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Sample records for achieve optimal clinical

  1. Achieving clinical integration.

    PubMed

    Redding, John

    2013-11-01

    To develop an effective and sustainable clinically integrated network (CIN) that positions a healthcare organization for value-based payment and other effects of healthcare reform, leaders of CIN initiatives should: Embrace progress rather than perfection; Constrain the development timeline by project managing in reverse; Ensure that physician leaders play an oversight role in the development process. PMID:24340650

  2. Optimism versus Pessimism and Academic Achievement Evaluation

    ERIC Educational Resources Information Center

    Harpaz-Itay, Yifat; Kaniel, Shlomo

    2012-01-01

    This article integrates three central theories of optimism-pessimism (OP). The combination of the shared components of these theories--outcome expectancies, emotions, and behavioral intention--may produce an integrative academic achievement evaluation. Little has been written regarding the differentiation between general and domain-specific OP, a…

  3. Prediction of Achievement in Clinical Pharmacy Courses

    ERIC Educational Resources Information Center

    Simon, Lee S.

    1978-01-01

    A study sought to identify student characteristics which account for academic achievement in clinical pharmacy courses. Preclinical grade point average was the best predictor. Subscales of the California Personality Inventory and the Myers-Briggs Type Indicator, work experience, sex, and age were the other predictor variables. (SW)

  4. The Effects of Academic Optimism on Elementary Reading Achievement

    ERIC Educational Resources Information Center

    Bevel, Raymona K.; Mitchell, Roxanne M.

    2012-01-01

    Purpose: The purpose of this paper is to explore the relationship between academic optimism (AO) and elementary reading achievement (RA). Design/methodology/approach: Using correlation and hierarchical linear regression, the authors examined school-level effects of AO on fifth grade reading achievement in 29 elementary schools in Alabama.…

  5. Academic Optimism and Student Achievement in Urban Elementary Schools

    ERIC Educational Resources Information Center

    Smith, Page A.; Hoy, Wayne K.

    2007-01-01

    Purpose: The aim of this study was two-fold: to demonstrate a general construct of schools called academic optimism and to show it was related to student achievement in urban elementary schools, even controlling for socioeconomic factors, and school size. Design/methodology/approach: Data were collected from 99 urban elementary schools in Texas…

  6. Variability in Clinical Integration Achieved by Athletic Training Students across Different Clinical Sport Assignments

    ERIC Educational Resources Information Center

    Dodge, Thomas M.; Mazerolle, Stephanie M.; Bowman, Thomas G.

    2015-01-01

    Context: Clinical integration impacts athletic training students' (ATSs) motivation and persistence. Research has yet to elucidate the manner in which different clinical placements can influence clinical integration. Objective: To examine differences in the levels of clinical integration achieved by ATSs across various clinical sport assignments.…

  7. Translational geroscience: emphasizing function to achieve optimal longevity.

    PubMed

    Seals, Douglas R; Melov, Simon

    2014-09-01

    Among individuals, biological aging leads to cellular and organismal dysfunction and an increased risk of chronic degenerative diseases and disability. This sequence of events in combination with the projected increases in the number of older adults will result in a worldwide healthcare burden with dire consequences. Superimposed on this setting are the adults now reaching traditional retirement ages--the baby boomers--a group that wishes to remain active, productive and physically and cognitively fit as they grow older. Together, these conditions are producing an unprecedented demand for increased healthspan or what might be termed "optimal longevity"-to live long, but well. To meet this demand, investigators with interests in the biological aspects of aging from model organisms to human epidemiology (population aging) must work together within an interactive process that we describe astranslational geroscience. An essential goal of this new investigational platform should be the optimization and preservation of physiological function throughout the lifespan, including integrative physical and cognitive function, which would serve to increase healthspan, compress morbidity and disability into a shorter period of late-life, and help achieve optimal longevity. To most effectively utilize this new approach, we must rethink how investigators and administrators working at different levels of the translational research continuum communicate and collaborate with each other, how best to train the next generation of scientists in this new field, and how contemporary biological-biomedical aging research should be organized and funded. PMID:25324468

  8. Translational Geroscience: Emphasizing function to achieve optimal longevity

    PubMed Central

    Seals, Douglas R.; Melov, Simon

    2014-01-01

    Among individuals, biological aging leads to cellular and organismal dysfunction and an increased risk of chronic degenerative diseases and disability. This sequence of events in combination with the projected increases in the number of older adults will result in a worldwide healthcare burden with dire consequences. Superimposed on this setting are the adults now reaching traditional retirement ages--the baby boomers--a group that wishes to remain active, productive and physically and cognitively fit as they grow older. Together, these conditions are producing an unprecedented demand for increased healthspan or what might be termed “optimal longevity”—to live long, but well. To meet this demand, investigators with interests in the biological aspects of aging from model organisms to human epidemiology (population aging) must work together within an interactive process that we describe as translational geroscience. An essential goal of this new investigational platform should be the optimization and preservation of physiological function throughout the lifespan, including integrative physical and cognitive function, which would serve to increase healthspan, compress morbidity and disability into a shorter period of late-life, and help achieve optimal longevity. To most effectively utilize this new approach, we must rethink how investigators and administrators working at different levels of the translational research continuum communicate and collaborate with each other, how best to train the next generation of scientists in this new field, and how contemporary biological-biomedical aging research should be organized and funded. PMID:25324468

  9. Optimal achieved blood pressure in acute intracerebral hemorrhage

    PubMed Central

    Arima, Hisatomi; Heeley, Emma; Delcourt, Candice; Hirakawa, Yoichiro; Wang, Xia; Woodward, Mark; Robinson, Thompson; Stapf, Christian; Parsons, Mark; Lavados, Pablo M.; Huang, Yining; Wang, Jiguang; Chalmers, John

    2015-01-01

    Objectives: To investigate the effects of intensive blood pressure (BP) lowering according to baseline BP levels and optimal achieved BP levels in patients with acute intracerebral hemorrhage (ICH). Methods: INTERACT2 was an open, blinded endpoint, randomized controlled trial in 2,839 patients with ICH within 6 hours of onset and elevated systolic BP (SBP) (150–220 mm Hg) who were allocated to receive intensive (target SBP <140 mm Hg within 1 hour, with lower limit of 130 mm Hg for treatment cessation) or guideline-recommended (target SBP <180 mm Hg) BP-lowering treatment. Outcome was physical function across all 7 levels of the modified Rankin Scale at 90 days. Results: Analysis of the randomized comparisons showed that intensive BP lowering produced comparable benefits on physical function at 90 days in 5 subgroups defined by baseline SBP of <160, 160–169, 170–179, 180–189, and ≥190 mm Hg (p homogeneity = 0.790). Analyses of achieved BP showed linear increases in the risk of physical dysfunction for achieved SBP above 130 mm Hg for both hyperacute (1–24 hours) and acute (2–7 days) phases while modest increases were also observed for achieved SBP below 130 mm Hg. Conclusions: Intensive BP lowering appears beneficial across a wide range of baseline SBP levels, and target SBP level of 130–139 mm Hg is likely to provide maximum benefit in acute ICH. Classification of evidence: This study provides Class I evidence that the effect of intensive BP lowering on physical function is not influenced by baseline BP. PMID:25552575

  10. Optimizing Clinical Research Participant Selection with Informatics

    PubMed Central

    Weng, Chunhua

    2015-01-01

    Clinical research participants are often not reflective of the real-world patients due to overly restrictive eligibility criteria. Meanwhile, unselected participants introduce confounding factors and reduce research efficiency. Biomedical Informatics, especially Big Data increasingly made available from electronic health records, offers promising aids to optimize research participant selection through data-driven transparency. PMID:26549161

  11. Optimized Delivery System Achieves Enhanced Endomyocardial Stem Cell Retention

    PubMed Central

    Behfar, Atta; Latere, Jean-Pierre; Bartunek, Jozef; Homsy, Christian; Daro, Dorothee; Crespo-Diaz, Ruben J.; Stalboerger, Paul G.; Steenwinckel, Valerie; Seron, Aymeric; Redfield, Margaret M.; Terzic, Andre

    2014-01-01

    Background Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention. Methods and Results Stem cell retention was simulated in silico using one and three-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol – a nickel and titanium alloy displaying shape memory and super-elasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared to a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle, without impact on biocompatibility or safety. Conclusions Modeling guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention. PMID:24326777

  12. Toward achieving optimal response: understanding and managing antidepressant side effects

    PubMed Central

    Kelly, Karen; Posternak, Michael; Jonathan, E. Alpert

    2008-01-01

    The safety and tolerability of antidepressants have improved considerably over the past two decades, Nevertheless, antidepressant side effects are still common and problematic. The majority of patients treated with contemporary agents experience one or more bothersome side effects. These side effects often create barriers to achieving depressive remission, as well as to preventing relapse and recurrence. Clinicians tend to underestimate the prevalence of side effects, and as many as one quarter of patients discontinue their antidepressants because of difficult-to-tolerate side effects; others may continue on antidepressant therapy but experience diminished quality of life related to troublesome side effects. This article reviews the prevalence of side effects, the impact of side effects on treatment adherence, and methodological issues including the challenge of distinguishing side effects from residual depressive symptoms, discontinuation effects, and general medical problems. In addition, we address the most common side effects such as sexual dysfunction, gastrointestinal problems, sleep disturbance, apathy, and fatigue, and offer strategies for management that may help patients achieve optimal response to pharmacotherapy. PMID:19170398

  13. Improving International Research with Clinical Specimens: 5 Achievable Objectives

    PubMed Central

    LaBaer, Joshua

    2012-01-01

    Our increased interest in translational research has created a large demand for blood, tissue and other clinical samples, which find use in a broad variety of research including genomics, proteomics, and metabolomics. Hundreds of millions of dollars have been invested internationally on the collection, storage and distribution of samples. Nevertheless, many researchers complain in frustration about their inability to obtain relevant and/or useful samples for their research. Lack of access to samples, poor condition of samples, and unavailability of appropriate control samples have slowed our progress in the study of diseases and biomarkers. In this editorial, I focus on five major challenges that thwart clinical sample use for translational research and propose near term objectives to address them. They include: (1) defining our biobanking needs; (2) increasing the use of and access to standard operating procedures; (3) mapping inter-observer differences for use in normalizing diagnoses; (4) identifying natural internal protein controls; and (5) redefining the clinical sample paradigm by building partnerships with the public. In each case, I believe that we have the tools at hand required to achieve the objective within 5 years. Potential paths to achieve these objectives are explored. However we solve these problems, the future of proteomics depends on access to high quality clinical samples, collected under standardized conditions, accurately annotated and shared under conditions that promote the research we need to do. PMID:22998582

  14. Different clinical electrodes achieve similar electrical nerve conduction block

    NASA Astrophysics Data System (ADS)

    Boger, Adam; Bhadra, Narendra; Gustafson, Kenneth J.

    2013-10-01

    Objective. We aim to evaluate the suitability of four electrodes previously used in clinical experiments for peripheral nerve electrical block applications. Approach. We evaluated peripheral nerve electrical block using three such clinical nerve cuff electrodes (the Huntington helix, the Case self-sizing Spiral and the flat interface nerve electrode) and one clinical intramuscular electrode (the Memberg electrode) in five cats. Amplitude thresholds for the block using 12 or 25 kHz voltage-controlled stimulation, onset response, and stimulation thresholds before and after block testing were determined. Main results. Complete nerve block was achieved reliably and the onset response to blocking stimulation was similar for all electrodes. Amplitude thresholds for the block were lowest for the Case Spiral electrode (4 ± 1 Vpp) and lower for the nerve cuff electrodes (7 ± 3 Vpp) than for the intramuscular electrode (26 ± 10 Vpp). A minor elevation in stimulation threshold and reduction in stimulus-evoked urethral pressure was observed during testing, but the effect was temporary and did not vary between electrodes. Significance. Multiple clinical electrodes appear suitable for neuroprostheses using peripheral nerve electrical block. The freedom to choose electrodes based on secondary criteria such as ease of implantation or cost should ease translation of electrical nerve block to clinical practice.

  15. WFH: closing the global gap--achieving optimal care.

    PubMed

    Skinner, Mark W

    2012-07-01

    For 50 years, the World Federation of Hemophilia (WFH) has been working globally to close the gap in care and to achieve Treatment for All patients, men and women, with haemophilia and other inherited bleeding disorders, regardless of where they might live. The WFH estimates that more than one in 1000 men and women has a bleeding disorder equating to 6,900,000 worldwide. To close the gap in care between developed and developing nations a continued focus on the successful strategies deployed heretofore will be required. However, in response to the rapid advances in treatment and emerging therapeutic advances on the horizon it will also require fresh approaches and renewed strategic thinking. It is difficult to predict what each therapeutic advance on the horizon will mean for the future, but there is no doubt that we are in a golden age of research and development, which has the prospect of revolutionizing treatment once again. An improved understanding of "optimal" treatment is fundamental to the continued evolution of global care. The challenges of answering government and payer demands for evidence-based medicine, and cost justification for the introduction and enhancement of treatment, are ever-present and growing. To sustain and improve care it is critical to build the body of outcome data for individual patients, within haemophilia treatment centers (HTCs), nationally, regionally and globally. Emerging therapeutic advances (longer half-life therapies and gene transfer) should not be justified or brought to market based only on the notion that they will be economically more affordable, although that may be the case, but rather more importantly that they will be therapeutically more advantageous. Improvements in treatment adherence, reductions in bleeding frequency (including microhemorrhages), better management of trough levels, and improved health outcomes (including quality of life) should be the foremost considerations. As part of a new WFH strategic plan

  16. Identification of Synergistic, Clinically Achievable, Combination Therapies for Osteosarcoma

    PubMed Central

    Yu, Diana; Kahen, Elliot; Cubitt, Christopher L.; McGuire, Jeremy; Kreahling, Jenny; Lee, Jae; Altiok, Soner; Lynch, Conor C.; Sullivan, Daniel M.; Reed, Damon R.

    2015-01-01

    Systemic therapy has improved osteosarcoma event-free and overall survival, but 30–50% of patients originally diagnosed will have progressive or recurrent disease, which is difficult to cure. Osteosarcoma has a complex karyotype, with loss of p53 in the vast majority of cases and an absence of recurrent, targetable pathways. In this study, we explored 54 agents that are clinically approved for other oncologic indications, agents in active clinical development, and others with promising preclinical data in osteosarcoma at clinically achievable concentrations in 5 osteosarcoma cell lines. We found significant single-agent activity of multiple agents and tested 10 drugs in all permutations of two-drug combinations to define synergistic combinations by Chou and Talalay analysis. We then evaluated order of addition to choose the combinations that may be best to translate to the clinic. We conclude that the repurposing of chemotherapeutics in osteosarcoma by using an in vitro system may define novel drug combinations with significant in vivo activity. In particular, combinations of proteasome inhibitors with histone deacetylase inhibitors and ixabepilone and MK1775 demonstrated excellent activity in our assays. PMID:26601688

  17. Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

    PubMed

    Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2016-07-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. PMID:27089522

  18. Reduced order constrained optimization (ROCO): Clinical application to lung IMRT

    PubMed Central

    Stabenau, Hans; Rivera, Linda; Yorke, Ellen; Yang, Jie; Lu, Renzhi; Radke, Richard J.; Jackson, Andrew

    2011-01-01

    Purpose: The authors use reduced-order constrained optimization (ROCO) to create clinically acceptable IMRT plans quickly and automatically for advanced lung cancer patients. Their new ROCO implementation works with the treatment planning system and full dose calculation used at Memorial Sloan-Kettering Cancer Center (MSKCC). The authors have implemented mean dose hard constraints, along with the point-dose and dose-volume constraints that the authors used for our previous work on the prostate.Methods: ROCO consists of three major steps. First, the space of treatment plans is sampled by solving a series of optimization problems using penalty-based quadratic objective functions. Next, an efficient basis for this space is found via principal component analysis (PCA); this reduces the dimensionality of the problem. Finally, a constrained optimization problem is solved over this basis to find a clinically acceptable IMRT plan. Dimensionality reduction makes constrained optimization computationally efficient.Results: The authors apply ROCO to 12 stage III non-small-cell lung cancer (NSCLC) cases, generating IMRT plans that meet all clinical constraints and are clinically acceptable, and demonstrate that they are competitive with the clinical treatment plans. The authors also test how many samples and PCA modes are necessary to achieve an adequate lung plan, demonstrate the importance of long-range dose calculation for ROCO, and evaluate the performance of nonspecific normal tissue (“rind”) constraints in ROCO treatment planning for the lung. Finally, authors show that ROCO can save time for planners, and they estimate that in the clinic, planning using their approach would save a median of 105 min for the patients in the study.Conclusions: New challenges arise when applying ROCO to the lung site, which include the lack of a class solution, a larger treatment site, an increased number of parameters and beamlets, a variable number of beams and beam arrangement, and

  19. The optimal polarizations for achieving maximum contrast in radar images

    NASA Technical Reports Server (NTRS)

    Swartz, A. A.; Yueh, H. A.; Kong, J. A.; Novak, L. M.; Shin, R. T.

    1988-01-01

    There is considerable interest in determining the optimal polarizations that maximize contrast between two scattering classes in polarimetric radar images. A systematic approach is presented for obtaining the optimal polarimetric matched filter, i.e., that filter which produces maximum contrast between two scattering classes. The maximization procedure involves solving an eigenvalue problem where the eigenvector corresponding to the maximum contrast ratio is an optimal polarimetric matched filter. To exhibit the physical significance of this filter, it is transformed into its associated transmitting and receiving polarization states, written in terms of horizontal and vertical vector components. For the special case where the transmitting polarization is fixed, the receiving polarization which maximizes the contrast ratio is also obtained. Polarimetric filtering is then applies to synthetic aperture radar images obtained from the Jet Propulsion Laboratory. It is shown, both numerically and through the use of radar imagery, that maximum image contrast can be realized when data is processed with the optimal polarimeter matched filter.

  20. Performance-optimized clinical IMRT planning on modern CPUs

    NASA Astrophysics Data System (ADS)

    Ziegenhein, Peter; Kamerling, Cornelis Ph; Bangert, Mark; Kunkel, Julian; Oelfke, Uwe

    2013-06-01

    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.

  1. Aircraft optimization by a system approach: Achievements and trends

    NASA Technical Reports Server (NTRS)

    Sobieszczanski-Sobieski, Jaroslaw

    1992-01-01

    Recently emerging methodology for optimal design of aircraft treated as a system of interacting physical phenomena and parts is examined. The methodology is found to coalesce into methods for hierarchic, non-hierarchic, and hybrid systems all dependent on sensitivity analysis. A separate category of methods has also evolved independent of sensitivity analysis, hence suitable for discrete problems. References and numerical applications are cited. Massively parallel computer processing is seen as enabling technology for practical implementation of the methodology.

  2. Multidisciplinary optimization for engineering systems: Achievements and potential

    NASA Technical Reports Server (NTRS)

    Sobieszczanski-Sobieski, Jaroslaw

    1989-01-01

    The currently common sequential design process for engineering systems is likely to lead to suboptimal designs. Recently developed decomposition methods offer an alternative for coming closer to optimum by breaking the large task of system optimization into smaller, concurrently executed and, yet, coupled tasks, identified with engineering disciplines or subsystems. The hierarchic and non-hierarchic decompositions are discussed and illustrated by examples. An organization of a design process centered on the non-hierarchic decomposition is proposed.

  3. Achieving Optimal Privacy in Trust-Aware Social Recommender Systems

    NASA Astrophysics Data System (ADS)

    Dokoohaki, Nima; Kaleli, Cihan; Polat, Huseyin; Matskin, Mihhail

    Collaborative filtering (CF) recommenders are subject to numerous shortcomings such as centralized processing, vulnerability to shilling attacks, and most important of all privacy. To overcome these obstacles, researchers proposed for utilization of interpersonal trust between users, to alleviate many of these crucial shortcomings. Till now, attention has been mainly paid to strong points about trust-aware recommenders such as alleviating profile sparsity or calculation cost efficiency, while least attention has been paid on investigating the notion of privacy surrounding the disclosure of individual ratings and most importantly protection of trust computation across social networks forming the backbone of these systems. To contribute to addressing problem of privacy in trust-aware recommenders, within this paper, first we introduce a framework for enabling privacy-preserving trust-aware recommendation generation. While trust mechanism aims at elevating recommender's accuracy, to preserve privacy, accuracy of the system needs to be decreased. Since within this context, privacy and accuracy are conflicting goals we show that a Pareto set can be found as an optimal setting for both privacy-preserving and trust-enabling mechanisms. We show that this Pareto set, when used as the configuration for measuring the accuracy of base collaborative filtering engine, yields an optimized tradeoff between conflicting goals of privacy and accuracy. We prove this concept along with applicability of our framework by experimenting with accuracy and privacy factors, and we show through experiment how such optimal set can be inferred.

  4. Gout: optimizing treatment to achieve a disease cure

    PubMed Central

    Bernal, José Antonio; Quilis, Neus; Andrés, Mariano; Sivera, Francisca; Pascual, Eliseo

    2016-01-01

    Gout is one of the most common inflammatory arthritides. The disease is due to the deposition of monosodium urate crystals. These deposits are reversible with proper treatment, suggesting that gout is a curable disease. The main aim in gout is to lower serum uric acid levels to a pre-established target; there are different urate-lowering drugs (xanthine oxidase inhibitors, uricosurics and uricases) through which this can be achieved. Proper treatment of gout also involves correct management of acute flares and their prevention. To ensure treatment adherence it is necessary to explain to the patient what the objectives are. PMID:26977282

  5. Concurrently adjusting interrelated control parameters to achieve optimal engine performance

    DOEpatents

    Jiang, Li; Lee, Donghoon; Yilmaz, Hakan; Stefanopoulou, Anna

    2015-12-01

    Methods and systems for real-time engine control optimization are provided. A value of an engine performance variable is determined, a value of a first operating condition and a value of a second operating condition of a vehicle engine are detected, and initial values for a first engine control parameter and a second engine control parameter are determined based on the detected first operating condition and the detected second operating condition. The initial values for the first engine control parameter and the second engine control parameter are adjusted based on the determined value of the engine performance variable to cause the engine performance variable to approach a target engine performance variable. In order to cause the engine performance variable to approach the target engine performance variable, adjusting the initial value for the first engine control parameter necessitates a corresponding adjustment of the initial value for the second engine control parameter.

  6. Achieving clinical equality in an influenza pandemic: patent realities.

    PubMed

    Kane, Eileen M

    2009-01-01

    pharmaceutical interventions. The national and international public health authorities are slowly integrating intellectual property considerations into pandemic planning. Further integration will anticipate the emergence of patent claims, identify any relevant patents, encourage access norms, and consider the use of legal mechanisms that could alleviate patent-mediated obstacles to the availability of critical products and methods that may be patented. Pandemic management must also co-exist with existing efforts to control seasonal influenza outbreaks. The article analyzes the intersection of patent nodes relevant to vaccine development and to antiviral distribution during a global influenza pandemic, identifying where such patents may facilitate or inhibit the availability of pharmaceutical countermeasures, and offers preliminary observations on the emerging novel H1N1 pandemic. The goal of international clinical equality is essential for the eradication of an influenza pandemic, and strategies for its achievement can also be applied to other diseases. PMID:20718133

  7. Multiphase Nano-Composite Coatings for Achieving Energy Optimization

    SciTech Connect

    Nainaparampil, Jose

    2012-03-26

    UES Inc. and ANL teamed in this work to develop novel coating systems for the protection of surfaces from thermal degradation mainly in two applications; Machining and Die casting. These coatings were specifically designed for the purpose by incorporating required material phases and the overall architecture, which led to reduce the energy usage and increase efficiency of the operations. Following the UES/ANL's feasibility work, the coatings were developed utilizing High power impulse magnetron sputtering (HiPMS) and Large area filtered arc deposition (LAFAD) techniques. Toughness, hardness and oxidation resistance: contrasting qualities have been mixed in the right proportion to attain the suitable material characteristic for the cause. Hafnium diboride (HfB2) based materials provided such a system and its properties were tamed to attain the right combination of toughness and hardness by working on the microstructure and architecture of coatings. An effective interfacing material (graded concentrations of topcoat) was also achieved in this work to provide the required adhesion between the substrate and the coating. Combination of an appropriate bond coat and a functional top coat provided the present thermal degradation resistant coating for cutting tools and die-casting applications. Laboratory level performance tests and industrial level application tests by partner companies (Beta Site Testing) were used for the development of these coatings.

  8. Achieving the World Health Organization's vision for clinical pharmacology.

    PubMed

    Martin, Jennifer H; Henry, David; Gray, Jean; Day, Richard; Bochner, Felix; Ferro, Albert; Pirmohamed, Munir; Mörike, Klaus; Schwab, Matthias

    2016-02-01

    Clinical pharmacology is a medical specialty whose practitioners teach, undertake research, frame policy, give information and advice about the actions and proper uses of medicines in humans and implement that knowledge in clinical practice. It involves a combination of several activities: drug discovery and development, training safe prescribers, providing objective and evidence-based therapeutic information to ethics, regulatory and pricing bodies, supporting patient care in an increasingly subspecialized arena where co-morbidities, polypharmacy, altered pharmacokinetics and drug interactions are common and developing and contributing to medicines policies for Governments. Clinical pharmacologists must advocate drug quality and they must also advocate for sustainability of the Discipline. However for this they need appropriate clinical service and training support. This Commentary discusses strategies to ensure the Discipline is supported by teaching, training and policy organizations, to communicate the full benefits of clinical pharmacology services, put a monetary value on clinical pharmacology services and to grow the clinical pharmacology workforce to support a growing clinical, academic and regulatory need. PMID:26466826

  9. Clinical decision support systems for improving diagnostic accuracy and achieving precision medicine.

    PubMed

    Castaneda, Christian; Nalley, Kip; Mannion, Ciaran; Bhattacharyya, Pritish; Blake, Patrick; Pecora, Andrew; Goy, Andre; Suh, K Stephen

    2015-01-01

    As research laboratories and clinics collaborate to achieve precision medicine, both communities are required to understand mandated electronic health/medical record (EHR/EMR) initiatives that will be fully implemented in all clinics in the United States by 2015. Stakeholders will need to evaluate current record keeping practices and optimize and standardize methodologies to capture nearly all information in digital format. Collaborative efforts from academic and industry sectors are crucial to achieving higher efficacy in patient care while minimizing costs. Currently existing digitized data and information are present in multiple formats and are largely unstructured. In the absence of a universally accepted management system, departments and institutions continue to generate silos of information. As a result, invaluable and newly discovered knowledge is difficult to access. To accelerate biomedical research and reduce healthcare costs, clinical and bioinformatics systems must employ common data elements to create structured annotation forms enabling laboratories and clinics to capture sharable data in real time. Conversion of these datasets to knowable information should be a routine institutionalized process. New scientific knowledge and clinical discoveries can be shared via integrated knowledge environments defined by flexible data models and extensive use of standards, ontologies, vocabularies, and thesauri. In the clinical setting, aggregated knowledge must be displayed in user-friendly formats so that physicians, non-technical laboratory personnel, nurses, data/research coordinators, and end-users can enter data, access information, and understand the output. The effort to connect astronomical numbers of data points, including '-omics'-based molecular data, individual genome sequences, experimental data, patient clinical phenotypes, and follow-up data is a monumental task. Roadblocks to this vision of integration and interoperability include ethical, legal

  10. Collective Responsibility, Academic Optimism, and Student Achievement in Taiwan Elementary Schools

    ERIC Educational Resources Information Center

    Wu, Hsin-Chieh

    2012-01-01

    Previous research indicates that collective efficacy, faculty trust in students and parents, and academic emphasis together formed a single latent school construct, called academic optimism. In the U.S., academic optimism has been proven to be a powerful construct that could effectively predict student achievement even after controlling for…

  11. Expertise, Ethics Expertise, and Clinical Ethics Consultation: Achieving Terminological Clarity.

    PubMed

    Iltis, Ana S; Sheehan, Mark

    2016-08-01

    The language of ethics expertise has become particularly important in bioethics in light of efforts to establish the value of the clinical ethics consultation (CEC), to specify who is qualified to function as a clinical ethics consultant, and to characterize how one should evaluate whether or not a person is so qualified. Supporters and skeptics about the possibility of ethics expertise use the language of ethics expertise in ways that reflect competing views about what ethics expertise entails. We argue for clarity in understanding the nature of expertise and ethics expertise. To be an ethics expert, we argue, is to be an expert in knowing what ought to be done. Any attempt to articulate expertise with respect to knowing what ought to be done must include an account of ethics that specifies the nature of moral truth and the means by which we access this truth or a theoretical account of ethics such that expertise in another domain is linked to knowing or being better at judging what ought to be done and the standards by which this "knowing" or "being better at judging" is determined. We conclude with a discussion of the implications of our analysis for the literature on ethics expertise in CEC. We do think that there are clear domains in which a clinical ethics consultant might be expert but we are skeptical about the possibility that this includes ethics expertise. Clinical ethics consultants should not be referred to as ethics experts. PMID:27256848

  12. Optimizing biologically targeted clinical trials for neurofibromatosis

    PubMed Central

    Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J

    2014-01-01

    Introduction The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2. Areas covered Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution. Expert opinion The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy. PMID:23425047

  13. Optimal clinical implementation of the Siemens virtual wedge

    SciTech Connect

    Walker, C.P.; Richmond, N.D.; Lambert, G.D

    2003-09-30

    Installation of a modern high-energy Siemens Primus linear accelerator at the Northern Centre for Cancer Treatment (NCCT) provided the opportunity to investigate the optimal clinical implementation of the Siemens virtual wedge filter. Previously published work has concentrated on the production of virtual wedge angles at 15 deg., 30 deg., 45 deg., and 60 deg. as replacements for the Siemens hard wedges of the same nominal angles. However, treatment plan optimization of the dose distribution can be achieved with the Primus, as its control software permits the selection of any virtual wedge angle from 15 degree sign to 60 degree sign in increments of 1 deg. The same result can also be produced from a combination of open and 60 deg. wedged fields. Helax-TMS models both of these modes of virtual wedge delivery by the wedge angle and the wedge fraction methods respectively. This paper describes results of timing studies in the planning of optimized patient dose distributions by both methods and in the subsequent treatment delivery procedures. Employment of the wedge fraction method results in the delivery of small numbers of monitor units to the beam's central axis; therefore, wedge profile stability and delivered dose with low numbers of monitor units were also investigated. The wedge fraction was proven to be the most efficient method when the time taken for both planning and treatment delivery were taken into consideration, and is now used exclusively for virtual wedge treatment delivery in Newcastle. It has also been shown that there are no unfavorable dosimetric consequences from its practical implementation.

  14. Feedback and assessment for clinical placements: achieving the right balance

    PubMed Central

    Burgess, Annette; Mellis, Craig

    2015-01-01

    During clinical placements, the provision of feedback forms an integral part of the learning process and enriches students’ learning experiences. The purpose of feedback is to improve the learner’s knowledge, skills, or behavior. Receipt of accurate feedback can help to narrow the gap between actual and desired performance. Effective and regular feedback has the potential to reinforce good practice and motivate the learner toward the desired outcome. Despite the obvious role of feedback in effective teaching and learning, a common complaint from students is that they do not receive adequate feedback. Unfortunately, skills in giving and receiving feedback are rarely taught to students or clinicians. This study aims to provide an understanding of the role of feedback within the learning process, consider consequences of inadequate or poorly given feedback, consider the barriers to the feedback process, provide practical guidelines for providing feedback, and consider the need for student and faculty development in feedback skills. PMID:26056511

  15. The Clinical Significance of Optimality Theory for Phonological Disorders

    ERIC Educational Resources Information Center

    Gierut, Judith A.; Morrisette, Michele L.

    2005-01-01

    Linguistic theory has made important contributions to the clinical assessment and treatment of children with functional phonological disorders. In this article, Optimality Theory (OT) is introduced as a new linguistic model of grammar. Basic assumptions of the model are described and extended to clinical assessment and treatment. The aim is (1) to…

  16. Executive functioning in individuals with a history of ASDs who have achieved optimal outcomes.

    PubMed

    Troyb, Eva; Rosenthal, Michael; Eigsti, Inge-Marie; Kelley, Elizabeth; Tyson, Katherine; Orinstein, Alyssa; Barton, Marianne; Fein, Deborah

    2014-01-01

    Executive functioning (EF) is examined among children and adolescents once diagnosed with an autism spectrum disorder (ASD), but who no longer meet diagnostic criteria. These individuals have average social and language skills, receive minimal school support and are considered to have achieved "optimal outcomes" (OOs). Since residual impairments in these individuals might be expected in deficits central to autism, and in developmentally advanced skills, EF was examined in 34 individuals who achieved OOs, 43 individuals with high-functioning autism (HFA), and 34 typically developing (TD) peers. Groups were matched on age (M = 13.49), gender, and nonverbal IQ (NVIQ) but differed on verbal IQ (VIQ; HFA < TD, OO). On direct assessment, all three groups demonstrated average EF; however, the OO and HFA groups exhibited more impulsivity and less efficient planning and problem-solving than the TD group, and more HFA participants exhibited below average inhibition than did OO and TD participants. Parent-report measures revealed average EF among the OO and TD groups; however, the OO group exhibited more difficulty than the TD group on set-shifting and working memory. HFA participants demonstrated more difficulty on all parent-reported EF domains, with a clinical impairment in attention-shifting. Results suggest that EF in OO appears to be within the average range, even for functions that were impaired among individuals with HFA. Despite their average performance, however, the OO and TD groups differed on measures of impulsivity, set-shifting, problem-solving, working memory, and planning, suggesting that the OO group does not have the above-average EF scores of the TD group despite their high-average IQs. PMID:23731181

  17. Achieving optimal aesthetics for direct and indirect restorations with microhybrid composite resins.

    PubMed

    Okuda, Wynn H

    2005-04-01

    In aesthetic dentistry, material science has played a key role in the development of natural-appearing restorations. Despite the progress, there have been challenges in achieving a harmonious integration of direct and indirect posterior restorations. Although porcelain restorations provide natural aesthetics, ceramics cannot be applied via direct techniques. Consequently, composite resins are valuable alternatives for conservative posterior restorations. In addition, because of their differing physical and optical properties, optimal aesthetic blending with porcelain and resin cannot be routinely achieved. This article explores the potential of composite resins as a direct and indirect restorative option in achieving the most favorable natural blend in the posterior region. PMID:15974036

  18. Academic Optimism of High School Teachers: Its Relationship to Organizational Citizenship Behaviors and Student Achievement

    ERIC Educational Resources Information Center

    Wagner, Charles A.; DiPaola, Michael F.

    2011-01-01

    The purpose of this study is to build on an emergent research base for academic optimism by testing the construct and its relationship to student achievement and organizational citizenship behaviors in schools in a sample of public high schools. All participants in this study were full-time teachers, guidance counselors, and other full-time…

  19. From Pharmacovigilance to Clinical Care Optimization

    PubMed Central

    Moseley, Edward; Moses, Christopher; Ryan, Padhraig; Somai, Melek; Stone, David; Tang, Kai-ou

    2014-01-01

    Abstract In order to ensure the continued, safe administration of pharmaceuticals, particularly those agents that have been recently introduced into the market, there is a need for improved surveillance after product release. This is particularly so because drugs are used by a variety of patients whose particular characteristics may not have been fully captured in the original market approval studies. Even well-conducted, randomized controlled trials are likely to have excluded a large proportion of individuals because of any number of issues. The digitization of medical care, which yields rich and accessible drug data amenable to analytic techniques, provides an opportunity to capture the required information via observational studies. We propose the development of an open, accessible database containing properly de-identified data, to provide the substrate for the required improvement in pharmacovigilance. A range of stakeholders could use this to identify delayed and low-frequency adverse events. Moreover, its power as a research tool could extend to the detection of complex interactions, potential novel uses, and subtle subpopulation effects. This far-reaching potential is demonstrated by our experience with the open Multi-parameter Intelligent Monitoring in Intensive Care (MIMIC) intensive care unit database. The new database could also inform the development of objective, robust clinical practice guidelines. Careful systematization and deliberate standardization of a fully digitized pharmacovigilance process is likely to save both time and resources for healthcare in general. PMID:26576325

  20. Computer-aided optimal design of custom scoliosis braces considering clinical and patient evaluations.

    PubMed

    Visser, Daniel; Xue, Deyi; Ronsky, Janet L; Harder, James; Zernicke, Ronald F

    2012-09-01

    Scoliosis causes an abnormal three dimensional curvature of the spine that is often treated by an orthotic device called brace. The objective of this research was to develop a new approach to automatically identify the optimal design of custom-built brace, based on clinical and patient evaluations. In this approach, torso geometry of the scoliosis patient was achieved using a 3-D imaging system that generated a 3-D torso surface model, which was modified using a custom CAD system to design the 3-D brace surface model. Two design parameters, a translational correction factor and a rotational correction factor, were selected to design the brace geometry from the torso geometry. The 3-D digital brace was evaluated by three clinical evaluation measures (imbalance, rib hump and principal axis angle reduction) and one patient evaluation measure (discomfort). A multi-objective optimization method was employed to identify the optimal design parameters considering both clinical and patient evaluations. PMID:21257222

  1. Robust, integrated computational control of NMR experiments to achieve optimal assignment by ADAPT-NMR.

    PubMed

    Bahrami, Arash; Tonelli, Marco; Sahu, Sarata C; Singarapu, Kiran K; Eghbalnia, Hamid R; Markley, John L

    2012-01-01

    ADAPT-NMR (Assignment-directed Data collection Algorithm utilizing a Probabilistic Toolkit in NMR) represents a groundbreaking prototype for automated protein structure determination by nuclear magnetic resonance (NMR) spectroscopy. With a [(13)C,(15)N]-labeled protein sample loaded into the NMR spectrometer, ADAPT-NMR delivers complete backbone resonance assignments and secondary structure in an optimal fashion without human intervention. ADAPT-NMR achieves this by implementing a strategy in which the goal of optimal assignment in each step determines the subsequent step by analyzing the current sum of available data. ADAPT-NMR is the first iterative and fully automated approach designed specifically for the optimal assignment of proteins with fast data collection as a byproduct of this goal. ADAPT-NMR evaluates the current spectral information, and uses a goal-directed objective function to select the optimal next data collection step(s) and then directs the NMR spectrometer to collect the selected data set. ADAPT-NMR extracts peak positions from the newly collected data and uses this information in updating the analysis resonance assignments and secondary structure. The goal-directed objective function then defines the next data collection step. The procedure continues until the collected data support comprehensive peak identification, resonance assignments at the desired level of completeness, and protein secondary structure. We present test cases in which ADAPT-NMR achieved results in two days or less that would have taken two months or more by manual approaches. PMID:22427982

  2. Preoperative treatment planning with intraoperative optimization can achieve consistent high-quality implants in prostate brachytherapy

    SciTech Connect

    Kudchadker, Rajat J.; Pugh, Thomas J.; Swanson, David A.; Bruno, Teresa L.; Bolukbasi, Yasemin; Frank, Steven J.

    2012-01-01

    Advances in brachytherapy treatment planning systems have allowed the opportunity for brachytherapy to be planned intraoperatively as well as preoperatively. The relative advantages and disadvantages of each approach have been the subject of extensive debate, and some contend that the intraoperative approach is vital to the delivery of optimal therapy. The purpose of this study was to determine whether high-quality permanent prostate implants can be achieved consistently using a preoperative planning approach that allows for, but does not necessitate, intraoperative optimization. To achieve this purpose, we reviewed the records of 100 men with intermediate-risk prostate cancer who had been prospectively treated with brachytherapy monotherapy between 2006 and 2009 at our institution. All patients were treated with iodine-125 stranded seeds; the planned target dose was 145 Gy. Only 8 patients required adjustments to the plan on the basis of intraoperative findings. Consistency and quality were assessed by calculating the correlation coefficient between the planned and implanted amounts of radioactivity and by examining the mean values of the dosimetric parameters obtained on preoperative and 30 days postoperative treatment planning. The amount of radioactivity implanted was essentially identical to that planned (mean planned radioactivity, 41.27 U vs. mean delivered radioactivity, 41.36 U; R{sup 2} = 0.99). The mean planned and day 30 prostate V100 values were 99.9% and 98.6%, respectively. The mean planned and day 30 prostate D90 values were 186.3 and 185.1 Gy, respectively. Consistent, high-quality prostate brachytherapy treatment plans can be achieved using a preoperative planning approach, mostly without the need for intraoperative optimization. Good quality assurance measures during simulation, treatment planning, implantation, and postimplant evaluation are paramount for achieving a high level of quality and consistency.

  3. Faculty Sense of Academic Optimism and Its Relationship to Students' Achievement in Well Performing High Schools

    ERIC Educational Resources Information Center

    Cromartie, Michael Tyrone

    2013-01-01

    The aim of this study was to determine the organizational characteristics and behaviors that contribute to sustaining a culture of academic optimism as a mechanism of student achievement. While there is a developing research base identifying both the individual elements of academic optimism as well as the academic optimism construct itself as…

  4. On the Achievable Efficiency-Fairness Tradeoff in Utility-Optimal MAC Protocols

    NASA Astrophysics Data System (ADS)

    Lee, Jang-Won; Chiang, Mung; Calderbank, A. Robert

    We use the network utility maximization (NUM) framework to create an efficient and fair medium access control (MAC) protocol for wireless networks. By adjusting the parameters in the utility objective functions of NUM problems, we control the tradeoff between efficiency and fairness of radio resource allocation through a rigorous and systematic design. In this paper, we propose a scheduling-based MAC protocol. Since it provides an upper-bound on the achievable performance, it establishes the optimality benchmarks for comparison with other algorithms in related work.

  5. Achieving optimal gingival esthetics around restored natural teeth and implants. Rationale, concepts, and techniques.

    PubMed

    Bichacho, N

    1998-10-01

    The role of prosthetic restorations in the final appearance of the surrounding soft tissues has long been recognized. Innovative prosthodontic concepts as described should be used to enhance the biologic as well as the esthetic data of the supporting tissues, in natural teeth and implants alike. Combined dental treatment modalities of different kinds (i.e., orthodontics, periodontal treatment) are often required for optimal results. Meticulous care and attention to the delicate soft tissues should be given throughout all phases of the treatment, with a view to achieving a functional, healthy, and esthetic oral environment. PMID:9891656

  6. Graduate-Entry Medical Student Variables that Predict Academic and Clinical Achievement

    ERIC Educational Resources Information Center

    Blackman, Ian; Darmawan, I Gusti Ngurah

    2004-01-01

    A hypothetical model was formulated to explore factors that influenced academic and clinical achievement for graduate-entry medical students completing their third year of university studies. Nine latent variables were considered including the students' background, previous successes with their undergraduate and postgraduate studies and their…

  7. Undergraduate Nurse Variables that Predict Academic Achievement and Clinical Competence in Nursing

    ERIC Educational Resources Information Center

    Blackman, Ian; Hall, Margaret; Darmawan, I Gusti Ngurah.

    2007-01-01

    A hypothetical model was formulated to explore factors that influenced academic and clinical achievement for undergraduate nursing students. Sixteen latent variables were considered including the students' background, gender, type of first language, age, their previous successes with their undergraduate nursing studies and status given for…

  8. Cultural Competency and Achieving Styles in Clinical Social Work: A Conceptual and Empirical Exploration.

    ERIC Educational Resources Information Center

    Lu, Yuhwa Eva; Lum, Doman; Chen, Sheying

    2001-01-01

    A study explored the relationship between linguistic/cultural differences and individual achieving styles among 900 clinical social workers, including Asian Americans, Latinos, American Indians, African Americans, Jewish Americans, and Whites. Findings are related to a model of cultural competency in which cross-cultural counselor-client…

  9. Proton beam scattering system optimization for clinical and research applications

    SciTech Connect

    Wroe, A. J.; Schulte, R. W.; Slater, J. D.; Barnes, S.; McAuley, G.; Slater, J. M.

    2013-04-15

    Purpose: To develop and test a method for optimizing and constructing a dual scattering system in passively scattered proton therapy. Methods: A beam optics optimization algorithm was developed to optimize the thickness of the first scatterer (S1) and the profile (of both the high-Z material and Lexan) of the second scatterer (S2) to deliver a proton beam matching a given set of parameters, including field diameter, fluence, flatness, and symmetry. A new manufacturing process was also tested that allows the contoured second scattering foil to be created much more economically and quickly using Cerrobend casting. Two application-specific scattering systems were developed and tested using both experimental and Monte Carlo techniques to validate the optimization process described. Results: A scattering system was optimized and constructed to deliver large uniform irradiations of radiobiology samples at low dose rates. This system was successfully built and tested using film and ionization chambers. The system delivered a uniform radiation field of 50 cm diameter (to a dose of {+-}7% of the central axis) while the depth dose profile could be tuned to match the specifications of the particular investigator using modulator wheels and range shifters. A second scattering system for intermediate field size (4 cm < diameter < 10 cm) stereotactic radiosurgery and radiation therapy (SRS and SRT) treatments was also developed and tested using GEANT4. This system improved beam efficiency by over 70% compared with existing scattering systems while maintaining field flatness and depth dose profile. In both cases the proton range uniformity across the radiation field was maintained, further indicating the accuracy of the energy loss formalism in the optimization algorithm. Conclusions: The methods described allow for rapid prototyping of scattering foils to meet the demands of both research and clinical beam delivery applications in proton therapy.

  10. Optimizing clinical environments for knowledge translation: strategies for nursing leaders.

    PubMed

    Scott, Shannon D; VandenBeld, Brenda; Cummings, Greta G

    2011-10-01

    Using findings from our recent study that found that a context of uncertainty in the work environment hindered nurses' research utilization, we suggest strategies for nurse managers and leaders to optimize clinical environments and support efforts to put research into clinical practice (knowledge translation). Two important sources of uncertainty were the complexity of teamwork and inconsistency in management and leadership styles. To reduce the uncertainty arising from teamwork, we propose (a) clarifying nurses' scopes of practice, (b) increasing knowledge sharing through supporting journal clubs and enhanced computer access and (c) creating safe venues for multidisciplinary dialogue. To reduce uncertainty arising from variations in management and leadership, we propose (a) developing policies that enhance the consistency of leadership and clarify the strategic direction of the management team, (b) clearly communicating those policies to nurses and (c) providing explicit rationales for treatment changes. Small, incremental steps can be taken to realize substantive changes in clinical environments in order to optimize nursing work environments for knowledge translation. PMID:22008623

  11. Optimizing perioperative decision making: improved information for clinical workflow planning.

    PubMed

    Doebbeling, Bradley N; Burton, Matthew M; Wiebke, Eric A; Miller, Spencer; Baxter, Laurence; Miller, Donald; Alvarez, Jorge; Pekny, Joseph

    2012-01-01

    Perioperative care is complex and involves multiple interconnected subsystems. Delayed starts, prolonged cases and overtime are common. Surgical procedures account for 40-70% of hospital revenues and 30-40% of total costs. Most planning and scheduling in healthcare is done without modern planning tools, which have potential for improving access by assisting in operations planning support. We identified key planning scenarios of interest to perioperative leaders, in order to examine the feasibility of applying combinatorial optimization software solving some of those planning issues in the operative setting. Perioperative leaders desire a broad range of tools for planning and assessing alternate solutions. Our modeled solutions generated feasible solutions that varied as expected, based on resource and policy assumptions and found better utilization of scarce resources. Combinatorial optimization modeling can effectively evaluate alternatives to support key decisions for planning clinical workflow and improving care efficiency and satisfaction. PMID:23304284

  12. Optimizing Perioperative Decision Making: Improved Information for Clinical Workflow Planning

    PubMed Central

    Doebbeling, Bradley N.; Burton, Matthew M.; Wiebke, Eric A.; Miller, Spencer; Baxter, Laurence; Miller, Donald; Alvarez, Jorge; Pekny, Joseph

    2012-01-01

    Perioperative care is complex and involves multiple interconnected subsystems. Delayed starts, prolonged cases and overtime are common. Surgical procedures account for 40–70% of hospital revenues and 30–40% of total costs. Most planning and scheduling in healthcare is done without modern planning tools, which have potential for improving access by assisting in operations planning support. We identified key planning scenarios of interest to perioperative leaders, in order to examine the feasibility of applying combinatorial optimization software solving some of those planning issues in the operative setting. Perioperative leaders desire a broad range of tools for planning and assessing alternate solutions. Our modeled solutions generated feasible solutions that varied as expected, based on resource and policy assumptions and found better utilization of scarce resources. Combinatorial optimization modeling can effectively evaluate alternatives to support key decisions for planning clinical workflow and improving care efficiency and satisfaction. PMID:23304284

  13. High-fidelity simulation: Assessment of student nurses' team achievements of clinical judgment.

    PubMed

    Hallin, Karin; Bäckström, Britt; Häggström, Marie; Kristiansen, Lisbeth

    2016-07-01

    Nursing educators have the challenge of preparing nursing students to handle complex patient care situations in real life, but much remains unknown about the ability to make clinical judgments. In this study, high-fidelity simulation (HFS) was used at a Swedish university to find answers about pre-licensure nursing students' success in clinical judgment in terms of team ability and relationships with theoretical achievements, and personal and scenario circumstances. The matrix Lasater Clinical Judgment Rubric (LCJR) was used to analyze and score the students' ability in teams to notice, interpret and respond to complex care situations. Overall, the results showed the student teams in their first meeting with HFS in a complex care situation achieved low clinical judgment points; most teams were in the stages of Beginning and Developing. For attaining high team achievements the majority of the students in the team should theoretically be "high performance". Being observers and having HFS experience before nursing education was significant too. However, age, health care experience, and assistant nurse degrees were of secondary importance. Further research at universities regionally, nationally, and internationally is needed. PMID:27428686

  14. Reversible Masking Using Low-Molecular-Weight Neutral Lipids to Achieve Optimal-Targeted Delivery

    PubMed Central

    Templeton, Nancy Smyth; Senzer, Neil

    2012-01-01

    Intravenous injection of therapeutics is required to effectively treat or cure metastatic cancer, certain cardiovascular diseases, and other acquired or inherited diseases. Using this route of delivery allows potential uptake in all disease targets that are accessed by the bloodstream. However, normal tissues and organs also have the potential for uptake of therapeutic agents. Therefore, investigators have used targeted delivery to attempt delivery solely to the target cells; however, use of ligands on the surface of delivery vehicles to target specific cell surface receptors is not sufficient to avoid nonspecific uptake. PEGylation has been used for decades to try to avoid nonspecific uptake but suffers from many problems known as “The PEGylation Dilemma.” We have solved this dilemma by replacing PEGylation with reversible masking using low-molecular-weight neutral lipids in order to achieve optimal-targeted delivery solely to target cells. Our paper will focus on this topic. PMID:22655199

  15. Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly

    PubMed Central

    Christofides, Elena A

    2016-01-01

    In acromegaly, achieving biochemical control (growth hormone [GH] level <1.0 ng/mL and age- and sex-normalized levels of insulin-like growth factor 1 [IGF-1]) through timely diagnosis and appropriate treatment provides an opportunity to improve patient outcomes. Diagnosis of acromegaly is challenging because it is rooted in observing subtle clinical manifestations, and it is typical for acromegaly to evolve for up to 10 years before it is recognized. This results in chronic exposure to elevated levels of GH and IGF-1 and delay in patients receiving appropriate treatment, which consequently increases mortality risk. In this review, the clinical impact of elevated GH and IGF-1 levels, the effectiveness of current therapies, and the potential role of novel treatments for acromegaly will be discussed. Clinical burden of acromegaly and benefits associated with management of GH and IGF-1 levels will be reviewed. Major treatment paradigms in acromegaly include surgery, medical therapy, and radiotherapy. With medical therapies, such as somatostatin analogs, dopamine agonists, and GH receptor antagonists, a substantial proportion of patients achieve reduced GH and normalized IGF-1 levels. In addition, signs and symptoms, quality of life, and comorbidities have also been reported to improve to varying degrees in patients who achieve biochemical control. Currently, there are several innovative therapies in development to improve patient outcomes, patient use, and access. Timely biochemical control of acromegaly ensures that the patient can ultimately improve morbidity and mortality from this disease and its extensive consequences. PMID:27471378

  16. Paving the critical path: how can clinical pharmacology help achieve the vision?

    PubMed

    Lesko, L J

    2007-02-01

    It has been almost 3 years since the launch of the FDA critical path initiative following the publication of the paper "Innovation or Stagnation: Challenges and Opportunities on the Critical Path of New Medical Product Development." The initiative was intended to create an urgency with the drug development enterprise to address the so-called "productivity problem" in modern drug development. Clinical pharmacologists are strategically aligned with solutions designed to reduce late phase clinical trial failures to show adequate efficacy and/or safety. This article reviews some of the ways that clinical pharmacologists can lead and implement change in the drug development process. It includes a discussion of model-based, semi-mechanistic drug development, drug/disease models that facilitate informed clinical trial designs and optimal dosing, the qualification process and criteria for new biomarkers and surrogate endpoints, approaches to streamlining clinical trials and new types of interaction between industry and FDA such as the end-of-phase 2A and voluntary genomic data submission meetings respectively. PMID:17259944

  17. Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity.

    PubMed

    Seals, Douglas R; Justice, Jamie N; LaRocca, Thomas J

    2016-04-15

    Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio-economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been 'compression of morbidity' and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, 'geroscience', is focused on healthspan extension. Superimposed on this background are new attitudes and demand for 'optimal longevity' - living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first-line function-preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel 'nutraceutical' compounds, serving as potential

  18. Academic abilities in children and adolescents with a history of autism spectrum disorders who have achieved optimal outcomes.

    PubMed

    Troyb, Eva; Orinstein, Alyssa; Tyson, Katherine; Helt, Molly; Eigsti, Inge-Marie; Stevens, Michael; Fein, Deborah

    2014-04-01

    This study examines the academic abilities of children and adolescents who were once diagnosed with an autism spectrum disorder, but who no longer meet diagnostic criteria for this disorder. These individuals have achieved social and language skills within the average range for their ages, receive little or no school support, and are referred to as having achieved "optimal outcomes." Performance of 32 individuals who achieved optimal outcomes, 41 high-functioning individuals with a current autism spectrum disorder diagnosis (high-functioning autism), and 34 typically developing peers was compared on measures of decoding, reading comprehension, mathematical problem solving, and written expression. Groups were matched on age, sex, and nonverbal IQ; however, the high-functioning autism group scored significantly lower than the optimal outcome and typically developing groups on verbal IQ. All three groups performed in the average range on all subtests measured, and no significant differences were found in performance of the optimal outcome and typically developing groups. The high-functioning autism group scored significantly lower on subtests of reading comprehension and mathematical problem solving than the optimal outcome group. These findings suggest that the academic abilities of individuals who achieved optimal outcomes are similar to those of their typically developing peers, even in areas where individuals who have retained their autism spectrum disorder diagnoses exhibit some ongoing difficulty. PMID:24096312

  19. Role of well-being therapy in achieving a balanced and individualized path to optimal functioning.

    PubMed

    Ruini, Chiara; Fava, Giovanni A

    2012-01-01

    A specific psychotherapeutic strategy for increasing psychological well-being and resilience, well-being therapy (WBT), based on Ryff's conceptual model, has been developed and tested in a number of randomized controlled trials. The findings indicate that flourishing and resilience can be promoted by specific interventions leading to a positive evaluation of one's self, a sense of continued growth and development, the belief that life is purposeful and meaningful, the possession of quality relations with others, the capacity to manage effectively one's life and a sense of self-determination. A decreased vulnerability to depression, mood swings and anxiety has been demonstrated after WBT in high-risk populations. School interventions based on the principles of WBT have been found to yield both promotion of well-being and decrease of distress compared with control groups. The differential technical characteristics and indications of WBT are described, with a special reference to the promotion of an individualized and balanced path to achieve optimal human functioning, avoiding the polarities in positive psychological dimensions. PMID:22570318

  20. Restricted and Repetitive Behaviors in Individuals with a History of ASDs Who Have Achieved Optimal Outcomes

    PubMed Central

    Troyb, Eva; Orinstein, Alyssa; Tyson, Katherine; Eigsti, Inge-Marie; Naigles, Letitia; Fein, Deborah

    2014-01-01

    Studies of Autism Spectrum Disorders (ASDs) suggest that Restricted and Repetitive Behaviors (RRBs) are particularly difficult to remediate. We examined present and past RRBs in 34 individuals who achieved optimal outcomes (OOs; lost their ASD diagnosis), 45 high-functioning individuals with ASD (HFA) and 34 typically developing (TD) peers. The OO group exhibited minimal residual RRBs at the time of the study. All OO participants were reported to have at least one RRB in early childhood and almost 90% met the RRB cutoff for ASD in early childhood, but RRBs were not more present in the OO than the TD group at the time of the study. History of RRBs in the HFA and OO groups differed only in oversensitivity to noise and insistence on sameness. Reports of current behavior indicated that RRB’s had almost totally disappeared in the OO group. Thus, although RRB’s were present in the OO group in childhood, they resolved along with social and communication deficits. PMID:25030967

  1. Using Visual and Narrative Methods to Achieve Fair Process in Clinical Care

    PubMed Central

    2011-01-01

    The Institute of Medicine has targeted patient-centeredness as an important area of quality improvement. A major dimension of patient-centeredness is respect for patient's values, preferences, and expressed needs. Yet specific approaches to gaining this understanding and translating it to quality care in the clinical setting are lacking. From a patient perspective quality is not a simple concept but is best understood in terms of five dimensions: technical outcomes; decision-making efficiency; amenities and convenience; information and emotional support; and overall patient satisfaction. Failure to consider quality from this five-pronged perspective results in a focus on medical outcomes, without considering the processes central to quality from the patient's perspective and vital to achieving good outcomes. In this paper, we argue for applying the concept of fair process in clinical settings. Fair process involves using a collaborative approach to exploring diagnostic issues and treatments with patients, explaining the rationale for decisions, setting expectations about roles and responsibilities, and implementing a core plan and ongoing evaluation. Fair process opens the door to bringing patient expertise into the clinical setting and the work of developing health care goals and strategies. This paper provides a step by step illustration of an innovative visual approach, called photovoice or photo-elicitation, to achieve fair process in clinical work with acquired brain injury survivors and others living with chronic health conditions. Applying this visual tool and methodology in the clinical setting will enhance patient-provider communication; engage patients as partners in identifying challenges, strengths, goals, and strategies; and support evaluation of progress over time. Asking patients to bring visuals of their lives into the clinical interaction can help to illuminate gaps in clinical knowledge, forge better therapeutic relationships with patients living

  2. Using visual and narrative methods to achieve fair process in clinical care.

    PubMed

    Lorenz, Laura S; Chilingerian, Jon A

    2011-01-01

    The Institute of Medicine has targeted patient-centeredness as an important area of quality improvement. A major dimension of patient-centeredness is respect for patient's values, preferences, and expressed needs. Yet specific approaches to gaining this understanding and translating it to quality care in the clinical setting are lacking. From a patient perspective quality is not a simple concept but is best understood in terms of five dimensions: technical outcomes; decision-making efficiency; amenities and convenience; information and emotional support; and overall patient satisfaction. Failure to consider quality from this five-pronged perspective results in a focus on medical outcomes, without considering the processes central to quality from the patient's perspective and vital to achieving good outcomes. In this paper, we argue for applying the concept of fair process in clinical settings. Fair process involves using a collaborative approach to exploring diagnostic issues and treatments with patients, explaining the rationale for decisions, setting expectations about roles and responsibilities, and implementing a core plan and ongoing evaluation. Fair process opens the door to bringing patient expertise into the clinical setting and the work of developing health care goals and strategies. This paper provides a step by step illustration of an innovative visual approach, called photovoice or photo-elicitation, to achieve fair process in clinical work with acquired brain injury survivors and others living with chronic health conditions. Applying this visual tool and methodology in the clinical setting will enhance patient-provider communication; engage patients as partners in identifying challenges, strengths, goals, and strategies; and support evaluation of progress over time. Asking patients to bring visuals of their lives into the clinical interaction can help to illuminate gaps in clinical knowledge, forge better therapeutic relationships with patients living

  3. Achieving optimal essential fatty acid status in vegetarians: current knowledge and practical implications.

    PubMed

    Davis, Brenda C; Kris-Etherton, Penny M

    2003-09-01

    Although vegetarian diets are generally lower in total fat, saturated fat, and cholesterol than are nonvegetarian diets, they provide comparable levels of essential fatty acids. Vegetarian, especially vegan, diets are relatively low in alpha-linolenic acid (ALA) compared with linoleic acid (LA) and provide little, if any, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Clinical studies suggest that tissue levels of long-chain n-3 fatty acids are depressed in vegetarians, particularly in vegans. n-3 Fatty acids have numerous physiologic benefits, including potent cardioprotective effects. These effects have been demonstrated for ALA as well as EPA and DHA, although the response is generally less for ALA than for EPA and DHA. Conversion of ALA by the body to the more active longer-chain metabolites is inefficient: < 5-10% for EPA and 2-5% for DHA. Thus, total n-3 requirements may be higher for vegetarians than for nonvegetarians, as vegetarians must rely on conversion of ALA to EPA and DHA. Because of the beneficial effects of n-3 fatty acids, it is recommended that vegetarians make dietary changes to optimize n-3 fatty acid status. PMID:12936959

  4. Diabetic gastrointestinal autonomic neuropathy: current status and new achievements for everyday clinical practice.

    PubMed

    Gatopoulou, A; Papanas, N; Maltezos, E

    2012-09-01

    Gastrointestinal symptoms occur frequently among patients with diabetes mellitus and are associated with considerable morbidity. Diabetic gastrointestinal autonomic neuropathy represents a complex disorder with multifactorial pathogenesis, which is still not well understood. It appears to involve a spectrum of metabolic and cellular changes that affect gastrointestinal motor and sensory control. It may affect any organ in the digestive system. Clinical manifestations are often underestimated, and therefore autonomic neuropathy should be suspected in all diabetic patients with unexplained gastrointestinal symptoms. Advances in technology have now enabled assessment of gastrointestinal motor function. Moreover, novel pharmacological approaches, along with endoscopic and surgical treatment options, contribute to improved outcomes. This review summarises the progress achieved in diabetic gastrointestinal autonomic neuropathy during the last years, focusing on clinical issues of practical importance to the everyday clinician. PMID:22863425

  5. 75 FR 47819 - Workshop on Optimizing Clinical Trial Design for the Development of Pediatric Cardiovascular Devices

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-09

    ... HUMAN SERVICES Food and Drug Administration Workshop on Optimizing Clinical Trial Design for the... ``Optimizing Clinical Trial Design for the Development of Pediatric Cardiovascular Devices.'' The topic to be... various efficient and pragmatic clinical trial designs that are conducive to overcoming the challenges...

