutions involving seven codes including the transport simulation code TRANSP (R. Budny and F. Poli, PPPL), three gyrokinetic codes: GEM (Y. Chen, Univ. of Colorado), GTC (J. McClenaghan, Z. Lin, UCI), and GYRO (E. Bass, R. Waltz, UCSD/GA), the hybrid code M3D-K (G.Y. Fu, PPPL), the gyro-fluid code TAEFL (D. Spong, ORNL), and the linear kinetic stability code NOVA-K (N. Gorelenkov, PPPL). A range of ITER parameters and profiles are specified by TRANSP simulation of a hybrid scenario case and a steady-state scenario case. Based on the specified ITER equilibria linear stability calculations are done to determine the stability boundary of alpha-driven high-n TAEs using the five initial value codes (GEM, GTC, GYRO, M3D-K, and TAEFL) and the kinetic stability code (NOVA-K). Both the effects of alpha particles and beam ions have been considered. Finally, the effects of the unstable modes on energetic particle transport have been explored using GEM and M3D-K.

  6. The molecular, cellular and clinical consequences of targeting the estrogen receptor following estrogen deprivation therapy.

    Science.gov (United States)

    Fan, Ping; Maximov, Philipp Y; Curpan, Ramona F; Abderrahman, Balkees; Jordan, V Craig

    2015-12-15

    During the past 20 years our understanding of the control of breast tumor development, growth and survival has changed dramatically. The once long forgotten application of high dose synthetic estrogen therapy as the first chemical therapy to treat any cancer has been resurrected, refined and reinvented as the new biology of estrogen-induced apoptosis. High dose estrogen therapy was cast aside once tamoxifen, from its origins as a failed "morning after pill", was reinvented as the first targeted therapy to treat any cancer. The current understanding of the mechanism of estrogen-induced apoptosis is described as a consequence of acquired resistance to long term antihormone therapy in estrogen receptor (ER) positive breast cancer. The ER signal transduction pathway remains a target for therapy in breast cancer despite "antiestrogen" resistance, but becomes a regulator of resistance. Multiple mechanisms of resistance come into play: Selective ER modulator (SERM) stimulated growth, growth factor/ER crosstalk, estrogen-induced apoptosis and mutations of ER. But it is with the science of estrogen-induced apoptosis that the next innovation in women's health will be developed. Recent evidence suggests that the glucocorticoid properties of medroxyprogesterone acetate blunt estrogen-induced apoptosis in estrogen deprived breast cancer cell populations. As a result breast cancer develops during long-term hormone replacement therapy (HRT). A new synthetic progestin with estrogen-like properties, such as the 19 nortestosterone derivatives used in oral contraceptives, will continue to protect the uterus from unopposed estrogen stimulation but at the same time, reinforce apoptosis in vulnerable populations of nascent breast cancer cells.

  7. What is the relationship between emotional intelligence and dental student clinical performance?

    Science.gov (United States)

    Victoroff, Kristin Zakariasen; Boyatzis, Richard E

    2013-04-01

    Emotional intelligence has emerged as a key factor in differentiating average from outstanding performers in managerial and leadership positions across multiple business settings, but relatively few studies have examined the role of emotional intelligence in the health care professions. The purpose of this study was to examine the relationship between emotional intelligence (EI) and dental student clinical performance. All third- and fourth-year students at a single U.S. dental school were invited to participate. Participation rate was 74 percent (100/136). Dental students' EI was assessed using the Emotional Competence Inventory-University version (ECI-U), a seventy-two-item, 360-degree questionnaire completed by both self and other raters. The ECI-U measured twenty-two EI competencies grouped into four clusters (Self-Awareness, Self-Management, Social Awareness, and Relationship Management). Clinical performance was assessed using the mean grade assigned by clinical preceptors. This grade represents an overall assessment of a student's clinical performance including diagnostic and treatment planning skills, time utilization, preparation and organization, fundamental knowledge, technical skills, self-evaluation, professionalism, and patient management. Additional variables were didactic grade point average (GPA) in Years 1 and 2, preclinical GPA in Years 1 and 2, Dental Admission Test academic average and Perceptual Ability Test scores, year of study, age, and gender. Multiple linear regression analyses were conducted. The Self-Management cluster of competencies (b=0.448, pemotional self-control, achievement orientation, initiative, trustworthiness, conscientiousness, adaptability, and optimism. In this sample, dental students' EI competencies related to Self-Management were significant predictors of mean clinical grade assigned by preceptors. Emotional intelligence may be an important predictor of clinical performance, which has important implications for

  8. A comparative study based on image quality and clinical task performance for CT reconstruction algorithms in radiotherapy.

    Science.gov (United States)

    Li, Hua; Dolly, Steven; Chen, Hsin-Chen; Anastasio, Mark A; Low, Daniel A; Li, Harold H; Michalski, Jeff M; Thorstad, Wade L; Gay, Hiram; Mutic, Sasa

    2016-01-01

    CT image reconstruction is typically evaluated based on the ability to reduce the radiation dose to as-low-as-reasonably-achievable (ALARA) while maintaining acceptable image quality. However, the determination of common image quality metrics, such as noise, contrast, and contrast-to-noise ratio, is often insufficient for describing clinical radiotherapy task performance. In this study we designed and implemented a new comparative analysis method associating image quality, radiation dose, and patient size with radiotherapy task performance, with the purpose of guiding the clinical radiotherapy usage of CT reconstruction algorithms. The iDose4 iterative reconstruction algorithm was selected as the target for comparison, wherein filtered back-projection (FBP) reconstruction was regarded as the baseline. Both phantom and patient images were analyzed. A layer-adjustable anthropomorphic pelvis phantom capable of mimicking 38-58 cm lateral diameter-sized patients was imaged and reconstructed by the FBP and iDose4 algorithms with varying noise-reduction-levels, respectively. The resulting image sets were quantitatively assessed by two image quality indices, noise and contrast-to-noise ratio, and two clinical task-based indices, target CT Hounsfield number (for electron density determination) and structure contouring accuracy (for dose-volume calculations). Additionally, CT images of 34 patients reconstructed with iDose4 with six noise reduction levels were qualitatively evaluated by two radiation oncologists using a five-point scoring mechanism. For the phantom experiments, iDose4 achieved noise reduction up to 66.1% and CNR improvement up to 53.2%, compared to FBP without considering the changes of spatial resolution among images and the clinical acceptance of reconstructed images. Such improvements consistently appeared across different iDose4 noise reduction levels, exhibiting limited interlevel noise (phantom size. The iDose4 algorithm with a moderate noise reduction

  9. Treatment of Non-Small Cell Lung Cancer (NSCLC) Using CT in Combination with a PET Examination to Minimize the Clinical Target Volume of the Mediastinum

    Institute of Scientific and Technical Information of China (English)

    Yusheng Shi; Xiaogang Deng; Longhua Chen

    2007-01-01

    OBJECTIVE To decrease radiation injury of the esophagus and lungs by utilizing a CT scan in combination with PET tumor imaging in order to minimize the clinical target area of locally advanced non-small cell lung cancer, without preventive radiation on the lymphatic drainage area. METHODS Of 76 patients with locally advanced non-small cell lung cancer (NSCLC), 32 received a PET examination before radiotherapy. Preventive radiation was not conducted in the mediastinum area without lymphatic metastasis, which was confirmed by CT and PET. For the other 44 patients, preventive radiation was performed in the lymphatic drainage area. PET examinations showed that the clinical target volume of the patients was decreased on average to about one third. The radiation therapy for patients of the two groups was the same, I.e. The dose for accelerated fractionated irradiation was 3 Gy/time and 5 time/week. The preventive dose was 42 to 45 Gy/time, 14 to 15 time/week, with 3-week treatment, and the therapeutic dose was 60 to 63 Gy/time, 20 to 21 time/week, with a period of 4 to 5 weeks.RESULTS The rate of missed lymph nodes beyond the irradiation field was 6.3% and 4.5% respectively in the group with and without PET examination (P = 0.831). The incidence of acute radioactive esophagitis was 15.6 % and 45.5% in the two groups respectively (P = 0.006). The incidence of acute radiation pneumonia and long-term pulmonary fibrosis in the two groups was 6.3% and 9.1%, and 68.8% and 75.0%, respectively (P = 0.982 and P = 0.547).CONCLUSION The recurrence rate in the lymph nodes beyond the target area was not increased after minimizing the clinical target volume (CTV), whereas radioactive injury to the lungs and esophageal injury was reduced, and especially with a significant decrease in the rate of acute radioactive esophagitis. The method of CT in combination with PET for minimizing the mediastinal CTV is superior to the conventional preventive radiation of the mediastinum.

  10. Impact of tDCS on performance and learning of target detection: interaction with stimulus characteristics and experimental design.

    Science.gov (United States)

    Coffman, B A; Trumbo, M C; Flores, R A; Garcia, C M; van der Merwe, A J; Wassermann, E M; Weisend, M P; Clark, V P

    2012-06-01

    We have previously found that transcranial direct current stimulation (tDCS) over right inferior frontal cortex (RIFC) enhances performance during learning of a difficult visual target detection task (Clark et al., 2012). In order to examine the cognitive mechanisms of tDCS that lead to enhanced performance, here we analyzed its differential effects on responses to stimuli that varied by repetition and target presence, differences related to expectancy by comparing performance in single- and double-blind task designs, and individual differences in skin stimulation and mood. Participants were trained for 1h to detect target objects hidden in a complex virtual environment, while anodal tDCS was applied over RIFC at 0.1 mA or 2.0 mA for the first 30 min. Participants were tested immediately before and after training and again 1h later. Higher tDCS current was associated with increased performance for all test stimuli, but was greatest for repeated test stimuli with the presence of hidden-targets. This finding was replicated in a second set of subjects using a double-blind task design. Accuracy for target detection discrimination sensitivity (d'; Z(hits)-Z(false alarms)) was greater for 2.0 mA current (1.77) compared with 0.1 mA (0.95), with no differences in response bias (β). Taken together, these findings indicate that the enhancement of performance with tDCS is sensitive to stimulus repetition and target presence, but not to changes in expectancy, mood, or type of blinded task design. The implications of these findings for understanding the cognitive mechanisms of tDCS are discussed. PMID:22450198

  11. 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.

  12. Clinical Response of Metastatic Breast Cancer to Multi-targeted Therapeutic Approach: A Single Case Report

    Directory of Open Access Journals (Sweden)

    Christian Meiners

    2011-03-01

    Full Text Available The present article describes the ongoing (partial remission of a female patient (41 years old from estrogen receptor (ER-positive/progesterone receptor (PR-negative metastatic breast cancer in response to a combination treatment directed towards the revitalization of the mitochondrial respiratory chain (oxidative phosphorylation, the suppression of NF-kappaB as a factor triggering the inflammatory response, and chemotherapy with capecitabine. The reduction of tumor mass was evidenced by a continuing decline of CA15-3 and CEA tumor marker serum levels and 18FDG-PET-CT plus magnetic resonance (MR imaging. It is concluded that such combination treatment might be a useful option for treating already formed metastases and for providing protection against the formation of metastases in ER positive breast cancer. The findings need to be corroborated by clinical trials. Whether similar results can be expected for other malignant tumor phenotypes relying on glycolysis as the main energy source remains to be elucidated.

  13. Targeted testing with diethylthiourea often reveals clinically relevant allergic contact dermatitis caused by neoprene rubber

    DEFF Research Database (Denmark)

    Dall, Anne B-H; Andersen, Klaus Ejner; Mortz, Charlotte G

    2012-01-01

    Background. Diethylthiourea is widely used in the rubber industry, particularly in neoprene rubber, and may cause allergic contact dermatitis. However, as thiourea allergens are not part of the European baseline series, the diagnosis of allergic contact dermatitis caused by thiourea compounds...... depends on clinical suspicion and aimed testing. Objectives. The aims of this study were to evaluate the occurrence of sensitization to diethylthiourea during a 19-year period by using data from the Allergen Bank database at the Department of Dermatology and Allergy Centre, Odense University Hospital, and...... Bank. The records for patients with positive reactions were evaluated retrospectively. Results. One hundred and fifty-one patients were tested by 27 different dermatologists in private practice, and positive reactions were found in 16% (24/151) of the patients; 88 patients were tested at the...

  14. Clinical Response of Metastatic Breast Cancer to Multi-targeted Therapeutic Approach: A Single Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Meiners, Christian [Gautinger Straße 3b, D-82234 Wessling (Germany)

    2011-03-17

    The present article describes the ongoing (partial) remission of a female patient (41 years old) from estrogen receptor (ER)-positive/progesterone receptor (PR)-negative metastatic breast cancer in response to a combination treatment directed towards the revitalization of the mitochondrial respiratory chain (oxidative phosphorylation), the suppression of NF-kappaB as a factor triggering the inflammatory response, and chemotherapy with capecitabine. The reduction of tumor mass was evidenced by a continuing decline of CA15-3 and CEA tumor marker serum levels and {sup 18}FDG-PET-CT plus magnetic resonance (MR) imaging. It is concluded that such combination treatment might be a useful option for treating already formed metastases and for providing protection against the formation of metastases in ER positive breast cancer. The findings need to be corroborated by clinical trials. Whether similar results can be expected for other malignant tumor phenotypes relying on glycolysis as the main energy source remains to be elucidated.

  15. Myeloid-derived suppressor cells as intruders and targets: clinical implications in cancer therapy.

    Science.gov (United States)

    Baniyash, Michal

    2016-07-01

    Chronic inflammation, typical of various diseases including cancer, is a "silent bomb within the body," leading to complications that are only evident in most cases upon their appearance, when disease is already deteriorated. Chronic inflammation is associated with accumulation of myeloid-derived suppressor cells (MDSCs), which lead to immunosuppression. MDSCs have numerous harmful effects as they support tumor initiation, tumor growth and spreading, which in turn, perpetuate the inflammatory and suppressive conditions, thus preventing anticancer responses. As the concept of the immune system combating many types of tumors was revived in recent years, immunotherapy has dramatically changed the view of cancer treatment, and numerous novel therapies have been developed and approved by the FDA. However, cumulative clinical data point at very limited success rates. It is most likely that the developing chronic inflammation and MDSC-induced immunosuppression interfere with responses to such treatments and hence are major obstacles in achieving higher response rates to immune-based therapies. Moreover, chemotherapies were shown to have adverse immunoregulatory effects, enhancing or decreasing MDSC levels and activity, thus affecting treatment success. Therefore, therapeutic manipulations of chronic inflammation and MDSCs during cancer development are likely to enhance efficacy of immune- and chemo-based treatments, switching chronic pro-cancer inflammatory environments to an anticancerous milieu. Based on the functional relevance of immune networking in tumors, it is critical to merge monitoring immune system biomarkers into the traditional patient's categorization and treatment regimens. This will provide new tools for clinical practice, allowing appropriate management of cancer patients toward a better-personalized medicine. PMID:27225641

  16. Correlation between clinical performance and degree of conversion of resin cements: a literature review

    Science.gov (United States)

    DE SOUZA, Grace; BRAGA, Roberto Ruggiero; CESAR, Paulo Francisco; LOPES, Guilherme Carpena

    2015-01-01

    Resin-based cements have been frequently employed in clinical practice to lute indirect restorations. However, there are numerous factors that may compromise the clinical performance of those cements. The aim of this literature review is to present and discuss some of the clinical factors that may affect the performance of current resin-based luting systems. Resin cements may have three different curing mechanisms: chemical curing, photo curing or a combination of both. Chemically cured systems are recommended to be used under opaque or thick restorations, due to the reduced access of the light. Photo-cured cements are mainly indicated for translucent veneers, due to the possibility of light transmission through the restoration. Dual-cured are more versatile systems and, theoretically, can be used in either situation, since the presence of both curing mechanisms might guarantee a high degree of conversion (DC) under every condition. However, it has been demonstrated that clinical procedures and characteristics of the materials may have many different implications in the DC of currently available resin cements, affecting their mechanical properties, bond strength to the substrate and the esthetic results of the restoration. Factors such as curing mechanism, choice of adhesive system, indirect restorative material and light-curing device may affect the degree of conversion of the cement and, therefore, have an effect on the clinical performance of resin-based cements. Specific measures are to be taken to ensure a higher DC of the luting system to be used. PMID:26398507

  17. Correlation between clinical performance and degree of conversion of resin cements: a literature review

    Directory of Open Access Journals (Sweden)

    Grace DE SOUZA

    2015-08-01

    Full Text Available AbstractResin-based cements have been frequently employed in clinical practice to lute indirect restorations. However, there are numerous factors that may compromise the clinical performance of those cements. The aim of this literature review is to present and discuss some of the clinical factors that may affect the performance of current resin-based luting systems. Resin cements may have three different curing mechanisms: chemical curing, photo curing or a combination of both. Chemically cured systems are recommended to be used under opaque or thick restorations, due to the reduced access of the light. Photo-cured cements are mainly indicated for translucent veneers, due to the possibility of light transmission through the restoration. Dual-cured are more versatile systems and, theoretically, can be used in either situation, since the presence of both curing mechanisms might guarantee a high degree of conversion (DC under every condition. However, it has been demonstrated that clinical procedures and characteristics of the materials may have many different implications in the DC of currently available resin cements, affecting their mechanical properties, bond strength to the substrate and the esthetic results of the restoration. Factors such as curing mechanism, choice of adhesive system, indirect restorative material and light-curing device may affect the degree of conversion of the cement and, therefore, have an effect on the clinical performance of resin-based cements. Specific measures are to be taken to ensure a higher DC of the luting system to be used.

  18. Scoring of the Physical Therapist Clinical Performance Instrument (PT-CPI): Analysis of 7 Years of Use

    OpenAIRE

    Proctor, Peggy L.; Dal Bello-Haas, Vanina P.; McQuarrie, Arlis M.; Sheppard, M. Suzanne; Scudds, Rhonda J.

    2010-01-01

    Purpose: The aims of this study were to (1) describe the completion rates of the 24 performance criteria (PCs) from the Physical Therapist Clinical Performance Instrument (PT-CPI) by clinical instructors; (2) evaluate change in PC visual analogue scores (VAS) with students' clinical experience; and (3) evaluate scoring patterns over time.

  19. Impacts of Refraction Index Mismatch on Performance of Target Detection and Imaging by Using Flat LHM Lens

    Institute of Scientific and Technical Information of China (English)

    FANG Jie-Ran; GONG Yu; DONG Xiao-Ting; WANG Gang

    2008-01-01

    Refraction index mismatch between flat left-handed metamaterial(LHM)lens and its surrounding medium generally destroys the focusing of flat LHM lens and degrades the performance of near-field target detection by usingflat LHM lens.For LHM lens of refraction index mismatch within±30%,numerical simulations demonstrate that lenses with large refraction index may suffer less resolution degradation than lenses with small refraction index,and the enhancement of refocused microwave backscattered from target can be subsided bly up to approximately 5.5 dB.The refraction index mismatch will also shift the target position in the reconstructed image so that theoretical prediction of target position needs to be modified.

  20. Clinical study on the changes of the tumor target volume and organs at risk in helical tomotherapy for nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    LU Na; FENG Lin-chun; CAI Bo-ning; HOU Jun; WANG Yun-lai; XIE Chuan-bin

    2012-01-01

    Background Helical tomotherapy (HT) is a new image-guided intensity-modulated radiation therapy (IMRT).The aim of this study was to evaluate the changes in the target volume and organs at risk (OARs) of patients with nasopharyngeal carcinoma (NPC) during helical tomotherapy.Methods Forty-three patients with NPC and treated via HT from March 2008 to January 2010 were reviewed retrospectively.Repeated CT scanning and plan adaptation were conducted at the 20th fraction during radiotherapy.The volumetric differences between the two scans were evaluated for nasopharyngeal tumor and retro- pharyngeal lymph nodes (GTVnx),neck lymph nodes (GTVnd),and parotid glands,as well as the axial diameter of the head.Results The median interval between the two scans was 25 days (23-28 days).The volumetric decrease in GTVnx was 30.1% (median,29.8%) and in GTVnd 41.6% (median,45.9%).The variation in the GTVnd volume was correlated with the weight loss of the patient.The volume of the left parotid gland decreased by 35.5% (median,33.4%) and of the right parotid glands decreased by 36.8% (median,33.5%).The axial diameter of the head decreased by 9.39% (median,9.1%).Conclusions The target volume and OARs of patients with NPC varied considerably during HT.These changes may have potential dosimetric effects on the target volume and/or OARs and influence the clinical outcome.Repeated CT scanning and replanning during the HT for NPC patients with a large target volume or an obvious weight loss are recommended.

  1. Attenuation of multi-targeted proliferation-linked signaling by 3,3'-diindolylmethane (DIM): from bench to clinic.

    Science.gov (United States)

    Banerjee, Sanjeev; Kong, Dejuan; Wang, Zhiwei; Bao, Bin; Hillman, Gilda G; Sarkar, Fazlul H

    2011-01-01

    Emerging evidence provide credible support in favor of the potential role of bioactive products derived from ingesting cruciferous vegetables such as broccoli, brussel sprouts, cauliflower and cabbage. Among many compounds, 3,3'-diindolylmethane (DIM) is generated in the acidic environment of the stomach following dimerization of indole-3-carbinol (I3C) monomers present in these classes of vegetables. Both I3C and DIM have been investigated for their use in preventing, inhibiting, and reversing the progression of cancer - as a chemopreventive agent. In this review, we summarize an updated, wide-ranging pleiotropic anti-tumor and biological effects elicited by DIM against tumor cells. It is unfeasible to point one single target as basis of cellular target of action of DIM. We emphasize key cellular and molecular events that are effectively modulated in the direction of inducing apoptosis and suppressing cell proliferation. Collectively, DIM orchestrates signaling through Ah receptor, NF-κB/Wnt/Akt/mTOR pathways impinging on cell cycle arrest, modulation of key cytochrome P450 enzymes, altering angiogenesis, invasion, metastasis and epigenetic behavior of cancer cells. The ability of DIM to selectively induce tumor cells to undergo apoptosis has been observed in preclinical models, and thus it has been speculated in improving the therapeutic efficacy of other anticancer agents that have diverse molecular targets. Consequently, DIM has moved through preclinical development into Phase I clinical trials, thereby suggesting that DIM could be a promising and novel agent either alone or as an adjunct to conventional therapeutics such as chemo-radio and targeted therapies. An important development has been the availability of DIM formulation with superior bioavailability for humans. Therefore, DIM appears to be a promising chemopreventive agent or chemo-radio-sensitizer for the prevention of tumor recurrence and/or for the treatment of human malignancies.

  2. 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. PMID:22986894

  3. Effects of structured written feedback by cards on medical students’ performance at mini clinical evaluation exercise (Mini-CEX) in an outpatient clinic

    OpenAIRE

    FARIBA HAGHANI; MOHAMMAD HATEF KHORAMI; MOHAMMAD FAKHARI

    2016-01-01

    Introduction: Feedback cards are recommended as a feasible tool for structured written feedback delivery in clinical education while effectiveness of this tool on the medical students’ performance is still questionable. The purpose of this study was to compare the effects of structured written feedback by cards as well as verbal feedback versus verbal feedback alone on the clinical performance of medical students at the Mini Clinical Evaluation Exercise (Mini-CEX) test in...

  4. The Correlation of Learning Styles with Student Performance In Academic and Clinical Course Work.

    Science.gov (United States)

    Cunningham, M. Jo; Trickey, Becki A.

    1983-01-01

    The purpose of this study was to determine any correlation between learning styles and performance in the academic and clinical course work of occupational therapy students at the Medical University of South Carolina. (Availability: RAM Associates LTD., P.O. Box N, Laurel, MD 20707) (SSH)

  5. Age-Related Decline and Diagnostic Performance of More and Less Prevalent Clinical Cases

    Science.gov (United States)

    St-Onge, Christina; Landry, Marjolaine; Xhignesse, Marianne; Voyer, Gilles; Tremblay-Lavoie, Stéphanie; Mamede, Sílvia; Schmidt, Henk; Rikers, Remy

    2016-01-01

    Since cognitive abilities have been shown to decrease with age, it is expected that older physicians would not perform as well as their younger counterparts on clinical cases unless their expertise can counteract the cognitive effects of aging. However, studies on the topic have shown contradictory results. This study aimed to further investigate…

  6. Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke P. C.; Bijzet, Johannes; Limburg, Pieter C.; Skinner, Martha; Hawkins, Philip N.; Butrimiene, Irena; Livneh, Avi; Lesnyak, Olga; Nasonov, Evgeney L.; Filipowicz-Sosnowska, Anna; Guel, Ahmet; Merlini, Giampaolo; Wiland, Piotr; Oezdogan, Huri; Gorevic, Peter D.; Ben Maiz, Hedi; Benson, Merrill D.; Direskeneli, Haner; Kaarela, Kalevi; Garceau, Denis; Hauck, Wendy; van Rijswijk, Martin

    2007-01-01

    Objective. Amyloid A protein quantification in fat tissue is a new immunochemical method for detecting AA amyloidosis, a rare but serious disease. The objective was to assess diagnostic performance in clinical AA amyloidosis. Methods. Abdominal subcutaneous fat tissue of patients with AA amyloidosis

  7. Simplified clinical prediction scores to target viral load testing in adults with suspected first line treatment failure in Phnom Penh, Cambodia.

    Directory of Open Access Journals (Sweden)

    Johan van Griensven

    Full Text Available BACKGROUND: For settings with limited laboratory capacity, 2013 World Health Organization (WHO guidelines recommend targeted HIV-1 viral load (VL testing to identify virological failure. We previously developed and validated a clinical prediction score (CPS for targeted VL testing, relying on clinical, adherence and laboratory data. While outperforming the WHO failure criteria, it required substantial calculation and review of all previous laboratory tests. In response, we developed four simplified, less error-prone and broadly applicable CPS versions that can be done 'on the spot'. METHODOLOGY/PRINCIPAL: Findings From May 2010 to June 2011, we validated the original CPS in a non-governmental hospital in Phnom Penh, Cambodia applying the CPS to adults on first-line treatment >1 year. Virological failure was defined as a single VL >1000 copies/ml. The four CPSs included CPS1 with 'current CD4 count' instead of %-decline-from-peak CD4; CPS2 with hemoglobin measurements removed; CPS3 having 'decrease in CD4 count below baseline value' removed; CPS4 was purely clinical. Score development relied on the Spiegelhalter/Knill-Jones method. Variables independently associated with virological failure with a likelihood ratio ≥ 1.5 or ≤ 0.67 were retained. CPS performance was evaluated based on the area-under-the-ROC-curve (AUROC and 95% confidence intervals (CI. The CPSs were validated in an independent dataset. A total of 1490 individuals (56.6% female, median age: 38 years (interquartile range (IQR 33-44; median baseline CD4 count: 94 cells/µL (IQR 28-205, median time on antiretroviral therapy 3.6 years (IQR 2.1-5.1, were included. Forty-five 45 (3.0% individuals had virological failure. CPS1 yielded an AUROC of 0.69 (95% CI: 0.62-0.75 in validation, CPS2 an AUROC of 0.68 (95% CI: 0.62-0.74, and CPS3, an AUROC of 0.67 (95% CI: 0.61-0.73. The purely clinical CPS4 performed poorly (AUROC-0.59; 95% CI: 0.53-0.65. CONCLUSIONS: Simplified CPSs retained

  8. Targeting CXCR1 on breast cancer stem cells: signaling pathways and clinical application modelling.

    Science.gov (United States)

    Brandolini, Laura; Cristiano, Loredana; Fidoamore, Alessia; De Pizzol, Maria; Di Giacomo, Erica; Florio, Tiziana Marilena; Confalone, Giuseppina; Galante, Angelo; Cinque, Benedetta; Benedetti, Elisabetta; Ruffini, Pier Adelchi; Cifone, Maria Grazia; Giordano, Antonio; Alecci, Marcello; Allegretti, Marcello; Cimini, Annamaria

    2015-12-22

    In breast cancer it has been proposed that the presence of cancer stem cells may drive tumor initiation, progression and recurrences. IL-8, up-regulated in breast cancer, and associated with poor prognosis, increases CSC self-renewal in cell line models. It signals via two cell surface receptors, CXCR1 and CXCR2. Recently, the IL-8/CXCR1 axis was proposed as an attractive pathway for the design of specific therapies against breast cancer stem cells. Reparixin, a powerful CXCR1 inhibitor, was effective in reducing in vivo the tumour-initiating population in several NOD/SCID mice breast cancer models, showing that the selective targeting of CXCR1 and the combination of reparixin and docetaxel resulted in a concomitant reduction of the bulk tumour mass and CSC population. The available data indicate that IL-8, expressed by tumour cells and induced by chemotherapeutic treatment, is a key regulator of the survival and self-renewal of the population of CXCR1-expressing CSC. Consequently, this investigation on the mechanism of action of the reparixin/paclitaxel combination, was based on the observation that reparixin treatment contained the formation of metastases in several experimental models. However, specific data on the formation of breast cancer brain metastases, which carry remarkable morbidity and mortality to a substantial proportion of advanced breast cancer patients, have not been generated. The obtained data indicate a beneficial use of the drug combination reparixin and paclitaxel to counteract brain tumour metastasis due to CSC, probably due to the combined effects of the two drugs, the pro-apoptotic action of paclitaxel and the cytostatic and anti-migratory effects of reparixin.

  9. Pre-clinical evaluation of a novel CEA-targeting near-infrared fluorescent tracer delineating colorectal and pancreatic tumors

    Science.gov (United States)

    Boonstra, Martin C.; Tolner, Berend; Schaafsma, Boudewijn E.; Boogerd, Leonora S.F.; Prevoo, Hendrica A.J.M; Bhavsar, Guarav; Kuppen, Peter J.K.; Sier, Cornelis F.M.; Bonsing, Bert A.; Frangioni, John V.; van de Velde, Cornelis J.H.; Chester, Kerry A.; Vahrmeijer, Alexander L.

    2016-01-01

    Surgery is the cornerstone of oncologic therapy with curative intent. However, identification of tumor cells in the resection margins is difficult, resulting in non-radical resections, increased cancer recurrence and subsequent decreased patient survival. Novel imaging techniques that aid in demarcating tumor margins during surgery are needed. Overexpression of carcinoembryonic antigen (CEA) is found in the majority of gastro-intestinal carcinomas, including colorectal and pancreas. We developed ssSM3E/800CW, a novel CEA-targeted near-infrared fluorescent (NIRF) tracer, based on a disulphide stabilized single-chain antibody fragment (ssScFv), to visualize colorectal and pancreatic tumors in a clinically translatable setting. The applicability of the tracer was tested for cell and tissue binding characteristics and dosing using immunohistochemistry, flow cytometry, cell-based plate assays and orthotopic colorectal (HT-29, well differentiated) and pancreatic (BXPC-3, poorly differentiated) xenogeneic human-mouse models. NIRF signals were visualized using the clinically compatible FLARE™ imaging system. Calculated clinically relevant doses of ssSM3E/800CW selectively accumulated in colorectal and pancreatic tumors/cells, with highest tumor-to-background ratios of 5.1±0.6 at 72 h post-injection, which proved suitable for intra-operative detection and delineation of tumor boarders and small (residual) tumor-nodules in mice, between 8 h and 96 h post-injection. Ex vivo fluorescence imaging and pathologic examination confirmed tumor-specificity and the distribution of the tracer. Our results indicate that ssSM3E/800CW shows promise as a diagnostic tool to recognize colorectal and pancreatic cancers for fluorescent-guided surgery applications. If successful translated clinically, this tracer could help improve the completeness of surgery and thus survival. PMID:25895046

  10. A comparative study based on image quality and clinical task performance for CT reconstruction algorithms in radiotherapy.

    Science.gov (United States)

    Li, Hua; Dolly, Steven; Chen, Hsin-Chen; Anastasio, Mark A; Low, Daniel A; Li, Harold H; Michalski, Jeff M; Thorstad, Wade L; Gay, Hiram; Mutic, Sasa

    2016-07-08

    CT image reconstruction is typically evaluated based on the ability to reduce the radiation dose to as-low-as-reasonably-achievable (ALARA) while maintaining acceptable image quality. However, the determination of common image quality metrics, such as noise, contrast, and contrast-to-noise ratio, is often insufficient for describing clinical radiotherapy task performance. In this study we designed and implemented a new comparative analysis method associating image quality, radiation dose, and patient size with radiotherapy task performance, with the purpose of guiding the clinical radiotherapy usage of CT reconstruction algorithms. The iDose4 iterative reconstruction algorithm was selected as the target for comparison, wherein filtered back-projection (FBP) reconstruction was regarded as the baseline. Both phantom and patient images were analyzed. A layer-adjustable anthropomorphic pelvis phantom capable of mimicking 38-58 cm lateral diameter-sized patients was imaged and reconstructed by the FBP and iDose4 algorithms with varying noise-reduction-levels, respectively. The resulting image sets were quantitatively assessed by two image quality indices, noise and contrast-to-noise ratio, and two clinical task-based indices, target CT Hounsfield number (for electron density determination) and structure contouring accuracy (for dose-volume calculations). Additionally, CT images of 34 patients reconstructed with iDose4 with six noise reduction levels were qualitatively evaluated by two radiation oncologists using a five-point scoring mechanism. For the phantom experiments, iDose4 achieved noise reduction up to 66.1% and CNR improvement up to 53.2%, compared to FBP without considering the changes of spatial resolution among images and the clinical acceptance of reconstructed images. Such improvements consistently appeared across different iDose4 noise reduction levels, exhibiting limited interlevel noise (images, when compared to FBP, was greater in larger patients than

  11. Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer.

    Science.gov (United States)

    Shamanna, Raghavendra A; Lu, Huiming; Croteau, Deborah L; Arora, Arvind; Agarwal, Devika; Ball, Graham; Aleskandarany, Mohammed A; Ellis, Ian O; Pommier, Yves; Madhusudan, Srinivasan; Bohr, Vilhelm A

    2016-03-22

    Werner syndrome protein (WRN) is a RecQ helicase that participates in DNA repair, genome stability and cellular senescence. The five human RecQ helicases, RECQL1, Bloom, WRN, RECQL4 and RECQL5 play critical roles in DNA repair and cell survival after treatment with the anticancer drug camptothecin (CPT). CPT derivatives are widely used in cancer chemotherapy to inhibit topoisomerase I and generate DNA double-strand breaks during replication. Here we studied the effects of CPT on the stability and expression dynamics of human RecQ helicases. In the cells treated with CPT, we observed distinct effects on WRN compared to other human RecQ helicases. CPT altered the cellular localization of WRN and induced its degradation by a ubiquitin-mediated proteasome pathway. WRN knockdown cells as well as CPT treated cells became senescent and stained positive for senescence-associated β-galactosidase at a higher frequency compared to control cells. However, the senescent phenotype was attenuated by ectopic expression of WRN suggesting functional implication of WRN degradation in CPT treated cells. Approximately 5-23% of breast cancer tumors are known to respond to CPT-based chemotherapy. Interestingly, we found that the extent of CPT-induced WRN degradation correlates with increasing sensitivity of breast cancer cells to CPT. The abundance of WRN decreased in CPT-treated sensitive cells; however, WRN remained relatively stable in CPT-resistant breast cancer cells. In a large clinical cohort of breast cancer patients, we find that WRN and topoisomerase I expression correlate with an aggressive tumor phenotype and poor prognosis. Our novel observations suggest that WRN abundance along with CPT-induced degradation could be a promising strategy for personalizing CPT-based cancer chemotherapeutic regimens.

