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 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...... the conditions upon which the market mechanism is performing within organizations. This paper aims to contribute to research by providing more insight to the conditions for the use of external benchmarking as an element in performance management in organizations. Our study explores a particular type...

  6. Targeting targeted agents: open issues for clinical trial design

    Directory of Open Access Journals (Sweden)

    Giannarelli Diana

    2009-05-01

    Full Text Available Abstract Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present. Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

  7. 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

  8. 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.

  9. 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

  10. Performance Targets and External Market Prices

    DEFF Research Database (Denmark)

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

    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 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...... 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....

  11. 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....

  12. Clinical Concerns About Clinical Performance Measurement

    OpenAIRE

    Werner, Rachel M.; Asch, David A.

    2007-01-01

    Performance measurement has become one of the foundations of current efforts to improve health care quality and has successfully increased compliance with practice guidelines in many settings. Despite the successes of performance measurement, many physicians remain apprehensive about its use because performance measurement “gets in the way of” delivering good care. There are several reasons clinicians might feel this way. First, performance measurement is increasingly being extended to areas ...

  13. 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....

  14. 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.

  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. Setting key performance targets for Croatian shipyards

    Directory of Open Access Journals (Sweden)

    Danijela Rabar

    2015-03-01

    Full Text Available The aim of this paper is to use the Data Envelopment Analysis (DEA method to measure and analyze different relative efficiencies of five Croatian shipyards. The indicators are chosen to capture different aspects of shipbuilding performance in Croatia. Window analysis is used to determine shipyard efficiency and observe possible changes in shipyard efficiency over time. This leads to identifying a subset of efficient best practice shipyards, whereas for others the magnitude of their inefficiency is ascertained along with the specified efficient input and output targets. The importance of window analysis is that its results serve as an early warning system to all inefficient shipyards. In identifying the sources of inefficiencies and formulating proposals for improving shipyard performance observed over a six-year period (2007-2012, the results presented in this paper can be used to enhance and alter decisions.

  17. MATERIALS PERFORMANCE TARGETED THRUST FY 2004 PROJECTS

    International Nuclear Information System (INIS)

    The Yucca Mountain site was recommended by the President to be a geological repository for commercial spent nuclear fuel and high-level radioactive waste. The multi-barrier approach was adopted for assessing and predicting system behavior, including both natural barriers and engineered barriers. A major component of the long-term strategy for safe disposal of nuclear waste is first to completely isolate the radionuclides in waste packages for long times and then to greatly retard the egress and transport of radionuclides from penetrated packages. The goal of the Materials Performance Targeted Thrust program is to further enhance the understanding of the role of engineered barriers in waste isolation. In addition, the Thrust will explore technical enhancements and seek to offer improvements in materials costs and reliability

  18. 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

  19. Clinical implementation of target tracking by breathing synchronized delivery

    International Nuclear Information System (INIS)

    Target-tracking techniques can be categorized based on the mechanism of the feedback loop. In real time tracking, breathing-delivery phase correlation is provided to the treatment delivery hardware. Clinical implementation of target tracking in real time requires major hardware modifications. In breathing synchronized delivery (BSD), the patient is guided to breathe in accordance with target motion derived from four-dimensional computed tomography (4D-CT). Violations of mechanical limitations of hardware are to be avoided at the treatment planning stage. Hardware modifications are not required. In this article, using sliding window IMRT delivery as an example, we have described step-by-step the implementation of target tracking by the BSD technique: (1) A breathing guide is developed from patient's normal breathing pattern. The patient tries to reproduce this guiding cycle by following the display in the goggles; (2) 4D-CT scans are acquired at all the phases of the breathing cycle; (3) The average tumor trajectory is obtained by deformable image registration of 4D-CT datasets and is smoothed by Fourier filtering; (4) Conventional IMRT planning is performed using the images at reference phase (full exhalation phase) and a leaf sequence based on optimized fluence map is generated; (5) Assuming the patient breathes with a reproducible breathing pattern and the machine maintains a constant dose rate, the treatment process is correlated with the breathing phase; (6) The instantaneous average tumor displacement is overlaid on the dMLC position at corresponding phase; and (7) DMLC leaf speed and acceleration are evaluated to ensure treatment delivery. A custom-built mobile phantom driven by a computer-controlled stepper motor was used in the dosimetry verification. A stepper motor was programmed such that the phantom moved according to the linear component of tumor motion used in BSD treatment planning. A conventional plan was delivered on the phantom with and without

  20. Method for evaluating performance of clinical pharmacists.

    Science.gov (United States)

    Schumock, G T; Leister, K A; Edwards, D; Wareham, P S; Burkhart, V D

    1990-01-01

    A performance-evaluation process that satisfies Joint Commission on Accreditation of Healthcare Organizations criteria and state policies is described. A three-part, criteria-based, weighted performance-evaluation tool specific for clinical pharmacists was designed for use in two institutions affiliated with the University of Washington. The three parts are self-appraisal and goal setting, peer evaluation, and supervisory evaluation. Objective criteria within each section were weighted to reflect the relative importance of that characteristic to the job that the clinical pharmacist performs. The performance score for each criterion is multiplied by the weighted value to produce an outcome score. The peer evaluation and self-appraisal/goal-setting parts of the evaluation are completed before the formal performance-evaluation interview. The supervisory evaluation is completed during the interview. For this evaluation, supervisors use both the standard university employee performance evaluation form and a set of specific criteria applicable to the clinical pharmacists in these institutions. The first performance evaluations done under this new system were conducted in May 1989. Pharmacists believed that the new system was more objective and allowed more interchange between the manager and the pharmacist. The peer-evaluation part of the system was seen as extremely constructive. This three-part, criteria-based system for evaluation of the job performance of clinical pharmacists could easily be adopted by other pharmacy departments. PMID:2301420

  1. 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.

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

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Kopp, Tamara; Riedl, Elisabeth; Bangert, Christine;

    2015-01-01

    advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized......, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index...... clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples....

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

    Science.gov (United States)

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

    2016-03-01

    In spite of decades of research, cancer survival has increased only modestly. This is because most research is based on models of primary tumors. Slow recognition has begun that disseminated, dormant cancer cells (micrometastatic cells) that are generally resistant to chemotherapy are the culprits in recurrence, and until these are targeted effectively we can expect only slow progress in increasing overall survival from cancer. This paper reviews efforts to understand the mechanisms by which cancer cells can become dormant, and thereby identify potential targets and drugs either on the market or in clinical trials that purport to prevent metastasis. This review targets the most recent literature because several excellent reviews have covered the literature from more than two years ago. The paper also describes recent work in the authors' laboratories to develop a screening-based approach that does not require understanding of mechanisms of action or the molecular target. Success of this approach shows that targeting micrometastatic cells is definitely feasible. PMID:26929788

  7. [Performing madness: the clinic as stage].

    Science.gov (United States)

    Herrn, Rainer; Friedland, Alexander

    2014-12-01

    In the second half of the nine- teenth century, clinical demonstrations became the dominant teaching method in psychiatry, playing a key role in medical-professional disputes, as well. This paper traces this widely used though historiographically neglected practice of knowledge implementation and mediation, as demonstrated in the psychiatric clinic of the Berlin Charité (Psychiatrische und Nervenklinik der Berliner Charité) from 1881 to 1927. Documentation of this practice, found within individual medical records, forms the basis of this research. The concept of 'theatricality' assists in uncovering the dramatic quality of the clinical demonstration: Psychiatric knowledge was not simply disseminated through such a practice; rather, such knowledge was first performatively created through the very logic of its presentation of exemplary patient histories, as well as through the examination and diagnostic positioning of its patients. The 'success' of such presentations depended on many variables, related to staff, time, place, and other situational factors. These include the presence of appropriate lecture halls, the availability and calculated selection of patients, and the employment of specific performative techniques by doctors for the sake of producing desired results. As one effect, clinical demonstrations also encouraged patients to both learn and rehearse behavior considered relevant to the particular diagnosis that was to be demonstrated. PMID:25671967

  8. 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......, 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...

  9. Clinical development of cancer therapeutics that target metabolism.

    Science.gov (United States)

    Clem, B F; O'Neal, J; Klarer, A C; Telang, S; Chesney, J

    2016-06-01

    Glucose and glutamine metabolism in cancer cells are markedly elevated relative to non-transformed normal cells. This metabolic reprogramming enables the production of adenosine triphosphate and the anabolic precursors needed for survival, growth and motility. The recent observations that mutant oncogenic proteins and the loss of tumor suppressors activate key metabolic enzymes suggest that selective inhibition of these enzymes may yield effective cancer therapeutics with acceptable toxicities. In support of this concept, pre-clinical studies of small molecule antagonists of several metabolic enzymes in tumor-bearing mice have demonstrated reasonable therapeutic indices. We will review the rationale for targeting metabolic enzymes as a strategy to treat cancer and will detail the results of several recent clinical trials of metabolic inhibitors in advanced cancer patients. PMID:26428335

  10. The design, construction and performance of the MICE target

    International Nuclear Information System (INIS)

    The pion-production target that serves the MICE Muon Beam consists of a titanium cylinder that is dipped into the halo of the ISIS proton beam. The design and construction of the MICE target system are described along with the quality-assurance procedures, electromagnetic drive and control systems, the readout electronics, and the data-acquisition system. The performance of the target is presented together with the particle rates delivered to the MICE Muon Beam. Finally, the beam loss in ISIS generated by the operation of the target is evaluated as a function of the particle rate, and the operating parameters of the target are derived.

  11. The design, construction and performance of the MICE target

    CERN Document Server

    Booth, C N; Howlett, L; Nicholson, R; Overton, E; Robinson, M; Smith, P J; Apollonio, M; Barber, G; Dobbs, A; Leaver, J; Long, K R; Shepherd, B; Adams, D; Capocci, E; McCarron, E; Tarrant, J

    2012-01-01

    The pion-production target that serves the MICE Muon Beam consists of a titanium cylinder that is dipped into the halo of the ISIS proton beam. The design and construction of the MICE target system are described along with the quality-assurance procedures, electromagnetic drive and control systems, the readout electronics, and the data-acquisition system. The performance of the target is presented together with the particle rates delivered to the MICE Muon Beam. Finally, the beam loss in ISIS generated by the operation of the target is evaluated as a function of the particle rate, and the operating parameters of the target are derived.

  12. 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.

  13. Companion diagnostics for targeted cancer drugs - clinical and regulatory aspects.

    Science.gov (United States)

    Olsen, Dana; Jørgensen, Jan Trøst

    2014-01-01

    Companion diagnostics (CDx) holds the promise of improving the predictability of the oncology drug development process and become an important tool for the oncologist in relation to the choice of treatment for the individual patient. A number of drug-diagnostic co-development programs have already been completed successfully, and in the clinic, the use of several targeted cancer drugs is now guided by a CDx. This central role of the CDx assays has attracted the attention of the regulators, and especially the US Food and Drug Administration has been at the forefront in relation to developing regulatory strategies for CDx and the drug-diagnostic co-development project. For an increasing number of cancer patients the treatment selection will depend on the result generated by a CDx assay, and consequently this type of assay has become critical for the care and safety of the patients. In order to secure that the CDx assays have a high degree of analytical and clinical validity, they must undergo an extensive non-clinical and clinical testing before release for routine patient management. This review will give a brief introduction to some of the scientific and medical challenges related to the CDx development with specific emphasis on the regulatory requirements in different regions of the world. PMID:24904822

  14. Companion Diagnostics for Targeted Cancer Drugs - Clinical and Regulatory Aspects

    Directory of Open Access Journals (Sweden)

    Jan TrøstJørgensen

    2014-05-01

    Full Text Available Companion diagnostics (CDx holds the promise of improving the predictability of the oncology drug development process and become an important tool for the oncologist in relation to the choice of treatment for the individual patient. A number of drug-diagnostic co-development programs have already been completed successfully, and in the clinic, the use of several targeted cancer drugs is now guided by a CDx. This central role of the CDx assays has attracted the attention of the regulators, and especially the US FDA has been at the forefront in relation to developing regulatory strategies for CDx and the drug-diagnostic co-development project. For an increasing number of cancer patients the treatment selection will depend on the result generated by a CDx assay, and consequently this type of assay has become critical for the care and safety of the patients. In order to secure that the CDx assays have a high degree of analytical and clinical validity they must undergo an extensive non-clinical and clinical testing before release for routine patient management. This review will give a brief introduction to some of the scientific and medical challenges related to the CDx development with specific emphasis on the regulatory requirements in different regions of the world.  

  15. 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

  16. 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.

  17. 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

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

    International Nuclear Information System (INIS)

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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. LANSCE [Manuel Lujan, Jr. Neutron Scattering Center] target system performance

    International Nuclear Information System (INIS)

    We measured neutron beam fluxes at LANSCE using gold foil activation techniques. We did an extensive computer simulation of the as-built LANSCE Target/Moderator/Reflector/Shield geometry. We 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

  8. Combined Recipe for Clinical Target Volume and Planning Target Volume Margins

    International Nuclear Information System (INIS)

    Purpose: To develop a combined recipe for clinical target volume (CTV) and planning target volume (PTV) margins. Methods and Materials: A widely accepted PTV margin recipe is Mgeo = aΣgeo + bσgeo, with Σgeo and σgeo standard deviations (SDs) representing systematic and random geometric uncertainties, respectively. On the basis of histopathology data of breast and lung tumors, we suggest describing the distribution of microscopic islets around the gross tumor volume (GTV) by a half-Gaussian with SD Σmicro, yielding as possible CTV margin recipe: Mmicro = ƒ(Ni) × Σmicro, with Ni the average number of microscopic islets per patient. To determine ƒ(Ni), a computer model was developed that simulated radiation therapy of a spherical GTV with isotropic distribution of microscopic disease in a large group of virtual patients. The minimal margin that yielded Dmin <95% in maximally 10% of patients was calculated for various Σmicro and Ni. Because Σmicro is independent of Σgeo, we propose they should be added quadratically, yielding for a combined GTV-to-PTV margin recipe: MGTV-PTV = √([aΣgeo]2 + [ƒ(Ni)Σmicro]2) + bσgeo. This was validated by the computer model through numerous simultaneous simulations of microscopic and geometric uncertainties. Results: The margin factor ƒ(Ni) in a relevant range of Σmicro and Ni can be given by: ƒ(Ni) = 1.4 + 0.8log(Ni). Filling in the other factors found in our simulations (a = 2.1 and b = 0.8) yields for the combined recipe: MGTV-PTV = √((2.1Σgeo)2 + ([1.4 + 0.8log(Ni)] × Σmicro)2) + 0.8σgeo. The average margin difference between the simultaneous simulations and the above recipe was 0.2 ± 0.8 mm (1 SD). Calculating Mgeo and Mmicro separately and adding them linearly overestimated PTVs by on average 5 mm. Margin recipes based on tumor control probability (TCP) instead of Dmin criteria yielded similar results. Conclusions: A general recipe for GTV-to-PTV margins is proposed, which shows that CTV and PTV margins

  9. Bioinformatic Challenges in Clinical Diagnostic Application of Targeted Next Generation Sequencing: Experience from Pheochromocytoma.

    Directory of Open Access Journals (Sweden)

    Joakim Crona

    Full Text Available Recent studies have demonstrated equal quality of targeted next generation sequencing (NGS compared to Sanger Sequencing. Whereas these novel sequencing processes have a validated robust performance, choice of enrichment method and different available bioinformatic software as reliable analysis tool needs to be further investigated in a diagnostic setting.DNA from 21 patients with genetic variants in SDHB, VHL, EPAS1, RET, (n=17 or clinical criteria of NF1 syndrome (n=4 were included. Targeted NGS was performed using Truseq custom amplicon enrichment sequenced on an Illumina MiSEQ instrument. Results were analysed in parallel using three different bioinformatics pipelines; (1 Commercially available MiSEQ Reporter, fully automatized and integrated software, (2 CLC Genomics Workbench, graphical interface based software, also commercially available, and ICP (3 an in-house scripted custom bioinformatic tool.A tenfold read coverage was achieved in between 95-98% of targeted bases. All workflows had alignment of reads to SDHA and NF1 pseudogenes. Compared to Sanger sequencing, variant calling revealed a sensitivity ranging from 83 to 100% and a specificity of 99.9-100%. Only MiSEQ reporter identified all pathogenic variants in both sequencing runs.We conclude that targeted next generation sequencing have equal quality compared to Sanger sequencing. Enrichment specificity and the bioinformatic performance need to be carefully assessed in a diagnostic setting. As acceptable accuracy was noted for a fully automated bioinformatic workflow, we suggest that processing of NGS data could be performed without expert bioinformatics skills utilizing already existing commercially available bioinformatics tools.

  10. 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...

  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. Seismic design and evaluation criteria based on target performance goals

    International Nuclear Information System (INIS)

    Seismic design and evaluation criteria have been developed based on target probabilistic performance goals. These criteria include selection of design/evaluation seismic input from probabilistic seismic hazard curves combined with commonly practiced deterministic response evaluation methods and acceptance criteria with controlled levels of conservatism. Conservatism is intentionally introduced in specification of material strengths and capacities, in the allowance of limited inelastic behavior, and by a seismic scale factor. Criteria have been developed following a graded approach for several performance goals ranging from that appropriate for normal-use facilities to that appropriate for facilities involving hazardous or critical operations. Performance goals are comprised of qualitative expressions of acceptable behavior and of quantitative probabilities that acceptable limits of behavior are maintained. The criteria are simple procedures but with a sound, rigorous basis for the achievement of goals

  13. Clinical Challenges to Current Molecularly Targeted Therapies in Lung Cancer

    Science.gov (United States)

    Chhabra, Gagan; Eggert, Ashley; Puri, Neelu

    2016-01-01

    Lung cancer is difficult to treat with a poor prognosis and a five year survival of 15%. Current molecularly targeted therapies are initially effective in non-small cell lung cancer (NSCLC) patients; however, they are plagued with difficulties including induced resistance and small therapeutically responsive populations. This mini review describes the mechanism of resistance to several molecularly targeted therapies which are currently being used to treat NSCLC. The major targets discussed are c-Met, EGFR, HER2, ALK, VEGFR, and BRAF. The first generation tyrosine kinase inhibitors (TKIs) resulted in resistance; however, second and third generation TKIs are being developed, which are generally more efficacious and have potential to treat NSCLC patients with resistance to first generation TKIs. Combination therapies could also be effective in preventing TKI resistance in NSCLC patients.

  14. A quantitative way to estimate clinical off-target effects for human membrane brain targets in CNS research and development

    Science.gov (United States)

    Spiros, Athan; Geerts, Hugo

    2012-01-01

    Although many preclinical programs in central nervous system research and development intend to develop highly selective and potent molecules directed at the primary target, they often act upon other off-target receptors. The simple rule of taking the ratios of affinities for the candidate drug at the different receptors is flawed since the affinity of the endogenous ligand for that off-target receptor or drug exposure is not taken into account. We have developed a mathematical receptor competition model that takes into account the competition between active drug moiety and the endogenous neurotransmitter to better assess the off-target effects on postsynaptic receptor activation under the correct target exposure conditions. As an example, we investigate the possible functional effects of the weak off-target effects for dopamine-1 receptor (D1R) in a computer simulation of a dopaminergic cortical synapse that is calibrated using published fast-cyclic rodent voltammetry and human imaging data in subjects with different catechol-O-methyltransferase genotypes. We identify the conditions under which off-target effects at the D1R can lead to clinically detectable consequences on cognitive tests, such as the N-back working memory test. We also demonstrate that certain concentrations of dimebolin (Dimebon), a recently tested Alzheimer drug, can affect D1R activation resulting in clinically detectable cognitive decrease. This approach can be extended to other receptor systems and can improve the selection of clinical candidate compounds by potentially dialing-out harmful off-target effects or dialing-in beneficial off-target effects in a quantitative and controlled way.

  15. 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

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

    OpenAIRE

    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 we...

  17. 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 ...

  18. 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

  19. 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.

  20. 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...

  1. Targeted Therapies for Lung Cancer: Clinical Experience and Novel Agents

    OpenAIRE

    Larsen, Jill E.; Cascone, Tina; Gerber, David E.; Heymach, John V; Minna, John D.

    2011-01-01

    Although lung cancer remains the leading cancer killer in the United States, recently a number of developments indicate future clinical benefit. These include evidence that computed tomography–based screening decreases lung cancer mortality, the use of stereotactic radiation for early-stage tumors, the development of molecular methods to predict chemotherapy sensitivity, and genome-wide expression and mutation analysis data that have uncovered oncogene “addictions” as important therapeutic ta...

  2. 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)

  3. 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

  4. Neutron Production and Nuclear Performance of Spallation Target Systems

    International Nuclear Information System (INIS)

    optimization of geometrically expendable high power target stations will finally rely on general Monte-Carlo particle transport codes having maximum predictive power. The performance and flexibility of program packages like HERMES, LCS or MCNPX and the validation (using our experiments and the literature) is demonstrated. The overall objective of our effort is to obtain a comprehensive understanding and modeling of nuclear reactions in a broad energy region, which are specific to spallation physics aspects. The essential goal can only be accomplished by means of a well-balanced combination of basic cross section measurements, nuclear model simulations and data evaluations. (author)

  5. Impact of target modifications on Magnetized Liner Inertial Fusion performance

    Science.gov (United States)

    Gomez, Matthew; Knapp, Patrick; Sefkow, Adam; Slutz, Stephen; Awe, Thomas; Hansen, Stephanie; Hahn, Kelly; Harding, Eric; Jennings, Christopher; McBride, Ryan; Sinars, Daniel; Rochau, Gregory; Peterson, Kyle

    2015-11-01

    Magnetized Liner Inertial Fusion (MagLIF) is a magnetically-driven fusion concept in which an axial magnetic field and laser heating are used to relax the implosion requirements of inertial confinement fusion. Initial experiments demonstrated the promise of the concept with relatively high yields (primary DD = 2e12), ion temperatures (2.5 keV), and magnetic field-radius products (>0.3 MG-cm). In order to better understand the portions of parameter space in which MagLIF can operate effectively, a series of experiments are being conducted to test the impact of various changes (e.g., laser-entrance-hole window thickness, imploding height of the target, endcap material, laser energy, laser spot size, initial fuel density). The impact of these changes on target performance (primary neutron yield, ion temperature, stagnation volume, etc.) will be discussed. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under Contract No. DE-AC04-94AL85000.

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

    Science.gov (United States)

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

    2016-04-01

    Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy. PMID:26923776

  7. 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

  8. 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

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

    Directory of Open Access Journals (Sweden)

    Laila Akhu-Zaheya

    2015-06-01

    Full Text Available 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 public universities in Jordan participated in the study. Results: The results showed that the mean of stress perceived by students was 45.9. Students’ assignment were perceived as the main source of stress (M= 10.7, SD= 4.5 followed by stress related to patients’ care (M= 10.5, SD= 5.5 and stress from teachers and nursing staff (M= 9.6, SD= 5.3. The lowest source of stress is from students’ lack of professional knowledge and skills (M= 3.96; SD= 2.8. The mean of students’ clinical performance is 73.4%. Students’ perceived stress has a significant negative correlation with students’ clinical performance (r= -.09; p <.05. The results also showed significant negative correlation between stress related to lack of professional knowledge and skills, and stress related to patient care and students’ clinical performance. Conclusion: This study expanded on students’ stress in clinical settings, and warrants further research in assessing its impact on their performance. Teachers should be aware of and help students to overcome and cope with said stress related factors in the clinical settings effectively.

  10. 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.

  11. 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.

  12. The evaluation study of high performance gas target system

    Energy Technology Data Exchange (ETDEWEB)

    Hur, Min Goo; Yang, Seung Dae; Kim, Sang Wook

    2008-06-15

    The object of this study is a improvement of a gas target and targetry for increasing the radioisotope production yields. The main results are as follows 1. Improvement of beam entrance of the gas target : In this work, deep hole grid was designed for improvement of beam entrance. Using FEM(Finite Elements Method) analysis, it was verified that this design is more effective than the old one. 2. Improvement of target gas loading and withdrawing system : For the targetry, Helium gas and vacuum lines was installed for evaluating the production yields. Using these lines, it was proved that the recovery yields was improved and the residual impurity was reduced. 3. Improvement of target cooling efficiency : In case of the cylindrical target, it is more effective to use short length of target cavity for the high production yields. For improving the cooling efficiency, cooling fin was suggested to the target design. It is more effective to put the cooling fins inside the target cavity for the suppressed target pressure and density reduction effect during the proton beam irradiation. In conclusion, the target with fins inside the target cavity was better for high current irradiation and mass RI production.

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

    OpenAIRE

    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 transition influences student performance during the first 2 weeks of clerkships; whether it influences students' overall performance in their first clerkship, and the degree to which the difficulty of t...

  14. 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.