  6. The biopharmaceutics risk assessment roadmap for optimizing clinical drug product performance.

    PubMed

    Selen, Arzu; Dickinson, Paul A; Müllertz, Anette; Crison, John R; Mistry, Hitesh B; Cruañes, Maria T; Martinez, Marilyn N; Lennernäs, Hans; Wigal, Tim L; Swinney, David C; Polli, James E; Serajuddin, Abu T M; Cook, Jack A; Dressman, Jennifer B

    2014-11-01

    The biopharmaceutics risk assessment roadmap (BioRAM) optimizes drug product development and performance by using therapy-driven target drug delivery profiles as a framework to achieve the desired therapeutic outcome. Hence, clinical relevance is directly built into early formulation development. Biopharmaceutics tools are used to identify and address potential challenges to optimize the drug product for patient benefit. For illustration, BioRAM is applied to four relatively common therapy-driven drug delivery scenarios: rapid therapeutic onset, multiphasic delivery, delayed therapeutic onset, and maintenance of target exposure. BioRAM considers the therapeutic target with the drug substance characteristics and enables collection of critical knowledge for development of a dosage form that can perform consistently for meeting the patient's needs. Accordingly, the key factors are identified and in vitro, in vivo, and in silico modeling and simulation techniques are used to elucidate the optimal drug delivery rate and pattern. BioRAM enables (1) feasibility assessment for the dosage form, (2) development and conduct of appropriate "learning and confirming" studies, (3) transparency in decision-making, (4) assurance of drug product quality during lifecycle management, and (5) development of robust linkages between the desired clinical outcome and the necessary product quality attributes for inclusion in the quality target product profile. PMID:25256402

  7. Calibration of STUD+ parameters to achieve optimally efficient broadband adiabatic decoupling in a single transient

    PubMed

    Bendall; Skinner

    1998-10-01

    for a single sech/tanh pulse. Residual splitting of the centerband, normally associated with incomplete or inefficient decoupling, is not seen in sech/tanh decoupling and therefore cannot be used as a measure of adiabatic decoupling efficiency. The calibrated experimental performance levels achieved in this study are within 20% of theoretical performance levels derived previously for ideal sech/tanh decoupling at high power, indicating a small scope for further improvement at practical RF power levels. The optimization procedures employed here will be generally applicable to any good combination of adiabatic inversion pulse and phase cycle. Copyright 1998 Academic Press. PMID:9761708

  8. Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice.

    PubMed

    Lee, Ho Sup; Min, Chang-Ki

    2016-09-01

    Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achieve long-term disease control. Many clinical trials have reported increased progression-free and overall survival rates after consolidation and maintenance therapy. The role of consolidation/maintenance therapy has been assessed in patients eligible and ineligible for transplantation and is a valuable option in clinical trial settings. However, the decision to use consolidation and/or maintenance therapy needs to be guided by the individual patient situation in actual clinical practice. This review analyzes the currently available evidence from several reported clinical trials to determine the optimal consolidation and maintenance therapy in clinical practice. PMID:27604793

  9. Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice

    PubMed Central

    Lee, Ho Sup; Min, Chang-Ki

    2016-01-01

    Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achieve long-term disease control. Many clinical trials have reported increased progression-free and overall survival rates after consolidation and maintenance therapy. The role of consolidation/maintenance therapy has been assessed in patients eligible and ineligible for transplantation and is a valuable option in clinical trial settings. However, the decision to use consolidation and/or maintenance therapy needs to be guided by the individual patient situation in actual clinical practice. This review analyzes the currently available evidence from several reported clinical trials to determine the optimal consolidation and maintenance therapy in clinical practice. PMID:27604793

  10. Achieving consensus for clinical trials: the REiNS International Collaboration.

    PubMed

    Plotkin, Scott R; Blakeley, Jaishri O; Dombi, Eva; Fisher, Michael J; Hanemann, C Oliver; Walsh, Karin S; Wolters, Pamela L; Widemann, Brigitte C

    2013-11-19

    The neurofibromatoses (NF)--including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis--are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. PMID:24249801

  11. Optimal microelectromechanical systems (MEMS) device for achieving high pyroelectric response of AlN

    NASA Astrophysics Data System (ADS)

    Kebede, Bemnnet; Coutu, Ronald A.; Starman, LaVern

    2014-03-01

    This paper discusses research being conducted on aluminum nitride (AlN) as a pyroelectric material for use in detecting applications. AlN is being investigated because of its high pyroelectric coefficient, thermal stability, and high Curie temperature. In order to determine suitability of the pyroelectric properties of AlN for use as a detector, testing of several devices was conducted. These devices were fabricated using microelectromechanical systems (MEMS) fabrication processes; the devices were also designed to allow for voltage and current measurements. The deposited AlN films used were 150 nm - 300 nm in thickness. Thin-films were used to rapidly increase the temperature response after the thermal stimulus was applied to the pyroelectric material. This is important because the pyroelectric effect is directly proportional to the rate of temperature change. The design used was a face-electrode bridge that provides thermal isolation which minimizes heat loss to the substrate, thereby increasing operation frequency of the pyroelectric device. A thermal stimulus was applied to the pyroelectric material and the response was measured across the electrodes. A thermal imaging camera was used to monitor the changes in temperature. Throughout the testing process, the annealing temperatures, type of layers, and thicknesses were also varied. These changes resulted in improved MEMS designs, which were fabricated to obtain an optimal design configuration for achieving a high pyroelectric response. A pyroelectric voltage response of 38.9 mVp-p was measured without filtering, 12.45 mVp-p was measured in the infrared (IR) region using a Si filter, and 6.38 mVp-p was measured in the short wavelength IR region using a long pass filter. The results showed that AlN's pyroelectric properties can be used in detecting applications.

  12. Identification and Treatment of Pathophysiological Comorbidities of Autism Spectrum Disorder to Achieve Optimal Outcomes.

    PubMed

    Frye, Richard E; Rossignol, Daniel A

    2016-01-01

    Despite the fact that the prevalence of autism spectrum disorder (ASD) continues to rise, no effective medical treatments have become standard of care. In this paper we review some of the pathophysiological abnormalities associated with ASD and their potential associated treatments. Overall, there is evidence for some children with ASD being affected by seizure and epilepsy, neurotransmitter dysfunction, sleep disorders, metabolic abnormalities, including abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, redox and mitochondrial metabolism, and immune and gastrointestinal disorders. Although evidence for an association between these pathophysiological abnormalities and ASD exists, the exact relationship to the etiology of ASD and its associated symptoms remains to be further defined in many cases. Despite these limitations, treatments targeting some of these pathophysiological abnormalities have been studied in some cases with high-quality studies, whereas treatments for other pathophysiological abnormalities have not been well studied in many cases. There are some areas of more promising treatments specific for ASD including neurotransmitter abnormalities, particularly imbalances in glutamate and acetylcholine, sleep onset disorder (with behavioral therapy and melatonin), and metabolic abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, and redox pathways. There is some evidence for treatments of epilepsy and seizures, mitochondrial and immune disorders, and gastrointestinal abnormalities, particularly imbalances in the enteric microbiome, but further clinical studies are needed in these areas to better define treatments specific to children with ASD. Clearly, there are some promising areas of ASD research that could lead to novel treatments that could become standard of care in the future, but more research is needed to better define subgroups of children with ASD who are affected by specific pathophysiological abnormalities and

  13. Identification and Treatment of Pathophysiological Comorbidities of Autism Spectrum Disorder to Achieve Optimal Outcomes

    PubMed Central

    Frye, Richard E.; Rossignol, Daniel A.

    2016-01-01

    Despite the fact that the prevalence of autism spectrum disorder (ASD) continues to rise, no effective medical treatments have become standard of care. In this paper we review some of the pathophysiological abnormalities associated with ASD and their potential associated treatments. Overall, there is evidence for some children with ASD being affected by seizure and epilepsy, neurotransmitter dysfunction, sleep disorders, metabolic abnormalities, including abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, redox and mitochondrial metabolism, and immune and gastrointestinal disorders. Although evidence for an association between these pathophysiological abnormalities and ASD exists, the exact relationship to the etiology of ASD and its associated symptoms remains to be further defined in many cases. Despite these limitations, treatments targeting some of these pathophysiological abnormalities have been studied in some cases with high-quality studies, whereas treatments for other pathophysiological abnormalities have not been well studied in many cases. There are some areas of more promising treatments specific for ASD including neurotransmitter abnormalities, particularly imbalances in glutamate and acetylcholine, sleep onset disorder (with behavioral therapy and melatonin), and metabolic abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, and redox pathways. There is some evidence for treatments of epilepsy and seizures, mitochondrial and immune disorders, and gastrointestinal abnormalities, particularly imbalances in the enteric microbiome, but further clinical studies are needed in these areas to better define treatments specific to children with ASD. Clearly, there are some promising areas of ASD research that could lead to novel treatments that could become standard of care in the future, but more research is needed to better define subgroups of children with ASD who are affected by specific pathophysiological abnormalities and

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

    PubMed Central

    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 < 0.001). Conclusions: A structured 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

  15. Robust Airfoil Optimization to Achieve Consistent Drag Reduction Over a Mach Range

    NASA Technical Reports Server (NTRS)

    Li, Wu; Huyse, Luc; Padula, Sharon; Bushnell, Dennis M. (Technical Monitor)

    2001-01-01

    We prove mathematically that in order to avoid point-optimization at the sampled design points for multipoint airfoil optimization, the number of design points must be greater than the number of free-design variables. To overcome point-optimization at the sampled design points, a robust airfoil optimization method (called the profile optimization method) is developed and analyzed. This optimization method aims at a consistent drag reduction over a given Mach range and has three advantages: (a) it prevents severe degradation in the off-design performance by using a smart descent direction in each optimization iteration, (b) there is no random airfoil shape distortion for any iterate it generates, and (c) it allows a designer to make a trade-off between a truly optimized airfoil and the amount of computing time consumed. For illustration purposes, we use the profile optimization method to solve a lift-constrained drag minimization problem for 2-D airfoil in Euler flow with 20 free-design variables. A comparison with other airfoil optimization methods is also included.

  16. The relationship between medical students’ epistemological beliefs and achievement on a clinical performance examination

    PubMed Central

    Oh, Sun-A; Chung, Eun-Kyung; Han, Eui-Ryoung; Woo, Young-Jong; Kevin, Deiter

    2016-01-01

    Purpose: This study was to explore the relationship between clinical performance examination (CPX) achievement and epistemological beliefs to investigate the potentials of epistemological beliefs in ill-structured medical problem solving tasks. Methods: We administered the epistemological beliefs questionnaire (EBQ) to fourth-year medical students and correlated the results with their CPX scores. The EBQ comprised 61 items reflecting five belief systems: certainty of knowledge, source of knowledge, rigidity of learning, ability to learn, and speed of knowledge acquisition. The CPX included scores for history taking, physical examination, and patient-physician interaction. Results: The higher epistemological beliefs group obtained significantly higher scores on the CPX with regard to history taking and patient-physician interaction. The epistemological beliefs scores on certainty of knowledge and source of knowledge were significantly positively correlated with patient-physician interaction. The epistemological beliefs scores for ability to learn were significantly positively correlated with those for history taking, physical examination, and patient-physician interaction. Conclusion: Students with more sophisticated and advanced epistemological beliefs stances used more comprehensive and varied approaches in the patient-physician interaction. Therefore, educational efforts that encourage discussions pertaining to epistemological views should be considered to improve clinical reasoning and problem-solving competence in the clinic setting. PMID:26838566

  17. Optimizing educational video through comparative trials in clinical environments

    PubMed Central

    Aronson, Ian David; Plass, Jan L.; Bania, Theodore C.

    2012-01-01

    Although video is increasingly used in public health education, studies generally do not implement randomized trials of multiple video segments in clinical environments. Therefore, the specific configurations of educational videos that will have the greatest impact on outcome measures ranging from increased knowledge of important public health issues, to acceptance of a voluntary HIV test, remain largely unknown. Interventions can be developed to run on affordable handheld computers, including inexpensive tablets or netbooks that each patient can use individually, and to integrate video delivery with automated data collection. These video interventions can then be used not only to educate patients who otherwise might not be reached, but to examine how content can be optimized for greater effectiveness as measured by cognitive and behavioral outcomes. This approach may prove especially valuable in high volume urban facilities, such as hospital emergency departments, that provide points of contact for lower income, lower literacy, and high-risk populations who may not otherwise interact with healthcare providers or researchers. This article describes the development and evaluation of an intervention that educates emergency department patients about HIV prevention and testing while comparatively examining a set of videos, each based upon competing educational theories. The computer-based video intervention and methodology are both highly replicable and can be applied to subject areas and settings far beyond HIV or the emergency department. PMID:22904607

  18. Early phase clinical trials to identify optimal dosing and safety

    PubMed Central

    Cook, Natalie; Hansen, Aaron R.; Siu, Lillian L.; Abdul Razak, Albiruni R.

    2014-01-01

    The purpose of early stage clinical trials is to determine the recommended dose and toxicity profile of an investigational agent or multi-drug combination. Molecularly targeted agents (MTAs) and immunotherapies have distinct toxicities from chemotherapies that are often not dose dependent and can lead to chronic and sometimes unpredictable side effects. Therefore utilizing a dose escalation method that has toxicity based endpoints may not be as appropriate for determination of recommended dose, and alternative parameters such as pharmacokinetic or pharmacodynamic outcomes are potentially appealing options. Approaches to enhance safety and optimize dosing include improved preclinical models and assessment, innovative model based design and dose escalation strategies, patient selection, the use of expansion cohorts and extended toxicity assessments. Tailoring the design of phase I trials by adopting new strategies to address the different properties of MTAs is required to enhance the development of these agents. This review will focus on the limitations to safety and dose determination that have occurred in the development of MTAs and immunotherapies. In addition, strategies are proposed to overcome these challenges to develop phase I trials that can more accurately define the recommended dose and identify adverse events. PMID:25160636

  19. Achieving Consistent Near-Optimal Pattern Recognition Accuracy Using Particle Swarm Optimization to Pre-Train Artificial Neural Networks

    ERIC Educational Resources Information Center

    Nikelshpur, Dmitry O.

    2014-01-01

    Similar to mammalian brains, Artificial Neural Networks (ANN) are universal approximators, capable of yielding near-optimal solutions to a wide assortment of problems. ANNs are used in many fields including medicine, internet security, engineering, retail, robotics, warfare, intelligence control, and finance. "ANNs have a tendency to get…

  20. A Study of the Relationships between Distributed Leadership, Teacher Academic Optimism and Student Achievement in Taiwanese Elementary Schools

    ERIC Educational Resources Information Center

    Chang, I-Hua

    2011-01-01

    The purpose of this study was to explore the relationships between distributed leadership, teachers' academic optimism and student achievement in learning. The study targeted public elementary schools in Taiwan and adopted stratified random sampling to investigate 1500 teachers. Teachers' perceptions were collected by a self-report scale. In…

  1. Should Schools Be Optimistic? An Investigation of the Association between Academic Optimism of Schools and Student Achievement in Primary Education

    ERIC Educational Resources Information Center

    Boonen, Tinneke; Pinxten, Maarten; Van Damme, Jan; Onghena, Patrick

    2014-01-01

    Academic emphasis, collective efficacy, and faculty trust in students and parents (3 school characteristics positively associated with student achievement) are assumed to form a higher order latent construct, "academic optimism" (Hoy, Tarter, & Woolfolk Hoy, 2006a, 2006b). The aim of the present study is to corroborate the latent…

  2. Academic Optimism and Collective Responsibility: An Organizational Model of the Dynamics of Student Achievement

    ERIC Educational Resources Information Center

    Wu, Jason H.

    2013-01-01

    This study was designed to examine the construct of academic optimism and its relationship with collective responsibility in a sample of Taiwan elementary schools. The construct of academic optimism was tested using confirmatory factor analysis, and the whole structural model was tested with a structural equation modeling analysis. The data were…

  3. Pre-operative Thresholds for Achieving Meaningful Clinical Improvement after Arthroscopic Treatment of Femoroacetabular Impingement

    PubMed Central

    Nwachukwu, Benedict U.; Fields, Kara G.; Nawabi, Danyal H.; Kelly, Bryan T.; Ranawat, Anil S.

    2016-01-01

    Objectives: Knowledge of the thresholds and determinants for successful femoroacetabular impingement (FAI) treatment is evolving. The primary purpose of this study was to define pre-operative outcome score thresholds that can be used to predict patients most likely to achieve meaningful clinically important difference (MCID) after arthroscopic FAI treatment. Secondarily determinants of achieving MCID were evaluated. Methods: A prospective institutional hip arthroscopy registry was reviewed to identify patients with FAI treated with arthroscopic labral surgery, acetabular rim trimming, and femoral osteochondroplasty. The modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS) and the international Hip Outcome Tool (iHOT-33) tools were administered at baseline and at one year post-operatively. MCID was calculated using a distribution-based method. A receiver operating characteristic (ROC) analysis was used to calculate cohort-based threshold values predictive of achieving MCID. Area under the curve (AUC) was used to define predictive ability (strength of association) with AUC >0.7 considered acceptably predictive. Univariate and multivariable analyses were used to analyze demographic, radiographic and intra-operative factors associated with achieving MCID. Results: There were 374 patients (mean + SD age, 32.9 + 10.5) and 56.4% were female. The MCID for mHHS, HOS activities of daily living (HOS-ADL), HOS Sports, and iHOT-33 was 8.2, 8.4,14.5, and 12.0 respectively. ROC analysis (threshold, % achieving MCID, strength of association) for these tools in our population was: mHHS (61.6, 78%, 0.68), HOS-ADL (83.8, 68%, 0.84), HOS-Sports (63.9, 64%, 0.74), and iHOT-33 (54.3, 82%, 0.65). Likelihood for achieving MCID declined above and increased below these thresholds. In univariate analysis female sex, femoral version, lower acetabular outerbridge score and increasing CT sagittal center edge angle (CEA) were predictive of achieving MCID. In multivariable analysis

  4. Optimizing Reconstruction with Periorbital Transplantation: Clinical Indications and Anatomic Considerations

    PubMed Central

    Sosin, Michael; Mundinger, Gerhard S.; Dorafshar, Amir H.; Iliff, Nicholas T.; Christensen, Joani M.; Christy, Michael R.; Bojovic, Branko

    2016-01-01

    Background: Complex periorbital subunit reconstruction is challenging because the goals of effective reconstruction vary from one individual to another. The purpose of this article is to explore the indications and anatomic feasibility of periorbital transplantation by reviewing our institutional repository of facial injury. Methods: Institutional review board approval was obtained at the R Adams Cowley Shock Trauma Center for a retrospective chart review conducted on patients with periorbital defects. Patient history, facial defects, visual acuity, and periorbital function were critically reviewed to identify indications for periorbital or total face (incorporating the periorbital subunit) vascularized composite allotransplantation. Cadaveric allograft harvest was then designed and performed for specific patient defects to determine anatomic feasibility. Disease conditions not captured by our patient population warranting consideration were reviewed. Results: A total of 7 facial or periorbital transplant candidates representing 6 different etiologies were selected as suitable indications for periorbital transplantation. Etiologies included trauma, burn, animal attack, and tumor, whereas proposed transplants included isolated periorbital and total face transplants. Allograft recovery was successfully completed in 4 periorbital subunits and 1 full face. Dual vascular supply was achieved in 5 of 6 periorbital subunits (superficial temporal and facial vessels). Conclusions: Transplantation of isolated periorbital structures or full face transplantation including periorbital structures is technically feasible. The goal of periorbital transplantation is to re-establish protective mechanisms of the eye, to prevent deterioration of visual acuity, and to optimize aesthetic outcomes. Criteria necessary for candidate selection and allograft design are identified by periorbital defect, periorbital function, ophthalmologic evaluation, and defect etiology. PMID:27014557

  5. Digital mammography--DQE versus optimized image quality in clinical environment: an on site study

    NASA Astrophysics Data System (ADS)

    Oberhofer, Nadia; Fracchetti, Alessandro; Springeth, Margareth; Moroder, Ehrenfried

    2010-04-01

    The intrinsic quality of the detection system of 7 different digital mammography units (5 direct radiography DR; 2 computed radiography CR), expressed by DQE, has been compared with their image quality/dose performances in clinical use. DQE measurements followed IEC 62220-1-2 using a tungsten test object for MTF determination. For image quality assessment two different methods have been applied: 1) measurement of contrast to noise ratio (CNR) according to the European guidelines and 2) contrast-detail (CD) evaluation. The latter was carried out with the phantom CDMAM ver. 3.4 and the commercial software CDMAM Analyser ver. 1.1 (both Artinis) for automated image analysis. The overall image quality index IQFinv proposed by the software has been validated. Correspondence between the two methods has been shown figuring out a linear correlation between CNR and IQFinv. All systems were optimized with respect to image quality and average glandular dose (AGD) within the constraints of automatic exposure control (AEC). For each equipment, a good image quality level was defined by means of CD analysis, and the corresponding CNR value considered as target value. The goal was to achieve for different PMMA-phantom thicknesses constant image quality, that means the CNR target value, at minimum dose. All DR systems exhibited higher DQE and significantly better image quality compared to CR systems. Generally switching, where available, to a target/filter combination with an x-ray spectrum of higher mean energy permitted dose savings at equal image quality. However, several systems did not allow to modify the AEC in order to apply optimal radiographic technique in clinical use. The best ratio image quality/dose was achieved by a unit with a-Se detector and W anode only recently available on the market.

  6. Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn's disease

    PubMed Central

    Ran, Zhi Hua; Gao, Xiang; Chen, Minhu; Zhong, Jie; Sheng, Jian-Qiu; Kamm, Michael A; Travis, Simon; Wallace, Kori; Mostafa, Nael M; Shapiro, Marisa; Li, Yao; Thakkar, Roopal B; Robinson, Anne M

    2016-01-01

    Background/Aims This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD). Methods Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220–450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8–26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored. Results Mean adalimumab serum concentrations during the induction phase were 13.9–18.1 µg/mL (160/80 mg group) and 7.5−9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups. Conclusions Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported. PMID:27175116

  7. Concise review: optimizing expansion of bone marrow mesenchymal stem/stromal cells for clinical applications.

    PubMed

    Hoch, Allison I; Leach, J Kent

    2014-05-01

    Bone marrow-derived mesenchymal stem/stromal cells (MSCs) have demonstrated success in the clinical treatment of hematopoietic pathologies and cardiovascular disease and are the focus of treating other diseases of the musculoskeletal, digestive, integumentary, and nervous systems. However, during the requisite two-dimensional (2D) expansion to achieve a clinically relevant number of cells, MSCs exhibit profound degeneration in progenitor potency. Proliferation, multilineage potential, and colony-forming efficiency are fundamental progenitor properties that are abrogated by extensive monolayer culture. To harness the robust therapeutic potential of MSCs, a consistent, rapid, and minimally detrimental expansion method is necessary. Alternative expansion efforts have exhibited promise in the ability to preserve MSC progenitor potency better than the 2D paradigm by mimicking features of the native bone marrow niche. MSCs have been successfully expanded when stimulated by growth factors, under reduced oxygen tension, and in three-dimensional bioreactors. MSC therapeutic value can be optimized for clinical applications by combining system inputs to tailor culture parameters for recapitulating the niche with probes that nondestructively monitor progenitor potency. The purpose of this review is to explore how modulations in the 2D paradigm affect MSC progenitor properties and to highlight recent efforts in alternative expansion techniques. PMID:24682286

  8. Achieving Finite Element Mesh Quality via Optimization of the Jacobian Matrix Norm and Associated Quantities, Part 1 - A Framework for Surface Mesh Optimization

    SciTech Connect

    Knupp, P.M.

    1999-01-18

    Structured mesh quality optimization methods are extended to optimization of unstructured triangular, quadrilateral, and mixed finite element meshes. N"ew interpretations of well-known nodally-bssed objective functions are made possible using matrices and matrix norms. The matrix perspective also suggests several new objective functions. Particularly significant is the interpretation of the Oddy metric and the Smoothness objective functions in terms of the condition number of the metric tensor and Jacobian matrix, respectively. Objective functions are grouped according to dimensionality to form weighted combinations. A simple unconstrained local optimum is computed using a modiiied N-ewton iteration. The optimization approach was implemented in the CUBIT mesh generation code and tested on several problems. Results were compared against several standard element-based quaIity measures to demonstrate that good mesh quality can be achieved with nodally-based objective functions.

  9. Optimal Experience and Reading Achievement in Virtual Environments among College Level Developmental Readers

    ERIC Educational Resources Information Center

    Burgess, Melissa L.

    2010-01-01

    In this mixed methods study the potential for developmental readers to experience optimal experience (flow) within the multi-user virtual environment, "Second Life," was examined. In an educational context, "Second Life" provided a space for constructivist learning, socialization, exploration, discovery and creativity. The communicative, social…

  10. Achieving diverse and monoallelic olfactory receptor selection through dual-objective optimization design.

    PubMed

    Tian, Xiao-Jun; Zhang, Hang; Sannerud, Jens; Xing, Jianhua

    2016-05-24

    Multiple-objective optimization is common in biological systems. In the mammalian olfactory system, each sensory neuron stochastically expresses only one out of up to thousands of olfactory receptor (OR) gene alleles; at the organism level, the types of expressed ORs need to be maximized. Existing models focus only on monoallele activation, and cannot explain recent observations in mutants, especially the reduced global diversity of expressed ORs in G9a/GLP knockouts. In this work we integrated existing information on OR expression, and constructed a comprehensive model that has all its components based on physical interactions. Analyzing the model reveals an evolutionarily optimized three-layer regulation mechanism, which includes zonal segregation, epigenetic barrier crossing coupled to a negative feedback loop that mechanistically differs from previous theoretical proposals, and a previously unidentified enhancer competition step. This model not only recapitulates monoallelic OR expression, but also elucidates how the olfactory system maximizes and maintains the diversity of OR expression, and has multiple predictions validated by existing experimental results. Through making an analogy to a physical system with thermally activated barrier crossing and comparative reverse engineering analyses, the study reveals that the olfactory receptor selection system is optimally designed, and particularly underscores cooperativity and synergy as a general design principle for multiobjective optimization in biology. PMID:27162367

  11. [Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram].

    PubMed

    Favré, P

    2012-02-01

    Such a prevalent disease as Major Depressive Disorder (MDD), associated with prominent impairment in physical and social functioning, implies as well an increased morbidity and mortality. Long-term treatments are required due to the frequent occurrence of relapses. Patient compliance is a core factor in both acute and continuation treatment, closely related to tolerability issues. We have partially reviewed the literature published on PubMed since 2004 which assess the relative antidepressant efficacy of escitalopram and comparator antidepressants in adult patients who met DSM-IV criteria for major depressive disorder (MDD). Clinically important differences exist between commonly prescribed antidepressants. These analyses are in favor of a superior efficacy and tolerability of long-term escitalopram treatment (10 to 20mg/day) compared with active controls, including selective serotonin re-uptake inhibitors (SSRIs) (paroxetine, citalopram, bupropion, fluoxetine, fluvoxamine, sertraline), serotonin/noradrenaline reuptake inhibitors (SNRIs) (venlafaxine, milnacipran and duloxetine) and noradrenergic and specific serotonergic antidepressants (NaSSAs) (mirtazapine). Cipriani et al. (2009) have performed a network meta-analysis of 12 new generation antidepressants. They have shown that clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favor of escitalopram and sertraline in acute treatment, defined as 8-week treatment. Kasper et al. (2009) conducted a post-hoc pooled analysis of data from two 6-month randomized controlled trials that revealed superior efficacy and tolerability of escitalopram when compared with paroxetine. The pooled analysis of four randomized, double-blind, active comparator, 6-month trials in MDD, by Wade et al. (2009), showed that short-term outcomes may predict long-term treatment compliance and outcomes. A higher probability of achieving remission was associated with responding

  12. Optimization of Composite Material System and Lay-up to Achieve Minimum Weight Pressure Vessel

    NASA Astrophysics Data System (ADS)

    Mian, Haris Hameed; Wang, Gang; Dar, Uzair Ahmed; Zhang, Weihong

    2013-10-01

    The use of composite pressure vessels particularly in the aerospace industry is escalating rapidly because of their superiority in directional strength and colossal weight advantage. The present work elucidates the procedure to optimize the lay-up for composite pressure vessel using finite element analysis and calculate the relative weight saving compared with the reference metallic pressure vessel. The determination of proper fiber orientation and laminate thickness is very important to decrease manufacturing difficulties and increase structural efficiency. In the present work different lay-up sequences for laminates including, cross-ply [ 0 m /90 n ] s , angle-ply [ ±θ] ns , [ 90/±θ] ns and [ 0/±θ] ns , are analyzed. The lay-up sequence, orientation and laminate thickness (number of layers) are optimized for three candidate composite materials S-glass/epoxy, Kevlar/epoxy and Carbon/epoxy. Finite element analysis of composite pressure vessel is performed by using commercial finite element code ANSYS and utilizing the capabilities of ANSYS Parametric Design Language and Design Optimization module to automate the process of optimization. For verification, a code is developed in MATLAB based on classical lamination theory; incorporating Tsai-Wu failure criterion for first-ply failure (FPF). The results of the MATLAB code shows its effectiveness in theoretical prediction of first-ply failure strengths of laminated composite pressure vessels and close agreement with the FEA results. The optimization results shows that for all the composite material systems considered, the angle-ply [ ±θ] ns is the optimum lay-up. For given fixed ply thickness the total thickness of laminate is obtained resulting in factor of safety slightly higher than two. Both Carbon/epoxy and Kevlar/Epoxy resulted in approximately same laminate thickness and considerable percentage of weight saving, but S-glass/epoxy resulted in weight increment.

  13. Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat model of Pneumocystis carinii pneumonia.

    PubMed Central

    Merali, S; Chin, K; Del Angel, L; Grady, R W; Armstrong, M; Clarkson, A B

    1995-01-01

    The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal models of Pneumocystis carinii pneumonia (PCP), with effective daily intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body weight-1 in mouse and rat models, respectively. Continuous infusion produced a moderately improved response in a rat model. The data reported here demonstrate that the response achieved by continuous infusion of 195 and 335 mg of DFO mesylate kg-1 day-1 in the rat model is associated with mean concentrations in plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since current clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prove to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in lung tissue compared with that observed in plasma may be important in the response of PCP to DFO. PMID:8540710

  14. Optimal parameters for clinical implementation of breast cancer patient setup using Varian DTS software.

    PubMed

    Ng, Sook Kien; Zygmanski, Piotr; Jeung, Andrew; Mostafavi, Hassan; Hesser, Juergen; Bellon, Jennifer R; Wong, Julia S; Lyatskaya, Yulia

    2012-01-01

    Digital tomosynthesis (DTS) was evaluated as an alternative to cone-beam computed tomography (CBCT) for patient setup. DTS is preferable when there are constraints with setup time, gantry-couch clearance, and imaging dose using CBCT. This study characterizes DTS data acquisition and registration parameters for the setup of breast cancer patients using nonclinical Varian DTS software. DTS images were reconstructed from CBCT projections acquired on phantoms and patients with surgical clips in the target volume. A shift-and-add algorithm was used for DTS volume reconstructions, while automated cross-correlation matches were performed within Varian DTS software. Triangulation on two short DTS arcs separated by various angular spread was done to improve 3D registration accuracy. Software performance was evaluated on two phantoms and ten breast cancer patients using the registration result as an accuracy measure; investigated parameters included arc lengths, arc orientations, angular separation between two arcs, reconstruction slice spacing, and number of arcs. The shifts determined from DTS-to-CT registration were compared to the shifts based on CBCT-to-CT registration. The difference between these shifts was used to evaluate the software accuracy. After findings were quantified, optimal parameters for the clinical use of DTS technique were determined. It was determined that at least two arcs were necessary for accurate 3D registration for patient setup. Registration accuracy of 2 mm was achieved when the reconstruction arc length was > 5° for clips with HU ≥ 1000; larger arc length (≥ 8°) was required for very low HU clips. An optimal arc separation was found to be ≥ 20° and optimal arc length was 10°. Registration accuracy did not depend on DTS slice spacing. DTS image reconstruction took 10-30 seconds and registration took less than 20 seconds. The performance of Varian DTS software was found suitable for the accurate setup of breast cancer patients

  15. Achieving Optimal Self-Adaptivity for Dynamic Tuning of Organic Semiconductors through Resonance Engineering.

    PubMed

    Tao, Ye; Xu, Lijia; Zhang, Zhen; Chen, Runfeng; Li, Huanhuan; Xu, Hui; Zheng, Chao; Huang, Wei

    2016-08-01

    Current static-state explorations of organic semiconductors for optimal material properties and device performance are hindered by limited insights into the dynamically changed molecular states and charge transport and energy transfer processes upon device operation. Here, we propose a simple yet successful strategy, resonance variation-based dynamic adaptation (RVDA), to realize optimized self-adaptive properties in donor-resonance-acceptor molecules by engineering the resonance variation for dynamic tuning of organic semiconductors. Organic light-emitting diodes hosted by these RVDA materials exhibit remarkably high performance, with external quantum efficiencies up to 21.7% and favorable device stability. Our approach, which supports simultaneous realization of dynamically adapted and selectively enhanced properties via resonance engineering, illustrates a feasible design map for the preparation of smart organic semiconductors capable of dynamic structure and property modulations, promoting the studies of organic electronics from static to dynamic. PMID:27403886

  16. Achieving progress through clinical governance? A national study of health care managers' perceptions in the NHS in England

    PubMed Central

    Freeman, T; Walshe, K

    2004-01-01

    Background: A national cross sectional study was undertaken to explore the perceptions concerning the importance of, and progress in, aspects of clinical governance among board level and directorate managers in English acute, ambulance, and mental health/learning disabilities (MH/LD) trusts. Participants: A stratified sample of acute, ambulance, and mental health/learning disabilities trusts in England (n = 100), from each of which up to 10 board level and 10 directorate level managers were randomly sampled. Methods: Fieldwork was undertaken between April and July 2002 using the Organisational Progress in Clinical Governance (OPCG) schedule to explore managers' perceptions of the importance of, and organisational achievement in, 54 clinical governance competency items in five aggregated domains: improving quality; managing risks; improving staff performance; corporate accountability; and leadership and collaboration. The difference between ratings of importance and achievement was termed a shortfall. Results: Of 1916 individuals surveyed, 1177 (61.4%) responded. The competency items considered most important and recording highest perceived achievement related to corporate accountability structures and clinical risks. The highest shortfalls between perceived importance and perceived achievement were reported in joint working across local health communities, feedback of performance data, and user involvement. When aggregated into domains, greatest achievement was perceived in the assurance related areas of corporate accountability and risk management, with considerably less perceived achievement and consequently higher shortfalls in quality improvement and leadership and collaboration. Directorate level managers' perceptions of achievement were found to be significantly lower than those of their board level colleagues on all domains other than improving performance. No differences were found in perceptions of achievement between different types of trusts, or between

  17. Achievable Convergence Angle and the Effect of Preparation Design on the Clinical Outcome of Full Veneer Crowns in Dogs

    PubMed Central

    Soukup, Jason W.; Snyder, Christopher J.; Karls, Tina L.; Riehl, Jessica

    2012-01-01

    Summary It is widely accepted that the convergence angle of a full veneer crown preparation should be as close to parallel as possible to attain adequate retention/resistance. The shape of the dog’s canine tooth limits the veterinary dentists’ ability to achieve the recommended convergence angle. However, the clinically achievable convergence angle of the canine tooth in dogs has not been evaluated. In addition, the convergence angle and other physical properties of a preparation, such as height and base diameter, have been shown to affect the retention/resistance of full veneer crowns, in vitro. This effect has not been evaluated clinically in the dog. Physical properties of 32 stone dies from full veneer crowns of canine teeth were studied to evaluate the clinically achievable convergence angle and the potential effect physical properties of the preparation had on the clinical outcome of the restoration. The clinically achievable convergence angle was much higher than the current recommendation. There was an association, albeit not statistically significant, between physical properties of a preparation (convergence angle, height, base diameter) and the clinical outcome of the restoration. PMID:21916370

  18. Optimal thickness of silicon membranes to achieve maximum thermoelectric efficiency: A first principles study

    NASA Astrophysics Data System (ADS)

    Mangold, Claudia; Neogi, Sanghamitra; Donadio, Davide

    2016-08-01

    Silicon nanostructures with reduced dimensionality, such as nanowires, membranes, and thin films, are promising thermoelectric materials, as they exhibit considerably reduced thermal conductivity. Here, we utilize density functional theory and Boltzmann transport equation to compute the electronic properties of ultra-thin crystalline silicon membranes with thickness between 1 and 12 nm. We predict that an optimal thickness of ˜7 nm maximizes the thermoelectric figure of merit of membranes with native oxide surface layers. Further thinning of the membranes, although attainable in experiments, reduces the electrical conductivity and worsens the thermoelectric efficiency.

  19. Clinical Outcome Metrics for Optimization of Robust Training

    NASA Technical Reports Server (NTRS)

    Ebert, Doug; Byrne, Vicky; Cole, Richard; Dulchavsky, Scott; Foy, Millennia; Garcia, Kathleen; Gibson, Robert; Ham, David; Hurst, Victor; Kerstman, Eric; McGuire, Kerry; Sargsyan, Ashot

    2015-01-01

    The objective of this research is to develop and use clinical outcome metrics and training tools to quantify the differences in performance of a physician vs non-physician crew medical officer (CMO) analogues during simulations.

  20. Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction.

    PubMed

    Ueda, T; Takesue, Y; Nakajima, K; Ichiki, K; Doita, A; Wada, Y; Tsuchida, T; Takahashi, Y; Ishihara, M; Ikeuchi, H; Uchino, M; Kimura, T

    2016-09-01

    We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 μg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 μg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 μg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 μg/ml. In conclusion, achievement of Cmin of 15-30 μg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients. PMID:27278654

  1. Optimization of the cooling profile to achieve crack-free Yb:S-FAP crystals

    NASA Astrophysics Data System (ADS)

    Fang, H. S.; Qiu, S. R.; Zheng, L. L.; Schaffers, K. I.; Tassano, J. B.; Caird, J. A.; Zhang, H.

    2008-08-01

    Yb:S-FAP [Yb 3+:Sr 5(PO 4) 3F] crystals are an important gain medium for diode-pumped laser applications. Growth of 7.0 cm diameter Yb:S-FAP crystals utilizing the Czochralski (CZ) method from SrF 2-rich melts often encounters cracks during the post-growth cool-down stage. To suppress cracking during cool-down, a numerical simulation of the growth system was used to understand the correlation between the furnace power during cool-down and the radial temperature differences within the crystal. The critical radial temperature difference, above which the crystal cracks, has been determined by benchmarking the simulation results against experimental observations. Based on this comparison, an optimal three-stage ramp-down profile was implemented, which produced high-quality, crack-free Yb:S-FAP crystals.

  2. Optimization of the cooling profile to achieve crack-free Yb:S-FAP crystals

    SciTech Connect

    Fang, H; Qiu, S; Kheng, L; Schaffers, K; Tassano, J; Caird, J; Zhang, H

    2007-08-20

    Yb:S-FAP [Yb{sup 3+}:Sr{sub 5}(PO{sub 4}){sub 3}F] crystals are an important gain medium for diode-pumped laser applications. Growth of 7.0 cm diameter Yb:S-FAP crystals utilizing the Czochralski (CZ) method from SrF{sub 2}-rich melts often encounter cracks during the post growth cool down stage. To suppress cracking during cool down, a numerical simulation of the growth system was used to understand the correlation between the furnace power during cool down and the radial temperature differences within the crystal. The critical radial temperature difference, above which the crystal cracks, has been determined by benchmarking the simulation results against experimental observations. Based on this comparison, an optimal three-stage ramp-down profile was implemented and produced high quality, crack-free Yb:S-FAP crystals.

  3. High direct drive illumination uniformity achieved by multi-parameter optimization approach: a case study of Shenguang III laser facility.

    PubMed

    Tian, Chao; Chen, Jia; Zhang, Bo; Shan, Lianqiang; Zhou, Weimin; Liu, Dongxiao; Bi, Bi; Zhang, Feng; Wang, Weiwu; Zhang, Baohan; Gu, Yuqiu

    2015-05-01

    The uniformity of the compression driver is of fundamental importance for inertial confinement fusion (ICF). In this paper, the illumination uniformity on a spherical capsule during the initial imprinting phase directly driven by laser beams has been considered. We aim to explore methods to achieve high direct drive illumination uniformity on laser facilities designed for indirect drive ICF. There are many parameters that would affect the irradiation uniformity, such as Polar Direct Drive displacement quantity, capsule radius, laser spot size and intensity distribution within a laser beam. A novel approach to reduce the root mean square illumination non-uniformity based on multi-parameter optimizing approach (particle swarm optimization) is proposed, which enables us to obtain a set of optimal parameters over a large parameter space. Finally, this method is applied to improve the direct drive illumination uniformity provided by Shenguang III laser facility and the illumination non-uniformity is reduced from 5.62% to 0.23% for perfectly balanced beams. Moreover, beam errors (power imbalance and pointing error) are taken into account to provide a more practical solution and results show that this multi-parameter optimization approach is effective. PMID:25969321

  4. Clinical Outcome Metrics for Optimization of Robust Training

    NASA Technical Reports Server (NTRS)

    Ebert, D.; Byrne, V. E.; McGuire, K. M.; Hurst, V. W., IV; Kerstman, E. L.; Cole, R. W.; Sargsyan, A. E.; Garcia, K. M,; Foy, M. H.; Dulchavsky, S. A.; Gibson, C. R.

    2015-01-01

    The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capabilities (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities". Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes.

  5. Effort tracking metrics provide data for optimal budgeting and workload management in therapeutic cancer clinical trials.

    PubMed

    James, Pam; Bebee, Patricia; Beekman, Linda; Browning, David; Innes, Mathew; Kain, Jeannie; Royce-Westcott, Theresa; Waldinger, Marcy

    2011-12-01

    Clinical trials operations struggle to achieve optimal distribution of workload in a dynamic data management and regulatory environment, and to achieve adequate cost recovery for personnel costs. The University of Michigan Comprehensive Cancer Center developed and implemented an effort tracking application to quantify data management and regulatory workload to more effectively assess and allocate work while improving charge capture. Staff recorded how much time they spend each day performing specific study-related and general office tasks. Aggregated data on staff use of the application from 2006 through 2009 were analyzed to gain a better understanding of what trial characteristics require the most data management and regulatory effort. Analysis revealed 4 major determinants of staff effort: 1) study volume (actual accrual), 2) study accrual rate, 3) study enrollment status, and 4) study sponsor type. Effort tracking also confirms that trials that accrued at a faster rate used fewer resources on a per-patient basis than slow-accruing trials. In general, industry-sponsored trials required the most data management and regulatory support, outweighing other sponsor types. Although it is widely assumed that most data management efforts are expended while a trial is actively accruing, the authors learned that 25% to 30% of a data manager's effort is expended while the study is either not yet open or closed to enrollment. Through the use of a data-driven effort tracking tool, clinical research operations can more efficiently allocate workload and ensure that study budgets are negotiated to adequately cover study-related expenses. PMID:22157555

  6. Optimizing Educational Video through Comparative Trials in Clinical Environments

    ERIC Educational Resources Information Center

    Aronson, Ian David; Plass, Jan L.; Bania, Theodore C.

    2012-01-01

    Although video is increasingly used in public health education, studies generally do not implement randomized trials of multiple video segments in clinical environments. Therefore, the specific configurations of educational videos that will have the greatest impact on outcome measures ranging from increased knowledge of important public health…

  7. Standardization and Optimization of Computed Tomography Protocols to Achieve Low-Dose

    PubMed Central

    Chin, Cynthia; Cody, Dianna D.; Gupta, Rajiv; Hess, Christopher P.; Kalra, Mannudeep K.; Kofler, James M.; Krishnam, Mayil S.; Einstein, Andrew J.

    2014-01-01

    The increase in radiation exposure due to CT scans has been of growing concern in recent years. CT scanners differ in their capabilities and various indications require unique protocols, but there remains room for standardization and optimization. In this paper we summarize approaches to reduce dose, as discussed in lectures comprising the first session of the 2013 UCSF Virtual Symposium on Radiation Safety in Computed Tomography. The experience of scanning at low dose in different body regions, for both diagnostic and interventional CT procedures, is addressed. An essential primary step is justifying the medical need for each scan. General guiding principles for reducing dose include tailoring a scan to a patient, minimizing scan length, use of tube current modulation and minimizing tube current, minimizing-tube potential, iterative reconstruction, and periodic review of CT studies. Organized efforts for standardization have been spearheaded by professional societies such as the American Association of Physicists in Medicine. Finally, all team members should demonstrate an awareness of the importance of minimizing dose. PMID:24589403

  8. Assessment of the Optimal Stimulus Pattern to Achieve Rapid Dorsal Hippocampal Kindling in Rats

    PubMed Central

    Etemadi, Fatemeh; Sayyah, Mohammad; Gholami Pourbadie, Hamid; Babapour, Vahab

    2015-01-01

    Introduction: Although hippocampus is the most famous brain area involved in temporal lobe epilepsy, hippocampal kindling (HK) develops very slowly. Hence, rapid kindling is usually preferred to the traditional kindling and it is widely used. In this article we aimed at finding the optimal stimulus pattern, which yields the fastest HK rate. Methods: Stimulus patterns with different duration (2, 3, 5 and 10 s) and inter-train interval (ITI) (5, 10 and 30 min) as well as number of trains in 24 h (8 and 12) were exerted to rats’ dorsal hippocampus. The stimuli were continued until appearance of 3 consecutive generalized seizures or maximum 7 days stimulations. Results: While the protocol with train duration of 10 s and ITI of 30 min caused the fastest kindling rate and the most growth of afterdischarges, the protocol with train duration of 5 s and ITI of 5 min was the most time-consuming protocol among protocols tested. Discussion: Rapid HK develops with a time course of days compared to weeks in traditional kindling. Train duration and inter-train interval are key factors for rapid HK. Among the patterns, 12 trains/24h of 50Hz monophasic square wave with 10 s duration and 30 min interval between trains, is the best stimulus pattern for eliciting rapid dorsal HK. PMID:27307955

  9. Evaluation of preceptors and skills achievement by clinical pharmacy clerkship students during their clinical rotations at University of Gondar, Ethiopia

    PubMed Central

    Belachew, Sewunet Admasu; Abegaz, Tadesse Melaku; Bhagavathula, Akshaya Srikanth; Getachew, Henok; Tefera, Yonas Getaye

    2016-01-01

    Aim To investigate the overall experiences of clinical pharmacy students during their clinical attachments and to understand the breadth and depth of clinical skills provided by their preceptors. Methods A cross-sectional study using a self-administered questionnaire containing 34 items to obtain feedback from the clerkship students from June to July 2015. Data analysis was performed to calculate mean, standard deviation, percentages, and multiple logistic regression using Statistical Package for the Social Sciences (SPSS) software Version 22. Statistical significance was set at P<0.01. Results All 58 clerkship students actively participated in the study, yielding a response rate of 100%. While students ranked their clerkship experience as moderate, >15% remarked that they did not receive enough opportunities to hone their pharmaceutical care documentation skills. A relatively high percentage of students (32.8%) strongly agreed that their preceptors had provided ample opportunity to discuss the patient problems at the bedside and encouraged them to express their opinions regarding patients’ drug therapeutic issues. This study also revealed that students’ continuity in developing their therapeutic and disease process knowledge was significantly associated with the preceptor’s ability to provide adequate training and orientation (P =0.01), engagement in clinical pharmacy activities (P =0.01), regular review of students’ work (P =0.01), and instruction to students before entering clinical sites (P =0.00). Conclusion The findings of this study reveal that a majority of the students were moderately satisfied with the clinical training program and preceptors need to demonstrate effective pharmaceutical care processes in their clinical sites. PMID:27099540

  10. Failure of Ivermectin per Rectum to Achieve Clinically Meaningful Serum Levels in Two Cases of Strongyloides Hyperinfection

    PubMed Central

    Bogoch, Isaac I.; Khan, Kamran; Abrams, Howard; Nott, Caroline; Leung, Elizabeth; Fleckenstein, Lawrence; Keystone, Jay S.

    2015-01-01

    Two cases of Strongyloides hyperinfection are presented. Ivermectin was initially administered orally and per rectum pending the availability of subcutaneous (SC) preparations. In neither case did rectal suppositories of ivermectin achieve clinically meaningful serum values. Clinicians should use SC preparations of ivermectin as early as possible in Strongyloides hyperinfection and dissemination. PMID:25918215

  11. Isometric Scaling in Developing Long Bones Is Achieved by an Optimal Epiphyseal Growth Balance

    PubMed Central

    Stern, Tomer; Aviram, Rona; Rot, Chagai; Galili, Tal; Sharir, Amnon; Kalish Achrai, Noga; Keller, Yosi; Shahar, Ron; Zelzer, Elazar

    2015-01-01

    One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of

  12. Endonasal endoscopic dacryocystorhinostomy: how to achieve optimal results with simple punch technique.

    PubMed

    Naraghi, Mohsen; Tabatabaii Mohammadi, Sayed Ziaeddin; Sontou, Alain Fabrice; Farajzadeh Deroee, Armin; Boroojerdi, Masoud

    2012-05-01

    Endonasal endoscopic dacryocystorhinostomy (EEDCR) has been popularized as a minimally invasive technique. Although preliminary reports revealed less success in comparison with external approaches, recent endonasal endoscopic surgeries on various types of DCR have preserved advantages of this technique while diminishing the failures. We described our experience on EEDCR, including the main advantages and disadvantages of it. Hundred consecutive cases of lachrymal problems underwent EEDCR utilizing simple punch removal of bone, instead of powered instrumentation or lasers. The medial aspect of the sac was removed in all of patients, while preserving normal mucosa around the sac. Hundred cases of EEDCR were performed on 81 patients, with 19 bilateral procedures. Nine procedures were performed under local anesthesia. Based on a mean 14 months follow-up, 95 cases were free of symptoms, revealing 95% success rate. The punch technique diminishes the expenses of powered or laser instrumentation with comparable results. It seems that preserving normal tissues and creating a patent rhinostomy with least surgical trauma and less subsequent scar, plays the most important role in achieving desirable results. PMID:22065173

  13. Optimized Cell Survival and Seeding Efficiency for Craniofacial Tissue Engineering Using Clinical Stem Cell Therapy

    PubMed Central

    Rajan, Archana; Eubanks, Emily; Edwards, Sean; Aronovich, Sharon; Travan, Suncica; Rudek, Ivan; Wang, Feng; Lanis, Alejandro

    2014-01-01

    Traumatic injuries involving the face are very common, yet the clinical management of the resulting craniofacial deficiencies is challenging. These injuries are commonly associated with missing teeth, for which replacement is compromised due to inadequate jawbone support. Using cell therapy, we report the upper jaw reconstruction of a patient who lost teeth and 75% of the supporting jawbone following injury. A mixed population of bone marrow-derived autologous stem and progenitor cells was seeded onto β-tricalcium phosphate (β-TCP), which served as a scaffold to deliver cells directly to the defect. Conditions (temperature, incubation time) to achieve the highest cell survival and seeding efficiency were optimized. Four months after cell therapy, cone beam computed tomography and a bone biopsy were performed, and oral implants were placed to support an engineered dental prosthesis. Cell seeding efficiency (>81%) of the β-TCP and survival during the seeding process (94%) were highest when cells were incubated with β-TCP for 30 minutes, regardless of incubation temperature; however, at 1 hour, cell survival was highest when incubated at 4°C. Clinical, radiographic, and histological analyses confirmed that by 4 months, the cell therapy regenerated 80% of the original jawbone deficiency with vascularized, mineralized bone sufficient to stably place oral implants. Functional and aesthetic rehabilitation of the patient was successfully completed with installation of a dental prosthesis 6 months following implant placement. This proof-of-concept clinical report used an evidence-based approach for the cell transplantation protocol used and is the first to describe a cell therapy for craniofacial trauma reconstruction. PMID:25378653

  14. Suprasellar cysts: clinical presentation, surgical indications, and optimal surgical treatment

    PubMed Central

    2011-01-01

    Background To describe the clinical presentation of suprasellar cysts (SSCs) and surgical indications, and compare the treatment methods of endoscopic ventriculocystostomy (VC) and ventriculocystocisternotomy (VCC). Methods We retrospectively reviewed the records of 73 consecutive patients with SSC who were treated between June 2002 and September 2009. Twenty-two patients were treated with VC and 51 with VCC. Outcome was assessed by clinical examination and magnetic resonance imaging. Results The patients were divided into five groups based on age at presentation: age less than 1 year (n = 6), 1-5 years (n = 36), 6-10 years (n = 15), 11-20 years (n = 11), and 21-53 years (n = 5). The main clinical presentations were macrocrania (100%), motor deficits (50%), and gaze disturbance (33.3%) in the age less than 1 year group; macrocrania (75%), motor deficits (63.9%), and gaze disturbance (27.8%) in the 1-5 years group; macrocrania (46.7%), symptoms of raised intracranial pressure (ICP) (40.0%), endocrine dysfunction (40%), and seizures (33.3%) in the 6-10 years group; symptoms of raised ICP (54.5%), endocrine dysfunction (54.5%), and reduced visual field or acuity (36.4%) in the 11-20 years group; and symptoms of raised ICP (80.0%) and reduced visual field or acuity (40.0%) in the 21-53 years group. The overall success rate of endoscopic fenestration was 90.4%. A Kaplan-Meier curve for long-term efficacy of the two treatment modalities showed better results for VCC than for VC (p = 0.008). Conclusions Different age groups with SSCs have different main clinical presentations. VCC appears to be more efficacious than VC. PMID:21586175

  15. Clinical Outcome Metrics for Optimization of Robust Training

    NASA Technical Reports Server (NTRS)

    Ebert, D.; Byrne, V. E.; McGuire, K. M.; Hurst, V. W., IV; Kerstman, E. L.; Cole, R. W.; Sargsyan, A. E.; Garcia, K. M.; Reyes, D.; Young, M.

    2016-01-01

    Introduction: The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capability's (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-Flight Medical Capabilities." Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes. Methods: Medical simulations will systematically compare success of individual diagnostic and therapeutic procedure simulations performed by physician and non-physician crew medical officer (CMO) analogs using clearly defined short-term (individual procedure) outcome metrics. In the subsequent step of the project, the procedure simulation outcomes will be used as input to a modified version of the NASA Integrated Medical Model (IMM) to analyze the effect of the outcome (degree of success) of individual procedures (including successful, imperfectly performed, and failed procedures) on overall long-term clinical outcomes and the consequent mission impacts. The procedures to be simulated are endotracheal intubation, fundoscopic examination, kidney/urinary ultrasound, ultrasound-guided intravenous catheter insertion, and a differential diagnosis exercise. Multiple assessment techniques will be used, centered on medical procedure simulation studies occurring at 3, 6, and 12 months after initial training (as depicted in the following flow diagram of the experiment design). Discussion: Analysis of procedure outcomes in the physician and non-physician groups and their subsets (tested at different elapsed times post training) will allow the team to 1) define differences between physician and non-physician CMOs in terms of both procedure performance

  16. Effectiveness of increasing the frequency of posaconazole syrup administration to achieve optimal plasma concentrations in patients with haematological malignancy.

    PubMed

    Park, Wan Beom; Cho, Joo-Youn; Park, Sang-In; Kim, Eun Jung; Yoon, Seonghae; Yoon, Seo Hyun; Lee, Jeong-Ok; Koh, Youngil; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Yu, Kyung-Sang; Kim, Eu Suk; Bang, Su Mi; Kim, Nam Joong; Kim, Inho; Oh, Myoung-Don; Kim, Hong Bin; Song, Sang Hoon

    2016-07-01

    Few data are available on whether adjusting the dose of posaconazole syrup is effective in patients receiving anti-cancer chemotherapy. The aim of this prospective study was to analyse the impact of increasing the frequency of posaconazole administration on optimal plasma concentrations in adult patients with haematological malignancy. A total of 133 adult patients receiving chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome who received posaconazole syrup 200 mg three times daily for fungal prophylaxis were enrolled in this study. Drug trough levels were measured by liquid chromatography-tandem mass spectrometry. In 20.2% of patients (23/114) the steady-state concentration of posaconazole was suboptimal (<500 ng/mL) on Day 8. In these patients, the frequency of posaconazole administration was increased to 200 mg four times daily. On Day 15, the median posaconazole concentration was significantly increased from 368 ng/mL [interquartile range (IQR), 247-403 ng/mL] to 548 ng/mL (IQR, 424-887 ng/mL) (P = 0.0003). The median increase in posaconazole concentration was 251 ng/mL (IQR, 93-517 ng/mL). Among the patients with initially suboptimal levels, 79% achieved the optimal level unless the steady-state level was <200 ng/mL. This study shows that increasing the administration frequency of posaconazole syrup is effective for achieving optimal levels in patients with haematological malignancy undergoing chemotherapy. PMID:27234674

  17. Challenges and Solutions in Optimizing Execution Performance of a Clinical Decision Support-Based Quality Measurement (CDS-QM) Framework

    PubMed Central

    Tippetts, Tyler J; Warner, Phillip B; Kukhareva, Polina V; Shields, David E; Staes, Catherine J; Kawamoto, Kensaku

    2015-01-01

    Given the close relationship between clinical decision support (CDS) and quality measurement (QM), it has been proposed that a standards-based CDS Web service could be leveraged to enable QM. Benefits of such a CDS-QM framework include semantic consistency and implementation efficiency. However, earlier research has identified execution performance as a critical barrier when CDS-QM is applied to large populations. Here, we describe challenges encountered and solutions devised to optimize CDS-QM execution performance. Through these optimizations, the CDS-QM execution time was optimized approximately three orders of magnitude, such that approximately 370,000 patient records can now be evaluated for 22 quality measure groups in less than 5 hours (approximately 2 milliseconds per measure group per patient). Several key optimization methods were identified, with the most impact achieved through population-based retrieval of relevant data, multi-step data staging, and parallel processing. These optimizations have enabled CDS-QM to be operationally deployed at an enterprise level. PMID:26958259

  18. Nursing Students Achieving Community Health Competencies through Undergraduate Clinical Experiences: A Gap Analysis.

    PubMed

    Pijl-Zieber, Em M; Barton, Sylvia; Awosoga, Oluwagbohunmi A; Konkin, Jill

    2015-01-01

    In Canada, it is widely believed that nursing practice and health care will move from acute care into the community. At the same time, increasing numbers of nursing students are engaged in non-traditional clinical experiences for their community health rotation. These clinical experiences occur at agencies not organizationally affiliated with the health care system and typically do not employ registered nurses (RNs). What has yet to be established is the degree to which nursing students are actually being prepared for community health nursing roles through their community health clinical rotations. In this paper we report the findings of a mixed method study that explored the gap between desired and observed levels of competence in community health of senior nursing students and new graduates. The gap was quantified and then the nature of the gap further explored through focus groups. PMID:26461843

  19. WISC-III and CAS: Which Correlates Higher with Achievement for a Clinical Sample?

    ERIC Educational Resources Information Center

    Naglieri, Jack A.; De Lauder, Brianna Y.; Goldstein, Sam; Schwebech, Adam

    2006-01-01

    The relationships between Wechsler Intelligence Scale for Children-Third Edition (WISC-III) and the Cognitive Assessment System (CAS) with the Woodcock-Johnson Tests of Achievement (WJ-III) were examined for a sample of 119 children (87 males and 32 females) ages 6 to 16. The sample was comprised of children who were referred to a specialty clinic…

  20. Optimizing the Use of Aripiprazole Augmentation in the Treatment of Major Depressive Disorder: From Clinical Trials to Clinical Practice

    PubMed Central

    Han, Changsu; Wang, Sheng-Min; Lee, Soo-Jung; Jun, Tae-Youn

    2015-01-01

    Major depressive disorder (MDD) is a recurrent, chronic, and devastating disorder leading to serious impairment in functional capacity as well as increasing public health care costs. In the previous decade, switching therapy and dose adjustment of ongoing antidepressants was the most frequently chosen subsequent treatment option for MDD. However, such recommendations were not based on firmly proven efficacy data from well-designed, placebo-controlled, randomized clinical trials (RCTs) but on practical grounds and clinical reasoning. Aripiprazole augmentation has been dramatically increasing in clinical practice owing to its unique action mechanisms as well as proven efficacy and safety from adequately powered and well-controlled RCTs. Despite the increased use of aripiprazole in depression, limited clinical information and knowledge interfere with proper and efficient use of aripiprazole augmentation for MDD. The objective of the present review was to enhance clinicians' current understanding of aripiprazole augmentation and how to optimize the use of this therapy in the treatment of MDD. PMID:26306301

  1. Dynamic whole-body PET parametric imaging: I. Concept, acquisition protocol optimization and clinical application

    NASA Astrophysics Data System (ADS)

    Karakatsanis, Nicolas A.; Lodge, Martin A.; Tahari, Abdel K.; Zhou, Y.; Wahl, Richard L.; Rahmim, Arman

    2013-10-01

    Static whole-body PET/CT, employing the standardized uptake value (SUV), is considered the standard clinical approach to diagnosis and treatment response monitoring for a wide range of oncologic malignancies. Alternative PET protocols involving dynamic acquisition of temporal images have been implemented in the research setting, allowing quantification of tracer dynamics, an important capability for tumor characterization and treatment response monitoring. Nonetheless, dynamic protocols have been confined to single-bed-coverage limiting the axial field-of-view to ˜15-20 cm, and have not been translated to the routine clinical context of whole-body PET imaging for the inspection of disseminated disease. Here, we pursue a transition to dynamic whole-body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. We investigate solutions to address the challenges of: (i) long acquisitions, (ii) small number of dynamic frames per bed, and (iii) non-invasive quantification of kinetics in the plasma. In the present study, a novel dynamic (4D) whole-body PET acquisition protocol of ˜45 min total length is presented, composed of (i) an initial 6 min dynamic PET scan (24 frames) over the heart, followed by (ii) a sequence of multi-pass multi-bed PET scans (six passes × seven bed positions, each scanned for 45 s). Standard Patlak linear graphical analysis modeling was employed, coupled with image-derived plasma input function measurements. Ordinary least squares Patlak estimation was used as the baseline regression method to quantify the physiological parameters of tracer uptake rate Ki and total blood distribution volume V on an individual voxel basis. Extensive Monte Carlo simulation studies, using a wide set of published kinetic FDG parameters and GATE and XCAT platforms, were conducted to optimize the acquisition protocol from a range of ten different clinically

  2. Interface for electronic data capture systems for clinical trials by optimal utilization of available hospital resources.

    PubMed

    Kaushik, Sashank; Khan, Anzalee; Kaushik, Saurabh; Lindenmayer, Jean-Pierre

    2008-01-01

    We describe Clinical Trials System (CTS), an innovative EDC system utilizing data from existing hospital-based electronic databases that supports information gathering and storing for various clinical trials. The complexities of designing electronic clinical trials systems and their ideal features are outlined. CTS optimally utilizes existing electronic databases in a well-organized and easy-to-reference format. CTS is currently incorporated within a large psychiatric center, allowing easy sharing of information and data among multidisciplinary clinical and research teams. PMID:18999083

  3. Reduction of exposure to acrylamide: achievements, potential of optimization, and problems encountered from the perspectives of a Swiss enforcement laboratory.