  12. Performance of an atlas-based autosegmentation software for delineation of target volumes for radiotherapy of breast and anorectal cancer

    International Nuclear Information System (INIS)

    Background and purpose: To validate atlas-based autosegmentation for contouring breast/anorectal targets. Methods and materials: ABAS uses atlases with defined CTVs as template cases to automatically delineate target volumes in other patient CT-datasets. Results are compared with manually contoured CTVs of breast/anorectal cancer according to RTOG-guidelines. The impact of using specific atlases matched to individual patient geometry was evaluated. Results were quantified by analyzing Dice Similarity Coefficient (DSC), logit(DSC) and Percent Overlap (PO). DSC >0.700 and logit(DSC) >0.847 are acceptable. In addition a new algorithm (STAPLE) was evaluated. Results: ABAS produced good results for the CTV of breast/anorectal cancer targets. Delineation of inguinal lymphatic drainage, however, was insufficient. Results for breast CTV were (DSC: 0.86–0.91 ([0, 1]), logit(DSC): 1.82–2.36 ([−∞, ∞]), PO: 75.5–82.89%) and for anorectal CTVA (DSC: 0.79–0.85, logit(DSC): 1.40–1.77, PO: 68–73.67%). Conclusions: ABAS produced satisfactory results for these clinical target volumes that are defined by more complex tissue interface geometry, thus streamlining and facilitating the radiotherapy workflow which is essential to face increasing demand and limited resources. STAPLE improved contouring outcome. Small target volumes not clearly defined are still to be delineated manually. Based on these results, ABAS has been clinically introduced for precontouring of CTVs/OARs.

  13. Effect of metabolic abnormalities on cognitive performance and clinical symptoms in schizophrenia

    Directory of Open Access Journals (Sweden)

    Wysokiński, Adam

    2013-12-01

    Full Text Available Aim. The objective of this study is to determine whether and how metabolic abnormalities are associated with clinical symptoms and cognitive performance in schizophrenia. Methods. 46 adult patients with schizophrenia taking first- or second generation antipsychotics were included in the study. The following data were collected: BMI, abdominal circumference, lipid panel and blood glucose, blood pressure and treatment of comorbidities. Clinical symptoms were assessed using PANSS, CDSS, CGI and SAS scales. Cognitive performance was assessed using CNS Vital Signs computerized battery of tests: Verbal Memory test, Visual Memory test, Finger Tapping Test, Symbol Digit Coding, Stroop Test, Shifting Attention Test, and Continuous Performance Test. Results. Dyslipidemia, raised LDL and raised blood glucose levels were the best predictors of more severe clinical symptoms (PANSS, PANSS P, PANSS G, CGI and lower neurocognitive index, worse cognitive flexibility, executive functions, complex attention composite memory, verbal memory, slower reaction time and worse performance in SAT, CPT, ST tests. Obesity was associated with worse results in VBM, VIM, FTT, SDC tests. Raised blood pressure was associated with improvements in all cognitive domains and better performance in SAT, CPT, ST tests. Discussion. There are several weak associations between severity of clinical symptoms and metabolic abnormalities. Most of these were for blood glucose levels and raised blood glucose. Lipids and glucose abnormalities are the best predictors of deteriorated cognitive performance. Contrary to previous observations, raised blood pressure was associated with better results in cognitive tests. Conclusions. These findings indicate that cognitive impairment and metabolic abnormalities may be linked in patients with schizophrenia

  14. Mutation Profiling of Clinically Advanced Cancers Using Next-Generation Sequencing for Targeted Therapy: A Lifespan Experience.

    Science.gov (United States)

    Friedman, Kenneth; Resnick, Murray B; Safran, Howard

    2015-10-01

    The application of modern molecular tests such as next-generation sequencing (NGS) to human malignancies has led to better understanding of tumor biology and the design of targeted molecular therapies. In the research setting, important genomic alterations in tumors have been discovered with potential therapeutic implications but data regarding the impact of this technology in a real world oncology practice is limited. As a result, we decided to review the results of NGS in 144 advanced-stage cancer patients referred to the oncology practices of Lifespan-affiliated centers in Rhode Island. Most cancers revealed genomic alterations in genes commonly mutated in cancer. However, several unexpected genomic alterations were discovered in certain cancers with potential therapeutic intervention. Most cancers contained "actionable" genomic alterations despite being of advanced stage. Our experience demonstrates that application of NGS in the clinical setting contributes both to increasing the therapeutic armamentarium as well as our understanding of tumor biology.

  15. Mutation Profiling of Clinically Advanced Cancers Using Next-Generation Sequencing for Targeted Therapy: A Lifespan Experience.

    Science.gov (United States)

    Friedman, Kenneth; Resnick, Murray B; Safran, Howard

    2015-10-01

    The application of modern molecular tests such as next-generation sequencing (NGS) to human malignancies has led to better understanding of tumor biology and the design of targeted molecular therapies. In the research setting, important genomic alterations in tumors have been discovered with potential therapeutic implications but data regarding the impact of this technology in a real world oncology practice is limited. As a result, we decided to review the results of NGS in 144 advanced-stage cancer patients referred to the oncology practices of Lifespan-affiliated centers in Rhode Island. Most cancers revealed genomic alterations in genes commonly mutated in cancer. However, several unexpected genomic alterations were discovered in certain cancers with potential therapeutic intervention. Most cancers contained "actionable" genomic alterations despite being of advanced stage. Our experience demonstrates that application of NGS in the clinical setting contributes both to increasing the therapeutic armamentarium as well as our understanding of tumor biology. PMID:26422540

  16. The correlation of student performance in preclinical and clinical prosthodontic assessments.

    Science.gov (United States)

    Curtis, Donald A; Lind, Samuel L; Brear, Sheila; Finzen, Frederick C

    2007-03-01

    Tracking student performance in preclinical and clinical courses can be helpful in developing and refining a curriculum. Our objective was to correlate student performance on three fixed prosthodontic examinations taken by eighty junior dental students. Examinations included a knowledge-based objective structured clinical examination (OSCE), a manual skills exercise completed on a typodont (Typodont), and a competency casting exam (Casting CE) on a patient. Multiple regression analysis indicated that the OSCE and Typodont exam scores, as independent variables, were not statistically significant predictors (P=0.07; P=0.87, respectively) of Casting CE exam performance, which was the dependent variable. Correlations were weak for the OSCE (r=0.21) and nearly nonexistent for the Typodont exam(r=0.03) when compared to the Casting CE. Our results indicate a weak correlation between an OSCE-based knowledge exam measuring students' knowledge of critical errors in preparations and castings and a competency exam involving the preparation of a full veneer crown. Results also indicate virtually no correlation between a typodont preparation examination designed to provide a measure of students' clinical skill and a clinical competency exam involving the preparation of a full crown. PMID:17389571

  17. Performance-based quality specifications: the relationship between process critical control parameters, critical quality attributes, and clinical performance.

    Science.gov (United States)

    Short, Steven M; Cogdill, Robert P; Drennen, James K; Anderson, Carl A

    2011-04-01

    The quality of pharmaceutical products is currently evaluated through a series of tests that do not explicitly communicate the clinical consequences of product variability. A previously published risk simulation platform was used to generate quantitative estimates of inefficacy and toxicity for 288 uniform lots of extended-release theophylline tablets displaying various levels of content uniformity and dissolution variability. These data were used to evaluate the univariate specifications utilized in the United States Pharmacopeia (USP) and . Simulation revealed that the specifications are too lenient for content uniformity, both in terms of inefficacy and toxicity, whereas the criteria for dissolution testing are too strict for inefficacy and inaccurate for toxicity. The USP tests also failed to pinpoint the clinical interaction between content uniformity and dissolution variability. Additionally, the simulation platform was used to define the underlying relationship between product quality attributes and clinical performance. Here, content uniformity and Weibull dissolution time constants were used as inputs to the design spaces, which were conditioned on quantitative estimates of inefficacy and toxicity. This methodology enhances the information content of the design space by omitting quality surrogates (e.g., dissolution, moisture content) that are utilized in current design space practices.

  18. Genetic aberrations in small B-cell lymphomas and leukemias: molecular pathology, clinical relevance and therapeutic targets.

    Science.gov (United States)

    Bogusz, Agata M; Bagg, Adam

    2016-09-01

    Small B-cell lymphomas and leukemias (SBCLs) are a clinically, morphologically, immunophenotypically and genetically heterogeneous group of clonal lymphoid neoplasms, including entities such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL) and hairy cell leukemia (HCL). The pathogenesis of some of these lymphoid malignancies is characterized by distinct translocations, for example t(11;14) in the majority of cases of MCL and t(14;18) in most cases of FL, whereas other entities are associated with a variety of recurrent but nonspecific numeric chromosomal abnormalities, as exemplified by del(13q14), del(11q22), and +12 in CLL, and yet others such as LPL and HCL that lack recurrent or specific cytogenetic aberrations. The recent surge in next generation sequencing (NGS) technology has shed more light on the genetic landscape of SBCLs through characterization of numerous driver mutations including SF3B1 and NOTCH1 in CLL, ATM and CCND1 in MCL, KMT2D and EPHA7 in FL, MYD88 (L265P) in LPL, KLF2 and NOTCH2 in splenic MZL (SMZL) and BRAF (V600E) in HCL. The identification of distinct genetic lesions not only provides greater insight into the molecular pathogenesis of these disorders but also identifies potential valuable biomarkers for prognostic stratification, as well as specific targets for directed therapy. This review discusses the well-established and recently identified molecular lesions underlying the pathogenesis of SBCLs, highlights their clinical relevance and summarizes novel targeted therapies. PMID:27121112

  19. 鼻咽癌临床靶区定义%Definition of clinical target volume (CTV) for nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    林少俊; 潘建基; 郭巧娟

    2011-01-01

    Radiation therapy is the mainstay treatment modality for nasopharyngeal carcinoma (NPC), and the outcome is well associated to radiation dose. As a precise radiation technology, intensity-modulated radiotherapy (IMRT) offers the possibility of improving survival and simultaneously protect the surrounding normal tissue. The improvement of local control by IMRT has been well confirmed by a number of studies form domestic and abroad. However, the selection and definition of clinical target volume (CTV) for nasopharyngeal carcinoma has not yet reached a consensus. This article aimed to discovery the direction and mode for future research of reducing the treatment volume by reviewing the domestic and international development of CTV.%鼻咽癌为放射剂量相关性恶性肿瘤,放射治疗是鼻咽癌的首选治疗方法.调强放射治疗作为精确的放疗技术为提高剂量、保护周围正常组织提供了可能,国内外多家放疗中心的研究结果己证实调强放疗可提高鼻咽癌局部控制率.然而,当前对鼻咽癌的亚临床靶区(clinical target volume,CTV)的界定尚未达成共识,本文通过回顾国内外鼻咽癌CTV定义的发展过程,探讨未来缩小鼻咽癌靶区定义的发展方向和模式.

  20. Performance Comparison of EKF/UKF/CKF for the Tracking of Ballistic Target

    Directory of Open Access Journals (Sweden)

    Wu Guang-bin

    2012-11-01

    Full Text Available This paper considers three well know nonlinear Kalman Filters for the tracking of a ballistic target. Extended Kalman Filter (EKF, Unscented Kalman Filter (UKF, and the Cubature Kalman Filter (CKF are applied for estimating the position, velocity and the ballistic coefficient of the ballistic target. The theory formulation and computer simulation has been done for the comparison of the three nonlinear Kalman Filters. Results show that all of them can accomplish the estimation task, but the UKF and CKF both have higher accuracy and less computation cost than the EKF.

  1. A memetic algorithm for path planning of curvature-constrained UAVs performing surveillance of multiple ground targets

    Institute of Scientific and Technical Information of China (English)

    Zhang Xing; Chen Jie; Xin Bin; Peng Zhihong

    2014-01-01

    The problem of generating optimal paths for curvature-constrained unmanned aerial vehicles (UAVs) performing surveillance of multiple ground targets is addressed in this paper. UAVs are modeled as Dubins vehicles so that the constraints of UAVs’ minimal turning radius can be taken into account. In view of the effective surveillance range of the sensors equipped on UAVs, the problem is formulated as a Dubins traveling salesman problem with neighborhood (DTSPN). Considering its prohibitively high computational complexity, the Dubins paths in the sense of terminal heading relaxation are introduced to simplify the calculation of the Dubins distance, and a boundary-based encoding scheme is proposed to determine the visiting point of every target neighborhood. Then, an evolutionary algorithm is used to derive the optimal Dubins tour. To further enhance the quality of the solutions, a local search strategy based on approximate gradient is employed to improve the visiting points of target neighborhoods. Finally, by a minor modification to the individual encoding, the algorithm is easily extended to deal with other two more sophisticated DTSPN variants (multi-UAV scenario and multiple groups of targets scenario). The performance of the algorithm is demonstrated through comparative experiments with other two state-of-the-art DTSPN algorithms identified in literature. Numerical simulations exhibit that the algorithm proposed in this paper can find high-quality solutions to the DTSPN with lower computational cost and produce significantly improved performance over the other algorithms.

  2. Modeling and performance of HF/OTH (High-Frequency/Over-the-Horizon) radar target identification systems

    Science.gov (United States)

    Strausberger, Donald J.

    Several Radar Target Identification (RTI) techniques have been developed at The Ohio State University in recent years. Using the ElectroScience Laboratory compact range a large database of coherent RCS measurement has been constructed for several types of targets (aircraft, ships, and ground vehicles) at a variety of polarizations, aspect angles, and frequency bands. This extensive database has been used to analyze the performance of several different classification algorithms through the use of computer simulations. In order to optimize classification performance, it was concluded that the radar frequency range should lie in the Rayleigh-resonance frequency range, where the wavelength is on the order of or larger than the target size. For aircraft and ships with general dimensions on the order of 10 meters to 100 meters it is apparent that the High Frequency (HF) band provides optimal classification performance. Since existing HF radars are currently being used for detection and tracking or aircraft and ships of these dimensions, it is natural to further investigate the possibility of using these existing radars as the measurement devices in a radar target classification system.

  3. A memetic algorithm for path planning of curvature-constrained UAVs performing surveillance of multiple ground targets

    Directory of Open Access Journals (Sweden)

    Zhang Xing

    2014-06-01

    Full Text Available The problem of generating optimal paths for curvature-constrained unmanned aerial vehicles (UAVs performing surveillance of multiple ground targets is addressed in this paper. UAVs are modeled as Dubins vehicles so that the constraints of UAVs’ minimal turning radius can be taken into account. In view of the effective surveillance range of the sensors equipped on UAVs, the problem is formulated as a Dubins traveling salesman problem with neighborhood (DTSPN. Considering its prohibitively high computational complexity, the Dubins paths in the sense of terminal heading relaxation are introduced to simplify the calculation of the Dubins distance, and a boundary-based encoding scheme is proposed to determine the visiting point of every target neighborhood. Then, an evolutionary algorithm is used to derive the optimal Dubins tour. To further enhance the quality of the solutions, a local search strategy based on approximate gradient is employed to improve the visiting points of target neighborhoods. Finally, by a minor modification to the individual encoding, the algorithm is easily extended to deal with other two more sophisticated DTSPN variants (multi-UAV scenario and multiple groups of targets scenario. The performance of the algorithm is demonstrated through comparative experiments with other two state-of-the-art DTSPN algorithms identified in literature. Numerical simulations exhibit that the algorithm proposed in this paper can find high-quality solutions to the DTSPN with lower computational cost and produce significantly improved performance over the other algorithms.

  4. Performance study on point target detection using super-resolution reconstruction

    NARCIS (Netherlands)

    Dijk, J.; Van Eekeren, A.W.M.; Schutte, K.; De Lange, D.-J.J.; Van Vliet, L.J.

    2009-01-01

    When bright moving objects are viewed with an electro-optical system at very long range, they will appear as small slightly blurred moving points in the recorded image sequence. Detection of point targets is seriously hampered by structure in the background, temporal noise and aliasing artifacts due

  5. Nociceptin Opioid Receptor (NOP) as a Therapeutic Target: Progress in Translation from Preclinical Research to Clinical Utility.

    Science.gov (United States)

    Zaveri, Nurulain T

    2016-08-11

    In the two decades since the discovery of the nociceptin opioid receptor (NOP) and its ligand, nociceptin/orphaninFQ (N/OFQ), steady progress has been achieved in understanding the pharmacology of this fourth opioid receptor/peptide system, aided by genetic and pharmacologic approaches. This research spawned an explosion of small-molecule NOP receptor ligands from discovery programs in major pharmaceutical companies. NOP agonists have been investigated for their efficacy in preclinical models of anxiety, cough, substance abuse, pain (spinal and peripheral), and urinary incontinence, whereas NOP antagonists have been investigated for treatment of pain, depression, and motor symptoms in Parkinson's disease. Translation of preclinical findings into the clinic is guided by PET and receptor occupancy studies, particularly for NOP antagonists. Recent progress in preclinical NOP research suggests that NOP agonists may have clinical utility for pain treatment and substance abuse pharmacotherapy. This review discusses the progress toward validating the NOP-N/OFQ system as a therapeutic target. PMID:26878436

  6. Targeted dual-energy single-source CT for characterisation of urinary calculi: experimental and clinical experience

    Energy Technology Data Exchange (ETDEWEB)

    Eiber, Matthias; Holzapfel, Konstantin; Rummeny, Ernst J.; Dobritz, Martin; Huber, Armin [Technische Universitaet Muenchen, Institute of Radiology, Klinikum rechts der Isar, Munich (Germany); Frimberger, Markus; Straub, Michael [Technische Universitaet Muenchen, Department of Urology, Munich (Germany); Schneider, Heike [Technische Universitaet Muenchen, Institute of Clinical Chemistry and Pathobiochemistry, Munich (Germany)

    2012-01-15

    To assess the accuracy of targeted dual-energy single-source multi-detector CT (MDCT) for characterisation of urinary calculi. For proof of principle, 71 ex-vivo calculi underwent single-source 256-slice MDCT. Low-dose CT was performed in 154 patients with suspected urinary calculi. In 104 patients with urinary calculi targeted dual-energy imaging within one breath-hold was added. 46 patients with sufficient material for infrared-spectroscopy were analysed. Potential anatomical misregistrations between 80- and 140-kV{sub p}-images and HU-values were measured. DEIs (dual-energy-indices) were compared with the standard of reference. Effective doses were calculated. In 26 of 46 patients no misregistration was present. Mean deviations were 2.7 mm in the z-axis (16 patients) and 4.3 mm in the axial plane (10 patients). The DEIs were 0.018 {+-} 0.016 for uric acid (UA), 0.035 {+-} 0.015 for mixed UA and 0.102 {+-} 0.015 for calcified stones in-vitro and 0.017 {+-} 0.002 for UA, 0.050 {+-} 0.019 for mixed UA and 0.122 {+-} 0.024 for calcified calculi in-vivo. Significant differences were noted among calcium, mixed UA and UA stones (p < 0.05). For the low-dose examination mean effective dose was 3.11 mSv. Targeted dual-energy resulted in an extra dose of 1.84 mSv (additional 59.1%). Targeted dual-energy imaging within one breath-hold is feasible for characterisation of urinary calculi using single-source MDCT allowing minimal anatomical discordance. (orig.)

  7. Significant alterations in reported clinical practice associated with increased oversight of organ transplant center performance.

    Science.gov (United States)

    Schold, Jesse D; Arrington, Charlotte J; Levine, Greg

    2010-09-01

    In the past several years, emphasis on quality metrics in the field of organ transplantation has increased significantly, largely because of the new conditions of participation issued by the Centers for Medicare and Medicaid Services. These regulations directly associate patients' outcomes and measured performance of centers with the distribution of public funding to institutions. Moreover, insurers and marketing ventures have used publicly available outcomes data from transplant centers for business decision making and advertisement purposes. We gave a 10-question survey to attendees of the Transplant Management Forum at the 2009 meeting of the United Network for Organ Sharing to ascertain how centers have responded to the increased oversight of performance. Of 63 responses, 55% indicated a low or near low performance rating at their center in the past 3 years. Respondents from low-performing centers were significantly more likely to indicate increased selection criteria for candidates (81% vs 38%, P = .001) and donors (77% vs 31%, P < .001) as well as alterations in clinical protocols (84% vs 52%, P = .007). Among respondents indicating lost insurance contracts (31%), these differences were also highly significant. Based on respondents' perceptions, outcomes of performance evaluations are associated with significant changes in clinical practice at transplant centers. The transplant community and policy makers should practice vigilance that performance evaluations and regulatory oversight do not inadvertently lead to diminished access to care among viable candidates or decreased transplant volume. PMID:20929114

  8. A Prospective Pathologic Study to Define the Clinical Target Volume for Partial Breast Radiation Therapy in Women With Early Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Brandon T., E-mail: Brandon.Nguyen@act.gov.au [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Canberra Hospital, Radiation Oncology Department, Garran, ACT (Australia); Deb, Siddhartha [Department of Anatomical Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Victorian Cancer Biobank, Cancer Council of Victoria, Carlton, Victoria (Australia); Fox, Stephen [Department of Anatomical Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Hill, Prudence [Department of Anatomical Pathology, St. Vincent' s Hospital Melbourne, Fitzroy, Victoria (Australia); Collins, Marnie [Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Chua, Boon H. [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); University of Melbourne, Parkville, Victoria (Australia)

    2012-12-01

    Purpose: To determine an appropriate clinical target volume for partial breast radiation therapy (PBRT) based on the spatial distribution of residual invasive and in situ carcinoma after wide local excision (WLE) for early breast cancer or ductal carcinoma in situ (DCIS). Methods and Materials: We performed a prospective pathologic study of women potentially eligible for PBRT who had re-excision and/or completion mastectomy after WLE for early breast cancer or DCIS. A pathologic assessment protocol was used to determine the maximum radial extension (MRE) of residual carcinoma from the margin of the initial surgical cavity. Women were stratified by the closest initial radial margin width: negative (>1 mm), close (>0 mm and {<=}1 mm), or involved. Results: The study population was composed of 133 women with a median age of 59 years (range, 27-82 years) and the following stage groups: 0 (13.5%), I (40.6%), II (38.3%), and III (7.5%). The histologic subtypes of the primary tumor were invasive ductal carcinoma (74.4%), invasive lobular carcinoma (12.0%), and DCIS alone (13.5%). Residual carcinoma was present in the re-excision and completion mastectomy specimens in 55.4%, 14.3%, and 7.2% of women with an involved, close, and negative margin, respectively. In the 77 women with a noninvolved radial margin, the MRE of residual disease, if present, was {<=}10 mm in 97.4% (95% confidence interval 91.6-99.5) of cases. Larger MRE measurements were significantly associated with an involved margin (P<.001), tumor size >30 mm (P=.03), premenopausal status (P=.03), and negative progesterone receptor status (P=.05). Conclusions: A clinical target volume margin of 10 mm would encompass microscopic residual disease in >90% of women potentially eligible for PBRT after WLE with noninvolved resection margins.

  9. Optical performance of thin films produced by the pulsed laser deposition of SiAlON and Er targets

    International Nuclear Information System (INIS)

    Highlights: • PLD production of Er-doped thin films from a low cost commercial SiAlON target. • The role of the ablation fluence on the composition, optical properties as well as on the light emission performance at 1.5 μm. • The optimized performance is obtained for the samples deposited at the higher used ablation energy density. Further improvement was achieved through annealing. - Abstract: We report the preparation and optical performance of thin films produced by pulsed laser deposition in vacuum at room temperature, by focusing an ArF excimer laser onto two separate targets: a commercial ceramic SiAlON and a metallic Er target. As a result of the alternate deposition Er:SiAlON films were formed. The as grown films exhibited an Er-related emission peaking at 1532 nm. The role of the PLD energy density during deposition on the final matrix film was investigated, in order to achieve an optimized matrix composition with enhanced optical properties, and its effect on the light emission performance

  10. Optical performance of thin films produced by the pulsed laser deposition of SiAlON and Er targets

    Energy Technology Data Exchange (ETDEWEB)

    Camps, I., E-mail: camps@io.cfmac.csic.es [Laser Processing Group, Instituto de Óptica, CSIC, C/Serrano 121, 28006 Madrid (Spain); Ramírez, J.M. [MIND-IN2UB, Departament d’Electrònica, Universitat de Barcelona, c/Martí i Franqués 1, 08028 Barcelona (Spain); Mariscal, A.; Serna, R. [Laser Processing Group, Instituto de Óptica, CSIC, C/Serrano 121, 28006 Madrid (Spain); Garrido, B. [MIND-IN2UB, Departament d’Electrònica, Universitat de Barcelona, c/Martí i Franqués 1, 08028 Barcelona (Spain); Perálvarez, M.; Carreras, J. [IREC, Fundació Privada Institut de Recerca en Energia de Catalunya (Spain); Barradas, N.P.; Alves, L.C. [C" 2TN, Instituto Superior Técnico, Universidade de Lisboa, E.N. 10, 2695-066 Bobadela (Portugal); Alves, E. [IPFN, Instituto Superior Técnico, Universidade de Lisboa, E.N. 10, 2695-066 Bobadela (Portugal)

    2015-05-01

    Highlights: • PLD production of Er-doped thin films from a low cost commercial SiAlON target. • The role of the ablation fluence on the composition, optical properties as well as on the light emission performance at 1.5 μm. • The optimized performance is obtained for the samples deposited at the higher used ablation energy density. Further improvement was achieved through annealing. - Abstract: We report the preparation and optical performance of thin films produced by pulsed laser deposition in vacuum at room temperature, by focusing an ArF excimer laser onto two separate targets: a commercial ceramic SiAlON and a metallic Er target. As a result of the alternate deposition Er:SiAlON films were formed. The as grown films exhibited an Er-related emission peaking at 1532 nm. The role of the PLD energy density during deposition on the final matrix film was investigated, in order to achieve an optimized matrix composition with enhanced optical properties, and its effect on the light emission performance.

  11. Is medical perspective on clinical governance practices associated with clinical units’ performance and mortality? A cross-sectional study through a record-linkage procedure

    Science.gov (United States)

    Sarchielli, Guido; De Plato, Giovanni; Cavalli, Mario; Albertini, Stefano; Nonni, Ilaria; Bencivenni, Lucia; Montali, Arianna; Ventura, Antonio; Montali, Francesca

    2016-01-01

    Objective: Assessment of the knowledge and application as well as perceived utility by doctors of clinical governance tools in order to explore their impact on clinical units’ performance measured through mortality rates and efficiency indicators. Methods: This research is a cross-sectional study with a deterministic record-linkage procedure. The sample includes n = 1250 doctors (n = 249 chiefs of clinical units; n = 1001 physicians) working in six public hospitals located in the Emilia-Romagna Region in Italy. Survey instruments include a checklist and a research-made questionnaire which were used for data collection about doctors’ knowledge and application as well as perceived utility of clinical governance tools. The analysis was based on clinical units’ performance indicators which include patients’ mortality, extra-region active mobility rate, average hospital stay, bed occupancy, rotation and turnover rates, and the comparative performance index as efficiency indicators. Results: The clinical governance tools are known and applied differently in all the considered clinical units. Significant differences emerged between roles and organizational levels at which the medical leadership is carried out. The levels of knowledge and application of clinical governance practices are correlated with the clinical units’ efficiency indicators (bed occupancy rate, bed turnover interval, and extra-region mobility). These multiple linear regression analyses highlighted that the clinical governance knowledge and application is correlated with clinical units’ mortality rates (odds ratio, −8.677; 95% confidence interval, −16.654, −0.700). Conclusion: The knowledge and application, as well as perceived utility by medical professionals of clinical governance tools, are associated with the mortality rates of their units and with some efficiency indicators. However, the medical frontline staff seems to not consider homogeneously useful the clinical

  12. A computer-assisted protocol for endovascular target interventions using a clinical MRI system for controlling untethered microdevices and future nanorobots.

    Science.gov (United States)

    Martel, Sylvain; Mathieu, Jean-Baptiste; Felfoul, Ouajdi; Chanu, Arnaud; Aboussouan, Eric; Tamaz, Samer; Pouponneau, Pierre; Yahia, L'Hocine; Beaudoin, Gilles; Soulez, Gilles; Mankiewicz, Martin

    2008-11-01

    The possibility of automatically navigating untethered microdevices or future nanorobots to conduct target endovascular interventions has been demonstrated by our group with the computer-controlled displacement of a magnetic sphere along a pre-planned path inside the carotid artery of a living swine. However, although the feasibility of propelling, tracking and performing real-time closed-loop control of an untethered ferromagnetic object inside a living animal model with a relatively close similarity to human anatomical conditions has been validated using a standard clinical Magnetic Resonance Imaging (MRI) system, little information has been published so far concerning the medical and technical protocol used. In fact, such a protocol developed within technological and physiological constraints was a key element in the success of the experiment. More precisely, special software modules were developed within the MRI software environment to offer an effective tool for experimenters interested in conducting such novel interventions. These additional software modules were also designed to assist an interventional radiologist in all critical real-time aspects that are executed at a speed beyond human capability, and include tracking, propulsion, event timing and closed-loop position control. These real-time tasks were necessary to avoid a loss of navigation control that could result in serious injury to the patient. Here, additional simulation and experimental results for microdevices designed to be targeted more towards the microvasculature have also been considered in the identification, validation and description of a specific sequence of events defining a new computer-assisted interventional protocol that provides the framework for future target interventions conducted in humans.

  13. Bound analysis of target displacement for seismic performance assessment of buildings

    Institute of Scientific and Technical Information of China (English)

    JIA Li-zhe; DUAN Zhong-dong; LU Qin-nian

    2008-01-01

    The earthquake demand spectrum is often assumed as the average spectrum in the seismic design code or based upon probabilistic models to take into account the uncertainties of ground motion. The average spectrum can not deal with the uncertainty of earthquake excitation. Furthermore, results of probabilistic analy-sis are suspicious when information describing the uncertainty is inadequate. Considering the uncertainties of peak acceleration of ground motion and characteristic period of response spectra using a double bounded convex set model, the bounds of the design spectrum and the demand spectrum were obtained based on Chinese seismiccode. Then the convex analysis method was integrated into the capacity spectrum procedure to study the bound characteristics of target displacement. Finally, the target displacement was derived with an interval, and it is more objective and robust with respect to probabilistic perspective.

  14. The Causal Effect of Scholarships Targeted at Low Income Students on Performance: Evidence from Italy

    OpenAIRE

    V. Rattini

    2014-01-01

    This paper exploits discontinuities in the assigment of scholarships targeted at low income students in an Italian University in order to evaluate the effects of monetary incentives on students' academic achievement. Results reveal positive and sizeable causal effects both in terms of credits and grades. Gender differentials also emerge: male students drive the results on credits outcome while females students drive the effect on grades. These results suggest that the scholarship design contr...

  15. Performance Enhancement of Underwater Target Tracking by Fusing Data of Array of Global Positioning System Sonobuoys

    OpenAIRE

    Ahmed El-Shafie; Abdallah Osman; Aboelmagd Noureldin; Aini Hussien

    2009-01-01

    Problem statement: An accurate knowledge of geographic positions of sonobuoys is critical for the conduct of antisubmarine warfare operations and detected target localization. Deployed from an airborne platform or a surface vessel, arrays of sonobuoys could be used to efficiently track and localize submarines. Lastly, some sonobuoys were being equipped with GPS for improving system accuracy and potentially allowing networked Sonobuoy positioning. However, the computation of the range using th...

  16. The Effects of Sensor Performance as Modeled by Signal Detection Theory on the Performance of Reinforcement Learning in a Target Acquisition Task

    Science.gov (United States)

    Quirion, Nate

    Unmanned Aerial Systems (UASs) today are fulfilling more roles than ever before. There is a general push to have these systems feature more advanced autonomous capabilities in the near future. To achieve autonomous behavior requires some unique approaches to control and decision making. More advanced versions of these approaches are able to adapt their own behavior and examine their past experiences to increase their future mission performance. To achieve adaptive behavior and decision making capabilities this study used Reinforcement Learning algorithms. In this research the effects of sensor performance, as modeled through Signal Detection Theory (SDT), on the ability of RL algorithms to accomplish a target localization task are examined. Three levels of sensor sensitivity are simulated and compared to the results of the same system using a perfect sensor. To accomplish the target localization task, a hierarchical architecture used two distinct agents. A simulated human operator is assumed to be a perfect decision maker, and is used in the system feedback. An evaluation of the system is performed using multiple metrics, including episodic reward curves and the time taken to locate all targets. Statistical analyses are employed to detect significant differences in the comparison of steady-state behavior of different systems.

  17. Improving performance in golf: current research and implications from a clinical perspective

    Science.gov (United States)

    Evans, Kerrie; Tuttle, Neil

    2015-01-01

    Golf, a global sport enjoyed by people of all ages and abilities, involves relatively long periods of low intensity exercise interspersed with short bursts of high intensity activity. To meet the physical demands of full swing shots and the mental and physical demands of putting and walking the course, it is frequently recommended that golfers undertake golf-specific exercise programs. Biomechanics, motor learning, and motor control research has increased the understanding of the physical requirements of the game, and using this knowledge, exercise programs aimed at improving golf performance have been developed. However, while it is generally accepted that an exercise program can improve a golfer's physical measurements and some golf performance variables, translating the findings from research into clinical practice to optimise an individual golfer's performance remains challenging. This paper discusses how biomechanical and motor control research has informed current practice and discusses how emerging sophisticated tools and research designs may better assist golfers improve their performance. PMID:26537808

  18. Improving performance in golf: current research and implications from a clinical perspective.

    Science.gov (United States)

    Evans, Kerrie; Tuttle, Neil

    2015-01-01

    Golf, a global sport enjoyed by people of all ages and abilities, involves relatively long periods of low intensity exercise interspersed with short bursts of high intensity activity. To meet the physical demands of full swing shots and the mental and physical demands of putting and walking the course, it is frequently recommended that golfers undertake golf-specific exercise programs. Biomechanics, motor learning, and motor control research has increased the understanding of the physical requirements of the game, and using this knowledge, exercise programs aimed at improving golf performance have been developed. However, while it is generally accepted that an exercise program can improve a golfer's physical measurements and some golf performance variables, translating the findings from research into clinical practice to optimise an individual golfer's performance remains challenging. This paper discusses how biomechanical and motor control research has informed current practice and discusses how emerging sophisticated tools and research designs may better assist golfers improve their performance. PMID:26537808

  19. Improving performance in golf: current research and implications from a clinical perspective

    Directory of Open Access Journals (Sweden)

    Kerrie Evans

    2015-10-01

    Full Text Available ABSTRACTGolf, a global sport enjoyed by people of all ages and abilities, involves relatively long periods of low intensity exercise interspersed with short bursts of high intensity activity. To meet the physical demands of full swing shots and the mental and physical demands of putting and walking the course, it is frequently recommended that golfers undertake golf-specific exercise programs. Biomechanics, motor learning, and motor control research has increased the understanding of the physical requirements of the game, and using this knowledge, exercise programs aimed at improving golf performance have been developed. However, while it is generally accepted that an exercise program can improve a golfer's physical measurements and some golf performance variables, translating the findings from research into clinical practice to optimise an individual golfer's performance remains challenging. This paper discusses how biomechanical and motor control research has informed current practice and discusses how emerging sophisticated tools and research designs may better assist golfers improve their performance.