  15. MET targeted therapy for lung cancer: clinical development and future directions

    Directory of Open Access Journals (Sweden)

    Feng Y

    2012-08-01

    Full Text Available Yan Feng,1,2 Patrick C Ma1–31Translational Hematology and Oncology Research, 2Solid Tumor Oncology, 3Aerodigestive Oncology Translational Research, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USAAbstract: MET, the receptor for hepatocyte growth factor, has been identified as a novel promising target in various human malignancies, including lung cancer. Research studies have demonstrated that MET signaling plays important physiologic roles in embryogenesis and early development, whereas its deregulation from an otherwise quiescent signaling state in mature adult tissues can lead to upregulated cell proliferation, survival, scattering, motility and migration, angiogenesis, invasion, and metastasis in tumorigenesis and tumor progression. The MET pathway can be activated through ligand (hepatocyte growth factor, HGF or MET receptor overexpression, genomic amplification, MET mutations, and alternative splicing. A number of novel therapeutic agents that target the MET/hepatocyte growth factor pathway have been tested in early-phase clinical studies with promising results. Phase III studies of MET targeting agents have recently been initiated. This paper will review the MET signaling pathway and biology in lung cancer, and the recent clinical development and advances of MET/hepatocyte growth factor targeting agents. Emphasis will be placed on discussing various unanswered issues and key strategies needed to optimize further clinical development of MET targeting personalized lung cancer therapy.Keywords: MET, HGF, lung cancer, targeted therapy

  16. [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

  17. 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

  18. 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.)

  19. 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.

  20. 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

  1. Appraising the performance of medical technologists in a clinical laboratory.

    Science.gov (United States)

    Ghorpade, J; Chen, M M

    1997-01-01

    Medical technologists and their coworkers serve as a critical link in the delivery of health care, yet their performance typically is appraised in a traditional way, causing stress for both managers and workers. Drawing on Total Quality Management concepts, this article proposes a framework for appraising performance in a clinical laboratory context and shows how it can be used to address the problems that managers face in providing constructive appraisals to laboratory personnel. PMID:10166906

  2. Clinical experiences with molecular targeted therapy in lung cancer in China

    OpenAIRE

    Wang, Yan; Yan SUN

    2015-01-01

    In the past decade, a dramatic shift has been witnessed in cancer therapy in China. Although traditional cytotoxic chemotherapy still remains the treatment of choice for many malignancies, targeted therapies are now a component of treatment for many types of cancer, including lung cancer. As molecular target agents are widely used in clinical practice and relevant studies have been conducted, we have accumulated valuable experience in the treatment strategy for advanced non-small cell lung ca...

  3. 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.

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

    OpenAIRE

    Qian, Yang; Zeng, Zhao-Chong; Ji, Yuan; Xiao, Yin-Ping

    2015-01-01

    Objectives 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). Methods 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 gen...

  5. Measurement of Neuropsychiatric Symptoms in Clinical Trials Targeting Alzheimer's Disease and Related Disorders

    OpenAIRE

    Emmanuel Mulin; Renaud David; Patrick Mallea; Robert, Philippe H.

    2010-01-01

    Behavioral and psychological symptoms (BPSD) are now known to be frequently associated to cognitive and functional decline in Alzheimer‘s disease and related disorders. They are present since the early stages of the disease and have negative impact on the disease process. BPSD assessment is crucial in clinical practice and also in future clinical trials targeting disease-modifying therapies for dementia. In this article, we will first review current assessment tools for BPSD, mainly global an...

  6. Targeting the schizophrenia genome: a fast track strategy from GWAS to clinic

    Science.gov (United States)

    Lencz, T; Malhotra, A K

    2015-01-01

    The Psychiatric Genomics Consortium–Schizophrenia Workgroup (PGC–SCZ) has recently published a genomewide association study (GWAS) identifying >100 genetic loci, encompassing a total of 341 protein-coding genes, attaining genomewide significance for susceptibility to schizophrenia. Given the extremely long time (12–15 years) and expense (>$1 billion) associated with the development of novel drug targets, repurposing of drugs with known and validated targets may be the most expeditious path toward deriving clinical utility from these GWAS findings. In the present study, we examined all genes within loci implicated by the PGC–SCZ GWAS against databases of targets of both approved and registered pharmaceutical compounds. We identified 20 potential schizophrenia susceptibility genes that encode proteins that are the targets of approved drugs. Of these, we prioritized genes/targets that are of clear neuropsychiatric interest and that are also sole members of the linkage disequilibrium block surrounding a PGC–SCZ GWAS hit. In addition to DRD2, 5 genes meet these criteria: CACNA1C, CACNB2, CACNA1I, GRIN2A and HCN1. An additional 20 genes coding for proteins that are the targets of drugs in registered clinical trials, but without approved indications, were also identified. Although considerable work is still required to fully explicate the biological implications of the PGC–SCZ GWAS results, pathways related to these known, druggable targets may represent a promising starting point. PMID:25869805

  7. 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.

  8. 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

  9. 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

  10. In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib.

    Science.gov (United States)

    Rolf, Michael G; Curwen, Jon O; Veldman-Jones, Margaret; Eberlein, Cath; Wang, Jianyan; Harmer, Alex; Hellawell, Caroline J; Braddock, Martin

    2015-10-01

    Off-target pharmacology may contribute to both adverse and beneficial effects of a new drug. In vitro pharmacological profiling is often applied early in drug discovery; there are fewer reports addressing the relevance of broad profiles to clinical adverse effects. Here, we have characterized the pharmacological profile of the active metabolite of fostamatinib, R406, linking an understanding of drug selectivity to the increase in blood pressure observed in clinical studies. R406 was profiled in a broad range of in vitro assays to generate a comprehensive pharmacological profile and key targets were further investigated using functional and cellular assay systems. A combination of traditional literature searches and text-mining approaches established potential mechanistic links between the profile of R406 and clinical side effects. R406 was selective outside the kinase domain, with only antagonist activity at the adenosine A3 receptor in the range relevant to clinical effects. R406 was less selective in the kinase domain, having activity at many protein kinases at therapeutically relevant concentrations when tested in multiple in vitro systems. Systematic literature analyses identified KDR as the probable target underlying the blood pressure increase observed in patients. While the in vitro pharmacological profile of R406 suggests a lack of selectivity among kinases, a combination of classical searching and text-mining approaches rationalized the complex profile establishing linkage between off-target pharmacology and clinically observed effects. These results demonstrate the utility of in vitro pharmacological profiling for a compound in late-stage clinical development. PMID:26516587

  11. 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

  12. 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.

  13. 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

  14. Priceless clinical pearls in the performance of cardiac CT.

    Science.gov (United States)

    Lepor, Norman E; Madyoon, Hooman; Friede, Gerald

    2008-01-01

    Cardiovascular CT represents an important innovation in cardiac imaging as a noninvasive modality for the diagnosis of coronary artery disease. As a screening examination, coronary CT has the ability to identify the presence, extent, location, and severity of coronary artery disease in patients at risk. As a diagnostic examination in patients with chest discomfort and dyspnea, it can not only evaluate for the presence of coronary artery disease but also evaluate the pulmonary vasculature and aorta. The ability to perform high-quality cardiac CT requires a combination of technical expertise and knowledge of cardiac anatomy. From our experience having performed over 6000 cardiac CTs, we provide the reader with a number of clinical and technical pearls that will enhance his or her ability to perform high-quality studies even in the more challenging patient. PMID:18418315

  15. Measurement of Neuropsychiatric Symptoms in Clinical Trials Targeting Alzheimer's Disease and Related Disorders

    Directory of Open Access Journals (Sweden)

    Emmanuel Mulin

    2010-07-01

    Full Text Available Behavioral and psychological symptoms (BPSD are now known to be frequently associated to cognitive and functional decline in Alzheimer‘s disease and related disorders. They are present since the early stages of the disease and have negative impact on the disease process. BPSD assessment is crucial in clinical practice and also in future clinical trials targeting disease-modifying therapies for dementia. In this article, we will first review current assessment tools for BPSD, mainly global and domain-specific scales, and new assessment methods, currently available or in development, including new scales, diagnostic criteria and new technologies such as ambulatory actigraphy.

  16. 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

  17. Guidelines for delineation of lymphatic clinical target volumes for high conformal radiotherapy: head and neck region

    International Nuclear Information System (INIS)

    The success of radiotherapy depends on the accurate delineation of the clinical target volume. The delineation of the lymph node regions has most impact, especially for tumors in the head and neck region. The purpose of this article was the development an atlas for the delineation of the clinical target volume for patients, who should receive radiotherapy for a tumor of the head and neck region. Literature was reviewed for localisations of the adjacent lymph node regions and their lymph drain in dependence of the tumor entity. On this basis the lymph node regions were contoured on transversal CT slices. The probability for involvement was reviewed and a recommendation for the delineation of the CTV was generated

  18. Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Navin Rauniyar

    2015-12-01

    Full Text Available The parallel reaction monitoring (PRM assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly specific and selective method for targeted quantification using quadrupole-Orbitrap hybrid instruments. In addition, this review discusses the label-based and label-free methods of quantification that can be performed with the targeted approach.

  19. 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

  20. Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    McTigue, Michele [Pfizer Inc., San Diego, CA (United States); Murray, Brion William [Pfizer Inc., San Diego, CA (United States); Chen, Jeffrey H. [Pfizer Inc., San Diego, CA (United States); Deng, Ya-Li [Pfizer Inc., San Diego, CA (United States); Solowiej, James [Pfizer Inc., San Diego, CA (United States); Kania, Robert S. [Pfizer Inc., San Diego, CA (United States)

    2012-09-17

    We performed analyses of compounds in clinical development which have shown that ligand efficient-molecules with privileged physical properties and low dose are less likely to fail in the various stages of clinical testing, have fewer postapproval withdrawals, and are less likely to receive black box safety warnings. However, detailed side-by-side examination of molecular interactions and properties within single drug classes are lacking. As a class, VEGF receptor tyrosine kinase inhibitors (VEGFR TKIs) have changed the landscape of how cancer is treated, particularly in clear cell renal cell carcinoma, which is molecularly linked to the VEGF signaling axis. Despite the clear role of the molecular target, member molecules of this validated drug class exhibit distinct clinical efficacy and safety profiles in comparable renal cell carcinoma clinical studies. The first head-to-head randomized phase III comparative study between active VEGFR TKIs has confirmed significant differences in clinical performance [Rini BI, et al. (2011) Lancet 378:193–1939]. To elucidate how fundamental drug potency–efficiency is achieved and impacts differentiation within the VEGFR TKI class, we determined potencies, time dependence, selectivities, and X-ray structures of the drug–kinase complexes using a VEGFR2 TK construct inclusive of the important juxtamembrane domain. Collectively, the studies elucidate unique drug–kinase interactions that are dependent on distinct juxtamembrane domain conformations, resulting in significant potency and ligand efficiency differences. Finally, the identified structural trends are consistent with in vitro measurements, which translate well to clinical performance, underscoring a principle that may be broadly applicable to prospective drug design for optimal in vivo performance.

  1. The incentive effects of performance measures and target setting

    OpenAIRE

    Kroos, P.

    2009-01-01

    Lavish executive compensation packages, and bonuses awarded to executives by financial institutions that only just received government bailouts, have fueled the currently popular perception that compensation is primarily determined by powerful managers granting themselves excessive compensation tenuously related with performance. This thesis challenges the widespread public notion that managerial power represents the primary determinant of compensation design by examining to what extent choic...

  2. 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...

  3. 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

  4. Optimized target ranking for high-performance CAD in CT colonography

    International Nuclear Information System (INIS)

    Most CAD systems that detect target lesions at a high sensitivity yield a large amount of initial detections that need to be analyzed by time-consuming FP reduction steps. We developed an optimized target ranking (OTR) method that minimizes the set of initial detections in a CAD system for CT colonography (CTC): the initial CAD detections from patient's volumetric CT scans are collected into a single by-patient detection pool, and an optimal classifier is used to select detections that are most likely to represent polyps based on training data. We optimized the OTR method by use of a training database including 71 CTC polyp cases, and integrated the method into a previously developed fully automated CAD system that was trained with 146 CTC cases from three institutions. We then compared the effect of the OTR method on the CAD system with that of a conventional by-feature candidate selection method by use of an independent testing database including 450 prospective asymptomatic CTC screening cases at a clinically acceptable range of an average of 0-3 false-positive detections per CT scan. The OTR method reduced the number of initial CAD detections by 89% without degrading the final 92% detection sensitivity for adenomas ≥8 mm, thereby exceeding the 85% sensitivity of prospective human CTC reading. In summary, the OTR method is an effective approach for reducing initial FP CAD detections without degrading the performance of automated polyp detection in CTC. (orig.)

  5. 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

  6. Neurooncology clinical trial design for targeted therapies: lessons learned from the North American Brain Tumor Consortium.

    Science.gov (United States)

    Chang, Susan M; Lamborn, Kathleen R; Kuhn, John G; Yung, W K Alfred; Gilbert, Mark R; Wen, Patrick Y; Fine, Howard A; Mehta, Minesh P; DeAngelis, Lisa M; Lieberman, Frank S; Cloughesy, Timothy F; Robins, H Ian; Abrey, Lauren E; Prados, Michael D

    2008-08-01

    The North American Brain Tumor Consortium (NABTC) is a multi-institutional consortium with the primary objective of evaluating novel therapeutic strategies through early phase clinical trials. The NABTC has made substantial changes to the design and methodology of its trials since its inception in 1994. These changes reflect developments in technology, new types of therapies, and advances in our understanding of tumor biology and biological markers. We identify the challenges of early clinical assessment of therapeutic agents by reviewing the clinical trial effort of the NABTC and the evolution of the protocol template used to design trials. To better prioritize effort and allocation of patient resources and funding, we propose an integrated clinical trial design for the early assessment of efficacy of targeted therapies in neurooncology. This design would mandate tissue acquisition prior to therapeutic intervention with the drug, allowing prospective evaluation of its effects. It would also include a combined phase 0/I pharmacokinetic study to determine the safety and biologically optimal dose of the agent and to verify successful modulation of the target prior to initiating a larger, phase II efficacy study. PMID:18559968

  7. Seismic design and evaluation criteria based on target performance goals

    International Nuclear Information System (INIS)

    The Department of Energy utilizes deterministic seismic design/evaluation criteria developed to achieve probabilistic performance goals. These seismic design and evaluation criteria are intended to apply equally to the design of new facilities and to the evaluation of existing facilities. In addition, the criteria are intended to cover design and evaluation of buildings, equipment, piping, and other structures. Four separate sets of seismic design/evaluation criteria have been presented each with a different performance goal. In all these criteria, earthquake loading is selected from seismic hazard curves on a probabilistic basis but seismic response evaluation methods and acceptable behavior limits are deterministic approaches with which design engineers are familiar. For analytical evaluations, conservatism has been introduced through the use of conservative inelastic demand-capacity ratios combined with ductile detailing requirements, through the use of minimum specified material strengths and conservative code capacity equations, and through the use of a seismic scale factor. For evaluation by testing or by experience data, conservatism has been introduced through the use of an increase scale factor which is applied to the prescribed design/evaluation input motion

  8. How Beyond Rule of 5 Drugs and Clinical Candidates Bind to Their Targets.

    Science.gov (United States)

    Doak, Bradley C; Zheng, Jie; Dobritzsch, Doreen; Kihlberg, Jan

    2016-03-24

    To improve discovery of drugs for difficult targets, the opportunities of chemical space beyond the rule of 5 (bRo5) were examined by retrospective analysis of a comprehensive set of structures for complexes between drugs and clinical candidates and their targets. The analysis illustrates the potential of compounds far beyond rule of 5 space to modulate novel and difficult target classes that have large, flat, and groove-shaped binding sites. However, ligand efficiencies are significantly reduced for flat- and groove-shape binding sites, suggesting that adjustments of how to use such metrics are required. Ligands bRo5 appear to benefit from an appropriate balance between rigidity and flexibility to bind with sufficient affinity to their targets, with macrocycles and nonmacrocycles being found to have similar flexibility. However, macrocycles were more disk- and spherelike, which may contribute to their superior binding to flat sites, while rigidification of nonmacrocycles lead to rodlike ligands that bind well to groove-shaped binding sites. These insights should contribute to altering perceptions of what targets are considered "druggable" and provide support for drug design in beyond rule of 5 space. PMID:26457449

  9. 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

  10. Performance targets for fusion-fission (hybrid) reactors

    International Nuclear Information System (INIS)

    The potential roles for various performance levels of hybrid power plants in the United States have been estimated for various scenarios which describe the systems with which the hybrid plants must compete. Due to the uncertainty in estimating the costs of hybrid power plants, a parametric approach was chosen to identify acceptable characteristics and associated tradeoffs. Because hybrid power plants produce substantial quantities of both plutonium and electricity, a simulation model is necessary which appropriately values each of these products. This would permit design tradeoffs and realistic interactions with other generating plants, such as Liquid Metal Fast Breeder Reactors (LMFBRs) and Light Water Reactors (LWRs), to be estimated. A linear programming model nearly identical to that used for the recent LMFBR cost-benefit analysis was utilized for this purpose

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-08-01

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

  13. 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.

  14. 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.

  15. 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.

  16. The Virginia/Basel/SLAC polarized target: operation and performance during experiment E143 at SLAC

    International Nuclear Information System (INIS)

    The polarized target system used for the electron beam experiment E143 at SLAC is decribed. It consists of a DNP style polarized solid target with 15NH3 respectively 15ND3 as target material. The magnet is a 5.1 T superconducting Helmholtz pair and the refrigerator is of the 4He evaporation type. The polarization is controlled by two NMR measurement coils. The in-beam performance and the polarization error are described. (HSI)

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

    International Nuclear Information System (INIS)

    The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer. A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m2]; E: epirubicin [90 mg/m2]; F: 5-fluorouracil [600 mg/m2]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined. The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group. As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses

  18. 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

  19. Genetic profiling of intrahepatic cholangiocarcinoma and its clinical implication in targeted therapy

    Science.gov (United States)

    Xie, Diyang; Ren, Zhenggang; Fan, Jia; Gao, Qiang

    2016-01-01

    Intrahepatic cholangiocarcinoma (iCCA) is a treatment-refractory primary liver cancer with an increasing incidence and mortality worldwide in recent years. Lack of a stereotyped genetic signature and limited understanding of genomic landscape make the development of effective targeted therapies challenging. Recent application of advanced technologies such as next-generation sequencing (NGS) has broadened our understanding of genetic heterogeneity in iCCA and many potentially actionable genetic alterations have been identified. This review explores the recent advances in defining genetic alterations in iCCAs, which may present potent therapeutic targets. Chromatin remodeling genes and genes encoding isocitrate dehydrogenase and tyrosine kinase receptors as well as their downstream effectors are among the most frequently altered genes. Clinical trials testing the effect of new targeted agents on iCCA patients, especially those with the above genetic markers are under way. However, the complex interplay of environmental and evolutionary factors contributing to the genetic variability in iCCA calls for a more cautionary use of NGS in tailoring targeted regimen to the patients. Next-generation functional testing may complement NGS to execute precision medicine in future.

  20. Genetic profiling of intrahepatic cholangiocarcinoma and its clinical implication in targeted therapy.

    Science.gov (United States)

    Xie, Diyang; Ren, Zhenggang; Fan, Jia; Gao, Qiang

    2016-01-01

    Intrahepatic cholangiocarcinoma (iCCA) is a treatment-refractory primary liver cancer with an increasing incidence and mortality worldwide in recent years. Lack of a stereotyped genetic signature and limited understanding of genomic landscape make the development of effective targeted therapies challenging. Recent application of advanced technologies such as next-generation sequencing (NGS) has broadened our understanding of genetic heterogeneity in iCCA and many potentially actionable genetic alterations have been identified. This review explores the recent advances in defining genetic alterations in iCCAs, which may present potent therapeutic targets. Chromatin remodeling genes and genes encoding isocitrate dehydrogenase and tyrosine kinase receptors as well as their downstream effectors are among the most frequently altered genes. Clinical trials testing the effect of new targeted agents on iCCA patients, especially those with the above genetic markers are under way. However, the complex interplay of environmental and evolutionary factors contributing to the genetic variability in iCCA calls for a more cautionary use of NGS in tailoring targeted regimen to the patients. Next-generation functional testing may complement NGS to execute precision medicine in future. PMID:27152236

  1. 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. PMID:27051587

  2. Treat-to-Target Approach in Daily Clinical Practice in Pakistani Patients with Early Rheumatoid Arthritis

    International Nuclear Information System (INIS)

    Objective: To determine the frequency of patients with early Rheumatoid Arthritis (RA) achieving disease remission and/or low disease activity after 6 months of treatment with conventional Disease Modifying Anti-Rheumatic Drugs (DMARDs) by using treat-to-target approach in routine clinical practice. Study Design: Descriptive study. Place and Duration of Study: Division of Rheumatology, Fatima Memorial Hospital (FMH), College of Medicine and Dentistry, Lahore, from March 2011 to February 2012. Methodology: Patients with early RA defined as disease duration <= 1 year were enrolled by purposive sampling, diagnosed as per American College of Rheumatology (ACR) 1987 criteria. Treat-to-target approach was defined as per European League Against Rheumatism (EULAR) 2010 guidelines for treatment of RA with conventional DMARDs. Outcome measures of remission and low disease activity were defined as per DAS 28 score criteria. Patient response to treatment was also determined by EULAR response criteria. Results: Out of 67 patients, 50 patients completed the 6 months study period, rest were lost to follow-up. All patients were started on Methotrexate and mean weekly dose at 6 months was 18.9 ± 3.8 mg. Remission was achieved in 17 (34%) and target of low disease activity was achieved in 29 (58%) of patients. EULAR good response was seen in 28 (56%), moderate response in 21 (42%) and no response to treatment in 1 (2%). Conclusion: By applying treat-to-target approach in early RA, achievement of clinical remission or low disease activity with conventional DMARDs is a realistic goal in routine practice. (author)

  3. Analytic Performance of Monopulse Spread Spectrum Tracking System in Multiple-target Scenario

    Science.gov (United States)

    Cong, Bo; Qu, Yuanxin; Zhang, Yongliang

    2016-02-01

    With the application of spread spectrum technique in satellite tracking, the accuracy of CDMA-based multiple-target tracking needs to be analyzed. In this paper,we present the analytic form of the multiple-target tracking performance through mathematical deduction, together with simulation results.

  4. 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

  5. Antibodies to autoantigen targets in myasthenia and their value in clinical practice

    Directory of Open Access Journals (Sweden)

    S. I. Dedaev

    2015-02-01

    Full Text Available Myasthenia gravis is a classic autoimmune disease, which clinical manifestations in the form of weakness and abnormal muscle fatigue, due to the damaging effect of polyclonal antibodies to different structures of the neuromuscular synapse and muscles. The study of autoimmune substrate with myasthenia is routine in many clinics dealing with the problems of neuromuscular pathology, and the identification of high concentration of serum antibodies to a number of antigenic structures is the gold standard in diagnosis.Determination of serum antibodies to various autoimmune targets is an important tool in clinical practice. The majority of patients shows the high concentration of antibodies to AchR that gives the opportunity to use it as an important diagnostic criterion. The specificity of changes in the concentration of AchR-antibodies due to pathogenetic treatment allows to objectify the suppression of autoimmune aggression and evaluate the reliability of remission. However, the absence of AchR-antibodies when there are clear clinical and electromyography signs of myasthenia gravis suggests an autoimmune attack against a number of other targets, the most studied of which is the MuSK. On the contrary, patients with myasthenia gravis associated with thymoma, almost always have a higher level of AchR-antibodies. The presence of thymoma is accompanied by the generation of antibodies to titin and RyR, which is also observed in persons with late-onset myasthenia without thymoma. High concentration of antibodies to these structures can be interpreted as a reliable sign of thymoma in patients younger than 60 years.

  6. Impact of beam smoothing method on direct drive target performance for the NIF

    International Nuclear Information System (INIS)

    The impact of smoothing method on the performance of a direct drive target is modeled and examined in terms of its l-mode spectrum. In particular, two classes of smoothing methods are compared, smoothing by spectral dispersion (SSD) and the induced spatial incoherence (ISI) method. It is found that SSD using sinusoidal phase modulation (FM) results in poor smoothing at low l-modes and therefore inferior target performance at both peak velocity and ignition. Modeling of the hydrodynamic nonlinearity shows that saturation tends to reduce the difference between target performance for the smoothing methods considered. However, using SSD with more generalized phase modulation results in a smoothed spatial spectrum, and therefore target performance, which is identical to that obtained with the ISI or similar method where random phase plates are present in both methods and identical beam divergence is assumed

  7. 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

  8. 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

  9. The effect of optical prepulse on direct-drive inertial confinement fusion target performance

    International Nuclear Information System (INIS)

    The effect of optical prepulses on the performance of imploding inertial confinement fusion (ICF) targets has been measured. The neutron yields from nearly identical spherical targets imploded by the OMEGA [T. R. Boehly , Opt. Commun. 133, 495 (1997)] laser were measured as a function of prepulse fluences in the drive laser. These experiments indicate that the cumulative prepulse fluence on target must be less than ∼0.2 J/cm2, which corresponds to a prepulse intensity contrast of ≥107. This effect is the result of damage to the Al barrier layer used on OMEGA ICF targets. To verify this, the effect of low-intensity irradiation on these Al layers was observed on planar targets using the time-resolved reflectivity and the time-integrated transmission measurements. These experiments show that damage to the Al layers begins at ∼0.1 J/cm2, consistent with the implosion performance results

  10. Effects of target and distractor saturations on the cognitive performance of an integrated display interface

    Science.gov (United States)

    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 20Δ E*ab units in the yellow saturation coding, whereas the color difference should be more than 40Δ E*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

  11. 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

  12. 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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    sensitivity, specificity and accuracy, the latter using a receiver-operating characteristics (ROC) analysis. In 96,534 clinical mammography examinations, sensitivity was 75% and specificity 99%. The presence of at least one high volume-reading radiologist in the clinic increased accuracy (AUC = 0.91 for <1...... that clinical mammography worked best in patient populations of purely symptomatic women. Our data indicate that to increase the accuracy of clinical mammography at the community level, the presence of an experienced radiologist should be prioritized ahead of raising the clinic size....