    PubMed

    Grob, Koni

    2005-01-01

    The most important initiatives taken in Switzerland to reduce exposure of consumers to acrylamide are the separate sale of potatoes low in reducing sugars for roasting and frying, the optimization of the raw material and preparation of french fries, and campaigns to implement suitable preparation methods in the gastronomy and homes. Industry works on improving a range of other products. Although these measures can reduce high exposures by some 80%, they have little effect on the background exposure resulting from coffee, bread, and numerous other products for which no substantial improvement is in sight. At this stage, improvements should be achieved by supporting voluntary activity rather than legal limits. Committed and consistent risk communication is key, and the support of improvements presupposes innovative approaches. PMID:15759749

  4. Nuclear imaging of the breast: Translating achievements in instrumentation into clinical use

    PubMed Central

    Hruska, Carrie B.; O'Connor, Michael K.

    2013-01-01

    Approaches to imaging the breast with nuclear medicine and/or molecular imaging methods have been under investigation since the late 1980s when a technique called scintimammography was first introduced. This review charts the progress of nuclear imaging of the breast over the last 20 years, covering the development of newer techniques such as breast specific gamma imaging, molecular breast imaging, and positron emission mammography. Key issues critical to the adoption of these technologies in the clinical environment are discussed, including the current status of clinical studies, the efforts at reducing the radiation dose from procedures associated with these technologies, and the relevant radiopharmaceuticals that are available or under development. The necessary steps required to move these technologies from bench to bedside are also discussed. PMID:23635248

  5. Nuclear imaging of the breast: Translating achievements in instrumentation into clinical use

    SciTech Connect

    Hruska, Carrie B.; O'Connor, Michael K.

    2013-05-15

    Approaches to imaging the breast with nuclear medicine and/or molecular imaging methods have been under investigation since the late 1980s when a technique called scintimammography was first introduced. This review charts the progress of nuclear imaging of the breast over the last 20 years, covering the development of newer techniques such as breast specific gamma imaging, molecular breast imaging, and positron emission mammography. Key issues critical to the adoption of these technologies in the clinical environment are discussed, including the current status of clinical studies, the efforts at reducing the radiation dose from procedures associated with these technologies, and the relevant radiopharmaceuticals that are available or under development. The necessary steps required to move these technologies from bench to bedside are also discussed.

  6. Optimism and Recovery After Acute Coronary Syndrome: A Clinical Cohort Study

    PubMed Central

    Ronaldson, Amy; Molloy, Gerard J.; Wikman, Anna; Poole, Lydia; Kaski, Juan-Carlos; Steptoe, Andrew

    2015-01-01

    ABSTRACT Objective Optimism is associated with reduced cardiovascular mortality, but its impact on recovery after acute coronary syndrome (ACS) is poorly understood. We hypothesized that greater optimism would lead to more effective physical and emotional adaptation after ACS and would buffer the impact of persistent depressive symptoms on clinical outcomes. Methods This prospective observational clinical study took place in an urban general hospital and involved 369 patients admitted with a documented ACS. Optimism was assessed with a standardized questionnaire. The main outcomes were physical health status, depressive symptoms, smoking, physical activity, and fruit and vegetable consumption measured 12 months after ACS, and composite major adverse cardiac events (cardiovascular death, readmission with reinfarction or unstable angina, and coronary artery bypass graft surgery) assessed over an average of 45.7 months. Results We found that optimism predicted better physical health status 12 months after ACS independently of baseline physical health, age, sex, ethnicity, social deprivation, and clinical risk factors (B = 0.65, 95% confidence interval [CI] = 0.10–1.20). Greater optimism also predicted reduced risk of depressive symptoms (odds ratio = 0.82, 95% CI = 0.74–0.90), more smoking cessation, and more fruit and vegetable consumption at 12 months. Persistent depressive symptoms 12 months after ACS predicted major adverse cardiac events over subsequent years (odds ratio = 2.56, 95% CI = 1.16–5.67), but only among individuals low in optimism (optimism × depression interaction; p = .014). Conclusions Optimism predicts better physical and emotional health after ACS. Measuring optimism may help identify individuals at risk. Pessimistic outlooks can be modified, potentially leading to improved recovery after major cardiac events. PMID:25738438

  7. Optimization Correction Strength Using Contra Bending Technique without Anterior Release Procedure to Achieve Maximum Correction on Severe Adult Idiopathic Scoliosis

    PubMed Central

    Rahyussalim, Ahmad Jabir; Saleh, Ifran; Purnaning, Dyah; Kurniawati, Tri

    2016-01-01

    Adult scoliosis is defined as a spinal deformity in a skeletally mature patient with a Cobb angle of more than 10 degrees in the coronal plain. Posterior-only approach with rod and screw corrective manipulation to add strength of contra bending manipulation has correction achievement similar to that obtained by conventional combined anterior release and posterior approach. It also avoids the complications related to the thoracic approach. We reported a case of 25-year-old male adult idiopathic scoliosis with double curve. It consists of main thoracic curve of 150 degrees and lumbar curve of 89 degrees. His curve underwent direct contra bending posterior approach using rod and screw corrective manipulation technique to achieve optimal correction. After surgery the main thoracic Cobb angle becomes 83 degrees and lumbar Cobb angle becomes 40 degrees, with 5 days length of stay and less than 800 mL blood loss during surgery. There is no complaint at two months after surgery; he has already come back to normal activity with good functional activity. PMID:27064801

  8. Optimizing LINAC-based stereotactic radiotherapy of uveal melanomas: 7 years' clinical experience

    SciTech Connect

    Dieckmann, Karin . E-mail: Karin.Dieckmann@akhwien.at; Georg, Dietmar; Bogner, Joachim; Zehetmayer, Martin; Petersch, Bernhard; Chorvat, Martin; Weitmann, Hajo; Poetter, Richard

    2006-11-15

    Purpose: To report on the clinical outcome of LINAC-based stereotactic radiotherapy (SRT) of uveal melanomas. Additionally, a new prototype (hardware and software) for automated eye monitoring and gated SRT using a noninvasive eye fixation technique is described. Patients and Methods: Between June 1997 and March 2004, 158 patients suffering from uveal melanoma were treated at a LINAC with 6 MV (5 x 14 Gy; 5 x 12 Gy prescribed to 80% isodose) photon beams. To guarantee identical patient setup during treatment planning (CT and MRI) and treatment delivery, patients were immobilized with a BrainLAB thermoplastic mask. Eye immobilization was achieved by instructing the patient to fixate on a light source integrated into the mask system. A mini-video camera was used to provide on-line information about the eye and pupil position, respectively. A new CT and magnetic resonance (MR) compatible prototype, based on head-and-neck fixation and the infrared tracking system ExacTrac, has been developed and evaluated since 2002. This system records maximum temporal and angular deviations during treatment and, based on tolerance limits, a feedback signal to the LINAC enables gated SRT. Results: After a median follow-up of 33.4 months (range, 3-85 months), local control was achieved in 98%. Fifteen patients (9.0%) developed metastases. Secondary enucleation was performed in 23 patients (13.8%). Long-term side effects were retinopathy (n = 70; 44%), cataract (n = 30; 23%), optic neuropathy (n = 65; 41%), and secondary neovascular glaucoma (n = 23; 13.8%). Typical situations when preset deviation criteria were exceeded were slow drifts (fatigue), large sudden eye movements (irritation), or eye closing (fatigue). In these cases, radiation was reliably interrupted by the gating system. In our clinical setup, the novel system for computer-controlled gated SRT of uveal melanoma was well tolerated by about 30 of the patients treated with this system so far. Conclusion: LINAC-based SRT of

  9. Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

    PubMed Central

    Jones, Bleddyn

    2015-01-01

    Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated. PMID:25790470

  10. Multi-armed Bandit Models for the Optimal Design of Clinical Trials: Benefits and Challenges

    PubMed Central

    Villar, Sofía S.; Bowden, Jack; Wason, James

    2016-01-01

    Multi-armed bandit problems (MABPs) are a special type of optimal control problem well suited to model resource allocation under uncertainty in a wide variety of contexts. Since the first publication of the optimal solution of the classic MABP by a dynamic index rule, the bandit literature quickly diversified and emerged as an active research topic. Across this literature, the use of bandit models to optimally design clinical trials became a typical motivating application, yet little of the resulting theory has ever been used in the actual design and analysis of clinical trials. To this end, we review two MABP decision-theoretic approaches to the optimal allocation of treatments in a clinical trial: the infinite-horizon Bayesian Bernoulli MABP and the finite-horizon variant. These models possess distinct theoretical properties and lead to separate allocation rules in a clinical trial design context. We evaluate their performance compared to other allocation rules, including fixed randomization. Our results indicate that bandit approaches offer significant advantages, in terms of assigning more patients to better treatments, and severe limitations, in terms of their resulting statistical power. We propose a novel bandit-based patient allocation rule that overcomes the issue of low power, thus removing a potential barrier for their use in practice. PMID:27158186

  11. Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

    SciTech Connect

    Giantsoudi, Drosoula; Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald

    2013-09-01

    Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

  12. Fostering Dental Students' Academic Achievements and Reflection Skills Through Clinical Peer Assessment and Feedback.

    PubMed

    Tricio, Jorge A; Woolford, Mark J; Escudier, Michael P

    2016-08-01

    Peer assessment is increasingly being encouraged to enhance dental students' learning. The aim of this study was to evaluate the educational impact in terms of academic achievements and reflective thinking of a formative prospective peer assessment and feedback protocol. Volunteer final-year dental students at King's College London Dental Institute, UK, received training on peer assessment, peer feedback, and self-reflection. At the beginning (baseline) and end (resultant) of the 2012-13 academic year, 86 students (55% of the year group) completed a reflection questionnaire (RQ). Sixty-eight of those students used a modified Direct Observation of Procedural Skills (DOPS) as a framework for peer assessment and peer feedback during a complete academic year. End-of-year, high-stakes examination grades and RQ scores from the participants and nonparticipants were statistically compared. The participants completed 576 peer DOPS. Those 22 students who peer assessed each other ≥10 times exhibited highly statistically significant differences and powerful positive effect sizes in their high-stakes exam grades (p=0.0001, d=0.74) and critical reflection skills (p=0.005, d=1.41) when compared to those who did not assess one another. Furthermore, only the same 22 students showed a statistically significant increase and positive effect size in their critical reflection skills from baseline to resultant (p=0.003, d=1.04). The results of this study suggest that the protocol used has the potential to impact dental students' academic and reflection skills, provided it is practiced in ten or more peer encounters and ensuring peer feedback is provided followed by self-reflection. PMID:27480702

  13. Magnetic resonance enterography in Crohn's disease: optimal use in clinical practice and clinical trials.

    PubMed

    Rimola, Jordi; Panés, Julián; Ordás, Ingrid

    2015-01-01

    The purpose of this review is to provide a practical appraisal of the usefulness of magnetic resonance enterography in the management of Crohn's disease and the potential utilities that this imaging modality may have in clinical research. Also, we review some basic technical considerations that clinicians should know to understand the value and limitations of the technique. Lastly, we outline the future trends and potential contributions of new technological advances in the field of magnetic resonance imaging that can improve the classic magnetic resonance enterography technique. PMID:25523557

  14. Laser thermokeratoplasty: analysis of in-vitro results and refractive changes achieved in a first clinical study

    NASA Astrophysics Data System (ADS)

    Brinkmann, Ralf; Geerling, Gerd; Kampmeier, Juergen; Koop, Norbert; Radt, Benno; Birngruber, Reginald

    1997-12-01

    Laser thermokeratoplasty (LTK) is a minimally invasive method to correct hyperopia and astigmatism. A cw mid-IR laser diode emitting at wavelengths around 1.86 micrometers was used to perform LTK on a first clinical trial. The coagulations were applied to the cornea by means of a specially designed focusing handpiece which was introduced into a corneal application mask fixed by a suction ring. Coagulation patterns consisting of 8 spots per ring were performed with a laser power between 100 - 150 mW and an irradiation time of 10 seconds both on single and on double rings. Significant refractive changes up to 19 D could initially be achieved followed by a strong regression within the first month. Three months post LTK, refractive changes achieved with the single and double ring have stabilized, yielding 1.2 and 1.8 D on the average, respectively. The method reveals only little adverse effects limited to the first days post-op. Force measurements were performed on corneal stripes, which were submerged for 10 s into an oil bath of constant temperature in order to investigate the absolute temperatures required for corneal collagen contraction. Only temperatures exceeding 90 degree(s)C induced a significant force. Analyzing the clinically used LTK parameters by temperature calculations revealed that only a small part of the heated stromal volume experienced sufficient high temperatures to induce significant collagen shrinkage.

  15. Exemplary Care and Learning Sites: A Model for Achieving Continual Improvement in Care and Learning in the Clinical Setting

    PubMed Central

    Ogrinc, Greg; Hoffman, Kimberly G.; Stevenson, Katherine M.; Shalaby, Marc; Beard, Albertine S.; Thörne, Karin E.; Coleman, Mary T.; Baum, Karyn D.

    2016-01-01

    Problem Current models of health care quality improvement do not explicitly describe the role of health professions education. The authors propose the Exemplary Care and Learning Site (ECLS) model as an approach to achieving continual improvement in care and learning in the clinical setting. Approach From 2008–2012, an iterative, interactive process was used to develop the ECLS model and its core elements—patients and families informing process changes; trainees engaging both in care and the improvement of care; leaders knowing, valuing, and practicing improvement; data transforming into useful information; and health professionals competently engaging both in care improvement and teaching about care improvement. In 2012–2013, a three-part feasibility test of the model, including a site self-assessment, an independent review of each site’s ratings, and implementation case stories, was conducted at six clinical teaching sites (in the United States and Sweden). Outcomes Site leaders reported the ECLS model provided a systematic approach toward improving patient (and population) outcomes, system performance, and professional development. Most sites found it challenging to incorporate the patients and families element. The trainee element was strong at four sites. The leadership and data elements were self-assessed as the most fully developed. The health professionals element exhibited the greatest variability across sites. Next Steps The next test of the model should be prospective, linked to clinical and educa tional outcomes, to evaluate whether it helps care delivery teams, educators, and patients and families take action to achieve better patient (and population) outcomes, system performance, and professional development. PMID:26760058

  16. Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

    PubMed

    Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

    2015-01-01

    Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. PMID:25670382

  17. Optimization of catheter ablation of atrial fibrillation: insights gained from clinically-derived computer models.

    PubMed

    Zhao, Jichao; Kharche, Sanjay R; Hansen, Brian J; Csepe, Thomas A; Wang, Yufeng; Stiles, Martin K; Fedorov, Vadim V

    2015-01-01

    Atrial fibrillation (AF) is the most common heart rhythm disturbance, and its treatment is an increasing economic burden on the health care system. Despite recent intense clinical, experimental and basic research activity, the treatment of AF with current antiarrhythmic drugs and catheter/surgical therapies remains limited. Radiofrequency catheter ablation (RFCA) is widely used to treat patients with AF. Current clinical ablation strategies are largely based on atrial anatomy and/or substrate detected using different approaches, and they vary from one clinical center to another. The nature of clinical ablation leads to ambiguity regarding the optimal patient personalization of the therapy partly due to the fact that each empirical configuration of ablation lines made in a patient is irreversible during one ablation procedure. To investigate optimized ablation lesion line sets, in silico experimentation is an ideal solution. 3D computer models give us a unique advantage to plan and assess the effectiveness of different ablation strategies before and during RFCA. Reliability of in silico assessment is ensured by inclusion of accurate 3D atrial geometry, realistic fiber orientation, accurate fibrosis distribution and cellular kinetics; however, most of this detailed information in the current computer models is extrapolated from animal models and not from the human heart. The predictive power of computer models will increase as they are validated with human experimental and clinical data. To make the most from a computer model, one needs to develop 3D computer models based on the same functionally and structurally mapped intact human atria with high spatial resolution. The purpose of this review paper is to summarize recent developments in clinically-derived computer models and the clinical insights they provide for catheter ablation. PMID:25984605

  18. Optimization of Catheter Ablation of Atrial Fibrillation: Insights Gained from Clinically-Derived Computer Models

    PubMed Central

    Zhao, Jichao; Kharche, Sanjay R.; Hansen, Brian J.; Csepe, Thomas A.; Wang, Yufeng; Stiles, Martin K.; Fedorov, Vadim V.

    2015-01-01

    Atrial fibrillation (AF) is the most common heart rhythm disturbance, and its treatment is an increasing economic burden on the health care system. Despite recent intense clinical, experimental and basic research activity, the treatment of AF with current antiarrhythmic drugs and catheter/surgical therapies remains limited. Radiofrequency catheter ablation (RFCA) is widely used to treat patients with AF. Current clinical ablation strategies are largely based on atrial anatomy and/or substrate detected using different approaches, and they vary from one clinical center to another. The nature of clinical ablation leads to ambiguity regarding the optimal patient personalization of the therapy partly due to the fact that each empirical configuration of ablation lines made in a patient is irreversible during one ablation procedure. To investigate optimized ablation lesion line sets, in silico experimentation is an ideal solution. 3D computer models give us a unique advantage to plan and assess the effectiveness of different ablation strategies before and during RFCA. Reliability of in silico assessment is ensured by inclusion of accurate 3D atrial geometry, realistic fiber orientation, accurate fibrosis distribution and cellular kinetics; however, most of this detailed information in the current computer models is extrapolated from animal models and not from the human heart. The predictive power of computer models will increase as they are validated with human experimental and clinical data. To make the most from a computer model, one needs to develop 3D computer models based on the same functionally and structurally mapped intact human atria with high spatial resolution. The purpose of this review paper is to summarize recent developments in clinically-derived computer models and the clinical insights they provide for catheter ablation. PMID:25984605

  19. Optimizing Management and Financial Performance of the Teaching Ambulatory Care Clinic

    PubMed Central

    Stahl, James E; Roberts, Mark S; Gazelle, Scott

    2003-01-01

    OBJECTIVE To examine how to optimize teaching ambulatory care clinics performance with regard to access to care, access to teaching, and financial viability. DESIGN Optimization analysis using computer simulation. METHODS A discrete-event simulation model of the teaching ambulatory clinic setting was developed. This method captures flow time, waiting time, competition for resources, and the interdependency of events, providing insight into system dynamics. Sensitivity analyses were performed on staffing levels, room availability, patient characteristics such as “new” versus “established” status, and clinical complexity and pertinent probabilities. MAIN RESULTS In the base-case, 4 trainees:preceptor, patient flow time (registration to check out) was 148 minutes (SD 5), wait time was 20.6 minutes (SD 4.4), the wait for precepting was 6.2 minutes (SD 1.2), and average daily net clinic income was $1,413. Utilization rates were preceptors (59%), trainees (61%), medical assistants (64%), and room (68%). Flow time and the wait times remained relatively constant for strategies with trainee:preceptor ratios <4:1 but increased with number of trainees steadily thereafter. Maximum revenue occurred with 3 preceptors and 5 trainees per preceptor. The model was relatively insensitive to the proportion of patients presenting who were new, and relatively sensitive to average evaluation and management (E/M) level. Flow and wait times rose on average by 0.05 minutes and 0.01 minutes per percent new patient, respectively. For each increase in average E/M level, flow time increased 8.4 minutes, wait time 1.2 minutes, wait for precepting 0.8 minutes, and net income increased by $490. CONCLUSION Teaching ambulatory care clinics appear to operate optimally, minimizing flow time and waiting time while maximizing revenue, with trainee-to-preceptor ratios between 3 and 7 to 1. PMID:12709093

  20. Study of PET scanner designs using clinical metrics to optimize the scanner axial FOV and crystal thickness

    NASA Astrophysics Data System (ADS)

    Surti, S.; Werner, M. E.; Karp, J. S.

    2013-06-01

    The aim of this study is to understand the trade-off between crystal thickness and scanner axial field-of-view FOV (AFOV) for clinical PET imaging. Clinical scanner design has evolved towards 20-25 mm thick crystals and 16-22 cm long scanner AFOV, as well as time-of-flight (TOF) imaging. While Monte Carlo studies demonstrate that longer AFOV and thicker crystals will lead to higher scanner sensitivity, cost has prohibited the building of commercial scanners with >22 cm AFOV. In this study, we performed a series of system simulations to optimize the use of a given amount of crystal material by evaluating the impact on system sensitivity and noise equivalent counts (NEC), as well as image quality in terms of lesion detectability. We evaluated two crystal types (LSO and LaBr3) and fixed the total crystal volume used for each type (8.2 L of LSO and 17.1 L of LaBr3) while varying the crystal thickness and scanner AFOV. In addition, all imaging times were normalized so that the total scan time needed to scan a 100 cm long object with multiple bed positions was kept constant. Our results show that the highest NEC cm-1 in a 35 cm diameter ×70 cm long line source cylinder is achieved for an LSO scanner with 10 mm long crystals and AFOV of 36 cm, while for LaBr3 scanners, the highest NEC cm-1 is obtained with 20 mm long crystals and an AFOV of 38 cm. Lesion phantom simulations show that the best lesion detection performance is achieved in scanners with long AFOV (≥36 cm) and using thin crystals (≤10 mm of LSO and ≤20 mm of LaBr3). This is due to a combination of improved NEC, as well as improved lesion contrast estimation due to better spatial resolution in thinner crystals. Alternatively, for lesion detection performance similar to that achieved in standard clinical scanner designs, the long AFOV scanners can be used to reduce the total scan time without increasing the amount of crystal used in the scanner. In addition, for LaBr3 based scanners, the reduced lesion

  1. Economic comparison of common treatment protocols and J5 vaccination for clinical mastitis in dairy herds using optimized culling decisions.

    PubMed

    Kessels, J A; Cha, E; Johnson, S K; Welcome, F L; Kristensen, A R; Gröhn, Y T

    2016-05-01

    This study used an existing dynamic optimization model to compare costs of common treatment protocols and J5 vaccination for clinical mastitis in US dairy herds. Clinical mastitis is an infection of the mammary gland causing major economic losses in dairy herds due to reduced milk production, reduced conception, and increased risk of mortality and culling for infected cows. Treatment protocols were developed to reflect common practices in dairy herds. These included targeted therapy following pathogen identification, and therapy without pathogen identification using a broad-spectrum antimicrobial or treating with the cheapest treatment option. The cost-benefit of J5 vaccination was also estimated. Effects of treatment were accounted for as changes in treatment costs, milk loss due to mastitis, milk discarded due to treatment, and mortality. Following ineffective treatments, secondary decisions included extending the current treatment, alternative treatment, discontinuing treatment, and pathogen identification followed by recommended treatment. Average net returns for treatment protocols and vaccination were generated using an existing dynamic programming model. This model incorporates cow and pathogen characteristics to optimize management decisions to treat, inseminate, or cull cows. Of the treatment protocols where 100% of cows received recommended treatment, pathogen-specific identification followed by recommended therapy yielded the highest average net returns per cow per year. Out of all treatment scenarios, the highest net returns were achieved with selecting the cheapest treatment option and discontinuing treatment, or alternate treatment with a similar spectrum therapy; however, this may not account for the full consequences of giving nonrecommended therapies to cows with clinical mastitis. Vaccination increased average net returns in all scenarios. PMID:26947301

  2. Optimal adaptive two-stage designs for early phase II clinical trials.

    PubMed

    Shan, Guogen; Wilding, Gregory E; Hutson, Alan D; Gerstenberger, Shawn

    2016-04-15

    Simon's optimal two-stage design has been widely used in early phase clinical trials for Oncology and AIDS studies with binary endpoints. With this approach, the second-stage sample size is fixed when the trial passes the first stage with sufficient activity. Adaptive designs, such as those due to Banerjee and Tsiatis (2006) and Englert and Kieser (2013), are flexible in the sense that the second-stage sample size depends on the response from the first stage, and these designs are often seen to reduce the expected sample size under the null hypothesis as compared with Simon's approach. An unappealing trait of the existing designs is that they are not associated with a second-stage sample size, which is a non-increasing function of the first-stage response rate. In this paper, an efficient intelligent process, the branch-and-bound algorithm, is used in extensively searching for the optimal adaptive design with the smallest expected sample size under the null, while the type I and II error rates are maintained and the aforementioned monotonicity characteristic is respected. The proposed optimal design is observed to have smaller expected sample sizes compared to Simon's optimal design, and the maximum total sample size of the proposed adaptive design is very close to that from Simon's method. The proposed optimal adaptive two-stage design is recommended for use in practice to improve the flexibility and efficiency of early phase therapeutic development. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26526165

  3. Optimal management of Alzheimer’s disease patients: Clinical guidelines and family advice

    PubMed Central

    Haberstroh, Julia; Hampel, Harald; Pantel, Johannes

    2010-01-01

    Family members provide most of the patient care and administer most of the treatments to patients with Alzheimer’s disease (AD). Family caregivers have an important impact on clinical outcomes, such as quality of life (QoL). As a consequence of this service, family caregivers suffer high rates of psychological and physical illness as well as social and financial burdens. Hence, it is important to involve family caregivers in multimodal treatment settings and provide interventions that are both suitable and specifically tailored to their needs. In recent years, several clinical guidelines have been presented worldwide for evidence-based treatment of AD and other forms of dementia. Most of these guidelines have considered family advice as integral to the optimal clinical management of AD. This article reviews current and internationally relevant guidelines with emphasis on recommendations concerning family advice. PMID:20520788

  4. Diffusion weighted MRI of the breast: Protocol optimization, guidelines for interpretation, and potential clinical applications

    PubMed Central

    Partridge, Savannah C.; McDonald, Elizabeth S.

    2013-01-01

    Synopsis There has been increasing interest in the use of diffusion weighted MRI (DWI) for breast imaging. This technique has shown promise for improving the positive predictive value of breast MRI for detection of breast cancer, evaluating tumor response to neoadjuvant chemotherapy, and as a non-contrast MRI alternative for breast cancer screening. However, there is currently no standardized approach to DWI of the breast and data quality varies widely. Prior to implementing DWI into clinical practice, it is important to understand the pertinent technical considerations and current evidence of clinical applications of DWI of the breast. This article provides an overview of basic principles of DWI, optimization of breast DWI protocols, imaging features of benign and malignant breast lesions, promising clinical applications, and potential future directions. PMID:23928248

  5. Reducing the Academic Risks of Over-Optimism: The Longitudinal Effects of Attributional Retraining on Cognition and Achievement

    ERIC Educational Resources Information Center

    Haynes, Tara L.; Ruthig, Joelle C.; Perry, Raymond P.; Stupnisky, Robert H.; Hall, Nathan C.

    2006-01-01

    Although optimism is generally regarded as a positive dispositional characteristic, unmitigated optimism can be problematic. The adaptiveness of overly optimistic expectations in novel or unfamiliar settings is questionable because individuals have little relevant experience on which to base such expectations. In this four-phase longitudinal…

  6. The role of observational studies in optimizing the clinical management of chronic myeloid leukemia

    PubMed Central

    Davis, Catherine; Zyczynski, Teresa; Khoury, H. Jean

    2015-01-01

    Survival has increased dramatically for patients with chronic phase chronic myeloid leukemia (CP-CML) using BCR-ABL targeted tyrosine kinase inhibitors, such that life expectancy is expected to approximate that of patients without CP-CML. Randomized controlled trials (RCTs) and observational studies provide valuable insights into the management of chronic diseases such as CP-CML. RCTs are undoubtedly the backbone of clinical research, and the ‘gold standard’ for evaluating the efficacy and safety of new therapies. However, many questions surrounding the optimal management of patients with CML remain unanswered, and it is widely accepted that these questions will be best answered by evaluating the use of available therapies in clinical practice. Observational studies can extend the knowledge base beyond the clinical trial setting and thus capture a more accurate picture of everyday clinical practice, particularly patients’ experiences of long-term CML treatment. There is therefore growing interest in and appreciation of the value of observational research. This review article will examine the relative merits of RCTs and observational studies in the setting of CML, highlighting those factors – such as the advancing age of the CML patient population and growing importance of patient-reported outcomes – that mean that observational studies should play an important role in shaping clinical practice. This article also provides an overview of what observational studies have told us thus far about the optimal management of patients with CML, outlines some of the key remaining unanswered clinical questions in CML, and summarizes ongoing observational studies designed to provide answers to these key questions. PMID:25642311

  7. Two Flavonolignans from Milk Thistle (Silybum marianum) Inhibit CYP2C9-Mediated Warfarin Metabolism at Clinically Achievable Concentrations

    PubMed Central

    Brantley, Scott J.; Oberlies, Nicholas H.; Kroll, David J.

    2010-01-01

    Milk thistle (Silybum marianum) is a popular herbal product used for hepatoprotection and chemoprevention. Two commercially available formulations are the crude extract, silymarin, and the semipurified product, silibinin. Silymarin consists of at least seven flavonolignans, of which the most prevalent are the diastereoisomers silybin A and silybin B; silibinin consists only of silybin A and silybin B. Based on a recent clinical study showing an interaction between a silymarin product and the CYP2C9 substrate losartan, the CYP2C9 inhibition properties of silybin A and silybin B and corresponding regioisomers, isosilybin A and isosilybin B, were evaluated using human liver microsomes (HLMs), recombinant CYP2C9 (rCYP2C9) enzymes, and the clinically relevant probe, (S)-warfarin. Silybin B was the most potent inhibitor in HLMs, followed by silybin A, isosilybin B, and isosilybin A (IC50 of 8.2, 18, 74, and >100 μM, respectively). Next, silybin A and silybin B were selected for further characterization. As with HLMs, silybin B was more potent than silybin A toward rCYP2C9*1 (6.7 versus 12 μM), rCYP2C9*2 (9.3 versus 19 μM), and rCYP2C9*3 (2.4 versus 9.3 μM). Using a matrix of five substrate (1–15 μM) and six inhibitor (1–80 μM) concentrations and HLMs, both diastereoisomers inhibited (S)-warfarin 7-hydroxylation in a manner described best by a mixed-type inhibition model (Ki values of 4.8 and 10 μM for silybin B and silybin A, respectively). These observations, combined with the high systemic silibinin concentrations (>5–75 μM) achieved in a phase I study involving prostate cancer patients, prompt clinical evaluation of a potential warfarin-milk thistle interaction. PMID:19934397

  8. Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations.

    PubMed

    Brantley, Scott J; Oberlies, Nicholas H; Kroll, David J; Paine, Mary F

    2010-03-01

    Milk thistle (Silybum marianum) is a popular herbal product used for hepatoprotection and chemoprevention. Two commercially available formulations are the crude extract, silymarin, and the semipurified product, silibinin. Silymarin consists of at least seven flavonolignans, of which the most prevalent are the diastereoisomers silybin A and silybin B; silibinin consists only of silybin A and silybin B. Based on a recent clinical study showing an interaction between a silymarin product and the CYP2C9 substrate losartan, the CYP2C9 inhibition properties of silybin A and silybin B and corresponding regioisomers, isosilybin A and isosilybin B, were evaluated using human liver microsomes (HLMs), recombinant CYP2C9 (rCYP2C9) enzymes, and the clinically relevant probe, (S)-warfarin. Silybin B was the most potent inhibitor in HLMs, followed by silybin A, isosilybin B, and isosilybin A (IC(50) of 8.2, 18, 74, and >100 microM, respectively). Next, silybin A and silybin B were selected for further characterization. As with HLMs, silybin B was more potent than silybin A toward rCYP2C9 1 (6.7 versus 12 microM), rCYP2C9 2 (9.3 versus 19 microM), and rCYP2C9 3 (2.4 versus 9.3 microM). Using a matrix of five substrate (1-15 microM) and six inhibitor (1-80 microM) concentrations and HLMs, both diastereoisomers inhibited (S)-warfarin 7-hydroxylation in a manner described best by a mixed-type inhibition model (K(i) values of 4.8 and 10 microM for silybin B and silybin A, respectively). These observations, combined with the high systemic silibinin concentrations (>5-75 microM) achieved in a phase I study involving prostate cancer patients, prompt clinical evaluation of a potential warfarin-milk thistle interaction. PMID:19934397

  9. Nonclinical Evaluations of Small-Molecule Oncology Drugs: Integration into Clinical Dose Optimization and Toxicity Management.

    PubMed

    Dambach, Donna M; Simpson, Natalie E; Jones, Thomas W; Brennan, Richard J; Pazdur, Richard; Palmby, Todd R

    2016-06-01

    Multidisciplinary approaches that incorporate nonclinical pharmacologic and toxicologic characterization of small-molecule oncology drugs into clinical development programs may facilitate improved benefit-risk profiles and clinical toxicity management in patients. The performance of the current nonclinical safety-testing scheme was discussed, highlighting current strengths and areas for improvement. While current nonclinical testing appears to predict the clinical outcome where the prevalence of specific adverse effects are high, nonclinical testing becomes less reliable for predicting clinical adverse effects that occur infrequently, as with some kinase inhibitors. Although adverse effects associated with kinase inhibitors can often be predicted on the basis of target biology, drugs can be promiscuous and inhibit targets with poorly defined function and associated risks. Improvements in adverse effect databases and better characterization of the biologic activities of drug targets may enable better use of computational modeling approaches in predicting adverse effects with kinase inhibitors. Assessing safety of a lead candidate in parallel with other drug properties enables incorporation of a molecule's best features during chemical design, eliminates the worst molecules early, and permits timely investigation/characterization of toxicity mechanisms for identified liabilities. A safety lead optimization and candidate identification strategy that reduces intrinsic toxicity and metabolic risk and enhances selectivity can deliver selective kinase inhibitors that demonstrate on-target adverse effects identified nonclinically. Integrating clinical and nonclinical data during drug development can facilitate better identification and management of oncology drugs. Follow-up nonclinical studies may be used to better understand the risks in a given patient population and minimize or manage these risks more appropriately. Clin Cancer Res; 22(11); 2618-22. ©2016 AACR SEE ALL

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

    PubMed

    Zang, Yong; Liu, Suyu; Yuan, Ying

    2016-07-01

    In developing targeted therapy, the marker-strategy design (MSD) provides an important approach to evaluate the predictive marker effect. This design first randomizes patients into non-marker-based or marker-based strategies. Patients allocated to the non-marker-based strategy are then further randomized to receive either the standard or targeted treatments, while patients allocated to the marker-based strategy receive treatments based on their marker statuses. Little research has been done on the statistical properties of the MSD, which has led to some widespread misconceptions and placed clinical researchers at high risk of using inefficient designs. In this article, we show that the commonly used between-strategy comparison has low power to detect the predictive effect and is valid only under a restrictive condition that the randomization ratio within the non-marker-based strategy matches the marker prevalence. We propose a Wald test that is generally valid and also uniformly more powerful than the between-strategy comparison. Based on that, we derive an optimal MSD that maximizes the power to detect the predictive marker effect by choosing the optimal randomization ratios between the two strategies and treatments. Our numerical study shows that using the proposed optimal designs can substantially improve the power of the MSD to detect the predictive marker effect. We use a lung cancer trial to illustrate the proposed optimal designs. PMID:26951724

  11. Optimizing Performance on Linux Clusters Using Advanced Communication Protocols: Achieving Over 10 Teraflops on a 8.6 Teraflops Linpack-Rated Linux Cluster

    SciTech Connect

    Krishnan, Manoj Kumar; Nieplocha, Jarek

    2005-04-26

    Advancements in high-performance networks (Quadrics, Infiniband or Myrinet) continue to improve the efficiency of modern clusters. However, the average application efficiency is as small fraction of the peak as the system’s efficiency. This paper describes techniques for optimizing application performance on Linux clusters using Remote Memory Access communication protocols. The effectiveness of these optimizations is presented in the context of an application kernel, dense matrix multiplication. The result was achieving over 10 teraflops on HP Linux cluster on which LINPACK performance is measured as 8.6 teraflops.

  12. Model for optimal space and staff efficiency in an otolaryngology clinic.

    PubMed

    Benninger, M S; Strode, S R

    1998-10-01

    Maximizing efficiency of staff and resources is one method of reducing costs without affecting quality. Using a methodology similar to that used to maximize efficiency of airline-gate use, we developed a model with which to evaluate nursing support staff and clinical examining-room resources in a general otolaryngology clinic. For 144 patients over 7 consecutive clinic days, with four otolaryngologists and various combinations of support staff and examining rooms, we measured space and staff resource use, including total clinic time, number of patients seen, patient waiting time, physician and nurse productivity, and examining-room use. A simulation model was used as the medium of analysis to define parameters of the patient encounter. We identified optimal efficiency when there were three examining rooms and one and one-half nursing staff per physician or five examining rooms and three nursing staff for two simultaneously practicing physicians. Compared with a model of two rooms and one nursing staff member, our ideal model increased the percentage of the physicians' time spent in direct contact with patients from 84% to 92%. Visit length decreased from 81 minutes to 57 minutes, the average time from check-in to examination decreased from 47 to 16 minutes, and it became possible for three additional patients to be seen each day. Additional rooms and support staff, in comparison with the optimally efficient distribution, did not significantly affect these parameters. Maximizing efficiency with the use of this methodology can decrease waiting times for patients, resulting in greater patient satisfaction, improved physician productivity, total number of patients seen, and increased total contact time between physicians and patients. PMID:9781998

  13. Optimal Methods to Screen Men and Women for Intimate Partner Violence: Results from an Internal Medicine Residency Continuity Clinic

    ERIC Educational Resources Information Center

    Kapur, Nitin A.; Windish, Donna M.

    2011-01-01

    Contradictory data exist regarding optimal methods and instruments for intimate partner violence (IPV) screening in primary care settings. The purpose of this study was to determine the optimal method and screening instrument for IPV among men and women in a primary-care resident clinic. We conducted a cross-sectional study at an urban, academic,…

  14. Optimal adaptive two-stage designs for phase II cancer clinical trials.

    PubMed

    Englert, Stefan; Kieser, Meinhard

    2013-11-01

    In oncology, single-arm two-stage designs with binary endpoint are widely applied in phase II for the development of cytotoxic cancer therapies. Simon's optimal design with prefixed sample sizes in both stages minimizes the expected sample size under the null hypothesis and is one of the most popular designs. The search algorithms that are currently used to identify phase II designs showing prespecified characteristics are computationally intensive. For this reason, most authors impose restrictions on their search procedure. However, it remains unclear to what extent this approach influences the optimality of the resulting designs. This article describes an extension to fixed sample size phase II designs by allowing the sample size of stage two to depend on the number of responses observed in the first stage. Furthermore, we present a more efficient numerical algorithm that allows for an exhaustive search of designs. Comparisons between designs presented in the literature and the proposed optimal adaptive designs show that while the improvements are generally moderate, notable reductions in the average sample size can be achieved for specific parameter constellations when applying the new method and search strategy. PMID:23868324

  15. Optimal Doses of Methotrexate Combined with Anti-TNF Therapy to Maintain Clinical Remission in Inflammatory Bowel Disease

    PubMed Central

    Rubin, David T

    2015-01-01

    Background and aims: Methotrexate (MTX) is sometimes used as part of combination therapy for the treatment of inflammatory bowel disease [IBD]; however, the optimal MTX dose for combination therapy has not been established. This study compared the efficacy of lower-dose and higher-dose MTX with anti tumor necrosis factor alpha (anti-TNF) therapy among IBD patients. Methods: Retrospective chart review was performed of 88 IBD patients at our center between 2010 and 2013. Low-dose MTX was defined as ≤ 12.5mg/week and high-dose MTX as 15–25mg/week. Patients who met the criteria for clinical remission [Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2] at baseline were followed for up to 42 months. Chart review occurred in 6-month intervals. The primary outcome was consecutive months in remission prior to relapse. Secondary outcomes included other indicators of worsening disease [endoscopic inflammation, steroid use, therapy escalation/addition, or surgery] and adverse events. Regression analysis and Kaplan–Meier survival analysis were completed. Results: We identified 73 [83%] dual-therapy patients, of whom 32 low-dose and 14 high-dose individuals achieved remission. When compared with high-dose patients, low-dose patients were more likely to relapse [log-rank test, p < 0.01]. Secondary indicators of worsening disease occurred during 34.4% of low-dose review periods and 31.4% of high-dose review periods [p = 0.67]; 3/52 [6%] low-dose patients and 3/21 [14%] high-dose patients [p = 0.34] discontinued MTX therapy due to adverse events. Conclusions: When combined with anti-TNF therapy, MTX at doses of >12.5mg/week was more effective at maintaining clinical remission than lower doses. These findings will guide management of combination therapy in IBD patients. PMID:25616487

  16. Academic Abilities in Children and Adolescents with a History of Autism Spectrum Disorders Who Have Achieved Optimal Outcomes

    ERIC Educational Resources Information Center

    Troyb, Eva; Orinstein, Alyssa; Tyson, Katherine; Helt, Molly; Eigsti, Inge-Marie; Stevens, Michael; Fein, Deborah

    2014-01-01

    This study examines the academic abilities of children and adolescents who were once diagnosed with an autism spectrum disorder, but who no longer meet diagnostic criteria for this disorder. These individuals have achieved social and language skills within the average range for their ages, receive little or no school support, and are referred to…

  17. Contemporary pre-clinical development of anticancer agents--what are the optimal preclinical models?

    PubMed

    Damia, Giovanna; D'Incalci, Maurizio

    2009-11-01

    The successful identification of novel effective anticancer drugs is largely dependent on the use of appropriate preclinical experimental models that should possibly mimic the complexity of different cancer diseases. The huge number of targets suitable for the design of new anticancer drugs is producing hundreds of novel molecules that require appropriate experimental models to investigate their mode of action and antitumour activity in order to select for clinical investigation the ones with higher chances of being clinically effective. However, our ability to predict the clinical efficacy of a new compound in the clinic based on preclinical data is still limited. This paper overviews the in vitro/in vivo preclinical systems that are currently used to test either compounds with an unknown mechanism of action or compounds designed to hit cancer-specific or cancer-related molecular targets. Examples of experimental models successfully used to identify novel compounds are provided. Xenografts are still the most commonly used in vivo models in drug development due to their high degree of reproducibility and because, in some cases, particularly when orthotopically transplanted, they maintain several biological properties of the human tumours they derive from. Genetic models are very useful for target validation, but are often not sufficiently reproducible to be used for drug evaluation. The variety of animal models can be effectively used to optimally test drugs that presumably act by a defined mode of action, but final success is highly dependent on the ability of drug development teams to integrate different expertises such as biology, chemistry, pharmacology, toxicology and clinical oncology into a clever and well orchestrated plan that keeps in consideration both the complexity of cancer diseases, involving alterations of different pathways, and the complexity of drugs whose pharmacological properties are crucial to obtain the desired effects. PMID:19762228

  18. Telemonitoring in heart failure patients with clinical decision support to optimize medication doses based on guidelines.

    PubMed

    Kropf, Martin; Modre-Osprian, Robert; Hayn, Dieter; Fruhwald, Friedrich; Schreier, Günter

    2014-01-01

    The European Society of Cardiology guidelines for heart failure management are based on strong evidence that adherence to optimal medication is beneficial for heart failure patients. Telemonitoring with integrated clinical decision support enables physicians to adapt medication dose based on up to date vital parameters and reduces the number of hospital visits needed solely for up-titration of heart failure medication. Although keeping track of weight and blood pressure changes is recommended during unstable phases, e.g. post-discharge and during up-titration of medication, guidelines are rather vague regarding telehealth aspects. In this paper, we focus on the evaluation of a clinical decision support system for adaption of heart failure medication and for detecting early deteriorations through monitoring of blood pressure, heart rate and weight changes. This clinical decision support system is currently used in INTENSE-HF, a large scale telemonitoring trial with heart failure patients. The aim of this paper was to apply the decision support algorithm to an existing telemonitoring dataset, to assess the ability of the decision support concept to adhere to the guidelines and to discuss its limitations and potential improvements. PMID:25570663

  19. SU-E-T-387: Achieving Optimal Patient Setup Imaging and Treatment Workflow Configurations in Multi-Room Proton Centers

    SciTech Connect

    Zhang, H; Prado, K; Langen, K; Yi, B; Mehta, M; Regine, W; D'Souza, W

    2014-06-01

    Purpose: To simulate patient flow in proton treatment center under uncertainty and to explore the feasibility of treatment preparation rooms to improve patient throughput and cyclotron utilization. Methods: Three center layout scenarios were modeled: (S1: In-Tx room imaging) patient setup and imaging (planar/volumetric) performed in treatment room, (S2: Patient setup in preparation room) each treatment room was assigned with preparation room(s) that was equipped with lasers only for patient setup and gross patient alignment, and (S3: Patient setup and imaging in preparation room) preparation room(s) was equipped with laser and volumetric imaging for patient setup, gross and fine patient alignment. A 'snap' imaging was performed in treatment room. For each scenario, the number of treatment rooms and the number of preparation rooms serving each treatment room were varied. We examined our results (average of 100 16-hour (two shifts) working days) by evaluating patient throughput and cyclotron utilization. Results: When the number of treatment rooms increased ([from, to]) [1, 5], daily patient throughput increased [32, 161], [29, 184] and [27, 184] and cyclotron utilization increased [13%, 85%], [12%, 98%], and [11%, 98%] for scenarios S1, S2 and S3 respectively. However, both measures plateaued after 4 rooms. With the preparation rooms, the throughput and the cyclotron utilization increased by 14% and 15%, respectively. Three preparation rooms were optimal to serve 1-3 treatment rooms and two preparation rooms were optimal to serve 4 or 5 treatment rooms. Conclusion: Patient preparation rooms for patient setup may increase throughput and decrease the need for additional treatment rooms (cost effective). Optimal number of preparation rooms serving each gantry room varies as a function of treatment rooms and patient setup scenarios. A 5th treatment room may not be justified by throughput or utilization.

  20. Achieving standardized medication data in clinical research studies: two approaches and applications for implementing RxNorm.

    PubMed

    Richesson, Rachel L; Smith, Susan B; Malloy, Jamie; Krischer, Jeffrey P

    2010-08-01

    The National Institutes of Health has proposed a roadmap for clinical research. Test projects of this roadmap include centralized data management for distributed research, the harmonization of clinical and research data, and the use of data standards throughout the research process. In 2003, RxNorm was named as a standard for codifying clinical drugs. Clinical researchers looking to implement RxNorm have few template implementation plans. Epidemiological studies and clinical trials (types of clinical research) have different requirements for model standards and best implementation tools. This paper highlights two different (epidemiological and intervention) clinical research projects, their unique requirements for a medication standard, the suitability of RxNorm as a standard for each, and application and process requirements for implementation. It is hoped that our experience of selecting and implementing the RxNorm standard to address varying study requirements in both domestic and international settings will be of value to other efforts. PMID:20703919

  1. Towards Clinically Optimized MRI-guided Surgical Manipulator for Minimally Invasive Prostate Percutaneous Interventions: Constructive Design*

    PubMed Central

    Eslami, Sohrab; Fischer, Gregory S.; Song, Sang-Eun; Tokuda, Junichi; Hata, Nobuhiko; Tempany, Clare M.; Iordachita, Iulian

    2013-01-01

    This paper undertakes the modular design and development of a minimally invasive surgical manipulator for MRI-guided transperineal prostate interventions. Severe constraints for the MRI-compatibility to hold the minimum artifact on the image quality and dimensions restraint of the bore scanner shadow the design procedure. Regarding the constructive design, the manipulator kinematics has been optimized and the effective analytical needle workspace is developed and followed by proposing the workflow for the manual needle insertion. A study of the finite element analysis is established and utilized to improve the mechanism weaknesses under some inevitable external forces to ensure the minimum structure deformation. The procedure for attaching a sterile plastic drape on the robot manipulator is discussed. The introduced robotic manipulator herein is aimed for the clinically prostate biopsy and brachytherapy applications. PMID:24683502

  2. Towards Clinically Optimized MRI-guided Surgical Manipulator for Minimally Invasive Prostate Percutaneous Interventions: Constructive Design.

    PubMed

    Eslami, Sohrab; Fischer, Gregory S; Song, Sang-Eun; Tokuda, Junichi; Hata, Nobuhiko; Tempany, Clare M; Iordachita, Iulian

    2013-12-31

    This paper undertakes the modular design and development of a minimally invasive surgical manipulator for MRI-guided transperineal prostate interventions. Severe constraints for the MRI-compatibility to hold the minimum artifact on the image quality and dimensions restraint of the bore scanner shadow the design procedure. Regarding the constructive design, the manipulator kinematics has been optimized and the effective analytical needle workspace is developed and followed by proposing the workflow for the manual needle insertion. A study of the finite element analysis is established and utilized to improve the mechanism weaknesses under some inevitable external forces to ensure the minimum structure deformation. The procedure for attaching a sterile plastic drape on the robot manipulator is discussed. The introduced robotic manipulator herein is aimed for the clinically prostate biopsy and brachytherapy applications. PMID:24683502

  3. Quality Control Methods for Optimal BCR-ABL1 Clinical Testing in Human Whole Blood Samples

    PubMed Central

    Stanoszek, Lauren M.; Crawford, Erin L.; Blomquist, Thomas M.; Warns, Jessica A.; Willey, Paige F.S.; Willey, James C.

    2014-01-01

    Reliable breakpoint cluster region (BCR)–Abelson (ABL) 1 measurement is essential for optimal management of chronic myelogenous leukemia. There is a need to optimize quality control, sensitivity, and reliability of methods used to measure a major molecular response and/or treatment failure. The effects of room temperature storage time, different primers, and RNA input in the reverse transcription (RT) reaction on BCR-ABL1 and β-glucuronidase (GUSB) cDNA yield were assessed in whole blood samples mixed with K562 cells. BCR-ABL1 was measured relative to GUSB to control for sample loading, and each gene was measured relative to known numbers of respective internal standard molecules to control for variation in quality and quantity of reagents, thermal cycler conditions, and presence of PCR inhibitors. Clinical sample and reference material measurements with this test were concordant with results reported by other laboratories. BCR-ABL1 per 103 GUSB values were significantly reduced (P = 0.004) after 48-hour storage. Gene-specific primers yielded more BCR-ABL1 cDNA than random hexamers at each RNA input. In addition, increasing RNA inhibited the RT reaction with random hexamers but not with gene-specific primers. Consequently, the yield of BCR-ABL1 was higher with gene-specific RT primers at all RNA inputs tested, increasing to as much as 158-fold. We conclude that optimal measurement of BCR-ABL1 per 103 GUSB in whole blood is obtained when gene-specific primers are used in RT and samples are analyzed within 24 hours after blood collection. PMID:23541592

  4. Optimal control-based bayesian detection of clinical and behavioral state transitions.

    PubMed

    Santaniello, Sabato; Sherman, David L; Thakor, Nitish V; Eskandar, Emad N; Sarma, Sridevi V

    2012-09-01

    Accurately detecting hidden clinical or behavioral states from sequential measurements is an emerging topic in neuroscience and medicine, which may dramatically impact neural prosthetics, brain-computer interface and drug delivery. For example, early detection of an epileptic seizure from sequential electroencephalographic (EEG) measurements would allow timely administration of anticonvulsant drugs or neurostimulation, thus reducing physical impairment and risks of overtreatment. We develop a Bayesian paradigm for state transition detection that combines optimal control and Markov processes. We define a hidden Markov model of the state evolution and develop a detection policy that minimizes a loss function of both probability of false positives and accuracy (i.e., lag between estimated and actual transition time). Our strategy automatically adapts to each newly acquired measurement based on the state evolution model and the relative loss for false positives and accuracy, thus resulting in a time varying threshold policy. The paradigm was used in two applications: 1) detection of movement onset (behavioral state) from subthalamic single unit recordings in Parkinson's disease patients performing a motor task; 2) early detection of an approaching seizure (clinical state) from multichannel intracranial EEG recordings in rodents treated with pentylenetetrazol chemoconvulsant. Our paradigm performs significantly better than chance and improves over widely used detection algorithms. PMID:22893447

  5. Rod Visual Pigment Optimizes Active State to Achieve Efficient G Protein Activation as Compared with Cone Visual Pigments*

    PubMed Central

    Kojima, Keiichi; Imamoto, Yasushi; Maeda, Ryo; Yamashita, Takahiro; Shichida, Yoshinori

    2014-01-01

    Most vertebrate retinas contain two types of photoreceptor cells, rods and cones, which show different photoresponses to mediate scotopic and photopic vision, respectively. These cells contain different types of visual pigments, rhodopsin and cone visual pigments, respectively, but little is known about the molecular properties of cone visual pigments under physiological conditions, making it difficult to link the molecular properties of rhodopsin and cone visual pigments with the differences in photoresponse between rods and cones. Here we prepared bovine and mouse rhodopsin (bvRh and mRh) and chicken and mouse green-sensitive cone visual pigments (cG and mG) embedded in nanodiscs and applied time-resolved fluorescence spectroscopy to compare their Gt activation efficiencies. Rhodopsin exhibited greater Gt activation efficiencies than cone visual pigments. Especially, the Gt activation efficiency of mRh was about 2.5-fold greater than that of mG at 37 °C, which is consistent with our previous electrophysiological data of knock-in mice. Although the active state (Meta-II) was in equilibrium with inactive states (Meta-I and Meta-III), quantitative determination of Meta-II in the equilibrium showed that the Gt activation efficiency per Meta-II of bvRh was also greater than those of cG and mG. These results indicated that efficient Gt activation by rhodopsin, resulting from an optimized active state of rhodopsin, is one of the causes of the high amplification efficiency of rods. PMID:24375403

  6. ITI choice for the optimal management of inhibitor patients - from a clinical and pharmacoeconomic perspective.

    PubMed

    Oldenburg, J; Austin, S K; Kessler, C M

    2014-09-01

    The development of alloantibody inhibitors against factor VIII (FVIII) represents the most significant complication of haemophilia care. Inhibitors tend to develop early in the course of treatment in about 20-30% of patients with severe haemophilia who receive on-demand or prophylactic FVIII therapy. Many factors are associated with inhibitor formation, including disease severity, major FVIII gene defects, family history and non-Caucasian race, as well as age at first treatment, intensity of early treatment, use of prophylaxis and product choice. As these latter treatment-related variables are modifiable, they provide opportunity to minimize inhibitor incidence at the clinical level. Data from the Bonn Centre in Germany have indicated an overall success rate of 78% for immune tolerance induction (ITI) therapy, with a failure rate of 15% and with some treatments either ongoing (3%) or withdrawn (4%). Similarly, data from the G-ITI study, the largest international multicentre ITI study using a single plasma-derived (pd) FVIII/von Willebrand factor (VWF) product, have demonstrated success rates (complete and partial) in primary and rescue ITI of 87% and 74%, respectively, with 85% of poor prognosis patients achieving success. Favourable clinical results based on success rates and time to tolerization continue to be reported for use of pdFVIII/VWF in ITI, with pdFVIII/VWF having a particular role in patients who require rescue ITI and those with a poor prognosis for success. Data from prospective, randomized, controlled clinical studies, such as RES.I.ST (Rescue Immune Tolerance Study), are eagerly awaited. Another factor to consider with ITI therapy is cost; preliminary data from an updated decision analytic model have provided early evidence that ITI has an economic advantage compared with on-demand or prophylactic therapy. PMID:24975701

  7. Strategies to optimize lithium-ion supercapacitors achieving high-performance: Cathode configurations, lithium loadings on anode, and types of separator

    NASA Astrophysics Data System (ADS)

    Cao, Wanjun; Li, Yangxing; Fitch, Brian; Shih, Jonathan; Doung, Tien; Zheng, Jim

    2014-12-01

    The Li-ion capacitor (LIC) is composed of a lithium-doped carbon anode and an activated carbon cathode, which is a half Li-ion battery (LIB) and a half electrochemical double-layer capacitor (EDLC). LICs can achieve much more energy density than EDLC without sacrificing the high power performance advantage of capacitors over batteries. LIC pouch cells were assembled using activated carbon (AC) cathode and hard carbon (HC) + stabilized lithium metal power (SLMP®) anode. Different cathode configurations, various SLMP loadings on HC anode, and two types of separators were investigated to achieve the optimal electrochemical performance of the LIC. Firstly, the cathode binders study suggests that the PTFE binder offers improved energy and power performances for LIC in comparison to PVDF. Secondly, the mass ratio of SLMP to HC is at 1:7 to obtain the optimized electrochemical performance for LIC among all the various studied mass ratios between lithium loading amounts and active anode material. Finally, compared to the separator Celgard PP 3501, cellulose based TF40-30 is proven to be a preferred separator for LIC.

  8. ACHIEVING NEW SOURCE PERFORMANCE STANDARDS (NSPS) EMISSION STANDARDS THROUGH INTEGRATION OF LOW-NOx BURNERS WITH AN OPTIMIZATION PLAN FOR BOILER COMBUSTION

    SciTech Connect

    Wayne Penrod; David Moyeda

    2003-04-01

    The objective of this project is to demonstrate the use of an Integrated Combustion Optimization System to achieve NO{sub x} emissions levels in the range of 0.15 to 0.22 lb/MMBtu while simultaneously enabling increased power output. The project consists of the integration of low-NO{sub x} burners and advanced overfire air technology with various process measurement and control devices on the Holcomb Station Unit 1 boiler. The project includes the use of sophisticated neural networks or other artificial intelligence technologies and complex software that can optimize several operating parameters, including NO{sub x} emissions, boiler efficiency, and CO emissions. The program is being performed in three phases. In Phase I, the boiler is being equipped with sensors that can be used to monitor furnace conditions and coal flow to permit improvements in boiler operation. In Phase II, the boiler will be equipped with burner modifications designed to reduce NO{sub x} emissions and automated coal flow dampers to permit on-line fuel balancing. In Phase III, the boiler will be equipped with an overfire air system to permit deep reductions in NO{sub x} emissions to be achieved. Integration of the overfire air system with the improvements made in Phases I and II will permit optimization of the boiler performance, output, and emissions. During this reporting period, efforts were focused on Phase I and Phase II activities. The furnace sensors were procured and installed in February 2003. Baseline testing was performed following the sensor installation. The low-NO{sub x} burner modifications, the coal flow dampers, and the coal flow monitoring system were procured and installed during a boiler outage in March 2003. Process design activities were performed to support design of the equipment installed and to develop specifications for the overfire air system. The overfire air system preliminary engineering design was initiated.

  9. Optimal prediction of carotid intraplaque hemorrhage using clinical and lumen imaging markers

    PubMed Central

    McLaughlin, Michael S.; Hinckley, Peter J.; Treiman, Scott M.; Kim, Seong-Eun; Stoddard, Gregory J.; Parker, Dennis L.; Treiman, Gerald S.; McNally, J. Scott

    2015-01-01

    Purpose MRI detects intraplaque hemorrhage (IPH) with high accuracy using the magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequence. Still, MRI is not readily available for all patients, and many receive CTA instead. Our goal was to determine essential clinical and lumen imaging predictors of IPH as indicators of its presence and clues to its pathogenesis. Methods In this retrospective cross sectional study, patients undergoing stroke workup with MRI/MRA underwent carotid IPH imaging. A total of 726 carotid plaques were analyzed, excluding vessels with non-carotid stroke sources (420), occlusions (7), or near-occlusions (3). Potential carotid imaging predictors of IPH included percent diameter and mm stenosis, plaque thickness, ulceration, and intraluminal thrombus. Clinical predictors were recorded and a multivariable logistic regression model was fitted. Backward-elimination was used to determine essential IPH predictors with a threshold two-sided p<.10. Receiver operating characteristic (ROC) analysis was also performed. Results Predictors of carotid IPH included plaque thickness (odds ratio, OR=2.20, p<.001), mm stenosis (OR=0.46, p<.001), ulceration (OR=4.25, p=.020), age (OR=1.11, p=.001) and male sex (OR=3.23, p=.077). The final model discriminatory value was excellent (area under the curve, AUC=0.932). This was significantly higher than models using only plaque thickness (AUC=0.881), mm stenosis (AUC=0.830) or ulceration (AUC=0.715) p<.001. Conclusions Optimal discrimination of carotid IPH requires information on plaque thickness, mm stenosis, ulceration, age and male sex. These factors predict IPH with high discriminatory power, and may provide clues to the pathogenesis of IPH. This model could be used to predict the presence of IPH when MRI is contraindicated. PMID:26338923

  10. Reliably Detecting Clinically Important Variants Requires Both Combined Variant Calls and Optimized Filtering Strategies.

    PubMed

    Field, Matthew A; Cho, Vicky; Andrews, T Daniel; Goodnow, Chris C

    2015-01-01

    A diversity of tools is available for identification of variants from genome sequence data. Given the current complexity of incorporating external software into a genome analysis infrastructure, a tendency exists to rely on the results from a single tool alone. The quality of the output variant calls is highly variable however, depending on factors such as sequence library quality as well as the choice of short-read aligner, variant caller, and variant caller filtering strategy. Here we present a two-part study first using the high quality 'genome in a bottle' reference set to demonstrate the significant impact the choice of aligner, variant caller, and variant caller filtering strategy has on overall variant call quality and further how certain variant callers outperform others with increased sample contamination, an important consideration when analyzing sequenced cancer samples. This analysis confirms previous work showing that combining variant calls of multiple tools results in the best quality resultant variant set, for either specificity or sensitivity, depending on whether the intersection or union, of all variant calls is used respectively. Second, we analyze a melanoma cell line derived from a control lymphocyte sample to determine whether software choices affect the detection of clinically important melanoma risk-factor variants finding that only one of the three such variants is unanimously detected under all conditions. Finally, we describe a cogent strategy for implementing a clinical variant detection pipeline; a strategy that requires careful software selection, variant caller filtering optimizing, and combined variant calls in order to effectively minimize false negative variants. While implementing such features represents an increase in complexity and computation the results offer indisputable improvements in data quality. PMID:26600436

  11. (90) Y/(177) Lu-labelled Cetuximab immunoconjugates: radiochemistry optimization to clinical dose formulation.

