Science.gov

Sample records for linear clinical progression

  1. Progressive Image Coding by Hierarchical Linear Approximation.

    ERIC Educational Resources Information Center

    Wu, Xiaolin; Fang, Yonggang

    1994-01-01

    Proposes a scheme of hierarchical piecewise linear approximation as an adaptive image pyramid. A progressive image coder comes naturally from the proposed image pyramid. The new pyramid is semantically more powerful than regular tessellation but syntactically simpler than free segmentation. This compromise between adaptability and complexity…

  2. Clinical management of progressive myopia.

    PubMed

    Aller, T A

    2014-02-01

    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

  3. 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

  4. Progress report on the SLAC Linear Collider

    SciTech Connect

    Rees, J.

    1986-06-01

    The SLAC Linear Collider project (SLC) is reported as being near completion. The performance specifications are tabulated both for the initial form and for eventual goals. Various parts of the SLC are described and the status of their construction is reported, including the front end electron gun and booster, the linac, damping ring, positron source, SLC arcs, and conventional facilities. 5 refs., 12 figs. (LEW)

  5. Progress in the Next Linear Collider Design

    NASA Astrophysics Data System (ADS)

    Raubenheimer, T. O.

    2001-07-01

    An electron/positron linear collider with a center-of-mass energy between 0.5 and 1 TeV would be an important complement to the physics program of the LHC. The Next Linear Collider (NLC) is being designed by a US collaboration (FNAL, LBNL, LLNL, and SLAC) which is working closely with the Japanese collaboration that is designing the Japanese Linear Collider (JLC). The NLC main linacs are based on normal conducting 11 GHz rf. This paper will discuss the technical difficulties encountered as well as the many changes that have been made to the NLC design over the last year. These changes include improvements to the X-band rf system as well as modifications to the injector and the beam delivery system. They are based on new conceptual solutions as well as results from the R&D programs which have exceeded initial specifications. The net effect has been to reduce the length of the collider from about 32 km to 25 km and to reduce the number of klystrons and modulators by a factor of two. Together these lead to significant cost savings.

  6. Progress report on the SLAC Linear Collider

    SciTech Connect

    Kozanecki, W.

    1987-11-01

    In this paper we report on the status of the SLAC Linear Collider (SLC), the prototype of a new generation of colliding beam accelerators. This novel type of machine holds the potential of extending electron-positron colliding beam studies to center-of-mass (c.m.) energies far in excess of what is economically achievable with colliding beam storage rings. If the technical challenges posed by linear colliders are solvable at a reasonable cost, this new approach would provide an attractive alternative to electron-positron rings, where, because of rapidly rising synchrotron radiation losses, the cost and size of the ring increases with the square of the c.m. energy. In addition to its role as a test vehicle for the linear collider principle, the SLC aims at providing an abundant source of Z/sup 0/ decays to high energy physics experiments. Accordingly, two major detectors, the upgraded Mark II, now installed on the SLC beam line, and the state-of-the-art SLD, currently under construction, are preparing to probe the Standard Model at the Z/sup 0/ pole. The SLC project was originally funded in 1983. Since the completion of construction, we have been commissioning the machine to bring it up to a performance level adequate for starting the high energy physics program. In the remainder of this paper, we will discuss the status, problems and performance of the major subsystems of the SLC. We will conclude with a brief outline of the physics program, and of the planned enhancements to the capabilities of the machine. 26 refs., 7 figs.

  7. Progress in linear optics, non-linear optics and surface alignment of liquid crystals

    SciTech Connect

    Ong, H.L.; Meyer, R.B.; Hurd, A.J.; Karn, A.J.; Arakelian, S.M.; Shen, Y.R.; Sanda, P.N.; Dove, D.B.; Jansen, S.A.; Hoffmann, R.

    1989-01-01

    We first discuss the progress in linear optics, in particular, the formulation and application of geometrical-optics approximation and its generalization. We then discuss the progress in non-linear optics, in particular, the enhancement of a first-order Freedericksz transition and intrinsic optical bistability in homeotropic and parallel oriented nematic liquid crystal cells. Finally, we discuss the liquid crystal alignment and surface effects on field-induced Freedericksz transition. 50 refs.

  8. Clinical Trials: Key to Medical Progress

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Clinical Trials: Key to Medical Progress Past Issues / Summer 2008 ... this page please turn Javascript on. Photo iStock Clinical trials are research studies that test how well new ...

  9. [From clinical judgment to linear regression model.

    PubMed

    Palacios-Cruz, Lino; Pérez, Marcela; Rivas-Ruiz, Rodolfo; Talavera, Juan O

    2013-01-01

    When we think about mathematical models, such as linear regression model, we think that these terms are only used by those engaged in research, a notion that is far from the truth. Legendre described the first mathematical model in 1805, and Galton introduced the formal term in 1886. Linear regression is one of the most commonly used regression models in clinical practice. It is useful to predict or show the relationship between two or more variables as long as the dependent variable is quantitative and has normal distribution. Stated in another way, the regression is used to predict a measure based on the knowledge of at least one other variable. Linear regression has as it's first objective to determine the slope or inclination of the regression line: Y = a + bx, where "a" is the intercept or regression constant and it is equivalent to "Y" value when "X" equals 0 and "b" (also called slope) indicates the increase or decrease that occurs when the variable "x" increases or decreases in one unit. In the regression line, "b" is called regression coefficient. The coefficient of determination (R(2)) indicates the importance of independent variables in the outcome.

  10. Clinical Approach to Progressive Supranuclear Palsy

    PubMed Central

    Ling, Helen

    2016-01-01

    Sixty years ago, Steele, Richardson and Olszewski designated progressive supranuclear palsy (PSP) as a new clinicopathological entity in their seminal paper. Since then, in addition to the classic Richardson’s syndrome (RS), different clinical phenotypic presentations have been linked with this four-repeat tauopathy. The clinical heterogeneity is associated with variability of regional distribution and severity of abnormal tau accumulation and neuronal loss. In PSP subtypes, the presence of certain clinical pointers may be useful for antemortem prediction of the underlying PSP-tau pathology. Midbrain atrophy on conventional MRI correlates with the clinical phenotype of RS but is not predictive of PSP pathology. Cerebrospinal fluid biomarkers and tau ligand positron emission tomography are promising biomarkers of PSP. A multidisciplinary approach to meet the patients’ complex needs is the current core treatment strategy for this devastating disorder. PMID:26828211

  11. International Linear Collider-A Technical Progress Report

    SciTech Connect

    Elsen, Eckhard; Harrison, Mike; Hesla, Leah; Ross, Marc; Royole-Degieux, Perrine; Takahashi, Rika; Walker, Nicholas; Warmbein, Barbara; Yamamoto, Akira; Yokoya, Kaoru; Zhang, Min; /Beijing, Inst. High Energy Phys.

    2011-11-04

    The International Linear Collider: A Technical Progress Report marks the halfway point towards the Global Design Effort fulfilling its mandate to follow up the ILC Reference Design Report with a more optimised Technical Design Report (TDR) by the end of 2012. The TDR will be based on much of the work reported here and will contain all the elements needed to propose the ILC to collaborating governments, including a technical design and implementation plan that are realistic and have been better optimised for performance, cost and risk. We are on track to develop detailed plans for the ILC, such that once results from the Large Hadron Collider (LHC) at CERN establish the main science goals and parameters of the next machine, we will be in good position to make a strong proposal for this new major global project in particle physics. The two overriding issues for the ILC R&D programme are to demonstrate that the technical requirements for the accelerator are achievable with practical technologies, and that the ambitious physics goals can be addressed by realistic ILC detectors. This GDE interim report documents the impressive progress on the accelerator technologies that can make the ILC a reality. It highlights results of the technological demonstrations that are giving the community increased confidence that we will be ready to proceed with an ILC project following the TDR. The companion detector and physics report document likewise demonstrates how detector designs can meet the ambitious and detailed physics goals set out by the ILC Steering Committee. LHC results will likely affect the requirements for the machine design and the detectors, and we are monitoring that very closely, intending to adapt our design as those results become available.

  12. [Ear keloid and clinical research progress].

    PubMed

    Du, Guangyuan; Zhu, Jiang

    2014-04-01

    Keloid refers to the damaged skin due to excessive fibroblast proliferation. Ear is one predilection site. The pathogenesis of ear keloid is not very clear, and the treatment is also varied. Surgery, postoperative radiotherapy and laser treatment, steroid hormones, pressure therapy are the basic treatment methods. Integrated application of a variety of treatments, classification research and new materials using revealed the prospect for the treatment of the disease. This thesis reviews literature about ear keloid in recent 10 years, and introduces this disease and clinical research progress.

  13. Optimal composite scores for longitudinal clinical trials under the linear mixed effects model.

    PubMed

    Ard, M Colin; Raghavan, Nandini; Edland, Steven D

    2015-01-01

    Clinical trials of chronic, progressive conditions use rate of change on continuous measures as the primary outcome measure, with slowing of progression on the measure as evidence of clinical efficacy. For clinical trials with a single prespecified primary endpoint, it is important to choose an endpoint with the best signal-to-noise properties to optimize statistical power to detect a treatment effect. Composite endpoints composed of a linear weighted average of candidate outcome measures have also been proposed. Composites constructed as simple sums or averages of component tests, as well as composites constructed using weights derived from more sophisticated approaches, can be suboptimal, in some cases performing worse than individual outcome measures. We extend recent research on the construction of efficient linearly weighted composites by establishing the often overlooked connection between trial design and composite performance under linear mixed effects model assumptions and derive a formula for calculating composites that are optimal for longitudinal clinical trials of known, arbitrary design. Using data from a completed trial, we provide example calculations showing that the optimally weighted linear combination of scales can improve the efficiency of trials by almost 20% compared with the most efficient of the individual component scales. Additional simulations and analytical results demonstrate the potential losses in efficiency that can result from alternative published approaches to composite construction and explore the impact of weight estimation on composite performance.

  14. Progressive multifocal leukoencephalopathy: Clinical and molecular aspects

    PubMed Central

    Tavazzi, Eleonora; White, Martyn K.; Khalili, Kamel

    2011-01-01

    The fatal CNS demyelinating disease, progressive multifocal leukoencephalopathy (PML), is rare and appears to occur almost always as a consequence of immune dysfunction. Thus it is associated with HIV/AIDS and also as a side-effect of certain immunomodulatory monoclonal antibody therapies. In contrast to the rarity of PML, the etiological agent of the disease, the polyomavirus JC (JCV) is widespread in populations worldwide. In the forty years since JCV was first isolated, much has been learned about the virus and the disease from laboratory and clinical observations. However, there are many aspects of the viral life cycle and the pathogenesis of the disease that still remain unclear and our understanding is constantly evolving. In this review, we will discuss our current understanding of the clinical features of PML and molecular characteristics of JCV and how they relate to each other. Clinical observations can inform molecular studies of the virus and likewise molecular findings concerning the life cycle of the virus can guide the development of novel therapeutic strategies. PMID:21936015

  15. Progress Report on the Improved Linear Ion Trap Physics Package

    NASA Technical Reports Server (NTRS)

    Prestage, John D.

    1995-01-01

    This article describes the first operational results from the extended linear ion trap frequency standard now being developed at JPL. This new design separates the state selection/interrogation region from the more critical microwave resonance region where the multiplied local oscillator (LO) signal is compared to the stable atomic transition. Hg+ ions have been trapped, shuttled back and forth between the resonance and state selection traps. In addition, microwave transitions between the Hg+ clock levels have been driven in the resonance trap and detected in the state selection trap.

  16. [Analysis Methods of Short-term Non-linear Heart Rate Variability and Their Application in Clinical Medicine].

    PubMed

    Chi, Xianglin; Zhou, Jianhua; Shi, Ping; Liu, Chengyu

    2016-02-01

    The linear analysis for heart rate variability (HRV), including time domain method, frequency domain method and time-frequency analysis, has reached a lot of consensus. The non-linear analysis has also been widely applied in biomedical and clinical researches. However, for non-linear HRV analysis, especially for short-term non-linear HRV analysis, controversy still exists, and a unified standard and conclusion has not been formed. This paper reviews and discusses three short-term non-linear HRV analysis methods (fractal dimension, entropy and complexity) and their principles, progresses and problems in clinical application in detail, in order to provide a reference for accurate application in clinical medicine.

  17. RECENT PROGRESS TOWARD A MUON RECIRCULATING LINEAR ACCELERATOR

    SciTech Connect

    Slawomir Bogacz, Vasiliy Morozov, Yves Roblin, Kevin Beard

    2012-07-01

    Both Neutrino Factories (NF) and Muon Colliders (MC) require very rapid acceleration due to the short lifetime of muons. After a capture and bunching section, a linac raises the energy to about 900 MeV, and is followed by one or more Recirculating Linear Accelerators (RLA), possibly followed by a Rapid Cycling Synchnotron (RCS) or Fixed-Field Alternating Gradient (FFAG) ring. A RLA reuses the expensive RF linac section for a number of passes at the price of having to deal with different energies within the same linac. Various techniques including pulsed focusing quadruopoles, beta frequency beating, and multipass arcs have been investigated via simulations to improve the performance and reduce the cost of such RLAs.

  18. Both Financial and Cognitive Decline Predict Clinical Progression in MCI.

    PubMed

    Gerstenecker, Adam; Triebel, Kristen L; Martin, Roy; Snyder, Scott; Marson, Daniel C

    2016-01-01

    We investigated the roles of financial/functional and cognitive abilities in predicting clinical progression in patients with mild cognitive impairment (MCI). In a longitudinal sample of 51 patients with consensus conference diagnosed MCI likely due to Alzheimer disease (AD), two-year change scores were calculated for a performance measure of functional ability, cognitive variables, and 3 outcome measures used to track progression in neurological disorders. We examined patterns of financial and cognitive decline across the 2-year study period, and used these data and the 3 outcome variables to construct discrete predictor models of clinical progression in MCI. We found that both financial skills and cognitive abilities declined over the 2-year study period, were significantly associated with clinical progression, and contributed unique variance to all 3 predictor models. The resulting models accounted for 40% to 75% of variance in clinical progression across outcome variables. Taken together, our results indicate that changes in both cognitive abilities and higher order functional skills appear integral to understanding clinical progression in MCI likely due to AD. Specifically, declines in financial skills contribute unique variance to measures commonly used to track progression in neurological disorders associated with aging, and thus represent an important functional marker of clinical progression in prodromal AD.

  19. Manual Linear Movements to Assess Spasticity in a Clinical Setting

    PubMed Central

    Marinelli, Lucio; Trompetto, Carlo; Mori, Laura; Vigo, Gabriele; Traverso, Elisabetta; Colombano, Federica; Abbruzzese, Giovanni

    2013-01-01

    In a clinical setting, where motor-driven systems are not readily available, the major difficulty in the assessment of the stretch reflex lies in the control of passive limb displacement velocity. A potential approach to this problem arises from the use of manual sinusoidal movements (made by continuous alternating flexions and extensions) paced by an external stimulus. Unfortunately, there are conditions in which sinusoidal movements induce interfering phenomena such as the shortening reaction or postactivation depression. In the present paper, a novel manual method to control the velocity of passive linear movements is described and the results obtained from both healthy subjects and spastic patients are reported. This method is based on the synchronisation of movements with tones played by a metronome at different speeds. In a first set of experiments performed in healthy subjects, we demonstrated consistent control of velocity during passive limb movements using this method. Four joints usually examined during muscle tone assessment were tested: wrist, elbow, knee and ankle joints. Following this, we conducted a longitudinal assessment of the stretch reflex amplitude in wrist flexor muscles in patients with spasticity treated with botulinum toxin type A. The evaluators were not only able to vary the movement velocity based on the metronome speed, but also could reproduce the respective speeds two weeks later, despite the changing degree of hypertonia. This method is easy to perform in a clinical setting and hardware requirements are minimal, making it an attractive and robust procedure for the widespread clinical assessment of reflex hypertonia. PMID:23335966

  20. [Clinical diagnosis progress and continuing medical education].

    PubMed

    Mukhin, N A; Svistunov, A A; Fomin, V V

    2014-01-01

    The paper discusses current approaches to diagnosing in an internal medicine clinic and to improving diagnostic tactics. It gives prospects for training physicians in current diagnostic approaches in the framework of the continuing medical education system.

  1. Progression parameters for emphysema: a clinical investigation.

    PubMed

    Stolk, Jan; Putter, Hein; Bakker, Els M; Shaker, Saher B; Parr, David G; Piitulainen, Eeva; Russi, Erich W; Grebski, Elzbieta; Dirksen, Asger; Stockley, Robert A; Reiber, Johan H C; Stoel, Berend C

    2007-09-01

    In patients with airflow limitation caused by cigarette smoking, lung density measured by computed tomography is strongly correlated with quantitative pathology scores of emphysema, but the ability of lung densitometry to detect progression of emphysema is disputed. We assessed the sensitivity of lung densitometry as a parameter of disease progression of emphysema in comparison to FEV(1) and gas transfer. At study baseline and after 30 months we measured computed tomography (CT)-derived lung density, spirometry and carbon monoxide diffusion coefficient in 144 patients with chronic obstructive pulmonary disease (COPD) in five different centers. Annual change in lung density was 1.31 g/L/year (CI 95%: -2.12 to -0.50 HU, p=0.0015, 39.5 mL/year (CI 95%: -100.0-21.0 mL, p=0.2) for FEV(1) (-39.5 mL) and 24.3 micromol/min/kPa/L/year for gas transfer (CI 95%: -61.0-12.5 micromol/min/kPa/L/year, p=0.2). Signal-to-noise ratio (mean change divided by standard error of the change) for the detection of annual change was 3.2 for lung densitometry, but 1.3 for both FEV(1) and gas diffusion. We conclude that detection of progression of emphysema was found to be 2.5-fold more sensitive using lung densitometry than by using currently recommended lung function parameters. Our results support CT scan as an efficacious test for novel drugs for emphysema. PMID:17644366

  2. [Clinical Research Progress on Transformed Lymphoma -Review].

    PubMed

    Wang, Bing-Jie; Cen, Xi-Nan; Ren, Han-Yun

    2016-08-01

    Histologic transformation (HT) is a frequent event in the clinical course of patients with indolent lymphoma with dismal outcome. The diagnosis of HT is based on clinical manifestation, PET-CT and pathologic biopsy, and the latter is a golden standard for HT. There are contradictory data about the impact of initial management on the risk of transformation. Patients who present with HT did not receive R-CHOP or chemotherapy-naive, should receive this regimen. For the subset of patients received R-CHOP prior to HT, the second line chemotherapy for DLBCL should be adopted. Consolidation with HDT-ASCT should be considered for the suitable young patients. The radio-immunotherapy and novel drugs showed a bright perspective for the patients with HT. PMID:27531806

  3. Spatial and temporal progressions of spatial statistical moments in linear chromatography.

    PubMed

    Lan, K; Jorgenson, J W

    2001-01-01

    Generalizations of existing models of chromatography allow the spatial and temporal progressions of all spatial statistical moments in linear chromatography to be given as the solution to a set of ordinary differential equations. Basic strategies of simplifying these equations are described.

  4. Identifying genetically driven clinical phenotypes using linear mixed models

    PubMed Central

    Mosley, Jonathan D.; Witte, John S.; Larkin, Emma K.; Bastarache, Lisa; Shaffer, Christian M.; Karnes, Jason H.; Stein, C. Michael; Phillips, Elizabeth; Hebbring, Scott J.; Brilliant, Murray H.; Mayer, John; Ye, Zhan; Roden, Dan M.; Denny, Joshua C.

    2016-01-01

    We hypothesized that generalized linear mixed models (GLMMs), which estimate the additive genetic variance underlying phenotype variability, would facilitate rapid characterization of clinical phenotypes from an electronic health record. We evaluated 1,288 phenotypes in 29,349 subjects of European ancestry with single-nucleotide polymorphism (SNP) genotyping on the Illumina Exome Beadchip. We show that genetic liability estimates are primarily driven by SNPs identified by prior genome-wide association studies and SNPs within the human leukocyte antigen (HLA) region. We identify 44 (false discovery rate q<0.05) phenotypes associated with HLA SNP variation and show that hypothyroidism is genetically correlated with Type I diabetes (rG=0.31, s.e. 0.12, P=0.003). We also report novel SNP associations for hypothyroidism near HLA-DQA1/HLA-DQB1 at rs6906021 (combined odds ratio (OR)=1.2 (95% confidence interval (CI): 1.1–1.2), P=9.8 × 10−11) and for polymyalgia rheumatica near C6orf10 at rs6910071 (OR=1.5 (95% CI: 1.3–1.6), P=1.3 × 10−10). Phenome-wide application of GLMMs identifies phenotypes with important genetic drivers, and focusing on these phenotypes can identify novel genetic associations. PMID:27109359

  5. Macular Preprocessing of Linear Acceleratory Stimuli: Implications for the Clinic

    NASA Technical Reports Server (NTRS)

    Ross, M. D.; Hargens, Alan R. (Technical Monitor)

    1996-01-01

    Three-dimensional reconstructions of innervation patterns in rat maculae were carried out using serial section images sent to a Silicon Graphics workstation from a transmission electron microscope. Contours were extracted from mosaicked sections, then registered and visualized using Biocomputation Center software. Purposes were to determine innervation patterns of type II cells and areas encompassed by vestibular afferent receptive fields. Terminals on type II cells typically are elongated and compartmentalized into parts varying in vesicular content; reciprocal and serial synapses are common. The terminals originate as processes of nearby calyces or from nerve fibers passing to calyces outside the immediate vicinity. Thus, receptive fields of the afferents overlap in unique ways. Multiple processes are frequent; from 4 to 6 afferents supply 12-16 terminals on a type II cell. Processes commonly communicate with two type II cells. The morphology indicates that extensive preprocessing of linear acceleratory stimuli occurs peripherally, as is true also of visual and olfactory systems. Clinically, this means that loss of individual nerve fibers may not be noticed behaviorally, due to redundancy (receptive field overlap). However, peripheral processing implies the presence of neuroactive agents whose loss can acutely or chronically alter normal peripheral function and cause balance disorders. (Platform presentation preferred - Theme 11)

  6. [Progress in clinical bone assessment using CT].

    PubMed

    Ito, Masako

    2013-03-01

    Clinical computed tomography (CT) provides the information of bone structure and mineral density in vivo . Based on three-dimensional bone structure, voluntary two-dimensional sections are available, as well as trabecular and cortical data separately. However, the trabecular structure, which size is smaller than the spatial resolution, cannot be measured precisely. A recently system, high-resolution peripheral quantitative CT (HR-pQCT) , can visualize and quantify the trabecular and cortical microstructure in vivo . Because of low radiation dose and high reproducibility, HR-pQCT system is expected to be a useful tool to assess the pathophysiological changes or the efficacy of anti-osteoporotic agents on bone. PMID:23445885

  7. A review of disease progression models of Parkinson's disease and applications in clinical trials.

    PubMed

    Venuto, Charles S; Potter, Nicholas B; Ray Dorsey, E; Kieburtz, Karl

    2016-07-01

    Quantitative disease progression models for neurodegenerative disorders are gaining recognition as important tools for drug development and evaluation. In Parkinson's disease (PD), several models have described longitudinal changes in the Unified Parkinson's Disease Rating Scale (UPDRS), one of the most utilized outcome measures for PD trials assessing disease progression. We conducted a literature review to examine the methods and applications of quantitative disease progression modeling for PD using a combination of key words including "Parkinson disease," "progression," and "model." For this review, we focused on models of PD progression quantifying changes in the total UPDRS scores against time. Four different models reporting equations and parameters have been published using linear and nonlinear functions. The reasons for constructing disease progression models of PD thus far have been to quantify disease trajectories of PD patients in active and inactive treatment arms of clinical trials, to quantify and discern symptomatic and disease-modifying treatment effects, and to demonstrate how model-based methods may be used to design clinical trials. The historical lack of efficiency of PD clinical trials begs for model-based simulations in planning for studies that result in more informative conclusions, particularly around disease modification. © 2016 International Parkinson and Movement Disorder Society.

  8. Monte Carlo simulation of a clinical linear accelerator.

    PubMed

    Lin, S Y; Chu, T C; Lin, J P

    2001-12-01

    The effects of the physical parameters of an electron beam from a Siemens PRIMUS clinical linear accelerator (linac) on the dose distribution in water were investigated by Monte Carlo simulation. The EGS4 user code, OMEGA/BEAM, was used in this study. Various incident electron beams, for example, with different energies, spot sizes and distances from the point source, were simulated using the detailed linac head structure in the 6 MV photon mode. Approximately 10 million particles were collected in the scored plane, which was set under the reticle to form the so-called phase space file. The phase space file served as a source for simulating the dose distribution in water using DOSXYZ. Dose profiles at Dmax (1.5 cm) and PDD curves were calculated following simulating about 1 billion histories for dose profiles and 500 million histories for percent depth dose (PDD) curves in a 30 x 30 x 30 cm3 water phantom. The simulation results were compared with the data measured by a CEA film and an ion chamber. The results show that the dose profiles are influenced by the energy and the spot size, while PDD curves are primarily influenced by the energy of the incident beam. The effect of the distance from the point source on the dose profile is not significant and is recommended to be set at infinity. We also recommend adjusting the beam energy by using PDD curves and, then, adjusting the spot size by using the dose profile to maintain the consistency of the Monte Carlo results and measured data. PMID:11761097

  9. Computational Approaches for Translational Clinical Research in Disease Progression

    PubMed Central

    McGuire, Mary F.; Iyengar, M. Sriram; Mercer, David W.

    2011-01-01

    Today, there is an ever-increasing amount of biological and clinical data available that could be used to enhance a systems-based understanding of disease progression through innovative computational analysis. In this paper we review a selection of published research regarding computational methodologies, primarily from systems biology, that support translational research from the molecular level to the bedside, with a focus on applications in trauma and critical care. Trauma is the leading cause of mortality in Americans under 45 years of age, and its rapid progression offers both opportunities and challenges for computational analysis of trends in molecular patterns associated with outcomes and therapeutic interventions. This review presents methods and domain-specific examples that may inspire the development of new algorithms and computational methods that utilize both molecular and clinical data for diagnosis, prognosis and therapy in disease progression. PMID:21712727

  10. The Nature of Progression in Parkinson’s Disease: An Application of Non-Linear, Multivariate, Longitudinal Random Effects Modelling

    PubMed Central

    Kuramoto, Lisa; Cragg, Jacquelyn; Nandhagopal, Ramachandiran; Mak, Edwin; Sossi, Vesna; de la Fuente-Fernández, Raul; Stoessl, A. Jon; Schulzer, Michael

    2013-01-01

    Background To date, statistical methods that take into account fully the non-linear, longitudinal and multivariate aspects of clinical data have not been applied to the study of progression in Parkinson’s disease (PD). In this paper, we demonstrate the usefulness of such methodology for studying the temporal and spatial aspects of the progression of PD. Extending this methodology further, we also explore the presymptomatic course of this disease. Methods Longitudinal Positron Emission Tomography (PET) measurements were collected on 78 PD patients, from 4 subregions on each side of the brain, using 3 different radiotracers. Non-linear, multivariate, longitudinal random effects modelling was applied to analyze and interpret these data. Results The data showed a non-linear decline in PET measurements, which we modelled successfully by an exponential function depending on two patient-related covariates duration since symptom onset and age at symptom onset. We found that the degree of damage was significantly greater in the posterior putamen than in the anterior putamen throughout the disease. We also found that over the course of the illness, the difference between the less affected and more affected sides of the brain decreased in the anterior putamen. Younger patients had significantly poorer measurements than older patients at the time of symptom onset suggesting more effective compensatory mechanisms delaying the onset of symptoms. Cautious extrapolation showed that disease onset had occurred some 8 to 17 years prior to symptom onset. Conclusions Our model provides important biological insights into the pathogenesis of PD, as well as its preclinical aspects. Our methodology can be applied widely to study many other chronic progressive diseases. PMID:24204641

  11. Ultrasound clinical progress monitoring: Who, where and how?

    PubMed

    Harrison, Gill

    2015-11-01

    Prior to assessment of final ultrasound clinical competency it is important to monitor clinical progress, provide high quality feedback and encourage skills development. The role of the supervisor, mentor and assessor are fundamental to the on-going progress monitoring of ultrasound trainees. This article forms the second part of a larger project which was to elicit ultrasound practitioners' opinions on how progress should be monitored, where and by whom. An on-line questionnaire was used to gain opinions from ultrasound practitioners. Totally, 116 responses were received from professionals with an interest in ultrasound assessment. Results suggested that experienced, qualified ultrasound practitioners should undertake the role of supervisor and assessor, having been prepared for that role by the training centre. Formative monitoring should take place both within the clinical department and possibly the training centre, using a range of methods. Following completion of the training, practitioners should have a preceptorship period to consolidate their knowledge and skills for 3 to 6 months or until further competencies have been demonstrated. Formative progress monitoring should be a recognised part of ultrasound training. Essentially, staff undertaking supervision and assessor roles should be supported and trained to ensure a high quality, consistent learning experience for ultrasound trainees. Additionally, they should provide appropriate feedback to the trainee and education centre.

  12. Estimating Typical Multiple Sclerosis Disability Progression Speed from Clinical Observations

    PubMed Central

    Brown, Murray G.; Asbridge, Mark; Hicks, Vern; Kirby, Sarah; Murray, Thomas J.; Andreou, Pantelis; Lin, Dong

    2014-01-01

    Introduction Multiple sclerosis (MS) is a chronic disease of the central nervous system. Estimates of MS natural history (NH) disability progression speed from clinical observations vary worldwide. This may reflect, in part, variance in censoring-bias) (missing observations) and assumptions about when irreversible disability progression events occurred. We test whether estimates of progression speed which assume midpoint survival time at irreversible disability endpoints are significantly faster than estimates which assume maximum survival time, and are more stable across study groups and time periods. Methods Our Nova Scotia NH study population includes 2,240 definite relapsing-onset multiple sclerosis (R-MS) natural history patients with 18,078 Expanded Disability Status Scale (EDSS) clinical observations in study period 1979–2010. Progression speed is measured by rate-of-change in range EDSS 0–6 and by survival time at irreversible endpoints EDSS 1–9. Midpoint censoring-bias-reduction methods are applied to clinical observations. Findings Typical EDSS increase per year in range EDSS 0–6, assuming midpoint survival time, is estimated to be 0.168 for all R-MS, 0.204 for eventually-DMD-treated patients and 0.155 for never-DMD-treated patients. Estimates assuming midpoint rather than maximum survival time are significantly faster: 16% faster for all R-MS natural history patients, 6% faster for eventually-DMD-treated patients, and 21% faster for never-DMD-treated patients. The variability of estimates across study groups and time periods decreased when midpoint survival time was assumed. Conclusions Estimates of typical disease progression speed from 1979–2010 Nova Scotia clinical observations are sensitive to censoring-bias and to analysts’ survival time assumptions. Censoring-bias-adjusted estimates of typical natural history disability progression speed in relapsing-onset multiple sclerosis patients are significantly faster, and less variable within

  13. Progressive diaphyseal dysplasia (Engelmann disease): scintigraphic-radiographic-clinical correlations

    SciTech Connect

    Kumar, B.; Murphy, W.A.; Whyte, M.P.

    1981-07-01

    Four patients (2 males, 2 females; ages 15-47 yrs.) with variable clinical, radiographic, and scintigraphic manifestations of progressive diaphyseal dysplasia (PDD) or Engelmann disease were studied with 99mTc methylene diphosphonate bone imaging and radiographic skeletal surveys. Comparison of the results of the two imaging procedures showed that some affected bones were scintigraphically normal but radiographically abnormal and vice versa. These findings suggest that the lesions of PDD may mature, causing a significant decrease in disease activity, and that abnormally increased radiopharmaceutical accumulation during bone scintigraphy appears to be a sensitive indicator of disease activity.

  14. Heart Xenotransplantation: Historical Background, Experimental Progress, and Clinical Prospects.

    PubMed

    Murthy, Raghav; Bajona, Pietro; Bhama, Jay K; Cooper, David K C

    2016-04-01

    If pig hearts could be transplanted successfully into patients with end-stage cardiac failure, the critical shortage of hearts from deceased human donors would be overcome. The several attempts at cardiac xenotransplantation carried out in the 20th century, usually with hearts from nonhuman primates (NHPs), are reviewed, as are the surgical techniques used in experimental heart transplantation in animals. For a number of reasons, the pig has been selected as the potential source of organs for clinical transplantation. The major pathobiological barriers that the pig presents, and progress in overcoming these barriers either by genetic engineering of the pig or by the administration of novel immunosuppressive agents, are described. Currently, non-life-supporting pig heterotopic heart transplantation in NHPs has extended to more than 2 years in 1 case, with life-supporting orthotopic heart transplantation of almost 2 months. Future approaches to resolve the remaining problems and the selection of patients for the initial clinical trials are briefly discussed.