  14. Performance-optimized clinical IMRT planning on modern CPUs

    International Nuclear Information System (INIS)

    Intensity modulated treatment plan optimization is a computationally expensive task. The feasibility of advanced applications in intensity modulated radiation therapy as every day treatment planning, frequent re-planning for adaptive radiation therapy and large-scale planning research severely depends on the runtime of the plan optimization implementation. Modern computational systems are built as parallel architectures to yield high performance. The use of GPUs, as one class of parallel systems, has become very popular in the field of medical physics. In contrast we utilize the multi-core central processing unit (CPU), which is the heart of every modern computer and does not have to be purchased additionally. In this work we present an ultra-fast, high precision implementation of the inverse plan optimization problem using a quasi-Newton method on pre-calculated dose influence data sets. We redefined the classical optimization algorithm to achieve a minimal runtime and high scalability on CPUs. Using the proposed methods in this work, a total plan optimization process can be carried out in only a few seconds on a low-cost CPU-based desktop computer at clinical resolution and quality. We have shown that our implementation uses the CPU hardware resources efficiently with runtimes comparable to GPU implementations, at lower costs. (paper)

  15. Risk of Hyponatraemia in Cancer Patients Treated with Targeted Therapies: A Systematic Review and Meta-Analysis of Clinical Trials

    Science.gov (United States)

    Berardi, Rossana; Santoni, Matteo; Rinaldi, Silvia; Nunzi, Emilia; Smerilli, Alessia; Caramanti, Miriam; Morgese, Francesca; Torniai, Mariangela; Savini, Agnese; Fiordoliva, Ilaria; Onofri, Azzurra; Pistelli, Mirco; Taccaliti, Augusto; Cascinu, Stefano

    2016-01-01

    Background Hyponatraemia has been reported with targeted therapies in cancer patients. Aim of the study was to perform an up-to-date meta-analysis in order to determine the incidence and relative risk (RR) in cancer patients treated with these agents. Materials and Methods The scientific literature regarding hyponatraemia was extensively reviewed using MEDLINE, PubMed, Embase and Cochrane databases. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% Confidence Intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. Results 4803 potentially relevant trials were identified: of them, 13 randomized phase III studies were included in this meta-analysis. 6670 patients treated with 8 targeted agents were included: 2574 patients had hepatocellular carcinoma, whilst 4096 had other malignancies. The highest incidences of all-grade hyponatraemia were observed with the combination of brivanib and cetuximab (63.4) and pazopanib (31.7), while the lowest incidence was reported by afatinib (1.7). The highest incidence of high-grade hyponatraemia was reported by cetuximab (34.8), while the lowest incidences were reported by gefitinib (1.0). Summary RR of developing all-grade and high-grade hyponatraemia with targeted agents was 1.36 and 1.52, respectively. The highest RRs of all-grade and high-grade hyponatraemia were associated with brivanib (6.5 and 5.2, respectively). Grouping by drug category, the RR of high-grade hyponatraemia with angiogenesis inhibitors was 2.69 compared to anti-Epidermal Growth Factor Receptors agents (1.12). Conclusion Treatment with biological therapy in cancer patients is associated with a significant increased risk of hyponatraemia, therefore frequent clinical monitoring should be emphasized when managing targeted agents. PMID:27167519

  16. 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.

  17. Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation.

    Science.gov (United States)

    Dietrich, W Dalton; Bramlett, Helen M

    2016-06-01

    The use of therapeutic hypothermia (TH) and targeted temperature management (TTM) for severe traumatic brain injury (TBI) has been tested in a variety of preclinical and clinical situations. Early preclinical studies showed that mild reductions in brain temperature after moderate to severe TBI improved histopathological outcomes and reduced neurological deficits. Investigative studies have also reported that reductions in post-traumatic temperature attenuated multiple secondary injury mechanisms including excitotoxicity, free radical generation, apoptotic cell death, and inflammation. In addition, while elevations in post-traumatic temperature heightened secondary injury mechanisms, the successful implementation of TTM strategies in injured patients to reduce fever burden appear to be beneficial. While TH has been successfully tested in a number of single institutional clinical TBI studies, larger randomized multicenter trials have failed to demonstrate the benefits of therapeutic hypothermia. The use of TH and TTM for treating TBI continues to evolve and a number of factors including patient selection and the timing of the TH appear to be critical in successful trial design. Based on available data, it is apparent that TH and TTM strategies for treating severely injured patients is an important therapeutic consideration that requires more basic and clinical research. Current research involves the evaluation of alternative cooling strategies including pharmacologically-induced hypothermia and the combination of TH or TTM approaches with more selective neuroprotective or reparative treatments. This manuscript summarizes the preclinical and clinical literature emphasizing the importance of brain temperature in modifying secondary injury mechanisms and in improving traumatic outcomes in severely injured patients. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26746342

  18. Performance and strategy comparisons of human listeners and logistic regression in discriminating underwater targets.

    Science.gov (United States)

    Yang, Lixue; Chen, Kean

    2015-11-01

    To improve the design of underwater target recognition systems based on auditory perception, this study compared human listeners with automatic classifiers. Performances measures and strategies in three discrimination experiments, including discriminations between man-made and natural targets, between ships and submarines, and among three types of ships, were used. In the experiments, the subjects were asked to assign a score to each sound based on how confident they were about the category to which it belonged, and logistic regression, which represents linear discriminative models, also completed three similar tasks by utilizing many auditory features. The results indicated that the performances of logistic regression improved as the ratio between inter- and intra-class differences became larger, whereas the performances of the human subjects were limited by their unfamiliarity with the targets. Logistic regression performed better than the human subjects in all tasks but the discrimination between man-made and natural targets, and the strategies employed by excellent human subjects were similar to that of logistic regression. Logistic regression and several human subjects demonstrated similar performances when discriminating man-made and natural targets, but in this case, their strategies were not similar. An appropriate fusion of their strategies led to further improvement in recognition accuracy. PMID:26627787

  19. 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

  20. 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.

  1. 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.

  2. 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...

  3. 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

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

    International Nuclear Information System (INIS)

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

  5. Quantifying warfighter performance in a target acquisition and aiming task using wireless inertial sensors.

    Science.gov (United States)

    Davidson, Steven P; Cain, Stephen M; McGinnis, Ryan S; Vitali, Rachel R; Perkins, Noel C; McLean, Scott G

    2016-09-01

    An array of inertial measurement units (IMUS) was experimentally employed to analyze warfighter performance on a target acquisition task pre/post fatigue. Eleven participants (5M/6F) repeated an exercise circuit carrying 20 kg of equipment until fatigued. IMUs secured to the sacrum, sternum, and a rifle quantified peak angular velocity magnitude (PAVM) and turn time (TT) on a target acquisition task (three aiming events with two 180° turns) within the exercise circuit. Turning performance of two turns was evaluated pre/post fatigue. Turning performance decreased with fatigue. PAVMs decreased during both turns for the sternum (p performance after fatigue. Similar methodologies can be applied to many movement tasks, including quantifying movement performance for load, fatigue, and equipment conditions. PMID:27184308

  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. 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...

  8. 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

  9. 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

  10. Prevention and management of chronic disease in Aboriginal and Islander Community Controlled Health Services in Queensland: a quality improvement study assessing change in selected clinical performance indicators over time in a cohort of services

    OpenAIRE

    Panaretto, K S; Gardner, K L; Button, S; Carson, A; Schibasaki, R; Wason, G; Baker, D.; Mein, J.; Dellit, A; Lewis, D; Wenitong, M; Ring, I

    2013-01-01

    Objective To evaluate clinical healthcare performance in Aboriginal Medical Services in Queensland and to consider future directions in supporting improvement through measurement, target setting and standards development. Design Longitudinal study assessing baseline performance and improvements in service delivery, clinical care and selected outcomes against key performance indicators 2009–2010. Setting 27 Aboriginal and Islander Community Controlled Health Services (AICCHSs) in Queensland, w...

  11. Improving material properties and performance of nuclear targets for transmutation-relevant experiments

    International Nuclear Information System (INIS)

    To improve the properties and performance of thin layers produced by molecular plating as targets for nuclear experiments investigations with lanthanide elements (i.e., natural Nd and 147Sm-enriched Sm) were carried out. Plating parameters like roughness of the deposition substrate, plating solvent, electrolyte concentration, and applied current density were varied. The influence of each parameter on the properties of the layers was studied by characterizing the deposits. The characterizations showed that nuclear targets perform differently depending on their layer properties. The results obtained from the investigations were applied for the quantitative preparation of homogeneous large-area (i.e., 42 cm2) 242Pu targets to be used for transmutation-relevant experiments. (author)

  12. 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.

  13. Automatic target recognition performance losses in the presence of atmospheric and camera effects

    Science.gov (United States)

    Chen, Xiaohan; Schmid, Natalia A.

    2010-04-01

    The importance of networked automatic target recognition systems for surveillance applications is continuously increasing. Because of the requirement of a low cost and limited payload, these networks are traditionally equipped with lightweight, low-cost sensors such as electro-optical (EO) or infrared sensors. The quality of imagery acquired by these sensors critically depends on the environmental conditions, type and characteristics of sensors, and absence of occluding or concealing objects. In the past, a large number of efficient detection, tracking, and recognition algorithms have been designed to operate on imagery of good quality. However, detection and recognition limits under nonideal environmental and/or sensor-based distortions have not been carefully evaluated. We introduce a fully automatic target recognition system that involves a Haar-based detector to select potential regions of interest within images, performs adjustment of detected regions, segments potential targets using a region-based approach, identifies targets using Bessel K form-based encoding, and performs clutter rejection. We investigate the effects of environmental and camera conditions on target detection and recognition performance. Two databases are involved. One is a simulated database generated using a 3-D tool. The other database is formed by imaging 10 die-cast models of military vehicles from different elevation and orientation angles. The database contains imagery acquired both indoors and outdoors. The indoors data set is composed of clear and distorted images. The distortions include defocus blur, sided illumination, low contrast, shadows, and occlusions. All images in this database, however, have a uniform (blue) background. The indoors database is applied to evaluate the degradations of recognition performance due to camera and illumination effects. The database collected outdoors includes a real background and is much more complex to process. The numerical results

  14. 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…

  15. Clinical performance of a new aspheric dual-optic accommodating intraocular lens

    Directory of Open Access Journals (Sweden)

    Marques EF

    2014-11-01

    Full Text Available Eduardo F Marques,1 António Castanheira-Dinis2 1Department of Ophthalmology, Hospital da Cruz Vermelha, Lisboa, Portugal; 2Visual Sciences Research Centre, Universidade de Lisboa, Portugal Purpose: To describe the clinical performance of a new dual-optic intraocular lens (IOL with an enhanced optic profile designed to mimic natural accommodation.Patients and methods: Prospective multicenter clinical study with the new dual-optic aspheric accommodating IOL (Synchrony Vu in 74 patients (148 eyes undergoing cataract surgery. Refractive target was emmetropia. Examinations at 1 month and 6 months included subjective refractions; visual acuities at near, intermediate, and far; mesopic contrast sensitivity with and without glare; safety data; and subjective survey on dysphotopsia (halos and glare.Results: Clinical data at 6 months showed 89% of the eyes within ±1.0 D spherical equivalent refraction. Mean binocular uncorrected and distance-corrected visual acuity was 20/20 at far (0.00±0.11 logMAR and -0.06±0.08 logMAR, respectively, 20/20 at intermediate (0.01±0.13 logMAR and -0.01±0.10 logMAR, respectively, and 20/25 at near (0.10±0.14 logMAR and 0.14±0.15 logMAR, respectively. Mesopic contrast sensitivity was within normal limits. Seventy-eight percent of the patients had no spectacles and 70% had no dysphotopsia. One eye had IOL repositioning within 1 month of surgery.Conclusion: The new aspheric Synchrony Vu accommodating IOL provided good visual performance at a range of distances without affecting quality of vision and with minimal safety considerations. Keywords: accommodating IOL, cataract surgery, intraocular lens, presbyopia

  16. The study on the potential clinical value of sentinel lymphoscintigraphy in the radiation target volume design of internal mammary nodes

    International Nuclear Information System (INIS)

    Objective: We explored the potential clinical value of SPECT sentinel lymphoscintigraphy combined with a positional CT in defining the radiation target volume of internal mammary lymph nodes (IMN). Methods: (1) Forty breast cancer patients were enrolled, using 99Tcm-sulfur colloid (SC) as radiotracer and GE Millennium VG Hawkeye as imaging instrument. The depth ( distance from center of IMN to the surface of pectoralis major) and width (distance between the center of IMN and mid-sternal line) of each IMN were measured in the Hawkeye fusion images. (2) Hawkeye CT and diagnostic enhanced CT images of the same patients were analyzed, with the same reference points selected and their depths and widths measured. The location accuracy by the positional CT was evaluated. (3) Hawkeye positional CT and diagnostic CT scan were performed respectively using the CT quality control model attached to Hawkeye. The distances between the center of spheres on the Hawkeye CT and diagnostic CT images were measured, and then the data were compared and the model location accuracy of Hawkeye evaluated. Statistical comparison for the depth and the width between left and right IMN were performed with the t-test. Result: (1) Seventy IMN in 40 patients were studied. The depth was 1.10-3.99 cm with an average of 2.15 cm. The width was 1.52-6.59 cm with an average of 4.37 cm. The difference of depth between left and right IMN was not statistically significant (t= 1.1, P= 0.275), neither was the width (t=0.8, P=0.408). Only 11.4% (8/70) of the IMN and 10.0% (4/40) of the patients could fit the routine field. (2) CT position system of Hawkeye for localization of IMN was similar to that of diagnostic CT. Conclusion: IMN lymphoscintigraphy using Hawkeye CT positional system may be helpful for defining individual IMN radiation target volume. (authors)

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

    Science.gov (United States)

    van de Donk, Niels W C J; Moreau, Philippe; Plesner, Torben; Palumbo, Antonio; Gay, Francesca; Laubach, Jacob P; Malavasi, Fabio; Avet-Loiseau, Hervé; Mateos, Maria-Victoria; Sonneveld, Pieter; Lokhorst, Henk M; Richardson, Paul G

    2016-02-11

    Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM, and preliminary results from studies with relapsed/refractory patients have shown enhanced therapeutic efficacy when daratumumab and isatuximab are combined with other agents. Furthermore, although elotuzumab (anti-SLAMF7) has no single agent activity in advanced MM, randomized trials in relapsed/refractory MM have demonstrated significantly improved progression-free survival when elotuzumab is added to lenalidomide-dexamethasone or bortezomib-dexamethasone. Importantly, there has been no significant additive toxicity when these monoclonal antibodies are combined with other anti-MM agents, other than infusion-related reactions specific to the therapeutic antibody. Prevention and management of infusion reactions is important to avoid drug discontinuation, which may in turn lead to reduced efficacy of anti-MM therapy. Therapeutic antibodies interfere with several laboratory tests. First, interference of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting antibodies, interfere with blood compatibility testing and thereby complicate the safe release of blood products. Neutralization of the therapeutic CD38 antibody or CD38 denaturation on reagent red blood cells mitigates daratumumab interference with transfusion laboratory serologic tests. Finally, therapeutic antibodies may complicate flow cytometric evaluation of normal and neoplastic plasma cells, since the therapeutic antibody can affect the availability of the epitope for binding

  18. Variation of clinical target volume definition in three-dimensional conformal radiation therapy for prostate cancer

    International Nuclear Information System (INIS)

    Purpose: Currently, three-dimensional conformal radiation therapy (3D-CRT) planning relies on the interpretation of computed tomography (CT) axial images for defining the clinical target volume (CTV). This study investigates the variation among multiple observers to define the CTV used in 3D-CRT for prostate cancer. Methods and Materials: Seven observers independently delineated the CTVs (prostate ± seminal vesicles [SV]) from the CT simulation data of 10 prostate cancer patients undergoing 3D-CRT. Six patients underwent CT simulation without the use of contrast material and serve as a control group. The other 4 had urethral and bladder opacification with contrast medium. To determine interobserver variation, we evaluated the derived volume, the maximum dimensions, and the isocenter for each examination of CTV. We assessed the reliability in the CTVs among the observers by correlating the variation for each class of measurements. This was estimated by intraclass correlation coefficient (ICC), with 1.00 defining absolute correlation. Results: For the prostate volumes, the ICC was 0.80 (95% confidence interval [CI]: 0.56-0.96). This changed to 0.92 (95% CI: 0.75-0.99) with the use of contrast material. Similarly, the maximal prostatic dimensions were reliable and improved. There was poor agreement in defining the SV. For this structure, the ICC never exceeded 0.28. The reliability of the isocenter was excellent, with the ICC exceeding 0.83 and 0.90 for the prostate ± SV, respectively. Conclusions: In 3D-CRT for prostate cancer, there was excellent agreement among multiple observers to define the prostate target volume but poor agreement to define the SV. The use of urethral and bladder contrast improved the reliability of localizing the prostate. For all CTVs, the isocenter was very reliable and should be used to compare the variation in 3D dosimetry among multiple observers

  19. Performance appraisal of estimation algorithms and application of estimation algorithms to target tracking

    Science.gov (United States)

    Zhao, Zhanlue

    This dissertation consists of two parts. The first part deals with the performance appraisal of estimation algorithms. The second part focuses on the application of estimation algorithms to target tracking. Performance appraisal is crucial for understanding, developing and comparing various estimation algorithms. In particular, with the evolvement of estimation theory and the increase of problem complexity, performance appraisal is getting more and more challenging for engineers to make comprehensive conclusions. However, the existing theoretical results are inadequate for practical reference. The first part of this dissertation is dedicated to performance measures which include local performance measures, global performance measures and model distortion measure. The second part focuses on application of the recursive best linear unbiased estimation (BLUE) or linear minimum mean square error (LIB-M-ISE) estimation to nonlinear measurement problem in target tracking. Kalman filter has been the dominant basis for dynamic state filtering for several decades. Beyond Kalman filter, a more fundamental basis for the recursive best linear unbiased filtering has been thoroughly investigated in a series of papers by my advisor Dr. X. Rong Li. Based on the so-called quasi-recursive best linear unbiased filtering technique, the constraints of the Kalman filter Linear-Gaussian assumptions can be relaxed such that a general linear filtering technique for nonlinear systems can be achieved. An approximate optimal BLUE filter is implemented for nonlinear measurements in target tracking which outperforms the existing method significantly in terms of accuracy, credibility and robustness.

  20. 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.

  1. 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.

  2. 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

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

    International Nuclear Information System (INIS)

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

  4. Impact Factors for Microinvasion in Intrahepatic Cholangiocarcinoma: A Possible System for Defining Clinical Target Volume

    International Nuclear Information System (INIS)

    Purpose: To quantify microscopic invasion of intrahepatic cholangiocarcinoma (IHC) into nontumor tissue and define the gross tumor volume (GTV)-to-clinical target volume (CTV) expansion necessary for radiotherapy. Methods and Materials: One-hundred IHC patients undergoing radical resection from January 2004 to July 2008 were enrolled in this study. Pathologic and clinical data including maximum tumor diameter, tumor boundary type, TNM stage, histologic grade, tumor markers, and liver enzymes were reviewed. The distance of microinvasion from the tumor boundary was measured by microscopy. The contraction coefficient for tumor measurements in radiographs and slide-mounted tissue was calculated. SPSS15.0 was used for statistical analysis. Results: Sixty-five patients (65%) exhibited tumor microinvasions. Microinvasions ranged from 0.4-8 mm, with 96% of patients having a microinvasion distance ≤6 mm measured on slide. The radiograph-to-slide contraction coefficient was 82.1%. The degree of microinvasion was correlated with tumor boundary type, TNM stage, histologic grade, and serum levels of carbohydrate antigen 19-9, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase and alkaline phosphatase. To define CTV accurately, we devised a scoring system based on combination of these factors. According to this system, a score ≤1.5 is associated with 96.1% sensitivity in detecting patients with a microextension ≤4.9 mm in radiographs, whereas a score ≥2 has a 95.1% sensitivity in detecting microextension ≤7.9 mm measured on radiograph. Conclusions: Patients with a score ≤1.5 and ≥2 require a radiographic GTV-to-CTV expansions of 4.9 and 7.9 mm, respectively, to encompass >95% of microinvasions.

  5. 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

  6. 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

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

    OpenAIRE

    Daisne, Jean-François; Blumhofer, Andreas

    2013-01-01

    Background Intensity modulated radiotherapy for head and neck cancer necessitates accurate definition of organs at risk (OAR) and clinical target volumes (CTV). This crucial step is time consuming and prone to inter- and intra-observer variations. Automatic segmentation by atlas deformable registration may help to reduce time and variations. We aim to test a new commercial atlas algorithm for automatic segmentation of OAR and CTV in both ideal and clinical conditions. Methods The updated Brai...

  8. 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.

  9. Some safety studies of the MEGAPIE spallation source target performed using computational fluid dynamics

    International Nuclear Information System (INIS)

    Such a target forms part of the evolutionary Accelerator-Driven System (ADS) concept in which neutrons are generated in an otherwise sub-critical core by spallation reactions resulting from bombardment by a proton beam. The international project MEGAPIE had the objective of demonstrating the feasibility of the spallation process for a particular target design under strict test conditions. The test was carried over a period of four months at the end of 2006 at the SINQ facility of the Paul Scherrer Institute in Switzerland. The design studies carried out for the MEGAPIE target prior to irradiation using Computational Fluid Dynamics (CFD) resulted in an optimum flow configuration being defined for the coolant circulation. Simultaneously, stresses in the structural components were examined using Finite Element Method (FEM) techniques. To this purpose, an interface program was written which enabled different specialist groups to carry out the thermal hydraulics and structural mechanics analyses within the project with fully consistent model data. Results for steady-state operation of the target show that the critical lower target components are adequately cooled, and that stresses and displacements are well within tolerances. Transient analyses were also performed to demonstrate the robustness of the design in the event of abnormal operation, including pump failure and burn-through of the target casing by the proton beam. In the latter case, the CFD analyses complemented and extended full-scale tests. (author)

  10. 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.

  11. 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...

  12. 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

  13. [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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

    OpenAIRE

    Barbara Merelli; Daniela Massi; Laura Cattaneo; Mario Mandalà

    2014-01-01

    In this review we summarize the biological role of PD-1/PD-L1 on cancer by focusing our attention in the biological rationale, clinical challenges and opportunities to target the PD-1/PD-L1 axis in melanoma.

  20. Quantifying the performance limits of human saccadic targeting during visual search

    Science.gov (United States)

    Eckstein, M. P.; Beutter, B. R.; Stone, L. S.

    2001-01-01

    In previous studies of saccadic targeting, the issue how visually guided saccades to unambiguous targets are programmed and executed has been examined. These studies have found different degrees of guidance for saccades depending on the task and task difficulty. In this study, we use ideal-observer analysis to estimate the visual information used for the first saccade during a search for a target disk in noise. We quantitatively compare the performance of the first saccadic decision to that of the ideal observer (ie absolute efficiency of the first saccade) and to that of the associated final perceptual decision at the end of the search (ie relative efficiency of the first saccade). Our results show, first, that at all levels of salience tested, the first saccade is based on visual information from the stimulus display, and its highest absolute efficiency is approximately 20%. Second, the efficiency of the first saccade is lower than that of the final perceptual decision after active search (with eye movements) and has a minimum relative efficiency of 19% at the lowest level of saliency investigated. Third, we found that requiring observers to maintain central fixation (no saccades allowed) decreased the absolute efficiency of their perceptual decision by up to a factor of two, but that the magnitude of this effect depended on target salience. Our results demonstrate that ideal-observer analysis can be extended to measure the visual information mediating saccadic target-selection decisions during visual search, which enables direct comparison of saccadic and perceptual efficiencies.

  1. 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.

  2. 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...

  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. 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.

  5. Reliable and Valid Assessment of Clinical Bronchoscopy Performance

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  6. 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...

  7. 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...

  8. 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

  9. 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

  10. 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

  11. Effect of target configuration on the neutronic performance of the gas-cooled ADS for transmutation

    International Nuclear Information System (INIS)

    The safe disposal and enclosure of high level radioactive waste (HLW) in long time rang is a great responsibility. In this respect Partitioning and Transmutation (P and T) represent a feasible way for efficient reduction and minimisation of the radiotoxic potential of highly radioactive transuranic elements including their radiological impact on the geological formations and environment. As a possible and promising option the use of the Accelerated-Driven Systems (ADS), consisting of a high power spallation neutron source and fuelled transmutation zone, is increasingly considered and proposed in the framework of national and international research and development programs for utilization. Due to the complexity of the particle beam transport in the target assembly and neutron multiplication as well as the interaction with the transmutation core a sophisticated model has to be developed in the framework of our transmutation research project aiming at the study of the neutronic behaviour and performance of the whole system. For this purpose the concept of Advanced Gas-cooled Accelerator driven Transmutation Experiment (AGATE) is taken as a reference for the target -core interaction study and neutronic optimization of the design and configuration. As a result of comprehensive study a unique target design entitled layered spallation target is proposed which allows an extended neutron flux field covering large fuel zone for efficient transmutation. The work in this paper is focused on the study of the neutronic performance of the target-core system in terms of neutronic yield, flux shape and distribution as well as the aspect of source neutron multiplication for further improvements. (orig.)