    PubMed

    Chakravarty, Rubel; Chakraborty, Sudipta; Sarma, Haladhar Dev; Nair, K V Vimalnath; Rajeswari, Ardhi; Dash, Ashutosh

    2016-07-01

    Radiolabelled monoclonal antibodies (mAbs) are increasingly being utilized in cancer theranostics, which is a significant move toward tailored treatment for individual patients. Cetuximab is a recombinant, human-mouse chimeric IgG1 mAb that binds to the epidermal growth factor receptor with high affinity. We have optimized a protocol for formulation of clinically relevant doses (~2.22 GBq) of (90) Y-labelled Cetuximab and (177) Lu-labelled Cetuximab by conjugation of the mAb with a suitable bifunctional chelator, N-[(R)-2-amino-3-(paraisothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N″,N″-pentaacetic acid (CHX-A″-DTPA). The radioimmunoconjugates demonstrated reasonably high specific activity (1.26 ± 0.27 GBq/mg for (90) Y-CHX-A″-DTPA-Cetuximab and 1.14 ± 0.15 GBq/mg for (177) Lu-CHX-A″-DTPA-Cetuximab), high radiochemical purity (>95%) and appreciable in vitro stability under physiological conditions. Preliminary biodistribution studies with both (90) Y-CHX-A″-DTPA-Cetuximab and (177) Lu-CHX-A″-DTPA-Cetuximab in Swiss mice bearing fibrosarcoma tumours demonstrated significant tumour uptake at 24-h post-injection (p.i.) (~16%ID/g) with good tumour-to-background contrast. The results of the biodistribution studies were further corroborated by ex vivo Cerenkov luminescence imaging after administration of (90) Y-CHX-A″-DTPA-Cetuximab in tumour-bearing mice. The tumour uptake at 24 h p.i. was significantly reduced with excess unlabelled Cetuximab, suggesting that the uptake was receptor mediated. The results of this study hold promise, and this strategy should be further explored for clinical translation. PMID:27264196

  12. Reliably Detecting Clinically Important Variants Requires Both Combined Variant Calls and Optimized Filtering Strategies

    PubMed Central

    Field, Matthew A.; Cho, Vicky

    2015-01-01

    A diversity of tools is available for identification of variants from genome sequence data. Given the current complexity of incorporating external software into a genome analysis infrastructure, a tendency exists to rely on the results from a single tool alone. The quality of the output variant calls is highly variable however, depending on factors such as sequence library quality as well as the choice of short-read aligner, variant caller, and variant caller filtering strategy. Here we present a two-part study first using the high quality ‘genome in a bottle’ reference set to demonstrate the significant impact the choice of aligner, variant caller, and variant caller filtering strategy has on overall variant call quality and further how certain variant callers outperform others with increased sample contamination, an important consideration when analyzing sequenced cancer samples. This analysis confirms previous work showing that combining variant calls of multiple tools results in the best quality resultant variant set, for either specificity or sensitivity, depending on whether the intersection or union, of all variant calls is used respectively. Second, we analyze a melanoma cell line derived from a control lymphocyte sample to determine whether software choices affect the detection of clinically important melanoma risk-factor variants finding that only one of the three such variants is unanimously detected under all conditions. Finally, we describe a cogent strategy for implementing a clinical variant detection pipeline; a strategy that requires careful software selection, variant caller filtering optimizing, and combined variant calls in order to effectively minimize false negative variants. While implementing such features represents an increase in complexity and computation the results offer indisputable improvements in data quality. PMID:26600436

  13. Spatio-temporal optimization of agricultural practices to achieve a sustainable development at basin level; framework of a case study in Colombia

    NASA Astrophysics Data System (ADS)

    Uribe, Natalia; corzo, Gerald; Solomatine, Dimitri

    2016-04-01

    The flood events present during the last years in different basins of the Colombian territory have raised questions on the sensitivity of the regions and if this regions have common features. From previous studies it seems important features in the sensitivity of the flood process were: land cover change, precipitation anomalies and these related to impacts of agriculture management and water management deficiencies, among others. A significant government investment in the outreach activities for adopting and promoting the Colombia National Action Plan on Climate Change (NAPCC) is being carried out in different sectors and regions, having as a priority the agriculture sector. However, more information is still needed in the local environment in order to assess were the regions have this sensitivity. Also the continuous change in one region with seasonal agricultural practices have been pointed out as a critical information for optimal sustainable development. This combined spatio-temporal dynamics of crops cycle in relation to climate change (or variations) has an important impact on flooding events at basin areas. This research will develop on the assessment and optimization of the aggregated impact of flood events due to determinate the spatio-temporal dynamic of changes in agricultural management practices. A number of common best agricultural practices have been identified to explore their effect in a spatial hydrological model that will evaluate overall changes. The optimization process consists on the evaluation of best performance in the agricultural production, without having to change crops activities or move to other regions. To achieve this objectives a deep analysis of different models combined with current and future climate scenarios have been planned. An algorithm have been formulated to cover the parametric updates such that the optimal temporal identification will be evaluated in different region on the case study area. Different hydroinformatics

  14. Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials

    PubMed Central

    Holpuch, Andrew S.; Desai, Kashappa-Goud H.; Schwendeman, Steven P.; Mallery, Susan R.

    2011-01-01

    Due to its characterized progression from recognized premalignant oral epithelial changes (i.e., oral epithelial dysplasia) to invasive cancer, oral squamous cell carcinoma represents an optimal disease for chemopreventive intervention prior to malignant transformation. The primary goal of oral cancer chemoprevention is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Over the last several decades, numerous oral cancer chemoprevention clinical trials have assessed the therapeutic efficacy of diverse chemopreventive agents. The standard of care for more advanced oral dysplastic lesions entails surgical excision and close clinical follow-up due to the potential (~33%) for local recurrence at a similar or more advanced histological stage. The purpose of this review was to identify prominent oral cancer chemoprevention clinical trials, assess their overall therapeutic efficacy, and delineate effects of local versus systemic drug administration. In addition, these compiled clinical trial data present concepts for consideration in the design and conduction of future clinical trials. PMID:22013393

  15. Using optimal combination of teaching-learning methods (open book assignment and group tutorials) as revision exercises to improve learning outcome in low achievers in biochemistry.

    PubMed

    Rajappa, Medha; Bobby, Zachariah; Nandeesha, H; Suryapriya, R; Ragul, Anithasri; Yuvaraj, B; Revathy, G; Priyadarssini, M

    2016-07-01

    Graduate medical students of India are taught Biochemistry by didactic lectures and they hardly get any opportunity to clarify their doubts and reinforce the concepts which they learn in these lectures. We used a combination of teaching-learning (T-L) methods (open book assignment followed by group tutorials) to study their efficacy in improving the learning outcome. About 143 graduate medical students were classified into low (<50%: group 1, n = 23), medium (50-75%: group 2, n = 74), and high (>75%: group 3, n = 46) achievers, based on their internal assessment marks. After the regular teaching module on the topics "Vitamins and Enzymology", all the students attempted an open book assignment without peer consultation. Then all the students participated in group tutorials. The effects on the groups were evaluated by pre and posttests at the end of each phase, with the same set of MCQs. Gain from group tutorials and overall gain was significantly higher in the low achievers, compared to other groups. High and medium achievers obtained more gain from open book assignment, than group tutorials. The overall gain was significantly higher than the gain obtained from open book assignment or group tutorials, in all three groups. All the three groups retained the gain even after 1 week of the exercise. Hence, optimal use of novel T-L methods (open book assignment followed by group tutorials) as revision exercises help in strengthening concepts in Biochemistry in this oft neglected group of low achievers in graduate medical education. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):321-325, 2016. PMID:26891594

  16. Clinically significant responses achieved with romidepsin across disease compartments in patients with cutaneous T-cell lymphoma

    PubMed Central

    Kim, Ellen J.; Kim, Youn H.; Rook, Alain H.; Lerner, Adam; Duvic, Madeleine; Reddy, Sunil; Robak, Tadeusz; Becker, Jürgen C.; Samtsov, Alexey; McCulloch, William; Waksman, Joel; Whittaker, Sean

    2015-01-01

    Cutaneous T-cell lymphoma (CTCL) is a rare heterogeneous group of non-Hodgkin lymphomas that arises in the skin but can progress to systemic disease (lymph nodes, blood, viscera). Historically, in clinical trials of CTCL there has been little consistency in how responses were defined in each disease “compartment”; some studies only assessed responses in the skin. The histone deacetylase inhibitor romidepsin is approved by the US Food and Drug Administration for the treatment of CTCL in patients who have received at least one prior systemic therapy. Phase II studies that led to approval used rigorous composite end points that incorporated disease assessments in all compartments. The objective of this analysis was to thoroughly examine the activity of romidepsin within each disease compartment in patients with CTCL. Romidepsin was shown to have clinical activity across disease compartments and is suitable for use in patients with CTCL having skin involvement only, erythroderma, lymphadenopathy and/or blood involvement. PMID:25791237

  17. The Clinical and Bacteriological Factors for Optimal Levofloxacin-Containing Triple Therapy in Second-Line Helicobacter pylori Eradication

    PubMed Central

    Tai, Wei-Chen; Lee, Chen-Hsiang; Chiou, Shue-Shian; Kuo, Chung-Mou; Kuo, Chung-Huang; Liang, Chih-Ming; Lu, Lung-Sheng; Chiu, Chien-Hua; Wu, Keng-Liang; Chiu, Yi-Chun; Hu, Tsung-Hui; Chuah, Seng-Kee

    2014-01-01

    Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily). They were prescribed with either a 10-day (group A) or 14-day (group B) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days) by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI] = 63.9–85.3%) and 90.5% (95% CI = 84.5–98.1%), respectively in the per protocol analysis (P = 0.008 in the per protocol analysis) and 67.1% (95% CI = 56.6–78.5%) and 84.8% (95% CI = 76.8–93.4%), respectively, in the intention-to-treat analysis (P = 0.009). The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14) but it dropped to 12.5% (1/8) when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful

  18. Sub-optimal achievement of guideline-derived lipid goals in management of diabetes patients with atherosclerotic cardiovascular disease, despite high use of evidence-based therapies.

    PubMed

    DeGuzman, Pamela B; Akosah, Kwame O; Simpson, Allan G; Barbieri, Kirk E; Megginson, Gregory C; Goldberg, Randal I; Beller, George A

    2012-04-01

    Guidelines recommend aggressive goals for lipid and blood pressure reduction for high risk patients with diabetes mellitus and atherosclerotic coronary disease. However, it remains unclear how many patients achieve treatment goals versus the number of people merely placed on treatment. We conducted an observational study in an academic cardiology clinic. A total of 926 patients with atherosclerotic cardiovascular disease and concomitant diabetes mellitus met criteria. Mean age was 68.4 ± 10.2, 65.6% were male, and 86.8% were Caucasian. By the last visit a high percentage of patients were receiving recommended medications. Mean LDL-cholesterol achieved was 80.4 mg/dl with 40.9% reaching ≤ 70 mg/dl, and 61.7% reaching SBP ≤ 130 mmHg. Many patients with diabetes mellitus and atherosclerotic cardiovascular disease are prescribed recommended medications; however, few achieve guidelines-specified therapeutic goals for LDL-cholesterol and blood pressure. Studies evaluating performance improvement should include percentage of patients reaching treatment goals. Mechanisms underlying the treatment gap need to be identified and addressed. PMID:22234950

  19. Achieving New Source Performance Standards (NSPS) Emission Standards Through Integration of Low-NOx Burners with an Optimization Plan for Boiler Combustion

    SciTech Connect

    Wayne Penrod

    2006-12-31

    The objective of this project was to demonstrate the use of an Integrated Combustion Optimization System to achieve NO{sub X} emission levels in the range of 0.15 to 0.22 lb/MMBtu while simultaneously enabling increased power output. The project plan consisted of the integration of low-NO{sub X} burners and advanced overfire air technology with various process measurement and control devices on the Holcomb Station Unit 1 boiler. The plan included the use of sophisticated neural networks or other artificial intelligence technologies and complex software to optimize several operating parameters, including NO{sub X} emissions, boiler efficiency, and CO emissions. The program was set up in three phases. In Phase I, the boiler was equipped with sensors that can be used to monitor furnace conditions and coal flow to permit improvements in boiler operation. In Phase II, the boiler was equipped with burner modifications designed to reduce NO{sub X} emissions and automated coal flow dampers to permit on-line fuel balancing. In Phase III, the boiler was to be equipped with an overfire air system to permit deep reductions in NO{sub X} emissions. Integration of the overfire air system with the improvements made in Phases I and II would permit optimization of boiler performance, output, and emissions. This report summarizes the overall results from Phases I and II of the project. A significant amount of data was collected from the combustion sensors, coal flow monitoring equipment, and other existing boiler instrumentation to monitor performance of the burner modifications and the coal flow balancing equipment.

  20. Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements

    PubMed Central

    Mantel, Irmela

    2015-01-01

    This Perspective discusses the pertinence of variable dosing regimens with anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) with regard to real-life requirements. After the initial pivotal trials of anti-VEGF therapy, the variable dosing regimens pro re nata (PRN), Treat-and-Extend, and Observe-and-Plan, a recently introduced regimen, aimed to optimize the anti-VEGF treatment strategy for nAMD. The PRN regimen showed good visual results but requires monthly monitoring visits and can therefore be difficult to implement. Moreover, application of the PRN regimen revealed inferior results in real-life circumstances due to problems with resource allocation. The Treat-and-Extend regimen uses an interval based approach and has become widely accepted for its ease of preplanning and the reduced number of office visits required. The parallel development of the Observe-and-Plan regimen demonstrated that the future need for retreatment (interval) could be reliably predicted. Studies investigating the observe-and-plan regimen also showed that this could be used in individualized fixed treatment plans, allowing for dramatically reduced clinical burden and good outcomes, thus meeting the real life requirements. This progressive development of variable dosing regimens is a response to the real-life circumstances of limited human, technical, and financial resources. This includes an individualized treatment approach, optimization of the number of retreatments, a minimal number of monitoring visits, and ease of planning ahead. The Observe-and-Plan regimen achieves this goal with good functional results. Translational Relevance: This perspective reviews the process from the pivotal clinical trials to the development of treatment regimens which are adjusted to real life requirements. The article discusses this translational process which– although not the classical interpretation of translation from fundamental to clinical

  1. Achievement of Optimal Medical Therapy Goals for US Adults with Coronary Artery Disease: Results from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

    PubMed Central

    Brown, Todd M.; Voeks, Jenifer H.; Bittner, Vera; Brenner, David A.; Cushman, Mary; Goff, David C.; Glasser, Stephen; Muntner, Paul; Tabereaux, Paul B.; Safford, Monika M.

    2014-01-01

    Objective In a non-clinical trial setting, to determine the proportion of individuals with coronary artery disease (CAD) with optimal risk factor levels based on the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial. Background In COURAGE, the addition of percutaneous coronary intervention (PCI) to optimal medical therapy did not reduce the risk of death or myocardial infarction in stable CAD patients but resulted in more revascularization procedures. Methods REGARDS is a national prospective cohort study of 30,239 African American and White community-dwelling individuals aged >45 years enrolled in 2003-7. We calculated the proportion of 3,167 participants with self-reported CAD meeting 7 risk factor goals based on COURAGE: 1) aspirin use, 2) systolic blood pressure <130 mmHg and diastolic blood pressure <85 mmHg (<80 mmHg if diabetic), 3) low density lipoprotein cholesterol <85 mg/dL, high density lipoprotein cholesterol >40 mg/dL, and triglycerides <150 mg/dL, 4) fasting glucose <126 mg/dL, 5) nonsmoking status, 6) body mass index <25 kg/m,2 and 7) exercise ≥4 days per week. Results The mean age of participants was 69±9 years, 33% were African American, and 35% were female. Overall, the median number of goals met was 4. Less than a quarter met ≥5 of the 7 goals, and 16% met all 3 goals for aspirin, blood pressure, and LDL-C. Older age, white race, higher income, more education, and higher physical functioning were independently associated with meeting more goals. Conclusions There is substantial room for improvement in risk factor reduction among US individuals with CAD. PMID:24534599

  2. Simple subgroup approximations to optimal treatment regimes from randomized clinical trial data

    PubMed Central

    Foster, Jared C.; Taylor, Jeremy M.G.; Kaciroti, Niko; Nan, Bin

    2015-01-01

    We consider the use of randomized clinical trial (RCT) data to identify simple treatment regimes based on some subset of the covariate space, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$A$\\end{document}. The optimal subset, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\hat {A}$\\end{document}, is selected by maximizing the expected outcome under a treat-if-in-\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$A$\\end{document} regime, and is restricted to be a simple, as it is desirable that treatment decisions be made with only a limited amount of patient information required. We consider a two-stage procedure. In stage 1, non-parametric regression is used to estimate treatment effects for each subject, and in stage 2 these treatment effect estimates are used to systematically evaluate many subgroups of a simple, prespecified form to identify \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\hat {A}$\\end{document}. The proposed methods were found to perform favorably compared with two existing methods in simulations, and were applied to prehypertension data from an RCT. PMID:25398774

  3. Linear energy transfer (LET)-Guided Optimization in intensity modulated proton therapy (IMPT): feasibility study and clinical potential

    PubMed Central

    Giantsoudi, Drosoula; Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald

    2013-01-01

    Purpose To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity-modulated proton therapy (IMPT). Methods and Materials A multi-criteria optimization (MCO) module was utilized to generate series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 headand- neck and 2 pancreatic cancer cases. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs, were evaluated for each patient, based on dose- and LET-volume histograms and 3D distributions. An LET-based RBE (relative biological effectiveness) model was employed to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results Mean LET values for the target varied up to 30% among the BPs for the head-and-neck cases, and up to 14% for the pancreatic cancer cases. Variations were more prominent in organs-atrisk (OARs), where mean LET values differed by up to a factor of 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions We present a novel strategy for optimizing proton therapy to maximize doseaveraged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, utilizing both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans, and aids in identifying the clinically optimum solution

  4. Assessing eating disorder risk: the pivotal role of achievement anxiety, depression and female gender in non-clinical samples.

    PubMed

    Fragkos, Konstantinos C; Frangos, Christos C

    2013-03-01

    The objective of the present study was to assess factors predicting eating disorder risk in a sample of undergraduate students. A structured questionnaire was employed on a random sample (n = 1865) consisting of the following sections: demographics, SCOFF (Sick, Control, One stone, Fat, Food) questionnaire for screening eating disorders and the Achievement Anxiety Test and the Depression, Anxiety and Stress Scale. The students at risk for eating disorders (SCOFF score ≥2) were 39.7%. Eating disorder risk was more frequent in females, students with divorced parents, students who lived alone, students who were seeking a romantic relationship or were married, students who were at a post-secondary vocational institute/college (private-public) educational level and who were more likely to have marks under merit level. Also, the mean scores for the psychological factors of depression, stress and anxiety were higher in students with eating disorder risk. A logistic regression model was produced depicting that depression, stress, female gender, being married and searching for a romantic relationship were risk factors of having an eating disorder risk. The suggested psychological model examined with structural equation modelling signified the role of academic anxiety as an immediate precursor of general anxiety. Hence, college populations in Greece need organized infrastructures of nutrition health services and campaigns to assist in reducing the risk of eating disorders. PMID:23482057

  5. Clinical NECR in 18F-FDG PET scans: optimization of injected activity and variable acquisition time. Relationship with SNR

    NASA Astrophysics Data System (ADS)

    Carlier, T.; Ferrer, L.; Necib, H.; Bodet-Milin, C.; Rousseau, C.; Kraeber-Bodéré, F.

    2014-10-01

    The injected activity and the acquisition time per bed position for 18F-FDG PET scans are usually optimized by using metrics obtained from phantom experiments. However, optimal activity and time duration can significantly vary from a phantom set-up and from patient to patient. An approach using a patient-specific noise equivalent count rate (NECR) modelling has been previously proposed for optimizing clinical scanning protocols. We propose using the clinical NECR on a large population as a function of the body mass index (BMI) for deriving the optimal injected activity and acquisition duration per bed position. The relationship between the NEC and the signal-to-noise ratio (SNR) was assessed both in a phantom and in a clinical setting. 491 consecutive patients were retrospectively evaluated and divided into 4 BMI subgroups. Two criteria were used to optimize the injected activity and the time per bed position was adjusted using the NECR value while keeping the total acquisition time constant. Finally, the relationship between NEC and SNR was investigated using an anthropomorphic phantom and a population of 507 other patients. While the first dose regimen suggested a unique injected activity (665 MBq) regardless of the BMI, the second dose regimen proposed a variable activity and a total acquisition time according to the BMI. The NEC improvement was around 35% as compared with the local current injection rule. Variable time per bed position was derived according to BMI and anatomical region. NEC and number of true events were found to be highly correlated with SNR for the phantom set-up and partially confirmed in the patient study for the BMI subgroup under 28 kg m-2 suggesting that for the scanner, the nonlinear reconstruction algorithm used in this study and BMI < 28 kg m-2, NEC, or the number of true events linearly correlated with SNR2.

  6. Primary TKA Patients with Quantifiably Balanced Soft-Tissue Achieve Significant Clinical Gains Sooner than Unbalanced Patients

    PubMed Central

    Gustke, Kenneth A.; Golladay, Gregory J.; Roche, Martin W.; Elson, Leah C.; Anderson, Christopher R.

    2014-01-01

    Although total knee arthroplasty has a high success rate, poor outcomes and early revision are associated with ligament imbalance. This multicenter evaluation was performed in order to provide 1-year followup of a previously reported group of patients who had sensor-assisted TKA, comparing the clinical outcomes of quantitatively balanced versus unbalanced patients. At 1 year, the balanced cohort scored 179.3 and 10.4 in KSS and WOMAC, respectively; the unbalanced cohort scored 156.1 and 17.9 in KSS and WOMAC (P < 0.001; P = 0.085). The average activity level scores of quantitatively balanced patients were 68.6 (corresponding to tennis, light jogging, and heavy yard work), while the average activity level of unbalanced patients was 46.7 (corresponding to light housework, and limited walking distances) (P = 0.015). Out of all confounding variables, a balanced articulation was the most significant contributing factor to improved postoperative outcomes (P < 0.001). PMID:25210632

  7. Clinical Evaluation of Direct Aperture Optimization When Applied to Head-And-Neck IMRT

    SciTech Connect

    Jones, Stephen Williams, Matthew

    2008-04-01

    Direct Machine Parameter Optimization (DMPO) is a leaf segmentation program released as an optional item of the Pinnacle planning system (Philips Radiation Oncology Systems, Milpitas, CA); it is based on the principles of direct aperture optimization where the size, shape, and weight of individual segments are optimized to produce an intensity modulated radiation treatment (IMRT) plan. In this study, we compare DMPO to the traditional method of IMRT planning, in which intensity maps are optimized prior to conversion into deliverable multileaf collimator (MLC) apertures, and we determine if there was any dosimetric improvement, treatment efficiency gain, or planning advantage provided by the use of DMPO. Eleven head-and-neck patients treated with IMRT had treatment plans generated using each optimization method. For each patient, the same planning parameters were used for each optimization method. All calculations were performed using Pinnacle version 7.6c software and treatments were delivered using a step-and-shoot IMRT method on a Varian 2100EX linear accelerator equipped with a 120-leaf Millennium MLC (Varian Medical Systems, Palo Alto, CA). Each plan was assessed based on the calculation time, a conformity index, the composite objective value used in the optimization, the number of segments, monitor units (MUs), and treatment time. The results showed DMPO to be superior to the traditional optimization method in all areas. Considerable advantages were observed in the dosimetric quality of DMPO plans, which also required 32% less time to calculate, 42% fewer MUs, and 35% fewer segments than the conventional optimization method. These reductions translated directly into a 29% decrease in treatment times. While considerable gains were observed in planning and treatment efficiency, they were specific to our institution, and the impact of direct aperture optimization on plan quality and workflow will be dependent on the planning parameters, planning system, and

  8. Heterogeneous Optimization Framework: Reproducible Preprocessing of Multi-Spectral Clinical MRI for Neuro-Oncology Imaging Research.

    PubMed

    Milchenko, Mikhail; Snyder, Abraham Z; LaMontagne, Pamela; Shimony, Joshua S; Benzinger, Tammie L; Fouke, Sarah Jost; Marcus, Daniel S

    2016-07-01

    Neuroimaging research often relies on clinically acquired magnetic resonance imaging (MRI) datasets that can originate from multiple institutions. Such datasets are characterized by high heterogeneity of modalities and variability of sequence parameters. This heterogeneity complicates the automation of image processing tasks such as spatial co-registration and physiological or functional image analysis. Given this heterogeneity, conventional processing workflows developed for research purposes are not optimal for clinical data. In this work, we describe an approach called Heterogeneous Optimization Framework (HOF) for developing image analysis pipelines that can handle the high degree of clinical data non-uniformity. HOF provides a set of guidelines for configuration, algorithm development, deployment, interpretation of results and quality control for such pipelines. At each step, we illustrate the HOF approach using the implementation of an automated pipeline for Multimodal Glioma Analysis (MGA) as an example. The MGA pipeline computes tissue diffusion characteristics of diffusion tensor imaging (DTI) acquisitions, hemodynamic characteristics using a perfusion model of susceptibility contrast (DSC) MRI, and spatial cross-modal co-registration of available anatomical, physiological and derived patient images. Developing MGA within HOF enabled the processing of neuro-oncology MR imaging studies to be fully automated. MGA has been successfully used to analyze over 160 clinical tumor studies to date within several research projects. Introduction of the MGA pipeline improved image processing throughput and, most importantly, effectively produced co-registered datasets that were suitable for advanced analysis despite high heterogeneity in acquisition protocols. PMID:26910516

  9. Optimizing cone beam CT scatter estimation in egs-cbct for a clinical and virtual chest phantom

    SciTech Connect

    Thing, Rune Slot; Mainegra-Hing, Ernesto

    2014-07-15

    Purpose: Cone beam computed tomography (CBCT) image quality suffers from contamination from scattered photons in the projection images. Monte Carlo simulations are a powerful tool to investigate the properties of scattered photons.egs-cbct, a recent EGSnrc user code, provides the ability of performing fast scatter calculations in CBCT projection images. This paper investigates how optimization of user inputs can provide the most efficient scatter calculations. Methods: Two simulation geometries with two different x-ray sources were simulated, while the user input parameters for the efficiency improving techniques (EITs) implemented inegs-cbct were varied. Simulation efficiencies were compared to analog simulations performed without using any EITs. Resulting scatter distributions were confirmed unbiased against the analog simulations. Results: The optimal EIT parameter selection depends on the simulation geometry and x-ray source. Forced detection improved the scatter calculation efficiency by 80%. Delta transport improved calculation efficiency by a further 34%, while particle splitting combined with Russian roulette improved the efficiency by a factor of 45 or more. Combining these variance reduction techniques with a built-in denoising algorithm, efficiency improvements of 4 orders of magnitude were achieved. Conclusions: Using the built-in EITs inegs-cbct can improve scatter calculation efficiencies by more than 4 orders of magnitude. To achieve this, the user must optimize the input parameters to the specific simulation geometry. Realizing the full potential of the denoising algorithm requires keeping the statistical uncertainty below a threshold value above which the efficiency drops exponentially.

  10. SU-E-T-593: Clinical Evaluation of Direct Aperture Optimization in Head/Neck and Prostate IMRT Treatment

    SciTech Connect

    Hosini, M; GALAL, M; Emam, I; Kamal, G; Algohary, M

    2014-06-01

    Purpose: To investigate the planning and dosimetric advantages of direct aperture optimization (DAO) over beam-let optimization in IMRT treatment of head and neck (H/N) and prostate cancers. Methods: Five Head and Neck as well as five prostate patients were planned using the beamlet optimizer in Elekta-Xio ver 4.6 IMRT treatment planning system. Based on our experience in beamlet IMRT optimization, PTVs in H/N plans were prescribed to 70 Gy delivered by 7 fields. While prostate PTVs were prescribed to 76 Gy with 9 fields. In all plans, fields were set to be equally spaced. All cases were re-planed using Direct Aperture optimizer in Prowess Panther ver 5.01 IMRT planning system at same configurations and dose constraints. Plans were evaluated according to ICRU criteria, number of segments, number of monitor units and planning time. Results: For H/N plans, the near maximum dose (D2) and the dose that covers 95% D95 of PTV has improved by 4% in DAO. For organs at risk (OAR), DAO reduced the volume covered by 30% (V30) in spinal cord, right parotid, and left parotid by 60%, 54%, and 53% respectively. This considerable dosimetric quality improvement achieved using 25% less planning time and lower number of segments and monitor units by 46% and 51% respectively. In DAO prostate plans, Both D2 and D95 for the PTV were improved by only 2%. The V30 of the right femur, left femur and bladder were improved by 35%, 15% and 3% respectively. On the contrary, the rectum V30 got even worse by 9%. However, number of monitor units, and number of segments decreased by 20% and 25% respectively. Moreover the planning time reduced significantly too. Conclusion: DAO introduces considerable advantages over the beamlet optimization in regards to organs at risk sparing. However, no significant improvement occurred in most studied PTVs.

  11. A Randomized Clinical Trial to Determine Optimal Infertility Treatment in Older Couples: The Forty and Over Treatment Trial (FORT-T)

    PubMed Central

    Goldman, Marlene B.; Thornton, Kim L.; Ryley, David; Alper, Michael M.; Fung, June L.; Hornstein, Mark D.; Reindollar, Richard H.

    2014-01-01

    Objective To determine optimal infertility therapy in women at the end of their reproductive potential. Design Randomized clinical trial. Setting Academic medical centers and private infertility center in a state with mandated insurance coverage. Patients Couples with ≥ 6 months of unexplained infertility; female partner aged 38–42. Interventions Randomized to treatment with 2 cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant. Main Outcome Measures Proportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after 2 treatment cycles and at the end of treatment. Results 154 couples were randomized to receive CC/IUI (N=51), FSH/IUI (N=52), or immediate IVF (N=51); 140 (90.9%) couples initiated treatment. Cumulative clinical pregnancy rates per couple after the first 2 cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatment, 71.4% (110/154) of couples conceived a clinically recognized pregnancy and 46.1% delivered at least one live-born baby. 84.2% of all live born infants resulting from treatment were achieved from IVF. There were 36% fewer treatment cycles in the IVF arm compared to either COH/IUI arm and couples conceived a pregnancy leading to a live birth after fewer treatment cycles. Conclusions An RCT to compare treatment initiated with 2 cycles of COH/IUI to immediate IVF in older women with unexplained infertility demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group. PMID:24796764

  12. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity

    PubMed Central

    Nunan, Robert; Harding, Keith G.; Martin, Paul

    2014-01-01

    The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound – defined as a barrier defect that has not healed in 3 months – has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments. PMID:25359790

  13. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity.

    PubMed

    Nunan, Robert; Harding, Keith G; Martin, Paul

    2014-11-01

    The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound - defined as a barrier defect that has not healed in 3 months - has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments. PMID:25359790

  14. Searching ClinicalTrials.gov and the International Clinical Trials Registry Platform to inform systematic reviews: what are the optimal search approaches?*

    PubMed Central

    Glanville, Julie M.; Duffy, Steven; McCool, Rachael; Varley, Danielle

    2014-01-01

    Background: Since 2005, International Committee of Medical Journal Editors (ICMJE) member journals have required that clinical trials be registered in publicly available trials registers before they are considered for publication. Objectives: The research explores whether it is adequate, when searching to inform systematic reviews, to search for relevant clinical trials using only public trials registers and to identify the optimal search approaches in trials registers. Methods: A search was conducted in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) for research studies that had been included in eight systematic reviews. Four search approaches (highly sensitive, sensitive, precise, and highly precise) were performed using the basic and advanced interfaces in both resources. Results: On average, 84% of studies were not listed in either resource. The largest number of included studies was retrieved in ClinicalTrials.gov and ICTRP when a sensitive search approach was used in the basic interface. The use of the advanced interface maintained or improved sensitivity in 16 of 19 strategies for Clinicaltrials.gov and 8 of 18 for ICTRP. No single search approach was sensitive enough to identify all studies included in the 6 reviews. Conclusions: Trials registers cannot yet be relied upon as the sole means to locate trials for systematic reviews. Trials registers lag behind the major bibliographic databases in terms of their search interfaces. Implications: For systematic reviews, trials registers and major bibliographic databases should be searched. Trials registers should be searched using sensitive approaches, and both the registers consulted in this study should be searched. PMID:25031558

  15. [Optimization of processing and storage of clinical samples to be used for the molecular diagnosis of pertussis].

    PubMed

    Pianciola, L; Mazzeo, M; Flores, D; Hozbor, D

    2010-01-01

    Pertussis or whooping cough is an acute, highly contagious respiratory infection, which is particularly severe in infants under one year old. In classic disease, clinical diagnosis may present no difficulties. In other cases, it requires laboratory confirmation. Generally used methods are: culture, serology and PCR. For the latter, the sample of choice is a nasopharyngeal aspirate, and the simplest method for processing these samples uses proteinase K. Although results are generally satisfactory, difficulties often arise regarding the mucosal nature of the specimens. Moreover, uncertainties exist regarding the optimal conditions for sample storage. This study evaluated various technologies for processing and storing samples. Results enabled us to select a method for optimizing sample processing, with performance comparable to commercial methods and far lower costs. The experiments designed to assess the conservation of samples enabled us to obtain valuable information to guide the referral of samples from patient care centres to laboratories where such samples are processed by molecular methods. PMID:20589331

  16. Wavelength optimization for in vivo multispectral photoacoustic/ultrasound tomography of hemoglobin oxygenation in ovarian cancer: clinical studies

    NASA Astrophysics Data System (ADS)

    Salehi, Hassan S.; Li, Hai; Kumavor, Patrick D.; Merkulov, Aleksey; Sanders, Melinda; Brewer, Molly; Zhu, Quing

    2015-03-01

    In this paper, wavelength selection for multispectral photoacoustic/ultrasound tomography was optimized to obtain accurate images of hemoglobin oxygen saturation (sO2) in vivo. Although wavelengths can be selected by theoretical methods, in practice the accuracy of reconstructed images will be affected by wavelength-specific and system-specific factors such as laser source power and ultrasound transducer sensitivity. By performing photoacoustic spectroscopy of mouse tumor models using 14 different wavelengths between 710 and 840 nm, we were able to identify a wavelength set which most accurately reproduced the results obtained using all 14 wavelengths via selection criteria. In clinical studies, the optimal wavelength set was successfully used to image human ovaries in vivo and noninvasively. Although these results are specific to our co-registered photoacoustic/ultrasound imaging system, the approach we developed can be applied to other functional photoacoustic and optical imaging systems.

  17. First clinical evaluation of an atrial haemodynamic sensor lead for automatic optimization of cardiac resynchronization therapy

    PubMed Central

    Duncker, David; Delnoy, Peter Paul; Nägele, Herbert; Mansourati, Jacques; Mont, Lluís; Anselme, Frédéric; Stengel, Petra; Anselmi, Francesca; Oswald, Hanno; Leclercq, Christophe

    2016-01-01

    Aims One option to improve cardiac resynchronization therapy (CRT) responder rates lies in the optimization of pacing intervals. A haemodynamic sensor embedded in the SonRtip atrial lead measures cardiac contractility and provides a systematic automatic atrioventricular and interventricular delays optimization. This multi-centre study evaluated the safety and performance of the lead, up to 1 year. Methods and results A total of 99 patients were implanted with the system composed of the lead and a CRT-Defibrillator device. Patients were followed at 1, 3, 6, and 12 months post-implant. The primary safety objective was to demonstrate that the atrial lead complication free rate was superior to 90% at 3-months follow-up visit. A lead handling questionnaire was filled by implanting investigators. Lead electrical performances and the performance of the system to compute AV and VV delays were evaluated at each study visit over 1 year. The complication free rate at 3 months post-implant was 99.0% [95%CI 94.5–100.0%], P < 0.001. Electrical performances of the lead were adequate whatever the atrial lead position and remained stable over the study period. The optimization algorithm was able to compute AV and VV delays in 97% of patients, during >75% of the weeks. Conclusion The atrial lead is safe to implant and shows stable electrical performance over time. It therefore offers a promising tool for automatic CRT optimization to further improve responder rates to CRT. PMID:25976907

  18. View-Angle Tilting and Slice-Encoding Metal Artifact Correction for Artifact Reduction in MRI: Experimental Sequence Optimization for Orthopaedic Tumor Endoprostheses and Clinical Application

    PubMed Central

    Jungmann, Pia M.; Ganter, Carl; Schaeffeler, Christoph J.; Bauer, Jan S.; Baum, Thomas; Meier, Reinhard; Nittka, Mathias; Pohlig, Florian; Rechl, Hans; von Eisenhart-Rothe, Ruediger; Rummeny, Ernst J.; Woertler, Klaus

    2015-01-01

    Background MRI plays a major role in follow-up of patients with malignant bone tumors. However, after limb salvage surgery, orthopaedic tumor endoprostheses might cause significant metal-induced susceptibility artifacts. Purposes To evaluate the benefit of view-angle tilting (VAT) and slice-encoding metal artifact correction (SEMAC) for MRI of large-sized orthopaedic tumor endoprostheses in an experimental model and to demonstrate clinical benefits for assessment of periprosthetic soft tissue abnormalities. Methods In an experimental setting, tumor endoprostheses (n=4) were scanned at 1.5T with three versions of optimized high-bandwidth turbo-spin-echo pulse sequences: (i) standard, (ii) VAT and (iii) combined VAT and SEMAC (VAT&SEMAC). Pulse sequences included coronal short-tau-inversion-recovery (STIR), coronal T1-weighted (w), transverse T1-w and T2-w TSE sequences. For clinical evaluation, VAT&SEMAC was compared to conventional metal artifact-reducing MR sequences (conventional MR) in n=25 patients with metal implants and clinical suspicion of tumor recurrence or infection. Diameters of artifacts were measured quantitatively. Qualitative parameters were assessed on a five-point scale (1=best, 5=worst): “image distortion”, “artificial signal changes at the edges” and “diagnostic confidence”. Imaging findings were correlated with pathology. T-tests and Wilcoxon-signed rank tests were used for statistical analyses. Results The true size of the prostheses was overestimated on MRI (P<0.05). A significant reduction of artifacts was achieved by VAT (P<0.001) and VAT&SEMAC (P=0.003) compared to the standard group. Quantitative scores improved in the VAT and VAT&SEMAC group (P<0.05). On clinical MR images, artifact diameters were significantly reduced in the VAT&SEMAC-group as compared with the conventional-group (P<0.001). Distortion and artificial signal changes were reduced and diagnostic confidence improved (P<0.05). In two cases, tumor-recurrence, in

  19. Optimizing supercritical carbon dioxide in the inactivation of bacteria in clinical solid waste by using response surface methodology

    SciTech Connect

    Hossain, Md. Sohrab; Nik Ab Rahman, Nik Norulaini; Balakrishnan, Venugopal; Alkarkhi, Abbas F.M.; Ahmad Rajion, Zainul; Ab Kadir, Mohd Omar

    2015-04-15

    Highlights: • Supercritical carbon dioxide sterilization of clinical solid waste. • Inactivation of bacteria in clinical solid waste using supercritical carbon dioxide. • Reduction of the hazardous exposure of clinical solid waste. • Optimization of the supercritical carbon dioxide experimental conditions. - Abstract: Clinical solid waste (CSW) poses a challenge to health care facilities because of the presence of pathogenic microorganisms, leading to concerns in the effective sterilization of the CSW for safe handling and elimination of infectious disease transmission. In the present study, supercritical carbon dioxide (SC-CO{sub 2}) was applied to inactivate gram-positive Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, and gram-negative Escherichia coli in CSW. The effects of SC-CO{sub 2} sterilization parameters such as pressure, temperature, and time were investigated and optimized by response surface methodology (RSM). Results showed that the data were adequately fitted into the second-order polynomial model. The linear quadratic terms and interaction between pressure and temperature had significant effects on the inactivation of S. aureus, E. coli, E. faecalis, and B. subtilis in CSW. Optimum conditions for the complete inactivation of bacteria within the experimental range of the studied variables were 20 MPa, 60 °C, and 60 min. The SC-CO{sub 2}-treated bacterial cells, observed under a scanning electron microscope, showed morphological changes, including cell breakage and dislodged cell walls, which could have caused the inactivation. This espouses the inference that SC-CO{sub 2} exerts strong inactivating effects on the bacteria present in CSW, and has the potential to be used in CSW management for the safe handling and recycling-reuse of CSW materials.

  20. Validation of an optimized SPM procedure for FDG-PET in dementia diagnosis in a clinical setting

    PubMed Central

    Perani, Daniela; Della Rosa, Pasquale Anthony; Cerami, Chiara; Gallivanone, Francesca; Fallanca, Federico; Vanoli, Emilia Giovanna; Panzacchi, Andrea; Nobili, Flavio; Pappatà, Sabina; Marcone, Alessandra; Garibotto, Valentina; Castiglioni, Isabella; Magnani, Giuseppe; Cappa, Stefano F.; Gianolli, Luigi

    2014-01-01

    Diagnostic accuracy in FDG-PET imaging highly depends on the operating procedures. In this clinical study on dementia, we compared the diagnostic accuracy at a single-subject level of a) Clinical Scenarios, b) Standard FDG Images and c) Statistical Parametrical (SPM) Maps generated via a new optimized SPM procedure. We evaluated the added value of FDG-PET, either Standard FDG Images or SPM Maps, to Clinical Scenarios. In 88 patients with neurodegenerative diseases (Alzheimer's Disease—AD, Frontotemporal Lobar Degeneration—FTLD, Dementia with Lewy bodies—DLB and Mild Cognitive Impairment—MCI), 9 neuroimaging experts made a forced diagnostic decision on the basis of the evaluation of the three types of information. There was also the possibility of a decision of normality on the FDG-PET images. The clinical diagnosis confirmed at a long-term follow-up was used as the gold standard. SPM Maps showed higher sensitivity and specificity (96% and 84%), and better diagnostic positive (6.8) and negative (0.05) likelihood ratios compared to Clinical Scenarios and Standard FDG Images. SPM Maps increased diagnostic accuracy for differential diagnosis (AD vs. FTD; beta 1.414, p = 0.019). The AUC of the ROC curve was 0.67 for SPM Maps, 0.57 for Clinical Scenarios and 0.50 for Standard FDG Images. In the MCI group, SPM Maps showed the highest predictive prognostic value (mean LOC = 2.46), by identifying either normal brain metabolism (exclusionary role) or hypometabolic patterns typical of different neurodegenerative conditions. PMID:25389519

  1. [CLINICAL FEATURES AND OPTIMIZATION OF THE TREATMENT OF CHILDREN WITH COMBINATION GASTRODUODENAL PATHOLOGY AND PRIMARY HYPERTENSION].

    PubMed

    Marushco, Y V; Zlobynets, A S

    2015-01-01

    The paper present dynamic of clinical picture, daily blood pressure monitoring results and subjective assessment of functional status in children with combination of chronic gastroduodenal pathology and primary hypertension when L-carnitine used with the standard treatment regimen. PMID:26118045

  2. Variation in Patient Profiles and Outcomes in US and Non-US Subgroups of the Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX Trial

    PubMed Central

    Vaduganathan, Muthiah; Harrington, Robert A.; Stone, Gregg W.; Steg, Ph. Gabriel; Gibson, C. Michael; Hamm, Christian W.; Price, Matthew J.; Prats, Jayne; Deliargyris, Efthymios N.; Mahaffey, Kenneth W.; White, Harvey D.

    2016-01-01

    Background— The Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX trial demonstrated superiority of cangrelor in reducing ischemic events at 48 hours in patients undergoing percutaneous coronary intervention compared with clopidogrel. Methods and Results— We analyzed all patients included in the modified intention-to-treat analysis in US (n=4097; 37.4%) and non-US subgroups (n=6845; 62.6%). The US cohort was older, had a higher burden of cardiovascular risk factors, and had more frequently undergone prior cardiovascular procedures. US patients more frequently underwent percutaneous coronary intervention for stable angina (77.9% versus 46.2%). Almost all US patients (99.1%) received clopidogrel loading doses of 600 mg, whereas 40.5% of non-US patients received 300 mg. Bivalirudin was more frequently used in US patients (56.7% versus 2.9%). At 48 hours, rates of the primary composite end point were comparable in the US and non-US cohorts (5.5% versus 5.2%; P=0.53). Cangrelor reduced rates of the primary composite end point compared with clopidogrel in US (4.5% versus 6.4%; odds ratio 0.70 [95% confidence interval 0.53–0.92]) and in non-US patients (4.8% versus 5.6%; odds ratio 0.85 [95% confidence interval 0.69–1.05]; interaction P=0.26). Similarly, rates of the key secondary end point, stent thrombosis, were reduced by cangrelor in both regions. Rates of Global Use of Strategies to Open Occluded Arteries (GUSTO)–defined severe bleeding were low and not significantly increased by cangrelor in either region. Conclusions— Despite broad differences in clinical profiles and indications for percutaneous coronary intervention by region in a large global cardiovascular clinical trial, cangrelor consistently reduced rates of ischemic end points compared with clopidogrel without an excess in severe bleeding in both the US and non-US subgroups. Clinical Trial Registration— URL: http

  3. Minimal residual disease: optimal methods, timing, and clinical relevance for an individual patient.

    PubMed

    Schrappe, Martin

    2012-01-01

    After approximately 20 years of development and after several prospective clinical trials, the detection of minimal residual disease (MRD) has emerged as part of state-of-the-art diagnostics to guide the majority of contemporary treatment programs both in pediatric and adult acute lymphoblastic leukemia (ALL). For ALL, several methods of MRD analysis are available, but 2 are widely applicable. One is based on the detection of aberrant expression of leukemia specific antigens by flow cytometry and the other one uses the specific rearrangements of the TCR or Ig genes, which can be detected by quantitative PCR in the DNA of leukemic cells. In some cases with known fusion genes such as BCR/ABL, RT-PCR can be used as a third method of identifying leukemic cells by analyzing RNA in patient samples. Clinical application of such sophisticated tools in the stratification and treatment of ALL requires reliable, reproducible, and quality-assured methods to ensure patient safety. PMID:23233572

  4. Effectiveness of Music Education for the Improvement of Reading Skills and Academic Achievement in Young Poor Readers: A Pragmatic Cluster-Randomized, Controlled Clinical Trial

    PubMed Central

    Cogo-Moreira, Hugo; de Ávila, Clara Regina Brandão; Ploubidis, George B.; Mari, Jair de Jesus

    2013-01-01

    Introduction Difficulties in word-level reading skills are prevalent in Brazilian schools and may deter children from gaining the knowledge obtained through reading and academic achievement. Music education has emerged as a potential method to improve reading skills because due to a common neurobiological substratum. Objective To evaluate the effectiveness of music education for the improvement of reading skills and academic achievement among children (eight to 10 years of age) with reading difficulties. Method 235 children with reading difficulties in 10 schools participated in a five-month, randomized clinical trial in cluster (RCT) in an impoverished zone within the city of São Paulo to test the effects of music education intervention while assessing reading skills and academic achievement during the school year. Five schools were chosen randomly to incorporate music classes (n = 114), and five served as controls (n = 121). Two different methods of analysis were used to evaluate the effectiveness of the intervention: The standard method was intention-to-treat (ITT), and the other was the Complier Average Causal Effect (CACE) estimation method, which took compliance status into account. Results The ITT analyses were not very promising; only one marginal effect existed for the rate of correct real words read per minute. Indeed, considering ITT, improvements were observed in the secondary outcomes (slope of Portuguese = 0.21 [p<0.001] and slope of math = 0.25 [p<0.001]). As for CACE estimation (i.e., complier children versus non-complier children), more promising effects were observed in terms of the rate of correct words read per minute [β = 13.98, p<0.001] and phonological awareness [β = 19.72, p<0.001] as well as secondary outcomes (academic achievement in Portuguese [β = 0.77, p<0.0001] and math [β = 0.49, p<0.001] throughout the school year). Conclusion The results may be seen as promising, but they are not, in themselves

  5. Forecasting COPD hospitalization in the clinic: optimizing the chronic respiratory questionnaire

    PubMed Central

    Abascal-Bolado, Beatriz; Novotny, Paul J; Sloan, Jeff A; Karpman, Craig; Dulohery, Megan M; Benzo, Roberto P

    2015-01-01

    Purpose Forecasting hospitalization in patients with COPD has gained significant interest in the field of COPD care. There is a need to find simple tools that can help clinicians to stratify the risk of hospitalization in these patients at the time of care. The perception of quality of life has been reported to be independently associated with hospitalizations, but questionnaires are impractical for daily clinical use. Individual questions from valid questionnaires can have robust predictive abilities, as has been suggested in previous reports, as a way to use patient-reported outcomes to forecast important events like hospitalizations in COPD. Our primary aim was to assess the predictive value of individual questions from the Chronic Respiratory Questionnaire Self-Assessment Survey (CRQ-SAS) on the risk of hospitalization and to develop a clinically relevant and simple algorithm that clinicians can use in routine practice to identify patients with an increased risk of hospitalization. Patients and methods A total of 493 patients with COPD prospectively recruited from an outpatient pulmonary clinic completed the CRQ-SAS, demographic information, pulmonary function testing, and clinical outcomes. The cohort had a mean age of 70 years, was 54% male, with forced expiratory volume in 1 second percentage predicted 42.8±16.7, and modified Medical Research Council dyspnea scale score of 2±1.13. Results Our analysis validated the original CRQ-SAS domains. Importantly, recursive partitioning analysis identified three CRQ-SAS items regarding fear or panic of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms that were highly predictive of hospitalization. We propose a robust (area under the curve =0.70) but short and easy algorithm for daily clinical care to forecast hospitalizations in patients with COPD. Conclusion We identified three themes – fear of breathlessness, dyspnea with basic activities of daily living, and depressive

  6. Optimizing clopidogrel dose response: a new clinical algorithm comprising CYP2C19 pharmacogenetics and drug interactions

    PubMed Central

    Saab, Yolande B; Zeenny, Rony; Ramadan, Wijdan H

    2015-01-01

    Purpose Response to clopidogrel varies widely with nonresponse rates ranging from 4% to 30%. A reduced function of the gene variant of the CYP2C19 has been associated with lower drug metabolite levels, and hence diminished platelet inhibition. Drugs that alter CYP2C19 activity may also mimic genetic variants. The aim of the study is to investigate the cumulative effect of CYP2C19 gene polymorphisms and drug interactions that affects clopidogrel dosing, and apply it into a new clinical-pharmacogenetic algorithm that can be used by clinicians in optimizing clopidogrel-based treatment. Method Clopidogrel dose optimization was analyzed based on two main parameters that affect clopidogrel metabolite area under the curve: different CYP2C19 genotypes and concomitant drug intake. Clopidogrel adjusted dose was computed based on area under the curve ratios for different CYP2C19 genotypes when a drug interacting with CYP2C19 is added to clopidogrel treatment. A clinical-pharmacogenetic algorithm was developed based on whether clopidogrel shows 1) expected effect as per indication, 2) little or no effect, or 3) clinical features that patients experience and fit with clopidogrel adverse drug reactions. Results The study results show that all patients under clopidogrel treatment, whose genotypes are different from *1*1, and concomitantly taking other drugs metabolized by CYP2C19 require clopidogrel dose adjustment. To get a therapeutic effect and avoid adverse drug reactions, therapeutic dose of 75 mg clopidogrel, for example, should be lowered to 6 mg or increased to 215 mg in patients with different genotypes. Conclusion The implementation of clopidogrel new algorithm has the potential to maximize the benefit of clopidogrel pharmacological therapy. Clinicians would be able to personalize treatment to enhance efficacy and limit toxicity. PMID:26445541

  7. Strategies for optimizing the clinical impact of immunotherapeutic agents such as sipuleucel-T in prostate cancer.

    PubMed

    Madan, Ravi A; Schwaab, Thomas; Gulley, James L

    2012-12-01

    Sipuleucel-T is a therapeutic cancer vaccine that has shown improved survival in men with metastatic castration-resistant prostate cancer. As a first-in-class agent, it has been met with both fan-fare and controversy. A broad review of immune-based therapies may reveal the delayed clinical impact of sipuleucel-T to be a class effect. As new strategies of immune-based therapy are developed, their effects can be optimized through better understanding of how they affect disease differently from more standard therapeutics. Furthermore, combination therapy with agents that can either work synergistically with immune-activating therapies or deplete immune-regulating cells may result in more vigorous immune responses and improved clinical outcomes. In addition, therapeutic vaccines may be ideal candidates to safely combine with standard-of-care therapies because of their nonoverlapping toxicity profile. The ultimate role of immunotherapy may not be to supplant standard therapies, but rather to work in concert with them to maximize clinical benefit for patients. PMID:23221788

  8. Quantum dot nanoparticle for optimization of breast cancer diagnostics and therapy in a clinical setting.

    PubMed

    Radenkovic, Dina; Kobayashi, Hisataka; Remsey-Semmelweis, Ernö; Seifalian, Alexander M

    2016-08-01

    Breast cancer is the most common cancer in the world. Sentinel lymph node (SLN) biopsy is used for staging of axillary lymph nodes. Organic dyes and radiocolloid are currently used for SLN mapping, but expose patients to ionizing radiation, are unstable during surgery and cause local tissue damage. Quantum dots (QD) could be used for SLN mapping without the need for biopsy. Surgical resection of the primary tumor is the optimal treatment for early-diagnosed breast cancer, but due to difficulties in defining tumor margins, cancer cells often remain leading to reoccurrences. Functionalized QD could be used for image-guided tumor resection to allow visualization of cancer cells. Near Infrared QD are photostable and have improved deep tissue penetration. Slow elimination of QD raises concerns of potential accumulation. Nevertheless, promising findings with cadmium-free QD in recent in vivo studies and first in-human trial suggest huge potential for cancer diagnostic and therapy. PMID:27013132

  9. Challenges in Acute Heart Failure Clinical Management: Optimizing Care Despite Incomplete Evidence and Imperfect Drugs

    PubMed Central

    Maisel, Alan S.; Storrow, Alan B.

    2015-01-01

    Acute heart failure is a common condition associated with considerable morbidity, mortality, and cost. However, evidence-based data on treating heart failure in the acute setting are limited, and current individual treatment options have variable efficacy. The healthcare team must often individualize patient care in ways that may extend beyond available clinical guidelines. In this review, we address the question, “How do you do the best you can clinically with incomplete evidence and imperfect drugs?” Expert opinion is provided to supplement guideline-based recommendations and help address the typical challenges that are involved in the management of patients with acute heart failure. Specifically, we discuss 4 key areas that are important in the continuum of patient care: differential diagnosis and risk stratification; choice and implementation of initial therapy; assessment of the adequacy of therapy during hospitalization or observation; and considerations for discharge/transition of care. A case study is presented to highlight the decision-making process throughout each of these areas. Evidence is accumulating that should help guide patients and healthcare providers on a path to better quality of care. PMID:25679083

  10. Waiting time reduction in intravitreal clinics by optimization of appointment scheduling: balancing demand and supply

    PubMed Central

    Ugarte, Marta

    2015-01-01

    This study was designed guided by the Model for Improvement framework to reduce waiting times and visit duration in the intravitreal therapy clinic, while improving patient and staff experience. In our aim to provide good quality, patient-centred care and constantly improve, we optimised the appointment profile and patient flow. We involved a multidisciplinary team (one consultant, junior doctors, staff nurses, technicians, and receptionist), as well as patients and relatives, to try to understand the main delays in the clinic. Process mapping, a fishbone diagram, run charts, together with feedback from patients and staff, provided an insight on the possible roots of the delays experienced by our patients. The results of the inquiry led us to take actions focused on optimising appointment scheduling. After implementing the new scheduling profile (with a gap in the middle of the session), various cycles of plan-do-study-act and a comparative, qualitative study by interviewing 10 patients demonstrated that the waiting times decreased, and patients and staff experience improved. PMID:26734454

  11. Waiting time reduction in intravitreal clinics by optimization of appointment scheduling: balancing demand and supply.

    PubMed

    Ugarte, Marta

    2015-01-01

    This study was designed guided by the Model for Improvement framework to reduce waiting times and visit duration in the intravitreal therapy clinic, while improving patient and staff experience. In our aim to provide good quality, patient-centred care and constantly improve, we optimised the appointment profile and patient flow. We involved a multidisciplinary team (one consultant, junior doctors, staff nurses, technicians, and receptionist), as well as patients and relatives, to try to understand the main delays in the clinic. Process mapping, a fishbone diagram, run charts, together with feedback from patients and staff, provided an insight on the possible roots of the delays experienced by our patients. The results of the inquiry led us to take actions focused on optimising appointment scheduling. After implementing the new scheduling profile (with a gap in the middle of the session), various cycles of plan-do-study-act and a comparative, qualitative study by interviewing 10 patients demonstrated that the waiting times decreased, and patients and staff experience improved. PMID:26734454

  12. Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management

    PubMed Central

    O’Driscoll, Tristan; Crank, Christopher W

    2015-01-01

    Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections. PMID:26244026

  13. Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management.

    PubMed

    O'Driscoll, Tristan; Crank, Christopher W

    2015-01-01

    Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections. PMID:26244026

  14. Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

    PubMed Central

    Wei, Datsen George; Chiang, Vicki; Fyne, Elizabeth; Balakrishnan, Mini; Barnes, Tiffany; Graupe, Michael; Hesselgesser, Joseph; Irrinki, Alivelu; Murry, Jeffrey P.; Stepan, George; Stray, Kirsten M.; Tsai, Angela; Yu, Helen; Spindler, Jonathan; Kearney, Mary; Spina, Celsa A.; McMahon, Deborah; Lalezari, Jacob; Sloan, Derek; Mellors, John; Geleziunas, Romas; Cihlar, Tomas

    2014-01-01

    Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 µM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART. PMID:24722454

  15. Optimizing Perfusion-Decellularization Methods of Porcine Livers for Clinical-Scale Whole-Organ Bioengineering

    PubMed Central

    Zhou, Yong-jie; Wang, Yu-jia; Du, Zheng-gui; Shi, Yu-jun; Li, Li; Bu, Hong

    2015-01-01

    Aim. To refine the decellularization protocol of whole porcine liver, which holds great promise for liver tissue engineering. Methods. Three decellularization methods for porcine livers (1% sodium dodecyl sulfate (SDS), 1% Triton X-100 + 1% sodium dodecyl sulfate, and 1% sodium deoxycholate + 1% sodium dodecyl sulfate) were studied. The obtained liver scaffolds were processed for histology, residual cellular content analysis, and extracellular matrix (ECM) components evaluation to investigate decellularization efficiency and ECM preservation. Rat primary hepatocytes were seeded into three kinds of scaffold to detect the biocompatibility. Results. The whole liver decellularization was successfully achieved following all three kinds of treatment. SDS combined with Triton had a high efficacy of cellular removal and caused minimal disruption of essential ECM components; it was also the most biocompatible procedure for primary hepatocytes. Conclusion. We have refined a novel, standardized, time-efficient, and reproducible protocol for the decellularization of whole liver which can be further adapted to liver tissue engineering. PMID:25918720

  16. [Clinical pharmacokinetics and practical consequences of optimal use of medroxyprogesterone acetate].

    PubMed

    Etienne, M C; Milano, G; Namer, M

    1993-05-01

    Medroxyprogesterone acetate (MPA) is one of the major drugs used in endocrine therapy for advanced breast cancer. However, its optimal dose is still not clearly established. Response to treatment and drug-related side effects were analyzed as a function of plasma MPA concentrations during prolonged MPA administration. MPA plasma concentrations were measured (HPLC assay) at steady state (Css min) in 129 patients (mean age 63 years, 34-87) treated by MPA (111 being treated orally exclusively, with daily doses ranging from 400 to 2000 mg). A wide inter-patient variability was noted in MPA Css min for the 70 patients receiving 1000 mg/day per os: median 51 ng/ml, range 10-269 ng/ml. Intra-patient analysis of the evolution of MPA Css min during prolonged treatment showed relative stability of MPA concentrations (mean coefficient of variation = 21%). A weak but nevertheless significant correlation was demonstrated between oral doses and MPA Css min (P = 0.016). Thirty-five percent of patients (45/129) developed MPA-related side effects which were associated with the highest plasma MPA concentrations: medians were 81 and 32 ng/ml for toxic and non-toxic treatments respectively (P < 0.001). Moreover, the cumulative incidence of side-effects constantly increases with the elevation of Css min. Objective response was assessable in 55 patients treated by MPA exclusively. Plasma MPA concentrations were significantly different between patients with PD and those with either CR, PR or SD: medians were 46 and 65 ng/ml respectively (P = 0.025). The cumulative incidence of objective response increases up to 70 ng/ml. Analysis of toxicity and response as a function of the oral dose did not reveal any significant relationship. These data suggested an optimal therapeutic window for MPA Css min located within 50-70 ng/ml. This study demonstrates that, as opposed to the administered dose, plasma MPA concentration is a determining factor for toxicity and response to therapy. PMID:8173196

  17. Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Baran, Christine; Honari, Golara; Lohser, Sara; Kyei, Angela; Bailin, Philip; Pogue, Brian W.

    2009-02-01

    Nonmelanoma skin carcinomas are the most common of all human cancers. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) has been used to treat these tumors, but has shown variable results. We are pursuing a multifaceted approach toward optimizing tumor responsiveness. First, a new paradigm is being developed in which tumors are pretreated with differentiation-inducing agents, e.g. methotrexate or Vitamin D, to enhance synthesis of protoporphyrin IX (PpIX) and improve tumor cell killing upon exposure to 635 nm light. This principle was first elucidated in cell culture studies, and has now been shown to hold true for murine skin tumors, and for a human subcutaneous tumor model (A431 cells injected in nude mice). Clinical trials to test methotrexate and Vitamin D as augmenting agents for ALA-PDT of nonmelanoma skin cancer are being designed. Second, better methods to measure PpIX in patients' skin tumors in real time are being developed. In a clinical study to measure PpIX in patients with dysplastic skin lesions, in vivo fluorescence dosimetry was used to measure the accumulation of PpIX over time, and revealed that intralesional PpIX may reach clinically-useful levels earlier than previously thought for the treatment of actinic keratoses. In a second clinical study to examine depth of PpIX production in nonmelanoma skin cancer, the depth of PpIX within BCC tumors was found at relatively deep levels (>1 mm) in some tumor nests, but not in others. Production of PpIX in deep squamous cell carcinoma was very low. In summary, molecular approaches such as differentiation therapy to enhance ALA-PDT for individual patients may ultimately be needed to help to improve skin cancer responses to this modality.

  18. Optimization of Brain T2 Mapping Using Standard CPMG Sequence In A Clinical Scanner

    NASA Astrophysics Data System (ADS)

    Hnilicová, P.; Bittšanský, M.; Dobrota, D.

    2014-04-01

    In magnetic resonance imaging, transverse relaxation time (T2) mapping is a useful quantitative tool enabling enhanced diagnostics of many brain pathologies. The aim of our study was to test the influence of different sequence parameters on calculated T2 values, including multi-slice measurements, slice position, interslice gap, echo spacing, and pulse duration. Measurements were performed using standard multi-slice multi-echo CPMG imaging sequence on a 1.5 Tesla routine whole body MR scanner. We used multiple phantoms with different agarose concentrations (0 % to 4 %) and verified the results on a healthy volunteer. It appeared that neither the pulse duration, the size of interslice gap nor the slice shift had any impact on the T2. The measurement accuracy was increased with shorter echo spacing. Standard multi-slice multi-echo CPMG protocol with the shortest echo spacing, also the smallest available interslice gap (100 % of slice thickness) and shorter pulse duration was found to be optimal and reliable for calculating T2 maps in the human brain.

  19. A Clinical Pitfall: Optimal Management of Single Dural-based Metastatic Carcinoma of the Breast Mimicking Meningioma.

    PubMed

    Li, Chiao-Zhu; Li, Chiao-Ching; Lin, Meng-Chi; Chih-Chuan, Hsieh; Chen, Nan-Fu; Chen, Chun-Lin; Tang, Chi-Tun

    2015-11-01

    Meningioma is the most common benign brain lesion in adults. Conservative treatment is suggested if there is no obvious neurological symptom or mass effect, but cerebral metastases require aggressive therapy. Single dural-based metastatic carcinoma mimicking meningioma is uncommon. Here is a case of clinical dilemma between meningioma and metastatic carcinoma mimicking meningioma. A woman with a history of invasive ductal carcinoma of the breast presented with headache and blurred vision. Brain computed tomography and magnetic resonance imaging (MRI) both gave the impression of meningioma. After surgical resection of the brain lesion, histopathology revealed that it was a metastatic lesion from the breast. This report discussed the optimal management of single dural-based metastatic carcinoma mimicking meningioma. PMID:26566041

  20. ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice?