  20. Can anterior cruciate ligament reconstruction be performed routinely in day clinic?

    Science.gov (United States)

    De Beule, J; Vandenneucker, H; Claes, S; Bellemans, J

    2014-09-01

    Anterior cruciate ligament reconstruction is performed as an outpatient procedure in selected cases. Whether it can be safely performed on a routine basis in day clinic remains unclear. Our hypothesis was that routinely performing outpatient anterior cruciate ligament reconstruction would be equally safe as compared to inpatient procedures. A cohort of 355 patients who underwent outpatient primary reconstruction was analysed at an average follow-up of 3.8 years. Four patients (1.1%) could not be discharged or were readmitted within 24 hours. The 1-month readmission rate was 1.4%. The overall complication rate was 12.1% (43 cases) of which 4.2% (15 patients) occurred within the first 30 days. Performing anterior cruciate ligament reconstructions routinely in day clinic is associated with almost negligible readmission rates and has similar complication rates as for standard in-hospital anterior cruciate ligament reconstructions. Outpatient anterior cruciate ligament reconstructions can therefore be safely performed without specific preoperative patient selection protocols.

  1. Prevalence of outsourcing and perception of clinical nutrition managers on performance of health care dietetics services.

    Science.gov (United States)

    Kwon, Junehee; Yoon, Barbara J H

    2003-08-01

    A nationwide survey of clinical dietitians and clinical nutrition managers was conducted to assess the prevalence of outsourcing in health care dietetics services and to evaluate perceived performance of dietetics services. A questionnaire was developed, validated by an expert panel, and pilot tested prior to data collection. Members of the Clinical Nutrition Management Dietetic Practice Group (N=1,668) were selected as the study sample. Of 431 respondents, 152 (35.3%) indicated that management of both patient and cafeteria foodservices was outsourced. When mean scores of perceived performance ratings were compared using t test, respondents from self-operated facilities rated several items related to patient and cafeteria food quality and material and human resource utilization higher than respondents at contract-managed facilities. No significant differences were found in performance related to decision-making process, buying power, or training programs. Results suggest that careful weighing of advantages and disadvantages of outsourcing is needed before making decisions regarding outsourcing dietetics services.

  2. The intra- and inter-rater reliability of five clinical muscle performance tests in patients with and without neck pain

    DEFF Research Database (Denmark)

    Juul, Tina; Langberg, Henning; Enoch, Flemming;

    2013-01-01

    This study investigates the reliability of muscle performance tests using cost- and time-effective methods similar to those used in clinical practice. When conducting reliability studies, great effort goes into standardising test procedures to facilitate a stable outcome. Therefore, several test...... trials are often performed. However, when muscle performance tests are applied in the clinical setting, clinicians often only conduct a muscle performance test once as repeated testing may produce fatigue and pain, thus variation in test results. We aimed to investigate whether cervical muscle...... performance tests, which have shown promising psychometric properties, would remain reliable when examined under conditions similar to those of daily clinical practice....

  3. Targeting, Segmenting and Positioning the Market for College Students to Increase Customer Satisfaction and Overall Performance

    Science.gov (United States)

    Wright, Robert E.

    2008-01-01

    Numerous studies have explored the relationship between marketing efforts and firm financial performance. Studies have looked at potential lifetime value of customers, to demonstrate the value of keeping customers. Various other studies have looked at the relationship between customer satisfaction and firm performance. However, few studies have…

  4. On the comparison of the ballistic performance of 10% zirconia toughened alumina and 95% alumina ceramic target

    International Nuclear Information System (INIS)

    Ballistic performance of different type of ceramic materials subjected to high velocity impact was investigated in many theoretical, experimental and numerical studies. In this study, a comparison of ballistic performance of 95% alumina ceramic and 10% zirconia toughened alumina (ZTA) ceramic tiles was analyzed theoretically and experimentally. Spherical cavity model based on the concepts of mechanics of compressible porous media of Galanov was used to analyze the relation of target resistance and static mechanical properties. Experimental studies were carried out on the ballistic performance of above two types of ceramic tiles based on the depth of penetration (DOP) method, when subjected to normal impact of tungsten long rod projectiles. Typical damaged targets were presented. The residual depth of penetration on after-effect target was measured in all experiments, and the ballistic efficiency factor of above two types ceramic plates were determined. Both theoretical and experimental results show that the improvement on ballistic resistance was clearly observed by increasing fracture toughness in ZTA ceramics.

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

    OpenAIRE

    Chantal Robitaille; Esther Dajczman; Hirsch, Andrew M; David Small; Pierre Ernst; Dana Porubska; Mark Palayew

    2015-01-01

    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.OBJECTIVE: The present quality assurance study evaluated airflow obstruc...

  6. 5-year clinical performance of resin composite versus resin modified glass ionomer restorative system in non-carious cervical lesions

    DEFF Research Database (Denmark)

    Franco, Eduardo Batista; Benetti, Ana Raquel; Ishikiriama, Sérgio Kiyoshi;

    2006-01-01

    To comparatively assess the 5-year clinical performance of a 1-bottle adhesive and resin composite system with a resin-modified glass ionomer restorative in non-carious cervical lesions.......To comparatively assess the 5-year clinical performance of a 1-bottle adhesive and resin composite system with a resin-modified glass ionomer restorative in non-carious cervical lesions....

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-15

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

  9. Clinical evaluation of the Nucleus® 6 cochlear implant system: Performance improvements with SmartSound iQ

    OpenAIRE

    Mauger, Stefan J.; Warren, Chris D; Knight, Michelle R; Goorevich, Michael; Nel, Esti

    2014-01-01

    Objective: This paper provides a detailed description of the Nucleus 6 system, and clinically evaluates user performance compared to the previous Nucleus 5 system in cochlear implant recipients. Additionally, it clinically evaluates a range of Nucleus 6 and Nucleus 5 programs to determine the performance benefits provided by new input processing technologies available in SmartSound iQ. Design Speech understanding tests were used to clinically validate the default Nucleus 6 program, by compari...

  10. [Performance evaluation of VITEK 2 system in meropenem susceptibility testing of clinical Pseudomonas aeruginosa isolates].

    Science.gov (United States)

    Acuner, Ibrahim Cağatay; Bayramoğlu, Gülçin; Birinci, Asuman; Cekiç Cihan, Ciğdem; Bek, Yüksel; Durupınar, Belma

    2011-07-01

    Pseudomonas aeruginosa is an important opportunistic pathogen associated with various community-acquired or nosocomial infections. Multi-drug resistant P.aeruginosa strains increasingly cause epidemics and spread in various hospital wards and geographic regions. Carbapenems are among the most effective antimicrobials in the treatment of multi-drug resistant P.aeruginosa infections, and meropenem is the most successful among alternatives in initial therapy. Particularly in severe infections, inappropriate or inadequate initial antimicrobial therapy is independently associated with adverse clinical and economic outcomes. Availability of accurate and rapid susceptibility testing is a priority. Most of the automated microbiology systems can provide rapid results within 8 to 12 hours. In comparison to standard methods, problems in the antimicrobial susceptibility testing of particular microorganisms and antimicrobial agents have been reported for automated microbiology systems. Failures have been reported previously especially in the susceptibility testing of P.aeruginosa versus carbapenem. Most of these studies are designed according to the Food and Drug Administration (FDA, USA) performance analysis scheme (Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test Systems) in a simplified form. However, there are many lacking issues in the design of most of these studies. Among these, insufficient sample size, use of inappropriate reference method, lack of reproducibility testing, and inadequate distribution of study isolates in interpretative categories are of notice. There are only few studies in the literature that evaluate the performance of automated systems in antimicrobial susceptibility testing of carbapenems in clinical P.aeruginosa isolates with a sufficient sample size (n ? 100). However, most of these studies still have one or more major deficiencies in the study design. Furthermore, none of these studies evaluate the performance of

  11. Feasibility and Merits of Performing Preclinical Imaging on Clinical Radiology and Nuclear Medicine Systems

    Directory of Open Access Journals (Sweden)

    Mehmet Bilgen

    2013-01-01

    Full Text Available Aim. Researchers have limited access to systems dedicated to imaging small laboratory animals. This paper aims to investigate the feasibility and merits of performing preclinical imaging on clinical systems. Materials and Methods. Scans were performed on rat and mouse models of diseases or injuries on four radiology systems, tomosynthesis, computed tomography (CT, positron emission tomography/computed tomography (PET-CT, and Magnetic Resonance Imaging (MRI, based on the availability at the author’s institute. Results. Tomosysthesis delineated soft tissue anatomy and hard tissue structure with superb contrast and spatial resolution at minimal scan time and effort. CT allowed high resolution volumetric visualization of bones. Molecular imaging with PET was useful for detecting cancerous tissue in mouse but at the expense of poor resolution. MRI depicted abnormal or intervened tissue at quality and resolution sufficient for experimental studies. The paper discussed limitations of the clinical systems in preclinical imaging as well as challenges regarding the need of additional gadgets, modifications, or upgrades required for longitudinally scanning animals under anesthesia while monitoring their vital signs. Conclusion. Clinical imaging technologies can potentially make cost-effective and efficient contributions to preclinical efforts in obtaining anatomical, structural, and functional information from the underlying tissue while minimally compromising the data quality in certain situations.

  12. Neutronic Design and Measured Performance of the Low Energy Neutron Source (LENS) Target Moderator Reflector Assembly

    CERN Document Server

    Lavelle, C M; Bogdanov, A; Derenchuk, V P; Kaiser, H; Leuschner, M B; Lone, M A; Lozowski, W; Nann, H; Von Przewoski, B; Remmes, N; Rinckel, T; Shin, Y; Snow, W M; Sokol, P E

    2008-01-01

    The Low Energy Neutron Source (LENS) is an accelerator-based pulsed cold neutron facility under construction at the Indiana University Cyclotron Facility (IUCF). The idea behind LENS is to produce pulsed cold neutron beams starting with ~MeV neutrons from (p,n) reactions in Be which are moderated to meV energies and extracted from a small solid angle for use in neutron instruments which can operate efficiently with relatively broad (~1 msec) neutron pulse widths. Although the combination of the features and operating parameters of this source is unique at present, the neutronic design possesses several features similar to those envisioned for future neutron facilities such as long-pulsed spallation sources (LPSS) and very cold neutron (VCN) sources. We describe the underlying ideas and design details of the target/moderator/reflector system (TMR) and compare measurements of its brightness, energy spectrum, and emission time distribution under different moderator configurations with MCNP simulations. Brightnes...

  13. INFLUENCE OF STOCHASTIC NOISE STATISTICS ON KALMAN FILTER PERFORMANCE BASED ON VIDEO TARGET TRACKING

    Institute of Scientific and Technical Information of China (English)

    Chen Ken; Napolitano; Zhang Yun; Li Dong

    2010-01-01

    The system stochastic noises involved in Kalman filtering are preconditioned on being ideally white and Gaussian distributed. In this research,efforts are exerted on exploring the influence of the noise statistics on Kalman filtering from the perspective of video target tracking quality. The correlation of tracking precision to both the process and measurement noise covariance is investigated; the signal-to-noise power density ratio is defined; the contribution of predicted states and measured outputs to Kalman filter behavior is discussed; the tracking precision relative sensitivity is derived and applied in this study case. The findings are expected to pave the way for future study on how the actual noise statistics deviating from the assumed ones impacts on the Kalman filter optimality and degradation in the application of video tracking.

  14. Performance comparison of multi-detector detection statistics in targeted compact binary coalescence GW search

    CERN Document Server

    Haris, K

    2016-01-01

    Global network of advanced Interferometric gravitational wave (GW) detectors are expected to be on-line soon. Coherent observation of GW from a distant compact binary coalescence (CBC) with a network of interferometers located in different continents give crucial information about the source such as source location and polarization information. In this paper we compare different multi-detector network detection statistics for CBC search. In maximum likelihood ratio (MLR) based detection approaches, the likelihood ratio is optimized to obtain the best model parameters and the best likelihood ratio value is used as statistic to make decision on the presence of signal. However, an alternative Bayesian approach involves marginalization of the likelihood ratio over the parameters to obtain the average likelihood ratio. We obtain an analytical expression for the Bayesian statistic using the two effective synthetic data streams for targeted search of non-spinning compact binary systems with an uninformative prior on...

  15. The American Society for Clinical Pathology resident in-service examination: does resident performance provide insight into the effectiveness of clinical pathology education?

    Science.gov (United States)

    McKenna, Barbara J

    2007-06-01

    The resident in-service examination in pathology is an in-training exercise that is taken by virtually all pathology residents in the United States as well as by some participants in Canada, Ireland, and Lebanon. Although all of the anatomic pathology topics in the examination, with only one exception-forensic pathology, show significant improvement in scores over the 4 years of residency training, three areas of clinical pathology training (laboratory administration, clinical chemistry, and microbiology) show significantly lower improvement in performance over the years of residency training. By contrast, transfusion medicine, hematopathology and the special topics section of the examination all demonstrate improved performance by residents over time. While the reason behind these differences must remain speculative at this time, these findings suggest that measures to improve effectiveness in clinical pathology training might be suggested by examining the differences between residency training practices between higher and lower performing areas of clinical pathology.

  16. Key Performance Indicators and Target Values for Multi-Megawatt Offshore Turbines

    DEFF Research Database (Denmark)

    Chaviaropoulos, Panagiotis K.; Natarajan, Anand; Jensen, Peter Hjuler

    2014-01-01

    on the basis of key performance indicators (KPIs). Following the European Wind Industrial Initiative the Levelized Cost of Electricity (LCOE) and its driving components are investigated, while quantifying the sensitivity of LCOE to its constituent factors. Methods whereby innovation in design can reduce...

  17. 56-month clinical performance of Class I and II resin composite restorations

    Directory of Open Access Journals (Sweden)

    Flavia Bittencourt Pazinatto

    2012-06-01

    Full Text Available OBJECTIVE: This study evaluated the 56-month clinical performance of Class I and II resin composite restorations. Filtek P60 was compared with Filtek Z250, which are both indicated for posterior restorations but differ in terms of handling characteristics. The null hypothesis tested was that there is no difference in the clinical performance of the two resin composites in posterior teeth. MATERIAL AND METHODS: Thirty-three patients were treated by the same operator, who prepared 48 Class I and 42 Class II cavities, which were restored with Single Bond/Filtek Z250 or Single Bond/Filtek P60 restorative systems. Restorations were evaluated by two independent examiners at baseline and after 56 months, using the modified USPHS criteria. Data were analyzed statistically using Chi-square and Fisher's Exact tests (a=0.05. RESULTS: After 56 months, 25 patients (31 Class I and 36 Class II were analyzed. A 3% failure rate occurred due to secondary caries and excessive loss of anatomic form for P60. For both restorative systems, there were no significant differences in secondary caries and postoperative sensitivity. However, significant changes were observed with respect to anatomic form, marginal discoloration, and marginal adaptation. Significant decreases in surface texture were observed exclusively for the Z250 restorations. CONCLUSIONS: Both restorative systems can be used for posterior restorations and can be expected to perform well in the oral environment.

  18. An Algorithm for Glaucoma Screening in Clinical Settings and Its Preliminary Performance Profile

    Directory of Open Access Journals (Sweden)

    S-Farzad Mohammadi

    2013-01-01

    Full Text Available Purpose: To devise and evaluate a screening algorithm for glaucoma in clinical settings. Methods: Screening included examination of the optic disc for vertical cupping (≥0.4 and asymmetry (≥0.15, Goldmann applanation tonometry (≥21 mmHg, adjusted or unadjusted for central corneal thickness, and automated perimetry. In the diagnostic step, retinal nerve fiber layer imaging was performed using scanning laser polarimetry. Performance of the screening protocol was assessed in an eye hospital-based program in which 124 non-physician personnel aged 40 years or above were examined. A single ophthalmologist carried out the examinations and in equivocal cases, a glaucoma subspecialist′s opinion was sought. Results: Glaucoma was diagnosed in six cases (prevalence 4.8%; 95% confidence interval, 0.01-0.09 of whom five were new. The likelihood of making a definite diagnosis of glaucoma for those who were screened positively was 8.5 times higher than the estimated baseline risk for the reference population; the positive predictive value of the screening protocol was 30%. Screening excluded 80% of the initial population. Conclusion: Application of a formal screening protocol (such as our algorithm or its equivalent in clinical settings can be helpful in detecting new cases of glaucoma. Preliminary performance assessment of the algorithm showed its applicability and effectiveness in detecting glaucoma among subjects without any visual complaint.

  19. Effects of ongoing task context and target typicality on prospective memory performance: the importance of associative cueing

    Science.gov (United States)

    Nowinski, Jessica Lang; Dismukes, Key R.

    2005-01-01

    Two experiments examined whether prospective memory performance is influenced by contextual cues. In our automatic activation model, any information available at encoding and retrieval should aid recall of the prospective task. The first experiment demonstrated an effect of the ongoing task context; performance was better when information about the ongoing task present at retrieval was available at encoding. Performance was also improved by a strong association between the prospective memory target as it was presented at retrieval and the intention as it was encoded. Experiment 2 demonstrated boundary conditions of the ongoing task context effect, which implicate the association between the ongoing and prospective tasks formed at encoding as the source of the context effect. The results of this study are consistent with predictions based on automatic activation of intentions.

  20. Clinical observed performance evaluation: a prospective study in final year students of surgery.

    LENUS (Irish Health Repository)

    Markey, G C

    2010-06-24

    We report a prospective study of clinical observed performance evaluation (COPE) for 197 medical students in the pre-qualification year of clinical education. Psychometric quality was the main endpoint. Students were assessed in groups of 5 in 40-min patient encounters, with each student the focus of evaluation for 8 min. Each student had a series of assessments in a 25-week teaching programme. Over time, several clinicians from a pool of 16 surgical consultants and registrars evaluated each student by direct observation. A structured rating form was used for assessment data. Variance component analysis (VCA), internal consistency and inter-rater agreement were used to estimate reliability. The predictive and convergent validity of COPE in relation to summative OSCE, long case, and overall final examination was estimated. Median number of COPE assessments per student was 7. Generalisability of a mean score over 7 COPE assessments was 0.66, equal to that of an 8 x 7.5 min station final OSCE. Internal consistency was 0.88-0.97 and inter-rater agreement 0.82. Significant correlations were observed with OSCE performance (R = 0.55 disattenuated) and long case (R = 0.47 disattenuated). Convergent validity was 0.81 by VCA. Overall final examination performance was linearly related to mean COPE score with standard error 3.7%. COPE permitted efficient serial assessment of a large cohort of final year students in a real world setting. Its psychometric quality compared well with conventional assessments and with other direct observation instruments as reported in the literature. Effect on learning, and translation to clinical care, are directions for future research.

  1. Multi-laboratory evaluations of the performance of Catellicoccus marimammalium PCR assays developed to target gull fecal sources

    Science.gov (United States)

    Sinigalliano, Christopher D.; Ervin, Jared S.; Van De Werfhorst, Laurie C.; Badgley, Brian D.; Ballestée, Elisenda; Bartkowiaka, Jakob; Boehm, Alexandria B.; Byappanahalli, Muruleedhara N.; Goodwin, Kelly D.; Gourmelon, Michèle; Griffith, John; Holden, Patricia A.; Jay, Jenny; Layton, Blythe; Lee, Cheonghoon; Lee, Jiyoung; Meijer, Wim G.; Noble, Rachel; Raith, Meredith; Ryu, Hodon; Sadowsky, Michael J.; Schriewer, Alexander; Wang, Dan; Wanless, David; Whitman, Richard; Wuertz, Stefan; Santo Domingo, Jorge W.

    2013-01-01

    Here we report results from a multi-laboratory (n = 11) evaluation of four different PCR methods targeting the 16S rRNA gene of Catellicoccus marimammalium originally developed to detect gull fecal contamination in coastal environments. The methods included a conventional end-point PCR method, a SYBR® Green qPCR method, and two TaqMan® qPCR methods. Different techniques for data normalization and analysis were tested. Data analysis methods had a pronounced impact on assay sensitivity and specificity calculations. Across-laboratory standardization of metrics including the lower limit of quantification (LLOQ), target detected but not quantifiable (DNQ), and target not detected (ND) significantly improved results compared to results submitted by individual laboratories prior to definition standardization. The unit of measure used for data normalization also had a pronounced effect on measured assay performance. Data normalization to DNA mass improved quantitative method performance as compared to enterococcus normalization. The MST methods tested here were originally designed for gulls but were found in this study to also detect feces from other birds, particularly feces composited from pigeons. Sequencing efforts showed that some pigeon feces from California contained sequences similar to C. marimammalium found in gull feces. These data suggest that the prevalence, geographic scope, and ecology of C. marimammalium in host birds other than gulls require further investigation. This study represents an important first step in the multi-laboratory assessment of these methods and highlights the need to broaden and standardize additional evaluations, including environmentally relevant target concentrations in ambient waters from diverse geographic regions.

  2. Examination of Performance Management Targets in Case of an International Corporation’s Eastern Hungarian Operating Unit

    Directory of Open Access Journals (Sweden)

    Nemeth Zoltan

    2016-06-01

    Full Text Available Nowadays, due to the social and economic changes, the human is already the main resource which determines the successfulness of corporations. The expertise in managing the human resources is a key factor of competitiveness therefore it has become a strategic question. Primary aim of the treatise is to outline the most important principles, targets and peculiarities of performance management system, which is a central element of human resource management, as well as its interconnectedness with the individual performance evaluation and human resource development through the mirror of one of today’s biggest Hungarian economic corporations. We aimed to explore, by means of document analysis as well as methods of case study and interview, how the targets of performance management are used for increasing the economic productivity, preserving the competitiveness, retaining and enhancing the satisfaction of workers. It can be stated that the PM system was continuously improved in case of the organization examined because the corporate goals and the expected performances were adjusted to the changing market demands over time but, at the same time the goal of differentiation has remained unchanged. Each worker evaluates his/her performance individually, the base of which is the extent of contribution to the corporate results. Based on the results, it can overall be stated that such a well-functioning performance management system is applied in the operating unit of the corporation examined which is strongly supported by the organizational culture and which contributes to the joint fulfilment of personal as well as organizational goals.

  3. Predicting Anxiety Among Patients In LPU Clinical Dispensary During Dental Treatment: Towards Student’s Clinical Performance Enhancement

    Directory of Open Access Journals (Sweden)

    Maribel D. Mayuga-Barrion

    2013-12-01

    Full Text Available The study aimed to determine the respondents’ profile in terms of age, gender, frequency of dental visit, and type of patient whether dental phobic or not; to determine the dental anxiety of patients in LPU dental dispensary; to identify the causes and severity of anxiety of the patients in LPU dental dispensary; to determine if there is a significant difference between the respondents’ demographic profile and their level of anxiety; and lastly, to propose a program that will help the patients cope with dental anxiety and a program that will enhance the students’ clinical performance. The study used the descriptive research design with the combination of content analysis of documents and related materials. Results showed that majority of the respondents belonged to age range of 14-18 years old range whereas for gender or sex, majority who avail of the clinic’s services are males. This is because women are more afraid than men in terms of dental problems. Further, younger people are more afraid than older ones. The weighted mean distribution of the level of anxiety showed that the level of anxiety of patients varies on moderately to not anxious. Feeling or experiencing pain during dental treatment ranked first followed by the fear or worry of not working the proposed treatment and thirdly, the dentist is in a hurry while treating also made the patients moderately anxious. Overall, the level of anxiety of patients is moderately anxious. Probing to asses gum disease, dislike the numb feeling and injection were the top three causes of dental anxiety. Only type of patient shows significant difference, thus the null hypothesis of no significant difference on the level of anxiety when grouped according to profile variables is rejected. This means that the level of anxiety of both phobic and not phobic differs.

  4. Diclofenac-β-cyclodextrin for colonic drug targeting: In vivo performance in rats.

    Science.gov (United States)

    Vieira, Amélia C F; Serra, Arménio C; Veiga, Francisco J; Gonsalves, António M d'A Rocha; Basit, Abdul W; Murdan, Sudaxshina

    2016-03-16

    The aim of this in vivo study was to assess the ability of the prodrug conjugate diclofenac-β-cyclodextrin to release diclofenac in the colon following oral administration, using sulfapyridine (a metabolite of sulfasalazine) as a marker of colonic absorption. Two groups of rats were used; the test rats received a suspension containing the two prodrugs, diclofenac-β-cyclodextrin and sulfasalazine, while the control rats received a suspension containing the corresponding free drugs, sodium diclofenac and sulfapyridine. The rats were fasted overnight with free access to water before and throughout the first 12h of the study. Blood was collected from the tail vein at pre-determined time points and the plasma analyzed for the concentrations of diclofenac and sulfapyridine. Following the oral administration of the two prodrugs, a more extended absorption profile was observed and Cmax was achieved 10h post-dose, in contrast to rapid absorption of the free drugs (tmax of diclofenac being 1.3h, and that of sulfapyridine being 2.1h). In addition to a later tmax, conjugation of diclofenac to β-cyclodextrin also resulted in a reduced Cmax and a reduced AUC. The same tmax for diclofenac-β-cyclodextrin as for sulfasalazine confirms the colonic metabolism of diclofenac-β-cyclodextrin. This study shows the potential of this new cyclodextrin-based prodrug to target and release diclofenac specifically in the colon following oral administration. PMID:26784980

  5. TARGET RELATIVE NAVIGATION PERFORMANCE RESULTS FROM SINPLEX: A MINIATURIZED NAVIGATION SYSTEM

    OpenAIRE

    Steffes, Stephen; Theil, Stephan; Dumke, Michael; Heise, David; Krüger, Hans; Sagliano, Marco; Samaan, Malak; Oosterling, Han; Boslooper, Erik; Duivenvoorde, Tom; Schulte, Jan; Söderholm, S.; Skaborn, Daniel; Yanson, Yuriy; Esposito, Marco

    2014-01-01

    The goal of the SINPLEX project is to develop an innovative solution to significantly reduce the mass of the navigation subsystem for exploration missions which include landing and/or rendezvous and capture phases. The system mass is reduced by functionally integrating the navigation sensors, using micro- and nanotechnology to miniaturize electronics and fusing the sensor data within a navigation filter to improve navigation performance. A breadboard system was built and includes ...

  6. Simulation-Based Mastery Learning with Deliberate Practice Improves Clinical Performance in Spinal Anesthesia

    Directory of Open Access Journals (Sweden)

    Ankeet D. Udani

    2014-01-01

    Full Text Available Introduction. Properly performing a subarachnoid block (SAB is a competency expected of anesthesiology residents. We aimed to determine if adding simulation-based deliberate practice to a base curriculum improved performance of a SAB. Methods. 21 anesthesia residents were enrolled. After baseline assessment of SAB on a task-trainer, all residents participated in a base curriculum. Residents were then randomized so that half received additional deliberate practice including repetition and expert-guided, real-time feedback. All residents were then retested for technique. SABs on all residents’ next three patients were evaluated in the operating room (OR. Results. Before completing the base curriculum, the control group completed 81% of a 16-item performance checklist on the task-trainer and this increased to 91% after finishing the base curriculum (P<0.02. The intervention group also increased the percentage of checklist tasks properly completed from 73% to 98%, which was a greater increase than observed in the control group (P<0.03. The OR time required to perform SAB was not different between groups. Conclusions. The base curriculum significantly improved resident SAB performance. Deliberate practice training added a significant, independent, incremental benefit. The clinical impact of the deliberate practice intervention in the OR on patient care is unclear.

  7. Simulation-based mastery learning with deliberate practice improves clinical performance in spinal anesthesia.

    Science.gov (United States)

    Udani, Ankeet D; Macario, Alex; Nandagopal, Kiruthiga; Tanaka, Maria A; Tanaka, Pedro P

    2014-01-01

    Introduction. Properly performing a subarachnoid block (SAB) is a competency expected of anesthesiology residents. We aimed to determine if adding simulation-based deliberate practice to a base curriculum improved performance of a SAB. Methods. 21 anesthesia residents were enrolled. After baseline assessment of SAB on a task-trainer, all residents participated in a base curriculum. Residents were then randomized so that half received additional deliberate practice including repetition and expert-guided, real-time feedback. All residents were then retested for technique. SABs on all residents' next three patients were evaluated in the operating room (OR). Results. Before completing the base curriculum, the control group completed 81% of a 16-item performance checklist on the task-trainer and this increased to 91% after finishing the base curriculum (P < 0.02). The intervention group also increased the percentage of checklist tasks properly completed from 73% to 98%, which was a greater increase than observed in the control group (P < 0.03). The OR time required to perform SAB was not different between groups. Conclusions. The base curriculum significantly improved resident SAB performance. Deliberate practice training added a significant, independent, incremental benefit. The clinical impact of the deliberate practice intervention in the OR on patient care is unclear.

  8. Budget goal commitment, clinical managers' use of budget information and performance.

    Science.gov (United States)

    Macinati, Manuela S; Rizzo, Marco G

    2014-08-01

    Despite the importance placed on accounting as a means to influence performance in public healthcare, there is still a lot to be learned about the role of management accounting in clinical managers' work behavior and their link with organizational performance. The article aims at analyzing the motivational role of budgetary participation and the intervening role of individuals' mental states and behaviors in influencing the relationship between budgetary participation and performance. According to the goal-setting theory, SEM technique was used to test the relationships among variables. The data were collected by a survey conducted in an Italian hospital. The results show that: (i) budgetary participation does not directly influence the use of budget information, but the latter is encouraged by the level of budget goal commitment which, as a result, is influenced by the positive motivational consequences of participative budgeting; (ii) budget goal commitment does not directly influence performance, but the relationship is mediated by the use of budget information. This study contributes to health policy and management accounting literature and has significant policy implications. Mainly, the findings prove that the introduction of business-like techniques in the healthcare sector can improve performance if attitudinal and behavioral variables are adequately stimulated.

  9. Budget goal commitment, clinical managers' use of budget information and performance.

    Science.gov (United States)

    Macinati, Manuela S; Rizzo, Marco G

    2014-08-01

    Despite the importance placed on accounting as a means to influence performance in public healthcare, there is still a lot to be learned about the role of management accounting in clinical managers' work behavior and their link with organizational performance. The article aims at analyzing the motivational role of budgetary participation and the intervening role of individuals' mental states and behaviors in influencing the relationship between budgetary participation and performance. According to the goal-setting theory, SEM technique was used to test the relationships among variables. The data were collected by a survey conducted in an Italian hospital. The results show that: (i) budgetary participation does not directly influence the use of budget information, but the latter is encouraged by the level of budget goal commitment which, as a result, is influenced by the positive motivational consequences of participative budgeting; (ii) budget goal commitment does not directly influence performance, but the relationship is mediated by the use of budget information. This study contributes to health policy and management accounting literature and has significant policy implications. Mainly, the findings prove that the introduction of business-like techniques in the healthcare sector can improve performance if attitudinal and behavioral variables are adequately stimulated. PMID:24929475

  10. Performance Evaluation of Target Detection with a Near-Space Vehicle-Borne Radar in Blackout Condition.

    Science.gov (United States)

    Li, Yanpeng; Li, Xiang; Wang, Hongqiang; Deng, Bin; Qin, Yuliang

    2016-01-06

    Radar is a very important sensor in surveillance applications. Near-space vehicle-borne radar (NSVBR) is a novel installation of a radar system, which offers many benefits, like being highly suited to the remote sensing of extremely large areas, having a rapidly deployable capability and having low vulnerability to electronic countermeasures. Unfortunately, a target detection challenge arises because of complicated scenarios, such as nuclear blackout, rain attenuation, etc. In these cases, extra care is needed to evaluate the detection performance in blackout situations, since this a classical problem along with the application of an NSVBR. However, the existing evaluation measures are the probability of detection and the receiver operating curve (ROC), which cannot offer detailed information in such a complicated application. This work focuses on such requirements. We first investigate the effect of blackout on an electromagnetic wave. Performance evaluation indexes are then built: three evaluation indexes on the detection capability and two evaluation indexes on the robustness of the detection process. Simulation results show that the proposed measure will offer information on the detailed performance of detection. These measures are therefore very useful in detecting the target of interest in a remote sensing system and are helpful for both the NSVBR designers and users.

  11. Reproductive health services for populations at high risk of HIV: Performance of a night clinic in Tete province, Mozambique

    Directory of Open Access Journals (Sweden)

    Delva Wim

    2010-05-01

    Full Text Available Abstract Background Different models exist to provide HIV/STI services for most-at-risk populations (MARP. Along the Tete traffic corridor in Mozambique, linking Malawi and Zimbabwe, a night clinic opening between 4 and 10 PM was established targeting female sex workers (FSW and long-distance truck drivers (LDD. The clinic offers free individual education and counselling, condoms, STI care, HIV testing, contraceptive services and outreach peer education. To evaluate this clinic model, we assessed relevance, service utilisation, efficiency and sustainability. Methods In 2007-2009, mapping and enumeration of FSW and LDD was conducted; 28 key informants were interviewed; 6 focus group discussions (FGD were held with FSW from Mozambique and Zimbabwe, and LDD from Mozambique and Malawi. Clinic outputs and costs were analysed. Results An estimated 4,415 FSW work in the area, or 9% of women aged 15-49, and on average 66 trucks stay overnight near the clinic. Currently on average, 475 clients/month visit the clinic (43% for contraception, 24% for counselling and testing and 23% for STI care. The average clinic running cost is US$ 1408/month, mostly for human resources. All informants endorsed this clinic concept and the need to expand the services. FGD participants reported high satisfaction with the services and mentioned good reception by the health staff, short waiting times, proximity and free services as most important. Participants were in favour of expanding the range of services, the geographical coverage and the opening times. Conclusions Size of the target population, satisfaction of clients and endorsement by health policy makers justify maintaining a separate clinic for MARP. Cost-effectiveness may be enhanced by broadening the range of SRHR-HIV/AIDS services, adapting opening times, expanding geographical coverage and targeting additional MARP. Long-term sustainability remains challenging and requires private-public partnerships or

  12. Confidence level in performing clinical procedures among medical officers in nonspecialist government hospitals in Penang, Malaysia.

    Science.gov (United States)

    Othman, Mohamad Sabri; Merican, Hassan; Lee, Yew Fong; Ch'ng, Kean Siang; Thurairatnam, Dharminy

    2015-03-01

    A prospective cross-sectional study was conducted at 3 government hospitals over 6 months to evaluate the confidence level of medical officers (MOs) to perform clinical procedure in nonspecialist government hospitals in Penang. An anonymous self-administered questionnaire in English was designed based on the elective and emergency procedures stated in the houseman training logbook. The questionnaire was distributed to the MOs from Penang State Health Department through the respective hospital directors and returned to Penang State Health Department on completion. The results showed that there was statistically significant difference between those who had undergone 12 months and 24 months as houseman in performing both elective and emergency procedures. MOs who had spent 24 months as housemen expressed higher confidence level than those who had only 12 months of experience. We also found that the confidence level was statistically and significantly influenced by visiting specialist and working together with cooperative experienced paramedics.