  12. 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...

  13. 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...

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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…

  19. High-resolution 3D simulations of NIF ignition targets performed on Sequoia with HYDRA

    Science.gov (United States)

    Marinak, M. M.; Clark, D. S.; Jones, O. S.; Kerbel, G. D.; Sepke, S.; Patel, M. V.; Koning, J. M.; Schroeder, C. R.

    2015-11-01

    Developments in the multiphysics ICF code HYDRA enable it to perform large-scale simulations on the Sequoia machine at LLNL. With an aggregate computing power of 20 Petaflops, Sequoia offers an unprecedented capability to resolve the physical processes in NIF ignition targets for a more complete, consistent treatment of the sources of asymmetry. We describe modifications to HYDRA that enable it to scale to over one million processes on Sequoia. These include new options for replicating parts of the mesh over a subset of the processes, to avoid strong scaling limits. We consider results from a 3D full ignition capsule-only simulation performed using over one billion zones run on 262,000 processors which resolves surface perturbations through modes l = 200. We also report progress towards a high-resolution 3D integrated hohlraum simulation performed using 262,000 processors which resolves surface perturbations on the ignition capsule through modes l = 70. These aim for the most complete calculations yet of the interactions and overall impact of the various sources of asymmetry for NIF ignition targets. This work was performed under the auspices of the Lawrence Livermore National Security, LLC, (LLNS) under Contract No. DE-AC52-07NA27344.

  20. Detection of Clostridium tetani in human clinical samples using tetX specific primers targeting the neurotoxin.

    Science.gov (United States)

    Ganesh, Madhu; Sheikh, Nasira K; Shah, Pooja; Mehetre, Gajanan; Dharne, Mahesh S; Nagoba, Basavraj S

    2016-01-01

    Tetanus resulting from ear injury remains an important health problem, particularly in the developing world. We report the successful detection of Clostridium tetani using tetX specific primers targeting the Cl. tetani neurotoxin. The sample was obtained from an ear discharge of a case of otogenic tetanus in a 2-year-old male child. Based on the culture results of the ear discharge, Gram staining and virulence testing by genotyping, a diagnosis of tetanus was confirmed. This is the first report from India on the successful detection of Cl. tetani in a human clinical sample using tetX specific primers targeting the Cl. tetani neurotoxin. PMID:26220795

  1. 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

  2. 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)

  3. 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'.

  4. 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.

  5. 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

  6. Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study

    OpenAIRE

    Ban, J-W.; Emparanza, J I; Urreta, I.; Burls, A

    2016-01-01

    BACKGROUND: Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules' performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. METHODS: Electronic databases were searched for system...

  7. 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...

  8. 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…

  9. 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.

  10. Evaluation of performance for the EAST upgraded divertor targets during type I ELMy H-mode

    Science.gov (United States)

    Qian, X. Y.; Peng, X. B.; Wang, L.; Song, Y. T.; Ye, M. Y.; Zhang, J. W.; Li, W. X.; Zhu, C. C.

    2016-02-01

    The long-pulse high-confinement (H-mode) plasma regime is considered to be a preferable scenario in future fusion devices, and in the period of normal operation during H-mode, edge-localised modes (ELMs) are one of the most serious threats to the performance and capability of divertor targets. The EAST recently achieved a variety of H-mode regimes with ELMs. For the purpose of studying the performance of the EAST upgraded divertor during type I ELMs, a series of simulations were performed by using three-dimensional (3D) finite element code. To make a visible outcome of the direct ELM impact on the divertor targets, a preliminary evaluation system with three indices to exhibit the influence has been developed. The indices that comprise temperature evolution, thermal penetration depth and crack initiation life, which could reveal the process of micro-crack formation, are calculated in both low and high-power scenarios for type I ELMs. The initial results indicate that the transient heat load has a significant influence in a very short thickness layer along the direction perpendicular to the plasma-facing surface throughout its duration. The conclusion could offer a pertinent guide to the next-step high-power long-pulse operation in EAST and would also be helpful for scientifically studying the damage and fatigue mechanism of the divertor in ITER and future fusion power reactors.

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

    Science.gov (United States)

    Ganguli, Arijit; Clewell, Jerry; Shillington, Alicia C

    2016-01-01

    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 these, 12 reported positive impacts. Conclusion The preponderance of evidence suggests a positive impact of PSPs on adherence, clinical and humanistic outcomes. Although less often measured, health care utilization and

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

    International Nuclear Information System (INIS)

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

  13. 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

  14. 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

  15. 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...

  16. 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

  17. Nurses’ evaluation of physicians’ non-clinical performance in emergency departments: advantages, disadvantages and lessons learned

    OpenAIRE

    Alameddine, Mohamad; Mufarrij, Afif; Saliba, Miriam; Mourad, Yara; Jabbour, Rima; Hitti, Eveline

    2015-01-01

    Background Peer evaluation is increasingly used as a method to assess physicians’ interpersonal and communication skills. We report on experience with soliciting registered nurses’ feedback on physicians’ non-clinical performance in the ED of a large academic medical center in Lebanon. Methods We utilized a secondary analysis of a de-identified database of ED nurses’ assessment of physicians’ non-clinical performance coupled with an evaluation of interventions carried out as a result of this ...

  18. 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...

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

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution.

  20. 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...

  1. 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

  2. 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.

  3. 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...

  4. 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.

  5. 77 FR 30016 - Clinical Study Design and Performance of Hospital Glucose Sensors

    Science.gov (United States)

    2012-05-21

    ... Sensors AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments... Study Design and Performance of Hospital Glucose Sensors.'' The purpose of this public meeting is to discuss clinical study design considerations and performance metrics for innovative glucose...

  6. 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…

  7. 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. PMID:26928213

  8. 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

  9. Exploring the key performance areas and assessment criteria for the evaluation of students’ clinical performance: a delphi study

    Directory of Open Access Journals (Sweden)

    C. Joseph

    2011-02-01

    Full Text Available Background: evaluating  students’ clinical  performance  is  an integral part of the quality assurance in a physiotherapy curriculum, however, the objectivity during clinical examination have been questioned on numerous occasions.  The  aim  of  this  study  was  to  explore  the  essential  key  clinical performance areas and the associated assessment criteria in order to develop a reliable clinical assessment form.Methods: A Delphi study was used to obtain consensus on the development of a reliable clinical performance assessment tool. The study population consisted of  purposively  selected  academic  physiotherapy  staff  from  the  University  of Western Cape as well as supervisors and clinicians involved in the examination of  physiotherapy  students  from  the  three  Universities  in  the  Western Cape.  Findings  from  the  Delphi  rounds  were analysed  descriptively. Fifty  percent  or  higher  agreement  on  an  element  was  interpreted  as  an  acceptable  level of consensus.Results: Eight key performance areas were identified with five assessment criteria per key performance area as well as the weighting per area. It was evident that evaluators differed on the expectations of physiotherapy students as well as the criteria used to assess them.Conclusions: The Delphi panel contributed to the formulation of a clinical assessment form through the identification of  relevant  key  performance  areas  and  assessment  criteria  as  they  relate  to undergraduate  physiotherapy  training. Consensus on both aspects was reached following discussion and calculation of mean ranking sores.Implications: This process of reaching consensus in determining clear criteria for measuring key performance areas contributes to the objectivity of the process of examinations.

  10. 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.

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Jun; Li, Minghui; Zhang, Tao; Han, Wei; Chen, Dongfu; Hui, Zhouguang; Lv, Jima; Zhang, Zhong; Zhang, Yin; Zhang, Liansheng; Zheng, Rong; Dai, Jianrong; Wang, Luhua, E-mail: wlhwq@yahoo.com [Department of Radiotherapy, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing (China)

    2014-02-15

    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.

  13. 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...

  14. 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

  15. DNA vaccines targeting human papillomavirus-associated diseases: progresses in animal and clinical studies

    OpenAIRE

    Han, Kyusun Torque; Sin, Jeong-Im

    2013-01-01

    Human papillomavirus (HPV) infection is a major cause of cervical cancer and its precancerous diseases. Cervical cancer is the second deadliest cancer killer among women worldwide. Moreover, HPV is also known to be a causative agent of oral, pharyngeal, anal and genital cancer. Recent application of HPV structural protein (L1)-targeted prophylactic vaccines (Gardasil® and Cervarix®) is expected to reduce the incidence of HPV infection and cervical cancer, and possibly other HPV-associated can...

  16. 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...

  17. Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies.

    Science.gov (United States)

    Ulbrich, Karel; Holá, Kateřina; Šubr, Vladimir; Bakandritsos, Aristides; Tuček, Jiří; Zbořil, Radek

    2016-05-11

    Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer-drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving hydrophobic and electrostatic interactions, coordination chemistry, and encapsulation in porous materials. Principles of covalent conjugation of drugs with SPIONs including thermo- and pH-degradable bonds, amide linkage, redox-cleavable bonds, and enzymatically-cleavable bonds are also thoroughly described. Finally, results of clinical trials obtained with polymeric and magnetic carriers are analyzed highlighting the potential advantages and future directions in targeted anticancer therapy. PMID:27109701

  18. 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

  19. Heart rate, anxiety and performance of residents during a simulated critical clinical encounter: a pilot study

    OpenAIRE

    Clarke, Samuel; Horeczko, Timothy; Cotton, Dale; Bair, Aaron

    2014-01-01

    Background High-fidelity patient simulation has been praised for its ability to recreate lifelike training conditions. The degree to which high fidelity simulation elicits acute emotional and physiologic stress among participants – and the influence of acute stress on clinical performance in the simulation setting – remain areas of active exploration. We examined the relationship between residents’ self-reported anxiety and a proxy of physiologic stress (heart rate) as well as their clinical ...

  20. 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...

  1. Performance of Clinical Signs in the Diagnosis of Dehydration in Children with Acute Gastroenteritis

    OpenAIRE

    Hoxha, Teuta; Xhelili, Luan; Azemi, Mehmedali; Avdiu, Muharrem; Ismaili-Jaha, Vlora; Efendija-Beqa, Urata; Grajcevci-Uka, Violeta

    2015-01-01

    Background: Acute evaluation and treatment of children presenting with dehydration represent one of the most common situation in the pediatric emergency department. To identify dehydration in infants and children before treatment, a number of symptoms and clinical signs have been evaluated. The aim of the study was to describe the performance of clinical signs in detecting dehydration in children. Methods: Two hundred children aged 1 month to 5 year were involved in our prospective study. The...

  2. 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...

  3. Effect of Compound Sulfadiazine Suspension on Growth Performance of Broiler in Clinical Efficacy Trial

    OpenAIRE

    Leilei Wang; Li Zhao; Zhihui Hao; Kefeng Xiao; Fenfang Yang; Zhaopeng Ding

    2014-01-01

    Compound Sulfadiazine suspension is used mainly to prevent and cure E. coli, Salmonella infection of chicken in veterinary clinical application. Effect of compound Sulfadiazine suspension on growth performance of broiler in clinical efficacy trial was studied in the study. One hundred eighty 15-day-old broilers were divided randomly into six groups, blank control group, negative control group, Trisulmixos gavage group, Trisulmixos drinking group, Sufuning gavage group and Sufuning drinking gr...

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

    OpenAIRE

    Groenewoud, Hanny; van der Heide, Agnes; Onwuteaka-Philipsen, Bregje; Willems, Dick; Maas, Paul; 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 (one conducted in 1990 and 1991 and the other in 1995 and 1996), with a total of 649 cases. We categorized clinical problems as technical problems, such as difficulty inserting an intravenous line; complications, such as myoclo...

  5. 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

  6. 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.

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

    International Nuclear Information System (INIS)

    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

  8. 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.

  9. 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

    2015-09-01

    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.

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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.

  16. Clinical perspectives on targeting of myeloid derived suppressor cells in the treatment of cancer.

    Science.gov (United States)

    Najjar, Yana G; Finke, James H

    2013-01-01

    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 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, cyclooxygenase 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. PMID:23508517

  17. Setting goals and targets for performance standards within the Swedish health care system.

    Science.gov (United States)

    Axelsson, L; Svensson, P G

    1994-01-01

    The development of any health care system towards setting goals and targets and intended outcomes--with national guidelines, a legislative framework, limited resources, consumer influence and competitive forces--makes great demands on the control mechanisms required. The Swedish health care system has no tradition of goal formulation of this type. Hence, the purpose of this article is to clarify the goal-setting process of performance standards, and to examine whether goal setting is a relevant method within the organization of a Swedish county council. Goal setting can be seen partly as a control method and partly as an administrative process. The approach used is a combination of qualitative and quantitative methods. Data have been collected from interviews, observations, notes taken in the field and available performance statistics. The analysis shows that working towards a goal is made easier through a common and simple concept. It 'stands and falls' with the management of the work and its manager. Good communications and information are important prerequisites if goal formulation, through dialogue, is to succeed. This process takes time and can be described as an iterative process, in which a common behaviour pattern develops a 'we-feeling' which spreads among the staff. It is important that the goal is relevant and directly related to the basic objects of the work. It is also crucial that the goal is realistic and reflects a priority. Goal formulation relating to performance standards can be a contributing factor to staff's experience of job satisfaction through increased engagement and motivation, and to the satisfaction of patients/relatives with the care given. It is difficult to formulate performance standards; there are many problems and obstacles. If goal formulation as a control method within the health care system in Sweden is to work, clearer manifestations of political will are necessary and also better measuring methods in order to guage

  18. A Public-Private Partnership Improves Clinical Performance In A Hospital Network In Lesotho.

    Science.gov (United States)

    McIntosh, Nathalie; Grabowski, Aria; Jack, Brian; Nkabane-Nkholongo, Elizabeth Limakatso; Vian, Taryn

    2015-06-01

    Health care public-private partnerships (PPPs) between a government and the private sector are based on a business model that aims to leverage private-sector expertise to improve clinical performance in hospitals and other health facilities. Although the financial implications of such partnerships have been analyzed, few studies have examined the partnerships' impact on clinical performance outcomes. Using quantitative measures that reflected capacity, utilization, clinical quality, and patient outcomes, we compared a government-managed hospital network in Lesotho, Africa, and the new PPP-managed hospital network that replaced it. In addition, we used key informant interviews to help explain differences in performance. We found that the PPP-managed network delivered more and higher-quality services and achieved significant gains in clinical outcomes, compared to the government-managed network. We conclude that health care public-private partnerships may improve hospital performance in developing countries and that changes in management and leadership practices might account for differences in clinical outcomes. PMID:26056200

  19. 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.

  20. A preliminary study of three-dimensional conformal radiotherapy with different clinical target volumes for esophageal cancer

    International Nuclear Information System (INIS)

    Objective: To investigate the value of prophylactic irradiation to the lymphatic drainage area in radical three-dimensional conformal radiotherapy (3DCRT) and to evaluate the efficacy and adverse effects of 3DCRT with different clinical target volumes. Methods: A retrospective analysis was performed on the records of 219 esophageal cancer patients without distant metastasis who received 3DCRT from January 2005 to December 2010. One hundred and five patients received involved-field irradiation (IFI) with a total dose of 54-66 Gy; 114 patients received elective nodal irradiation (ENI) with a total dose of 46-52 Gy; the prescribed dose to the primary lesion was 56-70 Gy. The Kaplan-Meier method was used to calculate local control (LC) and overall survival (OS) rates,and the log-rank test was used for univariate prognostic analysis. Results: The 1-, 3-, and 5-year sample sizes were 219, 172 and 67,respectively. The 1-,3-,and 5-year LC rates for IFI group were 63.0%, 39.1%, and 27.2%, respectively, versus 70.5%, 53.3%, and 51.7% for ENI group (χ2=6.22, P=0.013); the 1-, 3-, and 5-year OS rates for IFI group were 67.6%, 24.9%, and 15.0%, respectively, versus 73.7%, 45.1%, and 26.0% for ENI group (χ2=5.04, P=0.025). The univariate stratified analysis showed that the LC and OS rates were significantly higher in the ENI group than in the IFI group for patients with middle-or lower-thoracic primary lesion or N0 disease (P=0.007, 0.015; P=0.054, 0.013). Conclusions: For esophageal cancer patients with middle-or lower-thoracic primary lesion or without lymph node metastasis, prophylactic irradiation to the lymphatic drainage area can increase LC and OS rates. (authors)

  1. 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

  2. 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...

  3. Effect of the Target Motion Sampling temperature treatment method on the statistics and performance

    International Nuclear Information System (INIS)

    Highlights: • Use of the Target Motion Sampling (TMS) method with collision estimators is studied. • The expected values of the estimators agree with NJOY-based reference. • In most practical cases also the variances of the estimators are unaffected by TMS. • Transport calculation slow-down due to TMS dominates the impact on figures-of-merit. - Abstract: Target Motion Sampling (TMS) is a stochastic on-the-fly temperature treatment technique that is being developed as a part of the Monte Carlo reactor physics code Serpent. The method provides for modeling of arbitrary temperatures in continuous-energy Monte Carlo tracking routines with only one set of cross sections stored in the computer memory. Previously, only the performance of the TMS method in terms of CPU time per transported neutron has been discussed. Since the effective cross sections are not calculated at any point of a transport simulation with TMS, reaction rate estimators must be scored using sampled cross sections, which is expected to increase the variances and, consequently, to decrease the figures-of-merit. This paper examines the effects of the TMS on the statistics and performance in practical calculations involving reaction rate estimation with collision estimators. Against all expectations it turned out that the usage of sampled response values has no practical effect on the performance of reaction rate estimators when using TMS with elevated basis cross section temperatures (EBT), i.e. the usual way. With 0 Kelvin cross sections a significant increase in the variances of capture rate estimators was observed right below the energy region of unresolved resonances, but at these energies the figures-of-merit could be increased using a simple resampling technique to decrease the variances of the responses. It was, however, noticed that the usage of the TMS method increases the statistical deviances of all estimators, including the flux estimator, by tens of percents in the vicinity of very

  4. Application of C-arm CT-guided targeted puncturing technique in performing non-vascular interventional biopsy or interventional therapy

    International Nuclear Information System (INIS)

    Objective: to investigate the clinical value of C-arm CT-guided targeted puncturing technique in performing non, vascular interventional biopsy or interventional therapy. Methods: Thirty, one patients, who were encountered in authors' hospital during the period from July 2010 to September 2010, were involved in this study. C-arm CT-guided percutaneous targeted puncturing biopsy or interventional therapy was performed in all 31 patients. All patients had complete clinical data. The complications and positive rate of biopsy were recorded and analyzed. Results: Under C-arm CT-guidance, percutaneous interventional therapy was carried out in 13 patients. The interventional procedures included radiofrequency ablation therapy for hepatic cellular carcinoma (n=2), pelvic abscess draining (n=1), hepatic abscess draining (n=1), ethanol injection for liver cancer (n=4), sclerotic therapy with ethanol injection for renal cyst (n=2), sclerotic therapy with ethanol injection for liver cyst (n=2) and catheter-indwelling drainage for pancreatic pseudocyst (n=1). percutaneous interventional biopsy was performed in the remaining 18 cases, including liver (n=4), lung (n=7), mediastinum (n=2), bone and soft tissue (n=4) and neck mass (n=1). All the procedures were successfully accomplished, no technique, related complications occurred during the operation. For biopsy examination in 18 cases, the positive rate was 94.4% (17/18) and false, negative results was seen in one case with lung lesion. Conclusion: The percutaneous targeted puncturing technique with C, arm CT-guidance combines the advantages of both CT scanning and fluoroscopy. The use of real, time road, mapping function can effectively guide the puncturing and therapeutic management, which can not only optimize the workflow, save the operation time, but also improve the success rate and technical safety. Therefore, it is of great value to popularize this targeted puncturing technique. (authors)

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

    LENUS (Irish Health Repository)

    MacMahon Tone, J

    2009-06-01

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

  6. Targeted Proteomics of Human Metapneumovirus in Clinical Samples and Viral Cultures.

    Science.gov (United States)

    Foster, Matthew W; Gerhardt, Geoff; Robitaille, Lynda; Plante, Pier-Luc; Boivin, Guy; Corbeil, Jacques; Moseley, M Arthur

    2015-10-20

    The rapid, sensitive, and specific identification of infectious pathogens from clinical isolates is a critical need in the hospital setting. Mass spectrometry (MS) has been widely adopted for identification of bacterial pathogens, although polymerase chain reaction remains the mainstay for the identification of viral pathogens. Here, we explored the capability of MS for the detection of human metapneumovirus (HMPV), a common cause of respiratory tract infections in children. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) sequencing of a single HMPV reference strain (CAN97-83) was used to develop a multiple reaction monitoring (MRM) assay that employed stable isotope-labeled peptide internal standards for quantitation of HMPV. Using this assay, we confirmed the presence of HMPV in viral cultures from 10 infected patients and further assigned genetic lineage based on the presence/absence of variant peptides belonging to the viral matrix and nucleoproteins. Similar results were achieved for primary clinical samples (nasopharyngeal aspirates) from the same individuals. As validation, virus lineages, and variant coding sequences, were confirmed by next-generation sequencing of viral RNA obtained from the culture samples. Finally, separate dilution series of HMPV A and B lineages were used to further refine and assess the robustness of the assay and to determine limits of detection in nasopharyngeal aspirates. Our results demonstrate the applicability of MRM for identification of HMPV, and assignment of genetic lineage, from both viral cultures and clinical samples. More generally, this approach should prove tractable as an alternative to nucleic-acid based sequencing for the multiplexed identification of respiratory virus infections. PMID:26376123

  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. Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date.

    Science.gov (United States)

    Crassini, Kyle; Mulligan, Stephen P; Best, O Giles

    2015-08-16

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Despite significant advances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cells in vivo, the most notable of which are the pathways mediated by the B-cell receptor (BCR) and cytokine receptors. A better understanding of the pathogenesis of the disease, the underlying biology of the CLL-cell and the roles of the tumour microenvironment has provided the rationale for trials of a range of novel, more targeted therapeutic agents. In particular, clinical trials of ibrutinib and idelalisib, which target the Brutons tyrosine kinase and the delta isoform of phosphoinositol-3 kinase components of the BCR signaling pathway respectively, have shown extremely promising results. Here we review the current literature on the key signaling pathways and interactions of CLL cells that mediate the survival and proliferation of the leukemic cells. For each we describe the results of the recent clinical trials and in vitro studies of novel therapeutic agents. PMID:26301230

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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...

  15. Change in action: using positive deviance to improve student clinical performance.

    Science.gov (United States)

    Zaidi, Zareen; Jaffery, Tara; Shahid, Afshan; Moin, Shaheen; Gilani, Ahsen; Burdick, William

    2012-03-01

    At our medical college many students have lower ratings in their clinical performance once they start their clinical years (third year). This is contrary to their results in other written exams. Some students demonstrate better clinical performance. We used the six-step Positive Deviance (PD) Conceptual Framework to identify and disseminate the strategies employed by the successful students to improve group clinical performance. Fifty 3rd year students (of a 5-year MBBS program) rotating through internal medicine were assessed mid-rotation with mini-CEX and 360° evaluations. Twenty students (40%) who performed well were invited for in depth interviews in order to identify positive deviant behavior in their clinical skills learning practices. The seven students (14%) who reported novel behaviors were asked to develop strategies for dissemination of their learning behavior in their peers. They decided to work in small groups with their peers, using the identified PD behaviors to encourage learning of history taking and examining skills in their peers. Group performance was assessed at the end of rotation, using mini-CEX and 360° evaluation in comparison to a subsequent group of students in the same year that did not work in PD peer learning groups. For the 360° evaluation the EP(2) (generalizability coefficient) was 0.92 and for the mini-CEX the EP(2) was 0.95, taking into account the variances between participants, groups, time and the interactions effects; thus indicating good reliability of both the assessment methods. A statistically significant difference (p exam and 360 evaluation (p Learning strategies based on the PD framework can improve student's group performance. PMID:21553153

  16. 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…

  17. 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.

  18. 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.

  19. 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...

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

    International Nuclear Information System (INIS)

    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

  1. 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.

  2. 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.

  3. 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

  4. 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…

  5. Does sensitivity measured from screening test-sets predict clinical performance?

    Science.gov (United States)

    Soh, BaoLin P.; Lee, Warwick B.; Mello-Thoms, Claudia R.; Tapia, Kriscia A.; Ryan, John; Hung, Wai Tak; Thompson, Graham J.; Heard, Rob; Brennan, Patrick C.

    2014-03-01

    Aim: To examine the relationship between sensitivity measured from the BREAST test-set and clinical performance. Background: Although the UK and Australia national breast screening programs have regarded PERFORMS and BREAST test-set strategies as possible methods of estimating readers' clinical efficacy, the relationship between test-set and real life performance results has never been satisfactorily understood. Methods: Forty-one radiologists from BreastScreen New South Wales participated in this study. Each reader interpreted a BREAST test-set which comprised sixty de-identified mammographic examinations sourced from the BreastScreen Digital Imaging Library. Spearman's rank correlation coefficient was used to compare the sensitivity measured from the BREAST test-set with screen readers' clinical audit data. Results: Results shown statistically significant positive moderate correlations between test-set sensitivity and each of the following metrics: rate of invasive cancer per 10 000 reads (r=0.495; p DCIS per 10 000 reads (r=0.444; p < 0.01). Conclusion: Comparison between sensitivity measured from the BREAST test-set and real life detection rate demonstrated statistically significant positive moderate correlations which validated that such test-set strategies can reflect readers' clinical performance and be used as a quality assurance tool. The strength of correlation demonstrated in this study was higher than previously found by others.