  15. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression.

    PubMed

    Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

    2015-09-29

    Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

  16. Vascular Risk Factors and Clinical Progression in Spinocerebellar Ataxias

    PubMed Central

    Lo, Raymond Y.; Figueroa, Karla P.; Pulst, Stefan M.; Lin, Chi-Ying; Perlman, Susan; Wilmot, George; Gomez, Christopher M.; Schmahmann, Jeremy; Paulson, Henry; Shakkottai, Vikram G.; Ying, Sarah H.; Zesiewicz, Theresa; Bushara, Khalaf; Geschwind, Michael; Xia, Guangbin; Subramony, S. H.; Ashizawa, Tetsuo; Kuo, Sheng-Han

    2015-01-01

    Background The contributions of vascular risk factors to spinocerebellar ataxia (SCA) are not known. Methods We studied 319 participants with SCA 1, 2, 3, and 6 and repeatedly measured clinical severity using the Scale for Assessment and Rating of Ataxia (SARA) for 2 years. Vascular risk factors were summarized by CHA2DS2-VASc scores as the vascular risk factor index. We employed regression models to study the effects of vascular risk factors on ataxia onset and progression after adjusting for age, sex, and pathological CAG repeats. Our secondary analyses took hyperlipidemia into account. Results Nearly 60% of SCA participants were at low vascular risks with CHA2DS2-VASc = 0, and 31% scored 2 or greater. Higher CHA2DS2-VASc scores were not associated with either earlier onset or faster progression of ataxia. These findings were not altered after accounting for hyperlipidemia. Discussion Vascular risks are not common in SCAs and are not associated with earlier onset or faster ataxia progression. PMID:25713748

  17. Clinical Progression in Parkinson's Disease and the Neurobiology of Axons

    PubMed Central

    Cheng, Hsiao-Chun; Ulane, Christina M.; Burke, Robert E.

    2010-01-01

    In spite of tremendous growth in recent years in our knowledge of the molecular basis of Parkinson's disease and the molecular pathways of cell injury and death, we remain without therapies that forestall disease progression. While there are many possible explanations for this lack of success, one is that experimental therapeutics to date have not adequately focused on an important component of the disease process, that of axon degeneration. It remains unknown what neuronal compartment, either the soma or the axon, is involved at disease onset, although some have proposed that it is the axons and their terminals that take the initial brunt of injury. Nevertheless, this concept has not been formally incorporated into many of the current theories of disease pathogenesis, and it has not achieved a wide consensus. More importantly, in view of growing evidence that the molecular mechanisms of axon degeneration are separate and distinct from the canonical pathways of programmed cell death that mediate soma destruction, the possibility of early involvement of axons in PD has not been adequately emphasized as a rationale to explore the neurobiology of axons for novel therapeutic targets. We propose that it is ongoing degeneration of axons, not cell bodies, that is the primary determinant of clinically apparent progression of disease, and that future experimental therapeutics intended to forestall disease progression will benefit from a new focus on the distinct mechanisms of axon degeneration. PMID:20517933

  18. Palaeoenvironmental reconstructions from linear dunefields: recent progress, current challenges and future directions

    NASA Astrophysics Data System (ADS)

    Telfer, M. W.; Hesse, P. P.

    2013-10-01

    This paper reviews recent progress in the use of linear dunes as ‘geoproxies' of late Quaternary environmental change, summarises the challenges facing their use, and explores some potential solutions to these challenges. Large areas of the swathes of linear dunes which occupy the continental interior of southern Africa, Australia, and parts of central Asia and southern America currently have limited or negligible aeolian activity. They have been recognised as offering potential information about past environments for more than a century, but only with the widespread application of luminescence dating during the 1990s did they realistically start to offer the prospect of being an extensive, dateable proxy of late Quaternary palaeoenvironments and, possibly, palaeoclimates. Dating aeolian dune sands with luminescence methods is generally (although not always) relatively straightforward. Over the past twenty years, a large number (>1000) of luminescence ages have been added to the global dataset, yet there has also been significant criticism of some of the rationale underpinning much of the interpretation of the records derived. At the landscape scale, developments of arguably equal importance have come from improved geomorphological understanding based on the wider availability of remotely-sensed data and the paradigm of dunefield evolution as a self-organising complex system. Current challenges are identified in three key regions: incomplete understanding of how the process geomorphology of linear dunes affect the accumulation and preservation of sediment, a lack of clarity regarding the temporal and spatial scale of the response in a dynamic environmental setting and uncertainty surrounding the drivers of changing rates of net accumulation. Solutions to these challenges lie within diverse research methodologies. Certainly, further field study is required, with improvement required in understanding system responses to changing environmental stimuli at scales from

  19. Progress in Rett Syndrome: from discovery to clinical trials.

    PubMed

    Percy, Alan K

    2016-09-01

    Fifty years ago, Andreas Rett described a disorder in 22 females featuring prominent regression of fine motor and communication skills, cognitive impairment, stereotypic movements, periodic breathing, and gait abnormalities. This disorder became known as Rett syndrome (RTT) following the report of Hagberg et al. in 1983. Although RTT was scarcely recognized at that time in the United States, here the efforts of Rett and Hagberg led to rapid progress in recognition and diagnosis, a clearer understanding of its clinical and pathological underpinnings, and, ultimately, identification of mutations in the methyl-CpG-binding protein 2 (MECP2) gene as the primary cause of this unique and challenging neurodevelopmental disorder. Thereafter, a natural history study and critical translational research in animal models paved the way for potential disease-modifying agents to be assessed in human clinical trials. To be successful, the energies of the international community at all levels, including researchers in clinical and basic science, funding agencies, pharmaceutical companies, patient advocates, and, above all, parents and their children are essential. Otherwise, hopes for effective treatment, if not, a cure, will remain unfulfilled. PMID:27491553

  20. Progress in Rett Syndrome: from discovery to clinical trials.

    PubMed

    Percy, Alan K

    2016-09-01

    Fifty years ago, Andreas Rett described a disorder in 22 females featuring prominent regression of fine motor and communication skills, cognitive impairment, stereotypic movements, periodic breathing, and gait abnormalities. This disorder became known as Rett syndrome (RTT) following the report of Hagberg et al. in 1983. Although RTT was scarcely recognized at that time in the United States, here the efforts of Rett and Hagberg led to rapid progress in recognition and diagnosis, a clearer understanding of its clinical and pathological underpinnings, and, ultimately, identification of mutations in the methyl-CpG-binding protein 2 (MECP2) gene as the primary cause of this unique and challenging neurodevelopmental disorder. Thereafter, a natural history study and critical translational research in animal models paved the way for potential disease-modifying agents to be assessed in human clinical trials. To be successful, the energies of the international community at all levels, including researchers in clinical and basic science, funding agencies, pharmaceutical companies, patient advocates, and, above all, parents and their children are essential. Otherwise, hopes for effective treatment, if not, a cure, will remain unfulfilled.

  1. Dissecting the Syndrome of Schizophrenia: Progress toward Clinically Useful Biomarkers.

    PubMed

    Dean, Brian

    2011-01-01

    The search for clinically useful biomarkers has been one of the holy grails of schizophrenia research. This paper will outline the evolving notion of biomarkers and then outline outcomes from a variety of biomarkers discovery strategies. In particular, the impact of high-throughput screening technologies on biomarker discovery will be highlighted and how new or improved technologies may allow the discovery of either diagnostic biomarkers for schizophrenia or biomarkers that will be useful in determining appropriate treatments for people with the disorder. History tells those involved in biomarker research that the discovery and validation of useful biomarkers is a long process and current progress must always be viewed in that light. However, the approval of the first biomarker screen with some value in predicting responsiveness to antipsychotic drugs suggests that biomarkers can be identified and that these biomarkers that will be useful in diagnosing and treating people with schizophrenia.

  2. Primary progressive aphasia: linguistic patterns and clinical variants.

    PubMed

    Silveri, Maria Caterina; Pravatà, Emanuele; Brita, Anna Clelia; Improta, Erika; Ciccarelli, Nicoletta; Rossi, Paola; Colosimo, Cesare

    2014-08-01

    We investigated whether primary progressive aphasias (PPA) reflect non-random degradation of linguistic dimensions that might be supported by different neural subsystems and to what extent this degradation contributes to the emergence of clinical entities: semantic (S), logopenic (L) and nonfluent (NF) aphasia; apraxia of speech was also considered if associated with language disorders (AOS/aph). Forty-two aphasic patients are reported. Two main definable patterns of linguistic deficits tended to emerge that corresponded with identifiable patterns of brain atrophy, and probably diseases: the S variant, which principally expresses the impact of a "deep" cognitive (semantic) disorder on language, and AOS/aph in which "peripheral" executive components play a significant role. By contrast, NF aphasia emerged as a heterogeneous variant due to disorganization of various dimensions within the linguistic domain, that assumes different patterns depending on the differential distribution of atrophy in the perisylvian regions. PMID:24974082

  3. Progress of drug-loaded polymeric micelles into clinical studies.

    PubMed

    Cabral, Horacio; Kataoka, Kazunori

    2014-09-28

    Targeting tumors with long-circulating nano-scaled carriers is a promising strategy for systemic cancer treatment. Compared with free small therapeutic agents, nanocarriers can selectively accumulate in solid tumors through the enhanced permeability and retention (EPR) effect, which is characterized by leaky blood vessels and impaired lymphatic drainage in tumor tissues, and achieve superior therapeutic efficacy, while reducing side effects. In this way, drug-loaded polymeric micelles, i.e. self-assemblies of amphiphilic block copolymers consisting of a hydrophobic core as a drug reservoir and a poly(ethylene glycol) (PEG) hydrophilic shell, have demonstrated outstanding features as tumor-targeted nanocarriers with high translational potential, and several micelle formulations are currently under clinical evaluation. This review summarizes recent efforts in the development of these polymeric micelles and their performance in human studies, as well as our recent progress in polymeric micelles for the delivery of nucleic acids and imaging. PMID:24993430

  4. Influence of microwave disinfection on the linear dimensional stability of complete dentures: a clinical study.

    PubMed

    Basso, Michael Frederico Manzolli; Giampaolo, Eunice Teresinha; Vergani, Carlos Eduardo; Machado, Ana Lúcia; Pavarina, Ana Cláudia; Compagnoni, Marco Antonio

    2010-01-01

    This clinical study evaluated the effect of two microwave disinfection protocols at 650 W for 3 minutes (group 1, once a week; group 2, three times a week) on the linear dimensional stability of complete dentures. Measurements were taken across four reference points: before the first microwave disinfection (baseline) and after each week of disinfection. Furthermore, the dentures were monitored clinically. Group 2 showed significantly greater shrinkage than group 1 in all evaluated weeks. During clinical monitoring, no significant findings were observed. Even though dimensional changes occurred, the clinical evaluation did not yield any changes in either group.

  5. Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.

    PubMed

    Catanzaro, Daniele; Shackney, Stanley E; Schaffer, Alejandro A; Schwartz, Russell

    2016-01-01

    Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.

  6. Clinical characteristics and progression of liver abscess caused by toxocara

    PubMed Central

    Ha, Kyung Ho; Song, Jung Eun; Kim, Byung Seok; Lee, Chang Hyeong

    2016-01-01

    AIM: To evaluate the clinical characteristics and progression of liver abscess caused by toxocara. METHODS: We retrospectively reviewed the medical records of patients with serum IgG antibody to Toxocara canis and liver abscess diagnosed using abdominal computed tomography between February 2010 and February 2015. Among 84 patients exhibiting serum IgG antibody to Toxocara canis, 34 patients were diagnosed with liver asbscess and treated with albendazole. A follow-up period of 1 year was conducted. RESULTS: Mean patient age was 53 (34-79) years, with 26 (76.5%) patients being male. Twenty-one (61.7%) patients were moderate or heavy drinkers, 23 (67.6%) patients had a history of eating raw meat or liver and 6 (17.6%) patients owned pet dogs or cats. Main patient symptoms consisted of right upper quadrant pain, fever, and fatigue; 18 (52.9%) patients, however, presented with no symptoms. Lung involvement was detected in 444 (11.7%) patients. The eosinophil count increased in 29 (85.3%) patients at initial diagnosis, and decreased in most patients after albendazole treatment. The initial serum IgE level increased in 25 (73.5%) patients, but exhibited various response levels after albendazole treatment. Liver abscess formation improved in all patients. CONCLUSION: The liver abscess was improved with albendazole treatment. PMID:27366302

  7. Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

    PubMed Central

    Ontaneda, Daniel; Fox, Robert J.; Chataway, Jeremy

    2015-01-01

    Progressive multiple sclerosis is characterized by the gradual accrual of disability independent of relapses and can occur with disease onset (primary progressive) or preceded by a relapsing disease course (secondary progressive). An effective disease modifying treatment for progressive multiple sclerosis has not been identified, and the results of clinical trials to date have been generally disappointing. Ongoing advances in our understanding of pathogenesis, identification of novel targets for neuro-protection, and improved outcome measures have the potential to lead to effective treatments for progressive multiple sclerosis. In this review lessons learned from previous clinical trials and perspectives from current trials in progressive multiple sclerosis are summarized. Promising clinical, imaging, and biological markers will also be reviewed, along with novel clinical trial designs. PMID:25772899

  8. Alzheimer's disease progression model based on integrated biomarkers and clinical measures

    PubMed Central

    Qiu, Yue; Li, Liang; Zhou, Tian-yan; Lu, Wei

    2014-01-01

    Aim: Biomarkers and image markers of Alzheimer's disease (AD), such as cerebrospinal fluid Aβ42 and p-tau, are effective predictors of cognitive decline or dementia. The aim of this study was to integrate these markers with a disease progression model and to identify their abnormal ranges. Methods: The data of 395 participants, including 86 normal subjects, 108 early mild cognitive impairment (EMCI) subjects, 120 late mild cognitive impairment (LMCI) subjects, and 81 AD subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For the participants, baseline and long-term data on cerebrospinal fluid Aβ42 and p-tau, hippocampal volume, and ADAS-cog were available. Various linear and nonlinear models were tested to determine the associations among the ratio of Aβ42 to p-tau (the Ratio), hippocampal volume and ADAS-cog. Results: The most likely models for the Ratio, hippocampal volume, and ADAS-cog (logistic, Emax, and linear models, respectively) were used to construct the final model. Baseline disease state had an impact on all the 3 endpoints (the Ratio, hippocampal volume, and ADAS-cog), while APOEε4 genotype and age only influence the Ratio and hippocampal volume. Conclusion: The Ratio can be used to identify the disease stage for an individual, and clinical measures integrated with the Ratio improve the accuracy of mild cognitive impairment (MCI) to AD conversion forecasting. PMID:25088003

  9. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    PubMed Central

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne-Vibeke; Knoop, Ann S.; Jensen, Jeanette D.; Bak, Martin; Mollenhauer, Jan; Kruse, Torben A.; Thomassen, Mads

    2015-01-01

    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence. PMID:25730902

  10. Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice

    PubMed Central

    Koga, Tomohiro; Okada, Akitomo; Fukuda, Takaaki; Hidaka, Toshihiko; Ishii, Tomonori; Ueki, Yukitaka; Kodera, Takao; Nakashima, Munetoshi; Takahashi, Yuichi; Honda, Seiyo; Horai, Yoshiro; Watanabe, Ryu; Okuno, Hiroshi; Aramaki, Toshiyuki; Izumiyama, Tomomasa; Takai, Osamu; Miyashita, Taiichiro; Sato, Shuntaro; Kawashiri, Shin-ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Origuchi, Tomoki; Nakamura, Hideki; Aoyagi, Kiyoshi; Eguchi, Katsumi; Kawakami, Atsushi

    2016-01-01

    Abstract To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice. We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis. CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01–1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17–2.59), RA typical erosion at baseline (95%CI 1.56–21.1), and the introduction of bDMARDs (95%CI 0.06–0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years. We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients’ disease durations. PMID:27124044

  11. Clinical assessment of asthma progression in children and adults.

    PubMed

    Spahn, Joseph D; Covar, Ronina

    2008-03-01

    Asthma is a heterogeneous disorder with a variable course, characterized by episodes of cough, wheezing and shortness of breath, reversible airflow limitation, and bronchial hyperresponsiveness. It begins early in life in many subjects with intermittent symptoms occurring with viral respiratory tract infections. Over time, and in genetically susceptible children (those with an atopic predisposition), the disease becomes more persistent with symptoms occurring in the absence of respiratory tract infections. Children with persistent wheezing are eventually diagnosed with asthma, with those at greatest risk having developed allergic sensitization early in life. Among children with asthma, some will have lifelong asthma with active symptoms and progressive loss of lung function over time, whereas other children will undergo asthma remission in adolescence. Once in remission, the disease may remain quiescent, or it may relapse in midadult life. This review focuses on studies that have enhanced our understanding of the progression of asthma from infancy to adulthood. Studies evaluating progressive loss of lung function, the best-studied measure of asthma progression, are also reviewed, followed by a brief discussion of whether asthma progression can be modified by inhaled glucocorticoid therapy.

  12. A novel method for the measurement of linear body segment parameters during clinical gait analysis.

    PubMed

    Geil, Mark D

    2013-09-01

    Clinical gait analysis is a valuable tool for the understanding of motion disorders and treatment outcomes. Most standard models used in gait analysis rely on predefined sets of body segment parameters that must be measured on each individual. Traditionally, these parameters are measured using calipers and tape measures. The process can be time consuming and is prone to several sources of error. This investigation explored a novel method for rapid recording of linear body segment parameters using magnetic-field based digital calipers commonly used for a different purpose in prosthetics and orthotics. The digital method was found to be comparable to traditional in all linear measures and data capture was significantly faster with the digital method, with mean time savings for 10 measurements of 2.5 min. Digital calipers only record linear distances, and were less accurate when diameters were used to approximate limb circumferences. Experience in measuring BSPs is important, as an experienced measurer was significantly faster than a graduate student and showed less difference between methods. Comparing measurement of adults vs. children showed greater differences with adults, and some method-dependence. If the hardware is available, digital caliper measurement of linear BSPs is accurate and rapid.

  13. Clinical progression of transplanted large granular lymphocytic leukemia in Fischer 334 rats exposed to 60 Hz magnetic fields

    SciTech Connect

    Morris, James E. ); Sasser, Lyle B. ); Miller, Douglas L. ); Dagle, Gerald E.; Rafferty, C N.; Ebi, K L.; Anderson, Larry E. )

    1999-01-19

    The purpose of this study was to determine if 60 Hz magnetic fields could alter the clinical progression of leukemia in an animal model. Large granular lymphocytic (LGL) leukemia cells from spleens of leukemic rats were transplanted into young male Fischer rats, producing signs of leukemia in about 2-3 months. The animals were injected with 2.2 x 107 LGL leukemia cells at the initiation of the study and assigned to 4 treatment groups 108/group) as follows: (1) 10 G linearly polarized 60 Hz magnetic fields, (2) sham exposed null energized unit with residual 20 mG fields, (3) ambient controls < 1 mG, and (4) positive controls (a single 5 Gy whole body exposure to 60Co 4 days prior to initiation of exposure). The magnetic fields were activated 20h/day, 7 days/week. Eighteen Rats (18 from each treatment group) were bled, killed, and evaluated at a5, 6, 7, 8, 9, and 11 weeks of exposure. Hematological endpoints, changes in spleen growth, and LGL cell infiltration into the spleen and liver were measured to evaluate the leukemia progression. Significant differences were not detected between the magnetic field exposed groups and the ambient control group, although the clinical progress of leukemia was enhanced in the positive control animals. These data indicate that exposure to sinusoidal, linearly polarized 60 Hz, 10 G magnetic fields did not significantly alter the clinical progression of LGL leukemia. Furthermore, the data are in general agreement with previous results of a companion repeated-bleeding study.

  14. Progress with the JLC/NLC X-Band Linear Collider Design

    NASA Astrophysics Data System (ADS)

    Raubenheimer, T. O.

    An electron/positron linear collider with a center-of-mass energy between 0.5 and 1 TeV would be an important complement to the physics program of the LHC in the next decade. The Next Linear Collider (NLC) is being designed by a US collaboration (FNAL, LBNL, LLNL, and SLAC) which is working closely with the Japanese collaboration that is designing the Japanese Linear Collider (JLC). This paper will discuss the technical difficulties encountered as well as the changes that have been made to the NLC design over the last year. These changes include improvements to the X-band rf system as well as modifications to the beam delivery system. The net effect has been to reduce the length of the collider from about 32 km to 25 km and to reduce the number of klystrons and modulators by a factor of two. Together these lead to significant cost savings.

  15. Progress through Collaboration - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The National Cancer Institute (NCI), through the Office of Cancer Clinical Proteomics Research (OCCPR), has signed two Memorandums of Understanding (MOUs) in the areas of sharing proteomics reagents and protocols and also in regulatory science.

  16. The Clinical Use of Hypnotic Regression and Progression in Psychotherapy.

    ERIC Educational Resources Information Center

    Goldberg, Bruce

    1990-01-01

    Discusses concept of time in therapy, presenting theoretical and clinical foundations to illustrate the validity of guiding patients into past lives and future lifetimes through hypnosis to resolve self-defeating sequences. (Author/TE)

  17. Accuracy of linear measurement in the Galileos cone beam computed tomography under simulated clinical conditions

    PubMed Central

    Ganguly, R; Ruprecht, A; Vincent, S; Hellstein, J; Timmons, S; Qian, F

    2011-01-01

    Objectives The aim of this study was to determine the geometric accuracy of cone beam CT (CBCT)-based linear measurements of bone height obtained with the Galileos CBCT (Sirona Dental Systems Inc., Bensheim, Hessen, Germany) in the presence of soft tissues. Methods Six embalmed cadaver heads were imaged with the Galileos CBCT unit subsequent to placement of radiopaque fiduciary markers over the buccal and lingual cortical plates. Electronic linear measurements of bone height were obtained using the Sirona software. Physical measurements were obtained with digital calipers at the same location. This distance was compared on all six specimens bilaterally to determine accuracy of the image measurements. Results The findings showed no statistically significant difference between the imaging and physical measurements (P > 0.05) as determined by a paired sample t-test. The intraclass correlation was used to measure the intrarater reliability of repeated measures and there was no statistically significant difference between measurements performed at the same location (P > 0.05). Conclusions The Galileos CBCT image-based linear measurement between anatomical structures within the mandible in the presence of soft tissues is sufficiently accurate for clinical use. PMID:21697155

  18. Characterizing Non-Linear Dependencies Among Pairs of Clinical Variables and Imaging Data

    PubMed Central

    Caban, Jesus J.; Bagci, Ulas; Mehari, Alem; Alam, Shoaib; Fontana, Joseph R.; Kato, Gregory J.; Mollura, Daniel J.

    2012-01-01

    Advances in computer-aided diagnosis (CAD) systems have shown the benefits of using computer-based techniques to obtain quantitative image measurements of the extent of a particular disease. Such measurements provide more accurate information that can be used to better study the associations between anatomical changes and clinical findings. Unfortunately, even with the use of quantitative image features, the correlations between anatomical changes and clinical findings are often not apparent and definite conclusions are difficult to reach. This paper uses nonparametric exploration techniques to demonstrate that even when the associations between two-variables seems weak, advanced properties of the associations can be studied and used to better understand the relationships between individual measurements. This paper uses quantitative imaging findings and clinical measurements of 85 patients with pulmonary fibrosis to demonstrate the advantages of non-linear dependency analysis. Results show that even when the correlation coefficients between imaging and clinical findings seem small, statistical measurements such as the maximum asymmetry score (MAS) and maximum edge value (MEV) can be used to better understand the hidden associations between the variables. PMID:23366482

  19. Tendon Tissue Engineering: Progress, Challenges, and Translation to the Clinic

    PubMed Central

    Shearn, Jason T.; Kinneberg, Kirsten R.C.; Dyment, Nathaniel A.; Galloway, Marc T.; Kenter, Keith; Wylie, Christopher; Butler, David L.

    2013-01-01

    The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products. PMID:21625053

  20. Tendon tissue engineering: progress, challenges, and translation to the clinic.

    PubMed

    Shearn, J T; Kinneberg, K R; Dyment, N A; Galloway, M T; Kenter, K; Wylie, C; Butler, D L

    2011-06-01

    The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products.

  1. Defining natural history: assessment of the ability of college students to aid in characterizing clinical progression of Niemann-Pick disease, type C.

    PubMed

    Shin, Jenny; Epperson, Katrina; Yanjanin, Nicole M; Albus, Jennifer; Borgenheimer, Laura; Bott, Natalie; Brennan, Erin; Castellanos, Daniel; Cheng, Melissa; Clark, Michael; Devany, Margaret; Ensslin, Courtney; Farivari, Nina; Fernando, Shanik; Gabriel, Lauren; Gallardo, Rani; Castleman, Moriah; Gutierrez, Olimpia; Herschel, Allison; Hodge, Sarah; Horst, Anne; Howard, Mary; James, Evan; Jones, Lindsey; Kearns, Mary; Kelly, Mary; Kim, Christine; Kiser, Kinzie; Klazura, Gregory; Knoedler, Chris; Kolbus, Emily; Lange, Lauren; Lee, Joan; Li, Eileena; Lu, Wei; Luttrell, Andrew; Ly, Emily; McKeough, Katherine; McSorley, Brianna; Miller, Catherine; Mitchell, Sean; Moon, Abbey; Moser, Kevin; O'Brien, Shane; Olivieri, Paula; Patzwahl, Aaron; Pereira, Marie; Pymento, Craig; Ramelb, Erin; Ramos, Bryce; Raya, Teresa; Riney, Stephen; Roberts, Geoff; Robertshaw, Mark; Rudolf, Frannie; Rund, Samuel; Sansone, Stephanie; Schwartz, Lindsay; Shay, Ryan; Siu, Edwin; Spear, Timothy; Tan, Catherine; Truong, Marisa; Uddin, Mairaj; Vantrieste, Jennifer; Veloz, Omar; White, Elizabeth; Porter, Forbes D; Haldar, Kasturi

    2011-01-01

    Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease.

  2. Biologically effective dose distribution based on the linear quadratic model and its clinical relevance

    SciTech Connect

    Lee, S.P.; Smathers, J.B.; Withers, H.R.

    1995-09-30

    Radiotherapy plans based on physical dose distributions do not necessarily entirely reflect the biological effects under various fractionation schemes. Over the past decade, the linear-quadratic (LQ) model has emerged as a convenient tool to quantify biological effects for radiotherapy. In this work, we set out to construct a mechanism to display biologically oriented dose distribution based on the LQ model. A computer program that converts a physical dose distribution calculated by a commercially available treatment planning system to a biologically effective dose (BED) distribution has been developed and verified against theoretical calculations. This software accepts a user`s input of biological parameters for each structure of interest (linear and quadratic dose-response and repopulation kinetic parameters), as well as treatment scheme factors (number of fractions, fractional dose, and treatment time). It then presents a two-dimensional BED display in conjunction with anatomical structures. Furthermore, to facilitate clinicians` intuitive comparison with conventional fractionation regimen, a conversion of BED to normalized isoeffective dose (NID) is also allowed. We have demonstrated the feasibility of constructing a biologically oriented dose distribution for clinical practice of radiotherapy. The discordance between physical dose distributions and the biological counterparts based on the given treatment schemes was quantified. The computerized display of BED at nonprescription points greatly enhanced the versatility of this tool. Although the routine use of this implementation in clinical radiotherapy should be cautiously done, depending largely on the accuracy of the published biological parameters, it may, nevertheless, help the clinicians derive an optimal treatment plan with a particular fractionation scheme or use it as a quantitative tool for outcome analysis in clinical research. 45 refs., 3 figs., 5 tabs.

  3. Fluent Versus Nonfluent Primary Progressive Aphasia: A Comparison of Clinical and Functional Neuroimaging Features

    ERIC Educational Resources Information Center

    Clark, D.G.; Charuvastra, A.; Miller, B.L.; Shapira, J.S.; Mendez, M.F.

    2005-01-01

    To better characterize fluent and nonfluent variants of primary progressive aphasia (PPA). Although investigators have recognized both fluent and nonfluent patients with PPA (Mesulam, 2001), the clinical and neuroimaging features of these variants have not been fully defined. We present clinical and neuropsychological data on 47 PPA patients…

  4. Progressive Magnetic Resonance Image Reconstruction Based on Iterative Solution of a Sparse Linear System

    PubMed Central

    Fahmy, Ahmed S.; Gabr, Refaat E.; Heberlein, Keith; Hu, Xiaoping P.

    2006-01-01

    Image reconstruction from nonuniformly sampled spatial frequency domain data is an important problem that arises in computed imaging. Current reconstruction techniques suffer from limitations in their model and implementation. In this paper, we present a new reconstruction method that is based on solving a system of linear equations using an efficient iterative approach. Image pixel intensities are related to the measured frequency domain data through a set of linear equations. Although the system matrix is too dense and large to solve by direct inversion in practice, a simple orthogonal transformation to the rows of this matrix is applied to convert the matrix into a sparse one up to a certain chosen level of energy preservation. The transformed system is subsequently solved using the conjugate gradient method. This method is applied to reconstruct images of a numerical phantom as well as magnetic resonance images from experimental spiral imaging data. The results support the theory and demonstrate that the computational load of this method is similar to that of standard gridding, illustrating its practical utility. PMID:23165034

  5. Mass Spectrometry for Translational Proteomics: Progress and Clinical Implications

    SciTech Connect

    Baker, Erin Shammel; Liu, Tao; Petyuk, Vladislav A.; Burnum-Johnson, Kristin E.; Ibrahim, Yehia M.; Anderson, Gordon A.; Smith, Richard D.

    2012-08-31

    Mass spectrometry (MS)-based proteomics measurements have become increasingly utilized in a wide range of biological and biomedical applications, and have significantly enhanced the understanding of the complex and dynamic nature of the proteome and its connections to biology and diseases. While some MS techniques such as those for targeted analysis are increasingly applied with great success, others such as global quantitative analysis (for e.g. biomarker discovery) are more challenging and continue to be developed and refined to provide the desired throughput, sensitivity and/ or specificity. New MS capabilities and proteomics-based pipelines/strategies also keep enhancing for the advancement of clinical proteomics applications such as protein biomarker discovery and validation. Herein, we provide a brief review to summarize the current state of MS-based proteomics with respect to its advantages and present limitations, while highlighting its potential in future clinical applications.

  6. From selection hits to clinical leads: progress in aptamer discovery

    PubMed Central

    Maier, Keith E; Levy, Matthew

    2016-01-01

    Aptamers were discovered more than 25 years ago, yet only one has been approved by the US Food and Drug Administration to date. With some noteworthy advances in their chemical design and the enzymes we use to make them, aptamers and aptamer-based therapeutics have seen a resurgence in interest. New aptamer drugs are being approved for clinical evaluation, and it is certain that we will see increasingly more aptamers and aptamer-like drugs in the future. In this review, we will discuss the production of aptamers with an emphasis on the advances and modifications that enabled early aptamers to succeed in clinical trials as well as those that are likely to be important for future generations of these drugs. PMID:27088106

  7. Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy.

    PubMed

    Detappe, Alexandre; Kunjachan, Sijumon; Sancey, Lucie; Motto-Ros, Vincent; Biancur, Douglas; Drane, Pascal; Guieze, Romain; Makrigiorgos, G Mike; Tillement, Olivier; Langer, Robert; Berbeco, Ross

    2016-09-28

    Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment. PMID:27423325

  8. Some new progress on the light absorption properties of linear alkyl benzene solvent

    NASA Astrophysics Data System (ADS)

    Yu, Guang-You; Cao, De-Wen; Huang, Ai-Zhong; Yu, Lei; Loh, Chang-Wei; Wang, Wen-Wen; Qian, Zhi-Qiang; Yang, Hai-Bo; Huang, Huang; Xu, Zong-Qiang; Zhu, Xue-Yuan; Xu, Bin; Qi, Ming

    2016-01-01

    Linear alkyl benzene (LAB) will be used as the solvent in a liquid scintillator mixture for the JUNO antineutrino experiment. Its light absorption properties should therefore be understood prior to its effective use in the experiment. Attenuation length measurements at a light wavelength of 430 nm have been performed on samples of LAB prepared for the JUNO experiment. Inorganic impurities in LAB have also been studied for their possibilities of light absorption in our wavelength of interest. In view of a tentative plan by the JUNO collaboration to utilize neutron capture with hydrogen in the detector, we also present in this work a preliminary study on the carbon-hydrogen ratio and the attenuation length of the samples. Supported by China Ministry of Science and Technology(2013CB834300)

  9. Transfinite element methodology for nonlinear/linear transient thermal modelling/analysis - Progress and recent advances

    NASA Technical Reports Server (NTRS)

    Tamma, Kumar K.; Railkar, Sudhir B.