    PubMed

    Girard, Nicolas; Audigier-Valette, Clarisse; Cortot, Alexis B; Mennecier, Bertrand; Debieuvre, Didier; Planchard, David; Zalcman, Gérard; Moro-Sibilot, Denis; Cadranel, Jacques; Barlési, Fabrice

    2015-02-01

    Crizotinib (XALKORI™, Pfizer) is a tyrosine kinase inhibitor targeting ALK, MET and ROS1, currently approved for the treatment of adults with ALK-rearranged non-small-cell lung cancer. Optimizing the management of frequent crizotinib-related adverse events is crucial to ensure its continuous administration and reproduce the response and survival rates reported in clinical trials. Here, we propose some practical measures, which are mostly derived from the recommendations given to the investigators of the PROFILE 1001, 1005, 1007 and 1014 trials and are based on experience and scientific findings regarding the management of these disorders. While visual disturbances or bradycardia are frequent but benign, the severity of the cardiac and hepatic adverse events requires special attention potential to QT interval prolongations and to the monitoring of electrolyte levels and liver function, taking into account potential drug-drug interactions. PMID:25413260

  1. Optimized magnetic resonance diffusion protocol for ex-vivo whole human brain imaging with a clinical scanner

    NASA Astrophysics Data System (ADS)

    Scherrer, Benoit; Afacan, Onur; Stamm, Aymeric; Singh, Jolene; Warfield, Simon K.

    2015-03-01

    Diffusion-weighted magnetic resonance imaging (DW-MRI) provides a novel insight into the brain to facilitate our understanding of the brain connectivity and microstructure. While in-vivo DW-MRI enables imaging of living patients and longitudinal studies of brain changes, post-mortem ex-vivo DW-MRI has numerous advantages. Ex-vivo imaging benefits from greater resolution and sensitivity due to the lack of imaging time constraints; the use of tighter fitting coils; and the lack of movement artifacts. This allows characterization of normal and abnormal tissues with unprecedented resolution and sensitivity, facilitating our ability to investigate anatomical structures that are inaccessible in-vivo. This also offers the opportunity to develop today novel imaging biomarkers that will, with tomorrow's MR technology, enable improved in-vivo assessment of the risk of disease in an individual. Post-mortem studies, however, generally rely on the fixation of specimen to inhibit tissue decay which starts as soon as tissue is deprived from its blood supply. Unfortunately, fixation of tissues substantially alters tissue diffusivity profiles. In addition, ex-vivo DW-MRI requires particular care when packaging the specimen because the presence of microscopic air bubbles gives rise to geometric and intensity image distortion. In this work, we considered the specific requirements of post-mortem imaging and designed an optimized protocol for ex-vivo whole brain DW-MRI using a human clinical 3T scanner. Human clinical 3T scanners are available to a large number of researchers and, unlike most animal scanners, have a bore diameter large enough to image a whole human brain. Our optimized protocol will facilitate widespread ex-vivo investigations of large specimen.

  2. Thrombin generation assay: a new tool to predict and optimize clinical outcome in cardiovascular patients?

    PubMed

    Campo, Gianluca; Pavasini, Rita; Pollina, Alberto; Fileti, Luca; Marchesini, Jlenia; Tebaldi, Matteo; Ferrari, Roberto

    2012-12-01

    Antithrombotic therapy (including antiplatelet and anticoagulant drugs) is the cornerstone of the current medical treatment of patients with acute coronary syndromes (ACS). This therapy and particularly the new antiplatelet and anticoagulant drugs have significantly reduced the ischemic risk, but have increased bleeding complications. Recently, several studies have emphasized the negative prognostic impact on long-term mortality of these bleeding adverse events. Thus, new assays to estimate the bleeding risk and the efficacy of these antithrombotic drugs are clearly in demand. Regarding the anticoagulant drugs, new promising data have emerged about the thrombin generation assay (TGA). TGA measures the ability of plasma to generate thrombin. TGA may be used to check coagulation function, to value risk of thrombosis and to compare the efficacy of different anticoagulants employed in clinical management of patients with ACS. The TGA result is a curve which describes the variation of thrombin's amount during the activation of the coagulation cascade. All available anticoagulant drugs influence the principal parameters generated by TGA and so it is possible to evaluate the effects of the medical treatment. In this review we provide a brief description of the assay and we summarize the principals of previous studies by analyzing the relationship between anticoagulant drugs and TGA. Moreover, a brief summary of its ability to predict ischemic and bleeding risks has been provided. PMID:22688556

  3. Optimizing clinical trial design for multiple system atrophy: lessons from the rifampicin study.

    PubMed

    Singer, Wolfgang; Low, Phillip A

    2015-02-01

    Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by autonomic failure and parkinsonism/ataxia; no treatment exists to slow disease progression. A number of factors have prevented or compromised trials targeting disease modification. A major hurdle has been uncertainty about the number of patients needed to achieve adequate power. Information based on natural history studies suggested such numbers to be so large that only international multi-center models seemed feasible. When designing the rifampicin trial in MSA we sought to identify and apply strategies that would improve power and reduce the number needed to treat to allow for an oligocenter approach. Strategies included: (1) inclusion/exclusion criteria designed to enroll patients with relatively early, actively progressing disease; (2) minimizing dropouts; (3) pre-defined interim analysis; and (4) approaches to reduce scoring variability. The model allowed for the number needed to treat to be only 50 patients per treatment arm. Ten selected sites managed to reach the recruitment goal within 12 months. The dropout rate was less than 10%, and the goal of enrolling patients with actively progressing disease was accomplished as reflected by the progression rate in the placebo group. Data from this unfortunately negative trial can now be effectively used to more realistically power future trials. A number of ways to further improve trial design and feasibility have been identified and include rigorous site selection and training, designated primary site investigators, improved error trapping, early site visits, remedial training, and future biomarkers for earlier diagnosis and tracking of disease progression. PMID:25763826

  4. Optimization and Scale-up Culture of Human Endometrial Multipotent Mesenchymal Stromal Cells: Potential for Clinical Application

    PubMed Central

    Rajaraman, Gayathri; White, Jacinta; Tan, Ker Sin; Ulrich, Daniela; Rosamilia, Anna; Werkmeister, Jerome

    2013-01-01

    We have previously identified and purified multipotent mesenchymal stromal cell (MSC)-like cells in the highly regenerative endometrial lining of the human uterus (eMSC) as CD140b+CD146+ cells. Due to ease of accessibility with minimal morbidity via biopsy, we are proposing to use eMSC in cell-based therapies; however, culture conditions compliant with Good Manufacturing Practice have not been established for eMSC. The aim of this study was to optimize serum-free and xeno-free culture conditions for expansion of eMSC for potential clinical use. Real-time cell assessment (Xcelligence) and MTS viability assays were used to measure attachment and proliferation of freshly isolated, flow cytometry-sorted CD140b+CD146+ eMSC cultured in several commercially available and in-house serum-free and xeno-free media in combination with five attachment matrices (fibronectin, collagen, gelatin, laminin, and Cell Start-XF®). Comparisons were made with a standard serum-containing medium, DMEM/F-12/10% fetal bovine serum. Under all conditions examined, eMSC attachment and proliferation was greatest using a fibronectin matrix, with Lonza TP-SF® and our in-house DMEM/SF/FGF2/EGF serum-free xeno-product-containing medium similar to serum-containing medium. Hypoxia increased eMSC proliferation in the DMEM/SF/FGF2/EGF serum-free medium. Culture of eMSC for 7 days on a fibronectin matrix in DMEM/SF/FGF2/EGF serum-free media in 5% O2 maintained greater numbers of undifferentiated eMSC expressing CD140b, CD146, and W5C5 compared to culture under similar conditions in Lonza TP-SF medium. However, the percentage of cells expressing typical MSC phenotypic markers, CD29, CD44, CD73, and CD105, were similar for both media. EMSC showed greater expansion in 2D compared to 3D culture on fibronectin-coated microbeads using the optimized DMEM/SF/FGF2/EGF medium in 5% O2. In the optimized 2D culture conditions, eMSC retained CFU activity, multipotency, and MSC surface phenotype, representing the

  5. Optimization and scale-up culture of human endometrial multipotent mesenchymal stromal cells: potential for clinical application.

    PubMed

    Rajaraman, Gayathri; White, Jacinta; Tan, Ker Sin; Ulrich, Daniela; Rosamilia, Anna; Werkmeister, Jerome; Gargett, Caroline E

    2013-01-01

    We have previously identified and purified multipotent mesenchymal stromal cell (MSC)-like cells in the highly regenerative endometrial lining of the human uterus (eMSC) as CD140b⁺CD146⁺ cells. Due to ease of accessibility with minimal morbidity via biopsy, we are proposing to use eMSC in cell-based therapies; however, culture conditions compliant with Good Manufacturing Practice have not been established for eMSC. The aim of this study was to optimize serum-free and xeno-free culture conditions for expansion of eMSC for potential clinical use. Real-time cell assessment (Xcelligence) and MTS viability assays were used to measure attachment and proliferation of freshly isolated, flow cytometry-sorted CD140b⁺CD146⁺ eMSC cultured in several commercially available and in-house serum-free and xeno-free media in combination with five attachment matrices (fibronectin, collagen, gelatin, laminin, and Cell Start-XF®). Comparisons were made with a standard serum-containing medium, DMEM/F-12/10% fetal bovine serum. Under all conditions examined, eMSC attachment and proliferation was greatest using a fibronectin matrix, with Lonza TP-SF® and our in-house DMEM/SF/FGF2/EGF serum-free xeno-product-containing medium similar to serum-containing medium. Hypoxia increased eMSC proliferation in the DMEM/SF/FGF2/EGF serum-free medium. Culture of eMSC for 7 days on a fibronectin matrix in DMEM/SF/FGF2/EGF serum-free media in 5% O₂ maintained greater numbers of undifferentiated eMSC expressing CD140b, CD146, and W5C5 compared to culture under similar conditions in Lonza TP-SF medium. However, the percentage of cells expressing typical MSC phenotypic markers, CD29, CD44, CD73, and CD105, were similar for both media. EMSC showed greater expansion in 2D compared to 3D culture on fibronectin-coated microbeads using the optimized DMEM/SF/FGF2/EGF medium in 5% O₂. In the optimized 2D culture conditions, eMSC retained CFU activity, multipotency, and MSC surface phenotype

  6. Availability of color calibration for consistent color display in medical images and optimization of reference brightness for clinical use

    NASA Astrophysics Data System (ADS)

    Iwai, Daiki; Suganami, Haruka; Hosoba, Minoru; Ohno, Kazuko; Emoto, Yutaka; Tabata, Yoshito; Matsui, Norihisa

    2013-03-01

    Color image consistency has not been accomplished yet except the Digital Imaging and Communication in Medicine (DICOM) Supplement 100 for implementing a color reproduction pipeline and device independent color spaces. Thus, most healthcare enterprises could not check monitor degradation routinely. To ensure color consistency in medical color imaging, monitor color calibration should be introduced. Using simple color calibration device . chromaticity of colors including typical color (Red, Green, Blue, Green and White) are measured as device independent profile connection space value called u'v' before and after calibration. In addition, clinical color images are displayed and visual differences are observed. In color calibration, monitor brightness level has to be set to quite lower value 80 cd/m2 according to sRGB standard. As Maximum brightness of most color monitors available currently for medical use have much higher brightness than 80 cd/m2, it is not seemed to be appropriate to use 80 cd/m2 level for calibration. Therefore, we propose that new brightness standard should be introduced while maintaining the color representation in clinical use. To evaluate effects of brightness to chromaticity experimentally, brightness level is changed in two monitors from 80 to 270cd/m2 and chromaticity value are compared with each brightness levels. As a result, there are no significant differences in chromaticity diagram when brightness levels are changed. In conclusion, chromaticity is close to theoretical value after color calibration. Moreover, chromaticity isn't moved when brightness is changed. The results indicate optimized reference brightness level for clinical use could be set at high brightness in current monitors .

  7. Optimization of self-coherent reflective PON to achieve a new record 42 dB ODN power budget after 100 km at 1.25 Gbps.

    PubMed

    Straullu, S; Forghieri, F; Ferrero, V; Gaudino, R

    2012-12-31

    We demonstrate a greater than 42 dB optical distribution network power budget in the upstream of a 1.25 Gbps self-coherent reflective PON after 100 km of installed fibers, using off-the-shelf optoelectronic components, improving our previous result by 4 dB. We discuss all system optimizations introduced in the setup in order to reach such a result, including 8B/10B high-pass filtering and Faraday rotation at the ONU. PMID:23388785

  8. Appraising Reading Achievement.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    To determine quality sequence in pupil progress, evaluation approaches need to be used which guide the teacher to assist learners to attain optimally. Teachers must use a variety of procedures to appraise student achievement in reading, because no one approach is adequate. Appraisal approaches might include: (1) observation and subsequent…

  9. Optimizing supercritical carbon dioxide in the inactivation of bacteria in clinical solid waste by using response surface methodology.

    PubMed

    Hossain, Md Sohrab; Nik Ab Rahman, Nik Norulaini; Balakrishnan, Venugopal; Alkarkhi, Abbas F M; Ahmad Rajion, Zainul; Ab Kadir, Mohd Omar

    2015-04-01

    Clinical solid waste (CSW) poses a challenge to health care facilities because of the presence of pathogenic microorganisms, leading to concerns in the effective sterilization of the CSW for safe handling and elimination of infectious disease transmission. In the present study, supercritical carbon dioxide (SC-CO2) was applied to inactivate gram-positive Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, and gram-negative Escherichia coli in CSW. The effects of SC-CO2 sterilization parameters such as pressure, temperature, and time were investigated and optimized by response surface methodology (RSM). Results showed that the data were adequately fitted into the second-order polynomial model. The linear quadratic terms and interaction between pressure and temperature had significant effects on the inactivation of S. aureus, E. coli, E. faecalis, and B. subtilis in CSW. Optimum conditions for the complete inactivation of bacteria within the experimental range of the studied variables were 20 MPa, 60 °C, and 60 min. The SC-CO2-treated bacterial cells, observed under a scanning electron microscope, showed morphological changes, including cell breakage and dislodged cell walls, which could have caused the inactivation. This espouses the inference that SC-CO2 exerts strong inactivating effects on the bacteria present in CSW, and has the potential to be used in CSW management for the safe handling and recycling-reuse of CSW materials. PMID:25636860

  10. Wharton’s Jelly-Derived Mesenchymal Stem Cells: Phenotypic Characterization and Optimizing Their Therapeutic Potential for Clinical Applications

    PubMed Central

    Kim, Dae-Won; Staples, Meaghan; Shinozuka, Kazutaka; Pantcheva, Paolina; Kang, Sung-Don; Borlongan, Cesar V.

    2013-01-01

    Wharton’s jelly (WJ) is a gelatinous tissue within the umbilical cord that contains myofibroblast-like stromal cells. A unique cell population of WJ that has been suggested as displaying the stemness phenotype is the mesenchymal stromal cells (MSCs). Because MSCs’ stemness and immune properties appear to be more robustly expressed and functional which are more comparable with fetal than adult-derived MSCs, MSCs harvested from the “young” WJ are considered much more proliferative, immunosuppressive, and even therapeutically active stem cells than those isolated from older, adult tissue sources such as the bone marrow or adipose. The present review discusses the phenotypic characteristics, therapeutic applications, and optimization of experimental protocols for WJ-derived stem cells. MSCs derived from WJ display promising transplantable features, including ease of sourcing, in vitro expandability, differentiation abilities, immune-evasion and immune-regulation capacities. Accumulating evidence demonstrates that WJ-derived stem cells possess many potential advantages as transplantable cells for treatment of various diseases (e.g., cancer, chronic liver disease, cardiovascular diseases, nerve, cartilage and tendon injury). Additional studies are warranted to translate the use of WJ-derived stem cells for clinical applications. PMID:23727936

  11. Optimizing pulmonary rehabilitation in chronic obstructive pulmonary disease--practical issues: a Canadian Thoracic Society Clinical Practice Guideline.

    PubMed

    Marciniuk, Darcy D; Brooks, Dina; Butcher, Scott; Debigare, Richard; Dechman, Gail; Ford, Gordon; Pepin, Veronique; Reid, Darlene; Sheel, Andrew W; Stickland, Micheal K; Todd, David C; Walker, Shannon L; Aaron, Shawn D; Balter, Meyer; Bourbeau, Jean; Hernandez, Paul; Maltais, Francois; O'Donnell, Denis E; Bleakney, Donna; Carlin, Brian; Goldstein, Roger; Muthuri, Stella K

    2010-01-01

    Pulmonary rehabilitation (PR) participation is the standard of care for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite bronchodilator therapies. However, there are questions about specific aspects of PR programming including optimal site of rehabilitation delivery, components of rehabilitation programming, duration of rehabilitation, target populations and timing of rehabilitation. The present document was compiled to specifically address these important clinical issues, using an evidence-based, systematic review process led by a representative interprofessional panel of experts. The evidence reveals there are no differences in major patient-related outcomes of PR between nonhospital- (community or home sites) or hospital-based sites. There is strong support to recommend that COPD patients initiate PR within one month following an acute exacerbation due to benefits of improved dyspnea, exercise tolerance and health-related quality of life relative to usual care. Moreover, the benefits of PR are evident in both men and women, and in patients with moderate, severe and very severe COPD. The current review also suggests that longer PR programs, beyond six to eight weeks duration, be provided for COPD patients, and that while aerobic training is the foundation of PR, endurance and functional ability may be further improved with both aerobic and resistance training. PMID:20808973

  12. Key signaling pathways in the muscle-invasive bladder carcinoma: Clinical markers for disease modeling and optimized treatment.

    PubMed

    Kiselyov, Alex; Bunimovich-Mendrazitsky, Svetlana; Startsev, Vladimir

    2016-06-01

    In this review, we evaluate key molecular pathways and markers of muscle-invasive bladder cancer (MIBC). Overexpression and activation of EGFR, p63, and EMT genes are suggestive of basal MIBC subtype generally responsive to chemotherapy. Alterations in PPARγ, ERBB2/3, and FGFR3 gene products and their signaling along with deregulated p53, cytokeratins KRT5/6/14 in combination with the cellular proliferation (Ki-67), and cell cycle markers (p16) indicate the need for more radical treatment protocols. Similarly, the "bell-shape" dynamics of Shh expression levels may suggest aggressive MIBC. A panel of diverse biological markers may be suitable for simulation studies of MIBC and development of an optimized treatment protocol. We conducted a critical evaluation of PubMed/Medline and SciFinder databases related to MIBC covering the period 2009-2015. The free-text search was extended by adding the following keywords and phrases: bladder cancer, metastatic, muscle-invasive, basal, luminal, epithelial-to-mesenchymal transition, cancer stem cell, mutations, immune response, signaling, biological markers, molecular markers, mathematical models, simulation, epigenetics, transmembrane, transcription factor, kinase, predictor, prognosis. The resulting selection of ca 500 abstracts was further analyzed in order to select the latest publications relevant to MIBC molecular markers of immediate clinical significance. PMID:26547270

  13. A Study of the Pre-Licensure Nursing Students' Perception of the Simulation Learning Environment as Helpful in Achieving Clinical Competencies and Their Perception of the Impact of the Level of Fidelity

    ERIC Educational Resources Information Center

    Crary, Wendy M.

    2012-01-01

    The research question of this study was: to what degree do nursing students perceive using the High Fidelity Simulation (HFS) learning environment to be helpful in their ability to achieve clinical competency. The research sub-questions (7) explored the students' demographics as an influence on rating of reality and helpfulness and the…

  14. The content of African diets is adequate to achieve optimal efficacy with fixed-dose artemether-lumefantrine: a review of the evidence

    PubMed Central

    Premji, Zulfiqarali G; Abdulla, Salim; Ogutu, Bernhards; Ndong, Alice; Falade, Catherine O; Sagara, Issaka; Mulure, Nathan; Nwaiwu, Obiyo; Kokwaro, Gilbert

    2008-01-01

    A fixed-dose combination of artemether-lumefantrine (AL, Coartem®) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat. As the fat content of sub-Saharan African meals is approximately a third that of Western countries, it raises the question of whether fat consumption by African patients is sufficient for good efficacy. Data from healthy volunteers have indicated that drinking 36 mL soya milk (containing only 1.2 g of fat) results in 90% of the lumefantrine absorption obtained with 500 mL milk (16 g fat). African diets are typically based on a carbohydrate staple (starchy root vegetables, fruit [plantain] or cereals) supplemented by soups, relishes and sauces derived from vegetables, pulses, nuts or fish. The most important sources of dietary fat in African countries are oil crops (e.g. peanuts, soya beans) and cooking oils as red palm, peanut, coconut and sesame oils. Total fat intake in the majority of subSaharan countries is estimated to be in the range 30–60 g/person/day across the whole population (average 43 g/person/day). Breast-feeding of infants up to two years of age is standard, with one study estimating a fat intake of 15–30 g fat/day from breast milk up to the age of 18 months. Weaning foods typically contain low levels of fat, and the transition from breast milk to complete weaning is associated with a marked reduction in dietary fat. Nevertheless, fat intake >10 g/day has been reported in young children post-weaning. A randomized trial in Uganda reported no difference in the efficacy of AL between patients receiving supervised meals with a fixed fat content (~23 g fat) or taking AL unsupervised, suggesting that fat intake at home was sufficient for optimal efficacy. Moreover, randomized trials in African children aged 5–59 months have shown similar high cure rates to those observed

  15. The content of African diets is adequate to achieve optimal efficacy with fixed-dose artemether-lumefantrine: a review of the evidence.

    PubMed

    Premji, Zulfiqarali G; Abdulla, Salim; Ogutu, Bernhards; Ndong, Alice; Falade, Catherine O; Sagara, Issaka; Mulure, Nathan; Nwaiwu, Obiyo; Kokwaro, Gilbert

    2008-01-01

    A fixed-dose combination of artemether-lumefantrine (AL, Coartem(R)) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat.As the fat content of sub-Saharan African meals is approximately a third that of Western countries, it raises the question of whether fat consumption by African patients is sufficient for good efficacy. Data from healthy volunteers have indicated that drinking 36 mL soya milk (containing only 1.2 g of fat) results in 90% of the lumefantrine absorption obtained with 500 mL milk (16 g fat). African diets are typically based on a carbohydrate staple (starchy root vegetables, fruit [plantain] or cereals) supplemented by soups, relishes and sauces derived from vegetables, pulses, nuts or fish. The most important sources of dietary fat in African countries are oil crops (e.g. peanuts, soya beans) and cooking oils as red palm, peanut, coconut and sesame oils. Total fat intake in the majority of subSaharan countries is estimated to be in the range 30-60 g/person/day across the whole population (average 43 g/person/day). Breast-feeding of infants up to two years of age is standard, with one study estimating a fat intake of 15-30 g fat/day from breast milk up to the age of 18 months. Weaning foods typically contain low levels of fat, and the transition from breast milk to complete weaning is associated with a marked reduction in dietary fat. Nevertheless, fat intake >10 g/day has been reported in young children post-weaning. A randomized trial in Uganda reported no difference in the efficacy of AL between patients receiving supervised meals with a fixed fat content (~23 g fat) or taking AL unsupervised, suggesting that fat intake at home was sufficient for optimal efficacy. Moreover, randomized trials in African children aged 5-59 months have shown similar high cure rates to those observed in

  16. [Achievement of therapeutic objectives].

    PubMed

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. PMID:25043543

  17. Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

    PubMed

    Moorthy, V S; Diggs, C; Ferro, S; Good, M F; Herrera, S; Hill, A V; Imoukhuede, E B; Kumar, S; Loucq, C; Marsh, K; Ockenhouse, C F; Richie, T L; Sauerwein, R W

    2009-09-25

    Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes. PMID:19654061

  18. Dosimetry robustness with stochastic optimization

    NASA Astrophysics Data System (ADS)

    Nohadani, Omid; Seco, Joao; Martin, Benjamin C.; Bortfeld, Thomas

    2009-06-01

    All radiation therapy treatment planning relies on accurate dose calculation. Uncertainties in dosimetric prediction can significantly degrade an otherwise optimal plan. In this work, we introduce a robust optimization method which handles dosimetric errors and warrants for high-quality IMRT plans. Unlike other dose error estimations, we do not rely on the detailed knowledge about the sources of the uncertainty and use a generic error model based on random perturbation. This generality is sought in order to cope with a large variety of error sources. We demonstrate the method on a clinical case of lung cancer and show that our method provides plans that are more robust against dosimetric errors and are clinically acceptable. In fact, the robust plan exhibits a two-fold improved equivalent uniform dose compared to the non-robust but optimized plan. The achieved speedup will allow computationally extensive multi-criteria or beam-angle optimization approaches to warrant for dosimetrically relevant plans.

  19. Achieving Finite Element Mesh Quality via Optimization of the Jacobian Matrix Norm and Associated Quantities, Part II - A Framework for Volume Mesh Optimization and the Condition Number of the Jacobian Matrix

    SciTech Connect

    Knupp, P.M.

    1999-03-26

    Three-dimensional unstructured tetrahedral and hexahedral finite element mesh optimization is studied from a theoretical perspective and by computer experiments to determine what objective functions are most effective in attaining valid, high quality meshes. The approach uses matrices and matrix norms to extend the work in Part I to build suitable 3D objective functions. Because certain matrix norm identities which hold for 2 x 2 matrices do not hold for 3 x 3 matrices. significant differences arise between surface and volume mesh optimization objective functions. It is shown, for example, that the equivalence in two-dimensions of the Smoothness and Condition Number of the Jacobian matrix objective functions does not extend to three dimensions and further. that the equivalence of the Oddy and Condition Number of the Metric Tensor objective functions in two-dimensions also fails to extend to three-dimensions. Matrix norm identities are used to systematically construct dimensionally homogeneous groups of objective functions. The concept of an ideal minimizing matrix is introduced for both hexahedral and tetrahedral elements. Non-dimensional objective functions having barriers are emphasized as the most logical choice for mesh optimization. The performance of a number of objective functions in improving mesh quality was assessed on a suite of realistic test problems, focusing particularly on all-hexahedral ''whisker-weaved'' meshes. Performance is investigated on both structured and unstructured meshes and on both hexahedral and tetrahedral meshes. Although several objective functions are competitive, the condition number objective function is particularly attractive. The objective functions are closely related to mesh quality measures. To illustrate, it is shown that the condition number metric can be viewed as a new tetrahedral element quality measure.

  20. Optimization of the decision-making process for the selection of therapeutics to undergo clinical testing for spinal cord injury in the North American Clinical Trials Network.

    PubMed

    Guest, James; Harrop, James S; Aarabi, Bizhan; Grossman, Robert G; Fawcett, James W; Fehlings, Michael G; Tator, Charles H

    2012-09-01

    The North American Clinical Trials Network (NACTN) includes 9 clinical centers funded by the US Department of Defense and the Christopher Reeve Paralysis Foundation. Its purpose is to accelerate clinical testing of promising therapeutics in spinal cord injury (SCI) through the development of a robust interactive infrastructure. This structure includes key committees that serve to provide longitudinal guidance to the Network. These committees include the Executive, Data Management, and Neurological Outcome Assessments Committees, and the Therapeutic Selection Committee (TSC), which is the subject of this manuscript. The NACTN brings unique elements to the SCI field. The Network's stability is not restricted to a single clinical trial. Network members have diverse expertise and include experts in clinical care, clinical trial design and methodology, pharmacology, preclinical and clinical research, and advanced rehabilitation techniques. Frequent systematic communication is assigned a high value, as is democratic process, fairness and efficiency of decision making, and resource allocation. This article focuses on how decision making occurs within the TSC to rank alternative therapeutics according to 2 main variables: quality of the preclinical data set, and fit with the Network's aims and capabilities. This selection process is important because if the Network's resources are committed to a therapeutic, alternatives cannot be pursued. A proposed methodology includes a multicriteria decision analysis that uses a Multi-Attribute Global Inference of Quality matrix to quantify the process. To rank therapeutics, the TSC uses a series of consensus steps designed to reduce individual and group bias and limit subjectivity. Given the difficulties encountered by industry in completing clinical trials in SCI, stable collaborative not-for-profit consortia, such as the NACTN, may be essential to clinical progress in SCI. The evolution of the NACTN also offers substantial

  1. Optimization of cancer chemotherapy on the basis of pharmacokinetics and pharmacodynamics: from patients enrolled in clinical trials to those in the 'real world'.

    PubMed

    Fujita, Ken-Ichi; Sasaki, Yasutsuna

    2014-01-01

      Cytotoxic anticancer drugs are the most challenging therapeutic agents among all medicines with relatively narrow efficacy profiles. Therefore, medical oncologists have to practically manage the risk of severe toxic effects to optimize treatment outcomes. Dose and treatment-schedule recommendations for cytotoxic anticancer agents are determined on the basis of clinical trials. Patients enrolled in clinical trials are those likely to receive the drug in clinical practice, excluding those with conditions such as organ dysfunction, obesity, advanced age, or comorbidity. On the other hand, the 'real world' includes large numbers of such patients who do not meet the eligibility criteria of clinical trials. However, there is a paucity of data from sufficiently powered pharmacokinetic and pharmacodynamic studies to support dosage recommendations in such patients. Consequently, dose levels and treatment schedules for chemotherapy in these subjects are somewhat arbitrary and not evidence-based. Pharmacokinetic and pharmacodynamic studies of patients in the 'real world' are needed to address this issue. In this review article, we describe general aspects of clinical pharmacology in cancer patients enrolled in clinical trials and those in the 'real world,' and introduce recent findings regarding the pharmacokinetic and pharmacodynamic properties of irinotecan and S-1 in 'real world' cancer patients. PMID:24256625

  2. Mid-stage intervention achieves similar efficacy as conventional early-stage treatment using gene therapy in a pre-clinical model of retinitis pigmentosa

    PubMed Central

    Wert, Katherine J.; Sancho-Pelluz, Javier; Tsang, Stephen H.

    2014-01-01

    Deficiencies in rod-specific cyclic guanosine monophosphate (cGMP) phosphodiesterase-6 (PDE6) are the third most common cause of autosomal recessive retinitis pigmentosa (RP). Previously, viral gene therapy approaches on pre-clinical models with mutations in PDE6 have demonstrated that the photoreceptor cell survival and visual function can be rescued when the gene therapy virus is delivered into the subretinal space before the onset of disease. However, no studies have currently been published that analyze rescue effects after disease onset, a time when human RP patients are diagnosed by a clinician and would receive the treatment. We utilized the AAV2/8(Y733F)-Rho-Pde6α gene therapy virus and injected it into a pre-clinical model of RP with a mutation within the alpha subunit of PDE6: Pde6αD670G. These mice were previously shown to have long-term photoreceptor cell rescue when this gene therapy virus was delivered before the onset of disease. Now, we have determined that subretinal transduction of this rod-specific transgene at post-natal day (P) 21, when approximately half of the photoreceptor cells have undergone degeneration, is more efficient in rescuing cone than rod photoreceptor function long term. Therefore, AAV2/8(Y733F)-Rho-Pde6α is an effective gene therapy treatment that can be utilized in the clinical setting, in human patients who have lost portions of their peripheral visual field and are in the mid-stage of disease when they first present to an eye-care professional. PMID:24101599

  3. Mid-stage intervention achieves similar efficacy as conventional early-stage treatment using gene therapy in a pre-clinical model of retinitis pigmentosa.

    PubMed

    Wert, Katherine J; Sancho-Pelluz, Javier; Tsang, Stephen H

    2014-01-15

    Deficiencies in rod-specific cyclic guanosine monophosphate (cGMP) phosphodiesterase-6 (PDE6) are the third most common cause of autosomal recessive retinitis pigmentosa (RP). Previously, viral gene therapy approaches on pre-clinical models with mutations in PDE6 have demonstrated that the photoreceptor cell survival and visual function can be rescued when the gene therapy virus is delivered into the subretinal space before the onset of disease. However, no studies have currently been published that analyze rescue effects after disease onset, a time when human RP patients are diagnosed by a clinician and would receive the treatment. We utilized the AAV2/8(Y733F)-Rho-Pde6α gene therapy virus and injected it into a pre-clinical model of RP with a mutation within the alpha subunit of PDE6: Pde6α(D670G). These mice were previously shown to have long-term photoreceptor cell rescue when this gene therapy virus was delivered before the onset of disease. Now, we have determined that subretinal transduction of this rod-specific transgene at post-natal day (P) 21, when approximately half of the photoreceptor cells have undergone degeneration, is more efficient in rescuing cone than rod photoreceptor function long term. Therefore, AAV2/8(Y733F)-Rho-Pde6α is an effective gene therapy treatment that can be utilized in the clinical setting, in human patients who have lost portions of their peripheral visual field and are in the mid-stage of disease when they first present to an eye-care professional. PMID:24101599

  4. Long-Term (Six Years) Clinical Outcome Discrimination of Patients in the Vegetative State Could be Achieved Based on the Operational Architectonics EEG Analysis: A Pilot Feasibility Study

    PubMed Central

    Fingelkurts, Andrew A.; Fingelkurts, Alexander A.; Bagnato, Sergio; Boccagni, Cristina; Galardi, Giuseppe

    2016-01-01

    Electroencephalogram (EEG) recordings are increasingly used to evaluate patients with disorders of consciousness (DOC) or assess their prognosis outcome in the short-term perspective. However, there is a lack of information concerning the effectiveness of EEG in classifying long-term (many years) outcome in chronic DOC patients. Here we tested whether EEG operational architectonics parameters (geared towards consciousness phenomenon detection rather than neurophysiological processes) could be useful for distinguishing a very long-term (6 years) clinical outcome of DOC patients whose EEGs were registered within 3 months post-injury. The obtained results suggest that EEG recorded at third month after sustaining brain damage, may contain useful information on the long-term outcome of patients in vegetative state: it could discriminate patients who remain in a persistent vegetative state from patients who reach a minimally conscious state or even recover a full consciousness in a long-term perspective (6 years) post-injury. These findings, if confirmed in further studies, may be pivotal for long-term planning of clinical care, rehabilitative programs, medical-legal decisions concerning the patients, and policy makers. PMID:27347266

  5. Achieving optimal SERS through enhanced experimental design

    PubMed Central

    Fisk, Heidi; Westley, Chloe; Turner, Nicholas J.

    2016-01-01

    One of the current limitations surrounding surface‐enhanced Raman scattering (SERS) is the perceived lack of reproducibility. SERS is indeed challenging, and for analyte detection, it is vital that the analyte interacts with the metal surface. However, as this is analyte dependent, there is not a single set of SERS conditions that are universal. This means that experimental optimisation for optimum SERS response is vital. Most researchers optimise one factor at a time, where a single parameter is altered first before going onto optimise the next. This is a very inefficient way of searching the experimental landscape. In this review, we explore the use of more powerful multivariate approaches to SERS experimental optimisation based on design of experiments and evolutionary computational methods. We particularly focus on colloidal‐based SERS rather than thin film preparations as a result of their popularity. © 2015 The Authors. Journal of Raman Spectroscopy published by John Wiley & Sons, Ltd.

  6. Thin sheets achieve optimal wrapping of liquids

    NASA Astrophysics Data System (ADS)

    Paulsen, Joseph; Démery, Vincent; Davidovitch, Benny; Santangelo, Christian; Russell, Thomas; Menon, Narayanan

    2015-03-01

    A liquid drop can wrap itself in a sheet using capillary forces [Py et al., PRL 98, 2007]. However, the efficiency of ``capillary origami'' at covering the surface of a drop is hampered by the mechanical cost of bending the sheet. Thinner sheets deform more readily by forming small-scale wrinkles and stress-focussing patterns, but it is unclear how coverage efficiency competes with mechanical cost as thickness is decreased, and what wrapping shapes will emerge. We place a thin (~ 100 nm) polymer film on a drop whose volume is gradually decreased so that the sheet covers an increasing fraction of its surface. The sheet exhibits a complex sequence of axisymmetric and polygonal partially- and fully- wrapped shapes. Remarkably, the progression appears independent of mechanical properties. The gross shape, which neglects small-scale features, is correctly predicted by a simple geometric approach wherein the exposed area is minimized. Thus, simply using a thin enough sheet results in maximal coverage.

  7. Achieving Optimal Enrollments and Tuition Revenues.

    ERIC Educational Resources Information Center

    Ihlanfeldt, William

    A modern marketing approach to student recruitment is offered as a means of facilitating institutional planning, enhancing communication with prospective students, improving enrollment forecasting, and eliminating unexpected shortfalls in tuition income. Marketing is distinguished from mere salesmanship and discussed in a practical program of…

  8. Using Attitudinal Questionnaires to Achieve Benefits Optimization

    PubMed Central

    Lundsgaarde, Henry P.; Gardner, Reed M.; Menlove, Ron L.

    1989-01-01

    The evaluation of complex hospital medical and management information systems presents many complex methodological and logistical problems. Many studies, best characterized as outcome or summative evaluations, customarily document failures and successes associated with system implementation. We approach system implementation as an indeterminable process and evaluation as a management tool that can provide essential and timely feedback to both system developers and users. This paper discusses our ongoing and formative evaluation study of the transplacement of the HELP system from the LDS hospital in Salt Lake City to the McKay-Dee Hospital in Ogden, Utah. Surveys of future system users did not show any significant differences between three major groups of respondents (physicians, nurses, and staff) in terms of preferences for user education methods. The results of our work suggest that a formative evaluation study can facilitate system adoption and utilization without compromising concurrent needs of scientific objectivity.

  9. Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study

    PubMed Central

    2014-01-01

    Introduction The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response. Methods The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L). Results Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5). Conclusions This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in

  10. Similar Clinical and Surgical Outcomes Achieved with Early Compared to Late Anti-TNF Induction in Mild-to-Moderate Ulcerative Colitis: A Retrospective Cohort Study

    PubMed Central

    Fedorak, Darryl K.; Dieleman, Levinus A.; Halloran, Brendan P.

    2016-01-01

    Background. Biologic agents targeting tumor necrosis factor alpha are effective in the management of ulcerative colitis (UC), but their use is often postponed until after failure of other treatment modalities. Objectives. We aim to determine if earlier treatment with infliximab or adalimumab alters clinical and surgical outcomes in UC patients. Methods. A retrospective cohort study was conducted evaluating UC outpatients treated with infliximab or adalimumab from 2003 to 2014. Patients were stratified by time to first anti-TNF exposure; early initiation was defined as starting treatment within three years of diagnosis. Primary outcomes were colectomy, UC-related hospitalization, and clinical secondary loss of response. Kaplan-Meier analysis was used to assess time to the primary outcomes. Results. 115 patients were included (78 infliximab, 37 adalimumab). Median follow-up was 175.6 weeks (IQR 72.4–228.4 weeks). Fifty-seven (49.6%) patients received early anti-TNF therapy; median time to treatment in this group was 38.1 (23.3–91.0) weeks compared to 414.0 (254.0–561.3) weeks in the late initiator cohort (p < 0.0001). Patients treated with early anti-TNF therapy had more severe endoscopic disease at induction (mean Mayo endoscopy subscore 2.46 (SD ± 0.66) versus 1.86 (±0.67), p < 0.001) and trended towards increased risk of colectomy (17.5% versus 8.6%, p = 0.16) and UC-related hospitalization (43.9% versus 27.6%, p = 0.07). In multivariate regression analysis, early anti-TNF induction was not associated with colectomy (HR 2.02 [95% CI: 0.57–7.20]), hospitalization (HR 1.66 [0.84–3.30]), or secondary loss of response (HR 0.86 [0.52–1.42]). Conclusions. Anti-TNF therapy is initiated earlier in patients with severe UC but earlier treatment does not prevent hospitalization, colectomy, or secondary loss of response. PMID:27478817

  11. Implant-supported overdenture manufactured using CAD/CAM techniques to achieve horizontal path insertion between the primary and secondary structure: A clinical case report

    PubMed Central

    Agustín-Panadero, Rubén; Peñarrocha-Oltra, David; Gomar-Vercher, Sonia; Ferreiroa, Alberto

    2015-01-01

    This report describes the case of an edentulous patient with an atrophic maxilla and severe class III malocclusion. Prosthetic rehabilitation was performed using CAD/CAM techniques for manufacturing an implant-supported overdenture with horizontal insertion. A vestibulo-lingual insertion overdenture is a precision prosthesis with a fixation system affording a good fit between the primary and secondary structure. Both structures exhibit passive horizontal adjustment. This treatment option requires the same number of implants as implant-supported fixed dentures. The horizontal assembly system prevents the prosthesis from loosening or moving in response to axial and non-axial forces. The technique was used to rehabilitate a patient presenting an atrophic upper maxilla, with the insertion of 8 implants. No complications were reported at follow-up 3, 6 and 12 months after fitting of the prosthesis. This system offers solutions to the clinical and laboratory complications associated with hybrid prostheses, concealing emergence of the chimneys and improving implant-prosthesis hygiene. PMID:26140179

  12. Transdermal glimepiride delivery system based on optimized ethosomal nano-vesicles: Preparation, characterization, in vitro, ex vivo and clinical evaluation.

    PubMed

    Ahmed, Tarek A; El-Say, Khalid M; Aljaeid, Bader M; Fahmy, Usama A; Abd-Allah, Fathy I

    2016-03-16

    This work aimed to develop an optimized ethosomal formulation of glimepiride then loading into transdermal films to offer lower drug side effect, extended release behavior and avoid first pass effect. Four formulation factors were optimized for their effects on vesicle size (Y1), entrapment efficiency (Y2) and vesicle flexibility (Y3). Optimum desirability was identified and, an optimized formulation was prepared, characterized and loaded into transdermal films. Ex-vivo permeation study for the prepared films was conducted and, the permeation parameters and drug permeation mechanism were identified. Penetration through rat skin was studied using confocal laser microscope. In-vivo study was performed following transdermal application on human volunteers. The percent of alcohol was significantly affecting all the studied responses while the other factors and their interaction effects were varied on their effects on each response. The optimized ethosomal formulation showed observed values for Y1, Y2 and Y3 of 61 nm, 97.12% and 54.03, respectively. Ex-vivo permeation of films loaded with optimized ethosomal formulation was superior to that of the corresponding pure drug transdermal films and this finding was also confirmed after confocal laser microscope study. Permeation of glimepiride from the prepared films was in favor of Higushi-diffusion model and exhibited non-Fickian or anomalous release mechanism. In-vivo study revealed extended drug release behavior and lower maximum drug plasma level from transdermal films loaded with drug ethosomal formulation. So, the ethosomal formulation could be considered a suitable drug delivery system especially when loaded into transdermal vehicle with possible reduction in side effects and controlling the drug release. PMID:26775063

  13. [Achievement of therapeutic target in subjects on statin treatment in clinical practice. Results of the STAR (Statins Target Assessment in Real practice) study].

    PubMed

    Degli Esposti, Luca; Sangiorgi, Diego; Arca, Marcello; Vigna, Giovanni B; Budal, Stefano; Degli Esposti, Ezio

    2011-12-01

    The primary aim of the STAR Study (Statins Target Assessment in Real practice) was to determine the LDL-cholesterol reduction and to analyse patient's and therapeutic factors associated to LDL-cholesterol target attainment in newly treated subjects with statins in an unselected population in clinical practice setting. Administrative databases (including pharmaceutical prescriptions and hospital admissions) and laboratory test databases (including LDL-cholesterol values) of five local health units, distributed in Emilia Romagna, Toscana and Umbria, were linked. A retrospective cohort study was conducted and all subjects aged > or =18 years with a first prescription for statins (newly treated subjects) between January 1st, 2007 and June 30th, 2008 were included. All statin prescriptions over a 12 months follow-up period were considered and used to calculate adherence to treatment. Baseline and follow-up LDL-cholesterol, respectively, were defined according to the nearest determination to the first prescription for statins and to the end of the follow-up period. A total of 3.232 subjects was included, 1.516 males (47%) and 1.716 females (53%), with an average age equal to 65.9 +/- 11.3 years. Among included subjects, 22.,6% had a gap to LDL-cholesterol target <10%, 30.0% between 10 and 29%, 20.7% between 30 and 49%, and 26.7% . or =50%. Among those with a gap to target > or =50%, 30-49%, and 10-29%, respectively, LDL-cholesterol target was attained by 7.1%, 41.8%, and 62.% of subjects. LDL-cholesterol target attainment was associated to gap to target, adherence with treatment, and type of statin. PMID:22567731

  14. Rosuvastatin versus atorvastatin in achieving lipid goals in patients at high risk for cardiovascular disease in clinical practice: A randomized, open-label, parallel-group, multicenter study (DISCOVERY Alpha study)

    PubMed Central

    Binbrek, Azan S.; Elis, Avishay; Al-Zaibag, Muayed; Eha, Jaan; Keber, Irena; Cuevas, Ada M.; Mukherjee, Swati; Miller, Thomas R.

    2006-01-01

    Background: The majority of clinical trials investigating the clinical benefits of lipid-lowering therapies (LLTs) have focused on North American or western and nothern European populations. Therefore, it is timely to confirm the efficacy of these agents in other patient populations in routine clinical practice. Objective: The aim of the Direct Statin COmparison of low-density lipoprotein cholesterol (LDL-C) Values: an Evaluation of Rosuvastatin therapY (DISCOVERY) Alpha study was to compare the effects of rosuvastatin 10 mg with those of atorvastatin 10 mg in achieving LDL-C goals in the Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice guidelines. Methods: This randomized, open-label, parallel-group study was conducted at 93 centers in eastern Europe (Estonia, Latvia, Romania, Russia, Slovenia), Central and South America (Chile, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama), and the Middle East (Israel, Kuwait, Saudi Arabia, United Arab Emirates). Male and female patients aged ≥18 years with primary hypercholesterolemia (LDL-C level, >135 mg/dL if LLT-naive or ≥120 mg/dL if switching statins; triglyceride [TG] level, <400 mg/dL) and a 10-year coronary heart disease (CHD) risk >20% or a history of CHD or other established atherosclerotic disease were eligible for inclusion in the study. Patients were randomly assigned to receive rosuvastatin 10-mg or atorvastatin 10-mg tablets QD for 12 weeks. No formal statistical analyses or comparisons were performed on lipid changes between switched and LLT-naive patients because of the different lipid inclusion criteria for these patients. The primary end point was the proportion of patients achieving 1998 European LDL-C goals after 12 weeks of treatment. A subanalysis was performed to assess the effects of statins in patients who had received previous statin treatment versus those who were LLT-naive. Tolerability was assessed using

  15. A rigorous approach for selection of optimal variant sets for carrier screening with demonstration of clinical utility.

    PubMed

    Perreault-Micale, Cynthia; Davie, Jocelyn; Breton, Benjamin; Hallam, Stephanie; Greger, Valerie

    2015-07-01

    Carrier screening for certain diseases is recommended by major medical and Ashkenazi Jewish (AJ) societies. Most carrier screening panels test only for common, ethnic-specific variants. However, with formerly isolated ethnic groups becoming increasingly intermixed, this approach is becoming inadequate. Our objective was to develop a rigorous process to curate all variants, for relevant genes, into a database and then apply stringent clinical validity classification criteria to each in order to retain only those with clear evidence for pathogenicity. The resulting variant set, in conjunction with next-generation DNA sequencing (NGS), then affords the capability for an ethnically diverse, comprehensive, highly specific carrier-screening assay. The clinical utility of our approach was demonstrated by screening a pan-ethnic population of 22,864 individuals for Bloom syndrome carrier status using a BLM variant panel comprised of 50 pathogenic variants. In addition to carriers of the common AJ founder variant, we identified 57 carriers of other pathogenic BLM variants. All variants reported had previously been curated and their clinical validity documented, or were of a type that met our stringent, preassigned validity criteria. Thus, it was possible to confidently report an increased number of Bloom's syndrome carriers compared to traditional, ethnicity-based screening, while not reducing the specificity of the screening due to reporting variants of unknown clinical significance. PMID:26247052

  16. A rigorous approach for selection of optimal variant sets for carrier screening with demonstration of clinical utility

    PubMed Central

    Perreault-Micale, Cynthia; Davie, Jocelyn; Breton, Benjamin; Hallam, Stephanie; Greger, Valerie

    2015-01-01

    Carrier screening for certain diseases is recommended by major medical and Ashkenazi Jewish (AJ) societies. Most carrier screening panels test only for common, ethnic-specific variants. However, with formerly isolated ethnic groups becoming increasingly intermixed, this approach is becoming inadequate. Our objective was to develop a rigorous process to curate all variants, for relevant genes, into a database and then apply stringent clinical validity classification criteria to each in order to retain only those with clear evidence for pathogenicity. The resulting variant set, in conjunction with next-generation DNA sequencing (NGS), then affords the capability for an ethnically diverse, comprehensive, highly specific carrier-screening assay. The clinical utility of our approach was demonstrated by screening a pan-ethnic population of 22,864 individuals for Bloom syndrome carrier status using a BLM variant panel comprised of 50 pathogenic variants. In addition to carriers of the common AJ founder variant, we identified 57 carriers of other pathogenic BLM variants. All variants reported had previously been curated and their clinical validity documented, or were of a type that met our stringent, preassigned validity criteria. Thus, it was possible to confidently report an increased number of Bloom’s syndrome carriers compared to traditional, ethnicity-based screening, while not reducing the specificity of the screening due to reporting variants of unknown clinical significance. PMID:26247052

  17. Optimization and life-cycle cost of health clinic PV system for a rural area in southern Iraq using HOMER software

    SciTech Connect

    Al-Karaghouli, Ali; Kazmerski, L.L.

    2010-04-15

    This paper addresses the need for electricity of rural areas in southern Iraq and proposes a photovoltaic (PV) solar system to power a health clinic in that region. The total daily health clinic load is 31.6 kW h and detailed loads are listed. The National Renewable Energy Laboratory (NREL) optimization computer model for distributed power, ''HOMER,'' is used to estimate the system size and its life-cycle cost. The analysis shows that the optimal system's initial cost, net present cost, and electricity cost is US$ 50,700, US$ 60,375, and US$ 0.238/kW h, respectively. These values for the PV system are compared with those of a generator alone used to supply the load. We found that the initial cost, net present cost of the generator system, and electricity cost are US$ 4500, US$ 352,303, and US$ 1.332/kW h, respectively. We conclude that using the PV system is justified on humanitarian, technical, and economic grounds. (author)

  18. The clinical potential of high energy, intensity and energy modulated electron beams optimized by simulated annealing for conformal radiation therapy

    NASA Astrophysics Data System (ADS)

    Salter, Bill Jean, Jr.

    Purpose. The advent of new, so called IVth Generation, external beam radiation therapy treatment machines (e.g. Scanditronix' MM50 Racetrack Microtron) has raised the question of how the capabilities of these new machines might be exploited to produce extremely conformal dose distributions. Such machines possess the ability to produce electron energies as high as 50 MeV and, due to their scanned beam delivery of electron treatments, to modulate intensity and even energy, within a broad field. Materials and methods. Two patients with 'challenging' tumor geometries were selected from the patient archives of the Cancer Therapy and Research Center (CTRC), in San Antonio Texas. The treatment scheme that was tested allowed for twelve, energy and intensity modulated beams, equi-spaced about the patient-only intensity was modulated for the photon treatment. The elementary beams, incident from any of the twelve allowed directions, were assumed parallel, and the elementary electron beams were modeled by elementary beam data. The optimal arrangement of elementary beam energies and/or intensities was optimized by Szu-Hartley Fast Simulated Annealing Optimization. Optimized treatment plans were determined for each patient using both the high energy, intensity and energy modulated electron (HIEME) modality, and the 6 MV photon modality. The 'quality' of rival plans were scored using three different, popular objective functions which included Root Mean Square (RMS), Maximize Dose Subject to Dose and Volume Limitations (MDVL - Morrill et. al.), and Probability of Uncomplicated Tumor Control (PUTC) methods. The scores of the two optimized treatments (i.e. HIEME and intensity modulated photons) were compared to the score of the conventional plan with which the patient was actually treated. Results. The first patient evaluated presented a deeply located target volume, partially surrounding the spinal cord. A healthy right kidney was immediately adjacent to the tumor volume, separated

  19. Recommendations for Standardizing Glucose Reporting and Analysis to Optimize Clinical Decision Making in Diabetes: The Ambulatory Glucose Profile

    PubMed Central

    Bergenstal, Richard M.; Ahmann, Andrew J.; Bailey, Timothy; Beck, Roy W.; Bissen, Joan; Buckingham, Bruce; Deeb, Larry; Dolin, Robert H.; Garg, Satish K.; Goland, Robin; Hirsch, Irl B.; Klonoff, David C.; Kruger, Davida F.; Matfin, Glenn; Mazze, Roger S.; Olson, Beth A.; Parkin, Christopher; Peters, Anne; Powers, Margaret A.; Rodriguez, Henry; Southerland, Phil; Strock, Ellie S.; Tamborlane, William; Wesley, David M.

    2013-01-01

    Underutilization of glucose data and lack of easy and standardized glucose data collection, analysis, visualization, and guided clinical decision making are key contributors to poor glycemic control among individuals with type 1 diabetes mellitus. An expert panel of diabetes specialists, facilitated by the International Diabetes Center and sponsored by the Helmsley Charitable Trust, met in 2012 to discuss recommendations for standardizing the analysis and presentation of glucose monitoring data, with the initial focus on data derived from continuous glucose monitoring systems. The panel members were introduced to a universal software report, the Ambulatory Glucose Profile, and asked to provide feedback on its content and functionality, both as a research tool and in clinical settings. This article provides a summary of the topics and issues discussed during the meeting and presents recommendations from the expert panel regarding the need to standardize glucose profile summary metrics and the value of a uniform glucose report to aid clinicians, researchers, and patients. PMID:23567014

  20. Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia.

    PubMed

    Moree, Wilna J; Li, Bin-Feng; Zamani-Kord, Said; Yu, Jinghua; Coon, Timothy; Huang, Charles; Marinkovic, Dragan; Tucci, Fabio C; Malany, Siobhan; Bradbury, Margaret J; Hernandez, Lisa M; Wen, Jianyun; Wang, Hua; Hoare, Samuel R J; Petroski, Robert E; Jalali, Kayvon; Yang, Chun; Sacaan, Aida; Madan, Ajay; Crowe, Paul D; Beaton, Graham

    2010-10-01

    Analogs of the known H(1)-antihistamine R-dimethindene with suitable selectivity for key GPCRs, P450 enzymes and hERG channel were assessed for metabolism profile and in vivo properties. Several analogs were determined to exhibit diverse metabolism. One of these compounds, 10a, showed equivalent efficacy in a rat EEG/EMG model to a previously identified clinical candidate and a potentially superior pharmacokinetic profile as determined from a human microdose study. PMID:20800486

  1. Achieving Goal Blood Pressure.

    PubMed

    Laurent, Stéphane

    2015-07-01

    Both monotherapy and combination therapy options are appropriate for antihypertensive therapy according to the 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines. Most patients require more than one agent to achieve blood pressure (BP) control, and adding a second agent is more effective than doubling the dose of existing therapy. The addition of a third agent may be required to achieve adequate BP reductions in some patients. Single-pill fixed-dose combinations (FDCs) allow multiple-drug regimens to be delivered without any negative impact on patient compliance or persistence with therapy. FDCs also have documented beneficial clinical effects and use of FDCs containing two or three agents is recommended by the 2013 ESH/ESC guidelines. PMID:26002423

  2. Clinical application of low-dose phase contrast breast CT: methods for the optimization of the reconstruction workflow

    PubMed Central

    Pacilè, S.; Brun, F.; Dullin, C.; Nesterest, Y. I.; Dreossi, D.; Mohammadi, S.; Tonutti, M.; Stacul, F.; Lockie, D.; Zanconati, F.; Accardo, A.; Tromba, G.; Gureyev, T. E.

    2015-01-01

    Results are presented of a feasibility study of three-dimensional X-ray tomographic mammography utilising in-line phase contrast. Experiments were performed at SYRMEP beamline of Elettra synchrotron. A specially designed plastic phantom and a mastectomy sample containing a malignant lesion were used to study the reconstructed image quality as a function of different image processing operations. Detailed evaluation and optimization of image reconstruction workflows have been carried out using combinations of several advanced computed tomography algorithms with different pre-processing and post-processing steps. Special attention was paid to the effect of phase retrieval on the diagnostic value of the reconstructed images. A number of objective image quality indices have been applied for quantitative evaluation of the results, and these were compared with subjective assessments of the same images by three experienced radiologists and one pathologist. The outcomes of this study provide practical guidelines for the optimization of image processing workflows in synchrotron-based phase-contrast mammo-tomography. PMID:26309770

  3. Polymeric nanoparticles for oral delivery of 5-fluorouracil: Formulation optimization, cytotoxicity assay and pre-clinical pharmacokinetics study.

    PubMed

    Mattos, Ana Cristina de; Altmeyer, Clescila; Tominaga, Tania Toyomi; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2016-03-10

    Poly(lactic acid) (PLA) or poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) blend nanoparticles were developed loading 5-fluorouracil (5-FU), an antitumor agent broadly used in therapy. A 2(3) factorial experimental design was conducted to indicate an optimal formulation and demonstrate the influence of the interactions of components on the mean particle size and drug encapsulation efficiency. Optimized PLA nanoparticles presented 294nm and 51% of 5-FU encapsulation efficiency and PLA-PEG blend nanoparticles presented 283nm and 55% of 5-FU encapsulation efficiency. In vitro release assay demonstrated after 320h about 50% of 5-FU was released from PLA and PLA-PEG blend nanoparticles. Release kinetics of 5-FU from nanoparticles followed second order and the release mechanism calculated by Korsmeyer-Peppas model was diffusion and erosion. In the assessment of cytotoxicity over Hep-2 tumor cells, PLA or PLA-PEG blend nanoparticles presented similar IC50 value than free 5-FU. Pharmacokinetic parameters after oral administration of 5-FU were improved by nanoencapsulation. Bioavailability, Cmax, Tmax, t1/2 and distribution volume were significantly improved, while clearance were decreased. PEG presence in nanoparticles didn't influence physicochemical and biological parameters evaluated. PLA and PLA-PEG nanoparticles can be potential carriers for oral delivery of 5-FU. PMID:26775869

  4. Clinical application of low-dose phase contrast breast CT: methods for the optimization of the reconstruction workflow.

    PubMed

    Pacilè, S; Brun, F; Dullin, C; Nesterest, Y I; Dreossi, D; Mohammadi, S; Tonutti, M; Stacul, F; Lockie, D; Zanconati, F; Accardo, A; Tromba, G; Gureyev, T E

    2015-08-01

    Results are presented of a feasibility study of three-dimensional X-ray tomographic mammography utilising in-line phase contrast. Experiments were performed at SYRMEP beamline of Elettra synchrotron. A specially designed plastic phantom and a mastectomy sample containing a malignant lesion were used to study the reconstructed image quality as a function of different image processing operations. Detailed evaluation and optimization of image reconstruction workflows have been carried out using combinations of several advanced computed tomography algorithms with different pre-processing and post-processing steps. Special attention was paid to the effect of phase retrieval on the diagnostic value of the reconstructed images. A number of objective image quality indices have been applied for quantitative evaluation of the results, and these were compared with subjective assessments of the same images by three experienced radiologists and one pathologist. The outcomes of this study provide practical guidelines for the optimization of image processing workflows in synchrotron-based phase-contrast mammo-tomography. PMID:26309770

  5. Management of multivessel coronary disease after primary angioplasty: staged reintervention versus optimized clinical treatment and two-year follow-up

    PubMed Central

    de Paula, José Guilherme Rodrigues; de Godoy, Moacir Fernandes; dos Santos, Márcio Antônio; Pivatelli, Flávio Corrêa; Osti, Alan Vinicius Gamero; Trindade, Luciano Folchine; Novelli, Diego; Nakazone, Marcelo Arruda

    2014-01-01

    Objective In the clinical scenario of ST-segment elevation acute myocardial infarction, several patients with multivessel coronary atherosclerotic disease are discharged without a defined strategy to monitor the residual atherosclerotic lesions. The clinical endpoints evaluated were cardiovascular death, symptoms of angina pectoris, rehospitalization for a new acute coronary syndrome, and the necessity of reintervention during the two-year follow-up. Methods This observational, prospective, and historical study included multivessel coronary atherosclerotic disease patients who were admitted to a tertiary care university hospital with ST-segment elevation acute myocardial infarction and underwent primary percutaneous coronary intervention with stent implantation only at the culprit lesion site; these patients were monitored in the outpatient clinic according to two treatments: the Clinical Group - CG (optimized pharmacological therapy associated with counseling for a healthy diet and cardiac rehabilitation) or the Intervention Group - IG (new staged percutaneous coronary intervention or surgical coronary artery bypass graft surgery combined with the previously prescribed treatment). Results Of 143 patients consecutively admitted with ST-segment elevation acute myocardial infarction, 57 were eligible for the study (CG=44 and IG=13). Regarding the clinical endpoints, the cardiovascular death rate did not differ between the CG and IG. The symptom of angina pectoris and the rehospitalization rate for a new episode of acute coronary syndrome were accentuated in the CG (P=0.020 and P=0.049, respectively) mainly in individuals with evidence of ischemia evidenced by myocardial scintigraphy (P<0.001 and P=0.001, respectively) which culminated in an even greater need for reintervention (P=0.001) in this subgroup of patients. Conclusion The staged intervention was demonstrated to be safe and able to reduce angina pectoris and rehospitalization for a new episode of acute

  6. Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains.

    PubMed

    Mirguet, Olivier; Gosmini, Romain; Toum, Jérôme; Clément, Catherine A; Barnathan, Mélanie; Brusq, Jean-Marie; Mordaunt, Jacqueline E; Grimes, Richard M; Crowe, Miriam; Pineau, Olivier; Ajakane, Myriam; Daugan, Alain; Jeffrey, Phillip; Cutler, Leanne; Haynes, Andrea C; Smithers, Nicholas N; Chung, Chun-wa; Bamborough, Paul; Uings, Iain J; Lewis, Antonia; Witherington, Jason; Parr, Nigel; Prinjha, Rab K; Nicodème, Edwige

    2013-10-10

    The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure-activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers. PMID:24015967

  7. Optimal balance of efficacy and tolerability of oral triptans and telcagepant: a review and a clinical comment.

    PubMed

    Tfelt-Hansen, Peer

    2011-06-01

    Dose-response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and frovatriptan, and the CGRP antagonist telcagepant. The upper part of the efficacy curve of the triptans is generally flat, the so-called ceiling effect; and none of the oral triptans, even in high doses, are as effective as subcutaneous sumatriptan, In contrast, AEs increases with increasing dose without a ceiling effect. The optimal dose for the triptans is mainly determined by tolerability. Telcagepant has an excellent tolerability and can be used in migraine patients with cardiovascular co-morbidity. Based on the literature the triptans and telcagepant are rated in a table for efficacy and tolerability. PMID:21350792

  8. Designing evidence-based medicine training to optimize the transfer of skills from the classroom to clinical practice: applying the four component instructional design model.