  13. Clinical performance of a new silver dressing, Contreet Foam, for chronic exuding venous leg ulcers

    DEFF Research Database (Denmark)

    Karlsmark, T; Agerslev, R H; Bendz, S H;

    2003-01-01

    : The clinical performance of Contreet Foam was studied for four weeks in 25 patients with moderately to highly exuding delayed-healing venous leg ulcers. Healing was assessed on a weekly basis with reference to the wound-bed tissue composition, degree of odour and pain, dressing performance and the dressing......'s effect on the peri-ulcer area. Blood samples were analysed for silver content. RESULTS: Twenty-three out of 25 patients completed the study. One ulcer healed and no wound infections occurred during the study period. A mean 56% reduction in ulcer area (from 15.6 to 6.9 cm2) was recorded during the four...... weeks, and there was a mean 25% reduction in granulation tissue from dull to healthy after one week. Wound odour reduced significantly after one week. Mean dressing wear time was 3.1 days, and there were only minimal incidences of leakage. Serum silver levels did not exceed reference values. CONCLUSION...

  14. Noise performance of statistical model based iterative reconstruction in clinical CT systems

    Science.gov (United States)

    Li, Ke; Tang, Jie; Chen, Guang-Hong

    2014-03-01

    The statistical model based iterative reconstruction (MBIR) method has been introduced to clinical CT systems. Due to the nonlinearity of this method, the noise characteristics of MBIR are expected to differ from those of filtered backprojection (FBP). This paper reports an experimental characterization of the noise performance of MBIR equipped on several state-of-the-art clinical CT scanners at our institution. The thoracic section of an anthropomorphic phantom was scanned 50 times to generate image ensembles for noise analysis. Noise power spectra (NPS) and noise standard deviation maps were assessed locally at different anatomical locations. It was found that MBIR lead to significant reduction in noise magnitude and improvement in noise spatial uniformity when compared with FBP. Meanwhile, MBIR shifted the NPS of the reconstructed CT images towards lower frequencies along both the axial and the z frequency axes. This effect was confirmed by a relaxed slice thicknesstradeoff relationship shown in our experimental data. The unique noise characteristics of MBIR imply that extra effort must be made to optimize CT scanning parameters for MBIR to maximize its potential clinical benefits.

  15. EFFECTS OF MERGERS AND ACQUISITIONS ON FINANCIAL PERFORMANCE OF THE TARGET COMPANY

    OpenAIRE

    ADRIANA DUŢESCU; ANDREEA GABRIELA PONORÎCĂ; GEORGIANA OANA STĂNILĂ

    2013-01-01

    Many studies revealed the fact that mergers and acquisitions are a risky business. Disregarding the M&A advisers’ fees, evaluations show that most of the companies completing M&A transactions disappoint to deliver on promised financial performance. But, as many would say, it is an investment and the highest risks produce the highest results - whether they're good or bad. Within this paper, we were intending to analyse the rate of success of relevant M&A transactions that took place in 2007 in...

  16. On-Orbit Performance of the Bright Target Explorer (BRITE) Nanosatellite Astronomy Constellation

    OpenAIRE

    Sarda, Karan; Grant, Cordell; Chaumont, Monica; Yun Choi, Seung; Johnston-Lemke, Bryan; Zee, Robert

    2014-01-01

    In 2013, the first three satellites of the BRITE-Constellation mission, believed to be the world’s first satellite constellation dedicated to astronomy, were placed into orbit on two separate launches. To be eventually composed of at least six cooperating nanosatellites, BRITE-Constellation’s mission is to perform a survey of the most luminous stars in the Earth’s sky. In the push to observe ever fainter objects, these apparently bright stars, despite being prominent members of our most famil...

  17. High Performance Computing and Storage Requirements for Nuclear Physics: Target 2017

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Richard; Wasserman, Harvey

    2015-01-20

    In April 2014, NERSC, ASCR, and the DOE Office of Nuclear Physics (NP) held a review to characterize high performance computing (HPC) and storage requirements for NP research through 2017. This review is the 12th in a series of reviews held by NERSC and Office of Science program offices that began in 2009. It is the second for NP, and the final in the second round of reviews that covered the six Office of Science program offices. This report is the result of that review

  18. Key Elements of and Materials Performance Targets for Highly Insulating Window Frames

    OpenAIRE

    Gustavsen, Arild

    2012-01-01

    The thermal performance of windows is important for energy efficient buildings. Windows typically account for about 30-50 percent of the transmission losses though the building envelope, even if their area fraction of the envelope is far less. The reason for this can be found by comparing the thermal transmittance (U-factor) of windows to the U-factor of their opaque counterparts (wall, roof and floor constructions). In well insulated buildings the U-factor of walls, roofs an floors can be...

  19. Stepped care targeting psychological distress in head and neck and lung cancer patients: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Krebber Anne-Marie H

    2012-05-01

    Full Text Available Abstract Background Psychological distress is common in cancer survivors. Although there is some evidence on effectiveness of psychosocial care in distressed cancer patients, referral rate is low. Lack of adequate screening instruments in oncology settings and insufficient availability of traditional models of psychosocial care are the main barriers. A stepped care approach has the potential to improve the efficiency of psychosocial care. The aim of the study described herein is to evaluate efficacy of a stepped care strategy targeting psychological distress in cancer survivors. Methods/design The study is designed as a randomized clinical trial with 2 treatment arms: a stepped care intervention programme versus care as usual. Patients treated for head and neck cancer (HNC or lung cancer (LC are screened for distress using OncoQuest, a computerized touchscreen system. After stratification for tumour (HNC vs. LC and stage (stage I/II vs. III/IV, 176 distressed patients are randomly assigned to the intervention or control group. Patients in the intervention group will follow a stepped care model with 4 evidence based steps: 1. Watchful waiting, 2. Guided self-help via Internet or a booklet, 3. Problem Solving Treatment administered by a specialized nurse, and 4. Specialized psychological intervention or antidepressant medication. In the control group, patients receive care as usual which most often is a single interview or referral to specialized intervention. Primary outcome is the Hospital Anxiety and Depression Scale (HADS. Secondary outcome measures are a clinical level of depression or anxiety (CIDI, quality of life (EQ-5D, EORTC QLQ-C30, QLQ-HN35, QLQ-LC13, patient satisfaction with care (EORTC QLQ-PATSAT, and costs (health care utilization and work loss (TIC-P and PRODISQ modules. Outcomes are evaluated before and after intervention and at 3, 6, 9 and 12 months after intervention. Discussion Stepped care is a system of delivering and

  20. Evaluating assisted target recognition performance: an assessment of DARPA's SAIP system

    Science.gov (United States)

    Irvine, John M.

    1999-08-01

    New advanced imaging systems will soon be capable of collecting enormous volumes of imagery, placing a significant burden on the imagery analysts (IAs) that exploit these data. ATRs and other image understanding tools offer a way to assist IAs in exploiting large volumes of imagery more effectively and efficiently. The Defense Advanced Research Project Agency (DARPA) Semi-Automated IMINT Processing (SAIP) Program focuses on these technologies to assist IAs in the timely exploitation of SAR imagery. The SAIP system is an integrated set of imagery exploitation tools designed to improve the capability of the IA to support military missions in a tactical environment. To assess the utility of the SAIP technology, a mix of live and playback exercises were conducted. IAs exploited the imagery with the assistance of the SAIP technology. As a benchmark for comparison, the same imagery was exploited in an operational exploitation system without the benefit of SAIP assistance. This paper presents the methodology for assessing exploitation performance and discusses issues related to scoring exploitation performance. The results of a recent assessment event illustrate the issues and provide guidance for future work in this area.

  1. Mapping Patterns of Ipsilateral Supraclavicular Nodal Metastases in Breast Cancer: Rethinking the Clinical Target Volume for High-risk Patients

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Hao [Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Wang, Shu-Lian, E-mail: wsl20040118@yahoo.com [Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Li, Jing; Xue, Mei; Xiong, Zu-Kun [Department of Radiology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Jin, Jing; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Yu, Zi-Hao; Liu, Xin-Fan [Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Li, Ye-Xiong, E-mail: yexiong12@163.com [Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

    2015-10-01

    Purpose: To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target volume (CTV) of this region could be modified in high-risk subsets. Methods and Materials: Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. A modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting. Results: A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes. Conclusions: According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.

  2. Real-time and offline performance of pattern recognition myoelectric control using a generic electrode grid with targeted muscle reinnervation patients.

    Science.gov (United States)

    Tkach, Dennis C; Young, Aaron J; Smith, Lauren H; Rouse, Elliott J; Hargrove, Levi J

    2014-07-01

    Targeted muscle reinnervation (TMR) is a surgical technique that creates myoelectric prosthesis control sites for high-level amputees. The electromyographic (EMG) signal patterns provided by the reinnervated muscles are well-suited for pattern recognition control. Pattern recognition allows for control of a greater number of degrees of freedom (DOF) than the conventional, EMG amplitude-based approach. Previous pattern recognition studies have shown benefit in placing electrodes directly over the reinnervated muscles. Localizing the optimal TMR locations is inconvenient and time consuming. In this contribution, we demonstrate that a clinically practical grid arrangement of electrodes yields real-time control performance that is equivalent to, or better than, the site-specific electrode placement for simultaneous control of multiple DOFs using pattern recognition. Additional findings indicate that grid-like electrode arrangement yields significantly lower classification errors for classifiers with a large number of movement classes ( > 9). These findings suggest that a grid electrode arrangement can be effectively used to control a multi-DOF upper limb prosthesis while reducing the time and effort associated with fitting the prosthesis due to clinical localization of control sites on amputee patients.

  3. An Effective Model for a Comprehensive Performance Measurement of Clinical and Research Laboratory Centers

    Directory of Open Access Journals (Sweden)

    Ghazinoory S

    2011-01-01

    Full Text Available Bachground and objectives: Improvement of the effectiveness of services isone of the most important strategies in many clinical and research laboratorycenters. The increased client satisfaction (researchers or patients, resourcedevelopment innovation, efficacy, continuity of services and income are alsothe important strategies of these centers. For achieving these strategies, wecombined the qualitative and the quantitative approaches to evaluate theeffective model based on frameworks of the Balance Scorecard (BSC and theLaboratory Quality Management Systems (LQMS.Material and Methods: This paper describes the basic steps required fordesigning and developing of a model for performance measurement inlaboratory centers. For model validation, the relationship between the criteria,the strategies and the strategic objectives was evaluated using both the AHPmethod and the evaluation by the experts.Results: Implementation of the above mentioned model, conducted in one ofthe largest Laboratory centers, has resulted in a remarkable enhancement inthe efficiency (22%, profit (33%, level of quality of service (27% and inthe clients’ satisfaction (4%.Conclusion: This research model is a valuable tool for effective evaluationand continuous improvement of the clinical and research laboratory centers.Applying this model leads to increased resource productivity as well as theclients and community satisfaction from the laboratories services.Key words: Laboratory Centers, Performance Management, BalanceScorecard (BSC, Laboratory Quality Management Systems (LQMS

  4. Episiotomy and its relationship to various clinical variables that influence its performance

    Science.gov (United States)

    Ballesteros-Meseguer, Carmen; Carrillo-García, César; Meseguer-de-Pedro, Mariano; Canteras-Jordana, Manuel; Martínez-Roche, Mª Emilia

    2016-01-01

    Objective: to understand the episiotomy rate and its relationship with various clinical variables. Method: a descriptive, cross-sectional, analytic study of 12,093 births in a tertiary hospital. Variables: Parity, gestational age, start of labor, use of epidural analgesia, oxytocin usage, position during fetal explusion, weight of neonate, and completion of birth. The analysis was performed with SPSS 19.0. Results: the global percentage of episiotomies was 50%. The clinical variables that presented a significant association were primiparity (RR=2.98), gestational age >41 weeks (RR=1.2), augmented or induced labor (RR=1.33), epidural analgesia use (RR=1,95), oxytocin use (RR=1.58), lithotomy position during fetal expulsion (RR=6.4), and instrumentation (RR=1.84). Furthermore, maternal age ≥35 years (RR=0.85) and neonatal weight <2500 g (RR=0.8) were associated with a lower incidence of episiotomy. Conclusions: episiotomy is dependent on obstetric interventions performed during labor. If we wish to reduce the episiotomy rate, it will be necessary to bear in mind these risk factors when establishing policies for reducing this procedure. PMID:27224064

  5. Episiotomy and its relationship to various clinical variables that influence its performance

    Directory of Open Access Journals (Sweden)

    Carmen Ballesteros-Meseguer

    2016-01-01

    Full Text Available Objective: to understand the episiotomy rate and its relationship with various clinical variables. Method: a descriptive, cross-sectional, analytic study of 12,093 births in a tertiary hospital. Variables: Parity, gestational age, start of labor, use of epidural analgesia, oxytocin usage, position during fetal explusion, weight of neonate, and completion of birth. The analysis was performed with SPSS 19.0. Results: the global percentage of episiotomies was 50%. The clinical variables that presented a significant association were primiparity (RR=2.98, gestational age >41 weeks (RR=1.2, augmented or induced labor (RR=1.33, epidural analgesia use (RR=1,95, oxytocin use (RR=1.58, lithotomy position during fetal expulsion (RR=6.4, and instrumentation (RR=1.84. Furthermore, maternal age ≥35 years (RR=0.85 and neonatal weight <2500 g (RR=0.8 were associated with a lower incidence of episiotomy. Conclusions: episiotomy is dependent on obstetric interventions performed during labor. If we wish to reduce the episiotomy rate, it will be necessary to bear in mind these risk factors when establishing policies for reducing this procedure.

  6. Diagnostic tests for influenza and other respiratory viruses: determining performance specifications based on clinical setting.

    Science.gov (United States)

    Takahashi, Hiroshi; Otsuka, Yoshihito; Patterson, Bruce K

    2010-06-01

    The lack of sensitivity of rapid immunoassays in detecting the novel 2009 H1N1 influenza virus infection has led to recommendations on influenza diagnostic testing for clinicians treating patients as well as advising clinicians on testing decisions. Studies have also shown that rapid immunoassays for seasonal influenza virus show considerable variability in performance characteristics, based on age of patient, prevalence of disease, course of infection, and the quality of the kit used. While public health authorities are currently focused on influenza virus diagnostics, a lack of sensitivity of rapid immunoassays for other viral respiratory pathogens has been widely reported, such as the very limited value of rapid immunoassays for the detection of respiratory syncytial virus in adults. In light of the lack of sensitivity of diagnostic tests for suspected 2009 H1N1 influenza virus infection, as well as their variable performance characteristics for seasonal influenza virus, a number of recommendations have been made by public health authorities advising clinicians on the need for clinical judgment as an important part of testing and treatment decisions as well as reliance on local epidemiologic and surveillance data. With the availability of new molecular methodologies that are user-friendly and allow the front-line physician as well as hospital infection control programs to significantly improve respiratory viral diagnostics, there is a need to carefully determine the most optimal diagnostic testing methodology based on the clinical setting. This review will describe the historical, current, and changing dynamics of respiratory virus infection diagnostics.

  7. Clinical performance - a reflection of damage accumulation in ceramic dental crowns

    Energy Technology Data Exchange (ETDEWEB)

    Rekow, D.E. [Univ. of Medicine and Dentistry of New Jersey, Newark, NJ (United States). Dept. of Orthodontics; Thompson, V.P. [Univ. of Medicine and Dentistry of New Jersey, Newark, NJ (United States). New Jersey Dental School

    2001-07-01

    All-ceramic dental crowns have tremendous appeal for patients - their esthetics nearly match those of natural teeth. Unfortunately, the most esthetic materials are brittle and, consequently, are vulnerable to damage relating to shaping which is exacerbated during cyclic loading during normal chewing. Clinical performance of all-ceramic dental prostheses are directly dependent on damage introduced during fabrication and during fatigue loading associated with function. The accumulation of damage results in unacceptably high failure rates (where failure is defined as a complete fracture requiring replacement of the prosthesis). The relation between shaping damage and fatigue damage on clinical performance of all-ceramic dental crowns was investigated. Materials used commercially for all-ceramic crowns and investigated in this study included a series of different microstructures of machinable glass ceramics (Corning), aluminas and porcelains (Vita Zahnfabrik), and zirconia (Norton). As monolithic materials, strong, tough, fatigue-resistant materials are not sufficiently esthetic for crowns. Crowns fabricated from monolithic esthetic materials have high failure rates. Layering ceramics could provide acceptable strength through management of damage accumulation. (orig.)

  8. Performance of thirteen clinical rules to distinguish bacterial and presumed viral meningitis in Vietnamese children.

    Directory of Open Access Journals (Sweden)

    Nguyen Tien Huy

    Full Text Available BACKGROUND AND PURPOSE: Successful outcomes from bacterial meningitis require rapid antibiotic treatment; however, unnecessary treatment of viral meningitis may lead to increased toxicities and expense. Thus, improved diagnostics are required to maximize treatment and minimize side effects and cost. Thirteen clinical decision rules have been reported to identify bacterial from viral meningitis. However, few rules have been tested and compared in a single study, while several rules are yet to be tested by independent researchers or in pediatric populations. Thus, simultaneous test and comparison of these rules are required to enable clinicians to select an optimal diagnostic rule for bacterial meningitis in settings and populations similar to ours. METHODS: A retrospective cross-sectional study was conducted at the Infectious Department of Pediatric Hospital Number 1, Ho Chi Minh City, Vietnam. The performance of the clinical rules was evaluated by area under a receiver operating characteristic curve (ROC-AUC using the method of DeLong and McNemar test for specificity comparison. RESULTS: Our study included 129 patients, of whom 80 had bacterial meningitis and 49 had presumed viral meningitis. Spanos's rule had the highest AUC at 0.938 but was not significantly greater than other rules. No rule provided 100% sensitivity with a specificity higher than 50%. Based on our calculation of theoretical sensitivity and specificity, we suggest that a perfect rule requires at least four independent variables that posses both sensitivity and specificity higher than 85-90%. CONCLUSIONS: No clinical decision rules provided an acceptable specificity (>50% with 100% sensitivity when applying our data set in children. More studies in Vietnam and developing countries are required to develop and/or validate clinical rules and more very good biomarkers are required to develop such a perfect rule.

  9. Exploring the Process of Energy Generation in Pathophysiology by Targeted Metabolomics: Performance of a Simple and Quantitative Method

    Science.gov (United States)

    Riera-Borrull, Marta; Rodríguez-Gallego, Esther; Hernández-Aguilera, Anna; Luciano, Fedra; Ras, Rosa; Cuyàs, Elisabet; Camps, Jordi; Segura-Carretero, Antonio; Menendez, Javier A.; Joven, Jorge; Fernández-Arroyo, Salvador

    2016-01-01

    Abnormalities in mitochondrial metabolism and regulation of energy balance contribute to human diseases. The consequences of high fat and other nutrient intake, and the resulting acquired mitochondrial dysfunction, are essential to fully understand common disorders, including obesity, cancer, and atherosclerosis. To simultaneously and noninvasively measure and quantify indirect markers of mitochondrial function, we have developed a method based on gas chromatography coupled to quadrupole-time of flight mass spectrometry and an electron ionization interface, and validated the system using plasma from patients with peripheral artery disease, human cancer cells, and mouse tissues. This approach was used to increase sensibility in the measurement of a wide dynamic range and chemical diversity of multiple intermediate metabolites used in energy metabolism. We demonstrate that our targeted metabolomics method allows for quick and accurate identification and quantification of molecules, including the measurement of small yet significant biological changes in experimental samples. The apparently low process variability required for its performance in plasma, cell lysates, and tissues allowed a rapid identification of correlations between interconnected pathways. Our results suggest that delineating the process of energy generation by targeted metabolomics can be a valid surrogate for predicting mitochondrial dysfunction in biological samples. Importantly, when used in plasma, targeted metabolomics should be viewed as a robust and noninvasive source of biomarkers in specific pathophysiological scenarios.

  10. Radiopharmaceutical Chemistry of Targeted Radiopharmaceutics. Synthesis of 211At-Labeled Radiopharmaceuticals at High Activities for Clinical Use

    International Nuclear Information System (INIS)

    Targeted α-particle radiotherapy is an appealing approach to cancer treatment because of the potential for delivering curative doses of radiation to tumor with minimal damage to normal tissue due to a range equivalent to only a few cell diameters. Compared with β-emitters they have significant advantages from a radiobiological perspective. The LET of 211At α-particles is more than 400 times higher than the β-particles emitted by 90Y, in addition the distance between ionizing events is almost the same as that between the two strands of DNA, yielding a high probability of creating non-repairable DNA damage. It gives the ability to kill cancer cells not compromised by hypoxia, dose rate effects or cell cycle position, enhancing their attractiveness for targeted radiotherapy. However, translation of the concept to the clinic has been slow, many obstacles had to be surmounted before clinical studies could be initiated, the first clinical evaluation of a 211At- labeled mAb was made in 2001. This study circumvents many of the challenges to entering clinical studies with 211At. But several problems were encountered in maintaining efficient labeling with escalating radiation dose of alpha-particle likely related to radiolysis. The impact of the radiolysis produced by the α-particle over the labeling chemistry is much higher in comparison with typical β-emitters due to a deposition of energy in the solvent in a highly localized manner two orders of magnitude per unit volume higher than 90Y or 131I. Due to these difficulties a comprehensive basic science study about the radiolytic effects of astatine alpha-particles over the synthesis of 211At-labeled radiopharmaceuticals was carried out. Its main goal was overcoming the problem of the synthesis of 211At-labeled radiopharmaceuticals at the high activities necessaries for therapy and also to extend the shelf life of astatine elutions. Briefly this study held several steps, the first one was to study the role of solvent

  11. Performance Evaluation of an Automated ELISA System for Alzheimer's Disease Detection in Clinical Routine.

    Science.gov (United States)

    Chiasserini, Davide; Biscetti, Leonardo; Farotti, Lucia; Eusebi, Paolo; Salvadori, Nicola; Lisetti, Viviana; Baschieri, Francesca; Chipi, Elena; Frattini, Giulia; Stoops, Erik; Vanderstichele, Hugo; Calabresi, Paolo; Parnetti, Lucilla

    2016-07-22

    The variability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers undermines their full-fledged introduction into routine diagnostics and clinical trials. Automation may help to increase precision and decrease operator errors, eventually improving the diagnostic performance. Here we evaluated three new CSF immunoassays, EUROIMMUNtrademark amyloid-β 1-40 (Aβ1-40), amyloid-β 1-42 (Aβ1-42), and total tau (t-tau), in combination with automated analysis of the samples. The CSF biomarkers were measured in a cohort consisting of AD patients (n = 28), mild cognitive impairment (MCI, n = 77), and neurological controls (OND, n = 35). MCI patients were evaluated yearly and cognitive functions were assessed by Mini-Mental State Examination. The patients clinically diagnosed with AD and MCI were classified according to the CSF biomarkers profile following NIA-AA criteria and the Erlangen score. Technical evaluation of the immunoassays was performed together with the calculation of their diagnostic performance. Furthermore, the results for EUROIMMUN Aβ1-42 and t-tau were compared to standard immunoassay methods (INNOTESTtrademark). EUROIMMUN assays for Aβ1-42 and t-tau correlated with INNOTEST (r = 0.83, p < 0.001 for both) and allowed a similar interpretation of the CSF profiles. The Aβ1-42/Aβ1-40 ratio measured with EUROIMMUN was the best parameter for AD detection and improved the diagnostic accuracy of Aβ1-42 (area under the curve = 0.93). In MCI patients, the Aβ1-42/Aβ1-40 ratio was associated with cognitive decline and clinical progression to AD.The diagnostic performance of the EUROIMMUN assays with automation is comparable to other currently used methods. The variability of the method and the value of the Aβ1-42/Aβ1-40 ratio in AD diagnosis need to be validated in large multi-center studies. PMID:27447425

  12. Publishing history does not correlate with clinical performance among internal medicine residents.

    Science.gov (United States)

    Cavalcanti, Rodrigo B; Detsky, Allan S

    2010-05-01

    OBJECTIVES Selection criteria for applicants to the internal medicine programme at the University of Toronto have included the number and quality of scholarly items published. We sought to determine whether previous publishing record correlated with resident performance as measured by in-training evaluation reports (ITERs) and global impressions of clinical competency by site programme directors and senior educators (global impression). METHODS Data on the total number, quality and type of items published, as well as the timing of publishing with regard to pre-MD training, were abstracted from the curricula vitae of individuals who applied for residency during 2001-2005. These were correlated with overall, Expert and Scholar role ITER scores, and with global impression, using Spearman rank correlation scores. RESULTS We gathered publishing history data on 181 residents, for 162 of whom ITER data were available. Overall, 68.5% of residents had published, but only 14.9% had published during medical school. There was a weak correlation of borderline significance (rho = 0.15, P = 0.055) between overall ITER score and number of items published. No such correlation was found with CanMEDS Medical Expert and Scholar role scores. Global impression classified 33.9% of residents as top-rated. More top-rated residents had published (76.7% versus 65.1%; P = 0.07), but the number of items published during medical school were similar between top-rated and non-top-rated residents (16.1% versus 12.3%; P = 0.46). CONCLUSIONS Our results do not support publishing record as a predictor of residents' clinical performance. Surprisingly, the correlation between publishing record and Scholar role scores was also weak, possibly indicating an inability of the ITER to capture this competency. Further research is needed to identify predictors and measures of performance in scholarly activities. PMID:20345694

  13. Retrospective Analysis of Indication of Bone Scintigraphy Performed in Our Clinic

    Directory of Open Access Journals (Sweden)

    Fusun Aydogan

    2014-03-01

    Full Text Available Aim: Bone scintigraphy is one of the commonly used radionuclide imaging and it is successfully used in the diagnosis and follow-up of many diseases. The aim of this study is to determine the indications and filming protocols of bone scintigraphy which was performed in our clinic. Material and Method: Two hundred and fifty two patients (132 male, 120 female who was performed bone scintigprapy in our clinic between December 2011 and June 2013 included the study. Mean age was 50.1±20.2 years. Scintigraphic protocols were made in two ways as late static whole body imaging and three-phase bone scintigraphy according to the type of the diseases. Indications of scintigraphies and scintigraphic protocols were detected. Results: Bone scintigraphy was performed for diagnosis and monitoring of metastatic bone disease to 102 patients (40,5 %, for orthopedic applications to 57 patients (22,6 %, for diagnosis and monitoring of primary bone tumors to 29 patients (11,5 %, for diagnosis of osteomyelitis to 17 patients (6,7 %, for differential diagnosis of infection and loosening of the prosthesis to 12 patients (4,8 %, investigate the viability of the graft in 14 patients (4,6 %, for rheumatologic diseases to 9 patients (3,6 %, for investigate the pathological vertebral fractures and osteoporosis to 4 patients (1,6 %, for diagnosis the metabolic bone disease to 2 patients (0,8 %, for diagnosis of otitis externa to 5 patients (1,98 % and for for suspicion of malignancy to 1 patient (0,4 %. Late static whole body imaging protocol was applied to 136 patients (54 % and three-phase imaging protocol was applied to 116 patients (46 %. Discussion: The most common use of bone scintigraphy is the diagnosis and follow-up of metastatic bone disease. It is followed by reasons such as orthopedic applications, monitoring and diagnosis of primary bone tumors and diagnosis of osteomyelitis.

  14. Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.

    Science.gov (United States)

    Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

    2016-03-01

    [Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists.

  15. Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.

    Science.gov (United States)

    Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

    2016-03-01

    [Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists. PMID:27134355

  16. Why peer assessment helps to improve clinical performance in undergraduate physical therapy education: a mixed methods design

    NARCIS (Netherlands)

    Maas, M.J.M.; Sluijsmans, D.M.; Wees, P.J. van der; Heerkens, Y.F.; Nijhuis-Van der Sanden, M.W.; Vleuten, C.P.M. van der

    2014-01-01

    BACKGROUND: Peer Assessment (PA) in health professions education encourages students to develop a critical attitude towards their own and their peers' performance. We designed a PA task to assess students' clinical skills (including reasoning, communication, physical examination and treatment skills

  17. Why peer assessment helps to improve clinical performance in undergraduate physical therapy education : A mixed methods design

    NARCIS (Netherlands)

    Maas, Marjo; Sluijsmans, Dominique; Wees, Philip van der; Heerkens, Yvonne; Nijhuis-van der Sanden, Maria; Vleuten, Cees van der

    2014-01-01

    Background: Peer Assessment (PA) in health professions education encourages students to develop a critical attitude towards their own and their peers’ performance. We designed a PA task to assess students' clinical skills (including reasoning, communication, physical examination and treatment skills

  18. Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial

    OpenAIRE

    Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

    2016-01-01

    [Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression ...

  19. Targeting anti-apoptotic Bcl-2 by AT-101 to increase radiation efficacy: data from in vitro and clinical pharmacokinetic studies in head and neck cancer

    International Nuclear Information System (INIS)

    Pro-survival Bcl-2 family members can promote cancer development and contribute to treatment resistance. Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. Inhibition of anti-apoptotic Bcl-2 family members therefore represents an appealing strategy to overcome resistance to anti-cancer therapies. The aim of this study was to evaluate combined effects of radiation and the pan-Bcl-2 inhibitor AT-101 in HNSCC in vitro. In addition, we determined human plasma levels of AT-101 obtained from a phase I/II trial, and compared these with the effective in vitro concentrations to substantiate therapeutic opportunities. We examined the effect of AT-101, radiation and the combination on apoptosis induction and clonogenic survival in two HNSCC cell lines that express the target proteins. Apoptosis was assessed by bis-benzimide staining to detect morphological nuclear changes and/or by propidium iodide staining and flow-cytometry analysis to quantify sub-diploid apoptotic nuclei. The type of interaction between AT-101 and radiation was evaluated by calculating the Combination Index (CI) and by performing isobolographic analysis. For the pharmacokinetic analysis, plasma AT-101 levels were measured by HPLC in blood samples collected from patients enrolled in our clinical phase I/II study. These patients with locally advanced HNSCC were treated with standard cisplatin-based chemoradiotherapy and received dose-escalating oral AT-101 in a 2-weeks daily schedule every 3 weeks. In vitro results showed that AT-101 enhances radiation-induced apoptosis with CI’s below 1.0, indicating synergy. This effect was sequence-dependent. Clonogenic survival assays demonstrated a radiosensitizing effect with a DEF37 of 1.3 at sub-apoptotic concentrations of AT-101. Pharmacokinetic analysis

  20. TGLF Recalibration for ITER Standard Case Parameters FY2015: Theory and Simulation Performance Target Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Candy, J. [General Atomics, San Diego, CA (United States)

    2015-12-01

    This work was motivated by the observation, as early as 2008, that GYRO simulations of some ITER operating scenarios exhibited nonlinear zonal-flow generation large enough to effectively quench turbulence inside r /a ~ 0.5. This observation of flow-dominated, low-transport states persisted even as more accurate and comprehensive predictions of ITER profiles were made using the state-of-the-art TGLF transport model. This core stabilization is in stark contrast to GYRO-TGLF comparisons for modern-day tokamaks, for which GYRO and TGLF are typically in very close agreement. So, we began to suspect that TGLF needed to be generalized to include the effect of zonal-flow stabilization in order to be more accurate for the conditions of reactor simulations. While the precise cause of the GYRO-TGLF discrepancy for ITER parameters was not known, it was speculated that closeness to threshold in the absence of driven rotation, as well as electromagnetic stabilization, created conditions more sensitive the self-generated zonal-flow stabilization than in modern tokamaks. Need for nonlinear zonal-flow stabilization: To explore the inclusion of a zonal-flow stabilization mechanism in TGLF, we started with a nominal ITER profile predicted by TGLF, and then performed linear and nonlinear GYRO simulations to characterize the behavior at and slightly above the nominal temperature gradients for finite levels of energy transport. Then, we ran TGLF on these cases to see where the discrepancies were largest. The predicted ITER profiles were indeed near to the TGLF threshold over most of the plasma core in the hybrid discharge studied (weak magnetic shear, q > 1). Scanning temperature gradients above the TGLF power balance values also showed that TGLF overpredicted the electron energy transport in the low-collisionality ITER plasma. At first (in Q3), a model of only the zonal-flow stabilization (Dimits shift) was attempted. Although we were able to construct an ad hoc model of the zonal

  1. TGLF Recalibration for ITER Standard Case Parameters FY2015: Theory and Simulation Performance Target Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Candy, J. [General Atomics, San Diego, CA (United States)

    2015-12-01

    This work was motivated by the observation, as early as 2008, that GYRO simulations of some ITER operating scenarios exhibited nonlinear zonal-flow generation large enough to effectively quench turbulence inside r /a ~ 0.5. This observation of flow-dominated, low-transport states persisted even as more accurate and comprehensive predictions of ITER profiles were made using the state-of-the-art TGLF transport model. This core stabilization is in stark contrast to GYRO-TGLF comparisons for modern-day tokamaks, for which GYRO and TGLF are typically in very close agreement. So, we began to suspect that TGLF needed to be generalized to include the effect of zonal-flow stabilization in order to be more accurate for the conditions of reactor simulations. While the precise cause of the GYRO-TGLF discrepancy for ITER parameters was not known, it was speculated that closeness to threshold in the absence of driven rotation, as well as electromagnetic stabilization, created conditions more sensitive the self-generated zonal-flow stabilization than in modern tokamaks. Need for nonlinear zonal-flow stabilization: To explore the inclusion of a zonal-flow stabilization mechanism in TGLF, we started with a nominal ITER profile predicted by TGLF, and then performed linear and nonlinear GYRO simulations to characterize the behavior at and slightly above the nominal temperature gradients for finite levels of energy transport. Then, we ran TGLF on these cases to see where the discrepancies were largest. The predicted ITER profiles were indeed near to the TGLF threshold over most of the plasma core in the hybrid discharge studied (weak magnetic shear, q > 1). Scanning temperature gradients above the TGLF power balance values also showed that TGLF overpredicted the electron energy transport in the low-collisionality ITER plasma. At first (in Q3), a model of only the zonal-flow stabilization (Dimits shift) was attempted. Although we were able to construct an ad hoc model of the zonal

  2. Investigation of a portable performance measurement system for neurologic screening in clinics.

    Science.gov (United States)

    Kondraske, George V; Mulukutla, Rahul; Stewart, R Malcolm

    2006-01-01

    Motivated by the need for clinical screening for early detection of neurologic disease, a prototype portable instrument dubbed the human performance multimeter (HPMM) was developed. The HPMM is based on a set of lab-based performance capacity tests developed and evaluated over the last two decades. We attempted to integrate selected functionality of a set of modular lab-based instruments into a single, small package. In the present study, a 4th generation prototype was developed and evaluated for usability, measurement repeatability, and preliminary measurement validity. Five performance capacity tests (upper extremity coordination, isometric grip strength, simple response speed, rapid alternating movement, and steadiness/tremor) were administered to twenty healthy adult volunteers. Short-term reliability was investigated using a test-retest protocol. Most measures were found to possess good test-retest reliability (r>0.75). Preliminary validity was investigated by comparing results to those obtained with non-portable devices that served as models for the HPMM. Results were in good agreement with those instruments. It is concluded that measures of good fidelity can be obtained with this type of instrument. PMID:17946212

  3. Performance in quasi-firms: an example from the Community Clinical Oncology Program.

    Science.gov (United States)

    Lacey, L M; Hynes, D M; Kaluzny, A D

    1992-01-01

    In this analysis, the authors examined the effects of different sets of process, structure, and environmental variables on the performance of the CCOP as a quasi-firm. Specifically, they distinguished between internal organizational processes, structural, and size characteristics of the CCOP and the organizational environment created by prior NCI program experience and the relationship within the quasi-firm. The analysis revealed that these sets of organizational and environmental characteristics have differential effects on treatment accrual. The strongest predictors are those associated with the quasi-firm relationship between the CCOP and its chosen research bases. Any definitive policy implications for the design of organizational network relationships--especially the CCOPs--will require further analysis. Particular attention needs to be given to the longitudinal nature of the relationships and the ability of these organizational and environmental factors to affect other aspects of performance. Several points have been made within this initial assessment. First, the structural character of the CCOP and its relationship to its organizational environment are important factors affecting accrual performance. The subtleties of this multivariate model are not as important as simply demonstrating that the various internal and external characteristics of these organizations as quasi-firms simultaneously affect their ability to accrue patients to clinical trials. Secondly, the importance of research base relations, and particularly the significant role of nurses, needs to be emphasized. While CCOPs were originally designed as a network of physicians and hospitals, it appears that an infrastructure of professionally active nurses working within a larger organizational environment is critical to success--at least as defined by accrual to treatment protocols. Finally, the failure of prior experience with other NCI community programs to affect CCOP accrual performance

  4. What clinical activities do advanced-practice registered dietitian nutritionists perform? Results of a Delphi study.

    Science.gov (United States)

    Brody, Rebecca A; Byham-Gray, Laura; Touger-Decker, Riva; Passannante, Marian R; Rothpletz Puglia, Pamela; O'Sullivan Maillet, Julie

    2014-05-01

    Activities performed by advanced-practice registered dietitian nutritionists (RDNs) have yet to be clearly elucidated. The study aimed to gain consensus on the practice activities of advanced-practice RDNs who provide direct clinical nutrition care. A three-round Delphi study was conducted. Purposive sampling identified 117 RDN experts working as clinicians and/or managers in direct care settings that met inclusion criteria for advanced-level practice. In Round 1, 85 experts provided open-ended advanced-level practice activities linked to the Nutrition Care Process sections. Using content analysis, the responses were coded into activity statements. In Round 2, experts rated the essentiality of these activities. In Round 3, experts re-rated statements not reaching consensus while viewing their previous rating, the group median, and comments. Median ratings of 1.0 to 3.0 were defined as essential, 4.0 were neither essential nor nonessential, and 5.0 to 7.0 were nonessential. Consensus was reached when the interquartile range of responses to each question was <2.0. Seventy-six (89.4%) experts completed all rounds. From 770 comments, 129 activity statements were generated. All statements reached consensus: 97.7% as essential; 0.8% as nonessential; and 1.5% as neither. Of essential activities, 67.5% were highly essential with limited variability (median=1.0; interquartile range≤2.0). Advanced-practice RDNs' tasks are patient-centered and reflect complex care; involve a comprehensive and discriminating approach; are grounded in advanced knowledge and expertise in clinical nutrition; include use of advanced interviewing, education, and counseling strategies; and require communication with patient, families, and the health care team. The high-level of consensus from experts suggest advanced-level clinical nutrition practice exists and can be defined.