  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. Targeted approaches in the treatment of osteoporosis: differential mechanism of action of denosumab and clinical utility

    Directory of Open Access Journals (Sweden)

    Cavalli L

    2012-06-01

    Full Text Available Loredana Cavalli, Maria Luisa BrandiUnit of Mineral and Bone Metabolism Diseases, Department of Internal Medicine, Traumatologic Orthopedic Center, Florence, ItalyAbstract: Denosumab is a breakthrough biological drug approved by the Food and Drug Administration and European Medicines Agency for the treatment of osteoporosis in 2010. It is a fully human monoclonal antireceptor activator of nuclear factor kappa-B ligand antibody, which inhibits the activity of osteoclasts, resulting in an antiresorptive effect with a significant increase in bone mineral density. The FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months trial, comparing denosumab with no treatment in 7868 women with postmenopausal osteoporosis, showed an important reduction of fracture risk at hip, vertebral, and nonvertebral sites in the treated group, while no statistically significant difference in the incidence of adverse events was detected between denosumab and placebo groups. The specific action of denosumab directed against a key regulator of osteoclasts makes it a valuable tool in preventing the occurrence of skeletal events caused by bone destruction in patients with advanced malignancies. The drug was approved for postmenopausal osteoporosis in women at increased risk of fracture and for the treatment of bone loss associated with androgen deprivation therapy in men with prostate cancer.Keywords: osteoporosis, denosumab, targeted therapy, BMD, antibody, RANK-L

  8. 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

  9. Performance of speech-language pathology students in problem-based learning tutorials and in clinical practice.

    Science.gov (United States)

    Ho, Diana W L; Whitehill, Tara L; Ciocca, Valter

    2014-01-01

    The purpose of the study was to identify if performance of speech-language pathology students in problem-based learning (PBL) tutorials could predict subsequent clinical performance evaluated through (a) a non-standardized, custom clinical evaluation form (HKU form) and (b) a standardized competency assessment for speech pathology developed in Australia (COMPASS®). Students' scores from PBL tutorial performance were correlated with scores in clinical placement on both the HKU form and the COMPASS. Significant correlations were found between students' PBL tutorial performance (reflective journals and participation in the tutorial process) and their clinical performance (treatment and interpersonal skills) on the HKU clinical evaluation form. Significant correlations were also found between (a) PBL tutorial performance (participation in the tutorial process) and their clinical performance (all generic and occupational competencies, and the overall score) on the COMPASS, (b) PBL tutorial performance (reading forms) and two occupational competencies on the COMPASS, (c) PBL tutorial performance (reflective journals) and four occupational competencies and the overall score on the COMPASS. The results highlighted the need for validating the assessment for the learning process in PBL tutorials with empirical evidence and the advantage of assessing clinical performance through COMPASS in Hong Kong. Tutors, clinical supervisors and students should be given clear behavioral descriptors for expected performance in PBL tutorials and clinical practice at different year levels. PMID:23889172

  10. 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

  11. 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

  12. 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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  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. PMID:26422540

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. Clinical decision making in response to performance validity test failure in a psychiatric setting.

    Science.gov (United States)

    Marcopulos, Bernice A; Caillouet, Beth A; Bailey, Christopher M; Tussey, Chriscelyn; Kent, Julie-Ann; Frederick, Richard

    2014-01-01

    This study examined the clinical utility of a performance validity test (PVT) for screening consecutive referrals (N = 436) to a neuropsychology service at a state psychiatric hospital treating both civilly committed and forensic patients. We created a contingency table with Test of Memory Malingering (TOMM) pass/fail (355/81) and secondary gain present/absent (181/255) to examine pass rates associated with patient demographic, clinical and forensic status characteristics. Of the 81 failed PVTs, 48 had secondary gain defined as active criminal legal charges; 33 failed PVTs with no secondary gain. These individuals tended to be older, female, Caucasian, and civilly committed compared with the group with secondary gain who failed. From estimations of TOMM False Positive Rate and True Positive Rate we estimated base rates of neurocognitive malingering for our clinical population using the Test Validation Summary (TVS; Frederick & Bowden, 2009 ). Although PVT failure is clearly more common in a group with secondary gain (31%), there were a number of false positives (11%). Clinical ratings of patients without gain who failed suggested cognitive deficits, behavioral issues, and inattention. Low scores on PVTs in the absence of secondary gain provide useful information on test engagement and can inform clinical decisions about testing. PMID:24678658

  2. Magnetic bead-based nucleic acid purification kit: Clinical application and performance evaluation in stool specimens.

    Science.gov (United States)

    Yoon, Jihoon G; Kang, Jin Seok; Hwang, Seung Yong; Song, Jaewoo; Jeong, Seok Hoon

    2016-05-01

    Two different methods - the semi-automated magnetic bead-based kit (SK, Stool DNA/RNA Purification kit®) and the manual membrane column-based kit (QS, QIAamp® DNA Stool Mini kit) - for purifying nucleic acids from clinical stool samples were compared and evaluated. The SK kit was more user-friendly than QS due to the reduced manual processing, partial automation, and short turnaround time with half cost. Furthermore, SK produced high yields in both DNA and RNA extractions but poor purity in RNA extraction. In the assessment of rotavirus and Clostridium difficile infection, both kits had equivalent or more sensitive performance compared with the standard method. Although SK showed some interference and inhibition in nucleic acid extraction, the performance, including the repeatability, linearity, analytical sensitivity, and matrix effect, was sufficient for routine clinical use. PMID:27030641

  3. Effect of Compound Sulfadiazine Suspension on Growth Performance of Broiler in Clinical Efficacy Trial

    Directory of Open Access Journals (Sweden)

    Leilei Wang

    2014-04-01

    Full Text Available Compound Sulfadiazine suspension is used mainly to prevent and cure E. coli, Salmonella infection of chicken in veterinary clinical application. Effect of compound Sulfadiazine suspension on growth performance of broiler in clinical efficacy trial was studied in the study. One hundred eighty 15-day-old broilers were divided randomly into six groups, blank control group, negative control group, Trisulmixos gavage group, Trisulmixos drinking group, Sufuning gavage group and Sufuning drinking group, respectively. There were three repeating treatments in each group and ten broilers in each treatment. Results showed that compound Sulfadiazine suspension can promote the feed conversion rate of broiler when curing E. coli, Salmonella infection of chicken. Both from the perspective of efficacy and from the perspective of growth performance, giving drug by gavage were more effective than giving by drinking. When two products of Compound Sulfadiazine suspension were compared, the indicators of Sufuning were a little better Trisulmixos.

  4. Variability and robustness of scatterers in HRR/ISAR ground target data and its influence on the ATR performance

    Science.gov (United States)

    Schumacher, R.; Schimpf, H.; Schiller, J.

    2011-06-01

    The most challenging problem of Automatic Target Recognition (ATR) is the extraction of robust and independent target features which describe the target unambiguously. These features have to be robust and invariant in different senses: in time, between aspect views (azimuth and elevation angle), between target motion (translation and rotation) and between different target variants. Especially for ground moving targets in military applications an irregular target motion is typical, so that a strong variation of the backscattered radar signal with azimuth and elevation angle makes the extraction of stable and robust features most difficult. For ATR based on High Range Resolution (HRR) profiles and / or Inverse Synthetic Aperture Radar (ISAR) images it is crucial that the reference dataset consists of stable and robust features, which, among others, will depend on the target aspect and depression angle amongst others. Here it is important to find an adequate data grid for an efficient data coverage in the reference dataset for ATR. In this paper the variability of the backscattered radar signals of target scattering centers is analyzed for different HRR profiles and ISAR images from measured turntable datasets of ground targets under controlled conditions. Especially the dependency of the features on the elevation angle is analyzed regarding to the ATR of large strip SAR data with a large range of depression angles by using available (I)SAR datasets as reference. In this work the robustness of these scattering centers is analyzed by extracting their amplitude, phase and position. Therefore turntable measurements under controlled conditions were performed targeting an artificial military reference object called STANDCAM. Measures referring to variability, similarity, robustness and separability regarding the scattering centers are defined. The dependency of the scattering behaviour with respect to azimuth and elevation variations is analyzed. Additionally generic types

  5. Patterns of epidural progression following postoperative spine stereotactic body radiotherapy: implications for clinical target volume delineation.

    Science.gov (United States)

    Chan, Michael W; Thibault, Isabelle; Atenafu, Eshetu G; Yu, Eugene; John Cho, B C; Letourneau, Daniel; Lee, Young; Yee, Albert; Fehlings, Michael G; Sahgal, Arjun

    2016-04-01

    OBJECT The authors performed a pattern-of-failure analysis, with a focus on epidural disease progression, in patients treated with postoperative spine stereotactic body radiotherapy (SBRT). METHODS Of the 70 patients with 75 spinal metastases (cases) treated with postoperative spine SBRT, there were 26 cases of local disease recurrence and 25 cases with a component of epidural disease progression. Twenty-four of the 25 cases had preoperative epidural disease with subsequent epidural disease progression, and this cohort was the focus of this epidural-specific pattern-of-failure investigation. Preoperative, postoperative, and follow-up MRI scans were reviewed, and epidural disease was characterized based on location according to a system in which the vertebral anatomy is divided into 6 sectors, with the anterior compartment comprising Sectors 1, 2, and 6, and the posterior compartment comprising Sectors 3, 4, and 5. RESULTS Patterns of epidural progression are reported specifically for the 24 cases with preoperative epidural disease and subsequent epidural progression. Epidural disease progression within the posterior compartment was observed to be significantly lower in those with preoperative epidural disease confined to the anterior compartment than in those with preoperative epidural disease involving both anterior and posterior compartments (56% vs 93%, respectively; p = 0.047). In a high proportion of patients with epidural disease progression, treatment failure was found in the anterior compartment, including both those with preoperative epidural disease confined to the anterior compartment and those with preoperative epidural disease involving both anterior and posterior compartments (100% vs. 73%, respectively). When epidural disease was confined to the anterior compartment on the preoperative and postoperative MRIs, no epidural disease progression was observed in Sector 4, which is the most posterior sector. Postoperative epidural disease characteristics

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

    International Nuclear Information System (INIS)

    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 (P30 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

    OBJECTIVE: This study aimed to evaluate the safety and performance of a new sustained silver-releasing dressing, Contreet Foam (Coloplast A/S), in the treatment of moderately to highly exuding chronic venous leg ulcers in which healing is delayed due to the presence of bacteria. METHOD: 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......: Contreet Foam was found to be safe and performed well when used in the treatment of delayed-healing chronic venous leg ulcers, combining effective antibacterial properties with excellent exudate management. DECLARATION OF INTEREST: This study was supported by Coloplast A/S, Humlebaek, Denmark....

  12. The Evaluation of Human Resource Management Practices - Empirical Studies on Subjective Performance Evaluation, Target Agreements, and Intra-Firm Trainings

    OpenAIRE

    Breuer, Kathrin Anne

    2011-01-01

    As human capital is a major source of economic growth in today's organizations, there is a need for well-functioning human resource practices that are designed to guide and direct the effort of employees. This thesis investigates three relevant human resource practices: subjective performance evaluations, target agreements and intra-firm trainings. Four empirical papers are presented that reveal insights about biases in performance evaluations, gender differences in manager's evaluation behav...

  13. 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.

  14. Performance of the AOAC use-dilution method with targeted modifications: collaborative study.

    Science.gov (United States)

    Tomasino, Stephen F; Parker, Albert E; Hamilton, Martin A; Hamilton, Gordon C

    2012-01-01

    The U.S. Environmental Protection Agency (EPA), in collaboration with an industry work group, spearheaded a collaborative study designed to further enhance the AOAC use-dilution method (UDM). Based on feedback from laboratories that routinely conduct the UDM, improvements to the test culture preparation steps were prioritized. A set of modifications, largely based on culturing the test microbes on agar as specified in the AOAC hard surface carrier test method, were evaluated in a five-laboratory trial. The modifications targeted the preparation of the Pseudomonas aeruginosa test culture due to the difficulty in separating the pellicle from the broth in the current UDM. The proposed modifications (i.e., the modified UDM) were compared to the current UDM methodology for P. aeruginosa and Staphylococcus aureus. Salmonella choleraesuis was not included in the study. The goal was to determine if the modifications reduced method variability. Three efficacy response variables were statistically analyzed: the number of positive carriers, the log reduction, and the pass/fail outcome. The scope of the collaborative study was limited to testing one liquid disinfectant (an EPA-registered quaternary ammonium product) at two levels of presumed product efficacies, high and low. Test conditions included use of 400 ppm hard water as the product diluent and a 5% organic soil load (horse serum) added to the inoculum. Unfortunately, the study failed to support the adoption of the major modification (use of an agar-based approach to grow the test cultures) based on an analysis of method's variability. The repeatability and reproducibility standard deviations for the modified method were equal to or greater than those for the current method across the various test variables. However, the authors propose retaining the frozen stock preparation step of the modified method, and based on the statistical equivalency of the control log densities, support its adoption as a procedural change to

  15. Performance metrics for point target detection in consecutive frame IR imagery

    Science.gov (United States)

    Silverman, Jerry; Caefer, Charlene E.; Mooney, Jonathan M.

    1995-09-01

    In the companion paper, two algorithms for tracking point targets in consecutive frame staring IR imagery with evolving cloud clutter are described and compared by using representative example scenes. Here, our total data base of local airborne scenes with targets of opportunity are used for a more quantitative and comprehensive comparison. The use of real world data as well as our focus on temporal filtering over large number of consecutive frames triggered a search for more relevant metrics than those available. We present two new metrics which have most of the attributes sought. In each metric, gain is taken as a ratio of output to input signal to clutter. Maximum values rather than statistical measures are used for clutter. In the variation metric (VM), a temporal standard deviation for each pixel over 95 consecutive frames is computed and the maximum non-target result is taken as the input clutter. The input signal, a real target moving with sub-pixel velocity through sampled imagery, is estimated by a reference mean technique. Output signal and clutter are taken as maximum target and clutter affected pixels in algorithm filtered outputs. In the second metric, the use of an anti-median filter (AM) provides symmetric treatment of input and output as well as signal and clutter. The maximum target and non-target response to the AM filter on input frames and output frames defines the signal and clutter measures. Our set of real-world data is plotted as output versus input signal to clutter for each metric and each algorithm and the pros and cons of each metric is discussed. With either metric, the signal to clutter gain ratios are approximately 5 - 6 dB greater with the temporal filter algorithm than with the velocity filter algorithm.

  16. 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....

  17. 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...

  18. Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer

    International Nuclear Information System (INIS)

    Phosphatase of regenerating liver-3 (PRL-3) has deserved attention as a crucial molecule in the multiple steps of metastasis. In the present study, we examined the mechanisms regulating PRL-3 expression, and assessed the clinical potential of PRL-3-targeted therapy in gastric cancer. PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) treatment was evaluated against cancer cells with different genetic and expression status. PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40) among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20), but in none (0/37) among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (P = 0.021). PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression. We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression

  19. Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer

    Directory of Open Access Journals (Sweden)

    Nishimiya Hiroshi

    2011-04-01

    Full Text Available Abstract Background Phosphatase of regenerating liver-3 (PRL-3 has deserved attention as a crucial molecule in the multiple steps of metastasis. In the present study, we examined the mechanisms regulating PRL-3 expression, and assessed the clinical potential of PRL-3-targeted therapy in gastric cancer. Methods PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine treatment was evaluated against cancer cells with different genetic and expression status. Results PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40 among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20, but in none (0/37 among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (P = 0.021. PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression. Conclusions We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression.

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

    International Nuclear Information System (INIS)

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

  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. 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...

  3. 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

  4. 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

  5. Software-controlled, highly automated intrafraction prostate motion correction with intrafraction stereographic targeting: System description and clinical results

    International Nuclear Information System (INIS)

    Purpose: A new system for software-controlled, highly automated correction of intrafraction prostate motion,'' intrafraction stereographic targeting'' (iSGT), is described and evaluated. Methods: At our institute, daily prostate positioning is routinely performed at the start of treatment beam using stereographic targeting (SGT). iSGT was implemented by extension of the SGT software to facilitate fast and accurate intrafraction motion corrections with minimal user interaction. iSGT entails megavoltage (MV) image acquisitions with the first segment of selected IMRT beams, automatic registration of implanted markers, followed by remote couch repositioning to correct for intrafraction motion above a predefined threshold, prior to delivery of the remaining segments. For a group of 120 patients, iSGT with corrections for two nearly lateral beams was evaluated in terms of workload and impact on effective intrafraction displacements in the sagittal plane. Results: SDs of systematic (Σ) and random (σ) displacements relative to the planning CT measured directly after initial SGT setup correction were eff eff eff eff eff eff < 0.7 mm, requiring corrections in 82.4% of the fractions. Because iSGT is highly automated, the extra time added by iSGT is <30 s if a correction is required. Conclusions: Without increasing imaging dose, iSGT successfully reduces intrafraction prostate motion with minimal workload and increase in fraction time. An action level of 2 mm is recommended.

  6. Defining and Using Performance Indicators and Targets in Government M and E Systems

    OpenAIRE

    Castro, Manuel Fernando

    2011-01-01

    Developing effective national monitoring and evaluation (M&E) systems and/or performance budgeting initiatives requires well-defined formulation and implementation strategies for setting up performance indicators. These strategies vary depending on a country's priority for measuring results and on the scope and pace of its performance management reform objectives. Some countries have follo...

  7. 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.

  8. 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.

  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. The use of application-specific performance targets and engineering considerations to guide hydrogen storage materials development

    International Nuclear Information System (INIS)

    Highlights: •Portable power and material handling equipment as early market technology pathways. •Engineering based system-level storage-materials requirements. •Application based targets. -- Abstract: The Hydrogen and Fuel Cells Technologies Office, carried out through the DOE Office of Energy Efficiency and Renewable Energy, maintains a broad portfolio of activities to enable the commercialization of fuel cells across a range of near, mid and long-term applications. Improved, advanced hydrogen storage technologies are seen as a critical need for successful implementation of hydrogen fuel cells in many of these applications. To guide and focus materials development efforts, the DOE develops system performance targets for the specific applications of interest, and carries out system engineering analyses to determine the system-level performance delivered when the materials are incorporated into a complete system. To meet the needs of applications, it is important to consider the system-level performance, not just the material-level properties. An overview of the DOE’s hydrogen storage efforts in developing application-specific performance targets and systems engineering to guide hydrogen storage materials identification and development is herein provided

  11. 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.

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

    International Nuclear Information System (INIS)

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

  13. Permanent target for optical payload performance and data quality assessment: spectral characterization and a case study for calibration

    Science.gov (United States)

    Li, Chuanrong; Ma, Lingling; Gao, Caixia; Tang, Lingli; Wang, Ning; Liu, Yaokai; Zhao, Yongguang; Dou, Shuai; Zhang, Dandan; Li, Xiaohui

    2014-01-01

    To regularly evaluate the optical payload performance (geometric, radiometric, and spatial resolution) and the data quality for high-resolution airborne and satellite imaging systems, two new permanent targets (the knife-edge target and the fan-shaped target) made of gravel and with the advantages of year-round availability, lower maintenance operations, and a long lifetime were established in the Academy of Opto-Electronics Baotou site in China. The spectral properties of these targets are investigated in this study. Note that the anisotropy factor at 550 nm for the white gravel is approximately 6%, 12.5% 16.5%, 17.5%, 11.5%, and 5% at the principal plane for the observer zenith angle of 60 deg, 50 deg, 40 deg, 30 deg, 20 deg, and 10 deg (backscatter), respectively. The corresponding value for the gray gravel is 20.8%, 24.8%, 29.4%, 23.8%, 13%, and 3.7%, respectively, and 62.8%, 65.7%, 59.2%, 40.3%, 22.3%, and 9.0%, respectively, for the black gravel. The anisotropy of the black gravel is larger than that of the gray and white gravel areas. The nonuniformity of the target reflectivity is within 2.5%. Furthermore, a calibration for the optical payloads onboard the GF-1 satellite is performed with the knife-edge target, and the uncertainty analysis demonstrates that the uncertainty for this calibration is <2.12% when the relative error for the surface reflectance measurement, the aerosol optical depth, and the total column water vapor are approximately 1%, 10%, and 10%, respectively.

  14. 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.

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

    International Nuclear Information System (INIS)

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

  16. Getting better, but not well: A 1.5 year follow-up of cognitive performance and cortisol levels in clinical and non-Clinical burnout.

    Science.gov (United States)

    Oosterholt, Bart G; Maes, Joseph H R; Van der Linden, Dimitri; Verbraak, Marc J P M; Kompier, Michiel A J

    2016-05-01

    The purpose was to reexamine cognitive performance and cortisol levels of initial clinical burnout patients, non-clinical burnout individuals, and healthy controls. After 1.5-years of the initial measurement, clinical burnout patients showed a reduction of burnout symptoms and general physical and psychological complaints, but these were still elevated compared with controls. Nonetheless, they continued to report cognitive problems and still showed a minor impaired cognitive test performance. However, they no longer reported larger subjective costs associated with cognitive test performance and their cortisol awakening response (CAR) returned to a normal level. Compared with controls, non-clinical burnout individuals still reported the same, elevated, level of burnout symptoms, general physical and psychological complaints, and cognitive problems. Their cognitive test performance and associated subjective costs remained normal. However, they seemed to continue to display a lowered CAR. To conclude, after 1.5-years, clinical burnout patients got better, but not 'well', and non-clinical burnout individuals remained not 'well'. PMID:26930250

  17. 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...

  18. 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...

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Performance analysis of swarm optimization approaches for the generalized assignment problem in multi-target tracking applications

    OpenAIRE

    BOZDOĞAN, Ali Önder; YILMAZ, Asım Egemen; EFE, Murat

    2010-01-01

    The aim of this study is to investigate the suitability of selected swarm optimization algorithms to the generalized assignment problem as encountered in multi-target tracking applications. For this purpose, we have tested variants of particle swarm optimization and ant colony optimization algorithms to solve the 2D generalized assignment problem with simulated dense and sparse measurement/track matrices and compared their performance to that of the auction algorithm. We observed tha...

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

    Directory of Open Access Journals (Sweden)

    Cookson Richard

    2008-06-01

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

  5. 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…

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.)

  11. 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

  12. Do Primary Care Physician Perform Clinical Breast Exams Prior to Ordering a Mammogram?

    Science.gov (United States)

    Larson, Kelsey E; Cowher, Michael S; O'Rourke, Colin; Patel, Mita; Pratt, Debra

    2016-03-01

    Both the American Cancer Society and National Comprehensive Cancer Network recommend annual clinical breast examination (CBE) along with screening mammogram (SM) for patients starting at 40 years of age. However, patients with a palpable breast mass should have a diagnostic mammogram (DM) during workup. Review at our institution demonstrated that 11% of patients with newly diagnosed breast cancer and self-identified breast mass had SM instead of DM. This led us to question whether primary care physicians (PCP) perform CBE prior to ordering mammography. As part of the routine preimaging screening, patients were asked if they had undergone breast examination by a medical provider prior to mammogram order. Data on mammogram type, ordering physician specialty, and presence of symptoms on day of mammogram were recorded. Of 6,109 mammograms, 4,823 were ordered by PCPs. CBE was performed prior to 67.2% SM and 64.8% DM (p = 0.12). OB/GYN performed statistically significantly higher CBE (81.6%) compared to internal (45.4%) and family (50.5%) medicine physicians (p self-reported breast symptoms, 8.7% had SM ordered rather than DM. Despite recommendations, approximately 1/3 of women report not having CBE prior to mammogram. The chances of having a CBE varied significantly by PCP specialty. Lack of CBE can lead to incorrect type of mammogram, with possibly increased cost and delay in diagnosis. Further evaluation is needed to understand why CBE was not performed in some patients. PMID:26687763

  13. A pixellated γ-camera based on CdTe detectors clinical interests and performances

    Science.gov (United States)

    Chambron, J.; Arntz, Y.; Eclancher, B.; Scheiber, Ch; Siffert, P.; Hage Hali, M.; Regal, R.; Kazandjian, A.; Prat, V.; Thomas, S.; Warren, S.; Matz, R.; Jahnke, A.; Karman, M.; Pszota, A.; Nemeth, L.