    1988-01-01

    The 'transfinite element method' (TFEM) proposed by Tamma and Railkar (1987 and 1988) for the analysis of linear and nonlinear heat-transfer problems is described and demonstrated. The TFEM combines classical Galerkin and transform approaches with state-of-the-art FEMs to obtain a flexible hybrid modeling scheme. The fundamental principles of the TFEM and the derivation of the governing equations are reviewed, and numerical results for sample problems are presented in extensive graphs and briefly characterized. Problems analyzed include a square plate with a hole, a rectangular plate with natural and essential boundary conditions and varying thermal conductivity, the Space Shuttle thermal protection system, a bimaterial plate subjected to step temperature variations, and solidification in a semiinfinite liquid slab.

  10. Deformation Bands as Linear Elastic Fractures: Progress in Theory and Observation

    NASA Astrophysics Data System (ADS)

    Sternlof, K.; Pollard, D.

    2001-12-01

    Deformation bands (DBs) are thin, tabular, bounded features of highly localized shear and/or compaction that commonly occur as systematic and pervasive arrays in porous sandstone. They also constitute an active area of theoretical and experimental research into the compressive failure of granular materials. Based on our ongoing study of DBs in the field, we propose that they originate at stress concentrations and propagate as brittle fractures in a linear elastic medium. Furthermore, we suggest that individual DB morphology is largely dominated by the closing (anti-mode I) component of the displacement discontinuity accommodated. The notion of DBs as "anti-cracks" akin to pressure solution surfaces is not new. But close examination of real DB arrays within the unifying context of linear elastic fracture mechanics is needed to add depth and bring quantitative rigor to our understanding of the phenomenon. Thus, we are building a body of detailed data based on field observation and thin-section analysis to substantiate and expand our central hypothesis, while also laying the foundation for an effort to replicate realistic DB arrays using numerical modeling techniques. Our field effort focuses on the Jurassic Aztec Sandstone as exposed in and around the Valley of Fire State Park, Nevada. This area offers expansive and varied DB exposures within a thick and relatively consistent sequence of dune-dominated aeolian sandstone. We will present interim results, interpretations and conclusions specific to the elastic nature of DBs, in particular comparing our data to the three distinct fracture-tip models: the dislocation, and the crack with and without cohesive end zones. Each of these models predicts substantially different near-tip stress fields for the same material under the same remote loading conditions, leading to different expectations for basic DB shape, structure, and propagation and mechanical interaction behavior. These expectations will be compared to and judged

  11. Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression.

    PubMed

    Huijbers, Willem; Mormino, Elizabeth C; Schultz, Aaron P; Wigman, Sarah; Ward, Andrew M; Larvie, Mykol; Amariglio, Rebecca E; Marshall, Gad A; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A

    2015-04-01

    Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity--consistent with findings in genetic at-risk populations--and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer's disease continuum. Here, we examine the contribution of amyloid-β deposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model

  12. Progressing the utilisation of pharmacogenetics and pharmacogenomics into clinical care.

    PubMed

    Trent, Ronald J; Cheong, Pak Leng; Chua, Eng Wee; Kennedy, Martin A

    2013-06-01

    Understanding human genetic variation and how it impacts on gene function is a major focus in genomic-based research. Translation of this knowledge into clinical care is exemplified by pharmacogenetics/pharmacogenomics. The identification of particular gene variants that might influence drug uptake, metabolism, distribution or excretion promises a more effective personalised medicine approach in choosing the right drug or its dose for any particular individual. Adverse drug responses can then be avoided or mitigated. An understanding of germline or acquired (somatic) DNA mutations can also be used to identify drugs that are more likely to be therapeutically beneficial. This represents an area of growing interest in the treatment of cancer.

  13. [Progress of low-energy shockwave therapy in clinical application].

    PubMed

    Xin, Zhong-cheng; Liu, Jing; Wang, Lin; Li, Hui-xi

    2013-08-18

    A shock wave is a transient pressure disturbance that propagates rapidly in three-dimensional space. It is associated with a sudden rise from ambient pressure to its maximum pressure. Shock wave therapy in urology is primarily used to disintegrate urolithiasis. Recently, low-energy shock wave therapy (LESWT), which is a novel convenient and cost-effective therapeutic modality, is extended to treat other pathological conditions including coronary heart disease, musculoskeletal disorders and erectile dysfunction. However, the exact therapeutic mechanisms and clinical safety and efficacy of LESWT remain to be investigated. Based on the results of previous studies, it is suggested that LESWT could regulate angiogenesis-related growth factors expression including endothelial nitric oxide synthase (eNOS), vessel endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA), which might induce the ingrowth of neovascularization that improves blood supply and increases cell proliferation and eventual tissue regeneration for restore pathological changes. The further studies on cellular and molecular biological changes by LESWT for clarification its mechanism and clinical safety and efficacy studies are recommended.

  14. Advancing Clostridia to Clinical Trial: Past Lessons and Recent Progress

    PubMed Central

    Mowday, Alexandra M.; Guise, Christopher P.; Ackerley, David F.; Minton, Nigel P.; Lambin, Philippe; Dubois, Ludwig J.; Theys, Jan; Smaill, Jeff B.; Patterson, Adam V.

    2016-01-01

    Most solid cancers contain regions of necrotic tissue. The extent of necrosis is associated with poor survival, most likely because it reflects aggressive tumour outgrowth and inflammation. Intravenously injected spores of anaerobic bacteria from the genus Clostridium infiltrate and selectively germinate in these necrotic regions, providing cancer-specific colonisation. The specificity of this system was first demonstrated over 60 years ago and evidence of colonisation has been confirmed in multiple tumour models. The use of “armed” clostridia, such as in Clostridium Directed Enzyme Prodrug Therapy (CDEPT), may help to overcome some of the described deficiencies of using wild-type clostridia for treatment of cancer, such as tumour regrowth from a well-vascularised outer rim of viable cells. Successful preclinical evaluation of a transferable gene that metabolises both clinical stage positron emission tomography (PET) imaging agents (for whole body vector visualisation) as well as chemotherapy prodrugs (for conditional enhancement of efficacy) would be a valuable early step towards the prospect of “armed” clostridia entering clinical evaluation. The ability to target the immunosuppressive hypoxic tumour microenvironment using CDEPT may offer potential for synergy with recently developed immunotherapy strategies. Ultimately, clostridia may be most efficacious when combined with conventional therapies, such as radiotherapy, that sterilise viable aerobic tumour cells. PMID:27367731

  15. Pig Liver Xenotransplantation: A Review of Progress Toward the Clinic.

    PubMed

    Cooper, David K C; Dou, Ke-Feng; Tao, Kai-Shan; Yang, Zhao-Xu; Tector, A Joseph; Ekser, Burcin

    2016-10-01

    Experience with clinical liver xenotransplantation has largely involved the transplantation of livers from nonhuman primates. Experience with pig livers has been scarce. This brief review will be restricted to assessing the potential therapeutic impact of pig liver xenotransplantation in acute liver failure and the remaining barriers that currently do not justify clinical trials. A relatively new surgical technique of heterotopic pig liver xenotransplantation is described that might play a role in bridging a patient with acute liver failure until either the native liver recovers or a suitable liver allograft is obtained. Other topics discussed include the possible mechanisms for the development of the thrombocytopenis that rapidly occurs after pig liver xenotransplantation in a primate, the impact of pig complement on graft injury, the potential infectious risks, and potential physiologic incompatibilities between pig and human. There is cautious optimism that all of these problems can be overcome by judicious genetic manipulation of the pig. If liver graft survival could be achieved in the absence of thrombocytopenia or rejection for a period of even a few days, there may be a role for pig liver transplantation as a bridge to allotransplantation in carefully selected patients.

  16. Interventional multispectral photoacoustic imaging with a clinical linear array ultrasound probe for guiding nerve blocks

    NASA Astrophysics Data System (ADS)

    Xia, Wenfeng; West, Simeon J.; Nikitichev, Daniil I.; Ourselin, Sebastien; Beard, Paul C.; Desjardins, Adrien E.

    2016-03-01

    Accurate identification of tissue structures such as nerves and blood vessels is critically important for interventional procedures such as nerve blocks. Ultrasound imaging is widely used as a guidance modality to visualize anatomical structures in real-time. However, identification of nerves and small blood vessels can be very challenging, and accidental intra-neural or intra-vascular injections can result in significant complications. Multi-spectral photoacoustic imaging can provide high sensitivity and specificity for discriminating hemoglobin- and lipid-rich tissues. However, conventional surface-illumination-based photoacoustic systems suffer from limited sensitivity at large depths. In this study, for the first time, an interventional multispectral photoacoustic imaging (IMPA) system was used to image nerves in a swine model in vivo. Pulsed excitation light with wavelengths in the ranges of 750 - 900 nm and 1150 - 1300 nm was delivered inside the body through an optical fiber positioned within the cannula of an injection needle. Ultrasound waves were received at the tissue surface using a clinical linear array imaging probe. Co-registered B-mode ultrasound images were acquired using the same imaging probe. Nerve identification was performed using a combination of B-mode ultrasound imaging and electrical stimulation. Using a linear model, spectral-unmixing of the photoacoustic data was performed to provide image contrast for oxygenated and de-oxygenated hemoglobin, water and lipids. Good correspondence between a known nerve location and a lipid-rich region in the photoacoustic images was observed. The results indicate that IMPA is a promising modality for guiding nerve blocks and other interventional procedures. Challenges involved with clinical translation are discussed.

  17. Recent progress and clinical importance on pharmacogenetics in cancer therapy

    PubMed Central

    Soh, Thomas I Peng; Yong, Wei Peng; Innocenti, Federico

    2013-01-01

    Recent advances have provided unprecedented opportunities to identify prognostic and predictive markers of efficacy of cancer therapy. Genetic markers can be used to exclude patients who will not benefit from therapy, exclude patients at high risk of severe toxicity, and adjust dosing. Genomic approaches for marker discovery now include genome-wide association studies and tumor DNA sequencing. The challenge is now to select markers for which there is enough evidence to transition them to the clinic. The hurdles include the inherent low frequency of many of these markers, the lengthy validation process through trials, as well as legislative and economic hurdles. Attempts to answer questions about certain markers more quickly have led to an increased popularity of trials with enrichment design, especially in the light of the dramatic phase I results seen in recent months. Personalized medicine in oncology is a step closer to reality. PMID:21950596

  18. TWEAK and the progression of renal disease: clinical translation.

    PubMed

    Sanz, Ana B; Izquierdo, M Concepcion; Sanchez-Niño, Maria Dolores; Ucero, Alvaro C; Egido, Jesus; Ruiz-Ortega, Marta; Ramos, Adrián Mario; Putterman, Chaim; Ortiz, Alberto

    2014-02-01

    Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) activates the fibroblast growth factor-inducible-14 (Fn14) receptor. TWEAK has actions on intrinsic kidney cells and on inflammatory cells of potential pathophysiological relevance. The effects of TWEAK in tubular cells have been explored in most detail. In cultured murine tubular cells TWEAK induces the expression of inflammatory cytokines, downregulates the expression of Klotho, is mitogenic, and in the presence of sensitizing agents promotes apoptosis. Similar actions were observed on glomerular mesangial cells. In vivo TWEAK actions on healthy kidneys mimic cell culture observations. Increased expression of TWEAK and Fn14 was reported in human and experimental acute and chronic kidney injury. The role of TWEAK/Fn14 in kidney injury has been demonstrated in non-inflammatory compensatory renal growth, acute kidney injury and chronic kidney disease of immune and non-immune origin, including hyperlipidaemic nephropathy, lupus nephritis (LN) and anti-GBM nephritis. The nephroprotective effect of TWEAK or Fn14 targeting in immune-mediated kidney injury is the result of protection from TWEAK-induced injury of renal intrinsic cells, not from interference with the immune response. A phase I dose-ranging clinical trial demonstrated the safety of anti-TWEAK antibodies in humans. A phase II randomized placebo-controlled clinical trial exploring the efficacy, safety and tolerability of neutralizing anti-TWEAK antibodies as a tissue protection strategy in LN is ongoing. The eventual success of this trial may expand the range of kidney diseases in which TWEAK targeting should be explored.

  19. Microphthalmia with linear skin defects (MLS) syndrome: Clinical, cytogenetic, and molecular characterization

    SciTech Connect

    Lindsay, E.A.; Grillo, A.; Ferrero, G.B.; Baldini, A.; Ballabio, A.; Zoghbi, H.Y.; Roth, E.J.; Magenis, E.; Grompe, M.; Hulten, M.

    1994-01-15

    The microphthalmia with linear skin defects (MLS) syndrome (MIM309801) is a severe developmental disorder observed in XX individuals with distal Xp segmental monosomy. The phenotype of this syndrome overlaps with that of both Aicardi (MIM 305050) and Goltz (MIM 305600) syndromes, two X-linked dominant, male-lethal disorders. Here the authors report the clinical, cytogenetic, and molecular characterization of 3 patients with this syndrome. Two of these patients are females with a terminal Xpter-p22.2 deletion. One of these 2 patients had an aborted fetus with anencephaly and the same chromosome abnormality. The third patient is an XX male with Xp/Yp exchange spanning the SRY gene which results in distal Xp monosomy. The extensive clinical variability observed in these patients and the results of the molecular analysis suggest that X-inactivation plays an important role in determining the phenotype of the MLS syndrome. The authors propose that the MLS, Aicardi, and Goltz syndromes are due to the involvement of the same gene(s), and that different patterns of X-inactivation are responsible for the phenotypic differences observed in these 3 disorders. However, they cannot rule out that each component of the MLS phenotype is caused by deletion of a different gene (a contiguous gene syndrome). 24 refs., 4 figs., 1 tab.

  20. Plasma HIV-1 tropism and risk of short-term clinical progression to AIDS or death

    PubMed Central

    Casadellà Fontdevila, Maria; Cozzi-Lepri, Alessandro; Phillips, Andrew; Noguera Julian, Marc; Bickel, Marcus; Sedlacek, Dalibor; Kronborg, Gitte; Lazzarin, Adriano; Zilmer, Kai; Clotet, Bonaventura; Lundgren, Jens D; Paredes, Roger

    2014-01-01

    Introduction It is uncertain if plasma HIV-1 tropism is an independent predictor of short-term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case-control study within EuroSIDA to assess this question amongst people with current HIV RNA level >1000 copies/mL, including both people on ART and those ART naïve. Methods People with an AIDS diagnosis or who died from any causes for whom there was a stored plasma sample with HIV-1 RNA (VL)≥1,000 copies/mL available in the time window of 3–12 months prior to the event were identified. At least one control was selected for each case matched for age, VL and HCV status at the time of sampling. Controls were event-free after a matched duration of time from the date of sampling. Plasma HIV tropism was estimated using 454 and population sequencing (PS). Non-R5 HIV was defined as: (a) ≥2% of sequences with a Geno2Pheno (G2P) FPR≤3.75% by 454, and (b) a G2P FPR≤10% by PS. We also compared CD4 slopes over the 12 months following the date of sampling using a linear mixed model with random intercept according to HIV tropism and ART status. Results The study included 266 subjects, 100 cases and 166 controls, with sample taken on average in 2006; 23% and 24% had non-R5 HIV by 454 and PS respectively. There were 19% women, 25% MSM, 92% Caucasians, 22% HCV+. At the time of sampling, 26% were ART-naïve, 25% had started but were off ART and 49% were receiving ART. The median age, CD4 and viral load was 41 years, 350 cells/mm3 and 4.81 log c/mL, respectively. Baseline characteristics were well balanced by tropism. Factors independently associated with clinical progression or death were female gender (OR=2.12; 95% CI=1.04, 4.36; p=0.038), CD4+ count (OR=0.90 per 100 cells/mm3 higher; 95% CI 0.80, 1.00; p=0.058), being on ART (OR=2.72; 95% CI 1.15, 6.41; p=0.022) and calendar year of sample (OR=0.84 per more recent year; 95% CI=0.77, 0.91; p<0.001). Baseline plasma

  1. 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

  2. Non-progressive cerebellar ataxia and previous undetermined acute cerebellar injury: a mysterious clinical condition.

    PubMed

    Pinto, Wladimir Bocca Vieira de Rezende; Pedroso, José Luiz; Souza, Paulo Victor Sgobbi de; Albuquerque, Marcus Vinícius Cristino de; Barsottini, Orlando Graziani Povoas

    2015-10-01

    Cerebellar ataxias represent a wide group of neurological diseases secondary to dysfunctions of cerebellum or its associated pathways, rarely coursing with acute-onset acquired etiologies and chronic non-progressive presentation. We evaluated patients with acquired non-progressive cerebellar ataxia that presented previous acute or subacute onset. Clinical and neuroimaging characterization of adult patients with acquired non-progressive ataxia were performed. Five patients were identified with the phenotype of acquired non-progressive ataxia. Most patients presented with a juvenile to adult-onset acute to subacute appendicular and truncal cerebellar ataxia with mild to moderate cerebellar or olivopontocerebellar atrophy. Establishing the etiology of the acute triggering events of such ataxias is complex. Non-progressive ataxia in adults must be distinguished from hereditary ataxias.

  3. Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.

    PubMed

    van der Crabben, Saskia N; Harakalova, Magdalena; Brilstra, Eva H; van Berkestijn, Frédérique M C; Hofstede, Floris C; van Vught, Adrianus J; Cuppen, Edwin; Kloosterman, Wigard; Ploos van Amstel, Hans Kristian; van Haaften, Gijs; van Haelst, Mieke M

    2014-01-01

    Phosphatidyl inositol glycan (PIG) enzyme subclasses are involved in distinct steps of glycosyl phosphatidyl inositol anchor protein biosynthesis. Glycolsyl phosphatidyl inositol-anchored proteins have heterogeneous functions; they can function as enzymes, adhesion molecules, complement regulators and co-receptors in signal transduction pathways. Germline mutations in genes encoding different members of the PIG family result in diverse conditions with (severe) developmental delay, (neonatal) seizures, hypotonia, CNS abnormalities, growth abnormalities, and congenital abnormalities as hallmark features. The variability of clinical features resembles the typical diversity of other glycosylation pathway deficiencies such as the congenital disorders of glycosylation. Here, we report the first germline missense mutation in the PIGA gene associated with accelerated linear growth, obesity, central hypotonia, severe refractory epilepsy, cardiac anomalies, mild facial dysmorphic features, mildly elevated alkaline phosphatase levels, and CNS anomalies consisting of progressive cerebral atrophy, insufficient myelinization, and cortical MRI signal abnormalities. X-exome sequencing in the proband identified a c.278C>T (p.Pro93Leu) mutation in the PIGA gene. The mother and maternal grandmother were unaffected carriers and the mother showed 100% skewing of the X-chromosome harboring the mutation. These results together with the clinical similarity of the patient reported here and the previously reported patients with a germline nonsense mutation in PIGA support the determination that this mutation caused the phenotype in this family.

  4. Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.

    PubMed

    van der Crabben, Saskia N; Harakalova, Magdalena; Brilstra, Eva H; van Berkestijn, Frédérique M C; Hofstede, Floris C; van Vught, Adrianus J; Cuppen, Edwin; Kloosterman, Wigard; Ploos van Amstel, Hans Kristian; van Haaften, Gijs; van Haelst, Mieke M

    2014-01-01

    Phosphatidyl inositol glycan (PIG) enzyme subclasses are involved in distinct steps of glycosyl phosphatidyl inositol anchor protein biosynthesis. Glycolsyl phosphatidyl inositol-anchored proteins have heterogeneous functions; they can function as enzymes, adhesion molecules, complement regulators and co-receptors in signal transduction pathways. Germline mutations in genes encoding different members of the PIG family result in diverse conditions with (severe) developmental delay, (neonatal) seizures, hypotonia, CNS abnormalities, growth abnormalities, and congenital abnormalities as hallmark features. The variability of clinical features resembles the typical diversity of other glycosylation pathway deficiencies such as the congenital disorders of glycosylation. Here, we report the first germline missense mutation in the PIGA gene associated with accelerated linear growth, obesity, central hypotonia, severe refractory epilepsy, cardiac anomalies, mild facial dysmorphic features, mildly elevated alkaline phosphatase levels, and CNS anomalies consisting of progressive cerebral atrophy, insufficient myelinization, and cortical MRI signal abnormalities. X-exome sequencing in the proband identified a c.278C>T (p.Pro93Leu) mutation in the PIGA gene. The mother and maternal grandmother were unaffected carriers and the mother showed 100% skewing of the X-chromosome harboring the mutation. These results together with the clinical similarity of the patient reported here and the previously reported patients with a germline nonsense mutation in PIGA support the determination that this mutation caused the phenotype in this family. PMID:24259184

  5. Seizures during the management of high-grade gliomas: clinical relevance to disease progression.

    PubMed

    Kim, Young-Hoon; Park, Chul-Kee; Kim, Tae Min; Choi, Seung Hong; Kim, Yu Jung; Choi, Byung Se; Han, Jung Ho; Lee, Se-Hoon; Kim, Chae-Yong; Kim, In Ah; Heo, Dae Seog; Kim, Il Han; Kim, Dong Gyu; Jung, Hee-Won

    2013-05-01

    This study was performed to evaluate the incidence of seizures with its implications on disease progression and the diagnostic value of post-ictal magnetic resonance images (MRI) during the management of high-grade gliomas (HGGs). A total of 406 consecutive patients with newly diagnosed HGGs were retrospectively reviewed. The incidence of seizures during the management was investigated. In patients who experienced a seizure, the causality between seizures and disease progression was assessed by pre-ictal, post-ictal (<1 month), and follow-up (<3 months) MRI. After a median follow-up of 17.4 months (range 0.1-88.3), seizures developed in 127 patients (31 %). Of the 127 patients, radiological progression at the post-ictal MRI was found in 83 patients (65 %) and the follow-up MRI confirmed progression in 79 patients (62 %). Four other patients (3 %) were shown to be progression-free. Among those without radiological progression at the post-ictal MRI, the follow-up MRI confirmed progression-free in 31 patients (24 %); however, 13 patients (10 %) revealed eventual progression. In the patients with a seizure, absence of preoperative seizures (p = 0.003), <95 % tumor resection (p = 0.001), and pre-ictal Karnofsky Performance Scale score ≤ 70 (p = 0.025) were significantly associated with disease progression. During the management of HGG, 31 % of patients experienced seizures; of these patients, 72 % harbored progressive disease. The post-ictal MRI is useful for detecting disease progression; however, there are pitfalls. Clinical settings should be considered together for diagnosing disease progression in patients with seizures.

  6. [Top ten progressions of clinical research in fundus diseases in China].

    PubMed

    2014-11-01

    Ten research items in the past five years representing the progression of clinical research in fundus diseases in China were voted by specialists from the Ocular Fundus Disease Group of Ophthalmology Society of Chinese Medical Association. Choroidal neovascular disease, pediatric retinal disease, polypoidal choroidal vasculopathy, intraocular malignant tumor, and intraocular infection caused by specific pathogens are covered. Novel treatment, like anti-VEGF medication, PDT, minimally invasive vitrectomy, and intraocular injection, establishment of the Clinical Research Center of New Drug Development, and the epidemiologic study of fundus diseases are also included. These landmark research progressions represent the power and influence of Chinese fundus disease scholars in the world.

  7. A Probabilistic Reasoning Method for Predicting the Progression of Clinical Findings from Electronic Medical Records

    PubMed Central

    Goodwin, Travis; Harabagiu, Sanda M.

    2015-01-01

    In this paper, we present a probabilistic reasoning method capable of generating predictions of the progression of clinical findings (CFs) reported in the narrative portion of electronic medical records. This method benefits from a probabilistic knowledge representation made possible by a graphical model. The knowledge encoded in the graphical model considers not only the CFs extracted from the clinical narratives, but also their chronological ordering (CO) made possible by a temporal inference technique described in this paper. Our experiments indicate that the predictions about the progression of CFs achieve high performance given the COs induced from patient records. PMID:26306238

  8. Parallel linear dynamic models can mimic the McGurk effect in clinical populations.

    PubMed

    Altieri, Nicholas; Yang, Cheng-Ta

    2016-10-01

    One of the most common examples of audiovisual speech integration is the McGurk effect. As an example, an auditory syllable /ba/ recorded over incongruent lip movements that produce "ga" typically causes listeners to hear "da". This report hypothesizes reasons why certain clinical and listeners who are hard of hearing might be more susceptible to visual influence. Conversely, we also examine why other listeners appear less susceptible to the McGurk effect (i.e., they report hearing just the auditory stimulus without being influenced by the visual). Such explanations are accompanied by a mechanistic explanation of integration phenomena including visual inhibition of auditory information, or slower rate of accumulation of inputs. First, simulations of a linear dynamic parallel interactive model were instantiated using inhibition and facilitation to examine potential mechanisms underlying integration. In a second set of simulations, we systematically manipulated the inhibition parameter values to model data obtained from listeners with autism spectrum disorder. In summary, we argue that cross-modal inhibition parameter values explain individual variability in McGurk perceptibility. Nonetheless, different mechanisms should continue to be explored in an effort to better understand current data patterns in the audiovisual integration literature. PMID:27272510

  9. Purse-String Versus Linear Conventional Skin Wound Closure of an Ileostomy: A Randomized Clinical Trial

    PubMed Central

    Alvandipour, Mina; Gharedaghi, Babak; Khodabakhsh, Hamed

    2016-01-01

    Purpose Infection is one of the most frequent complications that can occur after ileostomy closure. The incidence of wound infection depends on the skin closure technique, but there is no agreement on the perfect closure method for an ileostomy wound. The aim of this study was to evaluate the incidence of infection, the patient's approval, and the patient's pain between purse-string closure (PSC) and the usual linear closure (LC) of a stoma wound. Methods This randomized clinical trial enrolled 66 patients who underwent a stoma closure from February 2015 to May 2015 in Sari Emam Khomeini Hospital. Patients were divided into 2 groups according to the stoma closing method: the PSC group (n = 34) and the LC group (n = 32). The incidences of infection for the 2 groups were compared, and the patients' satisfaction and pain with the stoma were determined by using a questionnaire. Results Infection occurred in 1 of 34 PSC patients (2.9%) and in 7 of 32 LC patients (21.8%), and this difference was statistically significant (P = 0.021). Patients in the PSC group were more satisfied with the resulting wound scar and its cosmetic appearance at one month and three months after surgery (P = 0.043). Conclusion After stoma closure, PSC was associated with a significantly lower incidence of wound infection and greater patient satisfaction compared to LC. However, the healing period for patients who underwent PSC was longer than it was for those who underwent LC. PMID:27626025

  10. Purse-String Versus Linear Conventional Skin Wound Closure of an Ileostomy: A Randomized Clinical Trial

    PubMed Central

    Alvandipour, Mina; Gharedaghi, Babak; Khodabakhsh, Hamed

    2016-01-01

    Purpose Infection is one of the most frequent complications that can occur after ileostomy closure. The incidence of wound infection depends on the skin closure technique, but there is no agreement on the perfect closure method for an ileostomy wound. The aim of this study was to evaluate the incidence of infection, the patient's approval, and the patient's pain between purse-string closure (PSC) and the usual linear closure (LC) of a stoma wound. Methods This randomized clinical trial enrolled 66 patients who underwent a stoma closure from February 2015 to May 2015 in Sari Emam Khomeini Hospital. Patients were divided into 2 groups according to the stoma closing method: the PSC group (n = 34) and the LC group (n = 32). The incidences of infection for the 2 groups were compared, and the patients' satisfaction and pain with the stoma were determined by using a questionnaire. Results Infection occurred in 1 of 34 PSC patients (2.9%) and in 7 of 32 LC patients (21.8%), and this difference was statistically significant (P = 0.021). Patients in the PSC group were more satisfied with the resulting wound scar and its cosmetic appearance at one month and three months after surgery (P = 0.043). Conclusion After stoma closure, PSC was associated with a significantly lower incidence of wound infection and greater patient satisfaction compared to LC. However, the healing period for patients who underwent PSC was longer than it was for those who underwent LC.

  11. Gene therapy for inborn errors of liver metabolism: progress towards clinical applications

    PubMed Central

    Brunetti-Pierri, Nicola

    2008-01-01

    The treatment for inborn errors of liver metabolism is based on dietary, drug, and cell therapies (orthotopic liver transplantation). However, significant morbidity and mortality still remain, and alternative strategies are needed. Gene replacement therapy has the potential of providing a definitive cure for patients with these diseases. Significant progress has been made in the pre-clinical arena and achievement of efficacy in different animal models has been reported using multiple gene transfer technologies. This article summarizes the gene transfer strategies being investigated, the pre-clinical data, and the available early clinical results for inborn errors of liver metabolism. PMID:19490653

  12. Robust Classification and Segmentation of Planar and Linear Features for Construction Site Progress Monitoring and Structural Dimension Compliance Control

    NASA Astrophysics Data System (ADS)

    Maalek, R.; Lichti, D. D.; Ruwanpura, J.

    2015-08-01

    The application of terrestrial laser scanners (TLSs) on construction sites for automating construction progress monitoring and controlling structural dimension compliance is growing markedly. However, current research in construction management relies on the planned building information model (BIM) to assign the accumulated point clouds to their corresponding structural elements, which may not be reliable in cases where the dimensions of the as-built structure differ from those of the planned model and/or the planned model is not available with sufficient detail. In addition outliers exist in construction site datasets due to data artefacts caused by moving objects, occlusions and dust. In order to overcome the aforementioned limitations, a novel method for robust classification and segmentation of planar and linear features is proposed to reduce the effects of outliers present in the LiDAR data collected from construction sites. First, coplanar and collinear points are classified through a robust principal components analysis procedure. The classified points are then grouped using a robust clustering method. A method is also proposed to robustly extract the points belonging to the flat-slab floors and/or ceilings without performing the aforementioned stages in order to preserve computational efficiency. The applicability of the proposed method is investigated in two scenarios, namely, a laboratory with 30 million points and an actual construction site with over 150 million points. The results obtained by the two experiments validate the suitability of the proposed method for robust segmentation of planar and linear features in contaminated datasets, such as those collected from construction sites.

  13. Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention.

    PubMed

    Zhang, Yanhang; Barocas, Victor H; Berceli, Scott A; Clancy, Colleen E; Eckmann, David M; Garbey, Marc; Kassab, Ghassan S; Lochner, Donna R; McCulloch, Andrew D; Tran-Son-Tay, Roger; Trayanova, Natalia A

    2016-09-01

    Cardiovascular diseases (CVDs) are the leading cause of death in the western world. With the current development of clinical diagnostics to more accurately measure the extent and specifics of CVDs, a laudable goal is a better understanding of the structure-function relation in the cardiovascular system. Much of this fundamental understanding comes from the development and study of models that integrate biology, medicine, imaging, and biomechanics. Information from these models provides guidance for developing diagnostics, and implementation of these diagnostics to the clinical setting, in turn, provides data for refining the models. In this review, we introduce multi-scale and multi-physical models for understanding disease development, progression, and designing clinical interventions. We begin with multi-scale models of cardiac electrophysiology and mechanics for diagnosis, clinical decision support, personalized and precision medicine in cardiology with examples in arrhythmia and heart failure. We then introduce computational models of vasculature mechanics and associated mechanical forces for understanding vascular disease progression, designing clinical interventions, and elucidating mechanisms that underlie diverse vascular conditions. We conclude with a discussion of barriers that must be overcome to provide enhanced insights, predictions, and decisions in pre-clinical and clinical applications.