    PubMed

    Maggio, Lauren A; Cate, Olle Ten; Irby, David M; O'Brien, Bridget C

    2015-11-01

    Evidence-based medicine (EBM) skills, although taught in medical schools around the world, are not optimally practiced in clinical environments because of multiple barriers, including learners' difficulty transferring EBM skills learned in the classroom to clinical practice. This lack of skill transfer may be partially due to the design of EBM training. To facilitate the transfer of EBM skills from the classroom to clinical practice, the authors explore one instructional approach, called the Four Component Instructional Design (4C/ID) model, to guide the design of EBM training. On the basis of current cognitive psychology, including cognitive load theory, the premise of the 4C/ID model is that complex skills training, such as EBM training, should include four components: learning tasks, supportive information, procedural information, and part-task practice. The combination of these four components can inform the creation of complex skills training that is designed to avoid overloading learners' cognitive abilities; to facilitate the integration of the knowledge, skills, and attitudes needed to execute a complex task; and to increase the transfer of knowledge to new situations. The authors begin by introducing the 4C/ID model and describing the benefits of its four components to guide the design of EBM training. They include illustrative examples of educational practices that are consistent with each component and that can be applied to teaching EBM. They conclude by suggesting that medical educators consider adopting the 4C/ID model to design, modify, and/or implement EBM training in classroom and clinical settings. PMID:25993279

  9. Optimization of OSEM parameters in myocardial perfusion imaging reconstruction as a function of body mass index: a clinical approach*

    PubMed Central

    de Barros, Pietro Paolo; Metello, Luis F.; Camozzato, Tatiane Sabriela Cagol; Vieira, Domingos Manuel da Silva

    2015-01-01

    Objective The present study is aimed at contributing to identify the most appropriate OSEM parameters to generate myocardial perfusion imaging reconstructions with the best diagnostic quality, correlating them with patients’ body mass index. Materials and Methods The present study included 28 adult patients submitted to myocardial perfusion imaging in a public hospital. The OSEM method was utilized in the images reconstruction with six different combinations of iterations and subsets numbers. The images were analyzed by nuclear cardiology specialists taking their diagnostic value into consideration and indicating the most appropriate images in terms of diagnostic quality. Results An overall scoring analysis demonstrated that the combination of four iterations and four subsets has generated the most appropriate images in terms of diagnostic quality for all the classes of body mass index; however, the role played by the combination of six iterations and four subsets is highlighted in relation to the higher body mass index classes. Conclusion The use of optimized parameters seems to play a relevant role in the generation of images with better diagnostic quality, ensuring the diagnosis and consequential appropriate and effective treatment for the patient. PMID:26543282

  10. SU-E-I-57: Evaluation and Optimization of Effective-Dose Using Different Beam-Hardening Filters in Clinical Pediatric Shunt CT Protocol

    SciTech Connect

    Gill, K; Aldoohan, S; Collier, J

    2014-06-01

    Purpose: Study image optimization and radiation dose reduction in pediatric shunt CT scanning protocol through the use of different beam-hardening filters Methods: A 64-slice CT scanner at OU Childrens Hospital has been used to evaluate CT image contrast-to-noise ratio (CNR) and measure effective-doses based on the concept of CT dose index (CTDIvol) using the pediatric head shunt scanning protocol. The routine axial pediatric head shunt scanning protocol that has been optimized for the intrinsic x-ray tube filter has been used to evaluate CNR by acquiring images using the ACR approved CT-phantom and radiation dose CTphantom, which was used to measure CTDIvol. These results were set as reference points to study and evaluate the effects of adding different filtering materials (i.e. Tungsten, Tantalum, Titanium, Nickel and Copper filters) to the existing filter on image quality and radiation dose. To ensure optimal image quality, the scanner routine air calibration was run for each added filter. The image CNR was evaluated for different kVps and wide range of mAs values using above mentioned beam-hardening filters. These scanning protocols were run under axial as well as under helical techniques. The CTDIvol and the effective-dose were measured and calculated for all scanning protocols and added filtration, including the intrinsic x-ray tube filter. Results: Beam-hardening filter shapes energy spectrum, which reduces the dose by 27%. No noticeable changes in image low contrast detectability Conclusion: Effective-dose is very much dependent on the CTDIVol, which is further very much dependent on beam-hardening filters. Substantial reduction in effective-dose is realized using beam-hardening filters as compare to the intrinsic filter. This phantom study showed that significant radiation dose reduction could be achieved in CT pediatric shunt scanning protocols without compromising in diagnostic value of image quality.

  11. Self-Beliefs and Student Goal Achievement

    ERIC Educational Resources Information Center

    Wesson, Caroline J.; Derrer-Rendall, Nicola M.

    2011-01-01

    Two preliminary studies are presented investigating the self-beliefs that may affect goal achievement in a student population. In Study 1, goal achievement on an abstract task, where goals are externally set by others, is considered in relation to students' levels of optimism. In Study 2, goal achievement on academic performance, where goals are…

  12. Clinical outcomes between optical path difference custom aspheric treatment and optimized prolate ablation photorefractive keratectomy in myopia exceeding 8 diopters

    PubMed Central

    Choi, B J; Park, Y M; Lee, J S

    2015-01-01

    Purpose Comparison of visual acuity, refractive, and wavefront outcomes associated with optimized prolate ablation (OPA) and optical path difference custom aspheric treatment (OPDCAT) algorithms for correction of myopia exceeding 8 diopters (D). Patients and Methods Patients were randomly assigned to have photorefractive keratectomy (PRK) with OPA (n=32) or OPDCAT (n=21) algorithms. Visual acuity, manifest refraction, ocular and corneal higher-order aberrations, corneal asphericity, modulated-transfer function, and point-spread function were compared 1, 3, and 6 months postoperatively. Results Mean manifest-refraction spherical equivalents at 6 months were −0.24 D in both groups. All patients in both groups had an uncorrected-distance visual acuity of 20/20 or better. Predictability (±1 D from intended refraction) at 6 months was 94% in the OPA group, and in the OPDCAT group it was 86%. The OPA group had less induced corneal and ocular spherical aberrations (SAs) than the OPDCAT group. Postoperative corneal asphericity change was lowest in the OPA group. Both the groups exhibited significantly-improved AreaRatio-Total value and insignificantly deteriorated AreaRatio-HO value throughout the postoperative period. The OPA group had significantly-higher AreaRatio-Total compared with OPDCAT group at both 1 and 6 months after the operation. Six months after surgery, the Strehl ratio had decreased in both groups, and there was no significant difference between the groups. Conclusion The OPA algorithms yielded higher-objective visual quality and predictability, induced less corneal and ocular SAs, and preserved more preoperative-corneal asphericity than the OPDCAT algorithms. PMID:25397788

  13. Towards optimal clinical and epidemiological registration of haematological malignancies: Guidelines for recording progressions, transformations and multiple diagnoses.

    PubMed

    Gavin, Anna; Rous, Brian; Marcos-Gragera, Rafael; Middleton, Richard; Steliarova-Foucher, Eva; Maynadie, Marc; Zanetti, Roberto; Visser, Otto

    2015-06-01

    Haematological malignancies (HM) represent over 6% of the total cancer incidence in Europe and affect all ages, ranging between 45% of all cancers in children and 7% in the elderly. Thirty per cent of childhood cancer deaths are due to HM, 8% in the elderly. Their registration presents specific challenges, mainly because HM may transform or progress in the course of the disease into other types of HM. In the context of cancer registration decisions have to be made about classifying subsequent notifications on the same patient as the same tumour (progression), a transformation or a new tumour registration. Allocation of incidence date and method of diagnosis must also be standardised. We developed European Network of Cancer Registries (ENCR) recommendations providing specific advice for cancer registries to use haematology and molecular laboratories as data sources, conserve the original date of incidence in case of change of diagnosis, make provision for recording both the original as well as transformed tumour and to apply precise rules for recording and counting multiple diagnoses. A reference table advising on codes which reflect a potential transformation or a new tumour is included. This work will help to improve comparability of data produced by population-based cancer registries, which are indispensable for aetiological research, health care planning and clinical research, an increasing important area with the application of targeted therapies. PMID:24630945

  14. An international observational study suggests that artificial intelligence for clinical decision support optimizes anemia management in hemodialysis patients.

    PubMed

    Barbieri, Carlo; Molina, Manuel; Ponce, Pedro; Tothova, Monika; Cattinelli, Isabella; Ion Titapiccolo, Jasmine; Mari, Flavio; Amato, Claudia; Leipold, Frank; Wehmeyer, Wolfgang; Stuard, Stefano; Stopper, Andrea; Canaud, Bernard

    2016-08-01

    Managing anemia in hemodialysis patients can be challenging because of competing therapeutic targets and individual variability. Because therapy recommendations provided by a decision support system can benefit both patients and doctors, we evaluated the impact of an artificial intelligence decision support system, the Anemia Control Model (ACM), on anemia outcomes. Based on patient profiles, the ACM was built to recommend suitable erythropoietic-stimulating agent doses. Our retrospective study consisted of a 12-month control phase (standard anemia care), followed by a 12-month observation phase (ACM-guided care) encompassing 752 patients undergoing hemodialysis therapy in 3 NephroCare clinics located in separate countries. The percentage of hemoglobin values on target, the median darbepoetin dose, and individual hemoglobin fluctuation (estimated from the intrapatient hemoglobin standard deviation) were deemed primary outcomes. In the observation phase, median darbepoetin consumption significantly decreased from 0.63 to 0.46 μg/kg/month, whereas on-target hemoglobin values significantly increased from 70.6% to 76.6%, reaching 83.2% when the ACM suggestions were implemented. Moreover, ACM introduction led to a significant decrease in hemoglobin fluctuation (intrapatient standard deviation decreased from 0.95 g/dl to 0.83 g/dl). Thus, ACM support helped improve anemia outcomes of hemodialysis patients, minimizing erythropoietic-stimulating agent use with the potential to reduce the cost of treatment. PMID:27262365

  15. Dementia Prevention: optimizing the use of observational data for personal, clinical, and public health decision-making

    PubMed Central

    Dacks, Penny A; Andrieu, Sandrine; Blacker, Deborah; Carman, Aaron J; Green, Allan M; Grodstein, Francine; Henderson, Victor W; James, Bryan D.; Lane, Rachel F; Lau, Joseph; Lin, Pei-Jung; Reeves, Barnaby C.; Shah, Raj C.; Vellas, Bruno; Yaffe, Kristine; Yurko-Mauro, Karin; Shineman, Diana W; Bennett, David A; Fillit, Howard M

    2015-01-01

    Worldwide, over 35 million people suffer from Alzheimer’s disease and related dementias. This number is expected to triple over the next 40 years. How can we improve the evidence supporting strategies to reduce the rate of dementia in future generations? The risk of dementia is likely influenced by modifiable factors such as exercise, cognitive activity, and the clinical management of diabetes and hypertension. However, the quality of evidence is limited and it remains unclear whether specific interventions to reduce these modifiable risk factors can, in turn, reduce the risk of dementia. Although randomized controlled trials are the gold-standard for causality, the majority of evidence for long-term dementia prevention derives from, and will likely continue to derive from, observational studies. Although observational research has some unavoidable limitations, its utility for dementia prevention might be improved by, for example, better distinction between confirmatory and exploratory research, higher reporting standards, investment in effectiveness research enabled by increased data-pooling, and standardized exposure and outcome measures. Informed decision-making by the general public on low-risk health choices that could have broad potential benefits could be enabled by internet-based tools and decision-aids to communicate the evidence, its quality, and the estimated magnitude of effect. PMID:26146610

  16. A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro.

    PubMed

    Navabi, H; Jasani, B; Reece, A; Clayton, A; Tabi, Z; Donninger, C; Mason, M; Adams, M

    2009-01-01

    Maturation of dendritic cells (DC) can be triggered in vitro by inflammatory cytokines or Toll-like receptor (TLR) ligands such as CpG or polyI:C. Corresponding, well-characterized agents which can be applied in clinical settings are sparse. We have evaluated a clinical grade, non-toxic analogue of polyI:C, poly(I:C12U) (Ampligen), as a potential adjuvant for cancer immunotherapy, for its ability to drive maturation of human myeloid DC. Our results provide evidence that poly(I:C12U) is effective in inducing optimal phenotypic (elevated levels of MHC-Class I/Class II, CD83, CCR7, CD86 and CD40 molecules) and functional maturation of human DC in vitro, capable of promoting the production of the inflammatory (Th1-type) cytokine IL-12, with significantly lower levels of IL-10 production, compared to that induced by the parent compound polyI:C. Importantly, poly(I:C12U) has a comparable effect on the maturation and function of DC derived either from healthy donors or cancer patients indicating that it is able to overcome any immune suppressive factors associated with the tumour bearing state. These characteristics make poly(I:C12U) a suitable agent for use as an adjuvant in cancer directed immunotherapeutic regimes. PMID:18977262

  17. Daily Review of Antimicrobial Use Facilitates the Early Optimization of Antimicrobial Therapy and Improves Clinical Outcomes of Patients with Bloodstream Infections.

    PubMed

    Niwa, Takashi; Watanabe, Tamayo; Goto, Takayuki; Ohta, Hirotoshi; Nakayama, Asami; Suzuki, Keiko; Shinoda, Yasutaka; Tsuchiya, Mayumi; Yasuda, Koji; Murakami, Nobuo; Itoh, Yoshinori

    2016-05-01

    Insufficient information is available to confirm the beneficial effects of implementing an antimicrobial stewardship program in reducing mortality of patients with bloodstream infections. A single institutional cohort study was conducted to evaluate clinical outcomes after implementation of a daily review of antimicrobials used to treat patients with bloodstream infections. Subjects were allocated to groups receiving either intervention or nonintervention. After implementation of an antimicrobial stewardship program, the day from the onset of infection required to administer effective intravenous antimicrobial treatment was significantly shortened (p=0.022), and the rate of de-escalation was significantly elevated (p<0.001) compared with the nonintervention group. Further, the rate of 30-d death associated with bloodstream infection was siginificantly reduced from 11.4 to 5.4% (p=0.030) compared with the nonintervention group. The incidence of adverse events was significantly lower in the intervention group than in the nonintervention group (7.7 vs. 28.0%, p<0.001). Our present findings suggest that daily review of the use of antimicrobials was highly effective for optimizing early antimicrobial therapy and improved clinical outcomes of patients with bloodstream infections. PMID:26923491

  18. Optimizing Viable Leukocyte Sampling from the Female Genital Tract for Clinical Trials: An International Multi-Site Study

    PubMed Central

    De Rosa, Stephen C.; Martinson, Jeffrey A.; Plants, Jill; Brady, Kirsten E.; Gumbi, Pamela P.; Adams, Devin J.; Vojtech, Lucia; Galloway, Christine G.; Fialkow, Michael; Lentz, Gretchen; Gao, Dayong; Shu, Zhiquan; Nyanga, Billy; Izulla, Preston; Kimani, Joshua; Kimwaki, Steve; Bere, Alfred; Moodie, Zoe; Landay, Alan L.; Passmore, Jo-Ann S.; Kaul, Rupert; Novak, Richard M.; McElrath, M. Juliana; Hladik, Florian

    2014-01-01

    towards implementing mucosal cell sampling in international clinical trials of HIV prevention. PMID:24454917

  19. Meta-analysis is not enough: The critical role of pathophysiology in determining optimal care in clinical nutrition.

    PubMed

    Soeters, Peter; Bozzetti, Federico; Cynober, Luc; Elia, Marinos; Shenkin, Alan; Sobotka, Lubos

    2016-06-01

    Evidence based medicine has preferably been based on prospective randomized controlled trials (PRCT's) and subsequent meta-analyses in many fields including nutrition and metabolism. These meta-analyses often yield convincing, contradictory or no proof of effectiveness. Consequently recommendations and guidelines of varying validity and quality have been published, often failing to convince the medical, insurance and government worlds to support nutritional care. Causes for lack of adequate proof of effectiveness are manifold. Many studies and meta-analyses lacked pathophysiological depth in design and interpretation. Study populations were not homogenous and endpoints not always clearly defined. Patients were included not at nutritional risk, unlikely to benefit from nutritional intervention. Others received nutrients in excess of requirements or tolerance due to organ failure. To include all available studies in a meta-analysis, study quality and homogeneity were only assessed on the basis of formal study design and outcome rather than on patient characteristics. Consequently, some studies showed benefit but included patients suffering harm, other studies were negative but contained patients that benefited. Recommendations did not always emphasize these shortcomings, confusing the medical and nutritional community and creating the impression that nutritional support is not beneficial. Strong reliance on meta-analyses and guidelines shifts the focus of education from studying clinical and nutritional physiology to memorizing guidelines. To prevent or improve malnutrition more physiological knowledge should be acquired to personalize nutritional practices and to more correctly value and evaluate the evidence. This also applies to the design and interpretation of PRCT's and meta-analyses. PMID:26615913

  20. Graded Achievement, Tested Achievement, and Validity

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2015-01-01

    Twenty-eight studies of grades, over a century, were reviewed using the argument-based approach to validity suggested by Kane as a theoretical framework. The review draws conclusions about the meaning of graded achievement, its relation to tested achievement, and changes in the construct of graded achievement over time. "Graded…

  1. Optimizing Clinical Operations as part of a Global Emergency Medicine Initiative in Kumasi, Ghana: Application of Lean Manufacturing Principals to Low Resource Health Systems

    PubMed Central

    Carter, Patrick M.; Desmond, Jeffery S.; Akanbobnaab, Christopher; Oteng, Rockefeller A.; Rominski, Sarah; Barsan, William G.; Cunningham, Rebecca

    2012-01-01

    Background Although many global health programs focus on providing clinical care or medical education, improving clinical operations can have a significant effect on patient care delivery, especially in developing health systems without high-level operations management. Lean manufacturing techniques have been effective in decreasing emergency department (ED) length of stay, patient waiting times, numbers of patients leaving without being seen, and door-to-balloon times for ST-elevation myocardial infarction in developed health systems; but use of Lean in low to middle income countries with developing emergency medicine systems has not been well characterized. Objectives To describe the application of Lean manufacturing techniques to improve clinical operations at Komfo Anokye Teaching Hospital in Ghana and to identify key lessons learned to aid future global EM initiatives. Methods A three-week Lean improvement program focused on the hospital admissions process at Komfo Anokye Teaching Hospital was completed by a 14-person team in six stages: problem definition, scope of project planning, value stream mapping, root cause analysis, future state planning, and implementation planning. Results The authors identified eight lessons learned during our use of Lean to optimize the operations of an ED in a global health setting: 1) the Lean process aided in building a partnership with Ghanaian colleagues; 2) obtaining and maintaining senior institutional support is necessary and challenging; 3) addressing power differences among the team to obtain feedback from all team members is critical to successful Lean analysis; 4) choosing a manageable initial project is critical to influence long-term Lean use in a new environment; 5) data intensive Lean tools can be adapted and are effective in a less resourced health system; 6) several Lean tools focused on team problem solving techniques worked well in a low resource system without modification; 7) using Lean highlighted that

  2. Analysis of Regional Timelines To Set Up a Global Phase III Clinical Trial in Breast Cancer: The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Experience

    PubMed Central

    de Azambuja, Evandro; Bradbury, Ian; Saini, Kamal S.; Bines, José; Simon, Sergio D.; Dooren, Veerle Van; Aktan, Gursel; Pritchard, Kathleen I.; Wolff, Antonio C.; Smith, Ian; Jackisch, Christian; Lang, Istvan; Untch, Michael; Boyle, Frances; Xu, Binghe; Baselga, Jose; Perez, Edith A.; Piccart-Gebhart, Martine

    2013-01-01

    Purpose. This study measured the time taken for setting up the different facets of Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO), an international phase III study being conducted in 44 participating countries. Methods. Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected in the ALTTO study. Analyses were conducted by grouping countries into either geographic regions or economic classes as per the World Bank's criteria. Results. South America had a significantly longer time to RA approval (median: 236 days, range: 21–257 days) than Europe (median: 52 days, range: 0–151 days), North America (median: 26 days, range: 22–30 days), and Asia-Pacific (median: 62 days, range: 37–75 days). Upper-middle economies had longer times to RA approval (median: 123 days, range: 21–257 days) than high-income (median: 47 days, range: 0–112 days) and lower-middle income economies (median: 57 days, range: 37–62 days). No significant difference was observed for time to EC/IRB approval across the studied regions (median: 59 days, range 0–174 days). Overall, the median time from EC/IRB approval to first recruited patient was 169 days (range: 26–412 days). Conclusion. This study highlights the long time intervals required to activate a global phase III trial. Collaborative research groups, pharmaceutical industry sponsors, and regulatory authorities should analyze the current system and enter into dialogue for optimizing local policies. This would enable faster access of patients to innovative therapies and enhance the efficiency of clinical research. PMID:23359433

  3. Sustaining excellence: clinical nurse specialist practice and magnet designation.

    PubMed

    Muller, Anne C; Hujcs, Marianne; Dubendorf, Phyllis; Harrington, Paul T

    2010-01-01

    Clinical nurse specialist practice is essential in providing the clinical expertise, leadership, and organizational influence necessary for attaining the excellence in care reflected by the American Nurses Credentialing Center's Magnet designation. Clinical nurse specialists, prepared as advanced practice nurses, bring clinical expertise, knowledge of advanced physiology, and pathology and a system-wide vision for process improvements. This unique curriculum specifically prepares clinical nurse specialists (CNSs) to immediately practice as leaders of interdisciplinary groups to improve outcomes. Clinical nurse specialist graduates possess an understanding of complex adaptive systems theory, advanced physical assessment, and pathophysiology and knowledge of optimal learning modalities, all applicable to improving the health care environment. Their practice specifically links complex clinical data with multidisciplinary partnering and understanding of organizational systems. The basis for optimal clinical practice change and sustained process improvement, foundational to Magnet designation, is grounded in the combined educational preparation and systems impact of CNS practice. This article describes the role of the CNS in achieving and sustaining Magnet designation in an urban, academic quaternary care center. Using the National Association of Clinical Nurse Specialists model of spheres of influence, focus is on the CNS's contribution to improving clinical outcomes, nurse satisfaction, and patient satisfaction. Exemplars demonstrating use of a champion model to implement practice improvement and rapid adoption of optimal practice guidelines are provided. These exemplars reflect improved and sustained patient care outcomes, and implementation strategies used to achieve these improvements are discussed. PMID:20716978

  4. Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

    SciTech Connect

    Coteron, Jose M.; Marco, Maria; Esquivias, Jorge; Deng, Xiaoyi; White, Karen L.; White, John; Koltun, Maria; El Mazouni, Farah; Kokkonda, Sreekanth; Katneni, Kasiram; Bhamidipati, Ravi; Shackleford, David M.; Angulo-Barturen, Inigo; Ferrer, Santiago B.; Jimenez-Diaz, Maria Belen; Gamo, Francisco-Javier; Goldsmith, Elizabeth J.; Charman, William N.; Bathurst, Ian; Floyd, David; Matthews, David; Burrows, Jeremy N.; Rathod, Pradipsinh K.; Charman, Susan A.; Phillips, Margaret A.

    2012-02-27

    Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmacokinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.

  5. Structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential

    PubMed Central

    Coteron, Jose M.; Marco, María; Esquivias, Jorge; Deng, Xiaoyi; White, Karen L.; White, John; Koltun, Maria; Mazouni, Farah El; Kokkonda, Sreekanth; Katneni, Kasiram; Bhamidipati, Ravi; Shackleford, David M.; Barturen, Iñigo Angulo; Ferrer, Santiago B.; Jiménez-Díaz, María Belén; Gamo, Francisco-Javier; Goldsmith, Elizabeth J.; Charman, William N.; Bathurst, Ian; Floyd, David; Matthews, David; Burrows, Jeremy N.; Rathod, Pradipsinh K.; Charman, Susan A.; Phillips, Margaret A.

    2011-01-01

    Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential anti-malarials we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmacokinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound towards clinical candidate status. PMID:21696174

  6. Prospective Optimization

    PubMed Central

    Sejnowski, Terrence J.; Poizner, Howard; Lynch, Gary; Gepshtein, Sergei; Greenspan, Ralph J.

    2014-01-01

    Human performance approaches that of an ideal observer and optimal actor in some perceptual and motor tasks. These optimal abilities depend on the capacity of the cerebral cortex to store an immense amount of information and to flexibly make rapid decisions. However, behavior only approaches these limits after a long period of learning while the cerebral cortex interacts with the basal ganglia, an ancient part of the vertebrate brain that is responsible for learning sequences of actions directed toward achieving goals. Progress has been made in understanding the algorithms used by the brain during reinforcement learning, which is an online approximation of dynamic programming. Humans also make plans that depend on past experience by simulating different scenarios, which is called prospective optimization. The same brain structures in the cortex and basal ganglia that are active online during optimal behavior are also active offline during prospective optimization. The emergence of general principles and algorithms for goal-directed behavior has consequences for the development of autonomous devices in engineering applications. PMID:25328167

  7. The electronic medical office: optimizing solutions.

    PubMed

    Kirschenbaum, Ira H; Mabrey, Jay D; Wood, George W; Alexander, A Herbert; Rhoades, Charles E; Alexander, Ian J; Golladay, Gregory J; Wheeless, Clifford

    2008-01-01

    Optimizing the care for patients in the orthopaedic clinical setting involves a wide range of issues. Surgical techniques, preoperative and postoperative care, long-term outcomes follow-up, continuing education, and patient communication are a few of the important areas that surgeons deal with on a regular basis. Successful management of this information has an impact on clinical outcomes, direct patient care, financial decisions, and management of the surgeon's time. The development of a comprehensive electronic medical office is a powerful and probably necessary tool to successfully manage such information and achieve the goals of an effective and safe orthopaedic practice. PMID:18399621

  8. First-Stage Development and Validation of a Web-Based Automated Dietary Modeling Tool: Using Constraint Optimization Techniques to Streamline Food Group and Macronutrient Focused Dietary Prescriptions for Clinical Trials

    PubMed Central

    Morrison, Evan; Sullivan, Emma; Dam, Hoa Khanh

    2016-01-01

    Background Standardizing the background diet of participants during a dietary randomized controlled trial is vital to trial outcomes. For this process, dietary modeling based on food groups and their target servings is employed via a dietary prescription before an intervention, often using a manual process. Partial automation has employed the use of linear programming. Validity of the modeling approach is critical to allow trial outcomes to be translated to practice. Objective This paper describes the first-stage development of a tool to automatically perform dietary modeling using food group and macronutrient requirements as a test case. The Dietary Modeling Tool (DMT) was then compared with existing approaches to dietary modeling (manual and partially automated), which were previously available to dietitians working within a dietary intervention trial. Methods Constraint optimization techniques were implemented to determine whether nonlinear constraints are best suited to the development of the automated dietary modeling tool using food composition and food consumption data. Dietary models were produced and compared with a manual Microsoft Excel calculator, a partially automated Excel Solver approach, and the automated DMT that was developed. Results The web-based DMT was produced using nonlinear constraint optimization, incorporating estimated energy requirement calculations, nutrition guidance systems, and the flexibility to amend food group targets for individuals. Percentage differences between modeling tools revealed similar results for the macronutrients. Polyunsaturated fatty acids and monounsaturated fatty acids showed greater variation between tools (practically equating to a 2-teaspoon difference), although it was not considered clinically significant when the whole diet, as opposed to targeted nutrients or energy requirements, were being addressed. Conclusions Automated modeling tools can streamline the modeling process for dietary intervention trials

  9. Achieving Cannabis Cessation - Evaluating N-acetylcysteine Treatment (ACCENT): Design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network

    PubMed Central

    McClure, Erin A.; Sonne, Susan C.; Winhusen, Theresa; Carroll, Kathleen M.; Ghitza, Udi E.; McRae-Clark, Aimee L.; Matthews, Abigail G.; Sharma, Gaurav; Van Veldhuisen, Paul; Vandrey, Ryan G.; Levin, Frances R.; Weiss, Roger D.; Lindblad, Robert; Allen, Colleen; Mooney, Larissa J.; Haynes, Louise; Brigham, Gregory S.; Sparenborg, Steve; Hasson, Albert L.; Gray, Kevin M.

    2014-01-01

    Despite recent advances in behavioral interventions for cannabis use disorders, effect sizes remain modest, and few individuals achieve long-term abstinence. One strategy to enhance outcomes is the addition of pharmacotherapy to complement behavioral treatment, but to date no efficacious medications targeting cannabis use disorders in adults through large, randomized controlled trials have been identified. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) is currently conducting a study to test the efficacy of N-acetylcysteine (NAC) versus placebo (PBO), added to contingency management, for cannabis cessation in adults (ages 18–50). This study was designed to replicate positive findings from a study in cannabis-dependent adolescents that found greater odds of abstinence with NAC compared to PBO. This paper describes the design and implementation of an ongoing 12-week, intent-to-treat, double-blind, randomized, placebo-controlled study with one follow-up visit four weeks post-treatment. Approximately 300 treatment-seeking cannabis-dependent adults will be randomized to NAC or PBO across six study sites in the United States. The primary objective of this 12-week study is to evaluate the efficacy of twice-daily orally-administered NAC (1200 mg) versus matched PBO, added to contingency management, on cannabis abstinence. NAC is among the first medications to demonstrate increased odds of abstinence in a randomized controlled study among cannabis users in any age group. The current study will assess the cannabis cessation efficacy of NAC combined with a behavioral intervention in adults, providing a novel and timely contribution to the evidence base for the treatment of cannabis use disorders. PMID:25179587

  10. Achieving cannabis cessation -- evaluating N-acetylcysteine treatment (ACCENT): design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network.

    PubMed

    McClure, Erin A; Sonne, Susan C; Winhusen, Theresa; Carroll, Kathleen M; Ghitza, Udi E; McRae-Clark, Aimee L; Matthews, Abigail G; Sharma, Gaurav; Van Veldhuisen, Paul; Vandrey, Ryan G; Levin, Frances R; Weiss, Roger D; Lindblad, Robert; Allen, Colleen; Mooney, Larissa J; Haynes, Louise; Brigham, Gregory S; Sparenborg, Steve; Hasson, Albert L; Gray, Kevin M

    2014-11-01

    Despite recent advances in behavioral interventions for cannabis use disorders, effect sizes remain modest, and few individuals achieve long-term abstinence. One strategy to enhance outcomes is the addition of pharmacotherapy to complement behavioral treatment, but to date no efficacious medications targeting cannabis use disorders in adults through large, randomized controlled trials have been identified. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) is currently conducting a study to test the efficacy of N-acetylcysteine (NAC) versus placebo (PBO), added to contingency management, for cannabis cessation in adults (ages 18-50). This study was designed to replicate positive findings from a study in cannabis-dependent adolescents that found greater odds of abstinence with NAC compared to PBO. This paper describes the design and implementation of an ongoing 12-week, intent-to-treat, double-blind, randomized, placebo-controlled study with one follow-up visit four weeks post-treatment. Approximately 300 treatment-seeking cannabis-dependent adults will be randomized to NAC or PBO across six study sites in the United States. The primary objective of this 12-week study is to evaluate the efficacy of twice-daily orally-administered NAC (1200 mg) versus matched PBO, added to contingency management, on cannabis abstinence. NAC is among the first medications to demonstrate increased odds of abstinence in a randomized controlled study among cannabis users in any age group. The current study will assess the cannabis cessation efficacy of NAC combined with a behavioral intervention in adults, providing a novel and timely contribution to the evidence base for the treatment of cannabis use disorders. PMID:25179587

  11. Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation: A Randomized, Double–Blind Clinical Trial Study Protocol

    PubMed Central

    Bolognini, Nadia; Crandell, David; Merabet, Lotfi B

    2016-01-01

    ) before and after the intervention. Results This clinical trial received institutional review board (IRB) approval in July of 2015 and enrollment started in December of 2015. To date 2 participants have been enrolled. The estimate enrollment rate is about 30 to 35 patients per year; thus we expect to complete enrollment in 4 years. Conclusions This factorial design will provide relevant data to evaluate whether tDCS combined with MT is more effective than each therapy alone, as well as with no intervention (sham/sham) in patients with chronic PLP after unilateral lower limb amputation. In addition, this randomized clinical trial will help to investigate the neurophysiological mechanisms underlying the disease, which could potentially provide relevant findings for further management of this chronic condition and also help to optimize the use of this novel intervention. Trial Registration Clinicaltrials.gov NCT02487966; https://clinicaltrials.gov/ct2/show/NCT02487966 (Archived by WebCite at http://www.webcitation.org/6i3GrKMyf) PMID:27383993

  12. Determining optimal clinical target volume margins on the basis of microscopic extracapsular extension of metastatic nodes in patients with non-small-cell lung cancer

    SciTech Connect

    Yuan Shuanghu; Meng Xue; Yu Jinming . E-mail: fishtigers@yahoo.com.cn; Mu Dianbin; Chao, K.S. Clifford; Zhang Jiandong; Zhong Weixia; Yu Yonghua; Wang Jialin; Sun Xindong; Yang Guoren; Wang Yongzheng

    2007-03-01

    Purpose: To determine the optimal clinical target volume (CTV) margins around the nodal gross tumor volume (GTV) in non-small-cell lung cancer (NSCLC) patients by assessing microscopic tumor extension beyond regional lymph node capsules. Methods and Materials: The incidence of nodal extracapsular extension (ECE) and relationship with nodal size were reviewed in 243 patients. Histologic sections of dissected regional lymph nodes up to 30 mm in size were examined to measure the extent of microscopic ECE. We determined the distribution of cases according to extent of ECE and the relationships between ECE extent and lymph node size, regional nodal disease extent, histologic type, and degree of differentiation. Results: The nodal ECE was seen in 41.6% of patients (101/243) and 33.4% of lymph nodes (214/640), and the incidence correlated to larger lymph node size positively. The extent of ECE was 0.7 mm in mean (range, 0-12.0 mm) and {<=}3 mm in 95% of the nodes. Positive correlations were found between extent of ECE and larger lymph node size ({>=}20 mm vs. 10-19 mm or <10 mm, p = 0.005), advanced nodal stage (N2 vs. N1, p = 0.046), and moderate or poor (vs. good or unknown) nodal differentiation (p = 0.002). ECE did not differ significantly by histologic type or nodal station. Conclusions: The incidence of ECE related to lymph node size, and ECE extent related to lymph node size, stage, and differentiation. It may be reasonable to recommend 3-mm CTV margins for pathologic lymph nodes <20 mm and more generous margins for lymph nodes {>=}20 mm.

  13. Gear optimization

    NASA Technical Reports Server (NTRS)

    Vanderplaats, G. N.; Chen, Xiang; Zhang, Ning-Tian

    1988-01-01

    The use of formal numerical optimization methods for the design of gears is investigated. To achieve this, computer codes were developed for the analysis of spur gears and spiral bevel gears. These codes calculate the life, dynamic load, bending strength, surface durability, gear weight and size, and various geometric parameters. It is necessary to calculate all such important responses because they all represent competing requirements in the design process. The codes developed here were written in subroutine form and coupled to the COPES/ADS general purpose optimization program. This code allows the user to define the optimization problem at the time of program execution. Typical design variables include face width, number of teeth and diametral pitch. The user is free to choose any calculated response as the design objective to minimize or maximize and may impose lower and upper bounds on any calculated responses. Typical examples include life maximization with limits on dynamic load, stress, weight, etc. or minimization of weight subject to limits on life, dynamic load, etc. The research codes were written in modular form for easy expansion and so that they could be combined to create a multiple reduction optimization capability in future.

  14. Outcomes of patients with myelodysplastic syndromes who achieve stable disease after treatment with hypomethylating agents.

    PubMed

    Nazha, Aziz; Sekeres, Mikkael A; Garcia-Manero, Guillermo; Barnard, John; Al Ali, Najla H; Roboz, Gail J; Steensma, David P; DeZern, Amy E; Zimmerman, Cassie; Jabbour, Elias J; Zell, Katrina; List, Alan F; Kantarjian, Hagop M; Maciejewski, Jaroslaw P; Komrokji, Rami S

    2016-02-01

    Treatment with hypomethylating agents (HMAs) improves overall survival (OS) in patients who achieve a response of stable disease (SD) or better (complete remission [CR], partial remission [PR], or hematologic improvement [HI]). It is not well established if patients who achieve SD at 4-6 months of therapy should be offered different therapies to optimize their response or continue with the same regimen. Clinical data were obtained from the MDS Clinical Research Consortium database. SD was defined as no evidence of progression and without achievement of any other responses. Of 291 patients treated with AZA or DAC, 55% achieved their best response (BR) at 4-6 months. Among patients with SD at 4-6 months, 29 (20%) achieved a better response at a later treatment time point. Younger patients with lower bone marrow blast percentages, and intermediate risk per IPSS-R were more likely to achieve a better response (CR, PR, or HI) after SD at 4-6 months. Patients with SD who subsequently achieved CR had superior OS compared to patients who remained with SD (28.1 vs. 14.4 months, respectively, p=.04). In conclusion, patients treated with HMAs who achieves CR after a SD status had longer survival with continuous treatment after 6 months. PMID:26777537

  15. Outcomes of patients with myelodysplastic syndromes who achieve stable disease after treatment with hypomethylating agents

    PubMed Central

    Nazha, Aziz; Sekeres, Mikkael A.; Garcia-Manero, Guillermo; Barnard, John; Al Ali, Najla H.; Roboz, Gail J.; Steensma, David P.; DeZern, Amy E.; Zimmerman, Cassie; Jabbour, Elias J.; Zell, Katrina; List, Alan F.; Kantarjian, Hagop M.; Maciejewski, Jaroslaw P.; Komrokji, Rami S.

    2016-01-01

    Treatment with hypomethylating agents (HMAs) improves overall survival (OS) in patients who achieve a response of stable disease (SD) or better (complete remission [CR], partial remission [PR], or hematologic improvement [HI]). It is not well established if patients who achieve SD at 4–6 months of therapy should be offered different therapies to optimize their response or continue with the same regimen. Clinical data were obtained from the MDS Clinical Research Consortium database. SD was defined as no evidence of progression and without achievement of any other responses. Of 291 patients treated with AZA or DAC, 55% achieved their best response (BR) at 4–6 months. Among patients with SD at 4–6 months, 29 (20%) achieved a better response at a later treatment time point. Younger patients with lower bone marrow blast percentages, and intermediate risk per IPSS-R were more likely to achieve a better response (CR, PR, or HI) after SD at 4–6 months. Patients with SD who subsequently achieved CR had superior OS compared to patients who remained with SD (28.1 vs. 14.4 months, respectively, p =.04). In conclusion, patients treated with HMAs who achieves CR after a SD status had longer survival with continuous treatment after 6 months. PMID:26777537

  16. Comparing Science Achievement Constructs: Targeted and Achieved

    ERIC Educational Resources Information Center

    Ferrara, Steve; Duncan, Teresa

    2011-01-01

    This article illustrates how test specifications based solely on academic content standards, without attention to other cognitive skills and item response demands, can fall short of their targeted constructs. First, the authors inductively describe the science achievement construct represented by a statewide sixth-grade science proficiency test.…

  17. Very Low Ventricular Pacing Rates Can Be Achieved Safely in a Heterogeneous Pacemaker Population and Provide Clinical Benefits: The CANadian Multi-Centre Randomised Study-Spontaneous AtrioVEntricular Conduction pReservation (CAN-SAVE R) Trial

    PubMed Central

    Thibault, Bernard; Ducharme, Anique; Baranchuk, Adrian; Dubuc, Marc; Dyrda, Katia; Guerra, Peter G; Macle, Laurent; Mondésert, Blandine; Rivard, Léna; Roy, Denis; Talajic, Mario; Andrade, Jason; Nitzsché, Rémi; Khairy, Paul

    2015-01-01

    Background It is well recognized that right ventricular apical pacing can have deleterious effects on ventricular function. We performed a head-to-head comparison of the SafeR pacing algorithm versus DDD pacing with a long atrioventricular delay in a heterogeneous population of patients with dual-chamber pacemakers. Methods and Results In a multicenter prospective double-blinded randomized trial conducted at 10 centers in Canada, 373 patients, age 71±11 years, with indications for dual chamber DC pacemakers were randomized 1:1 to SafeR or DDD pacing with a long atrioventricular delay (250 ms). The primary objective was twofold: (1) reduction in the proportion of ventricular paced beats at 1 year; and (2) impact on atrial fibrillation burden at 3 years, defined as the ratio between cumulative duration of mode-switches divided by follow-up time. Statistical significance of both co-primary end points was required for the trial to be considered positive. At 1 year of follow-up, the median proportion of ventricular-paced beats was 4.0% with DDD versus 0% with SafeR (P<0.001). At 3 years of follow-up, the atrial fibrillation burden was not significantly reduced with SafeR versus DDD (median 0.00%, interquartile range [0.00% to 0.23%] versus median 0.01%, interquartile range [0.00% to 0.44%], respectively, P=0.178]), despite a persistent reduction in the median proportion of ventricular-paced beats (10% with DDD compared to 0% with SafeR). Conclusions A ventricular-paced rate <1% was safely achieved with SafeR in a population with a wide spectrum of indications for dual-chamber pacing. However, the lower percentage of ventricular pacing did not translate into a significant reduction in atrial fibrillation burden. Clinical Trial Registration URL: https://www.clinicaltrials.gov/ Unique identifier: NCT01219621. PMID:26206737

  18. Varieties of Achievement Motivation.

    ERIC Educational Resources Information Center

    Kukla, Andre; Scher, Hal

    1986-01-01

    A recent article by Nicholls on achievement motivation is criticized on three points: (1) definitions of achievement motives are ambiguous; (2) behavioral consequences predicted do not follow from explicit theoretical assumptions; and (3) Nicholls's account of the relation between his theory and other achievement theories is factually incorrect.…

  19. Motivation and School Achievement.

    ERIC Educational Resources Information Center

    Maehr, Martin L.; Archer, Jennifer

    Addressing the question, "What can be done to promote school achievement?", this paper summarizes the literature on motivation relating to classroom achievement and school effectiveness. Particular attention is given to how values, ideology, and various cultural patterns impinge on classroom performance and serve to enhance motivation to achieve.…

  20. Mobility and Reading Achievement.

    ERIC Educational Resources Information Center

    Waters, Theresa Z.

    A study examined the effect of geographic mobility on elementary school students' achievement. Although such mobility, which requires students to make multiple moves among schools, can have a negative impact on academic achievement, the hypothesis for the study was that it was not a determining factor in reading achievement test scores. Subjects…

  1. PASS and Reading Achievement.

    ERIC Educational Resources Information Center

    Kirby, John R.

    Two studies examined the effectiveness of the PASS (Planning, Attention, Simultaneous, and Successive cognitive processes) theory of intelligence in predicting reading achievement scores of normally achieving children and distinguishing children with reading disabilities from normally achieving children. The first study dealt with predicting…

  2. [Update of planning tables of cholesterol-lowering therapy orientated to achieve LDL therapeutic targets].

    PubMed

    Masana, Luis; Plana, Núria

    2015-01-01

    This is the third update of a planning-table for use in cholesterol-lowering therapy, so as to obtain LDLc objectives. This is an easy to use laptop tool to help choose the best statin or combination therapy (statin plus ezetimibe) depending on the current LDL concentration of the patient, and the LDLc objective to achieve. It is based on a colour code that indicates the drugs that are efficient enough to help patients to achieve their LDL goal. Along with the table, recommendations are given for the best strategy in order to implement the optimal therapy in a maximum of two clinical encounters. PMID:25865752

  3. Stepwise multi-criteria optimization for robotic radiosurgery

    SciTech Connect

    Schlaefer, A.; Schweikard, A.

    2008-05-15

    Achieving good conformality and a steep dose gradient around the target volume remains a key aspect of radiosurgery. Clearly, this involves a trade-off between target coverage, conformality of the dose distribution, and sparing of critical structures. Yet, image guidance and robotic beam placement have extended highly conformal dose delivery to extracranial and moving targets. Therefore, the multi-criteria nature of the optimization problem becomes even more apparent, as multiple conflicting clinical goals need to be considered coordinate to obtain an optimal treatment plan. Typically, planning for robotic radiosurgery is based on constrained optimization, namely linear programming. An extension of that approach is presented, such that each of the clinical goals can be addressed separately and in any sequential order. For a set of common clinical goals the mapping to a mathematical objective and a corresponding constraint is defined. The trade-off among the clinical goals is explored by modifying the constraints and optimizing a simple objective, while retaining feasibility of the solution. Moreover, it becomes immediately obvious whether a desired goal can be achieved and where a trade-off is possible. No importance factors or predefined prioritizations of clinical goals are necessary. The presented framework forms the basis for interactive and automated planning procedures. It is demonstrated for a sample case that the linear programming formulation is suitable to search for a clinically optimal treatment, and that the optimization steps can be performed quickly to establish that a Pareto-efficient solution has been found. Furthermore, it is demonstrated how the stepwise approach is preferable compared to modifying importance factors.

  4. Regenerative Endodontic Treatment: Report of Two Cases with Different Clinical Management and Outcomes

    PubMed Central

    Khoshkhounejad, Mehrfam; Shokouhinejad, Noushin

    2015-01-01

    Endodontic intervention in necrotic immature permanent teeth is usually a clinical challenge. With appropriate case selection, regenerative treatment can be effective, providing a desirable outcome. However, there is still no consensus on the optimal disinfection protocol or the method to achieve predictable clinical outcome. This article presents two cases of regenerative treatment in necrotic immature teeth, using mineral trioxide aggregate (MTA) and BiodentineTM as coronal barriers and different irrigants, which led to different clinical outcomes. PMID:26884781

  5. Regenerative Endodontic Treatment: Report of Two Cases with Different Clinical Management and Outcomes.

    PubMed

    Khoshkhounejad, Mehrfam; Shokouhinejad, Noushin; Pirmoazen, Salma

    2015-06-01

    Endodontic intervention in necrotic immature permanent teeth is usually a clinical challenge. With appropriate case selection, regenerative treatment can be effective, providing a desirable outcome. However, there is still no consensus on the optimal disinfection protocol or the method to achieve predictable clinical outcome. This article presents two cases of regenerative treatment in necrotic immature teeth, using mineral trioxide aggregate (MTA) and Biodentine(TM) as coronal barriers and different irrigants, which led to different clinical outcomes. PMID:26884781

  6. Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes

    PubMed Central

    Kones, Richard

    2013-01-01

    Residual risk, the ongoing appreciable risk of major cardiovascular events (MCVE) in statin-treated patients who have achieved evidence-based lipid goals, remains a concern among cardiologists. Factors that contribute to this continuing risk are atherogenic non-low-density lipoprotein (LDL) particles and atherogenic processes unrelated to LDL cholesterol, including other risk factors, the inherent properties of statin drugs, and patient characteristics, ie, genetics and behaviors. In addition, providers, health care systems, the community, public policies, and the environment play a role. Major statin studies suggest an average 28% reduction in LDL cholesterol and a 31% reduction in relative risk, leaving a residual risk of about 69%. Incomplete reductions in risk, and failure to improve conditions that create risk, may result in ongoing progression of atherosclerosis, with new and recurring lesions in original and distant culprit sites, remodeling, arrhythmias, rehospitalizations, invasive procedures, and terminal disability. As a result, identification of additional agents to reduce residual risk, particularly administered together with statin drugs, has been an ongoing quest. The current model of atherosclerosis involves many steps during which disease may progress independently of guideline-defined elevations in LDL cholesterol. Differences in genetic responsiveness to statin therapy, differences in ability of the endothelium to regenerate and repair, and differences in susceptibility to nonlipid risk factors, such as tobacco smoking, hypertension, and molecular changes associated with obesity and diabetes, may all create residual risk. A large number of inflammatory and metabolic processes may also provide eventual therapeutic targets to lower residual risk. Classically, epidemiologic and other evidence suggested that raising high-density lipoprotein (HDL) cholesterol would be cardioprotective. When LDL cholesterol is aggressively lowered to targets, low HDL

  7. Heritability of Creative Achievement

    ERIC Educational Resources Information Center

    Piffer, Davide; Hur, Yoon-Mi

    2014-01-01

    Although creative achievement is a subject of much attention to lay people, the origin of individual differences in creative accomplishments remain poorly understood. This study examined genetic and environmental influences on creative achievement in an adult sample of 338 twins (mean age = 26.3 years; SD = 6.6 years). Twins completed the Creative…

  8. Confronting the Achievement Gap

    ERIC Educational Resources Information Center

    Gardner, David

    2007-01-01

    This article talks about the large achievement gap between children of color and their white peers. The reasons for the achievement gap are varied. First, many urban minorities come from a background of poverty. One of the detrimental effects of growing up in poverty is receiving inadequate nourishment at a time when bodies and brains are rapidly…

  9. States Address Achievement Gaps.

    ERIC Educational Resources Information Center

    Christie, Kathy

    2002-01-01

    Summarizes 2 state initiatives to address the achievement gap: North Carolina's report by the Advisory Commission on Raising Achievement and Closing Gaps, containing an 11-point strategy, and Kentucky's legislation putting in place 10 specific processes. The North Carolina report is available at www.dpi.state.nc.us.closingthegap; Kentucky's…

  10. Wechsler Individual Achievement Test.

    ERIC Educational Resources Information Center

    Taylor, Ronald L.

    1999-01-01

    This article describes the Wechsler Individual Achievement Test, a comprehensive measure of achievement for individuals in grades K-12. Eight subtests assess mathematics reasoning, spelling, reading comprehension, numerical operations, listening comprehension, oral expression, and written expression. Its administration, standardization,…

  11. Inverting the Achievement Pyramid

    ERIC Educational Resources Information Center

    White-Hood, Marian; Shindel, Melissa

    2006-01-01

    Attempting to invert the pyramid to improve student achievement and increase all students' chances for success is not a new endeavor. For decades, educators have strategized, formed think tanks, and developed school improvement teams to find better ways to improve the achievement of all students. Currently, the No Child Left Behind Act (NCLB) is…

  12. Achievement Test Program.

    ERIC Educational Resources Information Center

    Ohio State Dept. of Education, Columbus. Trade and Industrial Education Service.

    The Ohio Trade and Industrial Education Achievement Test battery is comprised of seven basic achievement tests: Machine Trades, Automotive Mechanics, Basic Electricity, Basic Electronics, Mechanical Drafting, Printing, and Sheet Metal. The tests were developed by subject matter committees and specialists in testing and research. The Ohio Trade and…

  13. General Achievement Trends: Maryland

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  14. General Achievement Trends: Arkansas

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  15. General Achievement Trends: Idaho

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  16. General Achievement Trends: Nebraska

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  17. General Achievement Trends: Colorado

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  18. General Achievement Trends: Iowa

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  19. General Achievement Trends: Hawaii

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  20. General Achievement Trends: Kentucky

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  1. General Achievement Trends: Florida

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  2. General Achievement Trends: Texas

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  3. General Achievement Trends: Oregon

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  4. General Achievement Trends: Virginia

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  5. Honoring Student Achievement

    ERIC Educational Resources Information Center

    Education Digest: Essential Readings Condensed for Quick Review, 2004

    2004-01-01

    Is the concept of "honor roll" obsolete? The honor roll has always been a way for schools to recognize the academic achievement of their students. But does it motivate students? In this article, several elementary school principals share their views about honoring student achievement. Among others, Virginia principal Nancy Moga said that students…

  6. Aiming at Achievement.

    ERIC Educational Resources Information Center

    Martinez, Paul

    The Raising Quality and Achievement Program is a 3-year initiative to support further education (FE) colleges in the United Kingdom in their drive to improve students' achievement and the quality of provision. The program offers the following: (1) quality information and advice; (2) onsite support for individual colleges; (3) help with…

  7. Achieving Perspective Transformation.

    ERIC Educational Resources Information Center

    Nowak, Jens

    Perspective transformation is a consciously achieved state in which the individual's perspective on life is transformed. The new perspective serves as a vantage point for life's actions and interactions, affecting the way life is lived. Three conditions are basic to achieving perspective transformation: (1) "feeling" experience, i.e., getting in…

  8. Achieving Public Schools

    ERIC Educational Resources Information Center

    Abowitz, Kathleen Knight

    2011-01-01

    Public schools are functionally provided through structural arrangements such as government funding, but public schools are achieved in substance, in part, through local governance. In this essay, Kathleen Knight Abowitz explains the bifocal nature of achieving public schools; that is, that schools are both subject to the unitary Public compact of…

  9. General Achievement Trends: Tennessee

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  10. Achievement-Based Resourcing.

    ERIC Educational Resources Information Center

    Fletcher, Mike; And Others

    1992-01-01

    This collection of seven articles examines achievement-based resourcing (ABR), the concept that the funding of educational institutions should be linked to their success in promoting student achievement, with a focus on the application of ABR to postsecondary education in the United Kingdom. The articles include: (1) "Introduction" (Mick…

  11. Estimation of Optimal Brachytherapy Utilization Rate in the Treatment of Malignancies of the Uterine Corpus by a Review of Clinical Practice Guidelines and the Primary Evidence

    SciTech Connect

    Thompson, Stephen R. Delaney, Geoff; Gabriel, Gabriel S.; Jacob, Susannah; Das, Prabir; Barton, Michael

    2008-11-01

    Purpose: Brachytherapy (BT) is an important treatment technique for uterine corpus malignancies. We modeled the optimal proportion of these cases that should be treated with BT-the optimal rate of brachytherapy utilization (BTU). We compared this optimal BTU rate with the actual BTU rate. Methods and Materials: Evidence-based guidelines and the primary evidence were used to construct a decision tree for BTU for malignancies of the uterine corpus. Searches of the literature to ascertain the proportion of patients who fulfilled the criteria for BT were conducted. The robustness of the model was tested by sensitivity analyses and peer review. A retrospective Patterns of Care Study of BT in New South Wales for 2003 was conducted, and the actual BTU for uterine corpus malignancies was determined. The actual BTU in other geographic areas was calculated from published reports. The differences between the optimal and actual rates of BTU were assessed. Results: The optimal uterine corpus BTU rate was estimated to be 40% (range, 36-49%). In New South Wales in 2003, the actual BTU rate was only 14% of the 545 patients with uterine corpus cancer. The actual BTU rate in 2001 was 11% in the Surveillance, Epidemiology, and End Results areas and 30% in Sweden. Conclusion: The results of this study have shown that BT for uterine corpus malignancies is underused in New South Wales and in the Surveillance, Epidemiology, and End Results areas. Our model of optimal BTU can be used as a quality assurance tool, providing an evidence-based benchmark against which can be measured actual patterns of practice. It can also be used to assist in determining the adequacy of BT resource allocation.

  12. Achieving lipid goals with rosuvastatin compared with simvastatin in high risk patients in real clinical practice: a randomized, open-label, parallel-group, multi-center study: the DISCOVERY-Beta study.

    PubMed

    Laks, Toivo; Keba, Ester; Leiner, Mariann; Merilind, Eero; Petersen, Mall; Reinmets, Sirje; Väli, Sille; Sööt, Terje; Otter, Karin

    2008-01-01

    The aim of this multi-center, open-label, randomized, parallel-group trial was to compare the efficacy of rosuvastatin with that of simvastatin in achieving the 1998 European Atherosclerosis Society (EAS) lipid treatment goals. 504 patients (> or =18 years) with primary hypercholesterolemia and a 10-year cardiovascular (CV) risk >20% or history of coronary heart disease (CHD) or other established atherosclerotic disease were randomized in a 2:1 ratio to receive rosuvastatin 10 mg or simvastatin 20 mg once daily for 12 weeks. A significantly higher proportion of patients achieved 1998 EAS low-density lipoprotein cholesterol (LDL-C) goal after 12 weeks of treatment with rosuvastatin 10 mg compared to simvastatin 20 mg (64 vs 51.5%, p < 0.01). Similarly, significantly more patients achieved the 1998 EAS total cholesterol (TC) goal and the 2003 EAS LDL-C and TC goals (p < 0.001) with rosuvastatin 10 mg compared with simvastatin 20 mg. The incidence of adverse events and the proportion of patients who discontinued study treatment were similar between treatment groups. In conclusion, in the DISCOVERY-Beta Study in patients with primary hypercholesterolemia greater proportion of patients in the rosuvastatin 10 mg group achieved the EAS LDL-C treatment goal compared with the simvastatin 20 mg group. Drug tolerability was similar across both treatment groups. PMID:19337553

  13. Achieving lipid goals with rosuvastatin compared with simvastatin in high risk patients in real clinical practice: a randomized, open-label, parallel-group, multi-center study: the DISCOVERY-Beta study

    PubMed Central

    Laks, Toivo; Keba, Ester; Leiner, Mariann; Merilind, Eero; Petersen, Mall; Reinmets, Sirje; Väli, Sille; Sööt, Terje; Otter, Karin

    2008-01-01

    The aim of this multi-center, open-label, randomized, parallel-group trial was to compare the efficacy of rosuvastatin with that of simvastatin in achieving the 1998 European Atherosclerosis Society (EAS) lipid treatment goals. 504 patients (≥18 years) with primary hypercholesterolemia and a 10-year cardiovascular (CV) risk >20% or history of coronary heart disease (CHD) or other established atherosclerotic disease were randomized in a 2:1 ratio to receive rosuvastatin 10 mg or simvastatin 20 mg once daily for 12 weeks. A significantly higher proportion of patients achieved 1998 EAS low-density lipoprotein cholesterol (LDL-C) goal after 12 weeks of treatment with rosuvastatin 10 mg compared to simvastatin 20 mg (64 vs 51.5%, p < 0.01). Similarly, significantly more patients achieved the 1998 EAS total cholesterol (TC) goal and the 2003 EAS LDL-C and TC goals (p < 0.001) with rosuvastatin 10 mg compared with simvastatin 20 mg. The incidence of adverse events and the proportion of patients who discontinued study treatment were similar between treatment groups. In conclusion, in the DISCOVERY-Beta Study in patients with primary hypercholesterolemia greater proportion of patients in the rosuvastatin 10 mg group achieved the EAS LDL-C treatment goal compared with the simvastatin 20 mg group. Drug tolerability was similar across both treatment groups. PMID:19337553

  14. Predicting Achievement and Motivation.

    ERIC Educational Resources Information Center

    Uguroglu, Margaret; Walberg, Herbert J.

    1986-01-01

    Motivation and nine other factors were measured for 970 students in grades five through eight in a study of factors predicting achievement and predicting motivation. Results are discussed. (Author/MT)

  15. Attractiveness and School Achievement

    ERIC Educational Resources Information Center

    Salvia, John; And Others

    1977-01-01

    The purpose of this study was to ascertain the relationship between rated attractiveness and two measures of school performance. Attractive children received significantly higher report cards and, to some degree, higher achievement test scores than their unattractive peers. (Author)

  16. Student Achievement and Motivation

    ERIC Educational Resources Information Center

    Flammer, Gordon H.; Mecham, Robert C.

    1974-01-01

    Compares the lecture and self-paced methods of instruction on the basis of student motivation and achieveme nt, comparing motivating and demotivating factors in each, and their potential for motivation and achievement. (Authors/JR)

  17. Lake Louise mutation detection meeting 2013: clinical translation of next-generation sequencing requires optimization of workflows and interpretation of variants.

    PubMed

    Smith, Amanda; Boycott, Kym M; Jarinova, Olga

    2014-02-01

    With the exponential reduction of the cost of next-generation sequencing (NGS), it is no longer the generation of data but the analysis and interpretation of massive amounts of sequencing data that are seen as key challenges for the effective integration of these technologies into clinical practice. Clinical geneticists, informaticians, and scientists from 17 countries gathered for the 12th International Symposium on Mutation in the Genome at the Fairmont Chateau Lake Louise (Canada) to discuss technological advances and applications of NGS and consider possible approaches to the challenges of clinical translation. Here, we provide an overview of the main themes of the meeting that included development of innovative solutions for variant sharing, tools and resources for NGS analysis, novel technology and methodology development, NGS-based discovery of disease pathogenesis, development of multigene NGS sequencing panels for clinical use, exploring diagnostic utility of whole-exome and whole-genome sequencing, and, finally, integration of genomic sequencing into the clinic. PMID:24282140

  18. [Let Us to Know the Post-Marketing Clinical Studies and Critical Situation of Study Groups -- Now We Should Talk about How to Achieve the Safe and Most Effective Treatment for Cancer Patients].

    PubMed

    Hamamoto, Maki

    2016-04-01

    Not to leave something to be regretted in the life of patients and their family, it is important to find the best way during and after treatment for cancer. We, cancer survivors association, propose a corporated actions among patients, administration, medical stuffs, and enterprises to solve the problems of clinical studies. And we express our opinion on the present problems and to do for patients and citizens. PMID:27220802

  19. Achieving yield gains in wheat.

    PubMed

    Reynolds, Matthew; Foulkes, John; Furbank, Robert; Griffiths, Simon; King, Julie; Murchie, Erik; Parry, Martin; Slafer, Gustavo

    2012-10-01

    Wheat provides 20% of calories and protein consumed by humans. Recent genetic gains are <1% per annum (p.a.), insufficient to meet future demand. The Wheat Yield Consortium brings expertise in photosynthesis, crop adaptation and genetics to a common breeding platform. Theory suggest radiation use efficiency (RUE) of wheat could be increased ~50%; strategies include modifying specificity, catalytic rate and regulation of Rubisco, up-regulating Calvin cycle enzymes, introducing chloroplast CO(2) concentrating mechanisms, optimizing light and N distribution of canopies while minimizing photoinhibition, and increasing spike photosynthesis. Maximum yield expression will also require dynamic optimization of source: sink so that dry matter partitioning to reproductive structures is not at the cost of the roots, stems and leaves needed to maintain physiological and structural integrity. Crop development should favour spike fertility to maximize harvest index so phenology must be tailored to different photoperiods, and sensitivity to unpredictable weather must be modulated to reduce conservative responses that reduce harvest index. Strategic crossing of complementary physiological traits will be augmented with wide crossing, while genome-wide selection and high throughput phenotyping and genotyping will increase efficiency of progeny screening. To ensure investment in breeding achieves agronomic impact, sustainable crop management must also be promoted through crop improvement networks. PMID:22860982

  20. An optimized polyamine moiety boosts the potency of human type II topoisomerase poisons as quantified by comparative analysis centered on the clinical candidate F14512.

    PubMed

    Palermo, Giulia; Minniti, Elirosa; Greco, Maria Laura; Riccardi, Laura; Simoni, Elena; Convertino, Marino; Marchetti, Chiara; Rosini, Michela; Sissi, Claudia; Minarini, Anna; De Vivo, Marco

    2015-10-01

    Combined computational-experimental analyses explain and quantify the spermine-vectorized F14512's boosted potency as a topoII poison. We found that an optimized polyamine moiety boosts drug binding to the topoII/DNA cleavage complex, rather than to the DNA alone. These results provide new structural bases and key reference data for designing new human topoII poisons. PMID:26234198

  1. Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687).