  5. Pemetrexed clinical studies in performance status 2 patients with non-small cell lung cancer (Review).

    Science.gov (United States)

    Zinner, Ralph; Visseren-Grul, Carla; Spigel, David R; Obasaju, Coleman

    2016-01-01

    Because poor performance status (PS) is an independent prognostic factor in non-small cell lung cancer (NSCLC), PS scores are widely used by oncologists to make treatment decisions. Advanced NSCLC patients with an Eastern Cooperative Oncology Group PS of 2 have poor prognoses and are frequently excluded from clinical trials. This article reviews the efficacy and safety of pemetrexed in this patient group. We identified English-language literature (through March 2015) involving completed and ongoing studies through searches of PubMed, meeting abstracts, ClinicalTrials.gov and the European Clinical Trials Register; search terms included 'pemetrexed,' 'NSCLC' and 'PS2'. Only studies reporting ≥1 subset analysis of PS2 patients receiving pemetrexed were chosen. Our search identified a total of ten pemetrexed studies in PS2 patients. Eight studies included only chemonaive patients, one study included both chemonaive patients and patients with one prior chemotherapy regimen and one study included only patients with one prior regimen. In subset analyses in these studies, PS2 patients had worse outcomes than PS0-1 patients regardless of treatment. In a phase 3 study, chemonaive advanced NSCLC patients with PS2 receiving pemetrexed‑carboplatin versus pemetrexed experienced improved overall survival [hazard ratio (HR)=0.62; P=0.001], progression-free survival (HR=0.46; Pstudies, PS2 patients treated with pemetrexed plus carboplatin as first-line therapy had improved response rates and survival. Additional research on PS2 patients is needed.

  6. A review of the clinical performance of the Aptima HPV assay.

    Science.gov (United States)

    Haedicke, Juliane; Iftner, Thomas

    2016-03-01

    This comprehensive review compiles published data from 62 original articles comparing different HPV tests and one meta-analysis on the clinical performance of the Aptima HR HPV (AHPV) assay in either screening or referral populations as well as for the purpose of test of cure. A number of publications with technical issues were also considered. Besides a brief introduction in the development of E6/E7 mRNA testing, the review summarizes data on analytical sensitivies and specificities, as well as on clinical sensitivity, specificity, NPV and PPV with histological endpoints CIN2+ and CIN3+, where available. Although most studies were of cross-sectional design, five studies with a longitudinal prospective design or component were identified. In addition to the study design, sample size, age and CIN2/3+ prevalence of the respective cohort are listed. This allows direct comparison of the published data in the respective groups. One major outcome of this review is the remarkably stable similar sensitivities of AHPV and HC2 independent from study design for detection of CIN2/3+ combined with a higher specificity of the AHPV. The second outcome was the longitudinal predictive value derived from registry linkage and other prospective studies that would support the applicability of the AHPV test in primary screening with at least a three year screening interval. PMID:26614686

  7. 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.

    2016-05-01

    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

  8. Technical and clinical breast cancer screening performance indicators for computed radiography versus direct digital radiography

    Energy Technology Data Exchange (ETDEWEB)

    Bosmans, Hilde; Lemmens, Kim; Zanca, Federica; Ongeval, Chantal van; Steen, Andre van [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Hauwere, An de; Thierens, Hubert [Ghent University, QCC, Ghent (Belgium); Herck, Koen van; Bleyen, Luc; Mortier, Griet [Ghent University, Centrum voor Preventie en Vroegtijdige Opsporing van Kanker, Department of Public Health, Ghent (Belgium); Martens, Patrick [Vroegtijdige Opsporing Borstklierkanker West-Vlaanderen vzw, Bruges (Belgium); Putte, Gretel vande; Kellen, Eliane; Limbergen, Erik van [Leuven University Center of Cancer Screening, Leuven (Belgium)

    2013-10-15

    To compare technical and clinical screening performance parameters between computed radiography (CR) and direct digital radiography (DR) systems. The number of women screened with CR was 73,008 and with DR 116,945. Technical and patient dose survey data of 25 CR and 37 DR systems were available. Technical performance was expressed by threshold thickness values at the mean glandular dose (MGD) level of routine practice. Clinical indicators included recall rate (RR), cancer detection rate (CDR), percentage of ductal carcinoma in situ (DCIS), percentage of cancers with T-scores smaller than 1 cm and positive predictive value (PPV). Contrast threshold values for the 0.1-mm gold disk were 1.44 {mu}m (SD 0.13 {mu}m) for CR and 1.20 {mu}m (SD 0.13 {mu}m for DR). MGD was 2.16 mGy (SD 0.36 mGy) and 1.35 mGy (SD 0.32 mGy) for CR and DR respectively. We obtained for CR, respectively DR, the following results: RR in the first round of 5.48 % versus 5.61 %; RR in subsequent rounds of 2.52 % versus 2.65 %; CDR of 0.52 % versus 0.53 %; DCIS of 0.08 % versus 0.11 %; a rate of cancers with T-scores smaller than 1 cm of 0.11 % versus 0.11 %; PPV of 18.45 % versus 18.64 %; none of them was significantly different. Our screening indicators are reassuring for the use of CR and DR, with CR operating at 60 % higher MGD. (orig.)

  9. Clinical usefulness of carotid arterial wave intensity in assessing left ventricular systolic and early diastolic performance.

    Science.gov (United States)

    Ohte, Nobuyuki; Narita, Hitomi; Sugawara, Motoaki; Niki, Kiyomi; Okada, Takashi; Harada, Akimitsu; Hayano, Junichiro; Kimura, Genjiro

    2003-07-01

    Wave intensity (WI) is a novel hemodynamic index, which is defined as (d P/d t) x (d U/d t) at any site of the circulation, where d P/d t and d U/d t are the derivatives of blood pressure and velocity with respect to time, respectively. However, the pathophysiological meanings of this index have not been fully elucidated in the clinical setting. Accordingly, we investigated this issue in 64 patients who underwent invasive evaluation of left ventricular (LV) function. WI was obtained at the right carotid artery using a color Doppler system for blood velocity measurement combined with an echo-tracking method for detecting vessel diameter changes. The vessel diameter changes were automatically converted to pressure waveforms by calibrating its peak and minimum values by systolic and diastolic brachial blood pressures. The WI of the patients showed two sharp positive peaks. The first peak was found at the very early phase of LV ejection, while the second peak was observed near end-ejection. The magnitude of the first peak of WI significantly correlated with the maximum rate of LV pressure rise (LV max. d P/d t) (r = 0.74, P WI significantly correlated with the time constant of LV relaxation (r = -0.77, P WI reflects LV contractile performance, and the amplitude of the second peak of WI is determined by LV behavior during the period from late systole to isovolumic relaxation. WI is a noninvasively obtained, clinically useful parameter for the evaluation of LV systolic and early diastolic performance at the same time.

  10. The evaluation of myomectomies performed during cesarean section in our clinic

    Science.gov (United States)

    Celal, Kadı; Hülya, Çıçek

    2011-01-01

    Background: We evaluated the data of patients who had applied myomectomy during cesarean section operation in our clinic between April, 2008 and December, 2010. Objective: I0 n this period, 3689 cesarean sections were done in our clinic, we analyzed their data retrospectively and determined 27 myomectomy cases during cesarean section operation. The age of the patients, the numbers of pregnancy, parities, the rates of abortus, indications of cesarean, pregnancy weeks, residential areas of myoms detected during the cesarean and their size, were recorded. Furthermore, pre-operative and post-operative hemoglobin (Hb) values, differences between hemoglobin values, whether there was bleeding or not, the need of blood transfusion if it occurred, the duration of operation and hospitaization and the pathological diagnoses of myomectomy materials, were examined. Materials and Methods: Retrospective study of myomectomies. Results: The mean age of patients was 29.6±5.9 (19-42) and mean gestational age was 39.2±1.0(37-42) weeks. The mean size of the fibroids was 5.94±6.29 cm3 (0.96-26.50 cm3). Subserous myoms were the most frequently seen ones (24 of 27 patients=89%) with fundal, corporal localizations in most of the instances. T0 he pre-operative and post-operative values of Hb were 11.8±1.52 (8.6-10.5) and 10.3±2.6 (6.9-13.3) g/dl respectively and the difference was statistically significant (P<0.001). Blood transfusion was not necessary in any patient. The mean duration of the operation was found to be 40.7±13.9 (13-60) minutes. Conclusion: Myomectomies can be performed safely during cesarean section by experienced obstetricians and gynecologists, and myomectomy performed for fibroids in appropriate localizations does not increase post-operative bleeding or maternal morbidity or mortality. PMID:22083246

  11. APOE Effects on Default Mode Network in Chinese Cognitive Normal Elderly: Relationship with Clinical Cognitive Performance.

    Directory of Open Access Journals (Sweden)

    Haiqing Song

    Full Text Available Functional connectivity in default mode network (DMN may be changed in Alzheimer's disease (AD patients and related risk populations, such as amnestic mild cognitive impairment (aMCI patients and APOE ε4 carriers. Exploring DMN changes and related behavioral performance of APOE ε4 population might provide valuable evidence for better understanding the development of AD.Subjects were enrolled from a population-based cohort established in a multi-center study in China. Forty-nine cognitive normal individuals were enrolled after standardized cognitive evaluations, MRI examination and APOE genotyping. Regions of interest (ROI-based functional connectivity analyses were performed, and voxel-based analyses were used to validate these findings. The correlation between DMN functional connectivity and behavioral performance was further evaluated between APOE ε4ε3 and ε3ε3 carriers.Comparing to ε3ε3 carriers, functional connectivity between left parahippocampal gyrus and right superior frontal cortex (LPHC-R.Sup.F, left parahippocampal gyrus and medial prefrontal cortex (ventral (LPHC-vMPFC were significantly increased in ε4ε3 carriers, while connectivity between cerebellar tonsils and retrosplenial was decreased. LPHC-R.Sup.F connectivity was positively correlated with the changes of delay recall from baseline to follow-up (r = 0.768, p = 0.009, while LPHC-vMPFC connectivity had a positive correlation with MMSE at baseline (r = 0.356, p = 0.018, and a negative correlation with long-delayed recognition at follow-up (r = -0.677, p = 0.031. Significantly increased functional connectivity in vMPFC was confirmed in voxel-based analyses by taking LPHC as seed region.APOE ε4 carriers present both increased and decreased functional connectivity in DMN, which is correlated with clinical cognitive performances. DMN changes might be an early sign for cognitive decline.

  12. Performing meta-analysis with incomplete statistical information in clinical trials

    Directory of Open Access Journals (Sweden)

    Hunter Anthony

    2008-08-01

    Full Text Available Abstract Background Results from clinical trials are usually summarized in the form of sampling distributions. When full information (mean, SEM about these distributions is given, performing meta-analysis is straightforward. However, when some of the sampling distributions only have mean values, a challenging issue is to decide how to use such distributions in meta-analysis. Currently, the most common approaches are either ignoring such trials or for each trial with a missing SEM, finding a similar trial and taking its SEM value as the missing SEM. Both approaches have drawbacks. As an alternative, this paper develops and tests two new methods, the first being the prognostic method and the second being the interval method, to estimate any missing SEMs from a set of sampling distributions with full information. A merging method is also proposed to handle clinical trials with partial information to simulate meta-analysis. Methods Both of our methods use the assumption that the samples for which the sampling distributions will be merged are randomly selected from the same population. In the prognostic method, we predict the missing SEMs from the given SEMs. In the interval method, we define intervals that we believe will contain the missing SEMs and then we use these intervals in the merging process. Results Two sets of clinical trials are used to verify our methods. One family of trials is on comparing different drugs for reduction of low density lipprotein cholesterol (LDL for Type-2 diabetes, and the other is about the effectiveness of drugs for lowering intraocular pressure (IOP. Both methods are shown to be useful for approximating the conventional meta-analysis including trials with incomplete information. For example, the meta-analysis result of Latanoprost versus Timolol on IOP reduction for six months provided in 1 was 5.05 ± 1.15 (Mean ± SEM with full information. If the last trial in this study is assumed to be with partial information

  13. Comparison of clinical characteristics and survival on patients with idiopathic pulmonary arterial hypertension and familial pulmonary arterial hypertension during conventional therapy era and targeted therapy era

    Institute of Scientific and Technical Information of China (English)

    徐希奇

    2014-01-01

    Objective To compare the clinical characteristics and survival on Chinese patients with idiopathic pulmonary arterial hypertension(IPAH)and familiar pulmonary arterial hypertension(FPAH)during conventional therapy era and targeted therapy era.Methods IPAH and FPAH patients who were referred between Jan 1999and Oct 2004 in Fuwai Hospital were defined as conventional therapy era group(before 2005 no PAH-specific drug was available in China).All patients in this group

  14. Artificial gait in complete spinal cord injured subjects: how to assess clinical performance

    Directory of Open Access Journals (Sweden)

    Karla Rocha Pithon

    2015-02-01

    Full Text Available Objective Adapt the 6 minutes walking test (6MWT to artificial gait in complete spinal cord injured (SCI patients aided by neuromuscular electrical stimulation. Method Nine male individuals with paraplegia (AIS A participated in this study. Lesion levels varied between T4 and T12 and time post injured from 4 to 13 years. Patients performed 6MWT 1 and 6MWT 2. They used neuromuscular electrical stimulation, and were aided by a walker. The differences between two 6MWT were assessed by using a paired t test. Multiple r-squared was also calculated. Results The 6MWT 1 and 6MWT 2 were not statistically different for heart rate, distance, mean speed and blood pressure. Multiple r-squared (r2 = 0.96 explained 96% of the variation in the distance walked. Conclusion The use of 6MWT in artificial gait towards assessing exercise walking capacity is reproducible and easy to apply. It can be used to assess SCI artificial gait clinical performance.

  15. The Effect of Student Self-Video of Performance on Clinical Skill Competency: A Randomised Controlled Trial

    Science.gov (United States)

    Maloney, Stephen; Storr, Michael; Morgan, Prue; Ilic, Dragan

    2013-01-01

    Emerging technologies and student information technology literacy are enabling new methods of teaching and learning for clinical skill performance. Facilitating experiential practice and reflection on performance through student self-video, and exposure to peer benchmarks, may promote greater levels of skill competency. This study examines the…

  16. Investigation of the clinical performance of a novel solid-state diagnostic dosimeter.

    Science.gov (United States)

    Tse, Jason; McLean, Donald

    2015-01-01

    This study investigated the clinical performance of a novel solid-state diagnostic dosimeter, the RaySafe Xi transparent detector, by comparing its performance to a reference-class ionization chamber. Firstly a comparison of dosimeter response "free-in-air" with standard beam qualities was made, followed by an investigation into its relative transparency in an X-ray field and angular sensitivity dependence. The second part of the study looked at the overall performance of the transparent detector under scatter conditions with a number of beam qualities, including standard beam and those hardened by copper (Cu) filtration of thickness up to 0.9 mm, as would be encountered in the equipment testing of fluoroscopy systems. Overall, the transparent detector has demonstrated equivalent measurement properties to the ionization chamber under standard conditions and provided similar X-ray attenuation as reflected by the nearly identical radiographic parameters selected for both dosimeters by the automatic dose rate control (ADRC) system. Yet, it also possessed an asymmetric angular response which respectively under- and overestimated the dose contribution from the rear and lateral directions by the same amount of 50%. The transparent detector provided comparable dose reading of ± 3% to the ionization chamber with standard beam qualities and backscatter radiation present. These results were in good agreement with those of free-in-air measurement, indicating that the angular under- and overresponse might potentially compensate one another for accurate measurement. However, for identical Cu filtered beam qualities and setups, the transparent detector on average overresponded by 5.4% across the useful tube voltage range. In conclusion, the transparent detector, with its novel design, is essentially equivalent, within a 5% tolerance, to an ionization chamber, except in situations where beams hardened with Cu filtration are used with backscatter radiation present requiring

  17. Military target task performance after wavefront-guided (WFG) and wavefront-optimized (WFO) photorefractive keratectomy (PRK)

    Science.gov (United States)

    Maurer, Tana; Deaver, Dawne; Howell, Christopher; Moyer, Steve; Nguyen, Oanh; Mueller, Greg; Ryan, Denise; Sia, Rose K.; Stutzman, Richard; Pasternak, Joseph; Bower, Kraig

    2014-06-01

    Major decisions regarding life and death are routinely made on the modern battlefield, where visual function of the individual soldier can be of critical importance in the decision-making process. Glasses in the combat environment have considerable disadvantages: degradation of short term visual performance can occur as dust and sweat accumulate on lenses during a mission or patrol; long term visual performance can diminish as lenses become increasingly scratched and pitted; during periods of intense physical trauma, glasses can be knocked off the soldier's face and lost or broken. Although refractive surgery offers certain benefits on the battlefield when compared to wearing glasses, it is not without potential disadvantages. As a byproduct of refractive surgery, elevated optical aberrations can be induced, causing decreases in contrast sensitivity and increases in the symptoms of glare, halos, and starbursts. Typically, these symptoms occur under low light level conditions, the same conditions under which most military operations are initiated. With the advent of wavefront aberrometry, we are now seeing correction not only of myopia and astigmatism but of other, smaller optical aberrations that can cause the above symptoms. In collaboration with the Warfighter Refractive Eye Surgery Program and Research Center (WRESP-RC) at Fort Belvoir and Walter Reed National Military Medical Center (WRNMMC), the overall objective of this study is to determine the impact of wavefront guided (WFG) versus wavefront-optimized (WFO) photorefractive keratectomy (PRK) on military task visual performance. Psychophysical perception testing was conducted before and after surgery to measure each participant's performance regarding target detection and identification using thermal imagery. The results are presented here.

  18. Comparison and Consensus Guidelines for Delineation of Clinical Target Volume for CT- and MR-Based Brachytherapy in Locally Advanced Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu [Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Erickson, Beth [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Gaffney, David K. [University of Utah Huntsman Cancer Hospital, Salt Lake City, Utah (United States); Beriwal, Sushil [University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Bhatia, Sudershan K. [University of Iowa, Iowa City, Iowa (United States); Lee Burnett, Omer [University of Alabama, Birmingham, Alabama (United States); D' Souza, David P.; Patil, Nikhilesh [London Health Sciences Centre and Western University, London, Ontario (Canada); Haddock, Michael G. [Mayo Medical Center, Rochester, Minnesota (United States); Jhingran, Anuja [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Jones, Ellen L. [University of North Carolina, Chapel Hill, North Carolina (United States); Kunos, Charles A. [Case Western Reserve University, Cleveland, Ohio (United States); Lee, Larissa J. [Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Lin, Lilie L. [University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mayr, Nina A. [University of Washington, Seattle, Washington (United States); Petersen, Ivy [Mayo Medical Center, Rochester, Minnesota (United States); Petric, Primoz [Division of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana (Slovenia); Department of Radiation Oncology, National Center for Cancer Care and Research, Doha (Qatar); Portelance, Lorraine [University of Miami Miller School of Medicine, Miami, Florida (United States); Small, William [Loyola University Strich School of Medicine, Chicago, Illinois (United States); Strauss, Jonathan B. [The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois (United States); and others

    2014-10-01

    Objective: To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy. Methods and Materials: Twenty-three experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case. Results: For all 3 cases, the mean tumor volume was smaller on MR than on CT (P<.001). The κ and conformity index estimates were slightly higher for CT, indicating a higher level of agreement on CT. The Dice coefficients were 89% for the stage IB2 case with a CR, 74% for the stage IIB case with a PR, and 57% for the stage IIB case with a CR. Conclusion: In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at (http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx)

  19. Comparison and Consensus Guidelines for Delineation of Clinical Target Volume for CT- and MR-Based Brachytherapy in Locally Advanced Cervical Cancer

    International Nuclear Information System (INIS)

    Objective: To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy. Methods and Materials: Twenty-three experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case. Results: For all 3 cases, the mean tumor volume was smaller on MR than on CT (P<.001). The κ and conformity index estimates were slightly higher for CT, indicating a higher level of agreement on CT. The Dice coefficients were 89% for the stage IB2 case with a CR, 74% for the stage IIB case with a PR, and 57% for the stage IIB case with a CR. Conclusion: In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at (http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx)

  20. Building a medical multimedia database system to integrate clinical information: an application of high-performance computing and communications technology.

    Science.gov (United States)

    Lowe, H J; Buchanan, B G; Cooper, G F; Vries, J K

    1995-01-01

    The rapid growth of diagnostic-imaging technologies over the past two decades has dramatically increased the amount of nontextual data generated in clinical medicine. The architecture of traditional, text-oriented, clinical information systems has made the integration of digitized clinical images with the patient record problematic. Systems for the classification, retrieval, and integration of clinical images are in their infancy. Recent advances in high-performance computing, imaging, and networking technology now make it technologically and economically feasible to develop an integrated, multimedia, electronic patient record. As part of The National Library of Medicine's Biomedical Applications of High-Performance Computing and Communications program, we plan to develop Image Engine, a prototype microcomputer-based system for the storage, retrieval, integration, and sharing of a wide range of clinically important digital images. Images stored in the Image Engine database will be indexed and organized using the Unified Medical Language System Metathesaurus and will be dynamically linked to data in a text-based, clinical information system. We will evaluate Image Engine by initially implementing it in three clinical domains (oncology, gastroenterology, and clinical pathology) at the University of Pittsburgh Medical Center.

  1. Building a medical multimedia database system to integrate clinical information: an application of high-performance computing and communications technology.

    Science.gov (United States)

    Lowe, H J; Buchanan, B G; Cooper, G F; Vries, J K

    1995-01-01

    The rapid growth of diagnostic-imaging technologies over the past two decades has dramatically increased the amount of nontextual data generated in clinical medicine. The architecture of traditional, text-oriented, clinical information systems has made the integration of digitized clinical images with the patient record problematic. Systems for the classification, retrieval, and integration of clinical images are in their infancy. Recent advances in high-performance computing, imaging, and networking technology now make it technologically and economically feasible to develop an integrated, multimedia, electronic patient record. As part of The National Library of Medicine's Biomedical Applications of High-Performance Computing and Communications program, we plan to develop Image Engine, a prototype microcomputer-based system for the storage, retrieval, integration, and sharing of a wide range of clinically important digital images. Images stored in the Image Engine database will be indexed and organized using the Unified Medical Language System Metathesaurus and will be dynamically linked to data in a text-based, clinical information system. We will evaluate Image Engine by initially implementing it in three clinical domains (oncology, gastroenterology, and clinical pathology) at the University of Pittsburgh Medical Center. PMID:7703940

  2. Proposing the lymphatic target volume for elective radiation therapy for pancreatic cancer: a pooled analysis of clinical evidence

    International Nuclear Information System (INIS)

    Radiation therapy is an important cancer treatment modality in both adjuvant and definitive setting, however, the use of radiation therapy for elective treatment of regional lymph nodes is controversial for pancreatic cancer. No consensus on proper selection and delineation of subclinical lymph nodal areas in adjuvant or definitive radiation therapy has been suggested either conclusively or proposed for further investigation. This analysis aims to study the pattern of lymph node metastasis through a pooled analysis of published results after radical tumor and lymph nodal resection with histological study in pancreatic cancer. Literature search using electronic databases including MEDLINE, EMBASE, and CANCERLIT from January 1970 to June 2009 was performed, supplemented by review of references. Eighteen original researches and a total of 5954 pancreatic cancer patients underwent radical surgical resection were included in this analysis. The probability of metastasis in regional lymph nodal stations (using Japan Pancreas Society [JPS] Classification) was calculated and analyzed based on the location and other characteristics of the primary disease. Commonly involved nodal regions in patients with pancreatic head tumor include lymph nodes around the common hepatic artery (Group 8, 9.79%), posterior pancreaticoduodenal lymph nodes (Group 13, 32.31%), lymph nodes around the superior mesenteric artery (Group 14, 15.85%), paraaortic lymph nodes (Group 16, 10.92%), and anterior pancreaticoduodenal lymph nodes (Group 17, 19.78%); The probability of metastasis in other lymph nodal regions were <9%. Commonly involved nodal regions in patients with pancreatic body/tail tumor include lymph nodes around the common hepatic artery (Group 8, 15.07%), lymph nodes around the celiac trunk (Group 9, 9.59%), lymph nodes along the splenic artery (Group 11, 35.62%), lymph nodes around the superior mesenteric artery (Group 14, 9.59%), paraaortic lymph nodes (Group 16, 16.44%), and inferior

  3. MIMO声呐目标检测性能分析%Analysis of MIMO sonar target detection performance

    Institute of Scientific and Technical Information of China (English)

    王福钋; 潘悦; 王永刚

    2012-01-01

    重点研究MIMO声呐的目标检测性能,为MIMO声呐布阵方式和工作模式等的选择提供理论依据.通过理论分析给出了MIMO声呐接收机工作特性(ROC)曲线的表达式,分别包括并列式和分布式MIMO声呐,同时给出了相控阵、SIMO和MISO等形式声呐的ROC表达式.通过示例比较了相同情况下并列式MIMO声呐、分布式MIMO声呐、相控阵声呐和常规多基地声呐的ROC曲线.结果表明,相同条件下相控阵声呐波束指向方向上的目标检测概率高于并列式MIMO声呐,做脉冲积累的并列式MIMO声呐可以得到与相控阵声呐相同的检测性能,低信噪比时并列式MIMO声呐和相控阵声呐的目标检测概率高于分布式MIMO声呐,高信噪比时分布式MIMO声呐可以得到较高的检测概率,采用多个发射阵元的分布式MIMO声呐性能优于使用一个发射阵元的常规多基地声呐.%Target detection performances of MIMO sonar are studied in this paper. They are one of the theoretic foundations of elements placement and work pattern. Receiver Expressions of Receiver Operating Characteristics ( ROC ) curves are given through theoretical analysis. Including collocated MIMO sonar and distributed MIMO sonar. Expressions of ROC curves such as phase array sonar, SIMO sonar and MISO sonar are also given. ROC curve comparisons of collocated MIMO sonar, distributed MIMO sonar, phase array sonar and multi-base sonar are given in the same condition. Results indicate that target detection performance of phase array sonar in the beam direction is better than collocated MIMO sonar. Collocated MIMO sonar with pulse accumulation can get the same performance as the phase array sonar. Performances of collocated MIMO sonar and phase array sonar are better than distributed MIMO sonar in low SNR condition. In high SNR condition, distributed MIMO sonar can get a better performance. Performance of distributed MIMO sonar with multiple transmitting notes is better than

  4. Clinical Neuropathology practice news 1-2014: Pyrosequencing meets clinical and analytical performance criteria for routine testing of MGMT promoter methylation status in glioblastoma

    Science.gov (United States)

    Preusser, Matthias; Berghoff, Anna S.; Manzl, Claudia; Filipits, Martin; Weinhäusel, Andreas; Pulverer, Walter; Dieckmann, Karin; Widhalm, Georg; Wöhrer, Adelheid; Knosp, Engelbert; Marosi, Christine; Hainfellner, Johannes A.

    2014-01-01

    Testing of the MGMT promoter methylation status in glioblastoma is relevant for clinical decision making and research applications. Two recent and independent phase III therapy trials confirmed a prognostic and predictive value of the MGMT promoter methylation status in elderly glioblastoma patients. Several methods for MGMT promoter methylation testing have been proposed, but seem to be of limited test reliability. Therefore, and also due to feasibility reasons, translation of MGMT methylation testing into routine use has been protracted so far. Pyrosequencing after prior DNA bisulfite modification has emerged as a reliable, accurate, fast and easy-to-use method for MGMT promoter methylation testing in tumor tissues (including formalin-fixed and paraffin-embedded samples). We performed an intra- and inter-laboratory ring trial which demonstrates a high analytical performance of this technique. Thus, pyrosequencing-based assessment of MGMT promoter methylation status in glioblastoma meets the criteria of high analytical test performance and can be recommended for clinical application, provided that strict quality control is performed. Our article summarizes clinical indications, practical instructions and open issues for MGMT promoter methylation testing in glioblastoma using pyrosequencing. PMID:24359605

  5. Stereotactic body radiation therapy for abdominal targets using volumetric intensity modulated arc therapy with RapidArc: Feasibility and clinical preliminary results

    International Nuclear Information System (INIS)

    Purpose. To report early clinical experience in stereotactic body radiation therapy (SBRT) delivered using volumetric intensity modulated arc therapy with RapidArc (RA) in patients with primary or metastatic tumours at abdominal sites. Material and methods. Thirty-seven consecutive patients were treated using RA. Of these, 16 had primary or metastatic liver tumours, nine had pancreatic cancer and 12 a nodal metastasis in the retro-peritoneum. Dose prescription varied from 45 to 75 Gy to the Clinical Target Volume in 3 to 6 fractions. The median follow-up was 12 months (6-22). Early local control and toxicity were investigated and reported. Results. Planning objectives on target volumes and organs at risk were met in most cases. Delivery time ranged from 2.8 ± 0.3 to 9.2 ± 2.4 minutes and pre-treatment plan verification resulted in a Gamma Agreement Index from 95.3 ± 3.8 to 98.3 ± 1.7%. At the time of analysis, local control (freedom from progression) at six months, was assessable in 24 of 37 patients and was achieved in 19 patients with a crude rate of 79.2%. Seven patients experienced treatment-related toxicity. Three patients experienced a mild and transient G1 enteritis and two showed a transient G1 liver damage. Two had late toxicity: one developed chronic enteritis causing G1 diarrhoea and G1 abdominal pain and one suffered at three months a G3 gastric bleeding. No patients experienced G4 acute toxicity. Conclusions. SBRT for abdominal targets delivered by means of RA resulted to be feasible with good early clinical results in terms of local control rate and acute toxicity profile. RA allowed to achieve required target coverage as well as to keep within normal tissue dose/volume constraints

  6. Stereotactic body radiation therapy for abdominal targets using volumetric intensity modulated arc therapy with RapidArc: Feasibility and clinical preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Scorsetti, Marta; Bignardi, Mario; Alongi, Filippo; Mancosu, Pietro; Navarria, Piera; Castiglioni, Simona; Pentimalli, Sara; Tozzi, Angelo (IRCCS Istituto Clinico Humanitas, Rozzano (Italy)), e-mail: pietro.mancosu@humanitas.it; Fogliata, Antonella; Cozzi, Luca (Oncology Inst. of Southern Switzerland, Bellinzona (Switzerland))

    2011-05-15

    Purpose. To report early clinical experience in stereotactic body radiation therapy (SBRT) delivered using volumetric intensity modulated arc therapy with RapidArc (RA) in patients with primary or metastatic tumours at abdominal sites. Material and methods. Thirty-seven consecutive patients were treated using RA. Of these, 16 had primary or metastatic liver tumours, nine had pancreatic cancer and 12 a nodal metastasis in the retro-peritoneum. Dose prescription varied from 45 to 75 Gy to the Clinical Target Volume in 3 to 6 fractions. The median follow-up was 12 months (6-22). Early local control and toxicity were investigated and reported. Results. Planning objectives on target volumes and organs at risk were met in most cases. Delivery time ranged from 2.8 +- 0.3 to 9.2 +- 2.4 minutes and pre-treatment plan verification resulted in a Gamma Agreement Index from 95.3 +- 3.8 to 98.3 +- 1.7%. At the time of analysis, local control (freedom from progression) at six months, was assessable in 24 of 37 patients and was achieved in 19 patients with a crude rate of 79.2%. Seven patients experienced treatment-related toxicity. Three patients experienced a mild and transient G1 enteritis and two showed a transient G1 liver damage. Two had late toxicity: one developed chronic enteritis causing G1 diarrhoea and G1 abdominal pain and one suffered at three months a G3 gastric bleeding. No patients experienced G4 acute toxicity. Conclusions. SBRT for abdominal targets delivered by means of RA resulted to be feasible with good early clinical results in terms of local control rate and acute toxicity profile. RA allowed to achieve required target coverage as well as to keep within normal tissue dose/volume constraints

  7. Initial Clinical Experience Performing Patient Treatment Verification With an Electronic Portal Imaging Device Transit Dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Berry, Sean L., E-mail: BerryS@MSKCC.org [Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York (United States); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Polvorosa, Cynthia; Cheng, Simon; Deutsch, Israel; Chao, K. S. Clifford; Wuu, Cheng-Shie [Department of Radiation Oncology, Columbia University, New York, New York (United States)

    2014-01-01

    Purpose: To prospectively evaluate a 2-dimensional transit dosimetry algorithm's performance on a patient population and to analyze the issues that would arise in a widespread clinical adoption of transit electronic portal imaging device (EPID) dosimetry. Methods and Materials: Eleven patients were enrolled on the protocol; 9 completed and were analyzed. Pretreatment intensity modulated radiation therapy (IMRT) patient-specific quality assurance was performed using a stringent local 3%, 3-mm γ criterion to verify that the planned fluence had been appropriately transferred to and delivered by the linear accelerator. Transit dosimetric EPID images were then acquired during treatment and compared offline with predicted transit images using a global 5%, 3-mm γ criterion. Results: There were 288 transit images analyzed. The overall γ pass rate was 89.1% ± 9.8% (average ± 1 SD). For the subset of images for which the linear accelerator couch did not interfere with the measurement, the γ pass rate was 95.7% ± 2.4%. A case study is presented in which the transit dosimetry algorithm was able to identify that a lung patient's bilateral pleural effusion had resolved in the time between the planning CT scan and the treatment. Conclusions: The EPID transit dosimetry algorithm under consideration, previously described and verified in a phantom study, is feasible for use in treatment delivery verification for real patients. Two-dimensional EPID transit dosimetry can play an important role in indicating when a treatment delivery is inconsistent with the original plan.