  14. Assessing progression of clinical reasoning through virtual patients: An exploratory study.

    PubMed

    Forsberg, Elenita; Ziegert, Kristina; Hult, Håkan; Fors, Uno

    2016-01-01

    To avoid test-driven learning, there have been discussions regarding the use of more formative assessments in health care education to promote students' deep learning. Feedback is important in formative assessment, but many students ignore it; therefore, interventions should be introduced which stimulate them to reflect on the new knowledge. The aim for this study was to explore if Virtual Patient (VP)-based formative assessments, in connection with self-evaluations, had an impact on postgraduate pediatric nursing students' development of clinical reasoning abilities. Students' self-evaluations served as the basis for measuring progress. Data was analysed using deductive content analysis. The findings showed a clear progression of the clinical reasoning ability of the students. After the first assessment, the students described feelings of uncertainty and that their knowledge gaps were exposed. At the mid-course assessment the awareness of improved clinical reasoning was obvious and the students were more certain of knowing how to solve the VP cases. In the final assessment, self-efficacy was expressed. VP-based assessments, in connection with self-evaluations, early in the education resulted in a gain of students' own identification of the concept of clinical reasoning, awareness of what to focus on during clinical practice and visualised expected clinical competence.

  15. HIV-1 Genetic Variability in Cuba and Implications for Transmission and Clinical Progression.

    PubMed

    Blanco, Madeline; Machado, Liuber Y; Díaz, Héctor; Ruiz, Nancy; Romay, Dania; Silva, Eladio

    2015-10-01

    INTRODUCTION Serological and molecular HIV-1 studies in Cuba have shown very low prevalence of seropositivity, but an increasing genetic diversity attributable to introduction of many HIV-1 variants from different areas, exchange of such variants among HIV-positive people with several coinciding routes of infection and other epidemiologic risk factors in the seropositive population. The high HIV-1 genetic variability observed in Cuba has possible implications for transmission and clinical progression. OBJECTIVE Study genetic variability for the HIV-1 env, gag and pol structural genes in Cuba; determine the prevalence of B and non-B subtypes according to epidemiologic and behavioral variables and determine whether a relationship exists between genetic variability and transmissibility, and between genetic variability and clinical disease progression in people living with HIV/AIDS. METHODS Using two molecular assays (heteroduplex mobility assay and nucleic acid sequencing), structural genes were characterized in 590 people with HIV-1 (480 men and 110 women), accounting for 3.4% of seropositive individuals in Cuba as of December 31, 2013. Nonrandom sampling, proportional to HIV prevalence by province, was conducted. Relationships between molecular results and viral factors, host characteristics, and patients' clinical, epidemiologic and behavioral variables were studied for molecular epidemiology, transmission, and progression analyses. RESULTS Molecular analysis of the three HIV-1 structural genes classified 297 samples as subtype B (50.3%), 269 as non-B subtypes (45.6%) and 24 were not typeable. Subtype B prevailed overall and in men, mainly in those who have sex with men. Non-B subtypes were prevalent in women and heterosexual men, showing multiple circulating variants and recombinant forms. Sexual transmission was the predominant form of infection for all. B and non-B subtypes were encountered throughout Cuba. No association was found between subtypes and

  16. Potential Clinical Value of Multiparametric PET in the Prediction of Alzheimer’s Disease Progression

    PubMed Central

    Chen, Xueqi; Zhou, Yun; Wang, Rongfu; Cao, Haoyin; Reid, Savina; Gao, Rui; Han, Dong

    2016-01-01

    Objective To evaluate the potential clinical value of quantitative functional FDG PET and pathological amyloid-β PET with cerebrospinal fluid (CSF) biomarkers and clinical assessments in the prediction of Alzheimer’s disease (AD) progression. Methods We studied 82 subjects for up to 96 months (median = 84 months) in a longitudinal Alzheimer’s Disease Neuroimaging Initiative (ADNI) project. All preprocessed PET images were spatially normalized to standard Montreal Neurologic Institute space. Regions of interest (ROI) were defined on MRI template, and standard uptake values ratios (SUVRs) to the cerebellum for FDG and amyloid-β PET were calculated. Predictive values of single and multiparametric PET biomarkers with and without clinical assessments and CSF biomarkers for AD progression were evaluated using receiver operating characteristic (ROC) analysis and logistic regression model. Results The posterior precuneus and cingulate SUVRs were identified for both FDG and amyloid-β PET in predicating progression in normal controls (NCs) and subjects with mild cognitive impairment (MCI). FDG parietal and lateral temporal SUVRs were suggested for monitoring NCs and MCI group progression, respectively. 18F-AV45 global cortex attained (78.6%, 74.5%, 75.4%) (sensitivity, specificity, accuracy) in predicting NC progression, which is comparable to the 11C-PiB global cortex SUVR’s in predicting MCI to AD. A logistic regression model to combine FDG parietal and posterior precuneus SUVR and Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) Total Mod was identified in predicating NC progression with (80.0%, 94.9%, 93.9%) (sensitivity, specificity, accuracy). The selected model including FDG posterior cingulate SUVR, ADAS-Cog Total Mod, and Mini-Mental State Exam (MMSE) scores for predicating MCI to AD attained (96.4%, 81.2%, 83.6%) (sensitivity, specificity, accuracy). 11C-PiB medial temporal SUVR with MMSE significantly increased 11C-PiB PET AUC to 0.915 (p<0

  17. Progressing a human embryonic stem-cell-based regenerative medicine therapy towards the clinic

    PubMed Central

    Whiting, Paul; Kerby, Julie; Coffey, Peter; da Cruz, Lyndon; McKernan, Ruth

    2015-01-01

    Since the first publication of the derivation of human embryonic stem cells in 1998, there has been hope and expectation that this technology will lead to a wave of regenerative medicine therapies with the potential to revolutionize our approach to managing certain diseases. Despite significant resources in this direction, the path to the clinic for an embryonic stem-cell-based regenerative medicine therapy has not proven straightforward, though in the past few years progress has been made. Here, with a focus upon retinal disease, we discuss the current status of the development of such therapies. We also highlight some of our own experiences of progressing a retinal pigment epithelium cell replacement therapy towards the clinic. PMID:26416684

  18. Cancer imaging by optical coherence tomography: preclinical progress and clinical potential.

    PubMed

    Vakoc, Benjamin J; Fukumura, Dai; Jain, Rakesh K; Bouma, Brett E

    2012-05-01

    The past decade has seen dramatic technological advances in the field of optical coherence tomography (OCT) imaging. These advances have driven commercialization and clinical adoption in ophthalmology, cardiology and gastrointestinal cancer screening. Recently, an array of OCT-based imaging tools that have been developed for preclinical intravital cancer imaging applications has yielded exciting new capabilities to probe and to monitor cancer progression and response in vivo. Here, we review these results, forecast the future of OCT for preclinical cancer imaging and discuss its exciting potential to translate to the clinic as a tool for monitoring cancer therapy.

  19. Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma

    PubMed Central

    McGuire, Mary F.; Iyengar, M. Sriram; Mercer, David W.

    2012-01-01

    Motivation Although trauma is the leading cause of death for those below 45 years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. Results In the node/molecular analysis of the first 24 hours from trauma, PSA uncovered 7 molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which 3 molecules had not been previously associated with any shock / trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships – activation, expression, inhibition, and transcription – and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on

  20. Crowdsourced analysis of clinical trial data to predict amyotrophic lateral sclerosis progression.

    PubMed

    Küffner, Robert; Zach, Neta; Norel, Raquel; Hawe, Johann; Schoenfeld, David; Wang, Liuxia; Li, Guang; Fang, Lilly; Mackey, Lester; Hardiman, Orla; Cudkowicz, Merit; Sherman, Alexander; Ertaylan, Gokhan; Grosse-Wentrup, Moritz; Hothorn, Torsten; van Ligtenberg, Jules; Macke, Jakob H; Meyer, Timm; Schölkopf, Bernhard; Tran, Linh; Vaughan, Rubio; Stolovitzky, Gustavo; Leitner, Melanie L

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with substantial heterogeneity in its clinical presentation. This makes diagnosis and effective treatment difficult, so better tools for estimating disease progression are needed. Here, we report results from the DREAM-Phil Bowen ALS Prediction Prize4Life challenge. In this crowdsourcing competition, competitors developed algorithms for the prediction of disease progression of 1,822 ALS patients from standardized, anonymized phase 2/3 clinical trials. The two best algorithms outperformed a method designed by the challenge organizers as well as predictions by ALS clinicians. We estimate that using both winning algorithms in future trial designs could reduce the required number of patients by at least 20%. The DREAM-Phil Bowen ALS Prediction Prize4Life challenge also identified several potential nonstandard predictors of disease progression including uric acid, creatinine and surprisingly, blood pressure, shedding light on ALS pathobiology. This analysis reveals the potential of a crowdsourcing competition that uses clinical trial data for accelerating ALS research and development. PMID:25362243

  1. Modeling progression risk for smoldering multiple myeloma: results from a prospective clinical study.

    PubMed

    Cherry, Benjamin M; Korde, Neha; Kwok, Mary; Manasanch, Elisabet E; Bhutani, Manisha; Mulquin, Marcia; Zuchlinski, Diamond; Yancey, Mary Ann; Maric, Irina; Calvo, Katherine R; Braylan, Raul; Stetler-Stevenson, Maryalice; Yuan, Constance; Tembhare, Prashant; Zingone, Adriana; Costello, Rene; Roschewski, Mark J; Landgren, Ola

    2013-10-01

    The risk of progression to multiple myeloma (MM) from the precursor condition smoldering MM (SMM) varies considerably among individual patients. Reliable markers for progression to MM are vital to advance the understanding of myeloma precursor disease and for the development of intervention trials designed to delay/prevent MM. The Mayo Clinic and Spanish PETHEMA have proposed models to stratify patient risk based on clinical parameters. The aim of our study was to define the degree of concordance between these two models by comparing the distribution of patients with SMM classified as low, medium and high risk for progression. A total of 77 patients with SMM were enrolled in our prospective natural history study. Per study protocol, each patient was assigned risk scores based on both the Mayo and the Spanish models. The Mayo Clinic model identified 38, 35 and four patients as low, medium and high risk, respectively. The Spanish PETHEMA model classified 17, 22 and 38 patients as low, medium and high risk, respectively. There was significant discordance in overall patient risk classification (28.6% concordance) and in classifying patients as low versus high (p < 0.0001), low versus non-low (p = 0.0007) and high versus non-high (p < 0.0001) risk. There is a need for prospectively validated models to characterize individual patient risk of transformation to MM. PMID:23311294

  2. Clinical cancer advances 2011: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.

    PubMed

    Vogelzang, Nicholas J; Benowitz, Steven I; Adams, Sylvia; Aghajanian, Carol; Chang, Susan Marina; Dreyer, Zoann Eckert; Janne, Pasi A; Ko, Andrew H; Masters, Greg A; Odenike, Olatoyosi; Patel, Jyoti D; Roth, Bruce J; Samlowski, Wolfram E; Seidman, Andrew D; Tap, William D; Temel, Jennifer S; Von Roenn, Jamie H; Kris, Mark G

    2012-01-01

    A message from ASCO'S President. It has been forty years since President Richard Nixon signed the National Cancer Act of 1971, which many view as the nation's declaration of the "War on Cancer." The bill has led to major investments in cancer research and significant increases in cancer survival. Today, two-thirds of patients survive at least five years after being diagnosed with cancer compared with just half of all diagnosed patients surviving five years after diagnosis in 1975. The research advances detailed in this year's Clinical Cancer Advances demonstrate that improvements in cancer screening, treatment, and prevention save and improve lives. But although much progress has been made, cancer remains one of the world's most serious health problems. In the United States, the disease is expected to become the nation's leading cause of death in the years ahead as our population ages. I believe we can accelerate the pace of progress, provided that everyone involved in cancer care works together to achieve this goal. It is this viewpoint that has shaped the theme for my presidential term: Collaborating to Conquer Cancer. In practice, this means that physicians and researchers must learn from every patient's experience, ensure greater collaboration between members of a patient's medical team, and involve more patients in the search for cures through clinical trials. Cancer advocates, insurers, and government agencies also have important roles to play. Today, we have an incredible opportunity to improve the quality of cancer care by drawing lessons from the real-world experiences of patients. The American Society of Clinical Oncology (ASCO) is taking the lead in this area, in part through innovative use of health information technology. In addition to our existing quality initiatives, ASCO is working with partners to develop a comprehensive rapid-learning system for cancer care. When complete, this system will provide physicians with personalized, real

  3. Concise review: Induced pluripotent stem cell-derived mesenchymal stem cells: progress toward safe clinical products.

    PubMed

    Jung, Yunjoon; Bauer, Gerhard; Nolta, Jan A

    2012-01-01

    Adult stem cell therapies have provided success for more than 50 years, through reconstitution of the hematopoietic system using bone marrow, umbilical cord blood, and mobilized peripheral blood transplantation. Mesenchymal stem cell (MSC)-mediated therapy is a fast-growing field that has proven safe and effective in the treatment of various degenerative diseases and tissue injuries. Since the first derivation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), there has been impressive progress toward developing safe clinical applications from PSCs. Recent successes in transgene-free iPSC reprogramming have brought attention to the potential of clinical applications of these pluripotent cells, but key hurdles must be overcome, which are discussed in this review. Looking to the future, it could be advantageous to derive MSC from iPSC or human ESC in cases where genetic engineering is needed, since in the PSCs, clones with "safe harbor" vector integration could be selected, expanded, and differentiated. Here, we describe the status of the progress of the use of MSC and PSCs in clinical trials and analyze the challenges that should be overcome before iPSC-derived MSC therapy can be used widely in the clinic.

  4. Ant colony method to control variance reduction techniques in the Monte Carlo simulation of clinical electron linear accelerators

    NASA Astrophysics Data System (ADS)

    García-Pareja, S.; Vilches, M.; Lallena, A. M.

    2007-09-01

    The ant colony method is used to control the application of variance reduction techniques to the simulation of clinical electron linear accelerators of use in cancer therapy. In particular, splitting and Russian roulette, two standard variance reduction methods, are considered. The approach can be applied to any accelerator in a straightforward way and permits, in addition, to investigate the "hot" regions of the accelerator, an information which is basic to develop a source model for this therapy tool.

  5. Joint modeling of the clinical progression and of the biomarkers' dynamics using a mechanistic model.

    PubMed

    Guedj, Jeremie; Thiébaut, Rodolphe; Commenges, Daniel

    2011-03-01

    Joint models are used to rigorously explore the relationship between the dynamics of biomarkers and clinical events. In the context of HIV infection, where the multivariate dynamics of HIV-RNA and CD4 are complex, a mechanistic approach based on a system of nonlinear differential equations naturally takes into account the correlation between the biomarkers. Using data from a randomized clinical trial comparing dual antiretroviral therapy to a single drug regimen, a full maximum likelihood approach is proposed to explore the relationship between the evolution of the biomarkers and the time to a clinical event. The role of each marker as an independent predictor of disease progression is assessed. We show that the joint dynamics of HIV-RNA and CD4 captures the effect of antiretroviral treatment; the CD4 dynamics alone is found to capture most but not all of the treatment effect. PMID:20377577

  6. Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech

    PubMed Central

    Whitwell, Jennifer L.; Weigand, Stephen D.; Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Senjem, Matthew L.; Gunter, Jeffrey L.; Lowe, Val J.; Jack, Clifford R.; Josephs, Keith A.

    2016-01-01

    Beta-amyloid (Aβ) deposition can be observed in primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified) and PAOS (n = 42) subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+) status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+) status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+) status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified PPA subjects

  7. Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech.

    PubMed

    Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Lowe, Val J; Jack, Clifford R; Josephs, Keith A

    2016-01-01

    Beta-amyloid (Aβ) deposition can be observed in primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified) and PAOS (n = 42) subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+) status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+) status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+) status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified PPA subjects

  8. Prognostic role of genetic biomarkers in clinical progression of prostate cancer

    PubMed Central

    Alvarez-Cubero, Maria Jesus; Martinez-Gonzalez, Luis Javier; Saiz, Maria; Carmona-Saez, Pedro; Alvarez, Juan Carlos; Pascual-Geler, Manrique; Lorente, Jose Antonio; Cozar, Jose Manuel

    2015-01-01

    The aim of this study was to analyze the use of 12 single-nucleotide polymorphisms in genes ELAC2, RNASEL and MSR1 as biomarkers for prostate cancer (PCa) detection and progression, as well as perform a genetic classification of high-risk patients. A cohort of 451 men (235 patients and 216 controls) was studied. We calculated means of regression analysis using clinical values (stage, prostate-specific antigen, Gleason score and progression) in patients and controls at the basal stage and after a follow-up of 72 months. Significantly different allele frequencies between patients and controls were observed for rs1904577 and rs918 (MSR1 gene) and for rs17552022 and rs5030739 (ELAC2). We found evidence of increased risk for PCa in rs486907 and rs2127565 in variants AA and CC, respectively. In addition, rs627928 (TT–GT), rs486907 (AG) and rs3747531 (CG–CC) were associated with low tumor aggressiveness. Some had a weak linkage, such as rs1904577 and rs2127565, rs4792311 and rs17552022, and rs1904577 and rs918. Our study provides the proof-of-principle that some of the genetic variants (such as rs486907, rs627928 and rs2127565) in genes RNASEL, MSR1 and ELAC2 can be used as predictors of aggressiveness and progression of PCa. In the future, clinical use of these biomarkers, in combination with current ones, could potentially reduce the rate of unnecessary biopsies and specific treatments. PMID:26251261

  9. Rhesus monkey model of liver disease reflecting clinical disease progression and hepatic gene expression analysis.

    PubMed

    Wang, Hong; Tan, Tao; Wang, Junfeng; Niu, Yuyu; Yan, Yaping; Guo, Xiangyu; Kang, Yu; Duan, Yanchao; Chang, Shaohui; Liao, Jianpeng; Si, Chenyang; Ji, Weizhi; Si, Wei

    2015-10-07

    Alcoholic liver disease (ALD) is a significant public health issue with heavy medical and economic burdens. The aetiology of ALD is not yet completely understood. The development of drugs and therapies for ALD is hampered by a lack of suitable animal models that replicate both the histological and metabolic features of human ALD. Here, we characterize a rhesus monkey model of alcohol-induced liver steatosis and hepatic fibrosis that is compatible with the clinical progression of the biochemistry and pathology in humans with ALD. Microarray analysis of hepatic gene expression was conducted to identify potential molecular signatures of ALD progression. The up-regulation of expression of hepatic genes related to liver steatosis (CPT1A, FASN, LEPR, RXRA, IGFBP1, PPARGC1A and SLC2A4) was detected in our rhesus model, as was the down-regulation of such genes (CYP7A1, HMGCR, GCK and PNPLA3) and the up-regulation of expression of hepatic genes related to liver cancer (E2F1, OPCML, FZD7, IGFBP1 and LEF1). Our results demonstrate that this ALD model reflects the clinical disease progression and hepatic gene expression observed in humans. These findings will be useful for increasing the understanding of ALD pathogenesis and will benefit the development of new therapeutic procedures and pharmacological reagents for treating ALD.

  10. Rhesus monkey model of liver disease reflecting clinical disease progression and hepatic gene expression analysis

    PubMed Central

    Wang, Hong; Tan, Tao; Wang, Junfeng; Niu, Yuyu; Yan, Yaping; Guo, Xiangyu; Kang, Yu; Duan, Yanchao; Chang, Shaohui; Liao, Jianpeng; Si, Chenyang; Ji, Weizhi; Si, Wei

    2015-01-01

    Alcoholic liver disease (ALD) is a significant public health issue with heavy medical and economic burdens. The aetiology of ALD is not yet completely understood. The development of drugs and therapies for ALD is hampered by a lack of suitable animal models that replicate both the histological and metabolic features of human ALD. Here, we characterize a rhesus monkey model of alcohol-induced liver steatosis and hepatic fibrosis that is compatible with the clinical progression of the biochemistry and pathology in humans with ALD. Microarray analysis of hepatic gene expression was conducted to identify potential molecular signatures of ALD progression. The up-regulation of expression of hepatic genes related to liver steatosis (CPT1A, FASN, LEPR, RXRA, IGFBP1, PPARGC1A and SLC2A4) was detected in our rhesus model, as was the down-regulation of such genes (CYP7A1, HMGCR, GCK and PNPLA3) and the up-regulation of expression of hepatic genes related to liver cancer (E2F1, OPCML, FZD7, IGFBP1 and LEF1). Our results demonstrate that this ALD model reflects the clinical disease progression and hepatic gene expression observed in humans. These findings will be useful for increasing the understanding of ALD pathogenesis and will benefit the development of new therapeutic procedures and pharmacological reagents for treating ALD. PMID:26442469

  11. Combining fixed and removable restorations with linear occlusion to treat combination syndrome: a clinical report.

    PubMed

    Jameson, W S

    2004-01-01

    Proper treatment sequencing is critical when a patient requires multiple fixed restorations in conjunction with a removable partial and complete denture. The vertical dimension, centric relation, and horizontal occlusal plane must be determined first, followed by a diagnostic wax-up that incorporates linear occlusal concepts to prevent anterior hyperfunction. A more predictable treatment outcome is possible when individual components are defined clearly.

  12. Primary Progressive Apraxia of Speech: Clinical Features and Acoustic and Neurologic Correlates

    PubMed Central

    Strand, Edythe A.; Clark, Heather; Machulda, Mary; Whitwell, Jennifer L.; Josephs, Keith A.

    2015-01-01

    Purpose This study summarizes 2 illustrative cases of a neurodegenerative speech disorder, primary progressive apraxia of speech (AOS), as a vehicle for providing an overview of the disorder and an approach to describing and quantifying its perceptual features and some of its temporal acoustic attributes. Method Two individuals with primary progressive AOS underwent speech-language and neurologic evaluations on 2 occasions, ranging from 2.0 to 7.5 years postonset. Performance on several tests, tasks, and rating scales, as well as several acoustic measures, were compared over time within and between cases. Acoustic measures were compared with performance of control speakers. Results Both patients initially presented with AOS as the only or predominant sign of disease and without aphasia or dysarthria. The presenting features and temporal progression were captured in an AOS Rating Scale, an Articulation Error Score, and temporal acoustic measures of utterance duration, syllable rates per second, rates of speechlike alternating motion and sequential motion, and a pairwise variability index measure. Conclusions AOS can be the predominant manifestation of neurodegenerative disease. Clinical ratings of its attributes and acoustic measures of some of its temporal characteristics can support its diagnosis and help quantify its salient characteristics and progression over time. PMID:25654422

  13. Defining, evaluating, and removing bias induced by linear imputation in longitudinal clinical trials with MNAR missing data.

    PubMed

    Helms, Ronald W; Reece, Laura Helms; Helms, Russell W; Helms, Mary W

    2011-03-01

    Missing not at random (MNAR) post-dropout missing data from a longitudinal clinical trial result in the collection of "biased data," which leads to biased estimators and tests of corrupted hypotheses. In a full rank linear model analysis the model equation, E[Y] = Xβ, leads to the definition of the primary parameter β = (X'X)(-1)X'E[Y], and the definition of linear secondary parameters of the form θ = Lβ = L(X'X)(-1)X'E[Y], including, for example, a parameter representing a "treatment effect." These parameters depend explicitly on E[Y], which raises the questions: What is E[Y] when some elements of the incomplete random vector Y are not observed and MNAR, or when such a Y is "completed" via imputation? We develop a rigorous, readily interpretable definition of E[Y] in this context that leads directly to definitions of β, Bias(β) = E[β] - β, Bias(θ) = E[θ] - Lβ, and the extent of hypothesis corruption. These definitions provide a basis for evaluating, comparing, and removing biases induced by various linear imputation methods for MNAR incomplete data from longitudinal clinical trials. Linear imputation methods use earlier data from a subject to impute values for post-dropout missing values and include "Last Observation Carried Forward" (LOCF) and "Baseline Observation Carried Forward" (BOCF), among others. We illustrate the methods of evaluating, comparing, and removing biases and the effects of testing corresponding corrupted hypotheses via a hypothetical but very realistic longitudinal analgesic clinical trial.

  14. Testing of evaluation bias for progression free survival endpoint in oncology clinical trials.

    PubMed

    Sun, Yan; Wu, Wenting; Sargent, Daniel

    2016-09-30

    Progression-free survival is an increasingly popular end point in oncology clinical trials. A complete blinded independent central review (BICR) is often required by regulators in an attempt to reduce the bias in progression-free survival (PFS) assessment. In this paper, we propose a new methodology that uses a sample-based BICR as an audit tool to decide whether a complete BICR is needed. More specifically, we propose a new index, the differential risk, to measure the reading discordance pattern, and develop a corresponding hypothesis testing procedure to decide whether the bias in local evaluation is acceptable. Simulation results demonstrate that our new index is sensitive to the change of discordance pattern; type I error is well controlled in the hypothesis testing procedure, and the calculated sample size provides the desired power. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27089832

  15. Clinical and ABCB11 profiles in Korean infants with progressive familial intrahepatic cholestasis

    PubMed Central

    Park, Ji Sook; Ko, Jae Sung; Seo, Jeong Kee; Moon, Jin Soo; Park, Sung Sup

    2016-01-01

    AIM: To investigate clinical profiles and mutations of ABCB11 in Koreans with progressive familial intrahepatic cholestasis 2 and review the differences between Koreans and others. METHODS: Of 47 patients with neonatal cholestasis, five infants had chronic intrahepatic cholestasis with normal γ-glutamyl transpeptidase. Direct sequencing analyses of ABCB11, including exons and introns, were performed from peripheral blood. RESULTS: Living donor-liver transplantation was performed in four patients because of rapidly progressive hepatic failure and hepatocellular carcinoma. Three missense mutations were found in two patients: compound heterozygous 677C>T (S226L)/3007G>A (G1003R) and heterozygous 2296G>A (G766R). The mutations were located near and in the transmembranous space. CONCLUSION: Alterations in the transmembrane of the bile salt export pump in the Korean infants were different from those previously reported in Chinese, Japanease, Taiwanese, and European patients. PMID:27239116

  16. Current progress of siRNA/shRNA therapeutics in clinical trials.

    PubMed

    Burnett, John C; Rossi, John J; Tiemann, Katrin

    2011-09-01

    Through a mechanism known as RNA interference (RNAi), small interfering RNA (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit gene expression offers a mechanism that can be exploited for novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed for more than a dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi-based therapeutics often require a delivery vehicle to transport them to the targeted cells. Thus, the clinical advancement of numerous siRNA drugs has relied on the development of siRNA carriers, including biodegradable nanoparticles, lipids, bacteria, and attenuated viruses. Most therapies permit systemic delivery of the siRNA drug, while others use ex vivo delivery by autologous cell therapy. Advancements in bioengineering and nanotechnology have led to improved control of delivery and release of some siRNA therapeutics. Likewise, progress in molecular biology has allowed for improved design of the siRNA molecules. Here, we provide an overview of siRNA therapeutics in clinical trials, including their clinical progress, the challenges they have encountered, and the future they hold in the treatment of human diseases.

  17. Sativex(®) and clinical-neurophysiological measures of spasticity in progressive multiple sclerosis.

    PubMed

    Leocani, Letizia; Nuara, Arturo; Houdayer, Elise; Schiavetti, Irene; Del Carro, Ubaldo; Amadio, Stefano; Straffi, Laura; Rossi, Paolo; Martinelli, Vittorio; Vila, Carlos; Sormani, Maria Pia; Comi, Giancarlo

    2015-11-01

    Despite the proven efficacy of Sativex(®) (9-delta-tetrahydrocannabinol plus cannabidiol) oromucosal spray in reducing spasticity symptoms in multiple sclerosis (MS), little is known about the neurophysiological correlates of such effects. The aim of the study was to investigate the effects of Sativex on neurophysiological measures of spasticity (H/M ratio) and corticospinal excitability in patients with progressive MS. This was a randomized, double-blind, placebo-controlled, crossover study. Consecutive subjects with progressive MS and lower limb spasticity referred to our center were randomized to 4 weeks' treatment (including 2 weeks' titration) with Sativex or placebo, with crossover after a 2-week washout. Clinical and neurophysiological measures (H/M ratio and cortical excitability) of spasticity were assessed. The H/M ratio was the primary outcome, with sample size calculation of 40 patients. Of 44 recruited patients, 34 were analyzed due to 6 drop-outs and 4 exclusions, which lowered the power of the study to show differences between treatments. Neurophysiological measures did not differ significantly according to treatment and did not correlate significantly with clinical response. Response on the modified Ashworth scale (at least 20 % improvement) was significantly more frequent after Sativex than placebo (50 vs 23.5 %; p = 0.041; McNemar). Side effects did not differ significantly according to treatment. Our findings confirm the clinical benefit of Sativex on MS spasticity. The lack of corresponding changes in corticospinal excitability and on the monosynaptic component, of the stretch reflex, although in a limited sample size, points to the involvement of other spinal and supraspinal mechanisms in the physiopathology of spasticity in progressive MS. PMID:26289497

  18. [The characteristics of the clinical manifestations and diagnostic criteria of progressive tubal pregnancy].

    PubMed

    Mundzhal, S; Zhuk, S I; Hryhorenko, A M

    2000-01-01

    An analysis was performed of clinical manifestations and chief diagnostic criteria of progressive tubal pregnancy to allow some judgement about their informative value. The findings secured show the presence of bloody discharges, gnawing pain in the lower area of the abdomen, nausea, vomiting to be of most informative value. In vaginal examination, the following findings can be regarded as main diagnostic criteria: the presence of tumour-like formation in the projection of the adnexa uteri, softening of the uterus sizes. The best supplementary investigatory methods capable of providing relevant information included determination of beta-HG by laboratory means, laparoscopic diagnosis and transvaginal ultrasonography.

  19. North American Clinical Trials Network for the Treatment of Spinal Cord Injury: goals and progress.

    PubMed

    Grossman, Robert G; Toups, Elizabeth G; Frankowski, Ralph F; Burau, Keith D; Howley, Susan

    2012-09-01

    The North American Clinical Trials Network (NACTN) for the Treatment of Spinal Cord Injury is a consortium of 10 neurosurgery departments, a data management center, and a pharmacological center. The NACTN was established with the goal of bringing recent molecular and cell-based discoveries in neuroprotection and regeneration from the laboratory into clinical trials that optimize meaningful data outcomes and maximum safety to patients. The requirements of planning and executing clinical trials in spinal cord injury (SCI) and the steps that the NACTN has taken to address these requirements are discussed and illustrated in articles in this issue of the Journal of Neurosurgery: Spine. The progress that the NACTN has made in meeting these goals can be summarized as organizing a network of hospitals capable of enrolling a sufficient number of patients for conducting Phase I and II trials; creating a Data Management Center and a database of the natural history of recovery after SCI (at the time of this writing 485 patients were enrolled in the database); creating a database of the incidence and severity of complications that occur during acute and subacute treatment after SCI; developing a Pharmacological Center capable of performing pharmacokinetic and pharmacodynamic studies of therapeutic drugs; completing enrollment of 36 patients in NACTN's first clinical trial, a Phase I study of riluzole, a neuroprotective drug; and performing pharmacokinetic and pharmacodynamic studies of riluzole in acute SCI.

  20. Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients.

    PubMed

    Harutyunyan, Nika M; Vardanyan, Suzie; Ghermezi, Michael; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R

    2016-07-01

    Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma.

  1. Monitoring progression in Friedreich ataxia (FRDA): the use of clinical scales.

    PubMed

    Bürk, Katrin; Schulz, Stefanie R; Schulz, Jörg B

    2013-08-01

    Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder associated with ataxia, dysarthria, pyramidal tract signs, sensory loss, cardiomyopathy and diabetes. There is no cure for FRDA so far. Studies of the natural history of the disease and future therapeutic trials require development of appropriate outcome markers. Since any therapeutic benefit is expected to modulate deterioration over time rather than to reverse disability, potential outcome measures must be sensitive instruments carefully analysed for their significance. Clinical scales may represent an appropriate measuring tool. Over the last few years the construction, evaluation and validation of sensitive clinical scales for the assessment of disease severity and progression in ataxia have had considerable impact on our understanding of the disease. Currently, there are three different scales that are most frequently applied: The International Cooperative Ataxia Rating Scale (ICARS), the Friedreich Ataxia Rating Scale (FARS) and the Scale for the Assessment and Rating of Ataxia (SARA). All scales have been validated and compared with regard to their testing properties.