    PubMed

    Barlind, Jonas G; Bauer, Udo A; Birch, Alan M; Birtles, Susan; Buckett, Linda K; Butlin, Roger J; Davies, Robert D M; Eriksson, Jan W; Hammond, Clare D; Hovland, Ragnar; Johannesson, Petra; Johansson, Magnus J; Kemmitt, Paul D; Lindmark, Bo T; Morentin Gutierrez, Pablo; Noeske, Tobias A; Nordin, Andreas; O'Donnell, Charles J; Petersson, Annika U; Redzic, Alma; Turnbull, Andrew V; Vinblad, Johanna

    2012-12-13

    A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers. PMID:23116186

  2. Multicriteria optimization of the spatial dose distribution

    SciTech Connect

    Schlaefer, Alexander; Viulet, Tiberiu; Muacevic, Alexander; Fürweger, Christoph

    2013-12-15

    Purpose: Treatment planning for radiation therapy involves trade-offs with respect to different clinical goals. Typically, the dose distribution is evaluated based on few statistics and dose–volume histograms. Particularly for stereotactic treatments, the spatial dose distribution represents further criteria, e.g., when considering the gradient between subregions of volumes of interest. The authors have studied how to consider the spatial dose distribution using a multicriteria optimization approach.Methods: The authors have extended a stepwise multicriteria optimization approach to include criteria with respect to the local dose distribution. Based on a three-dimensional visualization of the dose the authors use a software tool allowing interaction with the dose distribution to map objectives with respect to its shape to a constrained optimization problem. Similarly, conflicting criteria are highlighted and the planner decides if and where to relax the shape of the dose distribution.Results: To demonstrate the potential of spatial multicriteria optimization, the tool was applied to a prostate and meningioma case. For the prostate case, local sparing of the rectal wall and shaping of a boost volume are achieved through local relaxations and while maintaining the remaining dose distribution. For the meningioma, target coverage is improved by compromising low dose conformality toward noncritical structures. A comparison of dose–volume histograms illustrates the importance of spatial information for achieving the trade-offs.Conclusions: The results show that it is possible to consider the location of conflicting criteria during treatment planning. Particularly, it is possible to conserve already achieved goals with respect to the dose distribution, to visualize potential trade-offs, and to relax constraints locally. Hence, the proposed approach facilitates a systematic exploration of the optimal shape of the dose distribution.

  3. Medical Care in a Free Clinic: A Comprehensive Evaluation of Patient Experience, Incentives, and Barriers to Optimal Medical Care with Consideration of a Facility Fee

    PubMed Central

    Liu, Xinwei; Nash, Bee; Sullivan, Sara; Garris, Stephanie; Hardy, Marvin; Lee, Michael; Simms-Cendan, Judith; Pasarica, Magdalena

    2016-01-01

    Free and charitable clinics are important contributors to the health of the United States population. Recently, funding for these clinics has been declining, and it is, therefore, useful to identify what qualities patients value the most in clinics in an effort to allocate funding wisely. In order to identify targets and incentives for improvement of patients’ health, we performed a comprehensive analysis of patients’ experience at a free clinic by analyzing a patient survey (N=94). The survey also assessed patient opinions of a small facility fee, which could be used to offset the decrease in funds. Interestingly, our patients believed it is appropriate to be charged a facility fee (78%) because it increases involvement in their care (r = 0.69, p < 0.001) and self-respect (r = 0.66, p < 0.001). Incentives to medical care include continuity of care, faith-based care, having a patient medical provider partnership, and charging a facility fee. Barriers include affordable housing, transportation, medication, and accessible information. In order to improve medical care in the uninsured population, our study suggested that we need to: 1) offer continuity of medical care; 2) offer affordable preventive health screenings; 3) support affordable transportation, housing, and medications; and 4) consider including a facility fee. PMID:27014534

  4. CEBAF accelerator achievements

    SciTech Connect

    Y.C. Chao, M. Drury, C. Hovater, A. Hutton, G.A. Krafft, M. Poelker, C. Reece, M. Tiefenback

    2011-06-01

    In the past decade, nuclear physics users of Jefferson Lab's Continuous Electron Beam Accelerator Facility (CEBAF) have benefited from accelerator physics advances and machine improvements. As of early 2011, CEBAF operates routinely at 6 GeV, with a 12 GeV upgrade underway. This article reports highlights of CEBAF's scientific and technological evolution in the areas of cryomodule refurbishment, RF control, polarized source development, beam transport for parity experiments, magnets and hysteresis handling, beam breakup, and helium refrigerator operational optimization.

  5. Explorations in achievement motivation

    NASA Technical Reports Server (NTRS)

    Helmreich, Robert L.

    1982-01-01

    Recent research on the nature of achievement motivation is reviewed. A three-factor model of intrinsic motives is presented and related to various criteria of performance, job satisfaction and leisure activities. The relationships between intrinsic and extrinsic motives are discussed. Needed areas for future research are described.

  6. Achieving health care affordability.

    PubMed

    Payson, Norman C

    2002-10-01

    Not all plans are jumping headlong into the consumer-centric arena. In this article, the CEO of Oxford Health Plans discusses how advanced managed care can achieve what other consumer-centric programs seek to do--provide affordable, quality health care. PMID:12391815

  7. Issues in Achievement Testing.

    ERIC Educational Resources Information Center

    Baker, Eva L.

    This booklet is intended to help school personnel, parents, students, and members of the community understand concepts and research relating to achievement testing in public schools. The paper's sections include: (1) test use with direct effects on students (test of certification, selection, and placement); (2) test use with indirect effects on…

  8. Achieving Peace through Education.

    ERIC Educational Resources Information Center

    Clarken, Rodney H.

    While it is generally agreed that peace is desirable, there are barriers to achieving a peaceful world. These barriers are classified into three major areas: (1) an erroneous view of human nature; (2) injustice; and (3) fear of world unity. In a discussion of these barriers, it is noted that although the consciousness and conscience of the world…

  9. Achieving All Our Ambitions

    ERIC Educational Resources Information Center

    Hartley, Tricia

    2009-01-01

    National learning and skills policy aims both to build economic prosperity and to achieve social justice. Participation in higher education (HE) has the potential to contribute substantially to both aims. That is why the Campaign for Learning has supported the ambition to increase the proportion of the working-age population with a Level 4…

  10. Intelligence and Educational Achievement

    ERIC Educational Resources Information Center

    Deary, Ian J.; Strand, Steve; Smith, Pauline; Fernandes, Cres

    2007-01-01

    This 5-year prospective longitudinal study of 70,000+ English children examined the association between psychometric intelligence at age 11 years and educational achievement in national examinations in 25 academic subjects at age 16. The correlation between a latent intelligence trait (Spearman's "g"from CAT2E) and a latent trait of educational…

  11. SALT and Spelling Achievement.

    ERIC Educational Resources Information Center

    Nelson, Joan

    A study investigated the effects of suggestopedic accelerative learning and teaching (SALT) on the spelling achievement, attitudes toward school, and memory skills of fourth-grade students. Subjects were 20 male and 28 female students from two self-contained classrooms at Kennedy Elementary School in Rexburg, Idaho. The control classroom and the…

  12. NCLB: Achievement Robin Hood?

    ERIC Educational Resources Information Center

    Bracey, Gerald W.

    2008-01-01

    In his "Wall Street Journal" op-ed on the 25th of anniversary of "A Nation At Risk", former assistant secretary of education Chester E. Finn Jr. applauded the report for turning U.S. education away from equality and toward achievement. It was not surprising, then, that in mid-2008, Finn arranged a conference to examine the potential "Robin Hood…

  13. INTELLIGENCE, PERSONALITY AND ACHIEVEMENT.

    ERIC Educational Resources Information Center

    MUIR, R.C.; AND OTHERS

    A LONGITUDINAL DEVELOPMENTAL STUDY OF A GROUP OF MIDDLE CLASS CHILDREN IS DESCRIBED, WITH EMPHASIS ON A SEGMENT OF THE RESEARCH INVESTIGATING THE RELATIONSHIP OF ACHIEVEMENT, INTELLIGENCE, AND EMOTIONAL DISTURBANCE. THE SUBJECTS WERE 105 CHILDREN AGED FIVE TO 6.3 ATTENDING TWO SCHOOLS IN MONTREAL. EACH CHILD WAS ASSESSED IN THE AREAS OF…

  14. School Students' Science Achievement

    ERIC Educational Resources Information Center

    Shymansky, James; Wang, Tzu-Ling; Annetta, Leonard; Everett, Susan; Yore, Larry D.

    2013-01-01

    This paper is a report of the impact of an externally funded, multiyear systemic reform project on students' science achievement on a modified version of the Third International Mathematics and Science Study (TIMSS) test in 33 small, rural school districts in two Midwest states. The systemic reform effort utilized a cascading leadership strategy…

  15. Advancing Student Achievement

    ERIC Educational Resources Information Center

    Walberg, Herbert J.

    2010-01-01

    For the last half century, higher spending and many modern reforms have failed to raise the achievement of students in the United States to the levels of other economically advanced countries. A possible explanation, says Herbert Walberg, is that much current education theory is ill informed about scientific psychology, often drawing on fads and…

  16. Essays on Educational Achievement

    ERIC Educational Resources Information Center

    Ampaabeng, Samuel Kofi

    2013-01-01

    This dissertation examines the determinants of student outcomes--achievement, attainment, occupational choices and earnings--in three different contexts. The first two chapters focus on Ghana while the final chapter focuses on the US state of Massachusetts. In the first chapter, I exploit the incidence of famine and malnutrition that resulted to…

  17. Increasing Male Academic Achievement

    ERIC Educational Resources Information Center

    Jackson, Barbara Talbert

    2008-01-01

    The No Child Left Behind legislation has brought greater attention to the academic performance of American youth. Its emphasis on student achievement requires a closer analysis of assessment data by school districts. To address the findings, educators must seek strategies to remedy failing results. In a mid-Atlantic district of the Unites States,…

  18. Setting and Achieving Objectives.

    ERIC Educational Resources Information Center

    Knoop, Robert

    1986-01-01

    Provides basic guidelines which school officials and school boards may find helpful in negotiating, establishing, and managing objectives. Discusses characteristics of good objectives, specific and directional objectives, multiple objectives, participation in setting objectives, feedback on goal process and achievement, and managing a school…

  19. Schools Achieving Gender Equity.

    ERIC Educational Resources Information Center

    Revis, Emma

    This guide is designed to assist teachers presenting the Schools Achieving Gender Equity (SAGE) curriculum for vocational education students, which was developed to align gender equity concepts with the Kentucky Education Reform Act (KERA). Included in the guide are lesson plans for classes on the following topics: legal issues of gender equity,…

  20. Iowa Women of Achievement.

    ERIC Educational Resources Information Center

    Ohrn, Deborah Gore, Ed.

    1993-01-01

    This issue of the Goldfinch highlights some of Iowa's 20th century women of achievement. These women have devoted their lives to working for human rights, education, equality, and individual rights. They come from the worlds of politics, art, music, education, sports, business, entertainment, and social work. They represent Native Americans,…

  1. Achievements or Disasters?

    ERIC Educational Resources Information Center

    Goodwin, MacArthur

    2000-01-01

    Focuses on policy issues that have affected arts education in the twentieth century, such as: interest in discipline-based arts education, influence of national arts associations, and national standards and coordinated assessment. States that whether the policy decisions are viewed as achievements or disasters are for future determination. (CMK)

  2. Minority Achievement Report.

    ERIC Educational Resources Information Center

    Prince George's Community Coll., Largo, MD. Office of Institutional Research and Analysis.

    This report summarizes the achievements of Prince George's Community College (PGCC) with regard to minority outcomes. Table 1 summarizes the undergraduate enrollment trends for African Americans as well as total minorities from fall 1994 through fall 1998. Both the headcount number of African American students and the proportion of African…

  3. Project ACHIEVE final report

    SciTech Connect

    1997-06-13

    Project ACHIEVE was a math/science academic enhancement program aimed at first year high school Hispanic American students. Four high schools -- two in El Paso, Texas and two in Bakersfield, California -- participated in this Department of Energy-funded program during the spring and summer of 1996. Over 50 students, many of whom felt they were facing a nightmare future, were given the opportunity to work closely with personal computers and software, sophisticated calculators, and computer-based laboratories -- an experience which their regular academic curriculum did not provide. Math and science projects, exercises, and experiments were completed that emphasized independent and creative applications of scientific and mathematical theories to real world problems. The most important outcome was the exposure Project ACHIEVE provided to students concerning the college and technical-field career possibilities available to them.

  4. Current state of ST-segment myocardial infarction: evidence-based therapies and optimal patient outcomes in advanced systems of care.

    PubMed

    Thomas, Joseph L; French, William J

    2014-08-01

    Advances in reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) provide optimal patient outcomes. Reperfusion therapies, including contemporary primary percutaneous coronary intervention, represent decades of clinical evidence development in large clinical trials and national databases. However, rapid identification of STEMI and guideline-directed management of patients across broad populations have been best achieved in advanced systems of care. Current outcomes in STEMI reflect the evolution of both clinical data and idealized health care delivery networks. PMID:25091964

  5. Optimization of Droplet Digital PCR from RNA and DNA extracts with direct comparison to RT-qPCR: Clinical implications for quantification of Oseltamivir-resistant subpopulations.

    PubMed

    Taylor, Sean C; Carbonneau, Julie; Shelton, Dawne N; Boivin, Guy

    2015-11-01

    The recent introduction of Droplet Digital PCR (ddPCR) has provided researchers with a tool that permits direct quantification of nucleic acids from a wide range of samples with increased precision and sensitivity versus RT-qPCR. The sample interdependence of RT-qPCR stemming from the measurement of Cq and ΔCq values is eliminated with ddPCR which provides an independent measure of the absolute nucleic acid concentration for each sample without standard curves thereby reducing inter-well and inter-plate variability. Well-characterized RNA purified from H275-wild type (WT) and H275Y-point mutated (MUT) neuraminidase of influenza A (H1N1) pandemic 2009 virus was used to demonstrate a ddPCR optimization workflow to assure robust data for downstream analysis. The ddPCR reaction mix was also tested with RT-qPCR and gave excellent reaction efficiency (between 90% and 100%) with the optimized MUT/WT duplexed assay thus enabling the direct comparison of the two platforms from the same reaction mix and thermal cycling protocol. ddPCR gave a marked improvement in sensitivity (>30-fold) for mutation abundance using a mixture of purified MUT and WT RNA and increased precision (>10 fold, p<0.05 for both inter- and intra-assay variability) versus RT-qPCR from patient samples to accurately identify residual mutant viral population during recovery. PMID:26315318

  6. Rapid genotypic detection of rifampin- and isoniazid-resistant Mycobacterium tuberculosis directly in clinical specimens.

    PubMed

    Bang, Didi; Bengård Andersen, Ase; Thomsen, Vibeke Østergaard

    2006-07-01

    A multiplex PCR DNA strip assay (Genotype MTBDR) designed to detect rifampin (rpoB) and high-level isoniazid (katG) resistance mutations in Mycobacterium tuberculosis isolates was optimized for clinical specimens. Successful genotypic results were achieved with 36 of 38 (95%) smear-positive respiratory specimens, allowing rapid therapeutic adjustments in transmittable drug-resistant tuberculosis. PMID:16825393

  7. MR physics in practice: How to optimize acquisition quality and time for cardiac MRI

    PubMed Central

    Saloner, David; Liu, Jing; Haraldsson, Henrik

    2014-01-01

    Quality of the medical imaging is a key component for accurate disease diagnosis. How to optimize image quality while maintain scan time efficiency and patient comfort is important for the clinical routine MRI exams. In this chapter, we review both practical and advanced techniques to achieve high image quality, especially focusing on optimizing the trade-offs between the image quality (such as signal-to-noise and spatial resolution) and acquisition time. We provide practical examples for optimizing the image quality and scan time. PMID:25476668

  8. Optimization of therapy for severe aplastic anemia based on clinical, biologic, and treatment response parameters: conclusions of an international working group on severe aplastic anemia convened by the Blood and Marrow Transplant Clinical Trials Network, March 2010.

    PubMed

    Pulsipher, Michael A; Young, Neal S; Tolar, Jakub; Risitano, Antonio M; Deeg, H Joachim; Anderlini, Paolo; Calado, Rodrigo; Kojima, Seiji; Eapen, Mary; Harris, Richard; Scheinberg, Phillip; Savage, Sharon; Maciejewski, Jaroslaw P; Tiu, Ramon V; DiFronzo, Nancy; Horowitz, Mary M; Antin, Joseph H

    2011-03-01

    Although recent advances in therapy offer the promise for improving survival in patients with severe aplastic anemia (SAA), the small size of the patient population, lack of a mechanism in North America for longitudinal follow-up of patients, and inadequate cooperation among hematologists, scientists, and transplant physicians remain obstacles to conducting large studies that would advance the field. To address this issue, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) convened a group of international experts in March 2010 to define the most important questions in the basic science, immunosuppressive therapy (IST), and bone marrow transplantation (BMT) of SAA and propose initiatives to facilitate clinical and biologic research. Key conclusions of the working group were: (1) new patients should obtain accurate, expert diagnosis and early identification of biologic risk; (2) a population-based SAA outcomes registry should be established in North America to collect data on patients longitudinally from diagnosis through and after treatment; (3) a repository of biologic samples linked to the clinical data in the outcomes registry should be developed; (4) innovative approaches to unrelated donor BMT that decrease graft-versus-host disease are needed; and (5) alternative donor transplantation approaches for patients lacking HLA-matched unrelated donors must be improved. A partnership of BMT, IST, and basic science researchers will develop initiatives and partner with advocacy and funding organizations to address these challenges. Collaboration with similar study groups in Europe and Asia will be pursued. PMID:21034841

  9. Robust optimization methods for cardiac sparing in tangential breast IMRT

    SciTech Connect

    Mahmoudzadeh, Houra; Lee, Jenny; Chan, Timothy C. Y.; Purdie, Thomas G.

    2015-05-15

    Purpose: In left-sided tangential breast intensity modulated radiation therapy (IMRT), the heart may enter the radiation field and receive excessive radiation while the patient is breathing. The patient’s breathing pattern is often irregular and unpredictable. We verify the clinical applicability of a heart-sparing robust optimization approach for breast IMRT. We compare robust optimized plans with clinical plans at free-breathing and clinical plans at deep inspiration breath-hold (DIBH) using active breathing control (ABC). Methods: Eight patients were included in the study with each patient simulated using 4D-CT. The 4D-CT image acquisition generated ten breathing phase datasets. An average scan was constructed using all the phase datasets. Two of the eight patients were also imaged at breath-hold using ABC. The 4D-CT datasets were used to calculate the accumulated dose for robust optimized and clinical plans based on deformable registration. We generated a set of simulated breathing probability mass functions, which represent the fraction of time patients spend in different breathing phases. The robust optimization method was applied to each patient using a set of dose-influence matrices extracted from the 4D-CT data and a model of the breathing motion uncertainty. The goal of the optimization models was to minimize the dose to the heart while ensuring dose constraints on the target were achieved under breathing motion uncertainty. Results: Robust optimized plans were improved or equivalent to the clinical plans in terms of heart sparing for all patients studied. The robust method reduced the accumulated heart dose (D10cc) by up to 801 cGy compared to the clinical method while also improving the coverage of the accumulated whole breast target volume. On average, the robust method reduced the heart dose (D10cc) by 364 cGy and improved the optBreast dose (D99%) by 477 cGy. In addition, the robust method had smaller deviations from the planned dose to the

  10. Updates and achievements in virology.

    PubMed

    Buonaguro, Franco M; Campadelli-Fiume, Gabriella; De Giuli Morghen, Carlo; Palù, Giorgio

    2010-07-01

    The 4th European Congress of Virology, hosted by the Italian Society for Virology, attracted approximately 1300 scientists from 46 countries worldwide. It also represented the first conference of the European Society for Virology, which was established in Campidoglio, Rome, Italy in 2009. The main goal of the meeting was to share research activities and results achieved in European virology units/institutes and to strengthen collaboration with colleagues from both western and developing countries. The worldwide representation of participants is a testament to the strength and attraction of European virology. The 5-day conference brought together the best of current virology; topics covered all three living domains (bacteria, archaea and eucarya), with special sessions on plant and veterinary virology as well as human virology, including two oral presentations on mimiviruses. The conference included five plenary sessions, 31 workshops, one hepatitis C virus roundtable, ten special workshops and three poster sessions, as well as 45 keynote lectures, 191 oral presentations and 845 abstracts. Furthermore, the Gesellschaft fur Virologie Loeffler-Frosch medal award was given to Peter Vogt for his long-standing career and achievements; the Gardner Lecture of the European Society for Clinical Virology was presented by Yoshihiro Kawaoka, and the Pioneer in Virology Lecture of the Italian Society for Virology was presented by Ulrich Koszinowski. PMID:20624042

  11. Optimization of evaporative cooling

    NASA Astrophysics Data System (ADS)

    Sackett, C. A.; Bradley, C. C.; Hulet, R. G.

    1997-05-01

    Recent experiments have used forced evaporative cooling to produce Bose-Einstein condensation in dilute gases. The evaporative cooling process can be optimized to provide the maximum phase-space density with a specified number of atoms remaining. We show that this global optimization is approximately achieved by locally optimizing the cooling efficiency at each instant. We discuss how this method can be implemented, and present the results for our 7Li trap. The predicted behavior of the gas is found to agree well with experiment.

  12. A Structural Model of Medical Student Achievement.

    ERIC Educational Resources Information Center

    Sheehan, T. Joseph; Sanford, Keat

    1990-01-01

    The theoretical model of medical student performance begins with 38 measures, reduced to 18 without loss of information. These measures are shown to reflect five underlying theoretical interrelated variables: medical knowledge; clinical performance; science aptitude; college achievement; and attitudes and values. Results should be useful in…

  13. Denver airport pumping systems achieve optimal [Delta] T's

    SciTech Connect

    Mannion, G.F.; Krist, G.D. )

    1994-07-01

    This article describes how the pumping and generating systems at the new Denver Airport operate efficiently with the user loops in the buildings producing design temperature rise at all load levels. Fifteen miles east of Denver's Stapleton International Airport lies the newly completed Denver International Airport (DIA)--the world's largest and most high-tech airport. Besides being one of the largest construction projects in the works, it has many of the latest technical innovations available. Of particular interest to the HVAC industry is the design of the heating and cooling water systems. These systems provide environmental cooling and heating water to the three concourses, the airport office building, and the main terminal. The mechanical engineers for the project were all from the Denver area. The central plant design was the work of Behrent Engineering Co.; the three concourses were designed by Swanson-Rink Associates; and the main terminal and administrative office building were designed by Abeyta Engineering Consultants. The overall system concept was developed during the initial design phase by engineers from these firms, members of the DIA staff, and application engineers from several manufacturers.

  14. Earning the Stamp of Approval: How To Achieve Optimal Usability.

    ERIC Educational Resources Information Center

    Makar, Susan

    2003-01-01

    Describes the redesign of the Web site at the virtual library of the NIST (National Institute of Standards and Technology). Discusses usability problems with the original site, including navigation difficulties; focus groups to determine user needs; usability testing for the new Web site; and the importance of customer input. (LRW)

  15. The Effective Clinical Conference.

    ERIC Educational Resources Information Center

    Wink, Diane M.

    1995-01-01

    Examines the common problems with clinical conferences and suggests approaches to maximize student learning. Suggests that an effective clinical conference has three characteristics: (1) it is a group event; (2) it contributes to the achievement of course and clinical objectives; and (3) it provides a setting for students to explore personal…

  16. Optimization of a Class of Tryptophan Dendrimers That Inhibit HIV Replication Leads to a Selective, Specific, and Low-Nanomolar Inhibitor of Clinical Isolates of Enterovirus A71.

    PubMed

    Rivero-Buceta, Eva; Sun, Liang; Martínez-Gualda, Belén; Doyagüez, Elisa G; Donckers, Kim; Quesada, Ernesto; Camarasa, María-José; Delang, Leen; San-Félix, Ana; Neyts, Johan; Leyssen, Pieter

    2016-08-01

    Tryptophan dendrimers that inhibit HIV replication by binding to the HIV envelope glycoproteins gp120 and gp41 have unexpectedly also proven to be potent, specific, and selective inhibitors of the replication of the unrelated enterovirus A71. Dendrimer 12, a consensus compound that was synthesized on the basis of the structure-activity relationship analysis of this series, is 3-fold more potent against the BrCr lab strain and, surprisingly, inhibits a large panel of clinical isolates in the low-nanomolar/high-picomolar range. PMID:27246775

  17. Achieving Magnet status.

    PubMed

    Ellis, Beckie; Gates, Judy

    2005-01-01

    Magnet has become the gold standard for nursing excellence. It is the symbol of effective and safe patient care. It evaluates components that inspire safe care, including employee satisfaction and retention, professional education, and effective interdisciplinary collaboration. In an organization whose mission focuses on excellent patient care, Banner Thunderbird Medical Center found that pursuing Magnet status was clearly the next step. In this article, we will discuss committee selection, education, team building, planning, and the discovery process that define the Magnet journey. The road to obtaining Magnet status has permitted many opportunities to celebrate our achievements. PMID:16056158

  18. Impact of an integrated treatment algorithm based on platelet function testing and clinical risk assessment: results of the TRIAGE Patients Undergoing Percutaneous Coronary Interventions To Improve Clinical Outcomes Through Optimal Platelet Inhibition study.

    PubMed

    Chandrasekhar, Jaya; Baber, Usman; Mehran, Roxana; Aquino, Melissa; Sartori, Samantha; Yu, Jennifer; Kini, Annapoorna; Sharma, Samin; Skurk, Carsten; Shlofmitz, Richard A; Witzenbichler, Bernhard; Dangas, George

    2016-08-01

    Assessment of platelet reactivity alone for thienopyridine selection with percutaneous coronary intervention (PCI) has not been associated with improved outcomes. In TRIAGE, a prospective multicenter observational pilot study we sought to evaluate the benefit of an integrated algorithm combining clinical risk and platelet function testing to select type of thienopyridine in patients undergoing PCI. Patients on chronic clopidogrel therapy underwent platelet function testing prior to PCI using the VerifyNow assay to determine high on treatment platelet reactivity (HTPR, ≥230 P2Y12 reactivity units or PRU). Based on both PRU and clinical (ischemic and bleeding) risks, patients were switched to prasugrel or continued on clopidogrel per the study algorithm. The primary endpoints were (i) 1-year major adverse cardiovascular events (MACE) composite of death, non-fatal myocardial infarction, or definite or probable stent thrombosis; and (ii) major bleeding, Bleeding Academic Research Consortium type 2, 3 or 5. Out of 318 clopidogrel treated patients with a mean age of 65.9 ± 9.8 years, HTPR was noted in 33.3 %. Ninety (28.0 %) patients overall were switched to prasugrel and 228 (72.0 %) continued clopidogrel. The prasugrel group had fewer smokers and more patients with heart failure. At 1-year MACE occurred in 4.4 % of majority HTPR patients on prasugrel versus 3.5 % of primarily non-HTPR patients on clopidogrel (p = 0.7). Major bleeding (5.6 vs 7.9 %, p = 0.47) was numerically higher with clopidogrel compared with prasugrel. Use of the study clinical risk algorithm for choice and intensity of thienopyridine prescription following PCI resulted in similar ischemic outcomes in HTPR patients receiving prasugrel and primarily non-HTPR patients on clopidogrel without an untoward increase in bleeding with prasugrel. However, the study was prematurely terminated and these findings are therefore hypothesis generating. PMID:27100112

  19. Comparison of an effect-model-law-based method versus traditional clinical practice guidelines for optimal treatment decision-making: application to statin treatment in the French population

    PubMed Central

    Kahoul, Riad; Gueyffier, François; Amsallem, Emmanuel; Haugh, Margaret; Marchant, Ivanny; Boissel, François-Henri; Boissel, Jean-Pierre

    2014-01-01

    Healthcare authorities make difficult decisions about how to spend limited budgets for interventions that guarantee the best cost-efficacy ratio. We propose a novel approach for treatment decision-making, OMES—in French: Objectif thérapeutique Modèle Effet Seuil (in English: Therapeutic Objective–Threshold–Effect Model; TOTEM). This approach takes into consideration results from clinical trials, adjusted for the patients' characteristics in treatment decision-making. We compared OMES with the French clinical practice guidelines (CPGs) for the management of dyslipidemia with statin in a computer-generated realistic virtual population, representing the adult French population, in terms of the number of all-cause deaths avoided (number of avoided events: NAEs) under treatment and the individual absolute benefit. The total budget was fixed at the annual amount reimbursed by the French social security for statins. With the CPGs, the NAEs was 292 for an annual cost of 122.54 M€ compared with 443 with OMES. For a fixed NAEs, OMES reduced costs by 50% (60.53 M€ yr−1). The results demonstrate that OMES is at least as good as, and even better than, the standard CPGs when applied to the same population. Hence the OMES approach is a practical, useful alternative which will help to overcome the limitations of treatment decision-making based uniquely on CPGs. PMID:25209407

  20. Comparison of an effect-model-law-based method versus traditional clinical practice guidelines for optimal treatment decision-making: application to statin treatment in the French population.

    PubMed

    Kahoul, Riad; Gueyffier, François; Amsallem, Emmanuel; Haugh, Margaret; Marchant, Ivanny; Boissel, François-Henri; Boissel, Jean-Pierre

    2014-11-01

    Healthcare authorities make difficult decisions about how to spend limited budgets for interventions that guarantee the best cost-efficacy ratio. We propose a novel approach for treatment decision-making, OMES-in French: Objectif thérapeutique Modèle Effet Seuil (in English: Therapeutic Objective-Threshold-Effect Model; TOTEM). This approach takes into consideration results from clinical trials, adjusted for the patients' characteristics in treatment decision-making. We compared OMES with the French clinical practice guidelines (CPGs) for the management of dyslipidemia with statin in a computer-generated realistic virtual population, representing the adult French population, in terms of the number of all-cause deaths avoided (number of avoided events: NAEs) under treatment and the individual absolute benefit. The total budget was fixed at the annual amount reimbursed by the French social security for statins. With the CPGs, the NAEs was 292 for an annual cost of 122.54 M€ compared with 443 with OMES. For a fixed NAEs, OMES reduced costs by 50% (60.53 M€ yr(-1)). The results demonstrate that OMES is at least as good as, and even better than, the standard CPGs when applied to the same population. Hence the OMES approach is a practical, useful alternative which will help to overcome the limitations of treatment decision-making based uniquely on CPGs. PMID:25209407

  1. Optimal refrigerator

    NASA Astrophysics Data System (ADS)

    Allahverdyan, Armen E.; Hovhannisyan, Karen; Mahler, Guenter

    2010-05-01

    We study a refrigerator model which consists of two n -level systems interacting via a pulsed external field. Each system couples to its own thermal bath at temperatures Th and Tc , respectively (θ≡Tc/Th<1) . The refrigerator functions in two steps: thermally isolated interaction between the systems driven by the external field and isothermal relaxation back to equilibrium. There is a complementarity between the power of heat transfer from the cold bath and the efficiency: the latter nullifies when the former is maximized and vice versa. A reasonable compromise is achieved by optimizing the product of the heat-power and efficiency over the Hamiltonian of the two systems. The efficiency is then found to be bounded from below by ζCA=(1)/(1-θ)-1 (an analog of the Curzon-Ahlborn efficiency), besides being bound from above by the Carnot efficiency ζC=(1)/(1-θ)-1 . The lower bound is reached in the equilibrium limit θ→1 . The Carnot bound is reached (for a finite power and a finite amount of heat transferred per cycle) for lnn≫1 . If the above maximization is constrained by assuming homogeneous energy spectra for both systems, the efficiency is bounded from above by ζCA and converges to it for n≫1 .

  2. Optimal refrigerator.

    PubMed

    Allahverdyan, Armen E; Hovhannisyan, Karen; Mahler, Guenter

    2010-05-01

    We study a refrigerator model which consists of two n -level systems interacting via a pulsed external field. Each system couples to its own thermal bath at temperatures T h and T c, respectively (θ ≡ T c/T h < 1). The refrigerator functions in two steps: thermally isolated interaction between the systems driven by the external field and isothermal relaxation back to equilibrium. There is a complementarity between the power of heat transfer from the cold bath and the efficiency: the latter nullifies when the former is maximized and vice versa. A reasonable compromise is achieved by optimizing the product of the heat-power and efficiency over the Hamiltonian of the two systems. The efficiency is then found to be bounded from below by [formula: see text] (an analog of the Curzon-Ahlborn efficiency), besides being bound from above by the Carnot efficiency [formula: see text]. The lower bound is reached in the equilibrium limit θ → 1. The Carnot bound is reached (for a finite power and a finite amount of heat transferred per cycle) for ln n > 1. If the above maximization is constrained by assuming homogeneous energy spectra for both systems, the efficiency is bounded from above by ζ CA and converges to it for n > 1. PMID:20866207

  3. Transcranial Direct Current Stimulation Combined with Aerobic Exercise to Optimize Analgesic Responses in Fibromyalgia: A Randomized Placebo-Controlled Clinical Trial

    PubMed Central

    Mendonca, Mariana E.; Simis, Marcel; Grecco, Luanda C.; Battistella, Linamara R.; Baptista, Abrahão F.; Fregni, Felipe

    2016-01-01

    Fibromyalgia is a chronic pain syndrome that is associated with maladaptive plasticity in neural central circuits. One of the neural circuits that are involved in pain in fibromyalgia is the primary motor cortex. We tested a combination intervention that aimed to modulate the motor system: transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) and aerobic exercise (AE). In this phase II, sham-controlled randomized clinical trial, 45 subjects were assigned to 1 of 3 groups: tDCS + AE, AE only, and tDCS only. The following outcomes were assessed: intensity of pain, level of anxiety, quality of life, mood, pressure pain threshold, and cortical plasticity, as indexed by transcranial magnetic stimulation. There was a significant effect for the group-time interaction for intensity of pain, demonstrating that tDCS/AE was superior to AE [F(13, 364) = 2.25, p = 0.007] and tDCS [F(13, 364) = 2.33, p = 0.0056] alone. Post-hoc adjusted analysis showed a difference between tDCS/AE and tDCS group after the first week of stimulation and after 1 month intervention period (p = 0.02 and p = 0.03, respectively). Further, after treatment there was a significant difference between groups in anxiety and mood levels. The combination treatment effected the greatest response. The three groups had no differences regarding responses in motor cortex plasticity, as assessed by TMS. The combination of tDCS with aerobic exercise is superior compared with each individual intervention (cohen's d effect sizes > 0.55). The combination intervention had a significant effect on pain, anxiety and mood. Based on the similar effects on cortical plasticity outcomes, the combination intervention might have affected other neural circuits, such as those that control the affective-emotional aspects of pain. Trial registration: (www.ClinicalTrials.gov), identifier NTC02358902. PMID:27014012

  4. Robust optimization of intensity modulated proton therapy

    SciTech Connect

    Liu Wei; Zhang Xiaodong; Li Yupeng; Mohan, Radhe

    2012-02-15

    Purpose: Intensity modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT optimized based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. In this paper, a method that takes the uncertainties into account during plan optimization is used to mitigate the influence of uncertainties in IMPT. Methods: The authors use the so-called ''worst-case robust optimization'' to render IMPT plans robust in the face of uncertainties. For each iteration, nine different dose distributions are computed--one each for {+-} setup uncertainties along anteroposterior (A-P), lateral (R-L) and superior-inferior (S-I) directions, for {+-} range uncertainty, and the nominal dose distribution. The worst-case dose distribution is obtained by assigning the lowest dose among the nine doses to each voxel in the clinical target volume (CTV) and the highest dose to each voxel outside the CTV. Conceptually, the use of worst-case dose distribution is similar to the dose distribution achieved based on the use of PTV in traditional planning. The objective function value for a given iteration is computed using this worst-case dose distribution. The objective function used has been extended to further constrain the target dose inhomogeneity. Results: The worst-case robust optimization method is applied to a lung case, a skull base case, and a prostate case. Compared with IMPT plans optimized using conventional methods based on the PTV, our method yields plans that are considerably less sensitive to range and setup uncertainties. An interesting finding of the work presented here is that, in addition to reducing sensitivity to uncertainties, robust optimization also leads to improved optimality of treatment plans compared to the PTV-based optimization. This is reflected in reduction in plan scores and in the lower normal tissue doses for the

  5. Recognizing outstanding achievements

    NASA Astrophysics Data System (ADS)

    Speiss, Fred

    One function of any professional society is to provide an objective, informed means for recognizing outstanding achievements in its field. In AGU's Ocean Sciences section we have a variety of means for carrying out this duty. They include recognition of outstanding student presentations at our meetings, dedication of special sessions, nomination of individuals to be fellows of the Union, invitations to present Sverdrup lectures, and recommendations for Macelwane Medals, the Ocean Sciences Award, and the Ewing Medal.Since the decision to bestow these awards requires initiative and judgement by members of our section in addition to a deserving individual, it seems appropriate to review the selection process for each and to urge you to identify those deserving of recognition.

  6. Achieving closure at Fernald

    SciTech Connect

    Bradburne, John; Patton, Tisha C.

    2001-02-25

    When Fluor Fernald took over the management of the Fernald Environmental Management Project in 1992, the estimated closure date of the site was more than 25 years into the future. Fluor Fernald, in conjunction with DOE-Fernald, introduced the Accelerated Cleanup Plan, which was designed to substantially shorten that schedule and save taxpayers more than $3 billion. The management of Fluor Fernald believes there are three fundamental concerns that must be addressed by any contractor hoping to achieve closure of a site within the DOE complex. They are relationship management, resource management and contract management. Relationship management refers to the interaction between the site and local residents, regulators, union leadership, the workforce at large, the media, and any other interested stakeholder groups. Resource management is of course related to the effective administration of the site knowledge base and the skills of the workforce, the attraction and retention of qualified a nd competent technical personnel, and the best recognition and use of appropriate new technologies. Perhaps most importantly, resource management must also include a plan for survival in a flat-funding environment. Lastly, creative and disciplined contract management will be essential to effecting the closure of any DOE site. Fluor Fernald, together with DOE-Fernald, is breaking new ground in the closure arena, and ''business as usual'' has become a thing of the past. How Fluor Fernald has managed its work at the site over the last eight years, and how it will manage the new site closure contract in the future, will be an integral part of achieving successful closure at Fernald.

  7. Achievement Goals and Achievement Emotions: A Meta-Analysis

    ERIC Educational Resources Information Center

    Huang, Chiungjung

    2011-01-01

    This meta-analysis synthesized 93 independent samples (N = 30,003) in 77 studies that reported in 78 articles examining correlations between achievement goals and achievement emotions. Achievement goals were meaningfully associated with different achievement emotions. The correlations of mastery and mastery approach goals with positive achievement…

  8. Development of a Monte Carlo-Based Electron Beam Treatment Planning System: Clinical Application in Optimization of a Combined-Electron Technique for Treatment of Retinoblastoma.

    NASA Astrophysics Data System (ADS)

    Al-Beteri, Abdulkarim A.

    1990-06-01

    Development of a new three-dimensional Monte Carlo code for simulating electron transport in heterogeneous media for the purpose of electron-beam treatment planning is described. It involved the devising of improved mathematical representations for the probability distributions governing the processes of electron multiple-scattering and bremsstrahlung production. An efficient technique is used for random -sampling the probability distributions based on a modified acceptance-rejection sampling method that employs an envelope -type rejection function. In addition to predicting correct electron fluence differential in energy, angle, and both energy and angle at different depths in a variety of materials, the developed code is capable of predicting the following: (1) one-cubic-millimeter resolution electron absorbed-dose distributions in a heterogeneous phantom irradiated by electrons through circular, square, and rectangular fields at different SSD's; (2) perturbation patterns in the absorbed -dose distributions caused by the three most common perturbing agents encountered in the human body (body surface obliquity, bone heterogeneities, and air cavities); (3) dose enhancement anterior to a bone heterogeneity; (4) absorbed-dose perturbations caused by an air cavity adjacent to an irradiated volume but outside the radiation field. This study investigated the effect of heterogeneities on absorbed-dose distributions in phantoms irradiated by electron beams. Perturbation patterns are correctly predicted in depth-dose curves and in absorbed-dose distributions throughout an irradiated volume. For example, the code correctly predicts the doubling of the maximum absorbed dose along the beam central axis when a long narrow air cavity is centered in the field, and isodose level perturbations associated with surface obliquity and the presence of heterogeneities. The developed code is used in optimization of a combined-electron-beams irradiation technique for treatment of

  9. Thermal and clinical performance of a closed device designed for human oocyte vitrification based on the optimization of the warming rate.

    PubMed

    Gallardo, Miguel; Hebles, María; Migueles, Beatriz; Dorado, Mónica; Aguilera, Laura; González, Mercedes; Piqueras, Paloma; Montero, Lorena; Sánchez-Martín, Pascual; Sánchez-Martín, Fernando; Risco, Ramón

    2016-08-01

    Although it was qualitatively pointed out by Fahy et al. (1984), the key role of the warming rates in non-equillibrium vitrification has only recently been quantitatively established for murine oocytes by Mazur and Seki (2011). In this work we study the performance of a closed vitrification device designed under the new paradigm, for the vitrification of human oocytes. The vitrification carrier consists of a main straw in which a specifically designed capillary is mounted and where the oocytes are loaded by aspiration. It can be hermetically sealed before immersion in liquid nitrogen for vitrification, and it is warmed in a sterile water bath at 37 °C. Measured warming rates achieved with this design were of 600.000 ºC/min for a standard DMEM solution and 200.000 ºC/min with the vitrification solution for human oocytes. A cohort of 143 donor MII sibling human oocytes was split into two groups: control (fresh) and vitrified with SafeSpeed device. Similar results were found in both groups: survival (97.1%), fertilization after ICSI (74.7% in control vs. 77.3% in vitrified) and good quality embryos at day three (54.3% in control vs. 58.1% in vitrified) were settled as performance indicators. The pregnancy rate was 3/6 (50%) for the control, 2/3 (66%) for vitrified and 4/5 (80%) for mixed transfers. PMID:27312427

  10. Dynamic Optimization

    NASA Technical Reports Server (NTRS)

    Laird, Philip

    1992-01-01

    We distinguish static and dynamic optimization of programs: whereas static optimization modifies a program before runtime and is based only on its syntactical structure, dynamic optimization is based on the statistical properties of the input source and examples of program execution. Explanation-based generalization is a commonly used dynamic optimization method, but its effectiveness as a speedup-learning method is limited, in part because it fails to separate the learning process from the program transformation process. This paper describes a dynamic optimization technique called a learn-optimize cycle that first uses a learning element to uncover predictable patterns in the program execution and then uses an optimization algorithm to map these patterns into beneficial transformations. The technique has been used successfully for dynamic optimization of pure Prolog.

  11. Entrepreneur achievement. Liaoning province.

    PubMed

    Zhao, R

    1994-03-01

    This paper reports the successful entrepreneurial endeavors of members of a 20-person women's group in Liaoning Province, China. Jing Yuhong, a member of the Family Planning Association at Shileizi Village, Dalian City, provided the basis for their achievements by first building an entertainment/study room in her home to encourage married women to learn family planning. Once stocked with books, magazines, pamphlets, and other materials on family planning and agricultural technology, dozens of married women in the neighborhood flocked voluntarily to the room. Yuhong also set out to give these women a way to earn their own income as a means of helping then gain greater equality with their husbands and exert greater control over their personal reproductive and social lives. She gave a section of her farming land to the women's group, loaned approximately US$5200 to group members to help them generate income from small business initiatives, built a livestock shed in her garden for the group to raise marmots, and erected an awning behind her house under which mushrooms could be grown. The investment yielded $12,000 in the first year, allowing each woman to keep more than $520 in dividends. Members then soon began going to fairs in the capital and other places to learn about the outside world, and have successfully ventured out on their own to generate individual incomes. Ten out of twenty women engaged in these income-generating activities asked for and got the one-child certificate. PMID:12287775

  12. Supply-Chain Optimization Template

    NASA Technical Reports Server (NTRS)

    Quiett, William F.; Sealing, Scott L.

    2009-01-01

    The Supply-Chain Optimization Template (SCOT) is an instructional guide for identifying, evaluating, and optimizing (including re-engineering) aerospace- oriented supply chains. The SCOT was derived from the Supply Chain Council s Supply-Chain Operations Reference (SCC SCOR) Model, which is more generic and more oriented toward achieving a competitive advantage in business.

  13. Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung cancer (NSCLC) treated with target therapy: Result from 3 clinical trials of advanced NSCLC by 1 institution.

    PubMed

    He, Xiaobo; Zhang, Yang; Ma, Yuxiang; Zhou, Ting; Zhang, Jianwei; Hong, Shaodong; Sheng, Jin; Zhang, Zhonghan; Yang, Yunpeng; Huang, Yan; Zhang, Li; Zhao, Hongyun

    2016-08-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as standard therapies for advanced nonsmall cell lung cancer (NSCLC) patients with EGFR mutation positive. Because these targeted therapies could cause tumor necrosis and shrinkage, the purpose of the study is to search for a value of optimal tumor shrinkage as an appropriate indicator of outcome for advanced NSCLC.A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA registration clinical trial, TRUST study and ZD6474 study), who received Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD), respectively, during December 2003 and October 2007, were retrospectively analyzed. The response evaluation criteria in solid tumors (RECIST) were used to identify responders, who had complete response (CR) or partial responses (PR) and nonresponders who had stable disease (SD) or progressive disease (PD). Receiver operating characteristics (ROC) analysis was used to find the optimal tumor shrinkage as an indicator for tumor therapeutic outcome. Univariate and multivariate Cox regression analyses were performed to compare the progression-free survival (PFS) and overall survival (OS) between responders and nonresponders stratified based on radiologic criteria.Among the 88 NSCLC patients, 26 were responders and 62 were nonresponders based on RECIST 1.0. ROC indicated that 8.32% tumor diameter shrinkage in the sum of the longest tumor diameter (SLD) was the cutoff point of tumor shrinkage outcomes, resulting in 46 responders (≤8.32%) and 42 nonresponders (≥8.32%). Univariate and multivariate Cox regression analyses indicated that (1) the responders (≤8.32%) and nonresponders (≥ -8.32%) were significantly different in median PFS (13.40 vs 1.17 months, P < 0.001) and OS (19.80 vs 7.90 months, P < 0.001) and (2) -8.32% in SLD could be used as the optimal threshold for PFS (hazard ratio [HR], 8.11, 95% CI, 3.75 to 17.51, P < 0.001) and OS (HR, 2.36, 95

  14. Students' Goal Achievement: Exploring Individual and Situational Factors

    ERIC Educational Resources Information Center

    Derrer-Rendall, Nicola; Wesson, Caroline; Anderson, Lindsey; Bould, Emma

    2009-01-01

    Introduction: This paper reports a preliminary investigation of the individual and situational factors affecting goal achievement in a psychology student population. The impact of normative information on goal achievement is considered in relation to goal commitment, optimism, gender and academic setting. Method: Psychology students (n=121) from…

  15. Assisting Pupils in Mathematics Achievement (The Common Core Standards)

    ERIC Educational Resources Information Center

    Ediger, Marlow

    2011-01-01

    Mathematics teachers must expect reasonably high standards of achievement from pupils. Too frequently, pupils attain at a substandard level and more optimal achievement is necessary. Thus, pupils should have self esteem needs met in the school and classroom setting. Thus, learners feel that mathematics is worthwhile and effort must be put forth to…

  16. Shared clinical decision making

    PubMed Central

    AlHaqwi, Ali I.; AlDrees, Turki M.; AlRumayyan, Ahmad; AlFarhan, Ali I.; Alotaibi, Sultan S.; AlKhashan, Hesham I.; Badri, Motasim

    2015-01-01

    Objectives: To determine preferences of patients regarding their involvement in the clinical decision making process and the related factors in Saudi Arabia. Methods: This cross-sectional study was conducted in a major family practice center in King Abdulaziz Medical City, Riyadh, Saudi Arabia, between March and May 2012. Multivariate multinomial regression models were fitted to identify factors associated with patients preferences. Results: The study included 236 participants. The most preferred decision-making style was shared decision-making (57%), followed by paternalistic (28%), and informed consumerism (14%). The preference for shared clinical decision making was significantly higher among male patients and those with higher level of education, whereas paternalism was significantly higher among older patients and those with chronic health conditions, and consumerism was significantly higher in younger age groups. In multivariate multinomial regression analysis, compared with the shared group, the consumerism group were more likely to be female [adjusted odds ratio (AOR) =2.87, 95% confidence interval [CI] 1.31-6.27, p=0.008] and non-dyslipidemic (AOR=2.90, 95% CI: 1.03-8.09, p=0.04), and the paternalism group were more likely to be older (AOR=1.03, 95% CI: 1.01-1.05, p=0.04), and female (AOR=2.47, 95% CI: 1.32-4.06, p=0.008). Conclusion: Preferences of patients for involvement in the clinical decision-making varied considerably. In our setting, underlying factors that influence these preferences identified in this study should be considered and tailored individually to achieve optimal treatment outcomes. PMID:26620990

  17. Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design.

    PubMed

    Wei, Ping; Walls, Marlena; Qiu, Ming; Ding, Richard; Denlinger, Robert H; Wong, Anthony; Tsaparikos, Kosta; Jani, Jitesh P; Hosea, Natilie; Sands, Michelle; Randolph, Sophia; Smeal, Tod

    2010-06-01

    Aberrant regulation of Notch signaling has been implicated in tumorigenesis. Proteolytic release of the Notch intracellular domain (NICD) by gamma-secretase plays a key role in Notch-dependent nuclear signaling. gamma-Secretase is an attractive pharmaceutical target for therapeutic intervention in cancer. We describe the potent antitumor effects of PF-03084014, a small molecule that is a reversible, noncompetitive, and selective gamma-secretase inhibitor. The ability of PF-03084014 to inhibit gamma-secretase activity was shown by the reduction of endogenous NICD levels and by the downregulation of Notch target genes Hes-1 and cMyc in the T-cell acute lymphoblastic leukemia (T-ALL) cell line HPB-ALL. PF-03084014 caused cell growth inhibition of several T-ALL cell lines via cell cycle arrest and induction of apoptosis. PF-03084014 treatment also resulted in robust NICD reduction in HBP-ALL xenograft models. Broad antitumor efficacy at well-tolerated dose levels was observed in six Notch-dependent models. Additional mechanism-of-action studies showed inhibition of tumor cell proliferation and induction of apoptosis in HPB-ALL tumors, suggesting that the antitumor activity of PF-03084014 may be mediated by its direct effects on tumor cell growth or survival. Further studies on PF-03084014-induced gastrointestinal toxicity identified an intermittent dosing schedule that displayed reduced body weight loss and sustained antitumor efficacy. We also showed that glucocorticoids abrogated PF-03084014-induced gastrointestinal toxicity and delayed administration of glucocorticoids did not compromise its protection effect. Collectively, the results show that inhibition of Notch signaling by PF-03084014 while minimizing gastrointestinal toxicity presents a promising approach for development of therapies for Notch receptor-dependent cancers. This compound is being investigated for the treatment of T-ALL and advanced solid tumors in phase I clinical trials. PMID:20530712

  18. The Optimization of Molecular Detection of Clinical Isolates of Brucella in Blood Cultures by eryD Transcriptase Gene for Confirmation of Culture-Negative Samples

    PubMed Central

    Tabibnejad, Mahsa; Alikhani, Mohammad Yousef; Arjomandzadegan, Mohammad; Hashemi, Seyed Hamid; Naseri, Zahra

    2016-01-01

    Background Brucellosis is a zoonosis disease which is widespread across the world. Objectives The aim of the present study is the evaluation of culture-negative blood samples. Materials and Methods A total of 100 patients with suspected brucellosis were included in this experimental study and given positive serological tests. Diagnosis was performed on patients with clinical symptoms of the disease, followed by the detection of a titer that was equal to or more than 1:160 (in endemic areas) by the standard tube agglutination method. Blood samples were cultured by a BACTEC 9050 system, and subsequently by Brucella agar. At the same time, DNA from all blood samples was extracted by Qiagen Kit Company (Qia Amp Mini Kit). A molecular assay of blood samples was carried out by detection of eryD transcriptase and bcsp 31 genes in specific double PCR reactions. The specificity of the primers was evaluated by DNA from pure and approved Brucella colonies found in the blood samples, by DNA from other bacteria, and by ordinary PCR. DNA extraction from the pure colonies was carried out by both Qiagen Kit and Chelex 100 methods; the two were compared. Results 39 cases (39%) had positive results when tested by the BACTEC system, and 61 cases (61%) became negative. 23 culture-positive blood samples were randomly selected for PCR reactions; all showed 491 bp for the eryD gene and 223 bp for the bcsp 31 gene. Interestingly, out of 14 culture-negative blood samples, 13 cases showed positive bonds in PCR. The specificity of the PCR method was equal to 100%. DNA extraction from pure cultures was done by both Chelex 100 and Qiagen Kit; these showed the same results for all samples. Conclusions The results prove that the presented double PCR method could be used to detect positive cases from culture-negative blood samples. The Chelex 100 method is simpler and safer than the use of Qiagen Kit for DNA extraction. PMID:27330831

  19. RF Gun Optimization Study

    SciTech Connect

    A. S. Hofler; P. Evtushenko; M. Krasilnikov

    2007-08-01

    Injector gun design is an iterative process where the designer optimizes a few nonlinearly interdependent beam parameters to achieve the required beam quality for a particle accelerator. Few tools exist to automate the optimization process and thoroughly explore the parameter space. The challenging beam requirements of new accelerator applications such as light sources and electron cooling devices drive the development of RF and SRF photo injectors. RF and SRF gun design is further complicated because the bunches are space charge dominated and require additional emittance compensation. A genetic algorithm has been successfully used to optimize DC photo injector designs for Cornell* and Jefferson Lab**, and we propose studying how the genetic algorithm techniques can be applied to the design of RF and SRF gun injectors. In this paper, we report on the initial phase of the study where we model and optimize gun designs that have been benchmarked with beam measurements and simulation.

  20. The Homogeneity of School Achievement.

    ERIC Educational Resources Information Center

    Cahan, Sorel

    Since the measurement of school achievement involves the administration of achievement tests to various grades on various subjects, both grade level and subject matter contribute to within-school achievement variations. To determine whether achievement test scores vary most among different fields within a grade level, or within fields among…

  1. Optimal Bayesian adaptive trials when treatment efficacy depends on biomarkers.

    PubMed

    Zhang, Yifan; Trippa, Lorenzo; Parmigiani, Giovanni

    2016-06-01

    Clinical biomarkers play an important role in precision medicine and are now extensively used in clinical trials, particularly in cancer. A response adaptive trial design enables researchers to use treatment results about earlier patients to aid in treatment decisions of later patients. Optimal adaptive trial designs have been developed without consideration of biomarkers. In this article, we describe the mathematical steps for computing optimal biomarker-integrated adaptive trial designs. These designs maximize the expected trial utility given any pre-specified utility function, though we focus here on maximizing patient responses within a given patient horizon. We describe the performance of the optimal design in different scenarios. We compare it to Bayesian Adaptive Randomization (BAR), which is emerging as a practical approach to develop adaptive trials. The difference in expected utility between BAR and optimal designs is smallest when the biomarker subgroups are highly imbalanced. We also compare BAR, a frequentist play-the-winner rule with integrated biomarkers and a marker-stratified balanced randomization design (BR). We show that, in contrasting two treatments, BR achieves a nearly optimal expected utility when the patient horizon is relatively large. Our work provides novel theoretical solution, as well as an absolute benchmark for the evaluation of trial designs in personalized medicine. PMID:26575199

  2. Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty

    SciTech Connect

    Fredriksson, Albin Hårdemark, Björn; Forsgren, Anders

    2015-07-15

    Purpose: This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity-modulated radiation therapy treatments subject to setup uncertainty. Methods: The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goals to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set. Results: Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account. Conclusions: Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality.

  3. Optimization of Routine Identification of Clinically Relevant Gram-Negative Bacteria by Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and the Bruker Biotyper

    PubMed Central

    Ford, Bradley A.

    2013-01-01

    Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) might complement and one day replace phenotypic identification of bacteria in the clinical microbiology laboratory, but there is no consensus standard regarding the requirements for its validation prior to clinical use in the United States. The objective of this study was to assess the preanalytical variables influencing Gram-negative identification by use of the Bruker Biotyper MALDI-TOF MS system, including density of organism spotting on a stainless steel target plate and the direct overlay of organisms with formic acid. A heavy smear with formic acid overlay was either superior or equivalent to alternative smear conditions. Microbiological preanalytical variables were also assayed, such as culture medium, growth temperature, and use of serial subculture. Postanalytical analysis included the application of modified species-level identification acceptance criteria. Biotyper identifications were compared with those using traditional phenotypic methods, and discrepancies were resolved with 16S rRNA gene sequencing. Compared to the recommended score cutoffs of the manufacturer, the application of optimized Biotyper score cutoffs for species-level identification increased the rate of identification by 6.75% for the enteric Gram-negative bacteria and 4.25% for the nonfermenting Gram-negative bacteria. Various incubation temperatures, growth medium types, and repeat subcultures did not result in misidentification. We conclude that the Bruker MALDI Biotyper is a robust system for the identification of Gram-negative organisms in the clinical laboratory and that meaningful performance improvements can be made by implementing simple pre- and postanalytical techniques. PMID:23426923

  4. HEPEX - achievements and challenges!

    NASA Astrophysics Data System (ADS)

    Pappenberger, Florian; Ramos, Maria-Helena; Thielen, Jutta; Wood, Andy; Wang, Qj; Duan, Qingyun; Collischonn, Walter; Verkade, Jan; Voisin, Nathalie; Wetterhall, Fredrik; Vuillaume, Jean-Francois Emmanuel; Lucatero Villasenor, Diana; Cloke, Hannah L.; Schaake, John; van Andel, Schalk-Jan

    2014-05-01

    HEPEX is an international initiative bringing together hydrologists, meteorologists, researchers and end-users to develop advanced probabilistic hydrological forecast techniques for improved flood, drought and water management. HEPEX was launched in 2004 as an independent, cooperative international scientific activity. During the first meeting, the overarching goal was defined as: "to develop and test procedures to produce reliable hydrological ensemble forecasts, and to demonstrate their utility in decision making related to the water, environmental and emergency management sectors." The applications of hydrological ensemble predictions span across large spatio-temporal scales, ranging from short-term and localized predictions to global climate change and regional modeling. Within the HEPEX community, information is shared through its blog (www.hepex.org), meetings, testbeds and intercompaison experiments, as well as project reportings. Key questions of HEPEX are: * What adaptations are required for meteorological ensemble systems to be coupled with hydrological ensemble systems? * How should the existing hydrological ensemble prediction systems be modified to account for all sources of uncertainty within a forecast? * What is the best way for the user community to take advantage of ensemble forecasts and to make better decisions based on them? This year HEPEX celebrates its 10th year anniversary and this poster will present a review of the main operational and research achievements and challenges prepared by Hepex contributors on data assimilation, post-processing of hydrologic predictions, forecast verification, communication and use of probabilistic forecasts in decision-making. Additionally, we will present the most recent activities implemented by Hepex and illustrate how everyone can join the community and participate to the development of new approaches in hydrologic ensemble prediction.

  5. Harmony search optimization for HDR prostate brachytherapy

    NASA Astrophysics Data System (ADS)

    Panchal, Aditya

    implemented in this thesis was within 2% of the values computed by Varian BrachyVision for the prostate, within 3% for the rectum and bladder and 6% for the urethra. The calculation of dose compared to BrachyVision was determined to be different by only 0.38%. Isodose curves were also generated and were found to be similar to BrachyVision. The comparison between Harmony Search and genetic algorithm showed that Harmony Search was over 4 times faster when compared over multiple data sets. The optimal Harmony Memory Size was found to be 5 or lower; the Harmony Memory Considering Rate was determined to be 0.95, and the Pitch Adjusting Rate was found to be 0.9. Ultimately, the effect of multithreading showed that as intensive computations such as optimization and dose calculation are involved, the threads of execution scale with the number of processors, achieving a speed increase proportional to the number of processor cores. In conclusion, this work showed that Harmony Search is a viable alternative to existing algorithms for use in HDR prostate brachytherapy optimization. Coupled with the optimal parameters for the algorithm and a multithreaded simulation, this combination has the capability to significantly decrease the time spent on minimizing optimization problems in the clinic that are time intensive, such as brachytherapy, IMRT and beam angle optimization.

  6. Optimism and diet quality in the Women's Health Initiative.

    PubMed

    Hingle, Melanie D; Wertheim, Betsy C; Tindle, Hilary A; Tinker, Lesley; Seguin, Rebecca A; Rosal, Milagros C; Thomson, Cynthia A

    2014-07-01

    Diet quality has not been well studied in relation to positive psychological traits. Our purpose was to investigate the relationship between optimism and diet quality in postmenopausal women enrolled in the Women's Health Initiative observational study (OS) and clinical trials (CTs), and to determine whether optimism was associated with diet change after a 1-year dietary intervention. Diet quality was scored with the Alternate Healthy Eating Index (AHEI) and optimism assessed with the Life Orientation Test-Revised. Baseline characteristics were compared across AHEI quintiles or optimism tertiles using regression models with each variable of interest as a function of quintiles or tertiles (OS, n=87,630; CT, n=65,360). Association between optimism and baseline AHEI and change in AHEI over 1 year were tested using multivariate linear regression (CT, n=13,645). Potential interaction between optimism and trial arm and demographic/lifestyle factors on AHEI change was tested using likelihood ratio test (CT intervention, n=13,645; CT control, n=20,242). Women reporting high AHEI were non-Hispanic white, educated, physically active, past or never smokers, hormone therapy users, had lower body mass index and waist circumference, and were less likely to have chronic conditions. In the CT intervention, higher optimism was associated with higher AHEI at baseline and with greater change over 1 year (P=0.001). Effect modification by intervention status was observed (P=0.014), whereas control participants with highest optimism achieved threefold greater AHEI increase compared with those with the lowest optimism. These data support a relationship between optimism and dietary quality score in postmenopausal women at baseline and over 1 year. PMID:24556429

  7. Optimal strategies of social distancing and vaccination against seasonal influenza.

    PubMed

    Shim, Eunha

    2013-01-01

    Optimal control strategies for controlling seasonal influenza transmission in the US are of high interest, because of the significant epidemiological and economic burden of influenza. To evaluate optimal strategies of vaccination and social distancing, we used an age-structured dynamic model of seasonal influenza. We applied optimal control theory to identify the best way of reducing morbidity and mortality at a minimal cost. In combination with the Pontryagins maximum principle, we calculated time-dependent optimal policies of vaccination and social distancing to minimize the epidemiological and economic burden associated with seasonal influenza. We computed optimal age-specific intervention strategies and analyze them under various costs of interventions and disease transmissibility. Our results show that combined strategies have a stronger impact on the reduction of the final epidemic size. Our results also suggest that the optimal vaccination can be achieved by allocating most vaccines to preschool-age children (age under five) followed by young adults (age 20-39) and school age children (age 6-19). We find that the optimal vaccination rates for all age groups are highest at the beginning of the outbreak, requiring intense effort at the early phase of an epidemic. On the other hand, optimal social distancing of clinical cases tends to last the entire duration of an outbreak, and its intensity is relatively equal for all age groups. Furthermore, with higher transmissibility of the influenza virus (i.e. higher R0), the optimal control strategy needs to include more efforts to increase vaccination rates rather than efforts to encourage social distancing. Taken together, public health agencies need to consider both the transmissibility of the virus and ways to encourage early vaccination as well as voluntary social distancing of symptomatic cases in order to determine optimal intervention strategies against seasonal influenza. PMID:24245639

  8. Critical Pedagogy for Transformative Optimism

    ERIC Educational Resources Information Center

    Mayo, Peter

    2006-01-01

    This essay critically highlights the main features of a study that attaches importance to the concepts of time and optimism and their effects on the achievement and goals of high and low achievers in a North American and a Brazilian context. The focus on the time factor that serves as a leitmotif throughout the study gives this work its…

  9. Parametric Design Optimization By Integrating CAD Systems And Optimization Tools

    NASA Astrophysics Data System (ADS)

    Rehan, M.; Olabi, A. G.