  8. Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data

    Science.gov (United States)

    Joo, Seongjung; Kawabata, Hugh; Al, Maiwenn J.; Allison, Paul D.; Rutten‐van Mölken, Maureen P. M. H.; Frits, Michelle L.; Iannaccone, Christine K.; Shadick, Nancy A.; Weinblatt, Michael E.

    2016-01-01

    Objective To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M‐HAQ), the EuroQol 5‐domain (EQ‐5D; a quality‐of‐life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Results Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM‐HAQ −0.047; P = 0.0100) and CDAI ≤2.8 (−0.073; P = 0.0003) but not DAS28‐CRP <2.6 (−0.022; P = 0.1735). Target attainment was associated with significantly improved EQ‐5D (0.022–0.096; P < 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline‐recommended disease targets were 36–45% less likely to be hospitalized (P < 0.0500) and 23–45% less likely to utilize DME (P < 0.0100). Conclusion Attaining recommended target disease‐activity measures was associated with enhanced physical functioning and health‐related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients. PMID:26238974

  9. Aging Q3: an initiative to improve internal medicine residents' geriatrics knowledge, skills, and clinical performance.

    Science.gov (United States)

    Moran, William P; Zapka, Jane; Iverson, Patty J; Zhao, Yumin; Wiley, M Kathleen; Pride, Pamela; Davis, Kimberly S

    2012-05-01

    A growing number of older adults coupled with a limited number of physicians trained in geriatrics presents a major challenge to ensuring quality medical care for this population. Innovations to incorporate geriatrics education into internal medicine residency programs are needed. To meet this need, in 2009, faculty at the Medical University of South Carolina developed Aging Q(3)-Quality Education, Quality Care, and Quality of Life. This multicomponent initiative recognizes the need for improved geriatrics educational tools and faculty development as well as systems changes to improve the knowledge and clinical performance of residents. To achieve these goals, faculty employ multiple intervention strategies, including lectures, rounds, academic detailing, visual cues, and electronic medical record prompts and decision support. The authors present examples from specific projects, based on care areas including vision screening, fall prevention, and caring for patients with dementia, all of which are based on the Assessing Care of Vulnerable Elders quality indicators. The authors describe the principles driving the design, implementation, and evaluation of the Aging Q(3) program. They present data from multiple sources that illustrate the effectiveness of the interventions to meet the knowledge, skill level, and behavior goals. The authors also address major challenges, including the maintenance of the teaching and modeling interventions over time within the context of demanding primary care and inpatient settings. This organized, evidence-based approach to quality improvement in resident education, as well as faculty leadership development, holds promise for successfully incorporating geriatrics education into internal medicine residencies. PMID:22450181

  10. Clinical performance and survival of space maintainers: evaluation over a period of 5 years.

    Science.gov (United States)

    Rajab, Lamis D

    2002-01-01

    The study investigated the clinical performance of 387 space maintainers fitted in 358 patients aged from 3 to 9 years in the Department of Pediatric Dentistry at the Faculty of Dentistry-University of Jordan from 1996 to 2000. Failure occurred in 119 appliances (30.7%), of which 49.6% were due to solder breakage, 32.8% from cement loss, 11% from soft tissue lesions, 4.2% from eruption interference, and 2.5% were completely lost. By using the Kaplan-Meier method, the estimated median survival time for space maintainers was 18 months. Lingual arches had the lowest median survival time of 14 months. Bands and loops, Nance appliances, and removable partial dentures had similar probability of survival. Fixed bilateral mandibular appliances recorded lower survival time than fixed bilateral maxillary appliances. Gender, age, type of dentition, fixed vs. removable, year of placement of the appliance and number of space maintainers fitted simultaneously in the same patient had no significant effect on survival of the appliances.

  11. Predictive performance of the Domino, Hijazi, and Clements models during low-dose target-controlled ketamine infusions in healthy volunteers

    NARCIS (Netherlands)

    Absalom, A. R.; Lee, M.; Menon, D. K.; Sharar, S. R.; De Smet, T.; Halliday, J.; Ogden, M.; Corlett, P.; Honey, G. D.; Fletcher, P. C.

    2007-01-01

    Background. Healthy volunteers received low-dose target-controlled infusions (TCI) of ketamine controlled by the Domino model while cognitive function tests and functional neuroimaging were performed. The aim of the current study was to assess the predictive performance of the Domino model during th

  12. Clinical performance of KeraSoft® IC in irregular corneas

    Directory of Open Access Journals (Sweden)

    Su S

    2015-10-01

    Full Text Available Stephanie Su,1 Lynette Johns,2 Marjorie J Rah,3 Robert Ryan,1 Joseph Barr3 1Visionary Eye Associates of Rochester, Rochester, NY, USA; 2Custom Lab Channel Business, Bausch & Lomb Incorporated, Wilmington, MA, USA; 3Medical Affairs – Vision Care, Bausch & Lomb Incorporated, Rochester, NY, USA Purpose: This study evaluated the clinical performance of KeraSoft® IC (KIC soft contact lenses in subjects with irregular corneas.Patients and methods: This was a 12-month, prospective, open-label, observational study, which enrolled 43 subjects who were 18 years of age or older with irregular corneas. Subjects were fit according to the KIC Fitting Manual (kerasoftic.com. After achieving best fit according to the fitting manual, lenses were assessed for comfort, vision, centration, rotation, and movement. Subjects were instructed to wear their lenses between 8 and 16 hours each day. Assessments at the exit visit included logMAR visual acuity with high and low contrast, spherocylindrical overrefraction, slit-lamp findings, adverse events, and subjective outcomes.Results: The average base curve was 8.17±0.32 mm (n=70 eyes, and the average diameter dispensed was 14.53±0.12 mm (n=70 eyes. From the baseline to 12 months, there was statistically significant improvement in logMAR visual acuity with high contrast (P=0.038, but no significant difference in low-contrast visual acuity was observed (P>0.05. Slit-lamp findings were ≤ grade 1 for the majority of subjects (89%. Two nonserious adverse events were reported for two of the 84 enrolled eyes (two subjects. At 12 months, subjects reported improvements from habitual baseline for comfort and vision, both upon insertion and just before removal of lenses.Conclusion: Clinical outcomes at 12 months showed good visual, safety, and subjective outcomes for subjects with corneal irregularities who wore KeraSoft® IC soft contact lenses. Keywords: irregular corneas, keratoconus, soft contact lenses, KeraSoft® IC

  13. Clinical relevance of optimizing vitamin D status in soldiers to enhance physical and cognitive performance.

    Science.gov (United States)

    Wentz, Laurel M; Eldred, Jerad D; Henry, Michael D; Berry-Cabán, Cristóbal S

    2014-01-01

    Vitamin D deficiency initiates a loss of combat effectiveness by impairing physical and cognitive functioning of combat Operators. Synthesized in response to sunlight and consumed in the diet, vitamin D functions as a hormone and regulates gene expression for nearly 300 genes throughout the human body. These target genes are involved processes essential to combat operations, such as immune function, response to stress, inflammation, and regulation of calcium movement. Since widespread vitamin D deficiency is observed across the U.S. population, poor vitamin D status is expected in Servicemembers. Physical conditions linked to vitamin D deficiency include increased risk for muscle or bone injury, muscle weakness, and reduced neuromuscular function. Hormonally, vitamin D levels have been positively correlated with testosterone levels. Vitamin D deficiency is also associated with cognitive decline, depression, and may prolong recovery following mild traumatic brain injury (mTBI). Since vitamin D deficiency elevates systemic inflammation, poor vitamin D status at the time of brain injury may prolong the inflammatory response and exacerbate postconcussive symptoms. Furthermore, veterans with mTBI experience chronic endocrine dysfunction. While vitamin D status has not been assessed post-mTBI, it is plausible that vitamin D levels are altered along with testosterone and growth hormone, raising the question of whether vitamin D deficiency results from trauma-related hormonal abnormalities or whether vitamin D deficiency increases the risk for endocrine dysfunction. Through its association with testosterone production, vitamin D deficiency may increase the risk for posttraumatic stress disorder (PTSD) since testosterone levels are altered in veterans with PTSD. Therefore, vitamin D status has a significant impact on Operator health and performance. Supplementing vita-min D to deficient Operators provides a noninvasive and low-cost intervention to maintain combat force

  14. Determining performance characteristics of an NGS-based HLA typing method for clinical applications.

    Science.gov (United States)

    Duke, J L; Lind, C; Mackiewicz, K; Ferriola, D; Papazoglou, A; Gasiewski, A; Heron, S; Huynh, A; McLaughlin, L; Rogers, M; Slavich, L; Walker, R; Monos, D S

    2016-03-01

    This study presents performance specifications of an in-house developed human leukocyte antigen (HLA) typing assay using next-generation sequencing (NGS) on the Illumina MiSeq platform. A total of 253 samples, previously characterized for HLA-A, -B, -C, -DRB1 and -DQB1 were included in this study, which were typed at high-resolution using a combination of Sanger sequencing, sequence-specific primer (SSP) and sequence-specific oligonucleotide probe (SSOP) technologies and recorded at the two-field level. Samples were selected with alleles that cover a high percentage of HLA specificities in each of five different race/ethnic groups: European, African-American, Asian Pacific Islander, Hispanic and Native American. Sequencing data were analyzed by two software programs, Omixon's target and GenDx's NGSengine. A number of metrics including allele balance, sensitivity, specificity, precision, accuracy and remaining ambiguity were assessed. Data analyzed by the two software systems are shown independently. The majority of alleles were identical in the exonic sequences (third field) with both programs for HLA-A, -B, -C and -DQB1 in 97.7% of allele determinations. Among the remaining discrepant genotype calls at least one of the analysis programs agreed with the reference typing. Upon additional manual analysis 100% of the 2530 alleles were concordant with the reference HLA genotypes; the remaining ambiguities did not exceed 0.8%. The results demonstrate the feasibility and significant benefit of HLA typing by NGS as this technology is highly accurate, eliminates virtually all ambiguities, provides complete sequencing information for the length of the HLA gene and forms the basis for utilizing a single methodology for HLA typing in the immunogenetics labs.

  15. The value of the UK Clinical Aptitude Test in predicting pre-clinical performance: a prospective cohort study at Nottingham Medical School

    OpenAIRE

    James David; Yates Janet

    2010-01-01

    Abstract Background The UK Clinical Aptitude Test (UKCAT) was introduced in 2006 as an additional tool for the selection of medical students. It tests mental ability in four distinct domains (Quantitative Reasoning, Verbal Reasoning, Abstract Reasoning, and Decision Analysis), and the results are available to students and admissions panels in advance of the selection process. As yet the predictive validity of the test against course performance is largely unknown. The study objective was to d...

  16. 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;

    2016-01-01

    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......-modifying antirheumatic drug (DMARD)-naive patients with eRA started methotrexate (20 mg/week) and intra-articular triamcinolone (20 mg/ml) for 2 years. In addition, they were randomised to receive placebo adalimumab (DMARD group, n=91) or adalimumab (40 mg/every other week) (DMARD+adalimumab group, n=89) during....... RESULTS: One year after adalimumab withdrawal, treatment profiles and clinical responses did not differ between groups. In the DMARD/DMARD+adalimumab groups, the median 2-year methotrexate dose was 20/20 mg/week (p=0.45), triple DMARD therapy had been initiated in 33/27 patients (p=0.49), adalimumab...

  17. The impact of clinical and demographic variables on cognitive performance in methamphetamine-dependent individuals in rural South Carolina.

    Science.gov (United States)

    Price, Kimber L; DeSantis, Stacia M; Simpson, Annie N; Tolliver, Bryan K; McRae-Clark, Aimee L; Saladin, Michael E; Baker, Nathaniel L; Wagner, Mark T; Brady, Kathleen T

    2011-01-01

    Inconsistencies in reports on methamphetamine (METH) associated cognitive dysfunction may be attributed, at least in part, to the diversity of study sample features (eg, clinical and demographic characteristics). The current study assessed cognitive function in a METH-dependent population from rural South Carolina, and the impact of demographic and clinical characteristics on performance. Seventy-one male (28.2%) and female (71.8%) METH-dependent subjects were administered a battery of neurocognitive tests including the Test of Memory Malingering (TOMM), Shipley Institute of Living Scale, Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Grooved Pegboard Test, California Verbal Learning Test (CVLT), and Wisconsin Card Sorting Test (WCST). Demographic and clinical characteristics (eg, gender, frequency of METH use) were examined as predictors of performance. Subjects scored significantly lower than expected on one test of attention and one of fine motor function, but performed adequately on all other tests. There were no predictors of performance on attention; however, more frequent METH use was associated with better performance for males and worse for females on fine motor skills. The METH-dependent individuals in this population exhibit very limited cognitive impairment. The marked differences in education, Intellectual Quotient (IQ), and gender in our sample when compared to the published literature may contribute to these findings. Characterization of the impact of clinical and/or demographic features on cognitive deficits could be important in guiding the development of treatment interventions.

  18. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics.

    Directory of Open Access Journals (Sweden)

    Dennie T Frederick

    Full Text Available While response rates to BRAF inhibitiors (BRAFi are high, disease progression emerges quickly. One strategy to delay the onset of resistance is to target anti-apoptotic proteins such as BCL-2, known to be associated with a poor prognosis. We analyzed BCL-2 family member expression levels of 34 samples from 17 patients collected before and 10 to 14 days after treatment initiation with either vemurafenib or dabrafenib/trametinib combination. The observed changes in mRNA and protein levels with BRAFi treatment led us to hypothesize that combining BRAFi with a BCL-2 inhibitor (the BH3-mimetic navitoclax would improve outcome. We tested this hypothesis in cell lines and in mice. Pretreatment mRNA levels of BCL-2 negatively correlated with maximal tumor regression. Early increases in mRNA levels were seen in BIM, BCL-XL, BID and BCL2-W, as were decreases in MCL-1 and BCL2A. No significant changes were observed with BCL-2. Using reverse phase protein array (RPPA, significant increases in protein levels were found in BIM and BID. No changes in mRNA or protein correlated with response. Concurrent BRAF (PLX4720 and BCL2 (navitoclax inhibition synergistically reduced viability in BRAF mutant cell lines and correlated with down-modulation of MCL-1 and BIM induction after PLX4720 treatment. In xenograft models, navitoclax enhanced the efficacy of PLX4720. The combination of a selective BRAF inhibitor with a BH3-mimetic promises to be an important therapeutic strategy capable of enhancing the clinical efficacy of BRAF inhibition in many patients that might otherwise succumb quickly to de novo resistance. Trial registrations: ClinicalTrials.gov NCT01006980; ClinicalTrials.gov NCT01107418; ClinicalTrials.gov NCT01264380; ClinicalTrials.gov NCT01248936; ClinicalTrials.gov NCT00949702; ClinicalTrials.gov NCT01072175.

  19. Targeted Mutagenesis of the Hypophysiotropic Gnrh3 in Zebrafish (Danio rerio Reveals No Effects on Reproductive Performance.

    Directory of Open Access Journals (Sweden)

    Olivia Smith Spicer

    Full Text Available Gnrh is the major neuropeptide regulator of vertebrate reproduction, triggering a cascade of events in the pituitary-gonadal axis that result in reproductive competence. Previous research in mice and humans has demonstrated that Gnrh/GNRH null mutations result in hypogonadotropic hypogonadism and infertility. The goal of this study was to eliminate gnrh3 (the hypophysiotropic Gnrh form function in zebrafish (Danio rerio to determine how ontogeny and reproductive performance are affected, as well as factors downstream of Gnrh3 along the reproductive axis. Using the TALEN technology, we developed a gnrh3-/- zebrafish line that harbors a 62 bp deletion in the gnrh3 gene. Our gnrh3-/- zebrafish line represents the first targeted and heritable mutation of a Gnrh isoform in any organism. Using immunohistochemistry, we verified that gnrh3-/- fish do not possess Gnrh3 peptide in any regions of the brain. However, other than changes in mRNA levels of pituitary gonadotropin genes (fshb, lhb, and cga during early development, which are corrected by adulthood, there were no changes in ontogeny and reproduction in gnrh3-/- fish. The gnrh3-/- zebrafish are fertile, displaying normal gametogenesis and reproductive performance in males and females. Together with our previous results that Gnrh3 cell ablation causes infertility, these results indicate that a compensatory mechanism is being activated, which is probably primed early on upon Gnrh3 neuron differentiation and possibly confined to Gnrh3 neurons. Potential compensation factors and sensitive windows of time for compensation during development and puberty should be explored.

  20. Targeted Mutagenesis of the Hypophysiotropic Gnrh3 in Zebrafish (Danio rerio) Reveals No Effects on Reproductive Performance

    Science.gov (United States)

    Spicer, Olivia Smith; Wong, Ten-Tsao; Zmora, Nilli; Zohar, Yonathan

    2016-01-01

    Gnrh is the major neuropeptide regulator of vertebrate reproduction, triggering a cascade of events in the pituitary-gonadal axis that result in reproductive competence. Previous research in mice and humans has demonstrated that Gnrh/GNRH null mutations result in hypogonadotropic hypogonadism and infertility. The goal of this study was to eliminate gnrh3 (the hypophysiotropic Gnrh form) function in zebrafish (Danio rerio) to determine how ontogeny and reproductive performance are affected, as well as factors downstream of Gnrh3 along the reproductive axis. Using the TALEN technology, we developed a gnrh3-/- zebrafish line that harbors a 62 bp deletion in the gnrh3 gene. Our gnrh3-/- zebrafish line represents the first targeted and heritable mutation of a Gnrh isoform in any organism. Using immunohistochemistry, we verified that gnrh3-/- fish do not possess Gnrh3 peptide in any regions of the brain. However, other than changes in mRNA levels of pituitary gonadotropin genes (fshb, lhb, and cga) during early development, which are corrected by adulthood, there were no changes in ontogeny and reproduction in gnrh3-/- fish. The gnrh3-/- zebrafish are fertile, displaying normal gametogenesis and reproductive performance in males and females. Together with our previous results that Gnrh3 cell ablation causes infertility, these results indicate that a compensatory mechanism is being activated, which is probably primed early on upon Gnrh3 neuron differentiation and possibly confined to Gnrh3 neurons. Potential compensation factors and sensitive windows of time for compensation during development and puberty should be explored. PMID:27355207

  1. Evaluation of the team performance observation tool with targeted behavioral markers in simulation-based interprofessional education.

    Science.gov (United States)

    Zhang, Chao; Miller, Connie; Volkman, Kathleen; Meza, Jane; Jones, Katherine

    2015-05-01

    The primary aim of this study was to decrease the subjectivity of the Team Performance Observation Tool (TPOT) and determine the psychometric properties of this tool when using scenario-specific targeted behavioral markers (TBMs). We used a convenience sample of 47 physical therapy and 25 nursing students at an academic medical center who were organized in interprofessional teams of three to care for a simulated patient. The TPOT demonstrated satisfactory validity and reliability with the use of TBMs. We demonstrated significant correlations between the TPOT overall rating and two scenario-specific outcomes: (1) a negative correlation between the TPOT overall rating and the number of medical errors committed by the 24 teams (r = -0.531, p = 0.008) and (2) a positive correlation between the TPOT overall rating and a time-based functional outcome (r = 0.803, p < 0.001). We demonstrated substantial test-retest reliability (kappa = 0.707, p < 0.001), inter-rater reliability (kappa = 0.730), and good internal consistency reliability (Cronbach's α = 0.921). The results of our study support the use of scenario-specific TBMs to enhance the reliability and validity of the TPOT for use in the evaluation of team-based simulation scenarios. Further evaluation of the TPOT with TBMs from other simulation and training contexts is warranted. PMID:25421454

  2. EDF - 2015 full-year results: all targets reached, Strong operating performance in adverse market conditions, 2018 ambition reiterated

    International Nuclear Information System (INIS)

    A key player in energy transition, the EDF Group is an integrated electricity company, active in all areas of the business: generation, transmission, distribution, energy supply and trading, energy services. A global leader in low-carbon energies, the Group has developed a diversified generation mix based on nuclear power, hydropower, new renewable energies and thermal energy. The Group is involved in supplying energy and services to approximately 37.6 million customers, of which 27.8 million in France. The Group generated consolidated sales of Euro 75 billion in 2015, of which 47.2% outside of France. EDF is listed on the Paris Stock exchange. EDF achieved all its targets in 2015. The year was marked by strong operational performance, reflecting the significant efforts the teams made. With the end of the regulated Yellow and Green Tariffs, most clients turned to EDF. Nuclear output reached its highest level, since 2011 in France, and since 2005 in the United Kingdom. EDF is also continuing its significant development in renewable energy, with an additional 1 GW of net installed capacity. The transformation of EDF Group is essential in the unfavourable market conditions. EDF has embarked on this transformation, and is accelerating innovation to serve the energy transition

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  4. Survey and rapid detection of Klebsiella pneumoniae in clinical samples targeting the rcsA gene in Beijing, China

    Directory of Open Access Journals (Sweden)

    Derong eDong

    2015-05-01

    Full Text Available Klebsiella pneumoniae is a wide-spread nosocomial pathogen. A rapid and sensitive molecular method for the detection of K. pneumoniae in clinical samples is needed to guide therapeutic treatment. In this study, we first described a loop-mediated isothermal amplification (LAMP method for the rapid detection of capsular polysaccharide synthesis regulating gene rcsA from K. pneumoniae in clinical samples by using two methods including real-time turbidity monitoring and fluorescence detection to assess the reaction. Then dissemination of K. pneumoniae strains was investigated from ICU patients in three top hospitals in Beijing, China. The results showed that the detection limit of the LAMP method was 0.115 pg/µl DNA within 60 min under isothermal conditions (61°C, a 100-fold increase in sensitivity compared with conventional PCR. All 30 non- K. pneumoniae strains tested were negative for LAMP detection, indicating the high specificity of the LAMP reaction. To evaluate the application of the LAMP assay to clinical diagnosis, of 110 clinical sputum samples collected from ICU patients with clinically suspected multi-resistant infections in China, a total of 32 K. pneumoniae isolates were identified for LAMP-based surveillance of rcsA. All isolates belonged to nine different K. pneumoniae multilocus sequence typing (MLST groups. Strikingly, of the 32 K. pneumoniae strains, 18 contained the Klebsiella pneumoniae Carbapenemase (KPC-encoding gene blaKPC-2 and had high resistance to β-lactam antibiotics. Moreover, K. pneumoniae WJ-64 was discovered to contain blaKPC-2 and blaNDM-1 genes simultaneously in the isolate. Our data showed the high prevalence of blaKPC-2 among K. pneumoniae and co-occurrence of many resistant genes in the clinical strains signal a rapid and continuing evolution of K. pneumoniae. In conclusion, we have developed a rapid and sensitive visual K. pneumoniae detection LAMP assay, which could be a useful tool for clinical screening

  5. Survey and rapid detection of Klebsiella pneumoniae in clinical samples targeting the rcsA gene in Beijing, China.

    Science.gov (United States)

    Dong, Derong; Liu, Wei; Li, Huan; Wang, Yufei; Li, Xinran; Zou, Dayang; Yang, Zhan; Huang, Simo; Zhou, Dongsheng; Huang, Liuyu; Yuan, Jing

    2015-01-01

    Klebsiella pneumoniae is a wide-spread nosocomial pathogen. A rapid and sensitive molecular method for the detection of K. pneumoniae in clinical samples is needed to guide therapeutic treatment. In this study, we first described a loop-mediated isothermal amplification (LAMP) method for the rapid detection of capsular polysaccharide synthesis regulating gene rcsA from K. pneumoniaein clinical samples by using two methods including real-time turbidity monitoring and fluorescence detection to assess the reaction. Then dissemination of K. pneumoniae strains was investigated from ICU patients in three top hospitals in Beijing, China. The results showed that the detection limit of the LAMP method was 0.115 pg/μl DNA within 60 min under isothermal conditions (61°C), a 100-fold increase in sensitivity compared with conventional PCR. All 30 non- K. pneumoniae strains tested were negative for LAMP detection, indicating the high specificity of the LAMP reaction. To evaluate the application of the LAMP assay to clinical diagnosis, of 110 clinical sputum samples collected from ICU patients with clinically suspected multi-resistant infections in China, a total of 32 K. pneumoniae isolates were identified for LAMP-based surveillance of rcsA. All isolates belonged to nine different K. pneumoniae multilocus sequence typing (MLST) groups. Strikingly, of the 32 K. pneumoniae strains, 18 contained the Klebsiella pneumoniae Carbapenemase (KPC)-encoding gene bla KPC-2 and had high resistance to β-lactam antibiotics. Moreover, K. pneumoniae WJ-64 was discovered to contain bla KPC-2 and bla NDM-1genes simultaneously in the isolate. Our data showed the high prevalence of bla KPC-2 among K. pneumoniae and co-occurrence of many resistant genes in the clinical strains signal a rapid and continuing evolution of K. pneumoniae. In conclusion, we have developed a rapid and sensitive visual K. pneumoniae detection LAMP assay, which could be a useful tool for clinical screening, on

  6. ITC SOLUTIONS TO ACHIEVE PERFORMANCE AND EFFICIENCY OF HEALTH SERVICES: ONLINE VIRTUAL CLINIC

    Directory of Open Access Journals (Sweden)

    Adina BĂLAN

    2010-01-01

    Full Text Available The digital era modified the way people work, how the information and the informational resources are defined and organized. The organization which holds, uses and correctly reproduces the piece of information, the knowledge, the intellectual capital, becomes a leader in the proper field of activity. Following the actual tendencies in the digital era connected to the exchange of professional information, I can say that the exchange and sharing of digital information in a global multitude of interconnected computers are essential instruments that can contribute to the development and consolidation of the intellectual potential of the organization. This is why, the access of the individuals to information is an actual requirement of the development of the Romanian society in the context of globalization and world implication o contemporary processes and phenomena. The Digital integration eliminates the barriers that traditionally suppress the circuit of the medical information, lets the goods and services circulate to and from Romania by promoting efficiency as final purpose. Performance is needed in the health system, the transformation of the system of medical services by bringing the benefits of the medical science and technology to all individuals from every community. In order to accomplish these expectations it is needed that all the components that form the health system look at it as a whole and subscribe to modern solutions for improvement so that the quality of health should raise to an unprecedented level. Even if health systems differ from country to country from the organizational and financial point of view, they face the same challenges and problems, respectively the supply of medical care of better quality and keeping under control the health expenses. The use of information and communication technology in the field of medical assistance in order to stock, share, transmit and analyze clinical data and knowledge is more necessary

  7. A COMPARISON OF CLINICAL PERFORMANCE OF I-GEL WITH PROSEAL LMA IN PATIENTS UNDERGOING MASTECTOMY

    Directory of Open Access Journals (Sweden)

    Basheer Padinhare Madathil

    2016-04-01

    Full Text Available AIM To assess the ease of insertion of I-gel and ProSeal LMA and incidence of post op complications. Study design-A prospective randomised controlled trial comparing the clinical performance of I-gel and ProSeal LMA. METHODS After induction and good muscle relaxation LMA/I-gel was introduced as per randomised computer allocation. After insertion, nasogastric tube was inserted through the gastric channel. Parameters monitored were heart rate, nubp, SpO2, ETCO2 at 1, 5 minutes after insertion of the device and thereafter every 5 minutes till the end of surgery. In case of failure, airway was secured with an endotracheal tube. Ease of gastric tube insertion was noted at the end of surgery; postop complications were noted. Blood staining of the device, injury to the lips, teeth, and tongue were noted. Incidence of sore throat 24 hrs. after surgery was also noted. Statistical analysis was done with SPSS software. RESULTS Age, height, weight and BMI were comparable in both groups. The airway characteristics was also comparable in both the groups. Ease of introduction was also the same for both the groups, but the time taken was much lesser for I-gel group. The ease of insertion of gastric tube was much easier for the I-gel group. Blood staining of the device was more with the ProSeal LMA group. There was no injury to any of the structures mentioned above. Postop sore throat was more in the ProSeal LMA group. CONCLUSION From our study, we conclude that the airway can be secured much faster with I-gel than ProSeal LMA. Postop sore throat was much less for I-gel than ProSeal LMA. Both were comparable in number of attempts of insertion, gastric tube introduction. Trauma to the airway structures was also minimum with both I-gel and ProSeal LMA.

  8. Integration of imaging into clinical practice to assess the delivery and performance of macromolecular and nanotechnology-based oncology therapies.

    Science.gov (United States)

    Spence, Tara; De Souza, Raquel; Dou, Yannan; Stapleton, Shawn; Reilly, Raymond M; Allen, Christine

    2015-12-10

    Functional and molecular imaging has become increasingly used to evaluate interpatient and intrapatient tumor heterogeneity. Imaging allows for assessment of microenvironment parameters including tumor hypoxia, perfusion and proliferation, as well as tumor metabolism and the intratumoral distribution of specific molecular markers. Imaging information may be used to stratify patients for targeted therapies, and to define patient populations that may benefit from alternative therapeutic approaches. It also provides a method for non-invasive monitoring of treatment response at earlier time-points than traditional cues, such as tumor shrinkage. Further, companion diagnostic imaging techniques are becoming progressively more important for development and clinical implementation of targeted therapies. Imaging-based companion diagnostics are likely to be essential for the validation and FDA approval of targeted nanotherapies and macromolecular medicines. This review describes recent clinical advances in the use of functional and molecular imaging to evaluate the tumor microenvironment. Additionally, this article focuses on image-based assessment of distribution and anti-tumor effect of nano- and macromolecular systems.

  9. [Similarity of monozygotic twins regarding vocal performance and acoustic markers and possible clinical significance].

    Science.gov (United States)

    Fuchs, M; Oeken, J; Hotopp, T; Täschner, R; Hentschel, B; Behrendt, W

    2000-06-01

    Auditory similarities in voices of monozygotic twins have already been described in the literature. However, is there a clinical relevance? Thus, the present study was designed to identify parameters of vocal performance and acoustic features which are significantly more similar in monozygotic twins than in non-related persons. In our hypothesis, comparable prerequisites for an increased vocal load in a profession or in an artistic education of the voice could be due to these similarities. We compared intra-pair differences with data from a control group. Moreover, we examined the correlation of intra-pair differences with the age of the monozygotic twins. A greater difference in older twin pairs than in younger pairs could show the effect of an exogene influence. In addition to the few phoniatric studies in twins in the literature, we used current methods for acoustic analysis. We examined seven parameters of vocal performance and three acoustic features in 31 monozygotic twin pairs (median age 36 years, range 18-75 years) and compared them with 30 control group pairs, which consisted of non-related persons of the same age and sex, newly combined from the group of monozygotic twins ("statistical twins"). We found significant differences in seven of ten parameters (vocal range, highest and lowest vocal fundamental frequency, fundamental speaking frequency, maximum voice intensity, number of partials, vibrato of intensity; U-test by Mann-Whitney). No correlation of the differences of the identical twins with age was found in the examined parameters. The voices of identical twins are significantly more similar than those of non-related persons regarding the above mentioned features. Thus, the suitability of the voices of monozygotic twins for professions with a high demand on voice is comparable. Results of the group comparison correlate largely with the literature. The missing correlation with age could be due to the fact that the environmental effects were not

  10. Mathematical Model of Movement of the Observation and Tracking Head of an Unmanned Aerial Vehicle Performing Ground Target Search and Tracking

    Directory of Open Access Journals (Sweden)

    Izabela Krzysztofik

    2014-01-01

    Full Text Available The paper presents the kinematics of mutual movement of an unmanned aerial vehicle (UAV and a ground target. The controlled observation and tracking head (OTH is a device responsible for observing the ground, searching for a ground target, and tracking it. The preprogrammed movement of the UAV on the circle with the simultaneous movement of the head axis on Archimedes’ spiral during searching for a ground target, both fixed (bunkers, rocket missiles launching positions, etc. and movable (tanks, infantry fighting vehicles, etc., is considered. Dynamics of OTH during the performance of the above mentioned activities is examined. Some research results are presented in a graphical form.

  11. Peer influence on students' estimates of performance : social comparison in clinical rotations

    NARCIS (Netherlands)

    Raat, A. N. (Janet); Kuks, Jan B. M.; van Hell, E. Ally; Cohen-Schotanus, Janke

    2013-01-01

    Context During clinical rotations, students move from one clinical situation to another. Questions exist about students strategies for coping with these transitions. These strategies may include a process of social comparison because in this context it offers the student an opportunity to estimate h

  12. Clinical evaluation of the Nucleus® 6 cochlear implant system: Performance improvements with SmartSound iQ

    Science.gov (United States)

    Mauger, Stefan J; Warren, Chris D; Knight, Michelle R; Goorevich, Michael

    2014-01-01

    Objective: This paper provides a detailed description of the Nucleus 6 system, and clinically evaluates user performance compared to the previous Nucleus 5 system in cochlear implant recipients. Additionally, it clinically evaluates a range of Nucleus 6 and Nucleus 5 programs to determine the performance benefits provided by new input processing technologies available in SmartSound iQ. Design Speech understanding tests were used to clinically validate the default Nucleus 6 program, by comparing performance outcomes against up to five custom Nucleus 5 or Nucleus 6 programs in a range of listening environments. Clinical comparisons between programs were conducted across the following listening environments; quiet, speech weighted noise (co-located and spatially separated noise), and 4-talker babble (co-located and spatially separated noise). Study sample Twenty-one adult cochlear implant recipients participated. Results Significant speech understanding benefits were found with the default Nucleus 6 program compared to the participants’ preferred program using their Nucleus 5 processor and compared to a range of custom Nucleus 6 programs. All participants successfully accepted and upgraded to the new default Nucleus 6 SmartSound iQ program. Conclusion This study demonstrates the acceptance and clinical benefits of the Nucleus 6 cochlear implant system and SmartSound iQ. PMID:25005776

  13. Free Recall Episodic Memory Performance Predicts Dementia Ten Years prior to Clinical Diagnosis: Findings from the Betula Longitudinal Study

    OpenAIRE

    Boraxbekk, Carl-Johan; Lundquist, Anders; Nordin, Annelie; Nyberg, Lars; Nilsson, Lars-Göran; Adolfsson, Rolf

    2015-01-01

    Background/Aims: Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Methods: Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years ...