  2. Optimising translational oncology in clinical practice: strategies to accelerate progress in drug development.

    PubMed

    Stahel, R; Bogaerts, J; Ciardiello, F; de Ruysscher, D; Dubsky, P; Ducreux, M; Finn, S; Laurent-Puig, P; Peters, S; Piccart, M; Smit, E; Sotiriou, C; Tejpar, S; Van Cutsem, E; Tabernero, J

    2015-02-01

    Despite intense efforts, the socioeconomic burden of cancer remains unacceptably high and treatment advances for many common cancers have been limited, suggesting a need for a new approach to drug development. One issue central to this lack of progress is the heterogeneity and genetic complexity of many tumours. This results in considerable variability in therapeutic response and requires knowledge of the molecular profile of the tumour to guide appropriate treatment selection for individual patients. While recent advances in the molecular characterisation of different cancer types have the potential to transform cancer treatment through precision medicine, such an approach presents a major economic challenge for drug development, since novel targeted agents may only be suitable for a small cohort of patients. Identifying the patients who would benefit from individual therapies and recruiting sufficient numbers of patients with particular cancer subtypes into clinical trials is challenging, and will require collaborative efforts from research groups and industry in order to accelerate progress. A number of molecular screening platforms have already been initiated across Europe, and it is hoped that these networks, along with future collaborations, will benefit not only patients but also society through cost reductions as a result of more efficient use of resources. This review discusses how current developments in translational oncology may be applied in clinical practice in the future, assesses current programmes for the molecular characterisation of cancer and describes possible collaborative approaches designed to maximise the benefits of translational science for patients with cancer.

  3. Linear Colliders

    NASA Astrophysics Data System (ADS)

    Yamamoto, Akira; Yokoya, Kaoru

    2015-02-01

    An overview of linear collider programs is given. The history and technical challenges are described and the pioneering electron-positron linear collider, the SLC, is first introduced. For future energy frontier linear collider projects, the International Linear Collider (ILC) and the Compact Linear Collider (CLIC) are introduced and their technical features are discussed. The ILC is based on superconducting RF technology and the CLIC is based on two-beam acceleration technology. The ILC collaboration completed the Technical Design Report in 2013, and has come to the stage of "Design to Reality." The CLIC collaboration published the Conceptual Design Report in 2012, and the key technology demonstration is in progress. The prospects for further advanced acceleration technology are briefly discussed for possible long-term future linear colliders.

  4. Linear Colliders

    NASA Astrophysics Data System (ADS)

    Yamamoto, Akira; Yokoya, Kaoru

    An overview of linear collider programs is given. The history and technical challenges are described and the pioneering electron-positron linear collider, the SLC, is first introduced. For future energy frontier linear collider projects, the International Linear Collider (ILC) and the Compact Linear Collider (CLIC) are introduced and their technical features are discussed. The ILC is based on superconducting RF technology and the CLIC is based on two-beam acceleration technology. The ILC collaboration completed the Technical Design Report in 2013, and has come to the stage of "Design to Reality." The CLIC collaboration published the Conceptual Design Report in 2012, and the key technology demonstration is in progress. The prospects for further advanced acceleration technology are briefly discussed for possible long-term future linear colliders.

  5. Word-finding difficulty: a clinical analysis of the progressive aphasias

    PubMed Central

    Rohrer, Jonathan D.; Knight, William D.; Warren, Jane E.; Fox, Nick C.; Rossor, Martin N.; Warren, Jason D.

    2008-01-01

    The patient with word-finding difficulty presents a common and challenging clinical problem. The complaint of ‘word-finding difficulty’ covers a wide range of clinical phenomena and may signify any of a number of distinct pathophysiological processes. Although it occurs in a variety of clinical contexts, word-finding difficulty generally presents a diagnostic conundrum when it occurs as a leading or apparently isolated symptom, most often as the harbinger of degenerative disease: the progressive aphasias. Recent advances in the neurobiology of the focal, language-based dementias have transformed our understanding of these processes and the ways in which they breakdown in different diseases, but translation of this knowledge to the bedside is far from straightforward. Speech and language disturbances in the dementias present unique diagnostic and conceptual problems that are not fully captured by classical models derived from the study of vascular and other acute focal brain lesions. This has led to a reformulation of our understanding of how language is organized in the brain. In this review we seek to provide the clinical neurologist with a practical and theoretical bridge between the patient presenting with word-finding difficulty in the clinic and the evidence of the brain sciences. We delineate key illustrative speech and language syndromes in the degenerative dementias, compare these syndromes with the syndromes of acute brain damage, and indicate how the clinical syndromes relate to emerging neurolinguistic, neuroanatomical and neurobiological insights. We propose a conceptual framework for the analysis of word-finding difficulty, in order both better to define the patient's complaint and its differential diagnosis for the clinician and to identify unresolved issues as a stimulus to future work. PMID:17947337

  6. [Experiment studies of electron-positron interactions at the Stanford Linear Accelerator Center]. Progress report, calendar year 1993

    SciTech Connect

    Hertzbach, S.S.; Kofler, R.R.

    1993-12-31

    The High Energy Physics group at the University of Massachusetts has continued its` program of experimental studies of electron-positron interactions at the Stanford Linear Accelerator Center (SLAC). The group activities have included: analysis of data taken between 1982 and 1990 with the TPC detector at the PEP facility, continuing data collection and data analysis using the SLC/SLD facility, planning for the newly approved B-factory at SLAC, and participation in design studies for future high energy linear colliders. This report will briefly summarize these activities.

  7. Anti-dementia medications: current prescriptions in clinical practice and new agents in progress

    PubMed Central

    Stella, Florindo; Radanovic, Márcia; Canineu, Paulo Renato; de Paula, Vanessa J. R.

    2015-01-01

    Almost three decades after the publication of the first clinical studies with tacrine, the pharmacological treatment of Alzheimer’s disease (AD) remains a challenge. Randomized clinical trials have yielded evidence of significant – although modest and transient – benefit from cholinergic replacement therapy for people diagnosed with AD, and disease modification with antidementia compounds is still an urgent, unmet need. The natural history of AD is very long, and its pharmacological treatment must acknowledge different needs according to the stage of the disease process. Cognitive and functional deterioration evolves gradually since the onset of clinical symptoms, which may be preceded by several years or perhaps decades of silent, presymptomatic neurodegeneration. Therefore, the pharmacological treatment of AD must ideally comprise both a symptomatic effect to preserve or improve cognition and a disease-modifying effect to tackle the progression of the pathological process. Primary prevention is the ultimate goal, should these strategies be delivered to patients with preclinical AD. In this article, we briefly address the pharmaceutical compounds that are currently used for the symptomatic treatment of AD and discuss the ongoing strategies designed to modify its natural course. PMID:26301069

  8. Application of variance reduction techniques in Monte Carlo simulation of clinical electron linear accelerator

    NASA Astrophysics Data System (ADS)

    Zoubair, M.; El Bardouni, T.; El Gonnouni, L.; Boulaich, Y.; El Bakkari, B.; El Younoussi, C.

    2012-01-01

    Computation time constitutes an important and a problematic parameter in Monte Carlo simulations, which is inversely proportional to the statistical errors so there comes the idea to use the variance reduction techniques. These techniques play an important role in reducing uncertainties and improving the statistical results. Several variance reduction techniques have been developed. The most known are Transport cutoffs, Interaction forcing, Bremsstrahlung splitting and Russian roulette. Also, the use of a phase space seems to be appropriate to reduce enormously the computing time. In this work, we applied these techniques on a linear accelerator (LINAC) using the MCNPX computer Monte Carlo code. This code gives a rich palette of variance reduction techniques. In this study we investigated various cards related to the variance reduction techniques provided by MCNPX. The parameters found in this study are warranted to be used efficiently in MCNPX code. Final calculations are performed in two steps that are related by a phase space. Results show that, comparatively to direct simulations (without neither variance-reduction nor phase space), the adopted method allows an improvement in the simulation efficiency by a factor greater than 700.

  9. RETURN TO PLAY PROGRESSION FOR RUGBY FOLLOWING INJURY TO THE LOWER EXTREMITY: A CLINICAL COMMENTARY AND REVIEW OF THE LITERATURE

    PubMed Central

    Davis, Chelseana C.

    2016-01-01

    Background & Purpose Rugby requires unique demands from its players. Those involved in rehabilitation and care of these athletes must possess an understanding of both the game and various positions. There have been numerous reports focusing on the physiological demands and biomechanical analyses of various components of gameplay, but no specific progression has been developed to assist clinicians assessing the readiness to return of a player after injury. The purpose of this clinical commentary is to outline testing components, general gameplay guidelines, movement progressions, and sport and position-specific progressions related to rugby gameplay following a lower extremity injury. Description of Topic This commentary provides a recommended progression for clinical use for use in a return to rugby program. It includes metabolic considerations, advanced strengthening exercises, agility exercises, and incorporation of drills specific to the sport of rugby that may be performed with the clinician or with assistance from team members. This progression also includes testing parameters for each phase and guidance for clinicians regarding the ability to gauge readiness to return to sport. Discussion It is essential that an athlete returning to the sport of rugby undertake a guided, graduated return to sport progression to ensure safety and to decrease the risk of re-injury. This proposed return to sport progression outlines key parameters for both the sport as a whole and for various specific positions. Level of Evidence Level 5 – Clinical Commentary, Review of Literature PMID:27104062

  10. Clinically meaningful parameters of progression and long-term outcome of Parkinson disease: An international consensus statement.

    PubMed

    Puschmann, Andreas; Brighina, Laura; Markopoulou, Katerina; Aasly, Jan; Chung, Sun Ju; Frigerio, Roberta; Hadjigeorgiou, Georgios; Kõks, Sulev; Krüger, Rejko; Siuda, Joanna; Wider, Christian; Zesiewicz, Theresa A; Maraganore, Demetrius M

    2015-07-01

    Parkinson disease (PD) is associated with a clinical course of variable duration, severity, and a combination of motor and non-motor features. Recent PD research has focused primarily on etiology rather than clinical progression and long-term outcomes. For the PD patient, caregivers, and clinicians, information on expected clinical progression and long-term outcomes is of great importance. Today, it remains largely unknown what factors influence long-term clinical progression and outcomes in PD; recent data indicate that the factors that increase the risk to develop PD differ, at least partly, from those that accelerate clinical progression and lead to worse outcomes. Prospective studies will be required to identify factors that influence progression and outcome. We suggest that data for such studies is collected during routine office visits in order to guarantee high external validity of such research. We report here the results of a consensus meeting of international movement disorder experts from the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium, who convened to define which long-term outcomes are of interest to patients, caregivers and clinicians, and what is presently known about environmental or genetic factors influencing clinical progression or long-term outcomes in PD. We propose a panel of rating scales that collects a significant amount of phenotypic information, can be performed in the routine office visit and allows international standardization. Research into the progression and long-term outcomes of PD aims at providing individual prognostic information early, adapting treatment choices, and taking specific measures to provide care optimized to the individual patient's needs.

  11. Experimental Therapies and Ongoing Clinical Trials to Slow Down Progression of ADPKD

    PubMed Central

    Irazabal, Maria V.; Torres, Vicente E.

    2014-01-01

    The improvement of imaging techniques over the years has contributed to the understanding of the natural history of autosomal dominant polycystic kidney disease, and facilitated the observation of its structural progression. Advances in molecular biology and genetics have made possible a greater understanding of the genetics, molecular, and cellular pathophysiologic mechanisms responsible for its development and have laid the foundation for the development of potential new therapies. Therapies targeting genetic mechanisms in ADPKD have inherent limitations. As a result, most experimental therapies at the present time are aimed at delaying the growth of the cysts and associated interstitial inflammation and fibrosis by targeting tubular epithelial cell proliferation and fluid secretion by the cystic epithelium. Several interventions affecting many of the signaling pathways disrupted in ADPKD have been effective in animal models and some are currently being tested in clinical trials. PMID:23971644

  12. Progressive muscle proteome changes in a clinically relevant pig model of Duchenne muscular dystrophy.

    PubMed

    Fröhlich, Thomas; Kemter, Elisabeth; Flenkenthaler, Florian; Klymiuk, Nikolai; Otte, Kathrin A; Blutke, Andreas; Krause, Sabine; Walter, Maggie C; Wanke, Rüdiger; Wolf, Eckhard; Arnold, Georg J

    2016-01-01

    Duchenne muscular dystrophy (DMD) is caused by genetic deficiency of dystrophin and characterized by massive structural and functional changes of skeletal muscle tissue, leading to terminal muscle failure. We recently generated a novel genetically engineered pig model reflecting pathological hallmarks of human DMD better than the widely used mdx mouse. To get insight into the hierarchy of molecular derangements during DMD progression, we performed a proteome analysis of biceps femoris muscle samples from 2-day-old and 3-month-old DMD and wild-type (WT) pigs. The extent of proteome changes in DMD vs. WT muscle increased markedly with age, reflecting progression of the pathological changes. In 3-month-old DMD muscle, proteins related to muscle repair such as vimentin, nestin, desmin and tenascin C were found to be increased, whereas a large number of respiratory chain proteins were decreased in abundance in DMD muscle, indicating serious disturbances in aerobic energy production and a reduction of functional muscle tissue. The combination of proteome data for fiber type specific myosin heavy chain proteins and immunohistochemistry showed preferential degeneration of fast-twitch fiber types in DMD muscle. The stage-specific proteome changes detected in this large animal model of clinically severe muscular dystrophy provide novel molecular readouts for future treatment trials. PMID:27634466

  13. Progressive muscle proteome changes in a clinically relevant pig model of Duchenne muscular dystrophy

    PubMed Central

    Fröhlich, Thomas; Kemter, Elisabeth; Flenkenthaler, Florian; Klymiuk, Nikolai; Otte, Kathrin A.; Blutke, Andreas; Krause, Sabine; Walter, Maggie C.; Wanke, Rüdiger; Wolf, Eckhard; Arnold, Georg J.

    2016-01-01

    Duchenne muscular dystrophy (DMD) is caused by genetic deficiency of dystrophin and characterized by massive structural and functional changes of skeletal muscle tissue, leading to terminal muscle failure. We recently generated a novel genetically engineered pig model reflecting pathological hallmarks of human DMD better than the widely used mdx mouse. To get insight into the hierarchy of molecular derangements during DMD progression, we performed a proteome analysis of biceps femoris muscle samples from 2-day-old and 3-month-old DMD and wild-type (WT) pigs. The extent of proteome changes in DMD vs. WT muscle increased markedly with age, reflecting progression of the pathological changes. In 3-month-old DMD muscle, proteins related to muscle repair such as vimentin, nestin, desmin and tenascin C were found to be increased, whereas a large number of respiratory chain proteins were decreased in abundance in DMD muscle, indicating serious disturbances in aerobic energy production and a reduction of functional muscle tissue. The combination of proteome data for fiber type specific myosin heavy chain proteins and immunohistochemistry showed preferential degeneration of fast-twitch fiber types in DMD muscle. The stage-specific proteome changes detected in this large animal model of clinically severe muscular dystrophy provide novel molecular readouts for future treatment trials. PMID:27634466

  14. Protein synthesis directly from PCR: progress and applications of cell-free protein synthesis with linear DNA.

    PubMed

    Schinn, Song-Min; Broadbent, Andrew; Bradley, William T; Bundy, Bradley C

    2016-06-25

    A rapid, versatile method of protein expression and screening can greatly facilitate the future development of therapeutic biologics, proteomic drug targets and biocatalysts. An attractive candidate is cell-free protein synthesis (CFPS), a cell-lysate-based in vitro expression system, which can utilize linear DNA as expression templates, bypassing time-consuming cloning steps of plasmid-based methods. Traditionally, such linear DNA expression templates (LET) have been vulnerable to degradation by nucleases present in the cell lysate, leading to lower yields. This challenge has been significantly addressed in the recent past, propelling LET-based CFPS as a useful tool for studying, screening and engineering proteins in a high-throughput manner. Currently, LET-based CFPS has promise in fields such as functional proteomics, protein microarrays, and the optimization of complex biological systems. PMID:27085957

  15. Imaging changes following stereotactic radiosurgery for metastatic intracranial tumors: differentiating pseudoprogression from tumor progression and its effect on clinical practice

    PubMed Central

    Kleinberg, Lawrence; Rigamonti, Daniele

    2014-01-01

    Stereotactic radiosurgery has become standard adjuvant treatment for patients with metastatic intracranial lesions. There has been a growing appreciation for benign imaging changes following radiation that are difficult to distinguish from true tumor progression. These imaging changes, termed pseudoprogression, carry significant implications for patient management. In this review, we discuss the current understanding of pseudoprogression in metastatic brain lesions, research to differentiate pseudoprogression from true progression, and clinical implications of pseudoprogression on treatment decisions. PMID:24233257

  16. CLINICAL AND GENETIC PREDICTORS AND PROGNOSTIC MODEL OF RAPIDLY PROGRESSIVE HEPATIC FIBROSIS IN CHRONIC HEPATITIS C.

    PubMed

    Dubinskaya, G; Sizova, L; Koval, T; Kovalyova, Е; Kaydashev, I

    2016-07-01

    The search for risk factors for rapid progression of hepatic fibrosis (HF) in chronic hepatitis C (CHC) is a topical scientific and practical task. The purpose of the study is to identify clinical and genetic predictors and create the prognostic model of rapidly progressive HF in CHC. A retrospective cohort study of 125 patients with CHC has been carried out. The logistic regression and ROC-analysis have been applied for statistical data processing. The resulting analysis of 46 potential predictors of rapidly progressive HF in CHC identified the following significant ctiteria: male gender - ОR=3.44 [95% СΙ 1.60-7.39], р=0.001; increased levels of alanine aminotransferase (ALT) - ОR=4.93 [95% СΙ 1.54-15.76], р=0.007, particularly, moderate cytolytic activity - ОR=2.36 [95% СΙ 1.08-5.16], р=0.031; aspartate aminotransferase (АSТ) - ОR=3.65 [95% СΙ 1.41-9.43] р=0.007; γ-glutamiltranspeptidase (GGTP) - ОR=3.63 [95% СΙ 1.73-7.61], р=0.001; total bilirubin - ОR=3.53 [95% СΙ 1.47-8.47], р=0.005; alkaline phosphatase - ОR=9.18 [95% 1.11-75.80], р=0.039; alcohol intake>40 g/day (ОR=3.53 [95% СΙ 1.36-9.17], р=0.009), Gln11Gln genotype of the TLR7 gene (ОR=4.56 [95% СΙ 1.57-13.22], р=0.005), presence of chronic cholecystitis and/or pancreatitis (ОR=5.30 [95% СΙ 1.84-15.25], р=0.002). The prognostic model, comprising 6 predictors (level of GGTP>upper limit of normal (ULN), male gender, Gln11Gln genotype of the TLR7 gene chronic cholecystitis and/or pancreatitis, levels of total bilirubin and АSТ>ULN) have been created, demonstrating the statistical significance (p=0.000) and high operational characteristics (sensitivity - 85.5%, specificity - 68.3%, total number of the appropriate assignments - 76.8%, positive and negative predictive value - 72,6% and 82.7%,, respectively, the AUC ROC-curve - 0.840). Use of the created model will help to predict the rapid progression of HF in CHC and form the risk-group, requiring individual

  17. CLINICAL AND GENETIC PREDICTORS AND PROGNOSTIC MODEL OF RAPIDLY PROGRESSIVE HEPATIC FIBROSIS IN CHRONIC HEPATITIS C.

    PubMed

    Dubinskaya, G; Sizova, L; Koval, T; Kovalyova, Е; Kaydashev, I

    2016-07-01

    The search for risk factors for rapid progression of hepatic fibrosis (HF) in chronic hepatitis C (CHC) is a topical scientific and practical task. The purpose of the study is to identify clinical and genetic predictors and create the prognostic model of rapidly progressive HF in CHC. A retrospective cohort study of 125 patients with CHC has been carried out. The logistic regression and ROC-analysis have been applied for statistical data processing. The resulting analysis of 46 potential predictors of rapidly progressive HF in CHC identified the following significant ctiteria: male gender - ОR=3.44 [95% СΙ 1.60-7.39], р=0.001; increased levels of alanine aminotransferase (ALT) - ОR=4.93 [95% СΙ 1.54-15.76], р=0.007, particularly, moderate cytolytic activity - ОR=2.36 [95% СΙ 1.08-5.16], р=0.031; aspartate aminotransferase (АSТ) - ОR=3.65 [95% СΙ 1.41-9.43] р=0.007; γ-glutamiltranspeptidase (GGTP) - ОR=3.63 [95% СΙ 1.73-7.61], р=0.001; total bilirubin - ОR=3.53 [95% СΙ 1.47-8.47], р=0.005; alkaline phosphatase - ОR=9.18 [95% 1.11-75.80], р=0.039; alcohol intake>40 g/day (ОR=3.53 [95% СΙ 1.36-9.17], р=0.009), Gln11Gln genotype of the TLR7 gene (ОR=4.56 [95% СΙ 1.57-13.22], р=0.005), presence of chronic cholecystitis and/or pancreatitis (ОR=5.30 [95% СΙ 1.84-15.25], р=0.002). The prognostic model, comprising 6 predictors (level of GGTP>upper limit of normal (ULN), male gender, Gln11Gln genotype of the TLR7 gene chronic cholecystitis and/or pancreatitis, levels of total bilirubin and АSТ>ULN) have been created, demonstrating the statistical significance (p=0.000) and high operational characteristics (sensitivity - 85.5%, specificity - 68.3%, total number of the appropriate assignments - 76.8%, positive and negative predictive value - 72,6% and 82.7%,, respectively, the AUC ROC-curve - 0.840). Use of the created model will help to predict the rapid progression of HF in CHC and form the risk-group, requiring individual

  18. The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress.

    PubMed

    Chow, Matthew; Cao, Michelle

    2016-01-01

    Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep-wake regulation came from narcolepsy-cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep-wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep-wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders. PMID:27051324

  19. The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress

    PubMed Central

    Chow, Matthew; Cao, Michelle

    2016-01-01

    Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep–wake regulation came from narcolepsy–cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep–wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep–wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders. PMID:27051324

  20. 466 Bee venom Immunotherapy with Standardized Extract, Two Case Comunication and Clinical Progress

    PubMed Central

    Cardona, Aristoteles Alvarez; Nieto, Leticia Hernandez; Melendez, Alvaro Pedroza

    2012-01-01

    Background Bee venom immunotherapy is a safe and effective treatment, indicated in patients with previous history of severe systemic reactions to bee venom, demonstrating succesful desensitization in more than 90% of cases with standardized extract. Currently in Mexico there is no standardized extract commercially available for treatment, despite of having high activity of beekeeping and occupational exposure with at least 17,478 registered stings per year and an annually honey production of nearly 70 tons. Methods We present the clinical progress of 2 patients with history of severe systemic reactions to bee venom and occupational exposure, both with demonstrated sensitization by specific IgE and who underwent specific immunotherapy with standardized extract (Alk-US) reaching a maintenance weekly dose of 100 mcg (PLA2) for the last 4 years. Results Both patients sufered of accidental stings after reached the maintenance dose presenting mild local reactions to stings. Both patients had very different clinical course presenting a wide variety of adverse reactions during desensitization protocol; from mild local to generalized reactions all generally well tolerated allowed to reach the maintenance dose with succesful desensitization proved by accidental exposure without severe systemic reactions. Conclusions Bee venom specific immunotherapy with standardized extract is a well tolerated and efective treatment preventing the development of life threathening reactions in sensitized patients. It is important to promote the use and availability of standardized extract in developing countries with poor safety measures and high occupational exposure.

  1. Implantable electrochemical sensors for biomedical and clinical applications: progress, problems, and future possibilities.

    PubMed

    Li, Chang Ming; Dong, Hua; Cao, Xiaodong; Luong, John H T; Zhang, Xueji

    2007-01-01

    Biosensors are of great interest for their ability to monitor clinically important analytes such as blood gases, electrolytes, and metabolites. A classic example is to monitor the dynamics of blood-glucose levels for treating diabetes. However, the current practice, based on a three decade old technology, requires a drop of blood on a test strip, which is in dire need of replacement. The increasing demands and interests in developing implantable glucose sensors for treating diabetes has led to notable progress in this area, and various electrochemical sensors have been developed for intravascular and subcutaneous applications. However, implantations are plagued by biofouling, tissue destruction and infection around the implanted sensors and the response signals must be interpreted in terms of blood or plasma concentrations for clinical utility, rather than tissue fluid levels. This review focuses on the potentials and pitfalls of implantable electrochemical sensors and presents our opinions about future possibilities of such implantable devices with respect to biocompatibility issues, long-term calibration, and other aging effects on the sensors.

  2. The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress.

    PubMed

    Chow, Matthew; Cao, Michelle

    2016-01-01

    Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep-wake regulation came from narcolepsy-cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep-wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep-wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders.

  3. Pathological and Clinical Spectrum of Progressive Supranuclear Palsy: With Special Reference to Astrocytic Tau Pathology.

    PubMed

    Yokoyama, Yuichi; Toyoshima, Yasuko; Shiga, Atsushi; Tada, Mari; Kitamura, Hideaki; Hasegawa, Kazuko; Onodera, Osamu; Ikeuchi, Takeshi; Someya, Toshiyuki; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi

    2016-03-01

    Progressive supranuclear palsy (PSP) is a four-repeat tauopathy with tau-positive, argyrophilic tuft-shaped astrocytes (TAs). We performed a pathological and clinical investigation in 40 consecutive autopsied Japanese patients with pathological diagnoses of PSP or PSP-like disease. Unequivocal TAs were present in 22 cases, all of which were confirmed to be PSP. Such TAs were hardly detected in the other 18 cases, which instead exhibited tau-positive, argyrophilic astrocytes, appearing as comparatively small clusters with central nuclei of irregularly shaped, coarse structures (equivocal TAs). Cluster analysis of the distribution pattern of tau-related pathology for these 18 cases identified two subgroups, pallido-nigro-luysian atrophy (PNLA) Type 1 (n = 9) and Type 2 (n = 9), the former being distinguished from the latter by the presence of tau-related lesions in the motor cortex, pontine nucleus and cerebellar dentate nucleus in addition to the severely affected PNL system. The duration from symptom onset until becoming wheelchair-bound was significantly longer in PNLA Type 1. Immunoblotting of samples from the three disease conditions revealed band patterns of low-molecular-mass tau fragments at ∼35 kDa. These findings shed further light on the wide pathological and clinical spectrum of four-repeat tauopathy, representing PSP in the broad sense rather than classical PSP. PMID:25974705

  4. Joint modelling of longitudinal and multi-state processes: application to clinical progressions in prostate cancer.

    PubMed

    Ferrer, Loïc; Rondeau, Virginie; Dignam, James; Pickles, Tom; Jacqmin-Gadda, Hélène; Proust-Lima, Cécile

    2016-09-30

    Joint modelling of longitudinal and survival data is increasingly used in clinical trials on cancer. In prostate cancer for example, these models permit to account for the link between longitudinal measures of prostate-specific antigen (PSA) and time of clinical recurrence when studying the risk of relapse. In practice, multiple types of relapse may occur successively. Distinguishing these transitions between health states would allow to evaluate, for example, how PSA trajectory and classical covariates impact the risk of dying after a distant recurrence post-radiotherapy, or to predict the risk of one specific type of clinical recurrence post-radiotherapy, from the PSA history. In this context, we present a joint model for a longitudinal process and a multi-state process, which is divided into two sub-models: a linear mixed sub-model for longitudinal data and a multi-state sub-model with proportional hazards for transition times, both linked by a function of shared random effects. Parameters of this joint multi-state model are estimated within the maximum likelihood framework using an EM algorithm coupled with a quasi-Newton algorithm in case of slow convergence. It is implemented under R, by combining and extending mstate and JM packages. The estimation program is validated by simulations and applied on pooled data from two cohorts of men with localized prostate cancer. Thanks to the classical covariates available at baseline and the repeated PSA measurements, we are able to assess the biomarker's trajectory, define the risks of transitions between health states and quantify the impact of the PSA dynamics on each transition intensity. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Direct reconstruction of the source intensity distribution of a clinical linear accelerator using a maximum likelihood expectation maximization algorithm.

    PubMed

    Papaconstadopoulos, P; Levesque, I R; Maglieri, R; Seuntjens, J

    2016-02-01

    Direct determination of the source intensity distribution of clinical linear accelerators is still a challenging problem for small field beam modeling. Current techniques most often involve special equipment and are difficult to implement in the clinic. In this work we present a maximum-likelihood expectation-maximization (MLEM) approach to the source reconstruction problem utilizing small fields and a simple experimental set-up. The MLEM algorithm iteratively ray-traces photons from the source plane to the exit plane and extracts corrections based on photon fluence profile measurements. The photon fluence profiles were determined by dose profile film measurements in air using a high density thin foil as build-up material and an appropriate point spread function (PSF). The effect of other beam parameters and scatter sources was minimized by using the smallest field size ([Formula: see text] cm(2)). The source occlusion effect was reproduced by estimating the position of the collimating jaws during this process. The method was first benchmarked against simulations for a range of typical accelerator source sizes. The sources were reconstructed with an accuracy better than 0.12 mm in the full width at half maximum (FWHM) to the respective electron sources incident on the target. The estimated jaw positions agreed within 0.2 mm with the expected values. The reconstruction technique was also tested against measurements on a Varian Novalis Tx linear accelerator and compared to a previously commissioned Monte Carlo model. The reconstructed FWHM of the source agreed within 0.03 mm and 0.11 mm to the commissioned electron source in the crossplane and inplane orientations respectively. The impact of the jaw positioning, experimental and PSF uncertainties on the reconstructed source distribution was evaluated with the former presenting the dominant effect.

  6. Cross-section Trichometry: A Clinical Tool for Assessing the Progression and Treatment Response of Alopecia

    PubMed Central

    Wikramanayake, Tongyu Cao; Mauro, Lucia M; Tabas, Irene A; Chen, Anne L; Llanes, Isabel C; Jimenez, Joaquin J

    2012-01-01

    Background: To properly assess the progression and treatment response of alopecia, one must measure the changes in hair mass, which is influenced by both the density and diameter of hair. Unfortunately, a convenient device for hair mass evaluation had not been available to dermatologists until the recent introduction of the cross-section trichometer, which directly measures the cross-sectional area of an isolated bundle of hair. Objective: We sought to evaluate the accuracy and sensitivity of the HairCheck® device, a commercial product derived from the original cross-section trichometer. Materials and Methods: Bundles of surgical silk and human hair were used to evaluate the ability of the HairCheck® device to detect and measure small changes in the number and diameter of strands, and bundle weight. Results: Strong correlations were observed between the bundle's cross-sectional area, displayed as the numeric Hair Mass Index (HMI), the number of strands, the silk/hair diameter, and the bundle dry weight. Conclusion: HMI strongly correlated with the number and diameter of silk/hair, and the weight of the bundle, suggesting that it can serve as a valid indicator of hair mass. We have given the name cross-section trichometry (CST) to the methodology of obtaining the HMI using the HairCheck® system. CST is a simple modality for the quantification of hair mass, and may be used as a convenient and useful tool to clinically assess changes in hair mass caused by thinning, shedding, breakage, or growth in males and females with progressive alopecia or those receiving alopecia treatment. PMID:23766610

  7. JC Virus PCR Detection Is Not Infallible: A Fulminant Case of Progressive Multifocal Leukoencephalopathy with False-Negative Cerebrospinal Fluid Studies despite Progressive Clinical Course and Radiological Findings

    PubMed Central

    Babi, Mohamed-Ali; Pendlebury, William; Braff, Steven; Waheed, Waqar

    2015-01-01

    We describe a case with a false-negative PCR-based analysis for JC virus in cerebrospinal fluid (CSF) in a patient with clinical and radiological findings suggestive of progressive multifocal leukoencephalopathy (PML) who was on chronic immunosuppressive therapy for rheumatoid arthritis. Our patient developed rapidly progressive global decline with clinical and radiographic findings suggestive of PML, but JC virus PCR in CSF was negative. The patient passed away 3 months from the onset of her neurological symptoms. Autopsy confirmed the diagnosis of PML with presence of JC-polyoma virus by immunohistochemical staining. This case highlights the potential of false-negative JC virus PCR in CSF when radiographic and clinical features are suggestive of “possible PML.” We review the plausible causes of potential false-negative CSF results and suggest that when the clinical presentation is suspicious for PML repeat CSF analysis utilizing ultrasensitive PCR assay and subsequent brain biopsy should be considered if CSF remains negative. Additionally, appropriate exclusion of other neurologic conditions is essential. PMID:25861493

  8. Effect of Creatine Monohydrate on Clinical Progression in Patients With Parkinson Disease

    PubMed Central

    2015-01-01

    IMPORTANCE There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. DESIGN, SETTING, AND PATIENTS The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. INTERVENTIONS Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). MAIN OUTCOMES AND MEASURES The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5–4775) indicate worse outcomes. RESULTS The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95

  9. Rapid progression of intracranial melanoma metastases controlled with combined BRAF/MEK inhibition after discontinuation of therapy: a clinical challenge.