    2009-11-01

    Designing a cost effective product in minimum time is a complex process. In order to achieve this goal the requirement of optimum designs are becoming more important. One of the time consuming factor in the design optimization cycle is the modifications of Computer Aided Design (CAD) model after optimization. In conventional design optimization techniques the design engineer has to update the CAD model after receiving optimum design from optimization tools. It is worthwhile using parametric design optimization process to minimize the optimization cycle time. This paper presents a comprehensive study to integrate the optimization parameters between CAD system and optimization tools which were driven from a single user environment. Finally, design optimization of a Compressed Natural Gas (CNG) cylinder was implemented as case study. In this case study the optimization tools were fully integrated with CAD system, therefore, all the deliverables including; part design, drawings and assembly can be automatically updated after achieving the optimum geometry having minimum volume and satisfying all imposed constraints.

  10. Organ-specific Differences in Achieving Tolerance

    PubMed Central

    Madariaga, Maria Lucia L.; Kreisel, Daniel; Madsen, Joren C.

    2015-01-01

    Purpose of review When it comes to tolerance induction, kidney allografts behave differently from heart allografts which behave differently from lung allografts. Here, we examine how and why different organ allografts respond differently to the same tolerance induction protocol. Recent findings Allograft tolerance has been achieved in experimental and clinical kidney transplantation. However, inducing tolerance in experimental recipients of heart and lung allografts has proven to be more challenging. New protocols being developed in nonhuman primates based on mixed chimerism and co-transplantation of tolerogenic organs may provide mechanistic insights to help overcome these challenges. Summary Tolerance induction protocols that are successful in patients transplanted with “tolerance-prone” organs such as kidneys and livers will most likely not succeed in recipients of “tolerance-resistant” organs such as hearts and lungs. Separate clinical trials using more robust tolerance protocols will be required to achieve tolerance in heart and lung recipients. PMID:26147678

  11. MPQC: Performance Analysis and Optimization

    SciTech Connect

    Sarje, Abhinav; Williams, Samuel; Bailey, David

    2012-11-30

    MPQC (Massively Parallel Quantum Chemistry) is a widely used computational quantum chemistry code. It is capable of performing a number of computations commonly occurring in quantum chemistry. In order to achieve better performance of MPQC, in this report we present a detailed performance analysis of this code. We then perform loop and memory access optimizations, and measure performance improvements by comparing the performance of the optimized code with that of the original MPQC code. We observe that the optimized MPQC code achieves a significant improvement in the performance through a better utilization of vector processing and memory hierarchies.

  12. Clinical management of progressive myopia

    PubMed Central

    Aller, T A

    2014-01-01

    Myopia has been increasing in prevalence throughout the world, reaching over 90% in some East Asian populations. There is increasing evidence that whereas genetics clearly have an important role, the type of visual environment to which one is exposed to likely influences the onset, progression, and cessation of myopia. Consequently, attempts to either modify the environment or to reduce the exposure of the eye to various environmental stimuli to eye growth through the use of various optical devices are well under way at research centers around the globe. The most promising of current treatments include low-percentage atropine, bifocal soft contact lenses, orthokeratology, and multifocal spectacles. These methods are discussed briefly and are then categorized in terms of their expected degree of myopia progression control. A clinical strategy is presented for selecting the most effective treatment for the appropriate type of patient at the optimal stage of refractive development to achieve the maximum control of myopia progression. PMID:24357844

  13. The Impact of Reading Achievement on Overall Academic Achievement

    ERIC Educational Resources Information Center

    Churchwell, Dawn Earheart

    2009-01-01

    This study examined the relationship between reading achievement and achievement in other subject areas. The purpose of this study was to determine if there was a correlation between reading scores as measured by the Standardized Test for the Assessment of Reading (STAR) and academic achievement in language arts, math, science, and social studies…

  14. Attitude Towards Physics and Additional Mathematics Achievement Towards Physics Achievement

    ERIC Educational Resources Information Center

    Veloo, Arsaythamby; Nor, Rahimah; Khalid, Rozalina

    2015-01-01

    The purpose of this research is to identify the difference in students' attitude towards Physics and Additional Mathematics achievement based on gender and relationship between attitudinal variables towards Physics and Additional Mathematics achievement with achievement in Physics. This research focused on six variables, which is attitude towards…

  15. Predicting Mathematics Achievement: The Influence of Prior Achievement and Attitudes

    ERIC Educational Resources Information Center

    Hemmings, Brian; Grootenboer, Peter; Kay, Russell

    2011-01-01

    Achievement in mathematics is inextricably linked to future career opportunities, and therefore, understanding those factors that influence achievement is important. This study sought to examine the relationships among attitude towards mathematics, ability and mathematical achievement. This examination was also supported by a focus on gender…

  16. Factors Influencing Seminar Learning and Academic Achievement.

    PubMed

    Spruijt, Annemarie; Leppink, Jimmie; Wolfhagen, Ineke; Bok, Harold; Mainhard, Tim; Scherpbier, Albert; van Beukelen, Peter; Jaarsma, Debbie

    2015-01-01

    Many veterinary curricula use seminars, interactive educational group formats in which some 25 students discuss questions and issues relating to course themes. To get indications on how to optimize the seminar learning process for students, we aimed to investigate relationships between factors that seem to be important for the seminar learning process, and to determine how these seminar factors account for differences in students' achievement scores. A 57-item seminar evaluation (USEME) questionnaire was administered to students right after they attended a seminar. In total, 80 seminars distributed over years 1, 2, and 3 of an undergraduate veterinary medicine curriculum were sampled and 988 questionnaires were handed in. Principal factor analysis (PFA) was conducted on 410 questionnaires to examine which items could be grouped together as indicators of the same factor, and to determine correlations between the derived factors. Multilevel regression analysis was performed to explore the effects of these seminar factors and students' prior achievement scores on students' achievement scores. Within the questionnaire, four factors were identified that influence the seminar learning process: teacher performance, seminar content, student preparation, and opportunities for interaction within seminars. Strong correlations were found between teacher performance, seminar content, and group interaction. Prior achievement scores and, to a much lesser extent, the seminar factor group interaction appeared to account for differences in students' achievement scores. The factors resulting from the present study and their relation to the method of assessment should be examined further, for example, in an experimental setup. PMID:26075625

  17. Utility Theory for Evaluation of Optimal Process Condition of SAW: A Multi-Response Optimization Approach

    SciTech Connect

    Datta, Saurav; Biswas, Ajay; Bhaumik, Swapan; Majumdar, Gautam

    2011-01-17

    Multi-objective optimization problem has been solved in order to estimate an optimal process environment consisting of optimal parametric combination to achieve desired quality indicators (related to bead geometry) of submerged arc weld of mild steel. The quality indicators selected in the study were bead height, penetration depth, bead width and percentage dilution. Taguchi method followed by utility concept has been adopted to evaluate the optimal process condition achieving multiple objective requirements of the desired quality weld.

  18. [Research Reports on Academic Achievement.

    ERIC Educational Resources Information Center

    Latts, Sander; And Others

    1969-01-01

    Four counselors studied the relation between achievement and choice of major, achievement and motivation, counseling and motivation, and achievement and employment. To see if those with definite majors or career choices in mind did better than those without, 300 students were tested according to the certainty of their choice. No significant…

  19. Cherokee Culture and School Achievement.

    ERIC Educational Resources Information Center

    Brown, Anthony D.

    1980-01-01

    Compares the effect of cooperative and competitive behaviors of Cherokee and Anglo American elementary school students on academic achievement. Suggests changes in teaching techniques and lesson organization that might raise academic achievement while taking into consideration tribal traditions that limit scholastic achievement in an…

  20. Efficient Research Design: Using Value-of-Information Analysis to Estimate the Optimal Mix of Top-down and Bottom-up Costing Approaches in an Economic Evaluation alongside a Clinical Trial.

    PubMed

    Wilson, Edward C F; Mugford, Miranda; Barton, Garry; Shepstone, Lee

    2016-04-01

    In designing economic evaluations alongside clinical trials, analysts are frequently faced with alternative methods of collecting the same data, the extremes being top-down ("gross costing") and bottom-up ("micro-costing") approaches. A priori, bottom-up approaches may be considered superior to top-down approaches but are also more expensive to collect and analyze. In this article, we use value-of-information analysis to estimate the efficient mix of observations on each method in a proposed clinical trial. By assigning a prior bivariate distribution to the 2 data collection processes, the predicted posterior (i.e., preposterior) mean and variance of the superior process can be calculated from proposed samples using either process. This is then used to calculate the preposterior mean and variance of incremental net benefit and hence the expected net gain of sampling. We apply this method to a previously collected data set to estimate the value of conducting a further trial and identifying the optimal mix of observations on drug costs at 2 levels: by individual item (process A) and by drug class (process B). We find that substituting a number of observations on process A for process B leads to a modest £ 35,000 increase in expected net gain of sampling. Drivers of the results are the correlation between the 2 processes and their relative cost. This method has potential use following a pilot study to inform efficient data collection approaches for a subsequent full-scale trial. It provides a formal quantitative approach to inform trialists whether it is efficient to collect resource use data on all patients in a trial or on a subset of patients only or to collect limited data on most and detailed data on a subset. PMID:26762649

  1. Developmental Pathways from Parental Substance Use to Childhood Academic Achievement

    PubMed Central

    Brook, Judith S.; Saar, Naomi S.; Brook, David W.

    2010-01-01

    This cross-sectional study examined the pathways to childhood academic achievement in 209 African American and Puerto Rican children and their mothers. There were three pathways to childhood academic achievement: (a) the mother-child relationship and the child’s personality mediated between parental substance use and childhood academic achievement; (b) the child’s personality mediated between parental education and childhood academic achievement; and (c) there was a direct relationship between the child’s gender and childhood academic achievement. Policy and clinical implications suggest the importance of increasing educational opportunities for all parents, providing substance use treatment and self-esteem workshops, and altering the school curriculum. PMID:20525035

  2. Thermoacoustic Refrigerator's Stack Optimization

    NASA Astrophysics Data System (ADS)

    El-Fawal, Mawahib Hassan; Mohd-Ghazali, Normah; Yaacob, Mohd. Shafik; Darus, Amer Nordin

    2010-06-01

    The standing wave thermoacoustic refrigerator, which uses sound generation to transfer heat, was developed rapidly during the past four decades. It was regarded as a new, promising and environmentally benign alternative to conventional compression vapor refrigerators, although it was not competitive regarding the coefficient of performance (COP) yet. Thus the aim of this paper is to enhance thermoacoustic refrigerator's stack performance through optimization. A computational optimization procedure of thermoacoustic stack design was fully developed. The procedure was designed to achieve optimal coefficient of performance based on most of the design and operating parameters. Cooling load and acoustic power governing equations were set assuming the linear thermoacoustic theory. Lagrange multipliers method was used as an optimization technique tool to solve the governing equations. Numerical analyses results of the developed design procedure are presented. The results showed that the stack design parameters are the most significant parameters for the optimal overall performance. The coefficient of performance obtained increases by about 48.8% from the published experimental optimization methods. The results are in good agreement with past established studies.

  3. Characterizing the ideal clinical office system for nephrology.

    PubMed

    Maddux, Franklin W; Maddux, Dugan W

    2008-01-01

    Clinical information technology (IT) systems that support nephrology-specific content can facilitate the coordinated, progressive, and comprehensive care of all patients with renal disease including those with each stage of chronic kidney disease (CKD). The ideal clinical IT system should have flexible features to meet the needs of individualized practice patterns, yet also have tools to enhance continuity, measure performance, and deliver decision support features that assist the nephrologist in providing optimal care for the CKD patient. This article provides insight into the complexities of engaging in the process of technology adoption, including selection, integration, and implementation while emphasizing the utility of using a continuous quality improvement paradigm to identify and achieve positive results from the adoption and integration of a clinical IT system into outpatient clinical practice of nephrology. PMID:18155111

  4. Barriers to the Clinical Translation of Orthopedic Tissue Engineering

    PubMed Central

    2011-01-01

    Tissue engineering and regenerative medicine have been the subject of increasingly intensive research for over 20 years, and there is concern in some quarters over the lack of clinically useful products despite the large sums of money invested. This review provides one perspective on orthopedic applications from a biologist working in academia. It is suggested that the delay in clinical application is not atypical of new, biologically based technologies. Some barriers to progress are acknowledged and discussed, but it is also noted that preclinical studies have identified several promising types of cells, scaffolds, and morphogenetic signals, which, although not optimal, are worth advancing toward human trials to establish a bridgehead in the clinic. Although this transitional technology will be replaced by more sophisticated, subsequent systems, it will perform valuable pioneering functions and facilitate the clinical development of the field. Some strategies for achieving this are suggested. PMID:21682607

  5. Barriers to the clinical translation of orthopedic tissue engineering.

    PubMed

    Evans, Christopher H

    2011-12-01

    Tissue engineering and regenerative medicine have been the subject of increasingly intensive research for over 20 years, and there is concern in some quarters over the lack of clinically useful products despite the large sums of money invested. This review provides one perspective on orthopedic applications from a biologist working in academia. It is suggested that the delay in clinical application is not atypical of new, biologically based technologies. Some barriers to progress are acknowledged and discussed, but it is also noted that preclinical studies have identified several promising types of cells, scaffolds, and morphogenetic signals, which, although not optimal, are worth advancing toward human trials to establish a bridgehead in the clinic. Although this transitional technology will be replaced by more sophisticated, subsequent systems, it will perform valuable pioneering functions and facilitate the clinical development of the field. Some strategies for achieving this are suggested. PMID:21682607

  6. Students' Achievement Goals, Learning-Related Emotions and Academic Achievement.

    PubMed

    Lüftenegger, Marko; Klug, Julia; Harrer, Katharina; Langer, Marie; Spiel, Christiane; Schober, Barbara

    2016-01-01

    In the present research, the recently proposed 3 × 2 model of achievement goals is tested and associations with achievement emotions and their joint influence on academic achievement are investigated. The study was conducted with 388 students using the 3 × 2 Achievement Goal Questionnaire including the six proposed goal constructs (task-approach, task-avoidance, self-approach, self-avoidance, other-approach, other-avoidance) and the enjoyment and boredom scales from the Achievement Emotion Questionnaire. Exam grades were used as an indicator of academic achievement. Findings from CFAs provided strong support for the proposed structure of the 3 × 2 achievement goal model. Self-based goals, other-based goals and task-approach goals predicted enjoyment. Task-approach goals negatively predicted boredom. Task-approach and other-approach predicted achievement. The indirect effects of achievement goals through emotion variables on achievement were assessed using bias-corrected bootstrapping. No mediation effects were found. Implications for educational practice are discussed. PMID:27199836

  7. Students’ Achievement Goals, Learning-Related Emotions and Academic Achievement

    PubMed Central

    Lüftenegger, Marko; Klug, Julia; Harrer, Katharina; Langer, Marie; Spiel, Christiane; Schober, Barbara

    2016-01-01

    In the present research, the recently proposed 3 × 2 model of achievement goals is tested and associations with achievement emotions and their joint influence on academic achievement are investigated. The study was conducted with 388 students using the 3 × 2 Achievement Goal Questionnaire including the six proposed goal constructs (task-approach, task-avoidance, self-approach, self-avoidance, other-approach, other-avoidance) and the enjoyment and boredom scales from the Achievement Emotion Questionnaire. Exam grades were used as an indicator of academic achievement. Findings from CFAs provided strong support for the proposed structure of the 3 × 2 achievement goal model. Self-based goals, other-based goals and task-approach goals predicted enjoyment. Task-approach goals negatively predicted boredom. Task-approach and other-approach predicted achievement. The indirect effects of achievement goals through emotion variables on achievement were assessed using bias-corrected bootstrapping. No mediation effects were found. Implications for educational practice are discussed. PMID:27199836

  8. Process validation: achieving the Operational Qualification phase.

    PubMed

    Buffaloe, Vera

    2004-01-01

    The OQ phase of process validation is very important and is where the complete understanding of the process is determined by experimentation. This understanding is useful to: * establish optimal process parameters * understand variation that affect the process * aid in investigating process deviations. OQ is an important part of the entire process validation activity and essential to understanding a manufacturing process. The benefits of completing the OQ and overall process validation are the reasons that it makes business sense and receive the long-term benefits of producing high quality product and achieving customer satisfaction. PMID:15521514

  9. Dispositional Optimism

    PubMed Central

    Carver, Charles S.; Scheier, Michael F.

    2014-01-01

    Optimism is a cognitive construct (expectancies regarding future outcomes) that also relates to motivation: optimistic people exert effort, whereas pessimistic people disengage from effort. Study of optimism began largely in health contexts, finding positive associations between optimism and markers of better psychological and physical health. Physical health effects likely occur through differences in both health-promoting behaviors and physiological concomitants of coping. Recently, the scientific study of optimism has extended to the realm of social relations: new evidence indicates that optimists have better social connections, partly because they work harder at them. In this review, we examine the myriad ways this trait can benefit an individual, and our current understanding of the biological basis of optimism. PMID:24630971

  10. Optimal Centroid Position Estimation

    SciTech Connect

    Candy, J V; McClay, W A; Awwal, A S; Ferguson, S W

    2004-07-23

    The alignment of high energy laser beams for potential fusion experiments demand high precision and accuracy by the underlying positioning algorithms. This paper discusses the feasibility of employing online optimal position estimators in the form of model-based processors to achieve the desired results. Here we discuss the modeling, development, implementation and processing of model-based processors applied to both simulated and actual beam line data.

  11. Achievement as Resistance: The Development of a Critical Race Achievement Ideology among Black Achievers

    ERIC Educational Resources Information Center

    Carter, Dorinda J.

    2008-01-01

    In this article, Dorinda Carter examines the embodiment of a critical race achievement ideology in high-achieving black students. She conducted a yearlong qualitative investigation of the adaptive behaviors that nine high-achieving black students developed and employed to navigate the process of schooling at an upper-class, predominantly white,…

  12. Do Intelligence and Sustained Attention Interact in Predicting Academic Achievement?

    ERIC Educational Resources Information Center

    Steinmayr, Ricarda; Ziegler, Mattias; Trauble, Birgit

    2010-01-01

    Research in clinical samples suggests that the relationship between intelligence and academic achievement might be moderated by sustained attention. The present study aimed to explore whether this interaction could be observed in a non-clinical sample. We investigated a sample of 11th and 12th grade students (N = 231). An overall performance score…

  13. CT dose minimization using personalized protocol optimization and aggressive bowtie

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Yin, Zhye; Jin, Yannan; Wu, Mingye; Yao, Yangyang; Tao, Kun; Kalra, Mannudeep K.; De Man, Bruno

    2016-03-01

    In this study, we propose to use patient-specific x-ray fluence control to reduce the radiation dose to sensitive organs while still achieving the desired image quality (IQ) in the region of interest (ROI). The mA modulation profile is optimized view by view, based on the sensitive organs and the ROI, which are obtained from an ultra-low-dose volumetric CT scout scan [1]. We use a clinical chest CT scan to demonstrate the feasibility of the proposed concept: the breast region is selected as the sensitive organ region while the cardiac region is selected as IQ ROI. Two groups of simulations are performed based on the clinical CT dataset: (1) a constant mA scan adjusted based on the patient attenuation (120 kVp, 300 mA), which serves as baseline; (2) an optimized scan with aggressive bowtie and ROI centering combined with patient-specific mA modulation. The results shows that the combination of the aggressive bowtie and the optimized mA modulation can result in 40% dose reduction in the breast region, while the IQ in the cardiac region is maintained. More generally, this paper demonstrates the general concept of using a 3D scout scan for optimal scan planning.

  14. Gender Issues in Gifted Achievement: Are Girls Making Inroads While Boys Fall Behind?

    ERIC Educational Resources Information Center

    Rimm, Sylvia B.

    2015-01-01

    School and life achievement patterns for girls and women differ from those of boys and men. While girls have made dramatic progress in school, they need to be inspired to connect to lifelong achievement. Both research and clinical work at the Ohio-based Family Achievement Clinic find that more boys than girls underachieve in school. There is much…

  15. The Mechanics of Human Achievement

    PubMed Central

    Duckworth, Angela L.; Eichstaedt, Johannes C.; Ungar, Lyle H.

    2015-01-01

    Countless studies have addressed why some individuals achieve more than others. Nevertheless, the psychology of achievement lacks a unifying conceptual framework for synthesizing these empirical insights. We propose organizing achievement-related traits by two possible mechanisms of action: Traits that determine the rate at which an individual learns a skill are talent variables and can be distinguished conceptually from traits that determine the effort an individual puts forth. This approach takes inspiration from Newtonian mechanics: achievement is akin to distance traveled, effort to time, skill to speed, and talent to acceleration. A novel prediction from this model is that individual differences in effort (but not talent) influence achievement (but not skill) more substantially over longer (rather than shorter) time intervals. Conceptualizing skill as the multiplicative product of talent and effort, and achievement as the multiplicative product of skill and effort, advances similar, but less formal, propositions by several important earlier thinkers. PMID:26236393

  16. Optimal management of breakthrough cancer pain (BCP).

    PubMed

    Escobar, Y; Mañas, A; Juliá, J; Gálvez, R; Zaragozá, F; Margarit, C; López, R; Casas, A; Antón, A; Cruz, J J

    2013-07-01

    Breakthrough cancer pain (BCP) is common in patients with cancer, causing a negative impairment in quality of life. Recent diagnostic criteria allow for differentiation of background chronic pain and BCP, for which proportion of unpredictable episodes is very high. Five characteristics define BCP: rapid onset, high intensity, maximum intensity (minutes), mean duration 30 min, and unpredictable onset. Fentanyl is a synthetic opioid characterized by rapid absorption and start of the analgesic effects. In addition to comparing some of the marked differences between the four pharmaceutical forms of fentanyl marketed in Spain, this paper discusses the data collected in a comprehensive clinical trial program with fentanyl pectin nasal spray (FPNS), a formulation that takes advantage of the intranasal route and the PecSys™ technology. The FPNS formulation achieves analgesic action 5 min after application and significant pain relief at 10 min. FPNS, therefore, has key features to be an optimal treatment for BCP. PMID:23263914

  17. Unmet Promise: Raising Minority Achievement. The Achievement Gap.

    ERIC Educational Resources Information Center

    Johnston, Robert C.; Viadero, Debra

    2000-01-01

    This first in a four-part series on why academic achievement gaps persist discusses how to raise minority achievement. It explains how earlier progress in closing the gap has stalled, while at the same time, the greater diversity of student populations and the rapid growth of the Hispanic population and of other ethnic groups have reshaped the…

  18. To Achieve or Not to Achieve: The Question of Women.

    ERIC Educational Resources Information Center

    Gilmore, Beatrice

    Questionnaire and projective data from 323 women aged 18 to 50 were analyzed in order to study the relationships of need achievement and motive to avoid success to age, sex role ideology, and stage in the family cycle. Family background and educational variables were also considered. Level of need achievement was found to be significantly related…

  19. Mathematics Achievement in High- and Low-Achieving Secondary Schools

    ERIC Educational Resources Information Center

    Mohammadpour, Ebrahim; Shekarchizadeh, Ahmadreza

    2015-01-01

    This paper identifies the amount of variance in mathematics achievement in high- and low-achieving schools that can be explained by school-level factors, while controlling for student-level factors. The data were obtained from 2679 Iranian eighth graders who participated in the 2007 Trends in International Mathematics and Science Study. Of the…

  20. Distributed Optimization

    NASA Technical Reports Server (NTRS)

    Macready, William; Wolpert, David

    2005-01-01

    We demonstrate a new framework for analyzing and controlling distributed systems, by solving constrained optimization problems with an algorithm based on that framework. The framework is ar. information-theoretic extension of conventional full-rationality game theory to allow bounded rational agents. The associated optimization algorithm is a game in which agents control the variables of the optimization problem. They do this by jointly minimizing a Lagrangian of (the probability distribution of) their joint state. The updating of the Lagrange parameters in that Lagrangian is a form of automated annealing, one that focuses the multi-agent system on the optimal pure strategy. We present computer experiments for the k-sat constraint satisfaction problem and for unconstrained minimization of NK functions.

  1. Affective Processes and Academic Achievement.

    ERIC Educational Resources Information Center

    Feshbach, Norma Deitch; Feshbach, Seymour

    1987-01-01

    Data indicate that for girls, affective dispositional factors (empathy, depressive affectivity, aggression, and self-concept) are intimately linked to cognitive development and academic achievement. (PCB)

  2. Attribution theory in science achievement

    NASA Astrophysics Data System (ADS)

    Craig, Martin

    Recent research reveals consistent lags in American students' science achievement scores. Not only are the scores lower in the United States compared to other developed nations, but even within the United States, too many students are well below science proficiency scores for their grade levels. The current research addresses this problem by examining potential malleable factors that may predict science achievement in twelfth graders using 2009 data from the National Assessment of Educational Progress (NAEP). Principle component factor analysis was conducted to determine the specific items that contribute to each overall factor. A series of multiple regressions were then analyzed and formed the predictive value of each of these factors for science achievement. All significant factors were ultimately examined together (also using multiple regression) to determine the most powerful predictors of science achievement, identifying factors that predict science achievement, the results of which suggested interventions to strengthen students' science achievement scores and encourage persistence in the sciences at the college level and beyond. Although there is a variety of research highlighting how students in the US are falling behind other developing nations in science and math achievement, as yet, little research has addressed ways of intervening to address this gap. The current research is a starting point, seeking to identify malleable factors that contribute to science achievement. More specifically, this research examined the types of attributions that predict science achievement in twelfth grade students.

  3. Opportunistic invasive fungal infections: diagnosis & clinical management

    PubMed Central

    Badiee, Parisa; Hashemizadeh, Zahra

    2014-01-01

    Invasive fungal infections are a significant health problem in immunocompromised patients. The clinical manifestations vary and can range from colonization in allergic bronchopulmonary disease to active infection in local aetiologic agents. Many factors influence the virulence and pathogenic capacity of the microorganisms, such as enzymes including extracellular phospholipases, lipases and proteinases, dimorphic growth in some Candida species, melanin production, mannitol secretion, superoxide dismutase, rapid growth and affinity to the blood stream, heat tolerance and toxin production. Infection is confirmed when histopathologic examination with special stains demonstrates fungal tissue involvement or when the aetiologic agent is isolated from sterile clinical specimens by culture. Both acquired and congenital immunodeficiency may be associated with increased susceptibility to systemic infections. Fungal infection is difficult to treat because antifungal therapy for Candida infections is still controversial and based on clinical grounds, and for molds, the clinician must assume that the species isolated from the culture medium is the pathogen. Timely initiation of antifungal treatment is a critical component affecting the outcome. Disseminated infection requires the use of systemic agents with or without surgical debridement, and in some cases immunotherapy is also advisable. Preclinical and clinical studies have shown an association between drug dose and treatment outcome. Drug dose monitoring is necessary to ensure that therapeutic levels are achieved for optimal clinical efficacy. The objectives of this review are to discuss opportunistic fungal infections, diagnostic methods and the management of these infections. PMID:24718393

  4. Heuristic optimization of the scanning path of particle therapy beams

    SciTech Connect

    Pardo, J.; Donetti, M.; Bourhaleb, F.; Ansarinejad, A.; Attili, A.; Cirio, R.; Garella, M. A.; Giordanengo, S.; Givehchi, N.; La Rosa, A.; Marchetto, F.; Monaco, V.; Pecka, A.; Peroni, C.; Russo, G.; Sacchi, R.

    2009-06-15

    Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

  5. Integrated multidisciplinary design optimization of rotorcraft

    NASA Technical Reports Server (NTRS)

    Adelman, Howard M.; Mantay, Wayne R.

    1989-01-01

    The NASA/Army research plan for developing the logic elements for helicopter rotor design optimization by integrating appropriate disciplines and accounting for important interactions among the disciplines is discussed. The paper describes the optimization formulation in terms of the objective function, design variables, and constraints. The analysis aspects are discussed, and an initial effort at defining the interdisciplinary coupling is summarized. Results are presented on the achievements made in the rotor aerodynamic performance optimization for minimum hover horsepower, rotor dynamic optimization for vibration reduction, rotor structural optimization for minimum weight, and integrated aerodynamic load/dynamics optimization for minimum vibration and weight.

  6. General Achievement Trends: South Dakota

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  7. The Process of Science Achievement.

    ERIC Educational Resources Information Center

    Papanastasiou, Constantinos; Papanastasiou, Elena C.

    2002-01-01

    Investigates the science achievement of 8th grade students in Cyprus by using a structural equation model with three exogenous constructs--family's educational background, reinforcements, and school climate, and three endogenous constructs--teaching, student attitudes, and achievement. Proposes a model for the effects of family, school, student…

  8. Examination Regimes and Student Achievement

    ERIC Educational Resources Information Center

    Cosentino de Cohen, Clemencia

    2010-01-01

    Examination regimes at the end of secondary school vary greatly intra- and cross-nationally, and in recent years have undergone important reforms often geared towards increasing student achievement. This research presents a comparative analysis of the relationship between examination regimes and student achievement in the OECD. Using a micro…

  9. School Size and Student Achievement

    ERIC Educational Resources Information Center

    Riggen, Vicki

    2013-01-01

    This study examined whether a relationship between high school size and student achievement exists in Illinois public high schools in reading and math, as measured by the Prairie State Achievement Exam (PSAE), which is administered to all Illinois 11th-grade students. This study also examined whether the factors of socioeconomic status, English…

  10. Motivational Factors in School Achievement.

    ERIC Educational Resources Information Center

    Maehr, Martin L.

    A summary is presented of the literature on motivation relating to achievement in the classroom. Special attention is given to how values, ideology, and various cultural patterns may serve to enhance motivation to achieve in the classroom. In considering what determines motivation and personal investment in educational pursuits, the following…

  11. Parental Involvement and Academic Achievement

    ERIC Educational Resources Information Center

    Goodwin, Sarah Christine

    2015-01-01

    This research study examined the correlation between student achievement and parent's perceptions of their involvement in their child's schooling. Parent participants completed the Parent Involvement Project Parent Questionnaire. Results slightly indicated parents of students with higher level of achievement perceived less demand or invitations…

  12. General Achievement Trends: New Jersey

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  13. General Achievement Trends: North Carolina

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  14. Perils of Standardized Achievement Testing

    ERIC Educational Resources Information Center

    Haladyna, Thomas M.

    2006-01-01

    This article argues that the validity of standardized achievement test-score interpretation and use is problematic; consequently, confidence and trust in such test scores may often be unwarranted. The problem is particularly severe in high-stakes situations. This essay provides a context for understanding standardized achievement testing, then…

  15. Raising Boys' Achievement in Schools.

    ERIC Educational Resources Information Center

    Bleach, Kevan, Ed.

    This book offers insights into the range of strategies and good practice being used to raise the achievement of boys. Case studies by school-based practitioners suggest ideas and measures to address the issue of achievement by boys. The contributions are: (1) "Why the Likely Lads Lag Behind" (Kevan Bleach); (2) "Helping Boys Do Better in Their…

  16. Stress Correlates and Academic Achievement.

    ERIC Educational Resources Information Center

    Bentley, Donna Anderson; And Others

    An ongoing concern for educators is the identification of factors that contribute to or are associated with academic achievement; one such group of variables that has received little attention are those involving stress. The relationship between perceived sources of stress and academic achievement was examined to determine if reactions to stress…

  17. Achievement in Writing Geometry Proofs.

    ERIC Educational Resources Information Center

    Senk, Sharon L.

    In 1981 a nationwide assessment of achievement in writing geometry proofs was conducted by the Cognitive Development and Achievement in Secondary School Geometry project. Over 1,500 students in 11 schools in 5 states participated. This paper describes the sample, instruments, grading procedures, and selected results. Results include: (1) at the…

  18. Teaching the Low Level Achiever.

    ERIC Educational Resources Information Center

    Salomone, Ronald E., Ed.

    1986-01-01

    Intended for teachers of the English language arts, the articles in this issue offer suggestions and techniques for teaching the low level achiever. Titles and authors of the articles are as follows: (1) "A Point to Ponder" (Rachel Martin); (2) "Tracking: A Self-Fulfilling Prophecy of Failure for the Low Level Achiever" (James Christopher Davis);…

  19. Predicting Achievement in Foreign Language.

    ERIC Educational Resources Information Center

    Hart, Mary Elizabeth

    A review of research is inconclusive concerning the relationship between intelligence and language proficiency. A study of 10th grade students (n=35) examined scores on a high school entrance exam and achievement in foreign language after 1 year of study. Both math and reading showed a significant correlation with foreign language achievement; the…

  20. Superintendent Tenure and Student Achievement

    ERIC Educational Resources Information Center

    Simpson, Jennifer

    2013-01-01

    A correlational research design was used to examine the influence of superintendent tenure on student achievement in rural Appalachian Kentucky school districts. Superintendent tenure was compared to aggregated student achievement scores for 2011 and to changes in students' learning outcomes over the course of the superintendents' tenure. The…

  1. SWOC: Spectral Wavelength Optimization Code

    NASA Astrophysics Data System (ADS)

    Ruchti, G. R.

    2016-06-01

    SWOC (Spectral Wavelength Optimization Code) determines the wavelength ranges that provide the optimal amount of information to achieve the required science goals for a spectroscopic study. It computes a figure-of-merit for different spectral configurations using a user-defined list of spectral features, and, utilizing a set of flux-calibrated spectra, determines the spectral regions showing the largest differences among the spectra.

  2. Methods to optimize selective hyperthermia

    NASA Astrophysics Data System (ADS)

    Cowan, Thomas M.; Bailey, Christopher A.; Liu, Hong; Chen, Wei R.

    2003-07-01

    Laser immunotherapy, a novel therapy for breast cancer, utilizes selective photothermal interaction to raise the temperature of tumor tissue above the cell damage threshold. Photothermal interaction is achieved with intratumoral injection of a laser absorbing dye followed by non-invasive laser irradiation. When tumor heating is used in combination with immunoadjuvant to stimulate an immune response, anti-tumor immunity can be achieved. In our study, gelatin phantom simulations were used to optimize therapy parameters such as laser power, laser beam radius, and dye concentration to achieve maximum heating of target tissue with the minimum heating of non-targeted tissue. An 805-nm diode laser and indocyanine green (ICG) were used to achieve selective photothermal interactions in a gelatin phantom. Spherical gelatin phantoms containing ICG were used to simulate the absorption-enhanced target tumors, which were embedded inside gelatin without ICG to simulate surrounding non-targeted tissue. Different laser powers and dye concentrations were used to treat the gelatin phantoms. The temperature distributions in the phantoms were measured, and the data were used to determine the optimal parameters used in selective hyperthermia (laser power and dye concentration for this case). The method involves an optimization coefficient, which is proportional to the difference between temperatures measured in targeted and non-targeted gel. The coefficient is also normalized by the difference between the most heated region of the target gel and the least heated region. A positive optimization coefficient signifies a greater temperature increase in targeted gelatin when compared to non-targeted gelatin, and therefore, greater selectivity. Comparisons were made between the optimization coefficients for varying laser powers in order to demonstrate the effectinvess of this method in finding an optimal parameter set. Our experimental results support the proposed use of an optimization

  3. Study of Optimal Replacement of Thyroxine in the ElDerly (SORTED): protocol for a mixed methods feasibility study to assess the clinical utility of lower dose thyroxine in elderly hypothyroid patients: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background The population of the UK is ageing. There is compelling evidence that thyroid stimulating hormone distribution levels increase with age. Currently, in UK clinical practice elderly hypothyroid patients are treated with levothyroxine to lower their thyroid stimulating hormone levels to a standard non-age-related range. Evidence suggests that mortality is negatively associated with thyroid stimulating hormone levels. We report the protocol of a feasibility study working towards a full-scale randomized controlled trial to test whether lower dose levothyroxine has beneficial cardiovascular outcomes in the oldest old. Methods/design SORTED is a mixed methods study with three components: SORTED A: A feasibility study of a dual-center single-blinded randomized controlled trial of elderly hypothyroid patients currently treated with levothyroxine. Setting: Patients will be recruited from 20 general practices and two hospital trust endocrine units in Northumberland, Tyne and Wear. Participants: Target recruitment of 50 elderly hypothyroid patients currently treated with levothyroxine, identified in both primary and secondary care settings. Intervention: Reduced dose of levothyroxine to achieve an elevated serum thyroid stimulating hormone (target range 4.1 to 8.0 mU/L) versus standard levothyroxine replacement (target range 0.4 to 4.0 mU/L). Randomization: Using random permuted blocks, in a ratio of 1:1, randomization will be carried out by Newcastle Clinical Trials Unit. Outcomes: Study feasibility (recruitment and retention rates and medication compliance), acceptability of the trial design, assessment of mobility and falls risk, and change in cardiovascular risk factors. SORTED B: Qualitative study using in-depth interviews to understand patients’ willingness to take part in a randomized controlled trial and participants’ experience of the intervention. SORTED C: Retrospective cohort study of 400 treated hypothyroid patients aged 80 years or over

  4. Multiple anatomy optimization of accumulated dose

    SciTech Connect

    Watkins, W. Tyler Siebers, Jeffrey V.; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.

    2014-11-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

  5. Multiple anatomy optimization of accumulated dose

    PubMed Central

    Watkins, W. Tyler; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.; Siebers, Jeffrey V.

    2014-01-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated. PMID:25370619

  6. Optimal Fluoridation

    PubMed Central

    Lee, John R.

    1975-01-01

    Optimal fluoridation has been defined as that fluoride exposure which confers maximal cariostasis with minimal toxicity and its values have been previously determined to be 0.5 to 1 mg per day for infants and 1 to 1.5 mg per day for an average child. Total fluoride ingestion and urine excretion were studied in Marin County, California, children in 1973 before municipal water fluoridation. Results showed fluoride exposure to be higher than anticipated and fulfilled previously accepted criteria for optimal fluoridation. Present and future water fluoridation plans need to be reevaluated in light of total environmental fluoride exposure. PMID:1130041

  7. Optimal quantum cloning via spin networks

    SciTech Connect

    Chen Qing; Cheng Jianhua; Wang Kelin; Du Jiangfeng

    2006-09-15

    In this paper we demonstrate that optimal 1{yields}M phase-covariant cloning quantum cloning is available via free dynamical evolution of spin networks. By properly designing the network and the couplings between spins, we show that optimal 1{yields}M phase-covariant cloning can be achieved if the initial state is prepared as a specific symmetric state. Especially, when M is an odd number, the optimal phase-covariant cloning can be achieved without ancillas. Moreover, we demonstrate that the same framework is capable for optimal 1{yields}2 universal cloning.

  8. A two-stage sequential linear programming approach to IMRT dose optimization

    PubMed Central

    Zhang, Hao H; Meyer, Robert R; Wu, Jianzhou; Naqvi, Shahid A; Shi, Leyuan; D’Souza, Warren D

    2010-01-01

    The conventional IMRT planning process involves two stages in which the first stage consists of fast but approximate idealized pencil beam dose calculations and dose optimization and the second stage consists of discretization of the intensity maps followed by intensity map segmentation and a more accurate final dose calculation corresponding to physical beam apertures. Consequently, there can be differences between the presumed dose distribution corresponding to pencil beam calculations and optimization and a more accurately computed dose distribution corresponding to beam segments that takes into account collimator-specific effects. IMRT optimization is computationally expensive and has therefore led to the use of heuristic (e.g., simulated annealing and genetic algorithms) approaches that do not encompass a global view of the solution space. We modify the traditional two-stage IMRT optimization process by augmenting the second stage via an accurate Monte-Carlo based kernel-superposition dose calculations corresponding to beam apertures combined with an exact mathematical programming based sequential optimization approach that uses linear programming (SLP). Our approach was tested on three challenging clinical test cases with multileaf collimator constraints corresponding to two vendors. We compared our approach to the conventional IMRT planning approach, a direct-aperture approach and a segment weight optimization approach. Our results in all three cases indicate that the SLP approach outperformed the other approaches, achieving superior critical structure sparing. Convergence of our approach is also demonstrated. Finally, our approach has also been integrated with a commercial treatment planning system and may be utilized clinically. PMID:20071764

  9. Optimized multi-electrode stimulation increases focality and intensity at target

    NASA Astrophysics Data System (ADS)

    Dmochowski, Jacek P.; Datta, Abhishek; Bikson, Marom; Su, Yuzhuo; Parra, Lucas C.

    2011-08-01

    Transcranial direct current stimulation (tDCS) provides a non-invasive tool to elicit neuromodulation by delivering current through electrodes placed on the scalp. The present clinical paradigm uses two relatively large electrodes to inject current through the head resulting in electric fields that are broadly distributed over large regions of the brain. In this paper, we present a method that uses multiple small electrodes (i.e. 1.2 cm diameter) and systematically optimize the applied currents to achieve effective and targeted stimulation while ensuring safety of stimulation. We found a fundamental trade-off between achievable intensity (at the target) and focality, and algorithms to optimize both measures are presented. When compared with large pad-electrodes (approximated here by a set of small electrodes covering 25cm2), the proposed approach achieves electric fields which exhibit simultaneously greater focality (80% improvement) and higher target intensity (98% improvement) at cortical targets using the same total current applied. These improvements illustrate the previously unrecognized and non-trivial dependence of the optimal electrode configuration on the desired electric field orientation and the maximum total current (due to safety). Similarly, by exploiting idiosyncratic details of brain anatomy, the optimization approach significantly improves upon prior un-optimized approaches using small electrodes. The analysis also reveals the optimal use of conventional bipolar montages: maximally intense tangential fields are attained with the two electrodes placed at a considerable distance from the target along the direction of the desired field; when radial fields are desired, the maximum-intensity configuration consists of an electrode placed directly over the target with a distant return electrode. To summarize, if a target location and stimulation orientation can be defined by the clinician, then the proposed technique is superior in terms of both focality

  10. Risk modelling in portfolio optimization

    NASA Astrophysics Data System (ADS)

    Lam, W. H.; Jaaman, Saiful Hafizah Hj.; Isa, Zaidi

    2013-09-01

    Risk management is very important in portfolio optimization. The mean-variance model has been used in portfolio optimization to minimize the investment risk. The objective of the mean-variance model is to minimize the portfolio risk and achieve the target rate of return. Variance is used as risk measure in the mean-variance model. The purpose of this study is to compare the portfolio composition as well as performance between the optimal portfolio of mean-variance model and equally weighted portfolio. Equally weighted portfolio means the proportions that are invested in each asset are equal. The results show that the portfolio composition of the mean-variance optimal portfolio and equally weighted portfolio are different. Besides that, the mean-variance optimal portfolio gives better performance because it gives higher performance ratio than the equally weighted portfolio.

  11. Childhood Obesity and Cognitive Achievement.

    PubMed

    Black, Nicole; Johnston, David W; Peeters, Anna

    2015-09-01

    Obese children tend to perform worse academically than normal-weight children. If poor cognitive achievement is truly a consequence of childhood obesity, this relationship has significant policy implications. Therefore, an important question is to what extent can this correlation be explained by other factors that jointly determine obesity and cognitive achievement in childhood? To answer this question, we exploit a rich longitudinal dataset of Australian children, which is linked to national assessments in math and literacy. Using a range of estimators, we find that obesity and body mass index are negatively related to cognitive achievement for boys but not girls. This effect cannot be explained by sociodemographic factors, past cognitive achievement or unobserved time-invariant characteristics and is robust to different measures of adiposity. Given the enormous importance of early human capital development for future well-being and prosperity, this negative effect for boys is concerning and warrants further investigation. PMID:26123250

  12. Using Design To Achieve Sustainability

    EPA Science Inventory

    Sustainability is defined as meeting the needs of this generation without compromising the ability of future generations to meet their needs. This is a conditional statement that places the responsibility for achieving sustainability squarely in hands of designers and planners....

  13. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.

    PubMed

    Wicki, Andreas; Witzigmann, Dominik; Balasubramanian, Vimalkumar; Huwyler, Jörg

    2015-02-28

    Cancer is a leading cause of death worldwide. Currently available therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology towards the development of nanomedicine products holds great promise to improve therapeutic strategies against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multi-functionality. They can improve the pharmacokinetic and pharmacodynamic profiles of conventional therapeutics and may thus optimize the efficacy of existing anti-cancer compounds. In this review, we discuss state-of-the-art nanoparticles and targeted systems that have been investigated in clinical studies. We emphasize the challenges faced in using nanomedicine products and translating them from a preclinical level to the clinical setting. Additionally, we cover aspects of nanocarrier engineering that may open up new opportunities for nanomedicine products in the clinic. PMID:25545217

  14. Designing Sensor Networks by a Generalized Highly Optimized Tolerance Model

    NASA Astrophysics Data System (ADS)

    Miyano, Takaya; Yamakoshi, Miyuki; Higashino, Sadanori; Tsutsui, Takako

    A variant of the highly optimized tolerance model is applied to a toy problem of bioterrorism to determine the optimal arrangement of hypothetical bio-sensors to avert epidemic outbreak. Nonlinear loss function is utilized in searching the optimal structure of the sensor network. The proposed method successfully averts disastrously large events, which can not be achieved by the original highly optimized tolerance model.

  15. Does ownership matter for the provision of professionalized services? Hip operations at publicly and privately owned clinics in Denmark.

    PubMed

    Andersen, Lotte Bøgh; Jakobsen, Mads Leth Felsager

    2011-01-01

    In terms of clinical procedures (to take the example used in this article, hip operations), both public and private organizations provide highly professionalized services. For this service type, our knowledge about ownership differences is sparse. To begin to fill this gap, we investigate how the ownership of hip clinics affects professional behaviour, treatment quality and patient satisfaction. The comparison of private and public hip clinics is based on data from the Danish Hip Arthroplasty Register and the Danish Central Patient Register combined with 20 semi-structured interviews. We find that private clinics employ stronger individual financial incentives and try harder to increase the income/costs ratio than do public clinics. Private clinics optimize non-clinical factors such as waiting time much more than public clinics and have fewer complication-prone patients than public clinics. However, the clinical procedures are very similar in the two types of clinics. Private clinics do not achieve better clinical results, but patient satisfaction is nevertheless higher with private clinics. The implication is that ownership matters for highly professionalized services, but professionalism neutralizes some – but not all – ownership differences. PMID:22165152

  16. Revision of Achievement Goal Theory: Necessary and Illuminating.

    ERIC Educational Resources Information Center

    Harackiewicz, Judith M.; Barron, Kenneth E.; Pintrich, Paul R.; Elliot, Andrew J.; Thrash, Todd M.

    2002-01-01

    Discusses three reasons to revise achievement goal theory: the importance of separating approach from avoidance strivings, the positive potential of performance-approach goals, and identification of the ways performance-approach goals can combine with mastery approach goals to promote optimal motivation. Reviews theory and research to substantiate…

  17. University cardiology clinic.

    PubMed

    Borozanov, V

    2013-01-01

    In distant 1972, within framework of the Internal Clinic, a cardiologic department was organized which was soon, on 29.XII.1974, transformed into the Cardiology Clinic, later the Institute for Heart Diseases, and in 2008 was renamed the University Cardiology Clinic. The greater part of its foundation was possible owing to Prof. Dimitar Arsov and Prof. Radovan Percinkovski, who was the clinic's first director in the period from 1974 to 1984. In 1985, the Clinic moved into its own new building, and in that way was physically detached from the Internal Clinics. Until its move to the new building, the Clinic functioned in the Internal Clinics building, organized as an outpatient polyclinic and inpatient infirmary department with clinical beds, a coronary intensive care unit and a haemodynamics laboratory equipped with the most modern equipment of that time. Today the Clinic functions through two integral divisions: an inpatient infirmary department which comprises an intensive coronary care unit and fourteen wards which altogether have 139 clinical beds, and the diagnostic centre which comprises an emergency clinic and day hospital, a communal and consultative outpatients' clinic functioning on a daily basis, through which some 300-350 patients pass every day, and diagnostic laboratories with a capacity of nearly 100 non-invasive and 20-30 invasive diagnostic procedures daily. The Clinic is a teaching base, and its doctors are educators of students at the Medical, Dental and Pharmacy Faculties, and also of students at the High School for Nurses and X-ray technicians, but also for those in Internal Medicine and especially Cardiology. The Clinic is also a base for scientific Masters' and post-doctoral studies, and such higher degrees are achieved not only by doctors who work here, but also by doctors from Medical Centres both in the country and abroad. Doctors working in this institution publish widely, not only a great number of books and monographs, but also original

  18. Electrodialysis simulation to achieve optimum current density

    NASA Technical Reports Server (NTRS)

    Herrmann, Cal C.

    1993-01-01

    Electrodialysis is used to remove salts from waste or other water streams, to yield a concentrated brine and a substatially deionized product water. During the electrodialysis process, the boundary layer adjacent to the ion selective membrane can become depleted of ions, resulting in severe pH changes sometimes accompanied by precipitation, and power losses, by a process known as water splitting. In order to optimize the applied electric current density, to achieve maximum deionization without exceeding the limiting current at any point along the path, a simulation program has been created to plot ion concentrations and fluxes, and cell current densities and voltages along the electrodialysis path. A means for tapering the current density along the path is recommended.

  19. SU-E-T-357: Semi-Automated Knowledge-Based Radiation Therapy (KBRT) Planning for Head-And-Neck Cancer (HNC): Can KBRT Plans Achieve Better Results Than Manual Planning?

    SciTech Connect

    Lutzky, C; Grzetic, S; Lo, J; Das, S

    2014-06-01

    Purpose: Knowledge Based Radiation Therapy Treatment (KBRT) planning can be used to semi-automatically generate IMRT plans for new patients using constraints derived from previously manually-planned, geometrically similar patients. We investigate whether KBRT plans can achieve greater dose sparing than manual plans using optimized, organspecific constraint weighting factors. Methods: KBRT planning of HNC radiotherapy cases geometrically matched each new (query) case to one of the 105 clinically approved plans in our database. The dose distribution of the planned match was morphed to fit the querys geometry. Dose-volume constraints extracted from the morphed dose distribution were used to run the IMRT optimization with no user input. In the first version, all constraints were multiplied by a weighting factor of 0.7. The weighting factors were then systematically optimized (in order of OARs with increasing separation from the target) to maximize sparing to each OAR without compromising other OARs. The optimized, second version plans were compared against the first version plans and the clinically approved plans for 45 unilateral/bilateral target cases using the dose metrics: mean, median and maximum (brainstem and cord) doses. Results: Compared to the first version, the second version significantly reduced mean/median contralateral parotid doses (>2Gy) for bilateral cases. Other changes between the two versions were not clinically meaningful. Compared to the original clinical plans, both bilateral and unilateral plans in the second version had lower average dose metrics for 5 of the 6 OARs. Compared to the original plans, the second version achieved dose sparing that was at least as good for all OARs and better for the ipsilateral parotid (bilateral) and oral cavity (bilateral/unilateral). Differences in planning target volume coverage metrics were not clinically significant. Conclusion: HNC-KBRT planning generated IMRT plans with at least equivalent dose sparing to

  20. Primary Mental Abilities and Metropolitan Readiness Tests as Predictors of Achievement in the First Primary Year.

    ERIC Educational Resources Information Center

    University City School District, MO.

    The prediction of achievement provides teachers with necessary information to help children attain optimal achievement. If some skill prerequistites to learning which are not fully developed can be identified and strengthened, higher levels of achievement may result. The Metropolitan Readiness Tests (MRT) are routinely given to all University City…

  1. Lags in Minority Achievement Defy Traditional Explanations. The Achievement Gap.

    ERIC Educational Resources Information Center

    Viadero, Debra; Johnston, Robert C.

    2000-01-01

    This second in a four-part series on why academic achievement gaps exist notes that standard explanations for why minority students trail behind non-Hispanic whites are not good enough, suggesting that no single explanation for the gap exists, but instead a multitude of factors are influential. Poverty, though not the single most important cause,…

  2. Central Iowa Low Achiever Mathematics Project - Low Achiever Motivational Project.

    ERIC Educational Resources Information Center

    Zimmerman, Joseph T.

    The materials in this booklet are designed especially for the low achieving student in mathematics. Containing some materials from a course in general mathematics, the booklet is intended to be used in conjunction with conventional textbook materials and is designed to serve as a source of new ideas for teachers and to relieve the teacher of much…

  3. Inverse planning optimization method for intensity modulated radiation therapy.

    PubMed

    Lan, Yihua; Ren, Haozheng; Li, Cunhua; Min, Zhifang; Wan, Jinxin; Ma, Jianxin; Hung, Chih-Cheng

    2013-10-01

    In order to facilitate the leaf sequencing process in intensity modulated radiation therapy (IMRT), and design of a practical leaf sequencing algorithm, it is an important issue to smooth the planned fluence maps. The objective is to achieve both high-efficiency and high-precision dose delivering by considering characteristics of leaf sequencing process. The key factor which affects total number of monitor units for the leaf sequencing optimization process is the max flow value of the digraph which formulated from the fluence maps. Therefore, we believe that one strategy for compromising dose conformity and total number of monitor units in dose delivery is to balance the dose distribution function and the max flow value mentioned above. However, there are too many paths in the digraph, and we don't know the flow value of which path is the maximum. The maximum flow value among the horizontal paths was selected and used in the objective function of the fluence map optimization to formulate the model. The model is a traditional linear constrained quadratic optimization model which can be solved by interior point method easily. We believe that the smoothed maps from this model are more suitable for leaf sequencing optimization process than other smoothing models. A clinical head-neck case and a prostate case were tested and compared using our proposed model and the smoothing model which is based on the minimization of total variance. The optimization results with the same level of total number of monitor units (TNMU) show that the fluence maps obtained from our model have much better dose performance for the target/non-target region than the maps from total variance based on the smoothing model. This indicates that our model achieves better dose distribution when the algorithm suppresses the TNMU at the same level. Although we have just used the max flow value of the horizontal paths in the diagraph in the objective function, a good balance has been achieved between

  4. Optimal design of plate-fin heat exchangers by particle swarm optimization

    NASA Astrophysics Data System (ADS)

    Yousefi, M.; Darus, A. N.

    2011-12-01

    This study explores the application of Particle Swarm Optimization (PSO) for optimization of a cross-flow plate fin heat exchanger. Minimization total annual cost is the target of optimization. Seven design parameters, namely, heat exchanger length at hot and cold sides, fin height, fin frequency, fin thickness, fin-strip length and number of hot side layers are selected as optimization variables. A case study from the literature proves the effectiveness of the proposed algorithm in case of achieving more accurate results.

  5. CLINICAL BIOCHEMISTRY

    EPA Science Inventory

    Assessment of the health status of animals through measurement of cellular, biochemical, and macromolecular constituents in blood, secretions, and excretions has been variously referred to as clinical chemistry, clinical biochemistry, or clinical pathology. he genesis of this dis...

  6. Integrated multidisciplinary design optimization of rotorcraft

    NASA Technical Reports Server (NTRS)

    Adelman, Howard M.; Mantay, Wayne R.

    1989-01-01

    The NASA/Army research plan for developing the logic elements for helicopter rotor design optimization by integrating appropriate disciplines and accounting for important interactions among the disciplines is discussed. The optimization formulation is described in terms of the objective function, design variables, and constraints. The analysis aspects are discussed, and an initial effort at defining the interdisciplinary coupling is summarized. Results are presented on the achievements made in the rotor dynamic optimization for vibration reduction, rotor structural optimization for minimum weight, and integrated aerodynamic load/dynamics optimization for minimum vibration and weight.

  7. [Optimal Treatment for Rheumatoid Arthritis with Companion Diagnostics].

    PubMed

    Kumagai, Shunichi

    2015-11-01

    The medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introduction of biologics in addition to methotrexate, an anchor drug, has made it possible to not only suppress pain and inflammation (clinical remission), but also inhibit joint destruction (structural remission), leading to cure from the disease. Since the condition and pathology are heterogeneous among individual patients, optimal treatment for each patient based on the use of companion diagnostics is desired (precision medicine). ACPA is important to diagnose RA, but also to assess the prognosis. ACPA is also a part of companion diagnostics for preclinical RA because it has been found to be positive before the onset. Treatment should be performed under consideration of the disease state such as activity, prognosis regarding joint destruction, and complications. It is also important to clarify the patient characteristics, such as responsiveness to the drugs and risk of adverse effects. Biomarkers, such as proteomics and pharmacogenomics, have been reported as companion diagnostics for optimal treatment of RA. RA is a multifactorial disorder with clinically heterogeneous features. Gene-environment interaction is closely involved in the production of ACPA, and then secondary stimuli to joints may lead to symptoms of RA. Joint injury, emotional stress, and infections often trigger the onset of RA. It is possible to cure RA, achieving complete remission, by early aggressive treatment and returning to the pre-clinical state with environmental improvement. [Review] PMID:26995880

  8. Optimizing treatment parameters for the vascular malformations using 1064-nm Nd:YAG laser

    NASA Astrophysics Data System (ADS)

    Gong, Wei; Lin, He; Xie, Shusen

    2010-02-01

    Near infrared Nd:YAG pulsed laser treatment had been proved to be an efficient method to treat large-sized vascular malformations like leg telangiectasia for deep penetrating depth into skin and uniform light distribution in vessel. However, optimal clinical outcome was achieved by various laser irradiation parameters and the key factor governing the treatment efficacy was still unclear. A mathematical model in combination with Monte Carlo algorithm and finite difference method was developed to estimate the light distribution, temperature profile and thermal damage in epidermis, dermis and vessel during and after 1064 nm pulsed Nd:YAG laser irradiation. Simulation results showed that epidermal protection could be achieved during 1064 nm Nd:YAG pulsed laser irradiation in conjunction with cryogen spray cooling. However, optimal vessel closure and blood coagulation depend on a compromise between laser spot size and pulse duration.

  9. Potential-Based Achievement Goals

    ERIC Educational Resources Information Center

    Elliot, Andrew; Murayama, Kou; Kobeisy, Ahmed; Lichtenfeld, Stephanie

    2015-01-01

    Background: Self-based achievement goals use one's own intrapersonal trajectory as a standard of evaluation, and this intrapersonal trajectory may be grounded in one's past (past-based goals) or one's future potential (potential-based goals). Potential-based goals have been overlooked in the literature to date. Aims: The primary aim of the present…

  10. The Racial Academic Achievement Gap

    ERIC Educational Resources Information Center

    Green, Toneka M.

    2008-01-01

    Closing the racial academic achievement gap is a problem that must be solved in order for future society to properly function. Minorities including African-American and Latino students' standardized test scores are much lower than white students. By the end of fourth grade, African American, Latino, and poor students of all races are two years…

  11. The Achievement-Assessment Link

    ERIC Educational Resources Information Center

    Wallace, Virginia; Husid, Whitney

    2011-01-01

    The recent recession, school budget cuts, and predictions of school libraries' demise because of technology advances put pressure on school librarians to prove the utility, relevance, and value of school libraries to student learning. While national studies document that school libraries increase student achievement, school librarians must…

  12. Cooperative Learning and Student Achievement.

    ERIC Educational Resources Information Center

    Slavin, Robert E.

    1988-01-01

    Research evidence shows that cooperative learning strategies are not equally effective, though most positively affect self-esteem, intergroup relations, and the ability to work with others. To produce achievement gains, these methods must include both a group goal and individual accountability. Includes 19 references. (MLH)

  13. Curricular Diversity and Academic Achievement.

    ERIC Educational Resources Information Center

    Wilson, Reginald

    1991-01-01

    Educational achievement should be intellectually and philosophically divorced from cultural affirmation, which is merely a byproduct of the inclusion of diverse voices in the search for truth. A model based on the relationship between the valuation of oneself by others and by oneself is presented to explain differential effects of schooling on…

  14. School Readiness and Later Achievement

    ERIC Educational Resources Information Center

    Duncan, Greg J.; Dowsett, Chantelle J.; Claessens, Amy; Magnuson, Katherine; Huston, Aletha C.; Klebanov, Pamela; Pagani, Linda S.; Feinstein, Leon; Engel, Mimi; Brooks-Gunn, Jeanne; Sexton, Holly; Duckworth, Kathryn; Japel, Crista

    2007-01-01

    Using 6 longitudinal data sets, the authors estimate links between three key elements of school readiness--school-entry academic, attention, and socioemotional skills--and later school reading and math achievement. In an effort to isolate the effects of these school-entry skills, the authors ensured that most of their regression models control for…

  15. Teacher Certification and Student Achievement

    ERIC Educational Resources Information Center

    Moss, Patricia Lewis

    2012-01-01

    The purpose of this mixed-method study was to determine if there is a significant difference between the achievement of students who are taught by traditionally prepared teachers and that of students who are taught by alternatively prepared teachers. The study further addressed the perspectives of both groups of teachers regarding selected…

  16. Achieving Safety through Security Management

    NASA Astrophysics Data System (ADS)

    Ridgway, John

    Whilst the achievement of safety objectives may not be possible purely through the administration of an effective Information Security Management System (ISMS), your job as safety manager will be significantly eased if such a system is in place. This paper seeks to illustrate the point by drawing a comparison between two of the prominent standards within the two disciplines of security and safety management.

  17. School Desegregation and Black Achievement.

    ERIC Educational Resources Information Center

    Cook, Thomas; And Others

    Seven papers commissioned by the National Institute of Education in order to clarify the state of recent knowledge about the effects of school desegregation on the academic achievement of black students are contained in this report. The papers, which analyze 19 "core" empirical studies on this topic, include: (1) "What Have Black Children Gained…

  18. Graders' Mathematics Achievement

    ERIC Educational Resources Information Center

    Bond, John B.; Ellis, Arthur K.

    2013-01-01

    The purpose of this experimental study was to investigate the effects of metacognitive reflective assessment instruction on student achievement in mathematics. The study compared the performance of 141 students who practiced reflective assessment strategies with students who did not. A posttest-only control group design was employed, and results…

  19. Epistemological Beliefs and Academic Achievement

    ERIC Educational Resources Information Center

    Arslantas, Halis Adnan

    2016-01-01

    This study aimed to identify the relationship between teacher candidates' epistemological beliefs and academic achievement. The participants of the study were 353 teacher candidates studying their fourth year at the Education Faculty. The Epistemological Belief Scale was used which adapted to Turkish through reliability and validity work by…

  20. Measuring and Recording Student Achievement

    ERIC Educational Resources Information Center

    Universities UK, 2004

    2004-01-01

    The Measuring and Recording Student Achievement Scoping Group was established by Universities UK and the Standing Conference of Principals (SCOP), with the support of the Higher Education Funding Council for England (HEFCE) in October 2003 to review the recommendations from the UK Government White Paper "The Future of Higher Education" relating…