    2000-07-01

    A mobile gamma camera dedicated to nuclear cardiology, based on a 15 cm×15 cm detection matrix of 2304 CdTe detector elements, 2.83 mm×2.83 mm×2 mm, has been developed with a European Community support to academic and industrial research centres. The intrinsic properties of the semiconductor crystals - low-ionisation energy, high-energy resolution, high attenuation coefficient - are potentially attractive to improve the γ-camera performances. But their use as γ detectors for medical imaging at high resolution requires production of high-grade materials and large quantities of sophisticated read-out electronics. The decision was taken to use CdTe rather than CdZnTe, because the manufacturer (Eurorad, France) has a large experience for producing high-grade materials, with a good homogeneity and stability and whose transport properties, characterised by the mobility-lifetime product, are at least 5 times greater than that of CdZnTe. The detector matrix is divided in 9 square units, each unit is composed of 256 detectors shared in 16 modules. Each module consists in a thin ceramic plate holding a line of 16 detectors, in four groups of four for an easy replacement, and holding a special 16 channels integrated circuit designed by CLRC (UK). A detection and acquisition logic based on a DSP card and a PC has been programmed by Eurorad for spectral and counting acquisition modes. Collimators LEAP and LEHR from commercial design, mobile gantry and clinical software were provided by Siemens (Germany). The γ-camera head housing, its general mounting and the electric connections were performed by Phase Laboratory (CNRS, France). The compactness of the γ-camera head, thin detectors matrix, electronic readout and collimator, facilitates the detection of close γ sources with the advantage of a high spatial resolution. Such an equipment is intended to bedside explorations. There is a growing clinical requirement in nuclear cardiology to early assess the extent of an

  14. A pixellated γ-camera based on CdTe detectors clinical interests and performances

    International Nuclear Information System (INIS)

    A mobile gamma camera dedicated to nuclear cardiology, based on a 15 cmx15 cm detection matrix of 2304 CdTe detector elements, 2.83 mmx2.83 mmx2 mm, has been developed with a European Community support to academic and industrial research centres. The intrinsic properties of the semiconductor crystals - low-ionisation energy, high-energy resolution, high attenuation coefficient - are potentially attractive to improve the γ-camera performances. But their use as γ detectors for medical imaging at high resolution requires production of high-grade materials and large quantities of sophisticated read-out electronics. The decision was taken to use CdTe rather than CdZnTe, because the manufacturer (Eurorad, France) has a large experience for producing high-grade materials, with a good homogeneity and stability and whose transport properties, characterised by the mobility-lifetime product, are at least 5 times greater than that of CdZnTe. The detector matrix is divided in 9 square units, each unit is composed of 256 detectors shared in 16 modules. Each module consists in a thin ceramic plate holding a line of 16 detectors, in four groups of four for an easy replacement, and holding a special 16 channels integrated circuit designed by CLRC (UK). A detection and acquisition logic based on a DSP card and a PC has been programmed by Eurorad for spectral and counting acquisition modes. Collimators LEAP and LEHR from commercial design, mobile gantry and clinical software were provided by Siemens (Germany). The γ-camera head housing, its general mounting and the electric connections were performed by Phase Laboratory (CNRS, France). The compactness of the γ-camera head, thin detectors matrix, electronic readout and collimator, facilitates the detection of close γ sources with the advantage of a high spatial resolution. Such an equipment is intended to bedside explorations. There is a growing clinical requirement in nuclear cardiology to early assess the extent of an infarct

  15. 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.

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

    International Nuclear Information System (INIS)

    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

  17. 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

  18. 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.

  19. Inter-observer variability of clinical target volume delineation in radiotherapy treatment of pancreatic cancer: a multi-institutional contouring experience

    International Nuclear Information System (INIS)

    An observational multi-institutional study has been conducted aimed to evaluate the inter-observer variability in clinical target volume (CTV) delineation among different radiation oncologists in radiotherapy treatment of pancreatic cancer. A multi-institutional contouring dummy-run of two different cases of pancreatic cancer treated by postoperative and preoperative radiotherapy (RT) was performed. Clinical history, diagnostics, and planning CT imaging were available on AIRO website. Participants were requested to delineate CTVs according to their skills and knowledge. Aiming to quantify interobserver variability of CTVs delineations, the total volume, craniocaudal, laterolateral, and anteroposterior diameters were calculated. Descriptive statistic was calculated. The 95% Confidence Interval (95% CI) for coefficient of variation (CV) was estimated. The Dice Similarity Index (DSI) was used to evaluate the spatial overlap accuracy of the different CTVs compared with the CTVs of a national reference Centre considered as a benchmark. The mean DSI (mDSI) was calculated and reported. A total of 18 radiation oncologists from different Institutes submitted the targets. Less variability was observed for the Elective CTV rather than the Boost CTV, in both cases. The estimated CV were 28.8% (95% CI: 21.2 - 45.0%) and 20.0% (95% CI: 14.9 - 30.6%) for the Elective CTV, in adjuvant (Case 1) and neoadjuvant (Case 2) case, respectively. The mDSI value was 0.68 for the Elective CTVs in both cases (range 0.19 - 0.79 in postoperative vs range 0.35 - 0.79 in preoperative case). The mDSI was increased to 0.71 (Case 1) and 0.72 (Case 2) if the observers with a worse agreement have been excluded. On the other hand, a CV of 42.4% (95% CI: 30.1 - 72.4%) and 63.8% (95% CI: 43.9 - 119.2%) with a mDSI value of 0.44 and 0.52, were calculated for the Boost CTV in Case 1 and Case 2, respectively. The CV and mDSI obtained values for Elective CTVs showed an acceptable agreement among participants

  20. 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

  1. 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

  2. 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...

  3. 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.

  4. 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 ...

  5. 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

  6. 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

    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...

  7. Pharmacists' Perceptions of the Barriers and Facilitators to the Implementation of Clinical Pharmacy Key Performance Indicators

    Science.gov (United States)

    Minard, Laura V; Deal, Heidi; Harrison, Megan E; Toombs, Kent; Neville, Heather; Meade, Andrea

    2016-01-01

    Background In hospitals around the world, there has been no consensus regarding which clinical activities a pharmacist should focus on until recently. In 2011, a Canadian clinical pharmacy key performance indicator (cpKPI) collaborative was formed. The goal of the collaborative was to advance pharmacy practice in order to improve patient outcomes and enhance the quality of care provided to patients by hospital pharmacists. Following a literature review, which indicated that pharmacists can improve patient outcomes by carrying out specific activities, and an evidence-informed consensus process, a final set of eight cpKPIs were established. Canadian hospitals leading the cpKPI initiative are currently in the early stages of implementing these indicators. Objective To explore pharmacists' perceptions of the barriers and facilitators to the implementation of cpKPIs. Methods Clinical pharmacists employed by the Nova Scotia Health Authority were invited to participate in focus groups. Focus group discussions were audio-recorded and transcribed, and data was analyzed using thematic analysis. Findings Three focus groups, including 26 pharmacists, were conducted in February 2015. Three major themes were identified. Resisting the change was comprised of documentation challenges, increased workload, practice environment constraints, and competing priorities. Embracing cpKPIs was composed of seeing the benefit, demonstrating value, and existing supports. Navigating the unknown was made up of quality versus quantity battle, and insights into the future. Conclusions Although pharmacists were challenged by documentation and other changes associated with the implementation of cpKPIs, they demonstrated significant support for cpKPIs and were able to see benefits of the implementation. Pharmacists came up with suggestions for overcoming resistance associated with the implementation of cpKPIs and provided insights into the future of pharmacy practice. The identification of barriers

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. Building an idealized measurement system to improve clinical office practice performance.

    Science.gov (United States)

    Hess, A M; Nelson, E C; Johnson, D J; Wasson, J H

    1999-01-01

    The aim of this article is to introduce key concepts and approaches for building a better practice-based measurement. Physicians are being challenged to produce measurably higher quality of services, lower costs, and better clinical outcomes to remain viable. In the absence of provider-driven practice improvements and independent measurement systems, office practices will remain dependent on performance data from external forces as drivers of change. Three key questions will be addressed in our pursuit of better measurement systems for continuous improvement and competitive advantage: (1) What do we want a measurement system to tell us in the first place? (2) What might an idealized measurement system look like if we had one? (3) What are some of the challenges that office practices face in closing the gap between building an idealized measurement system and the current state of office practice measurement? PMID:10620956

  13. 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.

  14. [Operational costs and control of performance in surgical clinics between marketing and planning economics. Risk or perhaps quadrature of the circle].

    Science.gov (United States)

    Kraus, T W; Weber, W; Mieth, M; Funk, H; Klar, E; Herfarth, C

    2000-03-01

    Surgical hospitals can be seen as operational or even industrial production systems. Doctors have a major impact on both medical performance and costs. For active participation in the management process, knowledge of industrial controlling mechanisms is required. German hospitals currently receive no procedure-related financial revenues, such as prices or tariffs for defined medical treatment activities. Maximum clinical revenues are, furthermore, limited by principles of planned economy and can be increased only slightly by greater medical performance. Costs are the only target that can be autonomously influenced by the management. Operative controlling in hospitals aims at horizontal and vertical coordination of subunits and decentralization of process regulations. Hospital medical performance is not clearly defined, its quantitative measurement very problematic. Process-orientated clinical activities are not taken into account. A high percentage of hospital costs are fixed and can be influenced only by major structural interventions in the long term. Variable costs are primarily dependent on the quantity of clinical activities, but also heavily influenced by patient structure (comorbidity and risk profile). The various forms of industrial cost calculations, such as internal budgeting, internal markets or flexible plan-cost balancing, cannot be directly applied in hospital management. Based on these analyses, current operational concepts and strategic trends are listed to describe cost-management options in hospitals with focus on the German health reforms. PMID:10789045

  15. Intensity modulated radiotherapy (IMRT in patients with carcinomas of the paranasal sinuses: clinical benefit for complex shaped target volumes

    Directory of Open Access Journals (Sweden)

    Schulz-Ertner Daniela

    2006-07-01

    Full Text Available Abstract Introduction The aim of the study was to evaluate the clinical outcome of intensity modulated radiotherapy (IMRT in 46 patients with paranasal sinus tumors with special respect to treatment-related toxicity. Patients and methods We treated 46 patients with histologically proven tumors of the paranasal sinuses with IMRT. Histological classification included squamous cell carcinoma in 6, adenocarcinoma in 8, adenoidcystic carcinoma in 20 and melanoma in 8 patients, respectively. Six patients had been treated with RT during initial therapy after primary diagnosis, and IMRT was performed for the treatment of tumor progression as re-irradiation. Results Overall survival rates were 96% at 1 year, 90% at 3 years. Calculated from the initiation of IMRT as primary radiotherapy, survival rates at 1 and 3 years were 95% and 80%. In six patients IMRT was performed as re-irradiation, and survival rate calculated from re-irradiation was 63% at 1 year. Local control rates were 85% at 1, 81% at 2 and 49% at 3 years after primary RT and 50% at 1 year after re-irradiation. Distant metastases-free survival in patients treated with IMRT as primary RT was 83% after 1 and 64% after 3 years. For patients treated as primary irradiation with IMRT, the distant control rate was 83% at 1 year and 0% at 2 years. No severe radiation-induced side-effects could be observed. Conclusion IMRT for tumors of the paranasal sinuses is associated with very good tumor control rates. Treatment-related acute and long-term toxicity can be minimized as compared to historical results with conventional RT.

  16. 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

  17. 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.)

  18. 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 ...

  19. Elastic-plastic analysis of the transition divertor joint for high performance divertor target plate

    OpenAIRE

    Navaei, Dara

    2011-01-01

    The use of tungsten as a plasma-facing material necessitates a transition joint to the structural material of the primary coolant loop at some location in order to transport the coolant to the heat exchanger. A critical issue in transition joints is the thermal expansion mismatch between materials, which can lead to unacceptably high thermal stresses. Detailed 2D and 3D analyses were performed to study the behavior of a transition from tungsten to ferritic steel (FS) with an intermediate laye...

  20. 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

    2016-01-01

    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. PMID:26751445

  1. 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.

  2. 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

  3. A multiplexed targeted assay for high-throughput quantitative analysis of serum methylamines by ultra performance liquid chromatography coupled to high resolution mass spectrometry.

    Science.gov (United States)

    Kadar, Hanane; Dubus, Justine; Dutot, Jérémie; Hedjazi, Lyamine; Srinivasa, Suman; Fitch, Kathleen V; Grinspoon, Steven K; Nicholson, Jeremy K; Dumas, Marc-Emmanuel; Gauguier, Dominique

    2016-05-01

    Methylamines are biologically-active metabolites present in serum and urine samples, which play complex roles in metabolic diseases. Methylamines can be detected by proton nuclear magnetic resonance (NMR), but specific methods remain to be developed for their routine assay in human serum in clinical settings. Here we developed and validated a novel reliable "methylamine panel" method for simultaneous quantitative analysis of trimethylamine (TMA), its major detoxification metabolite trimethylamine-N-oxide (TMAO), and precursors choline, betaine and l-carnitine in human serum using Ultra Performance Liquid Chromatography (UPLC) coupled to High Resolution Mass Spectrometry (HRMS). Metabolite separation was carried out on a HILIC stationary phase. For all metabolites, the assay was linear in the range of 0.25-12.5 μmol/L and enabled to reach limit of detection of about 0.10 μmol/L. Relative standard deviations were below 16% for the three levels of concentrations. We demonstrated the strong reliability and robustness of the method, which was applied to serum samples from healthy individuals to establish the range of concentrations of the metabolites and their correlation relationships and detect gender differences. Our data provide original information for implementing in a clinical environment a MS-based diagnostic method with potential for targeted metabolic screening of patients at risk of cardiometabolic diseases. PMID:27036856

  4. Performance analysis of compression algorithms for noisy multispectral underwater images of small targets

    Science.gov (United States)

    Schmalz, Mark S.; Ritter, Gerhard X.; Caimi, Frank M.

    1997-07-01

    Underwater (UW) imagery presents several challenging problems for the developer of automated target recognition (ATR) algorithms, due to the presence of noise, point-spread function (PSF) effects resulting from camera or media inhomogeneities, and loss of contrast and resolution due to in-water scattering and absorption. Additional problems include the effects of sensor noise upon lossy image compression transformations, which can produce feature aliasing in the reconstructed imagery. Low-distortion, high- compression image transformations have been developed that facilitate transmission along a low-bandwidth uplink of compressed imagery acquired by a UW vehicle to a surface processing or viewing station. In early research that employed visual pattern image coding and the recently- developed BLAST transform, compression ratios ranging from 6,500:1 to 16,500:1 were reported, based on prefiltered six- band multispectral imagery of resolution 720 X 480 pixels. The prefiltering step, which removes unwanted background objects, is key to achieving high compression. This paper contains an analysis of several common compression algorithms, together with BLAST, to determine compression ratio, information loss, and computational efficiency achievable on a database of UW imagery. Information loss is derived rom the modulation transfer function, as well as several measures of spatial complexity that have been reported in the literature. Algorithms are expressed in image algebra, a concise notation that rigorously unifies linear and nonlinear mathematics in the image domain an has ben implemented on a variety of workstations and parallel processors. Thus, our algorithms are feasible, widely portable, and can be implemented on digital signal processors and fast parallel machines.

  5. An immersive “simulation week” enhances clinical performance of incoming surgical interns improved performance persists at 6 months follow-up

    Science.gov (United States)

    Singh, Pritam; Aggarwal, Rajesh; Pucher, Philip H.; Hashimoto, Daniel A.; Beyer-Berjot, Laura; Bharathan, Rasiah; Middleton, Katherine E.; Jones, Joanne; Darzi, Ara

    2015-01-01

    Background The transition from student to intern can be challenging. The “August” or “July effect” describes increased errors and reduced patient safety during this transition. The study objectives were to develop, pilot, and evaluate clinical performance after an immersive simulation course for incoming interns. Methods Graduating students were recruited for a 1-week immersive simulation course. Controls received no simulation training. Primary outcome (at baseline, and 1 and 6 months) was clinical performance on Objective Structured Clinical Examinations (OSCE) of clinical procedures and surgical technical skills. Secondary outcomes were self-reported confidence and clinical procedure logbook data. Results Nineteen students were recruited. Sixteen completed the 6-month follow-up, 10 in the intervention group and 6 in the control group. No differences were demonstrated between interventions and controls at baseline (OSCE [median, 66 vs 78; P = .181], technical skills [48 vs 52.5; P = .381], and confidence [101 vs 96; P = .368]). Interventions outperformed controls at 1 month (OSCE [111 vs 82; P = .001], technical skills [78.5 vs 63; P = .030], and confidence [142 vs 119; P < .001]), and 6 months (OSCE [107 vs 93; P = .007], technical skills [92.5 vs 69; P = .044], and confidence [148 vs 129; P = .022]). No differences were observed in numbers of clinical procedures performed at 1 (P = .958), 4 (P = .093), or 6 months (P = .713). Conclusion The immersive simulation course objectively improved subjects’ clinical skills, technical skills, and confidence. Despite similar clinical experience as controls, the intervention group’s improved performance persisted at 6 months follow-up. This feasible and effective intervention to ease transition from student to intern could reduce errors and enhance patient safety. PMID:25633735

  6. 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

  7. 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...

  8. 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...

  9. 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...

  10. Measuring agreement between rating interpretations and binary clinical interpretations of images: a simulation study of methods for quantifying the clinical relevance of an observer performance paradigm

    International Nuclear Information System (INIS)

    Laboratory receiver operating characteristic (ROC) studies, that are often used to evaluate medical imaging systems, differ from ‘live’ clinical interpretations in several respects which could compromise their clinical relevance. The aim was to develop methodology for quantifying the clinical relevance of a laboratory ROC study. A simulator was developed to generate ROC ratings data and binary clinical interpretations classified as correct or incorrect for a common set of images interpreted under clinical and laboratory conditions. The area under the trapezoidal ROC curve (AUC) was used as the laboratory figure-of-merit and the fraction of correct clinical decisions as the clinical figure-of-merit. Conventional agreement measures (Pearson, Spearman, Kendall and kappa) between the bootstrap-induced fluctuations of the two figures of merit were estimated. A jackknife pseudovalue transformation applied to the figures of merit was also investigated as a way to capture agreement existing at the individual image level that could be lost at the figure-of-merit level. It is shown that the pseudovalues define a relevance-ROC curve. The area under this curve (rAUC) measures the ability of the laboratory figure-of-merit-based pseudovalues to correctly classify incorrect versus correct clinical interpretations. Therefore, rAUC is a measure of the clinical relevance of an ROC study. The conventional measures and rAUC were compared under varying simulator conditions. It was found that design details of the ROC study, namely the number of bins, the difficulty level of the images, the ratio of disease-present to disease-absent images and the unavoidable difference between laboratory and clinical performance levels, can lead to serious underestimation of the agreement as indicated by conventional agreement measures, even for perfectly correlated data, while rAUC showed high agreement and was relatively immune to these details. At the same time rAUC was sensitive to factors such

  11. Effects of explicit knowledge and predictability on auditory distraction and target performance.

    Science.gov (United States)

    Max, Caroline; Widmann, Andreas; Schröger, Erich; Sussman, Elyse

    2015-11-01

    This study tested effects of task requirements and knowledge on auditory distraction effects. This was done by comparing the response to a pitch change (an irrelevant, distracting tone feature) that occurred predictably in a tone sequence (every 5th tone) under different task conditions. The same regular sound sequence was presented with task conditions varying in what information the participant was given about the predictability of the pitch change, and when this information was relevant for the task to be performed. In all conditions, participants performed a tone duration judgment task. Behavioral and event-related brain potential (ERP) measures were obtained to measure distraction effects and deviance detection. Predictable deviants produced behavioral distraction effects in all conditions. However, the P3a amplitude evoked by the predictable pitch change was largest when participants were uninformed about the regular structure of the sound sequence, showing an effect of knowledge on involuntary orienting of attention. In contrast, the mismatch negativity (MMN) component was only modulated when the regularity was relevant for the task and not by stimulus predictability itself. P3a and behavioral indices of distraction were not fully concordant. Overall, our results show differential effects of knowledge and predictability on auditory distraction effects indexed by neurophysiological (P3a) and behavioral measures. PMID:26386396

  12. 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.

  13. 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.

  14. 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…

  15. Analytical and clinical performances of immunoradiometric assay of total and free PSA developed locally

    International Nuclear Information System (INIS)

    A specific assay was developed for total and free PSA (PSAt, PSAf). Both assay use a two site IRMA with polyclonal anti PSA antibodies coated on tubes. Polyclonal antibodies were obtained after rabbit's immunisation using an under skin injection of pure PSA in multiple site. For quantification, two monoclonal antibodies were selected, the first highly specific to free PSA and the second recognising both free and bound PSA. A correlation study was performed comparatively with two commercial kits from CIS Bio and Immunotech. For that purpose, 464 serums samples ranging from 0.5 ng/ml to 3399 ng/ml were used to characterise the analytical performance of the new test. The analytical detection limit of the new test was equal to 0.05 ng/ml for the total PSA and 0.02ng/ml for the free PSA. The within run and between-day coefficients of variation were to 20 ng/ml. For BPH, no significant difference was found between the three test for the ratio PSAf/PSAt using a cut off of 14% (all were>to 14%). For the 120 patients with PC, all PSAt were > to 2 ng/ml. However the mean value of PSAt was higher for the commercial kits (14.74 ng/ml against 12.48ng/ml for the new test) but all ratio of PSAf/PSAt for the 120 newly diagnosed cancer were <14%. In conclusion, our immunoradiometric assay developed locally has a good analytical performance and its outputs are well correlated to clinical findings in prostate disease. Furthermore, a cut off of 14% for the ratio PSAf/PSAt appears to be the most accurate tools to depict a prostate cancer

  16. 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

  17. 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

  18. Performance portability study of an automatic target detection and classification algorithm for hyperspectral image analysis using OpenCL

    Science.gov (United States)

    Bernabe, Sergio; Igual, Francisco D.; Botella, Guillermo; Garcia, Carlos; Prieto-Matias, Manuel; Plaza, Antonio

    2015-10-01

    Recent advances in heterogeneous high performance computing (HPC) have opened new avenues for demanding remote sensing applications. Perhaps one of the most popular algorithm in target detection and identification is the automatic target detection and classification algorithm (ATDCA) widely used in the hyperspectral image analysis community. Previous research has already investigated the mapping of ATDCA on graphics processing units (GPUs) and field programmable gate arrays (FPGAs), showing impressive speedup factors that allow its exploitation in time-critical scenarios. Based on these studies, our work explores the performance portability of a tuned OpenCL implementation across a range of processing devices including multicore processors, GPUs and other accelerators. This approach differs from previous papers, which focused on achieving the optimal performance on each platform. Here, we are more interested in the following issues: (1) evaluating if a single code written in OpenCL allows us to achieve acceptable performance across all of them, and (2) assessing the gap between our portable OpenCL code and those hand-tuned versions previously investigated. Our study includes the analysis of different tuning techniques that expose data parallelism as well as enable an efficient exploitation of the complex memory hierarchies found in these new heterogeneous devices. Experiments have been conducted using hyperspectral data sets collected by NASA's Airborne Visible Infra- red Imaging Spectrometer (AVIRIS) and the Hyperspectral Digital Imagery Collection Experiment (HYDICE) sensors. To the best of our knowledge, this kind of analysis has not been previously conducted in the hyperspectral imaging processing literature, and in our opinion it is very important in order to really calibrate the possibility of using heterogeneous platforms for efficient hyperspectral imaging processing in real remote sensing missions.

  19. [The psychomotor test for research of eye-hand coordination at performance of monotonous activity on tracking target].

    Science.gov (United States)

    Dorokhov, V B; Arsen'ev, G N; Tkachenko, O N; Zakharchenko, D V; Lavrova, T P; Dementienko, V V

    2011-01-01

    Visual-motor coordination is necessary for successful performance of everyday activities. Many tasks, such as driving or operating devices in the workplace, require a variety of coordination patterns with different levels of compatibility between the eyes and the hand. The psychomotor test was developed which makes it possible to analyze visual-motor coordination disorders caused by a decrease in the level of wakefulness. A small circular target (14 mm in diameter) was moving with a low constant velosity (12 mm/s) in a circular trajectory (80 mm in diameter) with a period of 20 s. Subjects were instructed to keep the mouse-driven cursor inside a target, overstepping the limits of the moving target was considered as an error. To test the attention level, an additional stimulus was introduced which appeared for 3 seconds with an interval of 15 to 40 s. When the stimulus appeared, it was required to touch it with the cursor and click the mouse button. Cursor trajectories have a temporal resolution of 120 Hz. Eye movements were recorded with a PC-based Eyegaze Development System (LC Technologies, USA) measuring corneal reflectance with a collection rate of 120 Hz. Monotonous character of the test performance induced drowsiness and led to errors 25-30 minutes after the beginning of the experiment. Changes in physiological vigilance level was evaluated with EEG recording. Analysis of the dynamic characteristics of smooth and saccadic eye movements and hand movements showed their high sensitivity to a decrease in efficiency of operator's activity caused by a drop in the level of wakefulness. It is suggested that further development of this approach to measuring eye-hand coordination will promote working out a contactless method for the express diagnostics of the critical levels of drowsiness as well as for the definition of professional characteristics of an operator. PMID:21961322

  20. 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...... (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28>3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were.......12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04). CONCLUSIONS: An aggressive triamcinolone and synthetic DMARD treat-to-target strategy...