  14. Differential Gene Expression Profiles in Coronary Heart Disease Patients of Blood Stasis Syndrome in Traditional Chinese Medicine and Clinical Role of Target Gene

    Institute of Scientific and Technical Information of China (English)

    马晓娟; 殷惠军; 陈可冀

    2009-01-01

    Objective:To investigate the differential gene expression profiles in coronary heart disease(CHD) patients of blood-stasis syndrome(BSS) by oligonucleotide microarray technique,and the clinical significance of target gene.Methods:Subjects were assigned to CHD patients with BSS(n=8),CHD patients without BSS (n=8),and BSS patients without CHD(n=8) based on coronary angiography and the diagnostic criteria of BSS. The sex- and age-matched healthy volunteers(n=8) were enrolled as the control group.Venous bloo...

  15. Clinical and Pathological Complete Remission in a Patient With Metastatic Renal Cell Carcinoma (mRCC Treated With Sunitinib: Is mRCC Curable With Targeted Therapy?

    Directory of Open Access Journals (Sweden)

    Amishi Y. Shah

    2015-03-01

    Full Text Available We report a patient with metastatic clear-cell renal cell carcinoma (mRCC who presented with primary tumor in situ in the left kidney and metastases to bone, liver, lungs, and brain. After over 5 years of sunitinib therapy and subsequent cytoreductive left nephrectomy, the patient achieved radiographic complete response (CR and had pathologic CR in the nephrectomy specimen. Durable clinical and pathological CRs are possible with targeted agents, even with primary tumor in situ and widely disseminated metastases. Ongoing research will define the optimal duration of systemic therapy in exceptional responders and identify the molecular determinants of response and resistance.

  16. Renin-angiotensin system as a potential therapeutic target in stroke and retinopathy: experimental and clinical evidence.

    Science.gov (United States)

    Fouda, Abdelrahman Y; Artham, Sandeep; El-Remessy, Azza B; Fagan, Susan C

    2016-02-01

    As our knowledge expands, it is now clear that the renin-angiotensin (Ang) system (RAS) mediates functions other than regulating blood pressure (BP). The RAS plays a central role in the pathophysiology of different neurovascular unit disorders including stroke and retinopathy. Moreover, the beneficial actions of RAS modulation in brain and retina have been documented in experimental research, but not yet exploited clinically. The RAS is a complex system with distinct yet interconnected components. Understanding the different RAS components and their functions under brain and retinal pathological conditions is crucial to reap their benefits. The aim of the present review is to provide an experimental and clinical update on the role of RAS in the pathophysiology and treatment of stroke and retinopathy. Combining the evidence from both these disorders allows a unique opportunity to move both fields forward.

  17. Do Expert Clinical Teachers Have a Shared Understanding of What Constitutes a Competent Reasoning Performance in Case-Based Teaching?

    Science.gov (United States)

    Gauthier, Geneviève; Lajoie, Susanne P.

    2014-01-01

    To explore the assessment challenge related to case based learning we study how experienced clinical teachers--i.e., those who regularly teach and assess case-based learning--conceptualize the notion of competent reasoning performance for specific teaching cases. Through an in-depth qualitative case study of five expert teachers, we investigate…

  18. Clinical outcome 5 to 18 years after the Fontan operation performed on children younger than 5 years.

    NARCIS (Netherlands)

    Robbers-Visser, D.; Kapusta, L.; Osch-Gevers, L. van; Strengers, J.L.; Boersma, E.; Rijke, Y.B. de; Boomsma, F.; Bogers, A.J.; Helbing, W.A.

    2009-01-01

    OBJECTIVE: This study assessed clinical condition at midterm follow-up after total cavopulmonary connection for a functionally univentricular heart performed on children younger than 5 years. METHODS: Thirty-four Fontan patients (median age 10.4 years, range 6.8-20.7 years, 22 boys, median follow-up

  19. Clinical performance of two visual scoring systems in detecting and assessing activity status of occlusal caries in primary teeth

    DEFF Research Database (Denmark)

    Braga, M M; Ekstrand, K R; Martignon, S;

    2010-01-01

    This study aimed to compare the clinical performance of two sets of visual scoring criteria for detecting caries severity and assessing caries activity status in occlusal surfaces. Two visual scoring systems--the Nyvad criteria (NY) and the ICDAS-II including an adjunct system for lesion activity...

  20. [Radiotherapy of cancers of the pancreas and extrahepatic biliary tree. Gross tumor volume (GTV). Clinical target volume (CTV)].

    Science.gov (United States)

    Atlan, D; Mornex, F

    2001-10-01

    Anatomical data of pancreas, biliary tree, regional lymph nodes is required to define GTV and CTV. In case of postoperative irradiation, CTV is designed in collaboration with radiation oncologist and surgeon oncologist. For exclusive radiotherapy, endodigestive ultrasonography, CT scan and MRI could help radiation oncologist defining GTV. Although, accuracy of all the imaging techniques in past years remains poor. Currently, no available literature is published regarding security margins for the definition of CTV. Therefore, recommendations according to clinical experience are proposed. PMID:11715305

  1. The impact of patient support programs on adherence, clinical, humanistic, and economic patient outcomes: a targeted systematic review

    OpenAIRE

    Ganguli A; Clewell J; Shillington AC

    2016-01-01

    Arijit Ganguli,1 Jerry Clewell,2 Alicia C Shillington3 1Department of Health Economics and Outcomes Research, 2Department of Medical Affairs, AbbVie, North Chicago, IL, USA; 3EPI-Q Inc., Oak Brook, IL, USA Background: Patient support programs (PSPs), including medication management and counseling, have the potential to improve care in chronic disease states with complex therapies. Little is known about the program’s effects on improving clinical, adherence, humanistic, and cost ou...

  2. A multimodal approach to investigate biomarkers for psychosis in a clinical setting: the integrative neuroimaging studies in schizophrenia targeting for early intervention and prevention (IN-STEP) project.

    Science.gov (United States)

    Koike, Shinsuke; Takano, Yosuke; Iwashiro, Norichika; Satomura, Yoshihiro; Suga, Motomu; Nagai, Tatsuya; Natsubori, Tatsunobu; Tada, Mariko; Nishimura, Yukika; Yamasaki, Syudo; Takizawa, Ryu; Yahata, Noriaki; Araki, Tsuyoshi; Yamasue, Hidenori; Kasai, Kiyoto

    2013-01-01

    Longitudinal clinical investigations and biological measurements have determined not only progressive brain volumetric and functional changes especially around the onset of psychosis but also the abnormality of developmental pathways based on gene-environment interaction model. However, these studies have contributed little to clinical decisions on their diagnosis and therapeutic choices because of subtle differences between patients and healthy controls. A multi-modal approach may resolve this limitation and is favorable to explore the pathophysiology of psychosis. The integrative neuroimaging studies for schizophrenia targeting early intervention and prevention (IN-STEP) is a research project aimed at exploring the pathophysiological features of the onset of psychosis and investigating possible predictive biomarkers for the clinical treatment of psychosis. Since 2008, we have adopted blood sampling, neurocognitive batteries, neurophysiological assessment, structural imaging, and functional imaging longitudinally for help-seeking ultra-high-risk (UHR) individuals and patients with first-episode psychosis (FEP). Here, we intend to introduce the IN-STEP research study protocol and present preliminary clinical findings. Thirty-seven UHR individuals and 30 patients with FEP participated in this study. Six months later, there was no difference in objective and subjective scores between the groups, which suggests that young people having symptoms and functional deficits should be cared for regardless of their history of psychosis according to their clinical stages. The rate of transition to psychosis was 7.1%, 8.0%, and 35.3% (at 6, 12, and 24months, respectively). Through this research project, we expect to clarify the pathophysiological features around the onset of psychosis and improve the prognosis of psychosis through clinical application. PMID:23219075

  3. Clinical implications of the 2013 ESH/ESC hypertension guidelines: targets, choice of therapy, and blood pressure monitoring.

    Science.gov (United States)

    Kjeldsen, Sverre E; Aksnes, Tonje A; Ruilope, Luis M

    2014-06-01

    The European Society of Hypertension (ESH)/European Society of Cardiology (ESC) 2013 guidelines for the management of arterial hypertension included simplified blood pressure (BP) targets across patient groups, more balanced discussion on monotherapy vs. combination therapy, as well as reconfirmation of the importance of out-of-office BP measurements. In light of these updates, we wished to review some issues raised and take a fresh look at the role of calcium channel blocker (CCB) therapy; an established antihypertensive class that appears to be a favorable choice in many patients. Relaxed BP targets for high-risk hypertensive patients in the 2013 ESH/ESC guidelines were driven by a lack of commanding evidence for an aggressive approach. However, substantial evidence demonstrates cardiovascular benefits from more intensive BP lowering across patient groups. Individualized treatment of high-risk patients may be prudent until more solid evidence is available. Individual patient profiles and preferences and evidence for preferential therapy benefits should be considered when deciding upon the optimal antihypertensive regimen. CCBs appear to be a positive choice for monotherapy, and in combination with other agent classes, and may provide specific benefits beyond BP lowering. Ambulatory and home BP monitoring have an increasing role in defining the diagnosis and prognosis of hypertension (especially non-sustained); however, their value for comprehensive diagnosis and appropriate treatment selection should be more widely acknowledged. In conclusion, further evidence may be required on BP targets in high-risk patients, and optimal treatment selection based upon individual patient profiles and comprehensive diagnosis using out-of-office BP measurements may improve patient management. PMID:24842751

  4. Investigation and analysis of clinical trial research nurse to perform standard operating procedures

    Institute of Scientific and Technical Information of China (English)

    Yan Lin; Yan-Yun Wu; Mei-Hua Wu; Xiu-Yu Yang; Ming Zhou

    2016-01-01

    Objective: The aim of this study was to investigate the situations and factors that cause nurses not to follow standard operating procedures (SOPs) during the clinical trial process. Methods: Five cases involving patients enrolled in a clinical trial were divided into two groups, pre-SOP training and post-SOP training, to compare and observe the process problems and whether nurses fol-lowed SOPs in clinical trials. The causes of problems were analyzed and corrective measures were proposed. Results: Our results indicate significant improvement in compliance with SOPs after training. There were three occurrences of irregular behavior after training compared with 21 occurrences of irregular behavior before training. Conclusions: The quality of clinical trials can be improved if nurses strictly follow SOPs.

  5. Apolipoprotein E as a Therapeutic Target in Alzheimer's Disease: A Review of Basic Research and Clinical Evidence.

    Science.gov (United States)

    Yamazaki, Yu; Painter, Meghan M; Bu, Guojun; Kanekiyo, Takahisa

    2016-09-01

    Alzheimer's disease (AD) is a devastating neurodegenerative disorder that causes progressive cognitive decline. The majority of AD cases are sporadic and late-onset (>65 years old) making it the leading cause of dementia in the elderly. While both genetic and environmental factors contribute to the development of late-onset AD (LOAD), APOE polymorphism is a major genetic risk determinant for LOAD. In humans, the APOE gene has three major allelic variants: ε2, ε3, and ε4, of which APOE ε4 is the strongest genetic risk factor for LOAD, whereas APOE ε2 is protective. Mounting evidence suggests that APOE ε4 contributes to AD pathogenesis through multiple pathways including facilitated amyloid-β deposition, increased tangle formation, synaptic dysfunction, exacerbated neuroinflammation, and cerebrovascular defects. Since APOE modulates multiple biological processes through its corresponding protein apolipoprotein E (apoE), APOE gene and apoE properties have been a promising target for therapy and drug development against AD. In this review, we summarize the current evidence regarding how the APOE ε4 allele contributes to the pathogenesis of AD and how relevant therapeutic approaches can be developed to target apoE-mediated pathways in AD. PMID:27328687

  6. Advazorb® foam range: providing clinical performance and cost-effectiveness

    OpenAIRE

    Cook, Leanne

    2011-01-01

    The use of advanced wound dressings currently presents a costly burden to the NHS. Subsequently, clinicians need to ensure that such dressings are used appropriately and are clinically effective. This article discusses the merits of foam dressings within wound care and describes three clinical case reports using Advazorb® foam dressings (Advancis Medical) in the treatment of acute/chronic wounds. These foam dressings include a range of wound care solutions, which have been found to be clinica...

  7. Clinical performance of a hybrid resin composite with and without an intermediate layer of flowable resin composite: a 7-year evaluation

    DEFF Research Database (Denmark)

    van Dijken, Jan W V; Pallesen, Ulla

    2011-01-01

    The objective of this prospective clinical follow up was to evaluate the long term clinical performance of a hybrid resin composite in Class II restorations with and without intermediate layer of flowable resin composite.......The objective of this prospective clinical follow up was to evaluate the long term clinical performance of a hybrid resin composite in Class II restorations with and without intermediate layer of flowable resin composite....

  8. Observations and Performances “with distinction” by Physical Therapy Students in Clinical Education: Analysis of Checkboxes on the Physical Therapist Clinical Performance Instrument (PT-CPI) over a 4-Year Period

    Science.gov (United States)

    Booth, Randy

    2015-01-01

    ABSTRACT Purpose: To describe how often the 24 performance criteria of the Physical Therapist Clinical Performance Instrument (PT-CPI) were not observed and how often they were rated exceptionally well for physical therapy (PT) students in relation to clinical placement descriptors. Methods: Indicators of “not observed,” performance “with distinction,” and “significant concerns” were tabulated from 1,460 clinical placements between 2008 and 2012. The rates for these indicators were evaluated with respect to catchment area, practice setting (hospital/institutional or community-based), practice area (musculoskeletal, cardiorespiratory, neurology, paediatrics, geriatrics, or variety), and level (junior to senior). Results: Of the 24 PT-CPI criteria, 15 had observation rates >95%. Of the other nine criteria, some showed significant differences in observation rates across level, practice setting, and practice area. Ratings of “with distinction” were awarded most often for criteria related to professionalism and communication and were awarded more often in community-based settings than in hospital/institutional settings. For some criteria, “with distinction” was awarded more often in paediatrics placements than in other areas. The “significant concerns” checkboxes were rarely used. Conclusions: The overall observation rates were very similar to those reported elsewhere. The findings related to performance “with distinction” and observation rates relative to setting and practice area are new contributions to physical therapy knowledge. PMID:25931650

  9. Comparative Proteomic Analysis of Aminoglycosides Resistant and Susceptible Mycobacterium tuberculosis Clinical Isolates for Exploring Potential Drug Targets.

    Directory of Open Access Journals (Sweden)

    Divakar Sharma

    Full Text Available Aminoglycosides, amikacin (AK and kanamycin (KM are second line anti-tuberculosis drugs used to treat tuberculosis (TB and resistance to them affects the treatment. Membrane and membrane associated proteins have an anticipated role in biological processes and pathogenesis and are potential targets for the development of new diagnostics/vaccine/therapeutics. In this study we compared membrane and membrane associated proteins of AK and KM resistant and susceptible Mycobacterium tuberculosis isolates by 2DE coupled with MALDI-TOF/TOF-MS and bioinformatic tools. Twelve proteins were found to have increased intensities (PDQuest Advanced Software in resistant isolates and were identified as ATP synthase subunit alpha (Rv1308, Trigger factor (Rv2462c, Dihydrolipoyl dehydrogenase (Rv0462, Elongation factor Tu (Rv0685, Transcriptional regulator MoxR1(Rv1479, Universal stress protein (Rv2005c, 35kDa hypothetical protein (Rv2744c, Proteasome subunit alpha (Rv2109c, Putative short-chain type dehydrogenase/reductase (Rv0148, Bacterioferritin (Rv1876, Ferritin (Rv3841 and Alpha-crystallin/HspX (Rv2031c. Among these Rv2005c, Rv2744c and Rv0148 are proteins with unknown functions. Docking showed that both drugs bind to the conserved domain (Usp, PspA and SDR domain of these hypothetical proteins and GPS-PUP predicted potential pupylation sites within them. Increased intensities of these proteins and proteasome subunit alpha might not only be neutralized/modulated the drug molecules but also involved in protein turnover to overcome the AK and KM resistance. Besides that Rv1876, Rv3841 and Rv0685 were found to be associated with iron regulation signifying the role of iron in resistance. Further research is needed to explore how these potential protein targets contribute to resistance of AK and KM.

  10. Comparative Proteomic Analysis of Aminoglycosides Resistant and Susceptible Mycobacterium tuberculosis Clinical Isolates for Exploring Potential Drug Targets

    Science.gov (United States)

    Sharma, Divakar; Kumar, Bhavnesh; Lata, Manju; Joshi, Beenu; Venkatesan, Krishnamurthy; Shukla, Sangeeta; Bisht, Deepa

    2015-01-01

    Aminoglycosides, amikacin (AK) and kanamycin (KM) are second line anti-tuberculosis drugs used to treat tuberculosis (TB) and resistance to them affects the treatment. Membrane and membrane associated proteins have an anticipated role in biological processes and pathogenesis and are potential targets for the development of new diagnostics/vaccine/therapeutics. In this study we compared membrane and membrane associated proteins of AK and KM resistant and susceptible Mycobacterium tuberculosis isolates by 2DE coupled with MALDI-TOF/TOF-MS and bioinformatic tools. Twelve proteins were found to have increased intensities (PDQuest Advanced Software) in resistant isolates and were identified as ATP synthase subunit alpha (Rv1308), Trigger factor (Rv2462c), Dihydrolipoyl dehydrogenase (Rv0462), Elongation factor Tu (Rv0685), Transcriptional regulator MoxR1(Rv1479), Universal stress protein (Rv2005c), 35kDa hypothetical protein (Rv2744c), Proteasome subunit alpha (Rv2109c), Putative short-chain type dehydrogenase/reductase (Rv0148), Bacterioferritin (Rv1876), Ferritin (Rv3841) and Alpha-crystallin/HspX (Rv2031c). Among these Rv2005c, Rv2744c and Rv0148 are proteins with unknown functions. Docking showed that both drugs bind to the conserved domain (Usp, PspA and SDR domain) of these hypothetical proteins and GPS-PUP predicted potential pupylation sites within them. Increased intensities of these proteins and proteasome subunit alpha might not only be neutralized/modulated the drug molecules but also involved in protein turnover to overcome the AK and KM resistance. Besides that Rv1876, Rv3841 and Rv0685 were found to be associated with iron regulation signifying the role of iron in resistance. Further research is needed to explore how these potential protein targets contribute to resistance of AK and KM. PMID:26436944

  11. Comparative Proteomic Analysis of Aminoglycosides Resistant and Susceptible Mycobacterium tuberculosis Clinical Isolates for Exploring Potential Drug Targets.

    Science.gov (United States)

    Sharma, Divakar; Kumar, Bhavnesh; Lata, Manju; Joshi, Beenu; Venkatesan, Krishnamurthy; Shukla, Sangeeta; Bisht, Deepa

    2015-01-01

    Aminoglycosides, amikacin (AK) and kanamycin (KM) are second line anti-tuberculosis drugs used to treat tuberculosis (TB) and resistance to them affects the treatment. Membrane and membrane associated proteins have an anticipated role in biological processes and pathogenesis and are potential targets for the development of new diagnostics/vaccine/therapeutics. In this study we compared membrane and membrane associated proteins of AK and KM resistant and susceptible Mycobacterium tuberculosis isolates by 2DE coupled with MALDI-TOF/TOF-MS and bioinformatic tools. Twelve proteins were found to have increased intensities (PDQuest Advanced Software) in resistant isolates and were identified as ATP synthase subunit alpha (Rv1308), Trigger factor (Rv2462c), Dihydrolipoyl dehydrogenase (Rv0462), Elongation factor Tu (Rv0685), Transcriptional regulator MoxR1(Rv1479), Universal stress protein (Rv2005c), 35kDa hypothetical protein (Rv2744c), Proteasome subunit alpha (Rv2109c), Putative short-chain type dehydrogenase/reductase (Rv0148), Bacterioferritin (Rv1876), Ferritin (Rv3841) and Alpha-crystallin/HspX (Rv2031c). Among these Rv2005c, Rv2744c and Rv0148 are proteins with unknown functions. Docking showed that both drugs bind to the conserved domain (Usp, PspA and SDR domain) of these hypothetical proteins and GPS-PUP predicted potential pupylation sites within them. Increased intensities of these proteins and proteasome subunit alpha might not only be neutralized/modulated the drug molecules but also involved in protein turnover to overcome the AK and KM resistance. Besides that Rv1876, Rv3841 and Rv0685 were found to be associated with iron regulation signifying the role of iron in resistance. Further research is needed to explore how these potential protein targets contribute to resistance of AK and KM.

  12. Performance Analysis of Stand-Alone Photovoltaic (SAPV) System for Category I Health Clinic in Orlu, Imo State, Nigeria

    OpenAIRE

    Isaac A., Ezenugu; Anthony, Umoren Mfonobong; Nseobong. I., Okpura

    2016-01-01

    In this paper, performance analysis of stand-alone photovoltaic (SAPV) system for Primary Health Centre in Orlu, Imo state was conducted. The USAID categorisation of health clinics is used to identify the Primary Health Centre  as Category I Health Clinic with corresponding daily and yearly energy demand of approximately 11500 Wh/day and 4197.5 KWh/year respectively.  PVsyst software solution was used to model and simulate the entire PV system. 22-year air temperature and monthly and annual a...

  13. Accuracy of relocation, evaluation of geometric uncertainties and clinical target volume (CTV) to planning target volume (PTV) margin in fractionated stereotactic radiotherapy for intracranial tumors using relocatable Gill-Thomas-Cosman (GTC) frame.

    Science.gov (United States)

    Das, Saikat; Isiah, Rajesh; Rajesh, B; Ravindran, B Paul; Singh, Rabi Raja; Backianathan, Selvamani; Subhashini, J

    2011-01-01

    The present study is aimed at determination of accuracy of relocation of Gill-Thomas-Cosman frame during fractionated stereotactic radiotherapy. The study aims to quantitatively determine the magnitudes of error in anteroposterior, mediolateral and craniocaudal directions, and determine the margin between clinical target volume to planning target volume based on systematic and random errors. Daily relocation error was measured using depth helmet and measuring probe. Based on the measurements, translational displacements in anteroposterior (z), mediolateral (x), and craniocaudal (y) directions were calculated. Based on the displacements in x, y and z directions, systematic and random error were calculated and three-dimensional radial displacement vector was determined. Systematic and random errors were used to derive CTV to PTV margin. The errors were within ± 2 mm in 99.2% cases in anteroposterior direction (AP), in 99.6% cases in mediolateral direction (ML), and in 97.6% cases in craniocaudal direction (CC). In AP, ML and CC directions, systematic errors were 0.56, 0.38, 0.42 mm and random errors were 1.86, 1.36 and 0.73 mm, respectively. Mean radial displacement was 1.03 mm ± 0.34. CTV to PTV margins calculated by ICRU formula were 1.86, 1.45 and 0.93 mm; by Stroom's formula they were 2.42, 1.74 and 1.35 mm; by van Herk's formula they were 2.7, 1.93 and 1.56 mm (AP, ML and CC directions). Depth helmet with measuring probe provides a clinically viable way for assessing the relocation accuracy of GTC frame. The errors were within ± 2 mm in all directions. Systematic and random errors were more along the anteroposterior axes. According to the ICRU formula, a margin of 2 mm around the tumor seems to be adequate. PMID:21587166

  14. Active Learning Improves Nursing Student Clinical Performance in an Academic Institution in Macao

    Institute of Scientific and Technical Information of China (English)

    Cindy Sin U Leong; Lynn B. Clutter

    2015-01-01

    Objective: To assess the outcome of the application of active learning during practicum among nursing students using clinical assessment and evaluation scores as a measurement. Methods: Nursing students were instructed on the basics of active learning prior to the initiation of their clinical experience. The participants were divided into 5groups of nursing students ( n=56) across three levels ( years 2-4) in a public academic institute of a bachelor degree program in Macao. Final clinical evaluation was averaged and compared between groups with and without in-tervention. Results: These nursing students were given higher appraisals in verbal and written comments than previous students without interventian. The groups with the invention achieved higher clinical as-sessment and evaluation scores on average than comparable groups without the active learning in-tervention. One group of sophomore nursing students ( year 2) did not receive as high of evalua-tions as the other groups, receiving an average score of above 80. Conclusions: Nursing students must engage in active learning to demonstrate that they are will-ing to gain knowledge of theory, nursing skills and communication skills during the clinical practi-cum.

  15. Performance of Clinical Laboratories in South African Parasitology Proficiency Testing Surveys between 2004 and 2010

    OpenAIRE

    Poonsamy, Bhavani; Dini, Leigh; Frean, John

    2012-01-01

    Performance in proficiency testing (PT) schemes is an objective measure of a laboratory's best performance. We examined the performance of participants in two parasitology PT schemes in South Africa from 2004 through 2010. The average rates of acceptable scores over the period were 58% and 66% for the stool and blood parasite schemes, respectively. In our setting, participation in PT alone is insufficient to improve performance; a policy that provides additional resources and training seems n...

  16. Mass spectrometry in biomarker applications: from untargeted discovery to targeted verification, and implications for platform convergence and clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Richard D.

    2012-03-01

    It is really only in the last ten years that mass spectrometry (MS) has had a truly significant (but still small) impact on biomedical research. Much of this impact can be attributed to proteomics and its more basic applications. Early biomedical applications have included a number of efforts aimed at developing new biomarkers; however, the success of these endeavors to date have been quite modest - essentially confined to preclinical applications - and have often suffered from combinations of immature technology and hubris. Now that MS-based proteomics is reaching adolescence, it is appropriate to ask if and when biomarker-related applications will extend to the clinical realm, and what developments will be essential for this transition. Biomarker development can be described as a multistage process consisting of discovery, qualification, verification, research assay optimization, validation, and commercialization (1). From a MS perspective, it is possible to 'bin' measurements into 1 of 2 categories - those aimed at discovering potential protein biomarkers and those seeking to verify and validate biomarkers. Approaches in both categories generally involve digesting proteins (e.g., with trypsin) as a first step to yield peptides that can be effectively detected and identified with MS. Discovery-based approaches use broad 'unbiased' or 'undirected' measurements that attempt to cover as many proteins as possible in the hope of revealing promising biomarker candidates. A key challenge with this approach stems from the extremely large dynamic range (i.e., relative stoichiometry) of proteins of potential interest in biofluids such as plasma and the expectation that biomarker proteins of the greatest clinical value for many diseases may very well be present at low relative abundances (2). Protein concentrations in plasma extend from approximately 10{sup 10} pg/mL for albumin to approximately 10 pg/mL and below for interleukins and other

  17. In silico target predictions: defining a benchmarking data set and comparison of performance of the multiclass Naïve Bayes and Parzen-Rosenblatt window.

    Science.gov (United States)

    Koutsoukas, Alexios; Lowe, Robert; Kalantarmotamedi, Yasaman; Mussa, Hamse Y; Klaffke, Werner; Mitchell, John B O; Glen, Robert C; Bender, Andreas

    2013-08-26

    In this study, two probabilistic machine-learning algorithms were compared for in silico target prediction of bioactive molecules, namely the well-established Laplacian-modified Naïve Bayes classifier (NB) and the more recently introduced (to Cheminformatics) Parzen-Rosenblatt Window. Both classifiers were trained in conjunction with circular fingerprints on a large data set of bioactive compounds extracted from ChEMBL, covering 894 human protein targets with more than 155,000 ligand-protein pairs. This data set is also provided as a benchmark data set for future target prediction methods due to its size as well as the number of bioactivity classes it contains. In addition to evaluating the methods, different performance measures were explored. This is not as straightforward as in binary classification settings, due to the number of classes, the possibility of multiple class memberships, and the need to translate model scores into "yes/no" predictions for assessing model performance. Both algorithms achieved a recall of correct targets that exceeds 80% in the top 1% of predictions. Performance depends significantly on the underlying diversity and size of a given class of bioactive compounds, with small classes and low structural similarity affecting both algorithms to different degrees. When tested on an external test set extracted from WOMBAT covering more than 500 targets by excluding all compounds with Tanimoto similarity above 0.8 to compounds from the ChEMBL data set, the current methodologies achieved a recall of 63.3% and 66.6% among the top 1% for Naïve Bayes and Parzen-Rosenblatt Window, respectively. While those numbers seem to indicate lower performance, they are also more realistic for settings where protein targets need to be established for novel chemical substances.

  18. Design, Characterization, and Aerosol Dispersion Performance Modeling of Advanced Spray-Dried Microparticulate/Nanoparticulate Mannitol Powders for Targeted Pulmonary Delivery as Dry Powder Inhalers

    OpenAIRE

    Li, Xiaojian; Vogt, Frederick G; Hayes, Don; Mansour, Heidi M

    2014-01-01

    Background: The purpose was to design and characterize inhalable microparticulate/nanoparticulate dry powders of mannitol with essential particle properties for targeted dry powder delivery for cystic fibrosis mucolytic treatment by dilute organic solution spray drying, and, in addition, to tailor and correlate aerosol dispersion performance delivered as dry powder inhalers based on spray-drying conditions and solid-state physicochemical properties.

  19. Skin Cancer of the Head and Neck With Perineural Invasion: Defining the Clinical Target Volumes Based on the Pattern of Failure

    International Nuclear Information System (INIS)

    Purpose: To analyze patterns of failure in patients with head-and-neck cutaneous squamous cell carcinoma (HNCSCC) and clinical/radiologic evidence of perineural invasion (CPNI), in order to define neural clinical target volume (CTV) for treatment planning. Methods and Materials: Patients treated with three-dimensional (3D) conformal or intensity-modulated radiotherapy (IMRT) for HNCSCC with CPNI were included in the study. A retrospective review of the clinical charts, radiotherapy (RT) plans and radiologic studies has been conducted. Results: Eleven consecutive patients with HNCSCCs with CPNI were treated from 2000 through 2007. Most patients underwent multiple surgical procedures and RT courses. The most prevalent failure pattern was along cranial nerves (CNs), and multiple CNs were ultimately involved in the majority of cases. In all cases the involved CNs at recurrence were the main nerves innervating the primary tumor sites, as well as their major communicating nerves. We have found several distinct patterns of disease spread along specific CNs depending on the skin regions harboring the primary tumors, including multiple branches of CN V and VII. These patterns and the pertinent anatomy are detailed in the this article. Conclusions: Predictable disease spread patterns along cranial nerves supplying the primary tumor sites were found in this study. Awareness of these patterns, as well as knowledge of the relevant cranial nerve anatomy, should be the basis for CTV definition and delineation for RT treatment planning.

  20. Skin Cancer of the Head and Neck with Perineural Invasion: Defining the Clinical Target Volumes Based on the Pattern of Failure

    Science.gov (United States)

    Gluck, Iris; Ibrahim, Mohannad; Popovtzer, Aron; Teknos, Theodoros N.; Chepeha, Douglas B; Prince, Mark E; Moyer, Jeffrey S; Bradford, Carol R; Eisbruch, Avraham

    2009-01-01

    Purpose To analyze patterns of failure in patients with head and neck cutaneous squamous cell carcinoma (HNCSCC) and clinical/radiological evidence of perineural invasion (CPNI), in order to define neural clinical target volume (CTV) for treatment planning. Methods Patients treated with 3D conformal or intensity modulated radiotherapy (IMRT) for HNCSCC with CPNI were included in the study. A retrospective review of the clinical charts, radiotherapy (RT) plans and radiological studies has been conducted. Results Eleven consecutive patients with HNCSCCs with CPNI were treated from 2000 through 2007. Most patients received multiple surgical procedures and RT courses. The most prevalent failure pattern was along cranial nerves (CNs), and multiple CNs were ultimately involved in the majority of cases. In all cases the involved CNs at recurrence were the main nerves innervating the primary tumor sites, as well as their major communicating nerves. We have found several distinct patterns of disease spread along specific CNs depending on the skin regions harboring the primary tumors, including multiple branches of CN V and VII. These patterns and the pertinent anatomy are detailed in the paper. Conclusions Predictable disease spread patterns along cranial nerves supplying the primary tumor sites were found in this study. Awareness of these patterns, as well as knowledge of the relevant cranial nerve anatomy, should be the basis for CTV definition and delineation for RT treatment planning. PMID:18938044

  1. Evaluation of mid- and long-term consequences, clinical and social performance in Chernobyl acute radiation syndrome patients in a multi-centre clinical follow-up study

    International Nuclear Information System (INIS)

    Since the Chernobyl accident in 1986 nearly all survivors (n=199) of 237 patients with suspected acute radiation syndrome (ARS) underwent regular follow-up investigations in the scientific centres in Kiev and in Moscow. In a close collaboration with these centres we investigate the health status of this population in a five step approach. An integral part of this approach to patient evaluation and analysis of the mid- and long-term consequences of the Chernobyl accident is a 'Questionnaire for clinical, laboratory and functional follow-up of radiation-exposed persons', developed with these centres. Beyond this project we report as an interim some results of analyses performed by the scientific centers in Kiev and in Moscow about disorders of the cardiovascular system and the digestive tract, formation of cataract, generalized and local skin injuries and/or disorders as well as for a subpopulation (n=89) the Karnofsky performance score and working ability

  2. Experience as a doctor in the developing world: does it benefit the clinical and organisational performance in general practice?

    Directory of Open Access Journals (Sweden)

    de Wit Niek J

    2009-12-01

    Full Text Available Abstract Background Many physicians have medical experience in developing countries early in their career, but its association with their medical performance later is not known. To explore possible associations we compared primary care physicians (GPs with and without professional experience in a developing country in performance both clinical and organisational. Methods A retrospective survey using two databases to analyse clinical and organisational performance respectively. Analysis was done at the GP level and practice level. 517 GPs received a questionnaire regarding relevant working experience in a developing country. Indicators for clinical performance were: prescription, referral, external diagnostic procedures and minor procedures. We used the district health insurance data base covering 570.000 patients. Explorative secondary analysis of practice visits of 1004 GPs in 566 practices in the Netherlands from 1999 till 2001. We used a validated practice visit method (VIP; 385 indicators in 51 dimensions of practice management to compare having experience in a developing country or not. Results Almost 8% of the GPs had experience in a developing country of at least two years. These GPs referred 9,5% less than their colleagues and did more surgical procedures. However, in the multivariate analysis 'experience in a developing country' was not significantly associated with clinical performance or with other GP- and practice characteristics. 16% of the practices a GP or GPs with at least two years experience in a developing country. They worked more often in group and rural practices with less patients per fte GP and more often part-time. These practices are more hygienic, collaborate more with the hospital and score better on organisation of the practice. These practices score less on service and availability, spend less time on patients in the consultation and the quality of recording in the EMD is lower. Conclusions We found interesting

  3. Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Gehl, Julie

    2011-01-01

    Current technology has limited applicability for electroporation based treatment of deep-seated tumors, and is in general, not optimized in terms of compliance with clinically relevant parameters. Here we present a novel electrode device developed for electrotransfer of antineoplastic drugs and...

  4. An Effective Model for a Comprehensive Performance Measurement of Clinical and Research Laboratory Centers

    OpenAIRE

    Ghazinoory S; Assadifard R; Ebrahimi A; Dastmardi M

    2011-01-01

    Bachground and objectives: Improvement of the effectiveness of services isone of the most important strategies in many clinical and research laboratorycenters. The increased client satisfaction (researchers or patients), resourcedevelopment innovation, efficacy, continuity of services and income are alsothe important strategies of these centers. For achieving these strategies, wecombined the qualitative and the quantitative approaches to evaluate theeffective model based on frameworks of the ...