    PubMed

    N Cagney, Daniel; Alexander, Brian M; Hodi, F Stephen; Buchbinder, Elizabeth I; Ott, Patrick A; Aizer, Ayal A

    2016-09-01

    Novel systemic therapies with anti-tumor activity in the brain including small molecules targeting BRAF and MEK, and immune checkpoint inhibition, offer the possibility of improved control of intracranial disease. A number of prospective trials support the judicious use of modern systemic therapies in patients with melanoma and limited brain metastases .The intracranial clinical course of patients who progress extracranially on BRAF/MEK inhibition remains poorly described in the literature. In this report, we highlight a series of clinical cases, with rapid progression of intracranial disease following discontinuation of dabrafenib/trametinib for extracranial disease progression or toxicity, a previously unreported finding in the medical literature with significant implications for patient care.

  10. PREDICTING FOOT PROGRESSION ANGLE DURING GAIT USING TWO CLINICAL MEASURES IN HEALTHY ADULTS, A PRELIMINARY STUDY

    PubMed Central

    Winters, Kyle; Kampwerth, Teri; McAfee, Blake; Payne, Lisa; Roeckenhaus, Tara; Ross, Sandy A.

    2016-01-01

    ABSTRACT Background The foot progression angle (FPA) is related to the transverse plane rotation of the lower extremities and associated with many lower extremity conditions. Purpose The purpose of this study was to examine how two commonly used clinical measures, tibio-fibular torsion (TF) and hip rotation, can be used to predict FPA during gait in healthy adults. Study Design Cross-sectional study design Methods Passive hip internal and external rotation ranges of motion and TF torsion were measured with a 12-inch goniometer while the FPA (degree of toe-in/out) was measured with the GAITRite during midstance in sixty participants. The data was analyzed using a multiple regression model. Results Hip ER was not significant and was therefore excluded from the final model. The final model included passive hip IR and TF torsion (F = 19.64; p < .001; multiple R2 = .41; adjusted R2 = .39). Simple binary correlations showed that hip IR had a moderate negative correlation (r = -.40) with FPA (the greater the hip IR, the greater the in-toeing) while TF torsion had a positive correlation (r = .39) with FPA (the greater the external TF torsion. the greater the out-toeing). Conclusions Greater amount of passive hip IR predicts in-toeing while greater TF torsion predicts out-toeing of the foot during midstance phase of gait. Level of Evidence Level 2 PMID:27274426

  11. Direct cardiac reprogramming: progress and challenges in basic biology and clinical applications.

    PubMed

    Sadahiro, Taketaro; Yamanaka, Shinya; Ieda, Masaki

    2015-04-10

    The discovery of induced pluripotent stem cells changed the field of regenerative medicine and inspired the technological development of direct reprogramming or the process by which one cell type is directly converted into another without reverting a stem cell state by overexpressing lineage-specific factors. Indeed, direct reprogramming has proven sufficient in yielding a diverse range of cell types from fibroblasts, including neurons, cardiomyocytes, endothelial cells, hematopoietic stem/progenitor cells, and hepatocytes. These studies revealed that somatic cells are more plastic than anticipated, and that transcription factors, microRNAs, epigenetic factors, secreted molecules, as well as the cellular microenvironment are all important for cell fate specification. With respect to the field of cardiology, the cardiac reprogramming presents as a novel method to regenerate damaged myocardium by directly converting endogenous cardiac fibroblasts into induced cardiomyocyte-like cells in situ. The first in vivo cardiac reprogramming reports were promising to repair infarcted hearts; however, the low induction efficiency of fully reprogrammed, functional induced cardiomyocyte-like cells has become a major challenge and hampered our understanding of the reprogramming process. Nevertheless, recent studies have identified several critical factors that may affect the efficiency and quality of cardiac induction and have provided new insights into the mechanisms of cardiac reprogramming. Here, we review the progress in direct reprogramming research and discuss the perspectives and challenges of this nascent technology in basic biology and clinical applications.

  12. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis

    NASA Astrophysics Data System (ADS)

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-09-01

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862) while for subacute ILD patients (disease duration 3–6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM.

  13. Role of Chronic Inflammation in Myopia Progression: Clinical Evidence and Experimental Validation.

    PubMed

    Lin, Hui-Ju; Wei, Chang-Ching; Chang, Ching-Yao; Chen, Ter-Hsin; Hsu, Yu-An; Hsieh, Yi-Ching; Chen, Hsuan-Ju; Wan, Lei

    2016-08-01

    Prevention and treatment of myopia is an important public problem worldwide. We found a higher incidence of myopia among patients with inflammatory diseases such as type 1 diabetes mellitus (7.9%), uveitis (3.7%), or systemic lupus erythematosus (3.5%) compared to those without inflammatory diseases (p<0.001) using data from children (<18years old) in the National Health Insurance Research database. We then examined the inhibition of myopia by atropine in Syrian hamsters with monocular form deprivation (MFD), an experimental myopia model. We found atropine downregulated inflammation in MFD eyes. The expression levels of c-Fos, nuclear factor κB (NFκB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were upregulated in myopic eyes and downregulated upon treatment with atropine. The relationship between the inflammatory response and myopia was investigated by treating MFD hamsters with the immunosuppressive agent cyclosporine A (CSA) or the inflammatory stimulators lipopolysaccharide (LPS) or peptidoglycan (PGN). Myopia progression was slowed by CSA application but was enhanced by LPS and PGN administration. The levels of c-Fos, NF-κB, IL-6, and TNF-α were upregulated in LPS- and PGN-treated eyes and downregulated by CSA treatment. These findings provide clinical and experimental evidence that inflammation plays a crucial role in the development of myopia. PMID:27470424

  14. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis

    PubMed Central

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-01-01

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862); while for subacute ILD patients (disease duration 3–6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM. PMID:27615411

  15. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis.

    PubMed

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-01-01

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862); while for subacute ILD patients (disease duration 3-6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM. PMID:27615411

  16. Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification

    PubMed Central

    Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

    2016-01-01

    Background Individuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level. Methods Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework. Results Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions. Conclusions We developed an accurate prognostic model for predicting

  17. Progression of non-cavitated lesions in dentin through a nonsurgical approach: a preliminary 12-month clinical observation

    PubMed Central

    da Silveira, Ana Daniela Silva; Borges, Boniek Castillo Dutra; de Almeida Varela, Hugo; de Lima, Kenio Costa; Pinheiro, Isauremi Vieira de Assunção

    2012-01-01

    Objective: Considering the minimally invasive approach to dentistry, the scientific community has focused on non-invasive treatments for caries lesions. The aim of this study was to evaluate the efficacy of a nonsurgical approach to arrest occlusal non-cavitated dentin lesions through glass ionomer sealing. Methods: In this controlled clinical trial, 51 teeth with clinically non-cavitated occlusal caries radiographically located beneath the enamel-dentine junction (radiolucent area) were selected among patients presenting a moderate to high risk of caries. The teeth were randomly divided into two groups: an experimental group receiving an application of Vidrion-R (SS White) glass ionomer and a control group not submitted to any clinical intervention. Caries progression was monitored by clinical and radiographic examination at 4-monthly intervals over a period of one year. In addition, marginal integrity of the sealant was evaluated in the experimental group. Results: Clinical examination showed no statistical difference between the groups (P=.13). On the other hand, sealed teeth presented lower caries progression when analyzed by radiographic examination (P=.004). Conclusion: A glass ionomer sealant over non-cavitated occlusal caries lesions in dentin may not be sufficiently effective in arresting their progression. PMID:22229005

  18. T cell subsets: an immunological biomarker to predict progression to clinical arthritis in ACPA-positive individuals

    PubMed Central

    Hunt, L; Hensor, E M; Nam, J; Burska, A N; Parmar, R; Emery, P; Ponchel, F

    2016-01-01

    Objectives Anticitrullinated protein antibody (ACPA)+ individuals with non-specific musculoskeletal symptoms are at risk of inflammatory arthritis (IA). This study aims to demonstrate the predictive value of T cell subset quantification for progression towards IA and compare it with previously identified clinical predictors of progression. Methods 103 ACPA+ individuals without clinical synovitis were observed 3-monthly for 12 months and then as clinically indicated. The end point was the development of IA. Naïve, regulatory T cells (Treg) and inflammation related cells (IRCs) were quantified by flow cytometry. Areas under the ROC curve (AUC) were calculated. Adjusted logistic regressions and Cox proportional hazards models for time to progression to IA were constructed. Results Compared with healthy controls (age adjusted where appropriate), ACPA+ individuals demonstrated reduced naïve (22.1% of subjects) and Treg (35.8%) frequencies and elevated IRC (29.5%). Of the 103 subjects, 48(46.6%) progressed. Individually, T cell subsets were weakly predictive (AUC between 0.63 and 0.66), although the presence of 2 T cell abnormalities had high specificity. Three models were compared: model-1 used T cell subsets only, model-2 used previously published clinical parameters, model-3 combined clinical data and T cell data. Model-3 performed the best (AUC 0.79 (95% CI 0.70 to 0.89)) compared with model-1 (0.75 (0.65 to 0.86)) and particularly with model-2 (0.62 (0.54 to 0.76)) demonstrating the added value of T cell subsets. Time to progression differed significantly between high-risk, moderate-risk and low-risk groups from model-3 (p=0.001, median 15.4 months, 25.8 months and 63.4 months, respectively). Conclusions T cell subset dysregulation in ACPA+ individuals predates the onset of IA, predicts the risk and faster progression to IA, with added value over previously published clinical predictors of progression. PMID:27613874

  19. Esophageal and small intestinal manifestations of progressive systemic sclerosis. A clinical and experimental study.

    PubMed

    Hendel, L

    1994-09-01

    Progressive systemic sclerosis (PSS) is a systemic disease with a high frequency of gastro-intestinal involvement. The present thesis deals with the occurrence of, the complications to, and the treatment of the esophageal manifestations combined with more experimental studies on small intestine manifestations. The conclusions in this thesis are based on results achieved in 9 original previously published papers. The pattern of esophageal dysmotility is thoroughly evaluated in 156 consecutive PSS patients and is found to be identical to what is found in other large series of PSS patients. In paper no. I dysmotility variables are correlated to the occurrence of gastroesophageal reflux (GER) and it is shown that also in this group of patients with well defined dysmotility problems the only reliable GER test is pH-metry. Esophageal dysmotility furthers esophageal candidosis, which is further facilitated by anti-reflux treatment. This problem is evaluated in paper no. V. Progression of esophageal dysmotility in spite of D-penicillamine treatment is shown in paper no. VII and confirms the non-stable condition of the PSS patient in regard to esophageal manifestations and complications. This point is also outlined in paper no. IX concerning surveillance and continuous treatment of esophageal PSS. Esophageal stricturing is a well-known entity in PSS. The etiologic question of esophageal stricturing being a manifestation of PSS and/or a peptic complication, is approached in paper no. VIII. PSS manifestations of the small intestine are not as frequent as in the esophagus, in the present material only 19% presented with X-ray changes. However, bacterial count of duodenal juice as an indirect measurement of small intestinal dysmotility in paper no. VI indicates a much larger percentage of small intestinal involvement than revealed by X-ray. In paper no. VI the exocrine pancreatic function was assessed in 16 PSS patients. It is shown that the endogenous stimulation capacity is

  20. Evaluation of Study and Patient Characteristics of Clinical Studies in Primary Progressive Multiple Sclerosis: A Systematic Review

    PubMed Central

    Ziemssen, T.; Rauer, S.; Stadelmann, C.; Henze, T.; Koehler, J.; Penner, I.-K.; Lang, M.; Poehlau, D.; Baier-Ebert, M.; Schieb, H.; Meuth, S.

    2015-01-01

    Background So far, clinical studies in primary progressive MS (PPMS) have failed to meet their primary efficacy endpoints. To some extent this might be attributable to the choice of assessments or to the selection of the study population. Objective The aim of this study was to identify outcome influencing factors by analyzing the design and methods of previous randomized studies in PPMS patients without restriction to intervention or comparator. Methods A systematic literature search was conducted in MEDLINE, EMBASE, BIOSIS and the COCHRANE Central Register of Controlled Trials (inception to February 2015). Keywords included PPMS, primary progressive multiple sclerosis and chronic progressive multiple sclerosis. Randomized, controlled trials of at least one year’s duration were selected if they included only patients with PPMS or if they reported sufficient PPMS subgroup data. No restrictions with respect to intervention or comparator were applied. Study quality was assessed by a biometrics expert. Relevant baseline characteristics and outcomes were extracted and compared. Results Of 52 PPMS studies identified, four were selected. Inclusion criteria were notably different among studies with respect to both the definition of PPMS and the requirements for the presence of disability progression at enrolment. Differences between the study populations included the baseline lesion load, pretreatment status and disease duration. The rate of disease progression may also be an important factor, as all but one of the studies included a large proportion of patients with a low progression rate. In addition, the endpoints specified could not detect progression adequately. Conclusion Optimal PPMS study methods involve appropriate patient selection, especially regarding the PPMS phenotype and progression rate. Functional composite endpoints might be more sensitive than single endpoints in capturing progression. PMID:26393519

  1. Drug-associated progressive multifocal leukoencephalopathy: a clinical, radiological, and cerebrospinal fluid analysis of 326 cases.

    PubMed

    Maas, Roderick P P W M; Muller-Hansma, Annemarie H G; Esselink, Rianne A J; Murk, Jean-Luc; Warnke, Clemens; Killestein, Joep; Wattjes, Mike P

    2016-10-01

    The implementation of a variety of immunosuppressive therapies has made drug-associated progressive multifocal leukoencephalopathy (PML) an increasingly prevalent clinical entity. The purpose of this study was to investigate its diagnostic characteristics and to determine whether differences herein exist between the multiple sclerosis (MS), neoplasm, post-transplantation, and autoimmune disease subgroups. Reports of possible, probable, and definite PML according to the current diagnostic criteria were obtained by a systematic search of PubMed and the Dutch pharmacovigilance database. Demographic, epidemiologic, clinical, radiological, cerebrospinal fluid (CSF), and histopathological features were extracted from each report and differences were compared between the disease categories. In the 326 identified reports, PML onset occurred on average 29.5 months after drug introduction, varying from 14.2 to 37.8 months in the neoplasm and MS subgroups, respectively. The most common overall symptoms were motor weakness (48.6 %), cognitive deficits (43.2 %), dysarthria (26.3 %), and ataxia (24.1 %). The former two also constituted the most prevalent manifestations in each subgroup. Lesions were more often localized supratentorially (87.7 %) than infratentorially (27.4 %), especially in the frontal (64.1 %) and parietal lobes (46.6 %), and revealed enhancement in 27.6 % of cases, particularly in the MS (42.9 %) subgroup. Positive JC virus results in the first CSF sample were obtained in 63.5 %, while conversion after one or more negative outcomes occurred in 13.7 % of cases. 52.2 % of patients died, ranging from 12.0 to 83.3 % in the MS and neoplasm subgroups, respectively. In conclusion, despite the heterogeneous nature of the underlying diseases, motor weakness and cognitive changes were the two most common manifestations of drug-associated PML in all subgroups. The frontal and parietal lobes invariably constituted the predilection sites of drug

  2. Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer—20 Years of Progress

    PubMed Central

    Hardingham, Jennifer E; Grover, Phulwinder; Winter, Marnie; Hewett, Peter J; Price, Timothy J; Thierry, Benjamin

    2015-01-01

    Circulating tumor cells (CTC) may be defined as tumor- or metastasis-derived cells that are present in the bloodstream. The CTC pool in colorectal cancer (CRC) patients may include not only epithelial tumor cells, but also tumor cells undergoing epithelial–mesenchymal transition (EMT) and tumor stem cells. A significant number of patients diagnosed with early stage CRC subsequently relapse with recurrent or metastatic disease despite undergoing “curative” resection of their primary tumor. This suggests that an occult metastatic disease process was already underway, with viable tumor cells being shed from the primary tumor site, at least some of which have proliferative and metastatic potential and the ability to survive in the bloodstream. Such tumor cells are considered to be responsible for disease relapse in these patients. Their detection in peripheral blood at the time of diagnosis or after resection of the primary tumor may identify those early-stage patients who are at risk of developing recurrent or metastatic disease and who would benefit from adjuvant therapy. CTC may also be a useful adjunct to radiological assessment of tumor response to therapy. Over the last 20 years many approaches have been developed for the isolation and characterization of CTC. However, none of these methods can be considered the gold standard for detection of the entire pool of CTC. Recently our group has developed novel unbiased inertial microfluidics to enrich for CTC, followed by identification of CTC by imaging flow cytometry. Here, we provide a review of progress on CTC detection and clinical significance over the last 20 years. PMID:26605644

  3. Persistent Uroplakin Expression in Advanced Urothelial Carcinomas: Implications in Urothelial Tumor Progression and Clinical Outcome

    PubMed Central

    Huang, Hong-Ying; Shariat, Shahrokh F.; Sun, Tung-Tien; Lepor, Herbert; Shapiro, Ellen; Hsieh, Jer-Tsong; Ashfaq, Raheela; Lotan, Yair; Wu, Xue-Ru

    2007-01-01

    As the terminal differentiation products of human urothelium, uroplakins (UPs) would be expected to diminish during urothelial tumorigenesis. Surprisingly, recent studies found UPs to be retained even by well-advanced urothelial carcinomas, suggesting that the loss of UPs does not strictly parallel urothelial transformation. Little is known, however, about whether the status of UPs is associated with a particular pathological parameter, tumor’s biological behavior or patient outcome. Here we assessed UP expression by immunohistochemistry on tissue arrays from 285 patients with bladder urothelial carcinomas or non-tumor conditions. UPs were expressed in all 9 normal urothelial specimens, 63/74 (85%) patients with non-muscle-invasive urothelial carcinomas on transurethral resection, 104/202 (51.5%) patients who underwent radical cystectomy for advanced urothelial carcinomas, and 33/50 (66%) lymph node metastases. Normally associated with urothelial apical surface, UPs were localized aberrantly in tumors, including micro-luminal, basal-laminal, cytoplasmic or uniform patterns. In non-muscle-invasive diseases, there was no association between UP expression and disease recurrence, progression or mortality. In contrast, in invasive diseases, absent UP expression was significantly associated with advanced pathologic stage, lymph node metastases, disease recurrence and bladder cancer-specific mortality (p=0.042, p=0.035, p=0.023 and p=0.022, respectively) in univariate analyses. Furthermore, UP status was independent of key cell-cycle regulators, including p53, pRb, p27 and cyclin D1, thus excluding a functional link between these two groups of proteins. Our data demonstrate for the first time that persistent UP expression is associated with a favorable clinical outcome and that UPs may be used as adjunct markers for predicting the prognoses of patients with invasive and metastatic bladder carcinomas. Our results also suggest that UP-positive and –negative carcinomas

  4. MM2 subtype of sporadic Creutzfeldt-Jakob disease may underlie the clinical presentation of progressive supranuclear palsy.

    PubMed

    Petrovic, Igor N; Martin-Bastida, Antonio; Massey, Luke; Ling, Helen; O'Sullivan, Sean S; Williams, David R; Holton, Janice L; Revesz, Tamas; Ironside, James W; Lees, Andrew J; Silveira-Moriyama, Laura

    2013-04-01

    The classical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) is rapid progressive dementia often associated with myoclonus and ataxia followed by death in less than a year from diagnosis. The few patients in the literature who presented with parkinsonism and who were suspected to have progressive supranuclear palsy (PSP) all ran a malignant course and most of them died within 3 years of diagnosis. We screened the Queen Square Brain Bank database and, among 213 patients with a clinical diagnosis of PSP, we found ten patients with 3 years or less disease duration, including one patient with CJD pathology. We report this patient and review other similar cases from the literature. Ten additional cases with similar presentation were identified in the literature. The mean disease duration was 24.2 months. The classical clinical, radiological and laboratory findings for sCJD were absent in the majority of these cases. Clinical presentation of these patients consists of: early falls, prominent dementia, early vertical supranuclear gaze palsy and symmetric akinetic syndrome. In the patients who were subtyped at post-mortem, all four represented the MM2 subtype of sCJD. A rapidly progressive course of PSP with early falls, cognitive impairments and vertical supranuclear gaze palsy should raise suspicion of underlying sCJD pathology regardless of absence of supportive findings on ancillary tests. This case and the literature support the notion that biochemical properties of the prion protein can influence the clinical presentation of sCJD.

  5. Intermediate clinical endpoints: a bridge between progression-free survival and overall survival in ovarian cancer trials.

    PubMed

    Matulonis, Ursula A; Oza, Amit M; Ho, Tony W; Ledermann, Jonathan A

    2015-06-01

    Ovarian cancer patients are usually diagnosed at an advanced stage, experience recurrence after platinum-based chemotherapy, and eventually develop resistance to chemotherapy. Overall survival (OS), which has improved in recent years as more active treatments have been incorporated into patient care, is regarded as the most clinically relevant endpoint in ovarian cancer trials. However, although there remains a significant need for new treatments that prolong OS further without compromising quality of life, it has become increasingly difficult to detect an OS benefit for investigational treatments because of the use of multiple lines of chemotherapy to treat ovarian cancer. Progression-free survival (PFS), which measures the time to disease progression or death, is unaffected by postprogression therapies but does not evaluate the long-term impact of investigational treatments on tumor biology and responses to future therapies. Recent clinical trials of targeted agents in relapsed ovarian cancer have shown improvements in PFS but not OS, and this is possibly reflective of the long postprogression survival (PPS) period associated with this disease. Intermediate endpoints such as the time to second disease progression or death and the time to second subsequent therapy or death may provide supportive evidence for clinically meaningful PFS improvements and may be used to determine whether these improvements persist beyond the first disease progression and throughout subsequent lines of therapy. For clinical trials that have settings with a long PPS duration and/or involve multiple rounds of postprogression therapy, a primary endpoint of PFS supported by intermediate clinical endpoints and OS may provide a more comprehensive approach for evaluating efficacy.

  6. Amyotrophic lateral sclerosis progression: Iran-ALS clinical registry, a multicentre study.

    PubMed

    Shamshiri, Hosein; Fatehi, Farzad; Davoudi, Farnoush; Mir, Elham; Pourmirza, Behin; Abolfazli, Roya; Etemadifar, Masoud; Harirchian, Mohammad Hossein; Gharagozli, Koroush; Ayromlou, Hormoz; Basiri, Keivan; Zamani, Babak; Rohani, Mohammad; Sedighi, Behnaz; Roudbari, Ali; Delavar Kasmaei, Hossein; Nikkhah, Karim; Ranjbar Naeini, Alireza; Nafissi, Shahriar

    2015-01-01

    This study was designed to evaluate ALS progression among different subgroups of Iranian patients. Three hundred and fifty-eight patients from centres around the country were registered and their progression rate was evaluated using several scores including Manual Muscle Test scoring (MMT) and the revised ALS Functional Rating Scale (ALSFRS-R). Progression rate was analysed separately in subgroups regarding gender, onset site, stage of disease and riluzole consumption. A significant difference in MMT deterioration rate (p = 0.01) was noted between those who used riluzole and those who did not. No significant difference was observed in progression rates between male/female and bulbar-onset/limb-onset groups using riluzole. In conclusion, riluzole has a significant effect on muscle force deterioration rate but not functional scale. Progression rate was not influenced by site of onset or gender.

  7. Treatment with electromagnetic field alters the clinical course of chronic progressive multiple sclerosis--a case report.

    PubMed

    Sandyk, R

    1996-11-01

    It is estimated that 10-20% of patients with multiple sclerosis (MS) have a chronic progressive (CP) course characterized by an insidious of neurological deficits followed by steady progression of disability in the absence of symptomatic remission. No therapeutic modality has shown specific efficacy in the treatment of patients with CP MS and there are no data to indicate that any pharmacologic or other modality alters the clinical course of CP MS. Treatment with picotesla electromagnetic fields (EMFs) is a highly effective modality for the symptomatic management of MS including the chronic progressive form. In addition, this treatment also appears to alter the natural course of the disease in CP patients. A 36 year-old man experienced, at the age of 31, insidious weakness in the legs and several months later developed difficulties with balance with ataxia of gait. His gait abnormality progressed slowly over the following years and at the age of 35 he was severely disabled with spastic paraparesis and ataxia using a rolling walker for ambulation and a scooter for longer distances. In particular, his disability had progressed rapidly over the six months preceding the initiation of treatment with EMFs. He as classified have CP MS and his prognosis was considered extremely unfavorable due to the degree of cerebellar and pyramidal tract involvement and the rapid course of deterioration. In July 1995 the patient began experimental treatment with EMFs. While receiving three treatment sessions a week over 12 months he experienced improvement in cerebellar functions such as gait, balance and tremor as well as bowel and bladder functions, mood, sleep and cognitive function and resolution of diplopia, blurring of vision, dysarthria, paresthesias in the hands, and fatigue. Most remarkably, there was no further progression of the disease during the course of magnetic therapy. This case illustrated that treatment with EMFs, in addition to producing symptomatic improvement, also

  8. Extrapolation chamber mounted on perspex for calibration of high energy photon and electron beams from a clinical linear accelerator

    PubMed Central

    Ravichandran, R.; Binukumar, J. P.; Sivakumar, S. S.; Krishnamurthy, K.; Davis, C. A.

    2009-01-01

    The objective of the present study is to establish radiation standards for absorbed doses, for clinical high energy linear accelerator beams. In the nonavailability of a cobalt-60 beam for arriving at Nd, water values for thimble chambers, we investigated the efficacy of perspex mounted extrapolation chamber (EC) used earlier for low energy x-rays and beta dosimetry. Extrapolation chamber with facility for achieving variable electrode separations 10.5mm to 0.5mm using micrometer screw was used for calibrations. Photon beams 6 MV and 15 MV and electron beams 6 MeV and 15 MeV from Varian Clinac linacs were calibrated. Absorbed Dose estimates to Perspex were converted into dose to solid water for comparison with FC 65 ionisation chamber measurements in water. Measurements made during the period December 2006 to June 2008 are considered for evaluation. Uncorrected ionization readings of EC for all the radiation beams over the entire period were within 2% showing the consistency of measurements. Absorbed doses estimated by EC were in good agreement with in-water calibrations within 2% for photons and electron beams. The present results suggest that extrapolation chambers can be considered as an independent measuring system for absorbed dose in addition to Farmer type ion chambers. In the absence of standard beam quality (Co-60 radiations as reference Quality for Nd,water) the possibility of keeping EC as Primary Standards for absorbed dose calibrations in high energy radiation beams from linacs should be explored. As there are neither Standard Laboratories nor SSDL available in our country, we look forward to keep EC as Local Standard for hospital chamber calibrations. We are also participating in the IAEA mailed TLD intercomparison programme for quality audit of existing status of radiation dosimetry in high energy linac beams. The performance of EC has to be confirmed with cobalt-60 beams by a separate study, as linacs are susceptible for minor variations in dose

  9. Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study

    PubMed Central

    2014-01-01

    Background Progressive Supranuclear Palsy (PSP) is a sporadic and progressive neurodegenerative disease which belongs to the family of tauopathies and involves both cortical and subcortical structures. No effective therapy is to date available. Methods/design Autologous bone marrow (BM) mesenchymal stem cells (MSC) from patients affected by different type of parkinsonisms have shown their ability to improve the dopaminergic function in preclinical and clinical models. It is also possible to isolate and expand MSC from the BM of PSP patients with the same proliferation rate and immuphenotypic profile as MSC from healthy donors. BM MSC can be efficiently delivered to the affected brain regions of PSP patients where they can exert their beneficial effects through different mechanisms including the secretion of neurotrophic factors. Here we propose a randomized, placebo-controlled, double-blind phase I clinical trial in patients affected by PSP with MSC delivered via intra-arterial injection. Discussion To our knowledge, this is the first clinical trial to be applied in a no-option parkinsonism that aims to test the safety and to exploit the properties of autologous mesenchymal stem cells in reducing disease progression. The study has been designed to test the safety of this “first-in-man” approach and to preliminarily explore its efficacy by excluding the placebo effect. Trial registration NCT01824121 PMID:24438512

  10. Analysis of midwifery students' written reflections to evaluate progression in learning during clinical practice at birthing units.

    PubMed

    Persson, Eva K; Kvist, Linda J; Ekelin, Maria

    2015-03-01

    Written daily reflections during clinical practice on birthing units have been used during several years in midwifery education at Lund University, Sweden. However, the usefulness of these reflections for evaluation of progression in learning and professional development of students has to date not been evaluated. In order to analyse written reflections, two taxonomies developed by Bloom and Pettersen have been applied to the texts. Progression in the professional development of midwifery students can be seen through levels of complexity in cognitive and psycho-motor learning areas and also in the description of learning situations. Progression can be seen from a basic description of facts in simple situations at the beginning of the students' practice to a complex description of complicated situations towards the end of the practice. Written daily reflections appear to be a suitable method to help students to reflect in a structured way, thereby helping their professional development. Reflections can help clinical supervisors to understand the needs of the individual student and to support their knowledge accruement. Daily written reflections on clinical practice can be of use in other health education programs.

  11. Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease.

    PubMed

    Douaud, Gwenaëlle; Menke, Ricarda A L; Gass, Achim; Monsch, Andreas U; Rao, Anil; Whitcher, Brandon; Zamboni, Giovanna; Matthews, Paul M; Sollberger, Marc; Smith, Stephen

    2013-01-30

    Diffusion imaging is a promising marker of microstructural damage in neurodegenerative disorders, but interpretation of its relationship with underlying neuropathology can be complex. Here, we examined both volumetric and brain microstructure abnormalities in 13 amnestic patients with mild cognitive impairment (MCI), who progressed to probable Alzheimer's disease (AD) no earlier than 2 years after baseline scanning, in order to focus on early, and hence more sensitive, imaging markers. We compared them to 22 stable amnestic MCI patients with similar cognitive performance and episodic memory impairment but who did not show progression of symptoms for at least 3 years. Significant group differences were mainly found in the volume and microstructure of the left hippocampus, while white matter group differences were also found in the body of the fornix, left fimbria, and superior longitudinal fasciculus (SLF). Diffusion index abnormalities in the SLF were the sign of a subtle microstructural injury not detected by standard atrophy measures in the corresponding gray matter regions. The microstructural measure obtained in the left hippocampus using diffusion imaging showed the most substantial differences between the two groups and was the best single predictor of future progression to AD. An optimal prediction model (91% accuracy, 85% sensitivity, 96% specificity) was obtained by combining MRI measures and CSF protein biomarkers. These results highlight the benefit of using the information of brain microstructural damage, in addition to traditional gray matter volume, to detect early, subtle abnormalities in MCI prior to clinical progression to probable AD and, in combination with CSF markers, to accurately predict such progression.

  12. [A clinical trial of neutron capture therapy for brain tumors]. Technical progress report 1988

    SciTech Connect

    Zamenhof, R.G.

    1988-12-31

    This report describes progress made in refining of neutron-induced alpha tract autoradiography, in designing epithermal neutron bean at MITR-II and in planning treatment dosimetry using Monte Carlo techniques.