  1. 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

  2. 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)

  3. Coregistration of Prechemotherapy PET-CT for Planning Pediatric Hodgkin's Disease Radiotherapy Significantly Diminishes Interobserver Variability of Clinical Target Volume Definition

    International Nuclear Information System (INIS)

    Purpose: To assess the interobserver variability in clinical target volume (CTV) definitions when using registered 18F-labeled deoxyglucose positron emission tomography (FDG-PET-CT) versus side-by-side image sets in pediatric Hodgkin's disease (HD). Methods and Materials: Prechemotherapy FDG-PET-CT scans performed in the treatment position were acquired from 20 children (median age, 14 years old) with HD (stages 2A to 4B) and registered with postchemotherapy planning CT scans. The patients had a median age of 14 years and stages of disease ranging between 2A and 4B. Image sets were coregistered using a semiautomatic coregistration system. The biological target volume was defined on all the coregistered images as a guide to defining the initial site of involvement and to avoid false-positive or negative results. Five radiation oncologists independently defined the CTV for all 20 patients: once using separate FDG-PET-CT images as a guide (not registered) to define CTVa and once using the registered FDG-PET-CT data to define CTVb. The total volumes were compared, as well as their coefficients of variation (COV). To assess the interobserver variability, the percentages of intersection between contours drawn by all observers for each patient were calculated for CTVa and for CTVb. Results: The registration of a prechemotherapy FDG-PET-CT scan caused a change in the CTV for all patients. Comparing CTVa with CTVb showed that the mean CTVb increased in 14 patients (range, 0.61%-101.96%) and decreased in 6 patients (range, 2.97%-37.26%). The COV for CTVb significantly decreased for each patient; the mean COVs for CTVa and CTVb were 45% (21%-65%) and 32% (13%-57%), respectively (p = 0.0004). The percentage of intersection among all CTVbs for the five observers increased significantly by 89.77% (1.99%-256.41%) compared to that of CTVa (p = 0.0001). Conclusions: High observer variability can occur during CT-based definition of CTVs for children diagnosed with HD. Registration

  4. 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)

  5. 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

  6. Intensity modulated radiation therapy (IMRT: differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma

    Directory of Open Access Journals (Sweden)

    Delclos Marc E

    2011-06-01

    Full Text Available Abstract Background A strong dose-volume relationship exists between the amount of small bowel receiving low- to intermediate-doses of radiation and the rates of acute, severe gastrointestinal toxicity, principally diarrhea. There is considerable interest in the application of highly conformal treatment approaches, such as intensity-modulated radiation therapy (IMRT, to reduce dose to adjacent organs-at-risk in the treatment of carcinoma of the rectum. Therefore, we performed a comprehensive dosimetric evaluation of IMRT compared to 3-dimensional conformal radiation therapy (3DCRT in standard, preoperative treatment for rectal cancer. Methods Using RTOG consensus anorectal contouring guidelines, treatment volumes were generated for ten patients treated preoperatively at our institution for rectal carcinoma, with IMRT plans compared to plans derived from classic anatomic landmarks, as well as 3DCRT plans treating the RTOG consensus volume. The patients were all T3, were node-negative (N = 1 or node-positive (N = 9, and were planned to a total dose of 45-Gy. Pairwise comparisons were made between IMRT and 3DCRT plans with respect to dose-volume histogram parameters. Results IMRT plans had superior PTV coverage, dose homogeneity, and conformality in treatment of the gross disease and at-risk nodal volume, in comparison to 3DCRT. Additionally, in comparison to the 3DCRT plans, IMRT achieved a concomitant reduction in doses to the bowel (small bowel mean dose: 18.6-Gy IMRT versus 25.2-Gy 3DCRT; p = 0.005, bladder (V40Gy: 56.8% IMRT versus 75.4% 3DCRT; p = 0.005, pelvic bones (V40Gy: 47.0% IMRT versus 56.9% 3DCRT; p = 0.005, and femoral heads (V40Gy: 3.4% IMRT versus 9.1% 3DCRT; p = 0.005, with an improvement in absolute volumes of small bowel receiving dose levels known to induce clinically-relevant acute toxicity (small bowel V15Gy: 138-cc IMRT versus 157-cc 3DCRT; p = 0.005. We found that the IMRT treatment volumes were typically larger than that

  7. Impaired Physical Performance and Clinical Responses after a Recreational Bodybuilder's Self-Administration of Steroids: A Case Report

    OpenAIRE

    Veras, Katherine; Silva-Junior, Fernando Lopes; Lima-Silva, Adriano Eduardo; De-Oliveira, Fernando Roberto; Pires, Flávio de Oliveira

    2015-01-01

    We reported clinical and physical responses to 7 weeks of anabolic-androgenic steroid (AAS) self-administration in a male recreational bodybuilder. He was self-administrating a total of 3,250 mg of testosterone when his previous and current clinical and physical trials records were revisited. Body shape, performance, and biochemistry results were clustered into three phases labeled PRE (before the self-use), POST I (immediately at the cessation of the 7-week administration), and POST II (12 w...

  8. Self-perceived versus objectively measured competence in performing clinical practical procedures by final year medical students

    OpenAIRE

    Katowa-Mukwato, Patricia; Banda, Sekelani

    2016-01-01

    Objectives To determine and compare the self-perceived and objectively measured competence in performing 14 core-clinical practical procedures by Final Year Medical Students of the University of Zambia. Methods The study included 56 out of 60 graduating University of Zambia Medical Students of the 2012/2013 academic year. Self-perceived competence: students rated their competence on 14 core- clinical practical procedures using a self-administered questionnaire on a 5-point Likert scale. Objec...

  9. 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.

  10. Effects of tendon viscoelasticity in Achilles tendinosis on explosive performance and clinical severity in athletes.

    Science.gov (United States)

    Wang, H-K; Lin, K-H; Su, S-C; Shih, T T-F; Huang, Y-C

    2012-12-01

    The aim was to compare viscoelastic properties of Achilles tendons between legs in elite athletes with unilateral tendinosis, and to investigate relationships between the properties and explosive performance and clinical severity. Seventeen male athletes (mean ± standard deviation age, 27.3 ± 2.0 years) who had unilateral, chronic middle-portion tendinopathy of the Achilles tendon were assessed by the Victorian Institute of Sport Assessment questionnaire, measurements of tendon viscoelastic properties, voluntary electromechanical delay (EMD), normalized rate of force development (RFD), and one-leg hopping distance. Compared with the non-injured leg, the tendinopathic leg showed reduced tendon stiffness (-19.2%. P mechanical hysteresis (+21.2%, P = 0.004), lower elastic energy storage and release (-14.2%, P = 0.002 and -19.1%, P < 0.001), lower normalized RFD at one-fourth (-16.3%, P = 0.02), 2/4 (-17.3%, P = 0.006), and three-fourths maximal voluntary contraction (-13.7%, P = 0.02), longer soleus and medial gastrocnemius voluntary EMD (+26.9%, P = 0.009 and +24.0%, P = 0.004), and shorter hopping distances (-34.1%, P < 0.001). Tendon stiffness was correlated with normalized RFD, voluntary EMD in the medial gastrocnemius, and hopping distances (r ranged from -0.35 to 0.64, P < 0.05). Hysteresis was correlated to the soleus voluntary EMD and hopping distances (r = 0.42 and -0.39, P < 0.05). We concluded that altered tendon viscoelastic properties in Achilles tendinosis affect explosive performance in athletes. PMID:22830527

  11. Magnetic Resonance Imaging- Versus Computed Tomography-Based Target Volume Delineation of the Glandular Breast Tissue (Clinical Target Volume Breast) in Breast-Conserving Therapy: An Exploratory Study

    International Nuclear Information System (INIS)

    Purpose: To examine MRI and CT for glandular breast tissue (GBT) volume delineation and to assess interobserver variability. Methods and Materials: Fifteen breast cancer patients underwent a planning CT and MRI, consecutively, in the treatment position. Four observers (two radiation oncologists and two radiologists) delineated the GBT according to the CT and separately to the MR images. Volumes, centers of mass, maximum extensions with standard deviations (SD), and interobserver variability were quantified. Observers viewed delineation differences between MRI and CT and delineation differences among observers. Results: In cranio-lateral and cranio-medial directions, GBT volumes were delineated larger using MRI when compared with those delineated with CT. Center of mass on MRI shifted a mean (SD) 17% (4%) into the cranial direction and a mean 3% (4%) into the dorsal direction when compared with that on the planning CT. Only small variations between observers were noted. The GBT volumes were approximately 4% larger on MRI (mean [SD] ratio MRI to CT GBT volumes, 1.04 [0.06]). Findings were concordant with viewed MRI and CT images and contours. Conformity indices were only slightly different; mean conformity index was 77% (3%) for MRI and 79% (4%) for CT. Delineation differences arising from personal preferences remained recognizable irrespective of the imaging modality used. Conclusions: Contoured GBT extends substantially further into the cranio-lateral and cranio-medial directions on MRI when compared with CT. Interobserver variability is comparable for both imaging modalities. Observers should be aware of existing personal delineation preferences. Institutions are recommended to review and discuss target volume delineations and to design supplementary guidelines if necessary.

  12. The performance of the Health of the Nation Outcome Scales as measures of clinical severity.

    Science.gov (United States)

    Müller, Mario; Vandeleur, Caroline; Weniger, Godehard; Prinz, Susanne; Vetter, Stefan; Egger, Stephan T

    2016-05-30

    The aim of this study was to examine the performance of the Health of the Nation Outcome Scales (HoNOS) against other measures of functioning and mental health in a full three-year cohort of admissions to a psychiatric hospital. A sample of N=1719 patients (35.3% females, aged 17-78 years) was assessed using observer-rated measures and self-reports of psychopathology at admission. Self-reports were available from 51.7% of the sample (34.4% females, aged 17-76 years). Functioning and psychopathology were compared across five ICD-10 diagnostic groups: substance use disorders, schizophrenia and psychotic disorders, affective disorders, anxiety/somatoform disorders and personality disorders. Associations between the measures were examined, stratifying by diagnostic subgroup. The HoNOS were strongly linked to other measures primarily in psychotic disorders (except for the behavioral subscale), while those with substance use disorders showed rather poor links. Those with anxiety/somatoform disorders showed null or only small associations. This study raises questions about the overall validity of the HoNOS. It seems to entail different levels of validity when applied to different diagnostic groups. In clinical practice the HoNOS should not be used as a stand-alone instrument to assess outcome but rather as part of a more comprehensive battery including diagnosis-specific measures. PMID:27137958

  13. 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

  14. Identifying cases of undiagnosed, clinically significant COPD in primary care: qualitative insight from patients in the target population

    OpenAIRE

    Leidy, Nancy K.; Kim, Katherine; Bacci, Elizabeth D.; Yawn, Barbara P.; Mannino, David M.; Thomashow, Byron M; Barr, R Graham; Rennard, Stephen I; Houfek, Julia F; Han, Meilan K.; Meldrum, Catherine A.; Make, Barry J.; Bowler, Russ P; Steenrod, Anna W.; Murray, Lindsey T

    2015-01-01

    Background: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations. Aims: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care. Methods: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Ph...

  15. 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

  16. 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

  17. 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

  18. 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...

  19. Addressing Loss of Efficiency Due to Misclassification Error in Enriched Clinical Trials for the Evaluation of Targeted Therapies Based on the Cox Proportional Hazards Model

    Science.gov (United States)

    Tsai, Chen-An; Lee, Kuan-Ting; Liu, Jen-pei

    2016-01-01

    A key feature of precision medicine is that it takes individual variability at the genetic or molecular level into account in determining the best treatment for patients diagnosed with diseases detected by recently developed novel biotechnologies. The enrichment design is an efficient design that enrolls only the patients testing positive for specific molecular targets and randomly assigns them for the targeted treatment or the concurrent control. However there is no diagnostic device with perfect accuracy and precision for detecting molecular targets. In particular, the positive predictive value (PPV) can be quite low for rare diseases with low prevalence. Under the enrichment design, some patients testing positive for specific molecular targets may not have the molecular targets. The efficacy of the targeted therapy may be underestimated in the patients that actually do have the molecular targets. To address the loss of efficiency due to misclassification error, we apply the discrete mixture modeling for time-to-event data proposed by Eng and Hanlon [8] to develop an inferential procedure, based on the Cox proportional hazard model, for treatment effects of the targeted treatment effect for the true-positive patients with the molecular targets. Our proposed procedure incorporates both inaccuracy of diagnostic devices and uncertainty of estimated accuracy measures. We employed the expectation-maximization algorithm in conjunction with the bootstrap technique for estimation of the hazard ratio and its estimated variance. We report the results of simulation studies which empirically investigated the performance of the proposed method. Our proposed method is illustrated by a numerical example. PMID:27120450

  20. Clinical symptoms and performance on the continuous performance test in children with attention deficit hyperactivity disorder between subtypes: a natural follow-up study for 6 months

    Directory of Open Access Journals (Sweden)

    Chiang Yuan-Lin

    2011-04-01

    Full Text Available Abstract Background The aims of this study were to determine the time course of improvements in attention deficit hyperactivity disorder (ADHD clinical symptoms and neurocognitive function in a realistic clinical setting, and the differences in ADHD symptom improvement using different classifications of ADHD subtypes. Methods The Child Behavior Checklist (CBCL was completed by parents of ADHD children at the initial visit. The computerized Continuous Performance Test (CPT, Swanson, Nolan, and Pelham, and Version IV Scale for ADHD (SNAP-IV, and ADHD Rating Scale (ADHD-RS were performed at baseline, one month, three months, and six months later, respectively. Patient care including drug therapy was performed at the discretion of the psychiatrist. The ADHD patients were divided into DSM-IV subtypes (Inattentive, Hyperactive-impulsive and Combined type, and were additionally categorized into aggressive and non-aggressive subtypes by aggression scale in CBCL for comparisons. Results There were 50 ADHD patients with a mean age of 7.84 ± 1.64 years; 15 of them were inattentive type, 11 were hyperactive-impulsive type, and 24 were combined type. In addition, 28 of the ADHD patients were grouped into aggressive and 22 into non-aggressive subtypes. There were significant improvements in clinical symptoms of hyperactivity and inattention, and impulsivity performance in CPT during the 6-month treatment. The clinical hyperactive symptoms were significantly different between ADHD patients sub-grouping both by DSM-IV and aggression. Non-aggressive patients had significantly greater changes in distraction and impulsivity performances in CPT from baseline to month 6 than aggressive patients. Conclusions We found that ADHD symptoms, which included impulsive performances in CPT and clinical inattention and hyperactivity dimensions, had improved significantly over 6 months under pragmatic treatments. The non-aggressive ADHD patients might have a higher potential

  1. 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

  2. Use of VDOT's Pavement Management System to Proactively Plan and Monitor Pavement Maintenance and Rehabilitation Activities to Meet the Agency's Performance Target

    OpenAIRE

    Hosten, Akyiaa; Chowdhury, Tanveer; Shekharan, Raja A.; Ayotte, Matthew; Coggins, Eddie

    2015-01-01

    The Virginia Department of Transportation (VDOT) has an established Pavement Management Program that includes data collection, needs assessment, performance targets, and performance-based budgeting. As a part of data collection and needs assessment, an annual survey of pavement condition is used to estimate the current and project the future pavement maintenance and rehabilitation needs. Pavement condition targets are established, and are used to monitor and assess the effectiveness of mainte...

  3. Targeting Chromatin-Mediated Transcriptional Control of Gene Expression in Non-Small Cell Lung Cancer Therapy: Preclinical Rationale and Clinical Results.

    Science.gov (United States)

    Pasini, Alice; Delmonte, Angelo; Tesei, Anna; Calistri, Daniele; Giordano, Emanuele

    2015-10-01

    Targeting chromatin-mediated transcriptional control of gene expression is nowadays considered a promising new strategy, transcending conventional anticancer therapy. As a result, molecules acting as DNA demethylating agents or histone deacetylase inhibitors (HDACi) have entered the clinical arena in the last decade. Given the evidence suggesting that epigenetic regulation is significantly involved in lung cancer development and progression, the potential of epigenetically active compounds to modulate gene expression and reprogram cancer cells to a less aggressive phenotype is, at present, a promising strategy. Accordingly, a large number of compounds that interact with the epigenetic machinery of gene expression regulation are now being developed and tested as potential antitumor agents, either alone or in combination with standard therapy. The preclinical rationale and clinical data concerning the pharmacological modulation of chromatin organization in non-small cell lung cancer (NSCLC) is described in this review. Although preclinical data suggest that a pharmacological treatment targeting the epigenetic machinery has relevant activity over the neoplastic phenotype of NSCLC cells, clinical results are disappointing, leading only to short periods of disease stabilization in NSCLC patients. This evidence calls for a significant rethinking of strategies for an effective epigenetic therapy of NSCLC. The synergistic effect of concurrent epigenetic therapies, use at low doses, the priming of current treatments with previous epigenetic drugs, and the selection of clinical trial populations based on epigenetic biomarkers/signatures appear to be the cornerstones of a mature therapeutic strategy aiming to establish new regimens for reprogramming malignant cells and improving the clinical history of affected patients. PMID:26347133

  4. Effects of LifeSkills Training on Medical Students' Performance in Dealing with Complex Clinical Cases

    Science.gov (United States)

    Campo, Ana E.; Williams, Virginia; Williams, Redford B.; Segundo, Marisol A.; Lydston, David; Weiss, Stephen M.'

    2008-01-01

    Objective: Sound clinical judgment is the cornerstone of medical practice and begins early during medical education. The authors consider the effect of personality characteristics (hostility, anger, cynicism) on clinical judgment and whether a brief intervention can affect this process. Methods: Two sophomore medical classes (experimental,…

  5. 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

  6. 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

    for systematic bias. In the clinical study, two interventional radiologists conducted a total of 250 measurements in 14 patients with arteriovenous fistulas to determine clinical precision and enable testing for bias between measurers.Results: Accuracy was excellent for both catheters with a high...

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Identifying specific beliefs to target to improve restaurant employees' intentions for performing three important food safety behaviors.

    Science.gov (United States)

    Pilling, Valerie K; Brannon, Laura A; Shanklin, Carol W; Howells, Amber D; Roberts, Kevin R

    2008-06-01

    Current national food safety training programs appear ineffective at improving food safety practices in foodservice operations, given the substantial number of Americans affected by foodborne illnesses after eating in restaurants each year. The Theory of Planned Behavior (TpB) was used to identify important beliefs that may be targeted to improve foodservice employees' intentions for three food safety behaviors that have the most substantial affect on public health: hand washing, using thermometers, and proper handling of food contact surfaces. In a cross-sectional design, foodservice employees (n=190) across three midwestern states completed a survey assessing TpB components and knowledge for the three food safety behaviors. Multiple regression analyses were performed on the TpB components for each behavior. Independent-samples t tests identified TpB beliefs that discriminated between participants who absolutely intend to perform the behaviors and those with lower intention. Employees' attitudes were the one consistent predictor of intentions for performing all three behaviors. However, a unique combination of important predictors existed for each separate behavior. Interventions for improving employees' behavioral intentions for food safety should focus on TpB components that predict intentions for each behavior and should bring all employees' beliefs in line with those of the employees who already intend to perform the food safety behaviors. Registered dietitians; dietetic technicians, registered; and foodservice managers can use these results to enhance training sessions and motivational programs to improve employees' food safety behaviors. Results also assist these professionals in recognizing their responsibility for enforcing and providing adequate resources for proper food safety behaviors. PMID:18502232

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

    NARCIS (Netherlands)

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

    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

  13. 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

  14. 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 ...

  15. Suggestion for the prostatic fossa clinical target volume in adjuvant or salvage radiotherapy after a radical prostatectomy

    International Nuclear Information System (INIS)

    Background and purpose: To assess the location of recurrent tumors and suggest the optimal target volume in adjuvant or salvage radiotherapy (RT) after a radical prostatectomy (RP). Material and methods: From January 2000 to December 2012, 113 patients had been diagnosed with suspected recurrent prostate cancer by MRI scan and received salvage RT in the Samsung Medical Center. This study assessed the location of the suspected tumor recurrences and used the inferior border of the pubic symphysis as a point of reference. Results: There were 118 suspect tumor recurrences. The most common site of recurrence was the anastomotic site (78.8%), followed by the bladder neck (15.3%) and retrovesical area (5.9%). In the cranial direction, 106 (87.3%) lesions were located within 30 mm of the reference point. In the caudal direction, 12 lesions (10.2%) were located below the reference point. In the transverse plane, 112 lesions (94.9%) were located within 10 mm of the midline. Conclusions: A MRI scan acquired before salvage RT is useful for the localization of recurrent tumors and the delineation of the target volume. We suggest the optimal target volume in adjuvant or salvage RT after RP, which includes 97% of suspected tumor recurrences

  16. Fungal sterol C22-desaturase is not an antimycotic target as shown by selective inhibitors and testing on clinical isolates.

    Science.gov (United States)

    Müller, Christoph; Binder, Ulrike; Maurer, Elisabeth; Grimm, Christian; Giera, Martin; Bracher, Franz

    2015-09-01

    Inhibition of concise enzymes in ergosterol biosynthesis is one of the most prominent strategies for antifungal chemotherapy. Nevertheless, the enzymes sterol C5-desaturase and sterol C22-desaturase, which introduce double bonds into the sterol core and side chain, have not been fully investigated yet for their potential as antifungal drug targets. Lathosterol side chain amides bearing N-alkyl groups of proper length are known as potent inhibitors of the enzymes sterol C5-desaturase and sterol Δ(24)-reductase in mammalian cholesterol biosynthesis. Here we present the results of our evaluation of these amides for their ability to inhibit enzymes in fungal ergosterol biosynthesis. In the presence of inhibitor(s) an accumulation of sterols lacking a double bond at C22/23 (mainly ergosta-5,7-dien-3β-ol) was observed in Candida glabrata, Saccharomyces cerevisiae, and Yarrowia lipolytica. Hence, the lathosterol side chain amides were identified as selective inhibitors of the fungal sterol C22-desaturase, which was discussed as a specific target for novel antifungals. One representative inhibitor, (3S,20S)-20-N-butylcarbamoylpregn-7-en-3β-ol was subjected to antifungal susceptibility testing on patient isolates according to modified EUCAST guidelines. But, the test organisms showed no significant reduction of cell growth and/or viability up to an inhibitor concentration of 100μg/mL. This leads to the conclusion that sterol C22-desaturase is not an attractive target for the development of antifungals. PMID:26022150

  17. Embedded Measures of Performance Validity in the Rey Complex Figure Test in a Clinical Sample of Veterans.

    Science.gov (United States)

    Sugarman, Michael A; Holcomb, Erin M; Axelrod, Bradley N; Meyers, John E; Liethen, Philip C

    2016-01-01

    The purpose of this study was to determine how well scores from the Rey Complex Figure Test (RCFT) could serve as embedded measures of performance validity in a large, heterogeneous clinical sample at an urban-based Veterans' Affairs hospital. Participants were divided into credible performance (n = 244) and noncredible performance (n = 87) groups based on common performance validity tests during their respective clinical evaluations. We evaluated how well preselected RCFT scores could discriminate between the 2 groups using cut scores from single indexes as well as multivariate logistic regression prediction models. Additionally, we evaluated how well memory error patterns (MEPs) could discriminate between the 2 groups. Optimal discrimination occurred when indexes from the Copy and Recognition trials were simultaneous predictors in logistic regression models, with 91% specificity and at least 53% sensitivity. Logistic regression yielded superior discrimination compared with individual indexes and compared with the use of MEPs. Specific scores on the RCFT, including the Copy and Recognition trials, can serve as adequate indexes of performance validity, when using both cut scores and logistic regression prediction models. We provide logistic regression equations that can be applied in similar clinical settings to assist in determining performance validity. PMID:26384155

  18. 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…

  19. 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

  20. Design and performance of a real-time radon-space hybrid image processing system for FLIR target evaluation

    Science.gov (United States)

    Woolven, Steven; Chevrette, Paul C.

    1994-10-01

    A unique real-time hybrid optical-digital image processing system has been developed to perform analysis of low contrast visual and infrared images in radon-space. This system functions by implementing the forward radon transform (a mathematical tomographic transform of image data from two-dimensional image-space to one-dimensional radon-space) in a front-end optical processor, and a digital processing subsystem operating in radon-space instead of the more traditional image-space. The system works by optically converting the two-dimensional image-space data into a series of one-dimensional projections. All further processing is performed digitally in radon-space on the one-dimensional projections. Applications of interest such as the objective minimum resolvable temperature difference measurement of thermal imagers and automatic pattern recognition are discussed. Also, this paper discusses the topic of real-time object-moment analysis in radon-space which can be used for target identification under conditions of certain image distortions (size, rotation, translation, and contrast). Radon-space object-moments can be calculated using significantly less image data and fewer digital operations than those in image-space.

  1. [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

  2. 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...

  3. 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...

  4. 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

  5. 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

  6. 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....

  7. Performance of the hepatic encephalopathy scoring algorithm in a clinical trial of patients with cirrhosis and severe hepatic encephalopathy

    DEFF Research Database (Denmark)

    Hassanein, T.; Blei, A.T.; Perry, W.;

    2009-01-01

    . The HE Scoring Algorithm (HESA) combined clinical indicators with those derived from simple neuropsychological tests,the latter more often used in milder grades of HE (I / II). The performance of each indicator was compared across grades and sites. RESULTS: Results of HESA were also compared with the...... and disorientation to place (grade III), and lethargy and disorientation to time (grade II). Two clinical and four neuropsychological indicators were useful to classify patients as grade I. The Glasgow Coma Scale differed among the four stages of the WHC, but the differences between grades I and II...

  8. 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...

  9. 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.