  5. Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Gehl, Julie

    2011-01-01

    Current technology has limited applicability for electroporation based treatment of deep-seated tumors, and is in general, not optimized in terms of compliance with clinically relevant parameters. Here we present a novel electrode device developed for electrotransfer of antineoplastic drugs...

  6. Performance of microarray and liquid based capture methods for target enrichment for massively parallel sequencing and SNP discovery.

    Directory of Open Access Journals (Sweden)

    Anna Kiialainen

    Full Text Available Targeted sequencing is a cost-efficient way to obtain answers to biological questions in many projects, but the choice of the enrichment method to use can be difficult. In this study we compared two hybridization methods for target enrichment for massively parallel sequencing and single nucleotide polymorphism (SNP discovery, namely Nimblegen sequence capture arrays and the SureSelect liquid-based hybrid capture system. We prepared sequencing libraries from three HapMap samples using both methods, sequenced the libraries on the Illumina Genome Analyzer, mapped the sequencing reads back to the genome, and called variants in the sequences. 74-75% of the sequence reads originated from the targeted region in the SureSelect libraries and 41-67% in the Nimblegen libraries. We could sequence up to 99.9% and 99.5% of the regions targeted by capture probes from the SureSelect libraries and from the Nimblegen libraries, respectively. The Nimblegen probes covered 0.6 Mb more of the original 3.1 Mb target region than the SureSelect probes. In each sample, we called more SNPs and detected more novel SNPs from the libraries that were prepared using the Nimblegen method. Thus the Nimblegen method gave better results when judged by the number of SNPs called, but this came at the cost of more over-sampling.

  7. Atrial Substrate Modification in Atrial Fibrillation: Targeting GP or CFAE? Evidence from Meta-Analysis of Clinical Trials

    Science.gov (United States)

    Qin, Mu; Liu, Xu; Wu, Shao-Hui; Zhang, Xiao-Dong

    2016-01-01

    Several clinically relevant outcomes post atrial substrate modification in patients with atrial fibrillation (AF) have not been systematically analyzed among published studies on adjunctive cardiac ganglionated plexi (GP) or complex fractionated atrial electograms (CFAE) ablation vs. pulmonary vein isolation (PVI) alone. Out of 176 reports identified, the present meta-analysis included 14 randomized and non-randomized controlled trials (1613 patients) meeting inclusion criteria. Addition of GP ablation to PVI significantly increased freedom from atrial tachyarrhythmia in short- (OR: 1.72; P = 0.003) and long-term (OR: 2.0, P = 0.0006) follow-up, while adjunctive CFAE ablation did not after one or repeat procedure (P<0.05). The percentage of atrial tachycardia or atrial flutter (AT/AFL) after one procedure was higher for CFAE than GP ablation. In sub-analysis of non-paroxysmal AF, relative to PVI alone, adjunctive GP but not CFAE ablation significantly increased sinus rhythm maintenance (OR: 1.88, P = 0.01; and OR:1.24, P = 0.18, respectively). Meta regression analysis of the 14 studies indicated that sample size was significant source of heterogeneity either in outcomes after one or repeat procedure. In conclusion, in patients with AF, adjunctive GP but not CFAE ablation appeared to significantly add to the beneficial effects on sinus rhythm maintenance of PVI ablation alone; and CFAE ablation was associated with higher incidence of subsequent AT/AFL. PMID:27764185

  8. Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Andrea Sartore-Bianchi

    Full Text Available BACKGROUND: KRAS mutations occur in 35-45% of metastatic colorectal cancers (mCRC and preclude responsiveness to EGFR-targeted therapy with cetuximab or panitumumab. However, less than 20% patients displaying wild-type KRAS tumors achieve objective response. Alterations in other effectors downstream of the EGFR, such as BRAF, and deregulation of the PIK3CA/PTEN pathway have independently been found to give rise to resistance. We present a comprehensive analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression in mCRC patients treated with cetuximab or panitumumab, with the aim of clarifying the relative contribution of these molecular alterations to resistance. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyzed objective tumor response, progression-free (PFS and overall survival (OS together with the mutational status of KRAS, BRAF, PIK3CA and expression of PTEN in 132 tumors from cetuximab or panitumumab treated mCRC patients. Among the 106 non-responsive patients, 74 (70% had tumors with at least one molecular alteration in the four markers. The probability of response was 51% (22/43 among patients with no alterations, 4% (2/47 among patients with 1 alteration, and 0% (0/24 for patients with > or =2 alterations (p or =2 molecular alteration(s (p<0.001. CONCLUSIONS/SIGNIFICANCE: When expression of PTEN and mutations of KRAS, BRAF and PIK3CA are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to anti-EGFR therapies can be identified. We propose to define as 'quadruple negative', the CRCs lacking alterations in KRAS, BRAF, PTEN and PIK3CA. Comprehensive molecular dissection of the EGFR signaling pathways should be considered to select mCRC patients for cetuximab- or panitumumab-based therapies.

  9. Evaluation of Factors Affecting Continuous Performance Test Identical Pairs Version Score of Schizophrenic Patients in a Japanese Clinical Sample

    Directory of Open Access Journals (Sweden)

    Takayoshi Koide

    2012-01-01

    Full Text Available Aim. Cognitive impairment in schizophrenia strongly relates to social outcome and is a good candidate for endophenotypes. When we accurately measure drug efficacy or effects of genes or variants relevant to schizophrenia on cognitive impairment, clinical factors that can affect scores on cognitive tests, such as age and severity of symptoms, should be considered. To elucidate the effect of clinical factors, we conducted multiple regression analysis using scores of the Continuous Performance Test Identical Pairs Version (CPT-IP, which is often used to measure attention/vigilance in schizophrenia. Methods. We conducted the CPT-IP (4-4 digit and examined clinical information (sex, age, education years, onset age, duration of illness, chlorpromazine-equivalent dose, and Positive and Negative Symptom Scale (PANSS scores in 126 schizophrenia patients in Japanese population. Multiple regression analysis was used to evaluate the effect of clinical factors. Results. Age, chlorpromazine-equivalent dose, and PANSS-negative symptom score were associated with mean d′ score in patients. These three clinical factors explained about 28% of the variance in mean d′ score. Conclusions. As conclusion, CPT-IP score in schizophrenia patients is influenced by age, chlorpromazine-equivalent dose and PANSS negative symptom score.

  10. Efficacy and safety of monoclonal antibodies targeting interleukin-17 pathway for inflammatory arthritis: a meta-analysis of randomized controlled clinical trials

    Directory of Open Access Journals (Sweden)

    Wei M

    2016-09-01

    Full Text Available Min Wei,1 Dongmei Duan21Department of Orthopedics, 2Department of Traditional Chinese Medicine, People’s Liberation Army General Hospital, Beijing, People’s Republic of China Abstract: T-helper 17 (Th17 pathway plays an important and distinct role in autoimmunity and inflammation. A growing body of evidence demonstrates that interleukin-17 (IL-17 is also synthesized in inflammatory arthritis tissues and exerts potent proinflammatory and joint-destructive activities. Clinical studies have been performed to evaluate the therapeutic efficacy of antibodies blocking the IL-17 signaling pathway in patients with rheumatoid arthritis (RA. In this study, we performed a meta-analysis to systematically evaluate the clinical effects of IL-17 antibodies in RA patients. By searching PubMed, five randomized, placebo-controlled randomized controlled clinical trials that tested three antibodies against IL-17A (LY2439821 and secukinumab/AIN457 and the IL-17A receptor (brodalumab were identified. The primary outcomes that were analyzed include American College of Rheumatology (ACR Improvement Criteria and Disease Activity Score in 28 joints (DAS28. Meanwhile, the safety and adverse effects were also systematically analyzed. The results of the meta-analysis demonstrated that IL-17 antibody is effective in ameliorating the RA symptoms. Specifically, IL-17-blocking antibody significantly reduced ACR20 and ACR50. It also dramatically reduced DAS28, an index that measures tenderness and swelling severity of joints. The side effects of and intolerance to the antibody treatment were higher than those in the placebo control. The analysis result provides evidence-based information for clinical use of these agents in the treatment of inflammatory arthritis. Keywords: interleukin-17A, arthritis, meta-analysis, rheumatoid arthritis, clinical trials

  11. Clinical outcome of advanced and metastatic renal cell carcinoma treated with targeted therapy: is there a difference between young and old patients?

    Directory of Open Access Journals (Sweden)

    Zhang G

    2014-11-01

    Full Text Available Guiming Zhang,1,2,* Yao Zhu,1,2,* Dahai Dong,3 Weijie Gu,1,2 Hailiang Zhang,1,2 Lijiang Sun,3 Dingwei Ye1,2 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; 3Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China *These authors contributed equally to this work Background: To assess whether the clinical outcome of advanced and metastatic renal cell carcinoma (mRCC treated with targeted therapy differs between young and old patients. Patients and methods: A total of 327 patients with advanced renal cell carcinoma and mRCC who received targeted therapy in two Chinese clinical centers were analyzed retrospectively. The patients were stratified into three groups: young (aged <45 years, middle-aged (aged 45–64 years, and old (aged ≥65 years. Overall survival (OS and progression-free survival (PFS curves were drawn using the Kaplan–Meier method, and Cox's proportional hazard regression model was used to compare OS and PFS within age groups. Results: There were no significant differences among young, middle-aged, and old groups in terms of OS (P=0.087, whereas PFS in the old group was significantly better than in the young and middle-aged groups (P=0.043. Both OS and PFS in the younger groups (aged <65 years were significantly worse than in the old group (age ≥65 years; median OS, 28.1 vs 28.7 months [P=0.029]; median PFS, 11.4 vs 14 months [P=0.015]. No difference in OS or PFS was found between the young and middle-aged groups. After adjusting for sex, body mass index, smoking status, hypertension, diabetes mellitus, Eastern Cooperative Oncology Group score, history of cytokines, and Fuhrman grade, old age was an independent favorable prognostic factor for OS and PFS compared with younger age (<65 years (OS, hazard ratio, 0.552 [95

  12. Accuracy of target-controlled infusion of sufentanil in clinical anesthesia%两种舒芬太尼靶控输注系统的准确性

    Institute of Scientific and Technical Information of China (English)

    张兴安; 肖彬; 陈宇珂; 吴群林; 邵伟栋; 施冲

    2008-01-01

    Objective To estimate the accuracy of target-controlled infusion (TCI) d sufentanil using the pharmacokinetic parameters proposed by Gepts et al.in clinical anesthesia in Chinese patients.Methods Eighteen ASA Ⅰ or Ⅱ patients aged 21-64 yr undergoing elective surgery under general anesthesia were included in this study.Their body weights were within standard body weight+10%.Radial artery was carmulated before anesthesia for blood sampling.Induction of anesthesia was started with sufentanil TCI.Target plasma concentration (Cp) was set at 0.8 ng/ml.Ten minutes later TCI of propefol was started (Cp=3-4 mg/L).Tracheal intubation was facilitated with vecuronium 0.1 mg/kg as soon as consciousness was lost.Sufentanil TCI was continued at 0.2-0.8 ng/ml (Cp) after induction of anesthesia and terminated at 30 min before the end of surgery.Arterial blood samples were obtained before and at 1,3,5,10,20,40,60,90,120 and 150 rain after sufentanil TCI was started for determination of plasma sufentanil concentration (by ELISA).For each sample the bias,accuracy,divergence and wobble were calculated.Linear regression analysis was performed between volume of central compartment (V1) and body weight (m).The pharmacokinetic parameters proposd by Gepts were modified based on body weight using XLMEM program developed by Minto and Schnider.Another 12 patients received TCI of sufentanil using the modified pharmacokinetic parametem.Results When sufentanil was administered by TCI using original Gepts pharmacokinetic parameters,86 blood samples were measured (the samples obtained before TCI werenot included).PE =-13.7%-75%,bias=16.7%,accuracy=42.0%.After the parameters were modified based on body weight V1(L)=0.147 m+2.82.In the 12 patients when sufentanil was given by TCI using modified Gepts pharmacokinetic parameters 177 blood samples were measured.PE=-30.0%-37.8%;bias=4.0%;accuracy=22.3%;divergence=-4.4%/h and wobble=20.4%,showing a better correlation between the measured and predicted

  13. Predicting academic performance and clinical competency for international dental students: seeking the most efficient and effective measures.

    Science.gov (United States)

    Stacey, D Graham; Whittaker, John M

    2005-02-01

    Measures used in the selection of international dental students to a U.S. D.D.S. program were examined to identify the grouping that most effectively and efficiently predicted academic performance and clinical competency. Archival records from the International Dental Program (IDP) at Loma Linda University provided data on 171 students who had trained in countries outside the United States. The students sought admission to the D.D.S. degree program, successful completion of which qualified them to sit for U.S. licensure. As with most dental schools, competition is high for admission to the D.D.S. program. The study's goal was to identify what measures contributed to a fair and accurate selection process for dental school applicants from other nations. Multiple regression analyses identified National Board Part II and dexterity measures as significant predictors of academic performance and clinical competency. National Board Part I, TOEFL, and faculty interviews added no significant additional help in predicting eventual academic performance and clinical competency.

  14. The role of PPARγ-mediated signalling in skin biology and pathology: new targets and opportunities for clinical dermatology.

    Science.gov (United States)

    Ramot, Yuval; Mastrofrancesco, Arianna; Camera, Emanuela; Desreumaux, Pierre; Paus, Ralf; Picardo, Mauro

    2015-04-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that modulate the expression of multiple different genes involved in the regulation of lipid, glucose and amino acid metabolism. PPARs and cognate ligands also regulate important cellular functions, including cell proliferation and differentiation, as well as inflammatory responses. This includes a role in mediating skin and pilosebaceous unit homoeostasis: PPARs appear to be essential for maintaining skin barrier permeability, inhibit keratinocyte cell growth, promote keratinocyte terminal differentiation and regulate skin inflammation. They also may have protective effects on human hair follicle (HFs) epithelial stem cells, while defects in PPARγ-mediated signalling may promote the death of these stem cells and thus facilitate the development of cicatricial alopecia (lichen planopilaris). Overall, however, selected PPARγ modulators appear to act as hair growth inhibitors that reduce the proliferation and promote apoptosis of hair matrix keratinocytes. The fact that commonly prescribed PPARγ-modulatory drugs of the thiazolidine-2,4-dione class can exhibit a battery of adverse cutaneous effects underscores the importance of distinguishing beneficial from clinically undesired cutaneous activities of PPARγ ligands and to better understand on the molecular level how PPARγ-regulated cutaneous lipid metabolism and PPARγ-mediated signalling impact on human skin physiology and pathology. Surely, the therapeutic potential that endogenous and exogenous PPARγ modulators may possess in selected skin diseases, ranging from chronic inflammatory hyperproliferative dermatoses like psoriasis and atopic dermatitis, via scarring alopecia and acne can only be harnessed if the complexities of PPARγ signalling in human skin and its appendages are systematically dissected. PMID:25644500

  15. The Effects of Sex Steroids on Spatial Performance: A Review and an Experimental Clinical Investigation.

    Science.gov (United States)

    Liben, Lynn S.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan; Schwab, Jacqueline; Dubas, Judith Semon; Demers, Laurence M.; Lookingbill, Georgia; D'Arcangelo, M. Rose; Krogh, Holleen R.; Kulin, Howard E.

    2002-01-01

    Investigated the relationship between sex hormones and spatial performance among adolescents treated with sex steroids for delayed puberty. Found that spatial performance varied according to gender but did not vary with levels of actively circulating sex steroids. Reviewed physiological mechanisms, developmental periods, and past empirical work…

  16. The Pitfalls of Collegial Coaching: An Analysis of Collegial Coaching in Medical Education and Its Influence on Stimulating Reflection and Performance of Novice Clinical Teachers

    Science.gov (United States)

    Truijen, Karin J. P.; van Woerkom, Marianne

    2008-01-01

    Purpose: Competent clinical teachers are essential for clinical teaching. According to the literature, coaching can contribute to improved levels of reflection and better performance of clinical teachers. By engaging in a dialogue about coachee's teaching behaviour, coaches can stimulate reflection of novice teachers. This study aims to gain…

  17. The value of the UK Clinical Aptitude Test in predicting pre-clinical performance: a prospective cohort study at Nottingham Medical School

    Directory of Open Access Journals (Sweden)

    James David

    2010-07-01

    Full Text Available Abstract Background The UK Clinical Aptitude Test (UKCAT was introduced in 2006 as an additional tool for the selection of medical students. It tests mental ability in four distinct domains (Quantitative Reasoning, Verbal Reasoning, Abstract Reasoning, and Decision Analysis, and the results are available to students and admissions panels in advance of the selection process. As yet the predictive validity of the test against course performance is largely unknown. The study objective was to determine whether UKCAT scores predict performance during the first two years of the 5-year undergraduate medical course at Nottingham. Methods We studied a single cohort of students, who entered Nottingham Medical School in October 2007 and had taken the UKCAT. We used linear regression analysis to identify independent predictors of marks for different parts of the 2-year preclinical course. Results Data were available for 204/260 (78% of the entry cohort. The UKCAT total score had little predictive value. Quantitative Reasoning was a significant independent predictor of course marks in Theme A ('The Cell', (p = 0.005, and Verbal Reasoning predicted Theme C ('The Community' (p Conclusion This limited study from a single entry cohort at one medical school suggests that the predictive value of the UKCAT, particularly the total score, is low. Section scores may predict success in specific types of course assessment. The ultimate test of validity will not be available for some years, when current cohorts of students graduate. However, if this test of mental ability does not predict preclinical performance, it is arguably less likely to predict the outcome in the clinical years. Further research from medical schools with different types of curriculum and assessment is needed, with longitudinal studies throughout the course.

  18. Evaluation of Effective Factors on the Clinical Performance of General Surgeons in Tehran University of Medical Science, 2015

    Science.gov (United States)

    Farzianpour, Fereshteh; Mohamadi, Efat; najafpour, Zhila; Yousefinezhadi, Taraneh; Forootan, Sara; Foroushani, Abbas Rahimi

    2016-01-01

    Background and Objective: Existence of doctors with high performance is one of the necessary conditions to provide high quality services. There are different motivations, which could affect their performance. Recognizing Factors which effect the performance of doctors as an effective force in health care centers is necessary. The aim of this article was evaluate the effective factors which influence on clinical performance of general surgery of Tehran University of Medical Sciences in 2015. Methods: This is a cross-sectional qualitative-quantitative study. This research conducted in 3 phases-phases I: (use of library studies and databases to collect data), phase II: localization of detected factors in first phase by using the Delphi technique and phase III: prioritizing the affecting factors on performance of doctors by using qualitative interviews. Results: 12 articles were analyzed from 300 abstracts during the evaluation process. The output of assessment identified 23 factors was sent to surgeons and their assistants for obtaining their opinions. Quantitative analysis of the findings showed that “work qualification” (86.1%) and “managers and supervisors style” (50%) have respectively the most and the least impact on the performance of doctors. Finally 18 effective factors were identified and prioritized in the performance of general surgeons. Conclusion: The results showed that motivation and performance is not a single operating parameter and it depends on several factors according to cultural background. Therefore it is necessary to design, implementation and monitoring based on key determinants of effective interventions due to cultural background. PMID:27157161

  19. Multi-laboratory evaluations of the performance of Catellicoccus marimammalium PCR assays developed to target gull fecal sources

    Science.gov (United States)

    Here we report results from a multi-laboratory (n=11) evaluation of four different PCR methods targeting the 16S rRNA gene of Catellicoccus marimammalium used to detect fecal contamination from birds in coastal environments. The methods included conventional end-point PCR, a SYBR...

  20. Targeting poly(ADP-ribose)polymerase1 in neurological diseases: A promising trove for new pharmacological interventions to enter clinical translation.

    Science.gov (United States)

    Sriram, Chandra Shekhar; Jangra, Ashok; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Bezbaruah, Babul Kumar

    2014-10-01

    The highly conserved abundant nuclear protein poly(ADP-ribose)polymerase1 (PARP1) functions at the center of cellular stress response and is mainly implied in DNA damage repair mechanism. Apart from its involvement in DNA damage repair, it does sway multiple vital cellular processes such as cell death pathways, cell aging, insulator function, chromatin modification, transcription and mitotic apparatus function. Since brain is the principal organ vulnerable to oxidative stress and inflammatory responses, upon stress encounters robust DNA damage can occur and intense PARP1 activation may result that will lead to various CNS diseases. In the context of soaring interest towards PARP1 as a therapeutic target for newer pharmacological interventions, here in the present review, we are attempting to give a silhouette of the role of PARP1 in the neurological diseases and the potential of its inhibitors to enter clinical translation, along with its structural and functional aspects. PMID:25049175

  1. The impact of Gross Tumor Volume (GTV) and Clinical Target Volume (CTV) definition on the total accuracy in radiotherapy. Theoretical aspects and practical experiences

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, E.; Hess, C.F. [Dept. of Radiation Therapy, Univ. of Goettingen (Germany)

    2003-01-01

    Aim: To evaluate the impact of interobserver variability in the contouring of gross tumor volumes (GTVs) and clinical target volumes (CTVs) on the global geometric accuracy in radiation therapy. Material and Methods: In a review of the currently available literature, the magnitude of interobserver variability is analyzed, causes and consequences are discussed. Uncertainties due to inconsistencies in contouring are related to other sources of geometric errors, particularly patient positioning and organ motion. Results: Interobserver variability is a major - for some tumor locations probably the largest - factor contributing to geometric inaccuracy. Causes are multifactorial and include image- and observer-related factors, such as the subjective interpretation of image information. Conclusion: Consequences to reduce interobserver variability are proposed, among others the selection of adequate imaging modalities, intensified radiologic training, and the use of telecommunication tools. (orig.)

  2. Narrative descriptions should replace grades and numerical ratings for clinical performance in medical education in the United States

    Directory of Open Access Journals (Sweden)

    Janice Lynn Hanson

    2013-11-01

    Full Text Available Background: In medical education, evaluation of clinical performance is based almost universally on rating scales for defined aspects of performance and scores on examinations and checklists. Unfortunately, scores and grades do not capture progress and competence among learners in the complex tasks and roles required to practice medicine. While the literature suggests serious problems with the validity and reliability of ratings of clinical performance based on numerical scores, the critical issue is not that judgments about what is observed vary from rater to rater but that these judgments are lost when translated into numbers on a scale. As the Next Accreditation System of the Accreditation Council on Graduate Medical Education (ACGME takes effect, medical educators have an opportunity to create new processes of evaluation to document and facilitate progress of medical learners in the required areas of competence.Proposal and initial experience: Narrative descriptions of learner performance in the clinical environment, gathered using a framework for observation that builds a shared understanding of competence among the faculty, promise to provide meaningful qualitative data closely linked to the work of physicians. With descriptions grouped in categories and matched to milestones, core faculty can place each learner along the milestones’ continua of progress. This provides the foundation for meaningful feedback to facilitate the progress of each learner as well as documentation of progress toward competence.Implications: This narrative evaluation system addresses educational needs as well as the goals of the Next Accreditation System for explicitly documented progress. Educators at other levels of education and in other professions experience similar needs for authentic assessment and, with meaningful frameworks that describe roles and tasks, may also find useful a system built on descriptions of learner performance in actual work settings

  3. Clinical and epidemiological features of typhoid fever in Pemba, Zanzibar: assessment of the performance of the WHO case definitions.

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    Kamala Thriemer

    Full Text Available BACKGROUND: The gold standard for diagnosis of typhoid fever is blood culture (BC. Because blood culture is often not available in impoverished settings it would be helpful to have alternative diagnostic approaches. We therefore investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever. METHODOLOGY/PRINCIPAL FINDINGS: Participants with a body temperature ≥37.5°C or a history of fever were enrolled over 17 to 22 months in three hospitals on Pemba Island, Tanzania. Clinical signs and symptoms of participants upon presentation as well as blood and serum for BC and Widal testing were collected. Clinical signs and symptoms of typhoid fever cases were compared to other cases of invasive bacterial diseases and BC negative participants. The relationship of typhoid fever cases with rainfall, temperature, and religious festivals was explored. The performance of the WHO case definitions for suspected and probable typhoid fever and a local cut off titre for the Widal test was assessed. 79 of 2209 participants had invasive bacterial disease. 46 isolates were identified as typhoid fever. Apart from a longer duration of fever prior to admission clinical signs and symptoms were not significantly different among patients with typhoid fever than from other febrile patients. We did not detect any significant seasonal patterns nor correlation with rainfall or festivals. The sensitivity and specificity of the WHO case definition for suspected and probable typhoid fever were 82.6% and 41.3% and 36.3 and 99.7% respectively. Sensitivity and specificity of the Widal test was 47.8% and 99.4 both forfor O-agglutinin and H- agglutinin at a cut-off titre of 1:80. CONCLUSIONS/SIGNIFICANCE: Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test.

  4. Clinical Genotyping of Non-Small Cell Lung Cancers Using Targeted Next-Generation Sequencing: Utility of Identifying Rare and Co-mutations in Oncogenic Driver Genes.

    Science.gov (United States)

    Tafe, Laura J; Pierce, Kirsten J; Peterson, Jason D; de Abreu, Francine; Memoli, Vincent A; Black, Candice C; Pettus, Jason R; Marotti, Jonathan D; Gutmann, Edward J; Liu, Xiaoying; Shirai, Keisuke; Dragnev, Konstantin H; Amos, Christopher I; Tsongalis, Gregory J

    2016-09-01

    Detection of somatic mutations in non-small cell lung cancers (NSCLCs), especially adenocarcinomas, is important for directing patient care when targeted therapy is available. Here, we present our experience with genotyping NSCLC using the Ion Torrent Personal Genome Machine (PGM) and the AmpliSeq Cancer Hotspot Panel v2. We tested 453 NSCLC samples from 407 individual patients using the 50 gene AmpliSeq Cancer Hotspot Panel v2 from May 2013 to July 2015. Using 10 ng of DNA, up to 11 samples were simultaneously sequenced on the Ion Torrent PGM (316 and 318 chips). We identified variants with the Ion Torrent Variant Caller Plugin, and Golden Helix's SVS software was used for annotation and prediction of the significance of the variants. Three hundred ninety-eight samples were successfully sequenced (12.1% failure rate). In all, 633 variants in 41 genes were detected with a median of 2 (range of 0 to 7) variants per sample. Mutations detected in BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA were considered potentially actionable and were identified in 237 samples, most commonly in KRAS (37.9%), EGFR (11.1%), BRAF (4.8%), and PIK3CA (4.3%). In our patient population, all mutations in EGFR, KRAS, and BRAF were mutually exclusive. The Ion Torrent Ampliseq technology can be utilized on small biopsy and cytology specimens, requires very little input DNA, and can be applied in clinical laboratories for genotyping of NSCLC. This targeted next-generation sequencing approach allows for detection of common and also rare mutations that are clinically actionable in multiple patients simultaneously. PMID:27659017

  5. A chemical proteomics approach for the search of pharmacological targets of the antimalarial clinical candidate albitiazolium in Plasmodium falciparum using photocrosslinking and click chemistry.

    Science.gov (United States)

    Penarete-Vargas, Diana Marcela; Boisson, Anaïs; Urbach, Serge; Chantelauze, Hervé; Peyrottes, Suzanne; Fraisse, Laurent; Vial, Henri J

    2014-01-01

    Plasmodium falciparum is responsible for severe malaria which is one of the most prevalent and deadly infectious diseases in the world. The antimalarial therapeutic arsenal is hampered by the onset of resistance to all known pharmacological classes of compounds, so new drugs with novel mechanisms of action are critically needed. Albitiazolium is a clinical antimalarial candidate from a series of choline analogs designed to inhibit plasmodial phospholipid metabolism. Here we developed an original chemical proteomic approach to identify parasite proteins targeted by albitiazolium during their native interaction in living parasites. We designed a bifunctional albitiazolium-derived compound (photoactivable and clickable) to covalently crosslink drug-interacting parasite proteins in situ followed by their isolation via click chemistry reactions. Mass spectrometry analysis of drug-interacting proteins and subsequent clustering on gene ontology terms revealed parasite proteins involved in lipid metabolic activities and, interestingly, also in lipid binding, transport, and vesicular transport functions. In accordance with this, the albitiazolium-derivative was localized in the endoplasmic reticulum and trans-Golgi network of P. falciparum. Importantly, during competitive assays with albitiazolium, the binding of choline/ethanolamine phosphotransferase (the enzyme involved in the last step of phosphatidylcholine synthesis) was substantially displaced, thus confirming the efficiency of this strategy for searching albitiazolium targets. PMID:25470252

  6. A chemical proteomics approach for the search of pharmacological targets of the antimalarial clinical candidate albitiazolium in Plasmodium falciparum using photocrosslinking and click chemistry.

    Science.gov (United States)

    Penarete-Vargas, Diana Marcela; Boisson, Anaïs; Urbach, Serge; Chantelauze, Hervé; Peyrottes, Suzanne; Fraisse, Laurent; Vial, Henri J

    2014-01-01

    Plasmodium falciparum is responsible for severe malaria which is one of the most prevalent and deadly infectious diseases in the world. The antimalarial therapeutic arsenal is hampered by the onset of resistance to all known pharmacological classes of compounds, so new drugs with novel mechanisms of action are critically needed. Albitiazolium is a clinical antimalarial candidate from a series of choline analogs designed to inhibit plasmodial phospholipid metabolism. Here we developed an original chemical proteomic approach to identify parasite proteins targeted by albitiazolium during their native interaction in living parasites. We designed a bifunctional albitiazolium-derived compound (photoactivable and clickable) to covalently crosslink drug-interacting parasite proteins in situ followed by their isolation via click chemistry reactions. Mass spectrometry analysis of drug-interacting proteins and subsequent clustering on gene ontology terms revealed parasite proteins involved in lipid metabolic activities and, interestingly, also in lipid binding, transport, and vesicular transport functions. In accordance with this, the albitiazolium-derivative was localized in the endoplasmic reticulum and trans-Golgi network of P. falciparum. Importantly, during competitive assays with albitiazolium, the binding of choline/ethanolamine phosphotransferase (the enzyme involved in the last step of phosphatidylcholine synthesis) was substantially displaced, thus confirming the efficiency of this strategy for searching albitiazolium targets.

  7. Targeting Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts To Lead Small Molecule Inhibitors to Clinical Trials.

    Science.gov (United States)

    Fiore, Mario; Forli, Stefano; Manetti, Fabrizio

    2016-04-28

    The p38/MAPK-activated kinase 2 (MK2) pathway is involved in a series of pathological conditions (inflammation diseases and metastasis) and in the resistance mechanism to antitumor agents. None of the p38 inhibitors entered advanced clinical trials because of their unwanted systemic side effects. For this reason, MK2 was identified as an alternative target to block the pathway but avoiding the side effects of p38 inhibition. However, ATP-competitive MK2 inhibitors suffered from low solubility, poor cell permeability, and scarce kinase selectivity. Fortunately, non-ATP-competitive inhibitors of MK2 have been already discovered that allowed circumventing the selectivity issue. These compounds showed the additional advantage to be effective at lower concentrations in comparison to the ATP-competitive inhibitors. Therefore, although the significant difficulties encountered during the development of these inhibitors, MK2 is still considered as an attractive target to treat inflammation and related diseases to prevent tumor metastasis and to increase tumor sensitivity to chemotherapeutics.

  8. Capecitabine in combination with novel targeted agents in the management of metastatic breast cancer: underlying rationale and results of clinical trials.

    Science.gov (United States)

    Tripathy, Debu

    2007-04-01

    At present there is no established standard of care for metastatic breast cancer and prognosis remains poor, although the use of newer chemotherapeutic regimens has led to modest improvements in survival. Capecitabine, an oral prodrug of 5-fluorouracil, is a promising addition to these approaches, having already shown single-agent activity against metastatic breast cancer. Following a pivotal trial demonstrating that capecitabine confers increased survival when used in combination with docetaxel, it is being investigated intensively in combined regimens using other standard chemotherapeutic agents, as well as with novel molecularly targeted therapies. Among the novel agents, the most intensively studied in combination with capecitabine is trastuzumab. Despite preclinical data suggesting that these two agents might not show additive effects, clinical trials have been very encouraging for both heavily pretreated patients and for patients receiving first-line therapy in the metastatic setting. This work is being further extended in an ongoing trial in the neoadjuvant setting. An initial trial in combination with bevacizumab, enrolling heavily pretreated patients, was less successful, but following the example of the E2100 trial, this combination is being re-examined in less heavily treated patients. In addition, this review discusses ongoing trials with an array of newer molecularly targeted agents. Significant improvement in time to progression has already been demonstrated in the combination of lapatinib and capecitabine compared with capecitabine monotherapy; for the most part, however, these trials are still in early stages.

  9. A chemical proteomics approach for the search of pharmacological targets of the antimalarial clinical candidate albitiazolium in Plasmodium falciparum using photocrosslinking and click chemistry.

    Directory of Open Access Journals (Sweden)

    Diana Marcela Penarete-Vargas

    Full Text Available Plasmodium falciparum is responsible for severe malaria which is one of the most prevalent and deadly infectious diseases in the world. The antimalarial therapeutic arsenal is hampered by the onset of resistance to all known pharmacological classes of compounds, so new drugs with novel mechanisms of action are critically needed. Albitiazolium is a clinical antimalarial candidate from a series of choline analogs designed to inhibit plasmodial phospholipid metabolism. Here we developed an original chemical proteomic approach to identify parasite proteins targeted by albitiazolium during their native interaction in living parasites. We designed a bifunctional albitiazolium-derived compound (photoactivable and clickable to covalently crosslink drug-interacting parasite proteins in situ followed by their isolation via click chemistry reactions. Mass spectrometry analysis of drug-interacting proteins and subsequent clustering on gene ontology terms revealed parasite proteins involved in lipid metabolic activities and, interestingly, also in lipid binding, transport, and vesicular transport functions. In accordance with this, the albitiazolium-derivative was localized in the endoplasmic reticulum and trans-Golgi network of P. falciparum. Importantly, during competitive assays with albitiazolium, the binding of choline/ethanolamine phosphotransferase (the enzyme involved in the last step of phosphatidylcholine synthesis was substantially displaced, thus confirming the efficiency of this strategy for searching albitiazolium targets.

  10. Clinical Studies of Real-Time Monitoring of Lithotripter Performance Using Passive Acoustic Sensors

    Science.gov (United States)

    Leighton, T. G.; Fedele, F.; Coleman, A. J.; McCarthy, C.; Ryves, S.; Hurrell, A. M.; De Stefano, A.; White, P. R.

    2008-09-01

    This paper describes the development and clinical testing of a passive device which monitors the passive acoustic emissions generated within the patient's body during Extracorporeal Shock Wave Lithotripsy (ESWL). Designed and clinically tested so that it can be operated by a nurse, the device analyses the echoes generated in the body in response to each ESWL shock, and so gives real time shock-by-shock feedback on whether the stone was at the focus of the lithotripter, and if so whether the previous shock contributed to stone fragmentation when that shock reached the focus. A shock is defined as being `effective' if these two conditions are satisfied. Not only can the device provide real-time feedback to the operator, but the trends in shock `effectiveness' can inform treatment. In particular, at any time during the treatment (once a statistically significant number of shocks have been delivered), the percentage of shocks which were `effective' provides a treatment score TS(t) which reflec