  13. Efficacy of Trastuzumab in Routine Clinical Practice and After Progression for Metastatic Breast Cancer Patients: The Observational Hermine Study

    PubMed Central

    Antoine, Eric C.; Vincent-Salomon, Anne; Delozier, Thierry; Kerbrat, Pierre; Bethune-Volters, Anne; Guastalla, Jean-Paul; Spielmann, Marc; Mauriac, Louis; Misset, Jean-Louis; Serin, Daniel; Campone, Mario; Hebert, Christophe; Remblier, Céline; Bergougnoux, Loïc; Campana, Frank; Namer, Moïse

    2010-01-01

    Background. The Hermine study observed the use of trastuzumab for metastatic breast cancer (MBC) in routine practice, including patients who received trastuzumab treatment beyond progression (TBP). Patients and Methods. The study observed 623 patients for ≥2 years. Treatment was given according to oncologists' normal clinical practices. Endpoints included duration of treatment, efficacy, and cardiac safety. The TBP subanalysis compared overall survival (OS) in 177 patients who received first-line trastuzumab and either continued trastuzumab for ≥30 days following progression or stopped at or before progression. Results. The median treatment duration was 13.3 months. In the first-, second-, and third-line or beyond treatment groups, the median time to progression (TTP) were 10.3 months, 9.0 months, and 6.3 months, and the median OS times were 30.3 months, 27.1 months, and 23.2 months, respectively. Heart failure was observed in 2.6% of patients, although no cardiac-associated deaths occurred. In the TBP subanalysis, the median OS duration from treatment initiation and time of disease progression were longer in patients who continued receiving trastuzumab TBP (>27.8 months and 21.3 months, respectively) than in those who stopped (16.8 months and 4.6 months, respectively). However, the groups were not completely comparable, because patients who continued trastuzumab TBP had better prognoses at treatment initiation. The median TTP was longer in patients who continued trastuzumab TBP (10.2 months) than in those who stopped (7.1 months). Conclusion. The Hermine findings confirm that the pivotal trials of first-line trastuzumab treatment in MBC patients are applicable in clinical practice. The subanalysis suggests that trastuzumab TBP offers a survival benefit to MBC patients treated with first-line trastuzumab. PMID:20671105

  14. Long-term outcome in BRAFV600E melanoma patients treated with vemurafenib: Patterns of disease progression and clinical management of limited progression

    PubMed Central

    Puzanov, Igor; Amaravadi, Ravi K.; McArthur, Grant A.; Flaherty, Keith T.; Chapman, Paul B.; Sosman, Jeffrey A.; Ribas, Antoni; Shackleton, Mark; Hwu, Patrick; Chmielowski, Bartosz; Nolop, Keith B.; Lin, Paul S.; Kim, Kevin B.

    2016-01-01

    Introduction Vemurafenib induces tumour regression in most patients with BRAFV600E-mutant melanoma; eventually, most experience progressive disease (PD). Long-term follow-up of patients with BRAFV600E melanoma treated in the phase 1 vemurafenib trial is reported. Methods Patients received vemurafenib 240–1120 mg (dose escalation cohort) or 960 mg (extension cohort) orally twice daily. Clinical response was evaluated every 8 weeks by RECIST. Patients with PD amenable to local therapy (surgery or radiotherapy) were allowed to continue vemurafenib after progression. Overall survival (OS) from time of treatment initiation and from PD was estimated. Sites of PD were recorded. Results Forty-eight patients (escalation cohort, n = 16; extension cohort, n = 32) received therapeutic doses of vemurafenib (≥240 mg twice daily). Forty-three patients had PD by the time of this analysis, and 5 remained progression free (follow-up time, 1.2–56.1 months). Median OS was 14 months (range, 1.2–56.1); 3- and 4-year melanoma-specific survival rate in the extension cohort was 26% and 19%, respectively. Median OS was 26.0 months (range, 7.7–56.1) among 20 patients who continued vemurafenib after local therapy. Median treatment duration beyond initial PD was 3.8 months (range, 1.1–26.6). In the extension cohort, 6 and 5 patients were alive after 3 and 4 years, respectively, on vemurafenib monotherapy. Conclusions Some patients with melanoma achieved long-term survival with vemurafenib monotherapy. Continuation of vemurafenib after PD might be beneficial in some patients because remaining disease might continue to respond to BRAF inhibition. PMID:25980594

  15. Clinical, molecular and immune analysis of dabrafenib and trametinib in metastatic melanoma patients that progressed on BRAF inhibitor monotherapy: a phase II clinical trial

    PubMed Central

    Chen, Guo; McQuade, Jennifer L.; Panka, David J.; Hudgens, Courtney W.; Amin-Mansour, Ali; Mu, Xinmeng Jasmine; Bahl, Samira; Jane-Valbuena, Judit; Wani, Khalida M.; Reuben, Alexandre; Creasy, Caitlyn A.; Jiang, Hong; Cooper, Zachary A.; Roszik, Jason; Bassett, Roland L.; Joon, Aron Y.; Simpson, Lauren M.; Mouton, Rosalind D.; Glitza, Isabella C.; Patel, Sapna P.; Hwu, Wen-Jen; Amaria, Rodabe N.; Diab, Adi; Hwu, Patrick; Lazar, Alexander J.; Wargo, Jennifer A.; Garraway, Levi A.; Tetzlaff, Michael T.; Sullivan, Ryan J.; Kim, Kevin B.; Davies, Michael A.

    2016-01-01

    Importance Combined treatment with dabrafenib and trametinib (CombiDT) achieves clinical responses in only ~15% of BRAF inhibitor (BRAFi)-refractory metastatic melanoma patients, in contrast to the high activity observed in BRAFi-naïve patients. Identifying correlates of response and mechanisms of resistance in this population will facilitate clinical management and rational therapeutic development. Objective To determine correlates of benefit from CombiDT therapy in BRAFi-refractory metastatic melanoma patients. Design Single-center, single-arm prospective phase II study of CombiDT in patients with BRAFV600 metastatic melanoma resistant to BRAFi monotherapy conducted between September 2012 and October 2014. Setting University of Texas MD Anderson Cancer Center. Participants 28 patients were screened and 23 enrolled. Key eligibility criteria included: BRAFV600 metastatic melanoma, prior BRAFi monotherapy, measurable disease (RECIST 1.1), and accessible tumor for biopsy. Intervention Patients were treated with dabrafenib (150 mg twice daily) and trametinib (2 mg daily) continuously until disease progression or intolerance. All participants underwent a mandatory baseline biopsy, and optional biopsies were performed on-treatment and at progression. Whole-exome sequencing, RT-PCR for BRAF splicing, RNAseq and IHC were performed on tumor samples, and blood was analyzed for levels of circulating BRAFV600. Main outcome measures Primary endpoint was overall response rate (ORR). Progression-free survival (PFS) and overall survival (OS) were secondary clinical endpoints. Results Among evaluable patients, the confirmed ORR was 10%, disease control rate (DCR) was 45%, and median PFS was 13 weeks. Clinical benefit was associated with duration of prior BRAFi >6 months (DCR 73% vs. 11% for ≤6 months, p=0.02) and decrease in circulating BRAFV600 at day 8 of cycle 1 (DCR 75% vs. 18% for no decrease, p=0.015), but not by pre-treatment MAPK pathway mutations or activation. On

  16. Progressive myoclonic epilepsy: A clinical, electrophysiological and pathological study from South India.

    PubMed

    Sinha, S; Satishchandra, P; Gayathri, N; Yasha, T C; Shankar, S K

    2007-01-15

    Progressive myoclonic epilepsy (PME) is a syndrome complex encompassing different diagnostic entities and often cause problems in diagnosis. We describe the clinical, electrophysiological and pathological features of 97 patients with the diagnosis of PME evaluated over 25 years. Case records of confirmed patients of Neuronal ceroid lipofuscinosis (NCL = 40), Lafora body disease (LBD = 38), Myoclonic epilepsy with ragged red fibers (MERRF = 10), and probable Unverricht-Lundberg disease (ULD = 9) were reviewed. The mean age at onset in patients with NCL (n = 40) was 5.9+/-9.1 years (M:F:: 28:12). Subtypes of NCL were: late infantile (n = 19), infantile (n = 8), juvenile (n = 11) and adult (n = 2) NCL. EEG (n = 37) showed varying degree of diffuse slowing of background activity in 94.6% and epileptiform discharges in 81.1% of patients. Slow frequency photic stimulation evoked photo-convulsive response in 5 patients only. Giant SSEP was demonstrated in 7 and VEP study revealed a prolonged P100 (2) and absent waveform (7). Electrophysiological features of neuropathy were present in 3 patients. Presence of PAS and Luxol Fast Blue (LFB) positive, auto fluorescent (AF) ceroid material in brain tissue (n = 12) and electron microscopy of brain (n = 5), skin (n = 28) and muscle (n = 1) samples showing curvilinear and lamellar bodies established the diagnosis. Patients of LBD (mean age of onset at 14.4+/-3.9 years, M:F:: 24:14) with triad of PME symptoms were evaluated. EEG (n = 37) showed variable slowing of background activity in 94.6% and epileptiform discharges in 97.4%. Photosensitivity with fast frequency was observed only in 5 patients. CT (n = 32) and MRI (n = 4) revealed diffuse cortical atrophy. Giant SSEP was demonstrated in 24 patients of LBD while VEP study revealed a prolonged P100 (4) and absent waveform (8). Electrophysiological features of neuropathy were present in one patient. Diagnosis was established by the presence of PAS positive diastase resistant

  17. Anatomic, Clinical, and Neuropsychological Correlates of Spelling Errors in Primary Progressive Aphasia

    ERIC Educational Resources Information Center

    Shim, HyungSub; Hurley, Robert S.; Rogalski, Emily; Mesulam, M.-Marsel

    2012-01-01

    This study evaluates spelling errors in the three subtypes of primary progressive aphasia (PPA): agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S). Forty-one PPA patients and 36 age-matched healthy controls were administered a test of spelling. The total number of errors and types of errors in spelling to dictation of regular words,…

  18. Scoring of radiographic progression in randomised clinical trials in ankylosing spondylitis: a preference for paired reading order

    PubMed Central

    Wanders, A; Landewe, R; Spoorenberg, A; de Vlam, K; Mielants, H; Dougados, M; van der Linden, S; van der Heijde, D

    2004-01-01

    Objectives: To describe the influence of the reading order (chronological v paired) on radiographic scoring results in ankylosing spondylitis. To investigate whether this method is sufficiently sensitive to change because paired reading is requested for establishing drug efficacy in clinical trials. Methods: Films obtained from 166 patients (at baseline, 1 year, and 2 years) were scored by one observer, using the modified Stoke Ankylosing Spondylitis Spinal Score. Films were first scored chronologically, and were scored paired 6 months later. Results: Chronological reading showed significantly more progression than paired reading both at 1 year (mean (SD) progression 1.3 (2.6) v 0.5 (2.4) units) and at 2 years (2.1 (3.9) v 1.0 (2.9) units); between-method difference: p<0.001 at 1 year, and p<0.001 at 2 years. After 1 year, progression (>0 units) was found in 35/166 (21%) patients after paired reading and in 55/166 (33%) after chronological reading. After 2 years, these figures were 50/166 (30%) and 68/166 (41%), respectively. Sample size calculations showed that 94 patients in each treatment arm are required in a randomised clinical trial (RCT) to provide sufficient statistical power to detect a difference in 2 year progression if films are scored paired. Conclusion: Reading with chronological time order is more sensitive to change than reading with paired time order, but paired reading is sufficiently sensitive to pick up change with a follow up of 2 years, resulting in an acceptable sample size for RCTs. PMID:15297280

  19. Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies

    PubMed Central

    Väänänen, Riina-Minna; Mattsson, Jesse; Li, Yifeng; Tallgrén, Terhi; Tong Ochoa, Natalia; Bjartell, Anders; Åkerfelt, Malin; Taimen, Pekka; Boström, Peter J.

    2016-01-01

    The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest

  20. Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies.

    PubMed

    Alinezhad, Saeid; Väänänen, Riina-Minna; Mattsson, Jesse; Li, Yifeng; Tallgrén, Terhi; Tong Ochoa, Natalia; Bjartell, Anders; Åkerfelt, Malin; Taimen, Pekka; Boström, Peter J; Pettersson, Kim; Nees, Matthias

    2016-01-01

    The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest

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

    Cancer.gov

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

  2. Have genomic discoveries in inflammatory bowel disease translated into clinical progress?

    PubMed

    Weizman, Adam V; Silverberg, Mark S

    2012-04-01

    Inflammatory bowel disease (IBD) is a heterogeneous disease that can be challenging to diagnose and manage. As a result, significant efforts have been made in attempting to identify clinical, genomic, and serologic markers of disease that can aid in patient assessment and treatment. Recent genomic discoveries have the potential to change clinical practice by identifying those susceptible to IBD, predict natural history and guide choice of therapy. Panels of genetic and genomic markers are more likely to emerge as clinical tools, as opposed to individual allelic variants. Serology and biomarkers are already being used and guiding management but await integration with genomic panels before achieving their maximal potential. This article reviews the current state of IBD genetics and evolving molecular approaches that may have potential clinical impact.

  3. Standards for the electronic transfer of clinical data: progress and promises.

    PubMed

    McDonald, C J; Martin, D K; Overhage, J M

    1991-06-01

    Data exchange standards have two components: the message format or syntax and the dictionary of codes (semantics). For many applications, message standards already have been developed. For a few kinds of clinical entities, such as drugs, these code systems (e.g., the National Drug Code) are virtually complete, but a few gaps must be filled and an agreement must be reached about the level of granularity needed. The available codes for clinical descriptors are inadequate but the National Library of Medicine's Universal Medical Language (UML) project will do much to redress this deficiency. Codes for clinical variables such as blood pressure and blood glucose which have methods, units, normal ranges, and physiologic correlates are very inadequate. CPT4 provides some of the needed codes but has huge gaps. An early effort to extend CPT4 is included in ASTM 1238. Work being done by ASTM E31.12 and the Euclides project will offer robust codes for clinical laboratory measurements. If we want to pool data from different institutions for clinical and policy research, universal codes for observations are prerequisite. And agreement of an international coding system for observation-bearing variables should be a major agenda item for standards groups in the next year. Our goal has been to standardize the communication of clinical data between clinical systems, not the systems themselves or their internal operation. In fact, standardizing the internals of clinical application could be counterproductive at the present. It would deflect energy from, and delay the spread of, CDI standards. Moreover, it gives undue attention to computer systems, rather than the data they contain. The data are the most expensive part of any data system. They are the raison d'être for such systems. Computer systems come and go. The data last forever. Yet we have been mesmerized by the computer system while ignoring its contents. As a result, most computer-stored clinical data must live like the

  4. MicroRNA expression profiles predict progression and clinical outcome in lung adenocarcinoma

    PubMed Central

    Lin, Kang; Xu, Tao; He, Bang-Shun; Pan, Yu-Qin; Sun, Hui-Ling; Peng, Hong-Xin; Hu, Xiu-Xiu; Wang, Shu-Kui

    2016-01-01

    Lung cancer is one of the leading causes of cancer death worldwide. Accumulating evidence has indicated that microRNAs (miRNAs) can be proposed as promising diagnostic and prognostic markers for various cancers. The current study analyzed the miRNA expression profiles of 418 lung adenocarcinoma (LUAD) cases obtained from The Cancer Genome Atlas dataset, with the aim to investigate the relationship of miRNAs with progression and prognosis of LUAD. A total of 185 miRNAs were found to be differentially expressed between LUAD tumor tissues and adjacent normal tissues. Among them, 13, 10, 0, and 10 miRNAs were discovered to be associated with pathologic T, N, M, and Stage, respectively. Interestingly, mir-200 family (mir-200a, mir-200b, and mir-429) was shown to play a critical role in the progression of LUAD. In the multivariate Cox regression analysis, mir-1468 (P=0.009), mir-212 (P=0.026), mir-3653 (P=0.012), and mir-31 (P=0.002) were significantly correlated with recurrence-free survival. With regard to overall survival, mir-551b (P=0.011), mir-3653 (P=0.016), and mir-31 (P=0.001) were proven as independent prognostic markers. In summary, this study identified the cancer-specific miRNAs that may predict the progression and prognosis of LUAD. PMID:27695346

  5. MicroRNA expression profiles predict progression and clinical outcome in lung adenocarcinoma

    PubMed Central

    Lin, Kang; Xu, Tao; He, Bang-Shun; Pan, Yu-Qin; Sun, Hui-Ling; Peng, Hong-Xin; Hu, Xiu-Xiu; Wang, Shu-Kui

    2016-01-01

    Lung cancer is one of the leading causes of cancer death worldwide. Accumulating evidence has indicated that microRNAs (miRNAs) can be proposed as promising diagnostic and prognostic markers for various cancers. The current study analyzed the miRNA expression profiles of 418 lung adenocarcinoma (LUAD) cases obtained from The Cancer Genome Atlas dataset, with the aim to investigate the relationship of miRNAs with progression and prognosis of LUAD. A total of 185 miRNAs were found to be differentially expressed between LUAD tumor tissues and adjacent normal tissues. Among them, 13, 10, 0, and 10 miRNAs were discovered to be associated with pathologic T, N, M, and Stage, respectively. Interestingly, mir-200 family (mir-200a, mir-200b, and mir-429) was shown to play a critical role in the progression of LUAD. In the multivariate Cox regression analysis, mir-1468 (P=0.009), mir-212 (P=0.026), mir-3653 (P=0.012), and mir-31 (P=0.002) were significantly correlated with recurrence-free survival. With regard to overall survival, mir-551b (P=0.011), mir-3653 (P=0.016), and mir-31 (P=0.001) were proven as independent prognostic markers. In summary, this study identified the cancer-specific miRNAs that may predict the progression and prognosis of LUAD.

  6. Enhancing Adolescent and Young Adult Oncology Research Within the National Clinical Trials Network: Rationale, Progress, and Emerging Strategies.

    PubMed

    Weiss, Aaron R; Nichols, Craig R; Freyer, David R

    2015-10-01

    Adolescent and Young Adult Oncology (AYAO, including patients 15-39 years of age) is an emerging discipline in the field of cancer treatment and research. Poorer survival outcomes for this population and characteristic age-related challenges in care have called attention to the need for increased AYAO research. This chapter outlines pressing questions and reviews recent progress in AYAO research within the current organizational structure of the federal clinical trials enterprise, emphasizing how the United States National Cancer Institute's National Clinical Trials Network (NCTN) has created novel opportunities for collaborative AYAO research among the pediatric and adult NCTN groups. Potential strategies for expanding AYAO research, both within the NCTN and with other partners in the federal and advocacy domains are identified. PMID:26433555

  7. [Progress and challenges of clinical trials registration in Latin America and the Caribbean's].

    PubMed

    Reveiz, Ludovic; Saenz, Carla; Murasaki, Renato T; Cuervo, Luis G; Ramalho, Luciano

    2011-12-01

    Clinical trial registries are one of the main sources of information concerning health research interventions that have been or are being carried out throughout the world. The World Health Organization (WHO) established a minimum data set to be recorded (20 items), which was agreed upon internationally with the stakeholders, and established a network of primary and associated records. In addition to the register ClinicalTrial.Gov (of the United States of America), there are currently two primary registries in the Americas (from Brazil and Cuba) that meet WHO requirements and provide data to WHO's International Clinical Trials Registry Platform (ICTRP). Furthermore, there are important advances in the region related to the regulations, development and implementation of national registries and to the support of the ethics committees and editors to this initiative.

  8. Tophus measurement as an outcome measure for clinical trials of chronic gout: progress and research priorities.

    PubMed

    Dalbeth, Nicola; McQueen, Fiona M; Singh, Jasvinder A; MacDonald, Patricia A; Edwards, N Lawrence; Schumacher, H Ralph; Simon, Lee S; Stamp, Lisa K; Neogi, Tuhina; Gaffo, Angelo L; Khanna, Puja P; Becker, Michael A; Taylor, William J

    2011-07-01

    Despite the recognition that tophus regression is an important outcome measure in clinical trials of chronic gout, there is no agreed upon method of tophus measurement. A number of methods have been used in clinical trials of chronic gout, from simple physical measurement techniques to more complex advanced imaging methods. This article summarizes methods of tophus measurement and discusses their properties. Physical measurement using Vernier calipers meets most aspects of the Outcome Measures in Rheumatology (OMERACT) filter. Rigorous testing of the complex methods, particularly with respect to reliability and sensitivity to change, is needed to determine the appropriate use of these methods. Further information is also required regarding which method of physical measurement is best for use in future clinical trials. The need to develop and test a patient-reported outcome measure of tophus burden is also highlighted.

  9. Dendritic cells in cancer immunotherapy clinical trials: are we making progress?

    PubMed

    Butterfield, Lisa H

    2013-12-13

    Dendritic cells (DC) have been tested in cancer immunotherapy clinical trials for two decades. Over this time, the methods of DC culture (or manufacture) have evolved, the approaches for antigen loading have broadened, the maturation signals have varied and different sites of administration have been tested. The post-vaccination immunologic questions asked have also varied between trials and over time. In this review, I will consider multiple aspects of DC-based vaccines tested in cancer patients, including the cell culture, antigen loading, maturation, and delivery, as well as what we have learned from testing immune responses in vaccinated patients who have benefited clinically, and those who have not measurably benefited.

  10. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression

    PubMed Central

    Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D.; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

    2016-01-01

    The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma. Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines. We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK. Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%. Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression. Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants. In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

  11. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression.

    PubMed

    Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

    2016-04-19

    The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma.Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines.We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK.Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%.Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression.Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants.In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

  12. Annual Research Review: Progress in Using Brain Morphometry as a Clinical Tool for Diagnosing Psychiatric Disorders

    ERIC Educational Resources Information Center

    Haubold, Alexander; Peterson, Bradley S.; Bansal, Ravi

    2012-01-01

    Brain morphometry in recent decades has increased our understanding of the neural bases of psychiatric disorders by localizing anatomical disturbances to specific nuclei and subnuclei of the brain. At least some of these disturbances precede the overt expression of clinical symptoms and possibly are endophenotypes that could be used to diagnose an…

  13. 50 years of pediatric immunology: progress and future, a clinical perspective.

    PubMed

    Singh, Surjit; Gupta, Anju; Rawat, Amit

    2013-01-01

    Rapidly evolving advances in the field of immunology over the last few decades have impacted the practice of clinical medicine in many ways. In fact, understanding the immunological basis of disease has been pivotal in deciphering the pathogenesis of several disease processes, infective or otherwise. As of today, there is hardly any specialty of medicine which is not influenced by immunology. Pediatric rheumatological disorders, vasculitides, Human Immunodeficiency Virus (HIV) infection, Primary Immunodeficiency Diseases (PIDs) and autoimmune disorders fall under the domain of clinical immunology. This specialty is poised to emerge as a major clinical specialty in our country. The gulf between bench and bedside is narrowing down as our understanding of the complex immunological mechanisms gets better. However, a lot still needs to be done in this field as the morbidity and mortality of some of these conditions is unacceptably high in the Indian setup. A number of medical schools and institutes in the country now have the resources and the wherewithal to develop into specialized centres of clinical immunology. We need to concentrate on training more physicians and pediatricians in this field. The future is bright and the prospects exciting.

  14. [A clinical trial of neutron capture therapy for brain tumors]. Technical progress report, 1990

    SciTech Connect

    Zamenhof, R.G.

    1990-12-31

    This document briefly describes recent advances in the author`s laboratory. Topics described include neutron beam design, high- resolution autoradiography, boronated phenylalanine (BPA) distribution and survival studies in glioma bearing mice, computer- aided treatment planning, prompt gamma boron 10 analysis facility at MITI-II, non-rodent BPA toxicity studies, and preparations for clinical studies.

  15. Evaluation of the Brief Problem Checklist: Child and Caregiver Interviews to Measure Clinical Progress

    ERIC Educational Resources Information Center

    Chorpita, Bruce F.; Reise, Steven; Weisz, John R.; Grubbs, Kathleen; Becker, Kimberly D.; Krull, Jennifer L.

    2010-01-01

    Objective: To support ongoing monitoring of child response during treatment, we sought to develop a brief, easily administered, clinically relevant, and psychometrically sound measure. Method: We first developed child and caregiver forms of a 12-item Brief Problem Checklist (BPC) interview by applying item response theory and factor analysis to…

  16. Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box?

    PubMed

    Lawler, Mark; Sullivan, Richard

    2015-01-01

    Cancer clinical trials have been one of the key foundations for significant advances in oncology. However, there is a clear recognition within the academic, care delivery and pharmaceutical/biotech communities that our current model of clinical trial discovery and development is no longer fit for purpose. Delivering transformative cancer care should increasingly be our mantra, rather than maintaining the status quo of, at best, the often miniscule incremental benefits that are observed with many current clinical trials. As we enter the era of precision medicine for personalised cancer care (precision and personalised medicine), it is important that we capture and utilise our greater understanding of the biology of disease to drive innovative approaches in clinical trial design and implementation that can lead to a step change in cancer care delivery. A number of advances have been practice changing (e.g. imatinib mesylate in chronic myeloid leukaemia, Herceptin in erb-B2-positive breast cancer), and increasingly we are seeing the promise of a number of newer approaches, particularly in diseases like lung cancer and melanoma. Targeting immune checkpoints has recently yielded some highly promising results. New algorithms that maximise the effectiveness of clinical trials, through for example a multi-stage, multi-arm type design are increasingly gaining traction. However, our enthusiasm for the undoubted advances that have been achieved are being tempered by a realisation that these new approaches may have significant cost implications. This article will address these competing issues, mainly from a European perspective, highlight the problems and challenges to healthcare systems and suggest potential solutions that will ensure that the cost/value rubicon is addressed in a way that allows stakeholders to work together to deliver optimal cost-effective cancer care, the benefits of which can be transferred directly to our patients.

  17. Localization to Xq22 and clinical update of a family with X-linked recessive mental retardation with progression sensorineural deafness, progressive tapeto-retinal degeneration and dystonia

    SciTech Connect

    Tranebjaerg, L.; Schwartz, C.; Huggins, K.; Barker, D.; Stevenson, R.; Arena, J.F.; Gedde-Dahl, T.; Mikkelsen, M.; Mellgren, S.; Anderson, K. ||||

    1994-07-15

    In a reinvestigation of a six-generation Norwegian family, originally reported with non-syndromic X-linked recessive deafness by Mohr and Mageroy, we have demonstrated several syndromic manifestations. The 10 clinically characterized affected males range in age from 14-61 years, and show progressive mental deterioration and visual disability. Ophthalmological and electrophysiological studies showed myopia, decreased visual acuity, combined cone-rod dystrophy as well as central areolar dystrophy by means of ERG. Brain CT-scans showed cortical and central atrophy without predilection to specific areas. Linkage analysis, using X-chromosomal RFLPs and CA-repeats, yielded a maximum LOD score of 4.37 with linkage to DXS17. DXS17 is localized to Xq22. One recombinant with COL4A5 (deficient in Alport syndrome) was observed. Results from the studies of this family will be important in reclassification of non-syndromic X-linked deafness since the family now represents syndromic deafness and XLMR with a specific phenotype.

  18. SLAC Linear Collider

    SciTech Connect

    Richter, B.

    1985-12-01

    A report is given on the goals and progress of the SLAC Linear Collider. The status of the machine and the detectors are discussed and an overview is given of the physics which can be done at this new facility. Some ideas on how (and why) large linear colliders of the future should be built are given.

  19. Clinical Aspects of Melatonin Intervention in Alzheimer’s Disease Progression

    PubMed Central

    Cardinali, Daniel P; Furio, Analía M; Brusco, Luis I

    2010-01-01

    Melatonin secretion decreases in Alzheimer´s disease (AD) and this decrease has been postulated as responsible for the circadian disorganization, decrease in sleep efficiency and impaired cognitive function seen in those patients. Half of severely ill AD patients develop chronobiological day-night rhythm disturbances like an agitated behavior during the evening hours (so-called “sundowning”). Melatonin replacement has been shown effective to treat sundowning and other sleep wake disorders in AD patients. The antioxidant, mitochondrial and antiamyloidogenic effects of melatonin indicate its potentiality to interfere with the onset of the disease. This is of particularly importance in mild cognitive impairment (MCI), an etiologically heterogeneous syndrome that precedes dementia. The aim of this manuscript was to assess published evidence of the efficacy of melatonin to treat AD and MCI patients. PubMed was searched using Entrez for articles including clinical trials and published up to 15 January 2010. Search terms were “Alzheimer” and “melatonin”. Full publications were obtained and references were checked for additional material where appropriate. Only clinical studies with empirical treatment data were reviewed. The analysis of published evidence made it possible to postulate melatonin as a useful ad-on therapeutic tool in MCI. In the case of AD, larger randomized controlled trials are necessary to yield evidence of effectiveness (i.e. clinical and subjective relevance) before melatonin´s use can be advocated. PMID:21358972

  20. Progress in proteomics for clinical microbiology: MALDI-TOF MS for microbial species identification and more.

    PubMed

    van Belkum, Alex; Chatellier, Sonia; Girard, Victoria; Pincus, David; Deol, Parampal; Dunne, Wm Michael

    2015-01-01

    Although classical proteomic approaches are still used regularly in routine clinical diagnostic procedures, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) MS has recently moved into diagnostic microbiology laboratories. MALDI-TOF MS is currently replacing phenotypic microbial identification. Many laboratories now use MALDI-TOF MS for its high efficiency, both from a diagnostic and a cost-per-analysis point of view. The US FDA has now cleared two of the commercially available systems for in vitro diagnostics. This will further spark development of MS applications in antimicrobial susceptibility testing and epidemiology. This review summarizes the state of affairs of MALDI-TOF MS in clinical microbiology; however, this is an active field of research subject to rapid evolution. We emphasize assessment of the clinical relevance and studies focusing on data obtained through comparative analyses of different MALDI-TOF MS instrumentation and multicenter validation studies. The future of MALDI-TOF MS, including antimicrobial susceptibility testing and epidemiological typing, is also highlighted.

  1. Progress in epigenetic histone modification analysis by mass spectrometry for clinical investigations

    PubMed Central

    Önder, Özlem; Sidoli, Simone; Carroll, Martin; Garcia, Benjamin A.

    2016-01-01

    Chromatin biology and epigenetics are scientific fields in rapid expansion due to their fundamental role in understanding cell development, heritable characters and progression of diseases. Histone post-translational modifications (PTMs) are major regulators of the epigenetic machinery, due to their ability to modulate gene expression, DNA repair and chromosome condensation. Large- scale strategies based on mass spectrometry have been impressively improved in the last decade, so that global changes of histone PTM abundances are quantifiable with nearly routine proteomics analyses and it is now possible to determine combinatorial patterns of modifications. Presented here is an overview of the most utilized and newly developed proteomics strategies for histone PTM characterization and a number of case studies where epigenetic mechanisms have been comprehensively characterized. Moreover, a number of current epigenetics therapies are illustrated, with an emphasis on cancer PMID:26400466

  2. General anesthesia in fibrodysplasia ossificans progressive: a case report and clinical review.

    PubMed

    Liu, Jin-Xing; Hu, Rong; Sun, Yu; Jiang, Hong

    2014-01-01

    Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disorder of connective tissue characterized by heterotopic bone formation and progressive musculoskeletal disability. Soft-tissue trauma may exacerbate this condition and lead to further ossification. We described the anesthetic and perioperative management of a 23-year-old male with FOP scheduled for dental extraction requiring general anesthesia. Preoperative examination revealed multisystem involvement including cranial and cervical ankylosis and severe restrictive lung disease. Nasal fiber-optic endotracheal intubation was chosen in our patient. Anesthesia was maintained with total intravenous anesthesia and ventilation was controlled throughout the surgery. Endotracheal tube was remained for mechanical ventilation until the second postoperative day and aggressive respiratory physiotherapy was performed after extubation. Additionally, extreme caution was taken to a femoral vascular access and an arterial catheter. Positioning of the patient was meticulous and air warming blanket was used to minimize soft tissue trauma. No significant documented intraoperative and postoperative adverse events appeared attributable to the anesthesia.

  3. Statistics in review. Part 2: generalised linear models, time-to-event and time-series analysis, evidence synthesis and clinical trials.

    PubMed

    Moran, John L; Solomon, Patricia J

    2007-06-01

    In Part I, we reviewed graphical display and data summary, followed by a consideration of linear regression models. Generalised linear models, structured in terms of an exponential response distribution and link function, are now introduced, subsuming logistic and Poisson regression. Time-to-event ("survival") analysis is developed from basic principles of hazard rate, and survival, cumulative distribution and density functions. Semi-parametric (Cox) and parametric (accelerated failure time) regression models are contrasted. Time-series analysis is explicated in terms of trend, seasonal, and other cyclical and irregular components, and further illustrated by development of a classical Box-Jenkins ARMA (autoregressive moving average) model for monthly ICU-patient hospital mortality rates recorded over 11 years. Multilevel (random-effects) models and principles of meta-analysis are outlined, and the review concludes with a brief consideration of important statistical aspects of clinical trials: sample size determination, interim analysis and "early stopping".