  10. Thioredoxin-interacting Protein as a Common Regulation Target for Multiple Drugs in Clinical Therapy/Application

    Directory of Open Access Journals (Sweden)

    Pengxing Zhang

    2015-01-01

    Full Text Available Initially identified in HL60 cells treated with Vitamin D3, thioredoxin-interacting protein (TXNIP is considered as a major redox regulator and a potential connector between cellular redox state and metabolism. TXNIP plays an important role in the control of glucose and lipid metabolism, and it has been defined as a tumor suppressor gene in various solid tumors and hematological malignancies. This review gives an overview of the mechanism of various medicines including Lycium barbarum polysaccharide, Quercetin, trans-resveratrol, metformin, purple sweet potato color, nobiletin, taurine, suberoylanilide hydroxamic acid, and Theophylline, and their potential applications in the clinical treatment of many diseases.

  11. Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes

    International Nuclear Information System (INIS)

    Purpose: To determine the optimal clinical target volume margins around the gross nodal tumor volume in head-and-neck cancer by assessing microscopic tumor extension beyond cervical lymph node capsules. Methods and Materials: Histologic sections of 96 dissected cervical lymph nodes with extracapsular extension (ECE) from 48 patients with head-and-neck squamous cell carcinoma were examined. The maximum linear distance from the external capsule border to the farthest extent of the tumor or tumoral reaction was measured. The trends of ECE as a function of the distance from the capsule and lymph node size were analyzed. Results: The median diameter of all lymph nodes was 11.0 mm (range: 3.0-30.0 mm). The mean and median ECE extent was 2.2 mm and 1.6 mm, respectively (range: 0.4-9.0 mm). The ECE was <5 mm from the capsule in 96% of the nodes. As the distance from the capsule increased, the probability of tumor extension declined. No significant difference between the extent of ECE and lymph node size was observed. Conclusion: For N1 nodes that are at high risk for ECE but not grossly infiltrating musculature, 1 cm clinical target volume margins around the nodal gross tumor volume are recommended to cover microscopic nodal extension in head-and-neck cancer

  12. A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer. Reducing the interobserver variability in multicentre clinical studies

    International Nuclear Information System (INIS)

    Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study

  13. 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...

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. A Cone Beam CT-Based Study for Clinical Target Definition Using Pelvic Anatomy During Postprostatectomy Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT. Methods and Materials: The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CTref) volumes from seminal vesicle stump (SVS) to bladder-urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively. Results: A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CTref, mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm. Conclusions: Normal tissue anatomy was definable by CBCT imaging throughout the course of post-RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance

  1. Clinical signs as a guide for performing HSV-PCR in correct diagnosis of herpes simplex virus encephalitis

    Directory of Open Access Journals (Sweden)

    Abbas B

    2003-07-01

    Full Text Available Background: Clinical criteria (symptoms are not reliable enough to differentiate between different causes of encephalitis. The clinical presentation of herpes simplex virus encephalitis (HSVE is not classically constant and in such a patient, therefore, it is vital to make early diagnosis. Aims: To investigate satisfactory and crucial clinical signs as guide to perform HSV-PCR in a rapid diagnosis of herpes simplex virus encephalitis. Material and Methods: A total of 156 CSF specimens from 70 patients with clinically suspected HSVE or meningoencephalitis were tested. The criteria for cases suspected of HSVE were fever >380C, altered mental status and other critical manifestations. CSF features, irregularity in brain CT scan and MRI findings were also assessed. All the specimens were collected before and after Acyclovir treatment. Polymerase chain reaction was performed using primers, which amplified DNA sequences for both HSV-1 and HSV-2. Statistical Analysis: To analyze data, two-tailed Fisher's exact test and the X2-test with Yates' correction were used as appropriate. The odds ratio was used to express the strength of association between the clinical factors and the PCR results. Results: HSV-DNA was detected in 18% of the specimens, belonging to 25.7% of the patients. Results indicate that the majority of the clinical symptoms are not specific to definitive clinical diagnosis of HSVE, except alteration in the level of consciousness—odds ratio [0.27 (0.07-0.96 (P=0.033]; and lateralization sign—odds ratio [4.7 (0.98-22.6 (P=0.023]. However, laboratory data, including total white blood cell count, especially the number of lymphocytes, and MRI findings could be suggested for HSV-PCR examination. Conclusion: At the first admission, a preliminary finding of at least two important clinical features mentioned above along with the pattern of CSF cell and differential counts could be sufficient to perform HSV-PCR which could ultimately result in a

  2. 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...

  3. 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 ...

  4. Effort test performance in clinical acute brain injury, community brain injury, and epilepsy populations.

    Science.gov (United States)

    Hampson, Natalie E; Kemp, Steven; Coughlan, Anthony K; Moulin, Chris J A; Bhakta, Bipin B

    2014-01-01

    Effort tests have become commonplace within medico-legal and forensic contexts and their use is rising within clinical settings. It is recognized that some patients may fail effort tests due to cognitive impairment and not because of poor effort. However, investigation of the base rate of failure among clinical populations other than dementia is limited. Forty-seven clinical participants were recruited and comprised three subgroups: acute brain injury (N = 11), community brain injury (N = 20), and intractable epilepsy (N = 16). Base rates of failure on the Word Memory Test (WMT; Green, 2003 ) and six other less well-validated measures were investigated. A significant minority of patients failed effort tests according to standard cutoff scores, particularly patients with severe traumatic brain injury and marked frontal-executive features. The WMT was able to identify failures associated with significant cognitive impairment through the application of profile analysis and/or lowered cutoff levels. Implications for clinical assessment, effort test interpretation, and future research are discussed. PMID:25084843

  5. Human Patient Simulations: Evaluation of Self-Efficacy and Anxiety in Clinical Skills Performance

    Science.gov (United States)

    Onovo, Grace N.

    2013-01-01

    The relationship between self-efficacy (self-confidence) and anxiety levels, and the use of Human Patient Simulations (HPS) as a teaching-learning strategy, has not been sufficiently studied in the area of clinical nursing education. Despite the evidence in the literature indicating that HPS increases self-efficacy/self-confidence and decreases…

  6. A genetic variation in microRNA target site of ETS2 is associated with clinical outcomes of paclitaxel-cisplatin chemotherapy in non-small cell lung cancer.

    Science.gov (United States)

    Hong, Mi Jeong; Lee, Shin Yup; Choi, Jin Eun; Jin, Cheng Cheng; Kang, Hyo Jung; Baek, Sun Ah; Lee, So Yeon; Shin, Kyung Min; Jeong, Ji Yun; Lee, Won Kee; Yoo, Seung Soo; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Son, Ji Woong; Park, Jae Yong

    2016-03-29

    The present study was performed to investigate the association of single nucleotide polymorphisms (SNPs) located in the miRNA target sites with the clinical outcomes of first line paclitaxel-cisplatin chemotherapy in advanced NSCLC. Eighty SNPs in miRNA binding sites of cancer related genes selected from 18,500 miRNA:target bindings in crosslinking, ligation, and sequencing of hybrids (CLASH) data were investigated in 379 advanced NSCLC patients using a sequenom mass spectrometry-based genotype assay. qRT-PCR and luciferase assay were conducted to examine functional relevance of potentially functional SNPs in miRNA binding sites. Of the 80 SNPs analyzed, 16 SNPs were significantly associated with the clinical outcomes after chemotherapy. Among these, ANAPC1 rs3814026C>T, ETS2 rs461155A>G, SORBS1 rs7081076C>A and POLR2A rs2071504C>T could predict both chemotherapy response and survival. Notably, ETS2 rs461155A>G was significantly associated with decreased ETS2 mRNA expression in both tumor and paired normal lung tissues (Ptrend = 4 × 10-7, and 3 × 10-4, respectively). Consistently, a decreased expression of the reporter gene for the G allele of rs461155 compared with the A allele was observed by luciferase assay. These findings suggest that the four SNPs, especially ETS2 rs461155A>G, could be used as biomarkers predicting the clinical outcomes of NSCLC patients treated with first-line paclitaxel-cisplatin chemotherapy. PMID:26893365

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. A Study on Sub-Clinical Narcissistic Personality Score and Its Relationship with Academic Performance-An Indian Experience

    Directory of Open Access Journals (Sweden)

    Vaidhyanatha Balaji

    2014-12-01

    Full Text Available Sub-clinical narcissism is the presence of narcissistic personality traits in otherwise normal people. People with high levels of these traits said to have inflated self-esteem and possibly a high egotism. A 40 itemed Narcissistic Personality Inventory is used to measure this type of personality traits. Those individuals who score above 20 points from the available 40 points of NPI-40 Inventory is considered to be having higher levels of Subclinical Narcissism and prone to exhibit socially dislikeable personality traits. This study tried to address the relationship between supposedly negative personality traits of Sub-clinical Narcissism using NPI-40 Score against past and present academic performance of a group of students in a Private University setup. The study included 202 participants from a Business School Division of a Private University. Analysis showed that only at the current academic levels of the respondents, NPI-40 scores were significantly correlating with their academic performance. Research implications are discussed.

  13. Experimental and Clinical Advances in Immunotherapy Strategies for Spinal Cord Injury Target on MAIs and Their Receptors.

    Science.gov (United States)

    Lu, Xiu-Min; Wei, Jing-Xiang; Xiao, Lan; Shu, Ya-Hai; Wang, Yong-Tang

    2016-01-01

    In the injured adult mammalian central nervous system (CNS), the failure of axonal regeneration is thought to be attributed, at least in part, to various myelin-associated inhibitors (MAIs), such as Nogo, myelinassociated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp) around the damaged site. Interestingly, these three structurally different inhibitors share two common receptors, Nogo-66 receptor (NgR) and paired immunoglobulin-like receptor B (PirB), and transduce the inhibitory signal into neurons via their complex combinant and co-receptors, such as p75 neurotrophin receptor (p75NTR), Nogo receptor-interacting protein 1 (LINGO-1), and TROY. Accordingly, targeting of the whole myelin or just portions by immunization has been proved to be neuroprotective and is able to promote regeneration in the injured spinal cords. In the past few years, vaccine approaches were initially achieved and could induce the production of antibodies against inhibitors in myelin to block the inhibitory effects and promote functional recovery in spinal cord injury (SCI) models by immunizing with MAIs, such as purified myelin, spinal cord homogenates, or their receptors with the concept of protective autoimmunity formulated. However, for safety consideration, further work is necessary before the immunotherapy strategies can be adopted to treat human injured spinal cords. PMID:26635269

  14. Self-perceived versus objectively measured competence in performing clinical practical procedures by final year medical students

    Science.gov (United States)

    Banda, Sekelani

    2016-01-01

    Objectives To determine and compare the self-perceived and objectively measured competence in performing 14 core-clinical practical procedures by Final Year Medical Students of the University of Zambia. Methods The study included 56 out of 60 graduating University of Zambia Medical Students of the 2012/2013 academic year. Self-perceived competence: students rated their competence on 14 core- clinical practical procedures using a self-administered questionnaire on a 5-point Likert scale. Objective competence: it was measured by Objective Structured Clinical Examination (OSCE) by faculty using predetermined rating scales. Rank order correlation test was performed for self-perceived and objectively measured competence. Results Two thirds 36 (66.7%) of the participants perceived themselves as moderately competent, 15 (27.8%) rated themselves as highly competent while 3 (5.6%) had low self-perception. With objective competence, the majority 52 (92.8%) were barely competent while 4 (7.2%) were absolutely competent. When overall self-perception was compared to objectively measured competence, there was a discordance which was demonstrated by a negative correlation (Spearman rho -.123). Conclusions Significant numbers of students reported low self-competence in performing procedures such as endotracheal intubation, gastric lavage and cardiopulmonary resuscitation which most never performed during the clinical years of medical education. In addition, the negative correlation between self-perceived and objectively measured competence demonstrated the inability of students to assess and rate themselves objectively due to fear that others may know their weaknesses and realize that they are not as competent as expected at a specific level of training. PMID:27132255

  15. The clinical condition and functional performance of the heart in patients with persistent atrial fibrillation after electrical cardioversion.

    OpenAIRE

    Pysarevska K.О.

    2016-01-01

    Atrial fibrillation (AF) - one of the most common cardiac arrhythmia, which leads to increased mortality, increased risk of stroke, heart failure, worsening of quality of life. The aim of the study was to examine the clinical condition and hemodynamic performance of the heart in patients with non-valvular persistent AF before and 6 months after the restoration of sinus rhythm by electrical cardioversion (ECV). According to the study, it was found that the major diseases against which persiste...

  16. 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.

  17. Performance of the Liaison XL Murex HIV Ab/Ag Test on Clinical Samples Representing Current Epidemic HIV Variants

    OpenAIRE

    Lemee, Véronique; Leoz, Marie; Etienne, Manuel; De Oliveira, Fabienne; Plantier, Jean-Christophe

    2014-01-01

    Screening for HIV infection has improved since the first immunoassays. Today, diagnosis of HIV infection can be performed with fourth-generation tests that track both the patient's antibodies and HIV antigen. The objective of this study was to evaluate the clinical sensitivity and specificity of the new DiaSorin Liaison XL Murex HIV Ab/Ag assay compared to another fourth-generation assay, the Abbott Architect HIV Ag/Ab Combo kit. This work was performed on a large panel of 900 samples, includ...

  18. 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. PMID:15689612

  19. 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…

  20. Optimised labeling, preclinical and initial clinical aspects of CCK-2 receptor-targeting with 3 radiolabeled peptides

    International Nuclear Information System (INIS)

    Medullary thyroid carcinoma (MTC) expresses CCK-2 receptors. 111In-labeled DOTA-DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (DOTA-MG11), DOTA-DAsp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2 (DOTA-CCK), and 99mTc-labeled N4-Gly-DGlu-(Glu)5-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (99mTc-Demogastrin 2) are analogs developed for CCK-2 receptor-targeted scintigraphy. All 3 radiolabeled analogs were selected on the basis of their high CCK-2 receptor affinity and their good in vitro serum stability, with in vitro serum t1/2 values of several hours. Radiolabeling of DOTA-peptides with 111In requires a heating procedure, typically in the range of 80 deg. - 100 deg. C up to 30 min. Following this procedure with DOTA-MG11 resulted in a >98 % incorporation of 111In, however, with a radiochemical purity (RCP) of 111In involved 5 min heating at 80 deg. C and led to an incorporation of 111In of >98 %. In addition, all analogs were radiolabeled in the presence of quenchers to prevent radiolysis and oxidation resulting in a RCP of >90 %. All 3 radiolabeled analogs were i.v. administered to 6 MTC patients: radioactivity cleared rapidly by the kidneys, with no significant differences in the excretion pattern of the 3 radiotracers. All 3 radiolabeled analogs exhibited a low in vivo stability in patients, as revealed during analysis of blood samples, with the respective t1/2 found in the order of minutes. In patient blood, the rank of radiopeptide in vivo stability was: 99mTc-Demogastrin 2 (t1/2 10-15 min)>111In-DOTA-CCK (t1/2∼5-10 min)>111In-DOTA-MG11 (t1/2<5 min)

  1. Don't it make my brown eyes blue: co-witness misinformation about a target's appearance can impair target-absent line-up performance.

    Science.gov (United States)

    Zajac, Rachel; Henderson, Nicola

    2009-04-01

    Misinformation from another witness has been shown to impair eyewitness reports, but little is known about how it may influence eyewitness identification. In Experiment 1, adult pairs comprising one participant and one experimental confederate viewed a video clip of a staged theft. Half of the participants were then misinformed by the confederate that the thief's accomplice had blue eyes (in fact, they were brown). Next, individual participants described the accomplice and completed a target-absent photographic line-up task comprising blue-eyed members. Misinformed participants were several times more likely than controls to describe the accomplice as having blue eyes, and twice as likely to identify someone from the line-up. In Experiment 2, when line-up members' eye colour was digitally altered from blue to brown, the line-up effect disappeared, suggesting that the increase in identifications in Experiment 1 was not a generalised increase in willingness to choose from the line-up. In Experiment 3, we discounted the possibility that discussion alone could account for the line-up misinformation effect, by subjecting all participants to co-witness discussion. PMID:19156565

  2. 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

  3. Clinical and epidemiological features of typhoid fever in Pemba, Zanzibar: assessment of the performance of the WHO case definitions.

    Directory of Open Access Journals (Sweden)

    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. Performance and Verification of a Real-Time PCR Assay Targeting the gyrA Gene for Prediction of Ciprofloxacin Resistance in Neisseria gonorrhoeae.

    Science.gov (United States)

    Hemarajata, P; Yang, S; Soge, O O; Humphries, R M; Klausner, J D

    2016-03-01

    In the United States, 19.2% of Neisseria gonorrhoeae isolates are resistant to ciprofloxacin. We evaluated a real-time PCR assay to predict ciprofloxacin susceptibility using residual DNA from the Roche Cobas 4800 CT/NG assay. The results of the assay were 100% concordant with agar dilution susceptibility test results for 100 clinical isolates. Among 76 clinical urine and swab specimens positive for N. gonorrhoeae by the Cobas assay, 71% could be genotyped. The test took 1.5 h to perform, allowing the physician to receive results in time to make informed clinical decisions. PMID:26739156

  5. 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 reflects the effectiveness of the treatment up to that point. The TS(t) figure is automatically delivered by the device without user intervention. Two clinical studies of the device were conducted, the ethics guidelines permitting only use of the value of TS(t) obtained at the end of treatment (this value is termed the treatment score TS0). The acoustically-derived treatment score was compared with the treatment score CTS2 given by the consultant urologist at the three-week patient's follow-up appointment. In the first clinical study (phase 1), records could be compared for 30 out of the 118 patients originally recruited, and the results of phase 1 were used to refine the parameter values (the `rules') with which the acoustic device provides its treatment score. These rules were tested in phase 2, for which records were compared for 49 of the 85 patients recruited. Considering just the phase 2 results (since the phase 1 data were used to draw up the `rules' under which phase 2 operated

  6. Performance of online drug information databases as clinical decision support tools in infectious disease medication management.

    Science.gov (United States)

    Polen, Hyla H; Zapantis, Antonia; Clauson, Kevin A; Clauson, Kevin Alan; Jebrock, Jennifer; Paris, Mark

    2008-01-01

    Infectious disease (ID) medication management is complex and clinical decision support tools (CDSTs) can provide valuable assistance. This study evaluated scope and completeness of ID drug information found in online databases by evaluating their ability to answer 147 question/answer pairs. Scope scores produced highest rankings (%) for: Micromedex (82.3), Lexi-Comp/American Hospital Formulary Service (81.0), and Medscape Drug Reference (81.0); lowest includes: Epocrates Online Premium (47.0), Johns Hopkins ABX Guide (45.6), and PEPID PDC (40.8). PMID:18999059

  7. 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

  8. 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.)

  9. Success, clinical performance and patient satisfaction of direct fibre-reinforced composite fixed partial dentures - a two-year clinical study.

    Science.gov (United States)

    Malmstrom, H; Dellanzo-Savu, A; Xiao, J; Feng, C; Jabeen, A; Romero, M; Huang, J; Ren, Y; Yunker, M A

    2015-12-01

    To evaluate the success, clinical performance and patient satisfaction of directly placed fibre-reinforced composite (FRC) fixed partial dentures (FPDs) in 2 years. One hundred sixty-seven FRC FPDs (120 subjects) were directly fabricated to restore a single missing tooth by six Advanced Education in General Dentistry (AEGD) residents. The FRC FPDs recipients were randomised into two groups according to the fibre materials (pre-impregnated glass or polyethylene). Clinical performance was evaluated at baseline (2 weeks), 6, 12 and 24 months by two calibrated evaluators for prosthesis adaptation, colour match, marginal discoloration, surface roughness, caries and post-operative sensitivity using modified United State Public Health Service (USPHS) criteria. Prosthesis appearance, colour, chewing ability and overall satisfaction were evaluated by patients using a visual analogue scale (VAS). Kaplan-Meier estimation was used to estimate the prosthesis success. Ninety-four patients with 137 FRC FPDs returned (21·67% attrition rate for study subjects, 17·94% for FRC FPDs). Seventeen FRC FPDs failed, due to one-end (n = 4) or two-ends (n = 4) debonding or pontic fracture (n = 9). The cumulative 2-year success rate was 84·32% and survival rate was 92·7%; there were no statistically significant differences between the groups according to different missing tooth location, retention type or fibre materials (P > 0·05). Patient satisfaction regarding prosthesis appearance, col-our, chewing ability and overall satisfaction was rated high on the VAS (mean >80 mm) for all criteria at all time points. The FRC FPDs (restoring single tooth) fabricated by AEGD residents achieved acceptable success and survival rates in a 2-year follow-up. PMID:26172283

  10. Development of RTOG Consensus Guidelines for the Definition of the Clinical Target Volume for Postoperative Conformal Radiation Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: To define a prostate fossa clinical target volume (PF-CTV) for Radiation Therapy Oncology Group (RTOG) trials using postoperative radiotherapy for prostate cancer. Methods and Materials: An RTOG-sponsored meeting was held to define an appropriate PF-CTV after radical prostatectomy. Data were presented describing radiographic failure patterns after surgery. Target volumes used in previous trials were reviewed. Using contours independently submitted by 13 radiation oncologists, a statistical imputation method derived a preliminary 'consensus' PF-CTV. Results: Starting from the model-derived CTV, consensus was reached for a CT image-based PF-CTV. The PF-CTV should extend superiorly from the level of the caudal vas deferens remnant to >8-12 mm inferior to vesicourethral anastomosis (VUA). Below the superior border of the pubic symphysis, the anterior border extends to the posterior aspect of the pubis and posteriorly to the rectum, where it may be concave at the level of the VUA. At this level, the lateral border extends to the levator ani. Above the pubic symphysis, the anterior border should encompass the posterior 1-2 cm of the bladder wall; posteriorly, it is bounded by the mesorectal fascia. At this level, the lateral border is the sacrorectogenitopubic fascia. Seminal vesicle remnants, if present, should be included in the CTV if there is pathologic evidence of their involvement. Conclusions: Consensus on postoperative PF-CTV for RT after prostatectomy was reached and is available as a CT image atlas on the RTOG website. This will allow uniformity in defining PF-CTV for clinical trials that include postprostatectomy RT.

  11. Comparison of Two Different Bonding Agents on Clinical Performance of Fissure Sealants

    Directory of Open Access Journals (Sweden)

    A. Makarem

    2007-12-01

    Full Text Available Objective: Considering the fact that several bonding agents are available in market, clinical evaluations are required to find the durability of the sealants after using bonding agents. The purpose of this study was to compare the durability of the fissure sealant after applying two kinds of dentin bonding materials, AdheSE and Excite.Materials and Methods: In this clinical study sample group consisted of hundred permanent first molars teeth of forty two children. Convenience sampling method has been applied.After three, six and twelve month follow-up, marginal integrity, retention rate and caries in experimental groups were examined. Data were analyzed according to Fisher's Exact, Chi-Square and Mann-Whitney statistical tests.Results: There was no statistical significant difference between the two examined groups,considering marginal integrity, retention rate and caries. In AdheSE group, maxillary teeth had a better retention than mandibular ones.Conclusion: It seems that in pediatric dentistry use of Excite as a bonding agent before the placement of fissure sealant is preferable.

  12. Feasibility, reliability, and clinical validity of the Test of Attentional Performance for Children (KiTAP in Fragile X syndrome (FXS

    Directory of Open Access Journals (Sweden)

    Knox Andrew

    2012-02-01

    Full Text Available Abstract Background Attention and inhibition are core executive-function deficits in FRagile X syndrome (FXS. This pilot study evaluated the feasibility, reproducibility, and clinical relevance of the KiTAP, a computer-based pictorial measure of attention and inhibition with an enchanted-castle theme, in an FXS cohort. Methods The 8-subtest KiTAP battery (as many subtests as each could perform was given to 36 subjects with FXS, of variable age and cognitive/behavioral functioning, and 29 were retested, with an interval of 2 to 4 weeks between sessions. Subjects were rated by parents on the Aberrant Behavior Checklist-Community Edition (ABC-C and Behavior Assessment System for Children, Second Edition (BASC-2. Feasibility, ceiling and basal effects, and data range and distribution analyses were used to eliminate outliers and invalid data points. Reproducibility of scores was analyzed using intraclass correlation coefficients (ICCs and validity/clinical relevance was assessed by correlating KiTAP scores with ABC-C and BASC-2 scores. Results Most of the participants with FXS were able to complete the Alertness, Distractibility, Flexibility, and Go/NoGo subtests.About 50 to 60% completed the Visual Scanning and Vigilance subtests, and 20 to 25% completed the Sustained Attention and Divided Attention subtests. A panel of seven scores from four subtests were identified as feasible for most subjects, lacked excessive ceiling, basal, or learning effects, exhibited an acceptable range and distribution of scores, had good reproducibility (ICC > 0.7, and correlated with behavioral ratings for hyperactivity or attention (P Conclusions The KiTAP can be administered to cohorts with FXS over a wide range of function with valid reproducible scores. With additional validation, it could represent a useful outcome measure for assessment of attention/executive-function abilities in clinical trials targeted to these core deficits in FXS.

  13. Elution performance and clinical experience with 99 Mo-99m TC generator of RIPD, INST, Savar, Bangladesh at NMC, Comilla

    International Nuclear Information System (INIS)

    99m Tc is widely acceptable for its many reasonable criteria in diagnostic use for different clinical Nuclear Medicine studies. Since very beginning of the Nuclear Medicine services in our country, 99m Tc was available form the imported 99m Tc generator form abroad. From September 2000 to Dec