  4. The Long-term Clinical Outcome after Corneal Collagen Cross-linking in Korean Patients with Progressive Keratoconus

    PubMed Central

    Kim, Tae Gi; Kim, Ki Young; Han, Jung Bin

    2016-01-01

    Purpose To evaluate the long-term clinical effectiveness and safety of corneal collagen cross-linking (CXL) in progressive keratoconus compared with untreated contralateral eyes. Methods In this retrospective study, nine eyes of nine patients with progressive keratoconus who received CXL (treatment group) and nine untreated contralateral eyes with keratoconus (control group) were included. All patients were followed for at least 5 years and assessed with best-corrected visual acuity, maximum keratometry, mean keratometry, corneal astigmatism, and corneal thickness. Clinical data were collected preoperatively and at 1, 3, 6, 12, 24, 36, 48, and 60 months, postoperatively. Results Mean best-corrected visual acuity improved significantly from 0.58 ± 0.37 logarithm of minimum angle of resolution preoperatively to 0.39 ± 0.29 logarithm of minimum angle of resolution at 5 years after corneal CXL (p = 0.012). There was significant flattening of the maximum keratometry and mean keratometry from preoperative values of 63.39 ± 10.89 and 50.87 ± 6.27 diopter (D) to postoperative values of 60.89 ± 11.29 and 49.54 ± 7.23 D, respectively (p = 0.038, 0.021). Corneal astigmatism decreased significantly from 7.20 ± 1.83 D preoperatively to 5.41 ± 1.79 D postoperatively (p = 0.021). The thinnest corneal thickness decreased from 434.00 ± 54.13 to 365.78 ± 71.58 µm during 1 month after treatment, then increased to 402.67 ± 52.55 µm at 5 years, which showed a statistically significant decrease compared to the baseline (p = 0.020). In the untreated contralateral eyes, mean keratometry increased significantly at 2 years compared with the baseline (p = 0.043). Conclusions CXL seems to be an effective and safe treatment for halting the progression of keratoconus over a long-term follow-up period of up to 5 years in progressive keratoconus. PMID:27729752

  5. Progressive outer retinal necrosis syndrome: a comprehensive review of its clinical presentation, relationship to immune system status, and management.

    PubMed

    Austin

    2000-12-01

    Progressive outer retinal necrosis (PORN) syndrome is a form of the Varicella zoster virus (VZV) chorioretinitis found almost exclusively in people with the acquired immunodeficiency syndrome (AIDS). This destructive infection has an extremely rapid course that may lead to no light perception in affected eyes within days or weeks. Attempts at its treatment have had limited success. Rhegmatogenous retinal detachments often occur after the development of atrophic retinal holes, and silicone oil temponade has been found to be the most successful reattachment procedure. Unfortunately, cataract formation is common after such surgery. PORN needs to be differentiated from acute retinal necrosis (ARN) syndrome, a necrotizing retinitis that can also be caused by VZV. PORN and ARN are found at opposite ends of the spectrum of necrotizing herpetic retinopathies (NHR), where its clinical presentation depends upon immune system status. After a brief case presentation, the distinguishing clinical characteristics of PORN, its differentiation from ARN, attempts at its treatment, the role of the immune system status on its clinical appearance and treatment, and management of complications such as retinal detachment and subsequent cataracts are discussed.

  6. THE COOPERATIVE INTERNATIONAL NEUROMUSCULAR RESEARCH GROUP DUCHENNE NATURAL HISTORY STUDY: GLUCOCORTICOID TREATMENT PRESERVES CLINICALLY MEANINGFUL FUNCTIONAL MILESTONES AND REDUCES RATE OF DISEASE PROGRESSION AS MEASURED BY MANUAL MUSCLE TESTING AND OTHER COMMONLY USED CLINICAL TRIAL OUTCOME MEASURES

    PubMed Central

    HENRICSON, ERIK K.; ABRESCH, R. TED; CNAAN, AVITAL; HU, FENGMING; DUONG, TINA; ARRIETA, ADRIENNE; HAN, JAY; ESCOLAR, DIANA M.; FLORENCE, JULAINE M.; CLEMENS, PAULA R.; HOFFMAN, ERIC P.; McDONALD, CRAIG M.

    2014-01-01

    Introduction Glucocorticoid (GC) therapy in Duchenne muscular dystrophy (DMD) has altered disease progression, necessitating contemporary natural history studies. Methods The Cooperative Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 DMD males, ages 2–28 years. A comprehensive battery of measures was obtained. Results A novel composite functional “milestone” scale scale showed clinically meaningful mobility and upper limb abilities were significantly preserved in GC-treated adolescents/young adults. Manual muscle test (MMT)-based calculations of global strength showed that those patients <10 years of age treated with steroids declined by 0.4±0.39 MMT unit/year, compared with −0.4±0.39 MMT unit/year in historical steroid-naive subjects. Pulmonary function tests (PFTs) were relatively preserved in steroid-treated adolescents. The linearity and magnitude of decline in measures were affected by maturational changes and functional status. Conclusions In DMD, long-term use of GCs showed reduced strength loss and preserved functional capabilities and PFTs compared with previous natural history studies performed prior to the widespread use of GC therapy. PMID:23649481

  7. Treatment with electromagnetic fields reverses the long-term clinical course of a patient with chronic progressive multiple sclerosis.

    PubMed

    Sandyk, R

    1997-08-01

    It is estimated that 10-20% of patients with multiple sclerosis (MS) have a chronic progressive (CP) course characterized by an insidious onset of neurological deficits followed by steady progression of disability in the absence of symptomatic remission. To date no therapeutic modality has proven effective in reversing the clinical course of CP MS although there are indications that prolonged treatment with picotesla electromagnetic fields (EMFs) alters the clinical course of patients with CP MS. A 40 year-old woman presented in December of 1992 with CP MS with symptoms of spastic paraplegia, loss of trunk control, marked weakness of the upper limbs with loss of fine and gross motor hand functions, severe fatigue, cognitive deficits, mental depression, and autonomic dysfunction with neurogenic bladder and bowel incontinence. Her symptoms began at the age of 18 with weakness of the right leg and fatigue with long distance walking and over the ensuing years she experienced steady deterioration of functions. In 1985 she became wheelchair dependent and it was anticipated that within 1-2 years she would become functionally quadriplegic. In December of 1992 she began experimental treatment with EMFs. While receiving regularly weekly transcortical treatments with AC pulsed EMFs in the picotesla range intensity she experienced during the first year improvement in mental functions, return of strength in the upper extremities, and recovery of trunk control. During the second year she experienced the return of more hip functions and recovery of motor functions began in her legs. For the first time in years she can now initiate dorsiflexion of her ankles and actively extend her knees voluntarily. Over the past year she started to show signs of redevelopment of reciprocal gait. Presently, with enough function restored in her legs, she is learning to walk with a walker and is able to stand unassisted and maintain her balance for a few minutes. She also regained about 80% of

  8. Designing privacy-friendly digital whiteboards for mediation of clinical progress

    PubMed Central

    2014-01-01

    Background In hospitals, digital versions of dry-erase whiteboards are increasingly becoming more common. One of the purposes with such whiteboards is to support coordination of care by augmenting visibility and availability of clinical information. However, clinical information usually concerns patients and is regarded as sensitive personal health information, meaning that it should be access controlled. The purpose of this study is to explore how digital whiteboards can be designed for supporting coordination of care, by providing clinicians with useful information in a usable way, and at the same time protect patient privacy. Methods A demo application was designed, demonstrated and evaluated iteratively. In total, 15 professional ward nurses role-played a scenario in which the application played a central part. Afterwards, the participants were interviewed. All interviews were recorded, transcribed verbatim, and analysed qualitatively. Results The participants valued having updated clinical information presented on a digital whiteboard, even if the information was de-identified and abstracted. According to the participants, such information could possibly improve inter-departmental communication, reduce the number of electronic health record-logins, and make nurses more rapidly aware of new information. The participants expected that they would be able to re-identify much of the de-identified information in real situations based on their insight into their patients’ recent and expected care activities. Moreover, they also valued being able to easily access more detailed information and verify patient identities. While abstraction and de-identification was regarded to sufficiently protect the patients’ privacy, the nurses also pointed out the importance of having control over what can be seen by other patients and passers-by if detailed medical information was accessed on a digital whiteboard. Conclusions Presenting updated information from patient care

  9. Considering Cost-Effectiveness in Cardiology Clinical Guidelines: Progress and Prospects.

    PubMed

    Hlatky, Mark A

    2016-01-01

    Since the 1980s, when the American College of Cardiology (ACC) and the American Heart Association (AHA) established a joint task force to examine the use of cardiovascular procedures and therapies, cardiologists have been leaders in the development of clinical practice guidelines. The ACC/AHA guidelines development process has evolved considerably over the last 30 or more years. Guidelines now focus on clinical conditions, such as angina, instead of procedures, such as bypass surgery. There is a formal organizational structure, with dedicated staff, a standing committee on practice guidelines, and specific panels of volunteer experts on each topic. This process tightly manages conflicts of interest and strives for evidence-based, as opposed to opinion-based, guidelines, with a clear citation of the supporting evidence. Traditional clinical guidelines consider only what is best for the individual patient, and have explicitly not considered the cost to society. Nevertheless, in many guidelines development meetings, high cost was implicitly considered: if a procedure was extremely costly, the evidence needed to be very strong. The Guidelines Committee recognized that cost considerations ought to be made more transparent, and that the evidence on economic value should be explicitly cited when available. These considerations were formalized by a recent white paper on incorporating economic considerations into ACC/AHA guidelines. In considering value, it is necessary to assess the quality of the evidence as well as to define levels of value. The next ACC/AHA guideline will incorporate value as a part of its recommendations. This will be an evidence-based process in which published economic assessments relating to key questions will be reviewed.

  10. Technological progress in generation of induced pluripotent stem cells for clinical applications.

    PubMed

    Oh, Seung-Ick; Lee, Chang Kyu; Cho, Kyung Jin; Lee, Kyung-Ok; Cho, Ssang-Goo; Hong, Sunghoi

    2012-01-01

    Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is achieved by viral-mediated transduction of defined transcription factors. Generation of iPSCs is of great medical interest as they have the potential to be a source of patient-specific cells. For the eventual goal of clinical application, it is necessary to overcome the limitations of low reprogramming efficiency and chromosomal abnormalities due to viral DNA integration. In this paper, we summarize the current state of reprogramming technology for generation of iPSCs and also discuss potential approaches to the development of safe iPSCs for personalized cell-based replacement therapy.

  11. Ant colony method to control variance reduction techniques in the Monte Carlo simulation of clinical electron linear accelerators of use in cancer therapy

    NASA Astrophysics Data System (ADS)

    García-Pareja, S.; Vilches, M.; Lallena, A. M.

    2010-01-01

    The Monte Carlo simulation of clinical electron linear accelerators requires large computation times to achieve the level of uncertainty required for radiotherapy. In this context, variance reduction techniques play a fundamental role in the reduction of this computational time. Here we describe the use of the ant colony method to control the application of two variance reduction techniques: Splitting and Russian roulette. The approach can be applied to any accelerator in a straightforward way and permits the increasing of the efficiency of the simulation by a factor larger than 50.

  12. International Standardization of the Clinical Dosimetry of Beta Radiation Brachytherapy Sources: Progress of an ISO Standard

    NASA Astrophysics Data System (ADS)

    Soares, Christopher

    2006-03-01

    In 2004 a new work item proposal (NWIP) was accepted by the International Organization for Standardization (ISO) Technical Committee 85 (TC85 -- Nuclear Energy), Subcommittee 2 (Radiation Protection) for the development of a standard for the clinical dosimetry of beta radiation sources used for brachytherapy. To develop this standard, a new Working Group (WG 22 - Ionizing Radiation Dosimetry and Protocols in Medical Applications) was formed. The standard is based on the work of an ad-hoc working group initiated by the Dosimetry task group of the Deutsches Insitiut für Normung (DIN). Initially the work was geared mainly towards the needs of intravascular brachytherapy, but with the decline of this application, more focus has been placed on the challenges of accurate dosimetry for the concave eye plaques used to treat ocular melanoma. Guidance is given for dosimetry formalisms, reference data to be used, calibrations, measurement methods, modeling, uncertainty determinations, treatment planning and reporting, and clinical quality control. The document is currently undergoing review by the ISO member bodies for acceptance as a Committee Draft (CD) with publication of the final standard expected by 2007. There are opportunities for other ISO standards for medical dosimetry within the framework of WG22.

  13. Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

    PubMed Central

    Tsutsumi, Lissa S.; Owusu, Yaw B.; Hurdle, Julian G.; Sun, Dianqing

    2014-01-01

    Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance. PMID:24236721

  14. Progress of clinical practice on the management of burn-associated pain: Lessons from animal models.

    PubMed

    McIntyre, Matthew K; Clifford, John L; Maani, Christopher V; Burmeister, David M

    2016-09-01

    Opioid-based analgesics provide the mainstay for attenuating burn pain, but they have a myriad of side effects including respiratory depression, nausea, impaired gastrointestinal motility, sedation, dependence, physiologic tolerance, and opioid-induced hyperalgesia. To test and develop novel analgesics, validated burn-relevant animal models of pain are indispensable. Herein we review such animal models, which are mostly limited to rodent models of burn-induced, inflammatory, and neuropathic pain. The latter two are pain syndromes that provide insight into the pain caused by systemic pro-inflammatory cytokines and direct injury to nerves (e.g., after severe burn), respectively. To date, no single animal model optimally mimics the complex pathophysiology and pain that a human burn patient experiences. No currently available burn-pain model examines effects of pharmacological intervention on wound healing. As cornerstones of pain and wound healing, pro-inflammatory mediators may be utilized for insight into both processes. Moreover, common clinical concerns such as systemic inflammatory response syndrome and multiple organ dysfunction remain unaddressed. For development of analgesics, these aberrations can significantly alter the potential efficacy and/or adverse effects of a prescribed analgesic following burn trauma. We therefore suggest that a multi-model strategy would be the most clinically relevant when evaluating novel analgesics for use in burn patients. PMID:26906668

  15. Progress of clinical practice on the management of burn-associated pain: Lessons from animal models.

    PubMed

    McIntyre, Matthew K; Clifford, John L; Maani, Christopher V; Burmeister, David M

    2016-09-01

    Opioid-based analgesics provide the mainstay for attenuating burn pain, but they have a myriad of side effects including respiratory depression, nausea, impaired gastrointestinal motility, sedation, dependence, physiologic tolerance, and opioid-induced hyperalgesia. To test and develop novel analgesics, validated burn-relevant animal models of pain are indispensable. Herein we review such animal models, which are mostly limited to rodent models of burn-induced, inflammatory, and neuropathic pain. The latter two are pain syndromes that provide insight into the pain caused by systemic pro-inflammatory cytokines and direct injury to nerves (e.g., after severe burn), respectively. To date, no single animal model optimally mimics the complex pathophysiology and pain that a human burn patient experiences. No currently available burn-pain model examines effects of pharmacological intervention on wound healing. As cornerstones of pain and wound healing, pro-inflammatory mediators may be utilized for insight into both processes. Moreover, common clinical concerns such as systemic inflammatory response syndrome and multiple organ dysfunction remain unaddressed. For development of analgesics, these aberrations can significantly alter the potential efficacy and/or adverse effects of a prescribed analgesic following burn trauma. We therefore suggest that a multi-model strategy would be the most clinically relevant when evaluating novel analgesics for use in burn patients.

  16. Transition of adult T-cell leukemia/lymphoma clones during clinical progression.

    PubMed

    Aoki, Sakura; Firouzi, Sanaz; López, Yosvany; Yamochi, Tadanori; Nakano, Kazumi; Uchimaru, Kaoru; Utusnomiya, Atae; Iwanaga, Masako; Watanabe, Toshiki

    2016-09-01

    Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm caused by the transformation of HTLV-1-infected T cells. ATLL, especially its aggressive form, is known for its poor prognosis, even with intensive chemotherapy. ATLL cells are considered to be monoclonal; however, multiclonal proliferation or emergence of a new clone over time has been reported based on Southern blot analysis, although direct molecular evidence remains elusive. Furthermore, it is thought that clonal change may be a cause of early drug resistance in ATLL. To directly analyze potential clonal changes in ATLL during its clinical course, we used inverse PCR to detect integration sites in combination with a newly developed method using next-generation sequencing, and compared ATLL cell clonality at different time points. The results of inverse PCR indicated that the major clone was altered in three of 19 patients. Together with results from five patients, using this new method, we found direct evidence of clonal change occurring during the clinical course or in response to chemotherapy in ATLL. These results also highlight the importance of clonality analysis for understanding the mechanisms of ATLL development and drug resistance. PMID:27383637

  17. Recent Progress in Lab-on-a-Chip Technology and Its Potential Application to Clinical Diagnoses

    PubMed Central

    2013-01-01

    We present the construction of the lab-on-a-chip (LOC) system, a state-of-the-art technology that uses polymer materials (i.e., poly[dimethylsiloxane]) for the miniaturization of conventional laboratory apparatuses, and show the potential use of these microfluidic devices in clinical applications. In particular, we introduce the independent unit components of the LOC system and demonstrate how each component can be functionally integrated into one monolithic system for the realization of a LOC system. In specific, we demonstrate microscale polymerase chain reaction with the use of a single heater, a microscale sample injection device with a disposable plastic syringe and a strategy for device assembly under environmentally mild conditions assisted by surface modification techniques. In this way, we endeavor to construct a totally integrated, disposable microfluidic system operated by a single mode, the pressure, which can be applied on-site with enhanced device portability and disposability and with simple and rapid operation for medical and clinical diagnoses, potentially extending its application to urodynamic studies in molecular level. PMID:23610705

  18. Photodynamic therapy: Progress toward a scientific and clinical network in Latin America.

    PubMed

    Buzzá, Hilde H; da Silva, Ana Paula; Vollet Filho, José Dirceu; Ramirez, Dora Patricia; Trujillo, José Roberto; Inada, Natalia M; Moriyama, Lilian T; Kurachi, Cristina; Bagnato, Vanderlei S

    2016-03-01

    Cancer is one of the major challenges for Latin America health services, since the skin cancer is the most frequent lesion. This manuscript addresses an initiative for the treatment of basal cell carcinomas (BCC) by photodynamic therapy (PDT) based on a government-funded national program in Brazil. The program provides clinical training and facilitates access to drugs/equipment and significantly reduces PDT costs. It also lays foundations for the establishment of a Latin American research network to improve prevention, early detection and treatment of diseases. Centers have been established by direct contact (conferences, visits to healthcare facilities and official departments). A local training was divided into complementary theoretical and practical parts. This is an ongoing project that has involved 10 countries: Brazil, Bolivia Chile, Ecuador, El Salvador, Colombia, Cuba, Mexico, Peru and Venezuela, The initial results are encouraging and have provided assessment of Latin America patients relating, for example, the most common skin phototypes with incidence of BCC in such countries. The network is expected to produce relevant scientific information for PDT introduction in many countries. The experience acquired by local teams shall enable them to innovate PDT protocols and increase the number of skilled contributors/researchers to broaden knowledge on the ever-crescent PDT field in Latin America. The establishment of a collaboration network and introduction of other projects and experience exchange shall become an easier process with time. This PDT clinical research network is a start for the strengthening of Science in South Hemisphere countries.

  19. Bullous keratopathy as a progressive disease: evidence from clinical and laboratory imaging studies.

    PubMed

    Morishige, Naoyuki; Sonoda, Koh-Hei

    2013-11-01

    Bullous keratopathy is categorized as a corneal endothelial disease. However, pathological changes, including subepithelial fibrosis and the accumulation of extracellular matrix, have been detected in the corneal stroma of individuals with this condition. In vivo confocal microscopy allows the visualization of human corneal cellular structures and has provided information regarding how eyes are affected by various diseases. However, the determination of disease pathogenesis on the basis of in vivo confocal microscopic observations is problematic. We evaluated the structural alterations in the corneal stroma of eyes affected by bullous keratopathy using second harmonic generation microscopy and laser confocal immunofluorescence microscopy of whole-mount preparations. Using these approaches, we detected the transdifferentiation of keratocytes into fibroblasts and myofibroblasts at the anterior and posterior stroma and the presence of subepithelial fibrosis at the anterior stroma and disorganized collagen lamellae at the posterior stroma of the bullous keratopathy cornea. These changes were only detected in specimens from eyes with stromal edema lasting at least 12 months. Similar time-dependent changes were apparent by using in vivo confocal microscopy in the corneal stroma of patients with bullous keratopathy after performing a Descemet stripping automated endothelial keratoplasty surgery and were associated with an unfavorable outcome with regard to postoperative visual acuity. Our observations suggest that pathological changes in the corneal stroma of patients with bullous keratopathy are progressive and affect postoperative visual acuity after a Descemet stripping automated endothelial keratoplasty surgery is performed. PMID:24104939

  20. Reasoning with Linear Orders: Differential Parietal Cortex Activation in Sub-Clinical Depression. An fMRI Investigation in Sub-Clinical Depression and Controls

    PubMed Central

    Hinton, Elanor C.; Wise, Richard G.; Singh, Krish D.; von Hecker, Ulrich

    2015-01-01

    The capacity to learn new information and manipulate it for efficient retrieval has long been studied through reasoning paradigms, which also has applicability to the study of social behavior. Humans can learn about the linear order within groups using reasoning, and the success of such reasoning may vary according to affective state, such as depression. We investigated the neural basis of these latter findings using functional neuroimaging. Using BDI-II criteria, 14 non-depressed (ND) and 12 mildly depressed volunteers took part in a linear-order reasoning task during functional magnetic resonance imaging. The hippocampus, parietal, and prefrontal cortices were activated during the task, in accordance with previous studies. In the learning phase and in the test phase, greater activation of the parietal cortex was found in the depressed group, which may be a compensatory mechanism in order to reach the same behavioral performance as the ND group, or evidence for a different reasoning strategy in the depressed group. PMID:25646078

  1. Measurement of the restricted linear energy transfer of stray radiation close to the treatment volume of 12 and 18 MeV clinical photon beams

    SciTech Connect

    Makrigiorgos, G.; Antonadou, D.; Proukakis, C.; Throuvalas, N.

    1989-03-01

    The restricted dose mean linear energy transfer (LET) (L-bar/sub 500,//sub D/ ) of the stray radiation field a few centimeters outside the treatment volume has been measured for 12 and 18 MV photons produced by a clinical Therac-20 (AECL) accelerator. The measurements were performed as a function of field size and distance from the edge of the treatment volume, using the method of the high-pressure ionization chamber. Contrary to what was found in a previous investigation for a clinical Co-60 unit and despite the presence of photoneutrons (in the case of 18 MV photons), the L-bar/sub 500,//sub D/ outside the beam does not increase significantly relative to the L-bar/sub 500,//sub D/ of the primary beam.

  2. Functional Activities Questionnaire items that best discriminate and predict progression from clinically normal to mild cognitive impairment

    PubMed Central

    Marshall, Gad A.; Zoller, Amy S.; Lorius, Natacha; Amariglio, Rebecca E.; Locascio, Joseph J.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.

    2015-01-01

    Background Impairment in instrumental activities of daily living (IADL) emerges in the transition from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) dementia. Some IADL scales are sensitive to early deficits in MCI, but none have been validated for detecting subtle functional changes in clinically normal (CN) elderly at risk for AD. Methods Data from 624 subjects participating in the Alzheimer’s Disease Neuroimaging Initiative and 524 subjects participating in the Massachusetts Alzheimer’s Disease Research Center, which are two large cohorts including CN elderly and MCI subjects, were used to determine which Functional Activities Questionnaire items best discriminate between and predict progression from CN to MCI. Results We found that “Remembering appointments” and “assembling tax records” best discriminated between CN and MCI subjects, while worse performance on “paying attention and understanding a TV program”, “paying bills/balancing checkbook”, and “heating water and turning off the stove” predicted greater hazard of progressing from a diagnosis of CN to MCI. Conclusions These results demonstrate that certain questions are especially sensitive in detecting the earliest functional changes in CN elderly at risk for AD. As the field moves toward earlier intervention in preclinical AD, it is important to determine which IADL changes can be detected at that stage and track decline over time. PMID:26017560

  3. 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.

  4. Chronic progressive external ophthalmoplegia in a heredo-ataxia: neurogenic or myogenic? A clinical, neuropathological and submicroscopic study.

    PubMed

    Bastiaensen, L A; Jaspar, H H; Stadhouders, A M; Egberink, G J; Korten, J J

    1977-12-01

    A patient with Friedreich's disease and chronic progressive external ophthalmoplegia is descirbed. An investigation was performed into the nature of the ocular motor disorders, which appeared clinically to be supranuclear. The EMG of the ocular muscles suggested myopathy. A specimen of ocular muscle was obtained by biopsy and examined with the light microscope and-for the first time-under the electron microscope. Signs of mitochondrial myopathy were found alongside neurogenic features. Postmortem examination of the central nervous system confirmed the diagnosis of Friedreich's disease with lesions of the motor cells in the anterior horn of the spinal cord. No evidence was found for a supranuclear or inernuclear origin of the ocular palsies, but 20-30 per cent of the neutrons in the nuclei III and IV were atrophic. Lesions of the non-medullated motor nerve fibres were also visible under the electron microscope. That the origin of the c. p. e. o. in this heredo-ataxia is neurogenic-nuclear is postulated on the grounds of the neuropathological and electronmicroscopic findings. Resemblances to the microscopic and submicroscopic and submicroscopic appearance of many types of "ocular myopathy" and "ophthalmoplegia-plus" throw doubt upon the myogenic character of these conditions. Possibly chronic, slowly progressive atrophy in the nuclear areas of the ocular motor nerves must in these cases also be held responsible for the c. p. e. o. Perhaps Moebius's Kern-Schwund theory may be revived after 85 years. PMID:605773

  5. Experience With Afatinib in Patients With Non-Small Cell Lung Cancer Progressing After Clinical Benefit From Gefitinib and Erlotinib

    PubMed Central

    Fischer, Jürgen R.; Grohé, Christian; Gütz, Sylvia; Thomas, Michael; Kimmich, Martin; Schneider, Claus-Peter; Laack, Eckart; Märten, Angela

    2014-01-01

    Background. Afatinib, an irreversible ErbB family blocker, demonstrated superiority to chemotherapy as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is also active in patients progressing on EGFR tyrosine kinase inhibitors (EGFR-TKIs). We report the results of a large cohort of NSCLC patients receiving afatinib within a compassionate-use program (CUP). Patients and Methods. Patients with advanced NSCLC progressing after one line or more of chemotherapy and one line or more of EGFR-TKI treatment with either an EGFR mutation or documented clinical benefit were enrolled. Data collection was not monitored or verified by central review. The intention of this CUP was to provide controlled preregistration access to afatinib for patients with life-threatening diseases and no other treatment option. Results. From May 2010 to October 2013, 573 patients (65% female; median age: 64 years [range: 28–89 years]) were enrolled, with strong participation of community oncologists. Comorbidities were allowed, including second malignancies in 11% of patients. EGFR mutation status was available in 391 patients (72%), and 83% tested mutation positive. Median time to treatment failure (TTF) of 541 patients treated with afatinib was 3.7 months (range: 0.0 to >29.0 months). Median TTF was 4.0 and 2.7 months in patients with adenocarcinomas and squamous cell carcinomas, respectively, and 4.6 months in patients with EGFR-mutated NSCLC. Adverse events were generally manageable. Conclusion. Afatinib was able to be given in a real-world setting to heavily pretreated patients with EGFR-mutated or EGFR-TKI-sensitive NSCLC. Acknowledging the constraints of data collection in a CUP, afatinib appears to be safe and to confer some clinical benefit in this population. PMID:25232040

  6. [Clinical feature and ATP8B1 mutation analysis of a patient with progressive familial intrahepatic cholestasis type I].

    PubMed

    Cheng, Ying; Guo, Li; Song, Yuan-Zong

    2016-08-01

    Progressive familial intrahepatic cholestasis type I (PFIC1) is an autosomal recessive disorder caused by biallelic mutations of ATP8B1 gene, with progressive cholestasis as the main clinical manifestation. This paper reports the clinical and genetic features of a PFIC1 patient definitely diagnosed by ATP8B1 genetic analysis. The patient, a boy aged 14 months, was referred to the hospital with the complaint of jaundiced skin and sclera over 10 months. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined etiology. On physical examination, hepatosplenomegaly was discovered in addition to jaundice of the skin and sclera. The liver was palpable 4 cm below the right subcostal margin and 2 cm below the xiphoid while the spleen 2 cm below the left subcostal margin. The liver function test revealed elevated levels of serum total bile acids, bilirubin, and transaminases; however, the γ-glutamyl transferase level was normal. The diagnosis was genetic cholestasis of undetermined origin. At the age of 1 year and 8 months, a Roux-en-Y cholecystocolonic bypass operation was performed, and thereafter the jaundice disappeared. At 5 years and 1 month, via whole genome sequencing analysis and Sanger sequencing confirmation, the boy was found to be a homozygote of mutation c.2081T>A(p.I694N) of ATP8B1 gene, and thus PFIC1 was definitely diagnosed. The boy was followed up until he was 6 years, and jaundice did not recur, but the long-term outcome remains to be observed. PMID:27530795

  7. Assessing the HIV Care Continuum in Latin America: progress in clinical retention, cART use and viral suppression

    PubMed Central

    Rebeiro, Peter F; Cesar, Carina; Shepherd, Bryan E; De Boni, Raquel B; Cortés, Claudia P; Rodriguez, Fernanda; Belaunzarán-Zamudio, Pablo; Pape, Jean W; Padgett, Denis; Hoces, Daniel; McGowan, Catherine C; Cahn, Pedro

    2016-01-01

    Introduction We assessed trends in HIV Care Continuum outcomes associated with delayed disease progression and reduced transmission within a large Latin American cohort over a decade: clinical retention, combination antiretroviral therapy (cART) use and viral suppression (VS). Methods Adults from Caribbean, Central and South America network for HIV epidemiology clinical cohorts in seven countries contributed data between 2003 and 2012. Retention was defined as two or more HIV care visits annually, >90 days apart. cART was defined as prescription of three or more antiretroviral agents annually. VS was defined as HIV-1 RNA <200 copies/mL at last measurement annually. cART and VS denominators were subjects with at least one visit annually. Multivariable modified Poisson regression was used to assess temporal trends and examine associations between age, sex, HIV transmission mode, cohort, calendar year and time in care. Results Among 18,799 individuals in retention analyses, 14,380 in cART analyses and 13,330 in VS analyses, differences existed between those meeting indicator definitions versus those not by most characteristics. Retention, cART and VS significantly improved from 2003 to 2012 (63 to 77%, 74 to 91% and 53 to 82%, respectively; p<0.05, each). Female sex (risk ratio (RR)=0.97 vs. males) and injection drug use as HIV transmission mode (RR=0.83 vs. male sexual contact with males (MSM)) were significantly associated with lower retention, but unrelated with cART or VS. MSM (RR=0.96) significantly decreased the probability of cART compared with heterosexual transmission. Conclusions HIV Care Continuum outcomes improved over time in Latin America, though disparities for vulnerable groups remain. Efforts must be made to increase retention, cART and VS, while engaging in additional research to sustain progress in these settings. PMID:27065108

  8. Macular Ganglion Cell -Inner Plexiform Layer Thickness Is Associated with Clinical Progression in Mild Cognitive Impairment and Alzheimers Disease

    PubMed Central

    Choi, Seong Hye; Park, Sang Jun

    2016-01-01

    Purpose We investigated the association of the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thicknesses with disease progression in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods We recruited 42 patients with AD, 26 with MCI, and 66 normal elderly controls. The thicknesses of the RNFL and GCIPL were measured via spectral-domain optic coherent tomography in all participants at baseline. The patients with MCI or AD underwent clinical and neuropsychological tests at baseline and once every year thereafter for 2 years. Results The Clinical Dementia Rating scale-Sum of Boxes (CDR-SB) score exhibited significant negative relationships with the average GCIPL thickness (β = -0.15, p < 0.05) and the GCIPL thickness in the superotemporal, superonasal, and inferonasal sectors. The composite memory score exhibited significant positive associations with the average GCIPL thickness and the GCIPL thickness in the superotemporal, inferonasal, and inferotemporal sectors. The temporal RNFL thickness, the average and minimum GCIPL thicknesses, and the GCIPL thickness in the inferonasal, inferior, and inferotemporal sectors at baseline were significantly reduced in MCI patients who were converted to AD compared to stable MCI patients. The change of CDR-SB from baseline to 2 years exhibited significant negative associations with the average (β = -0.150, p = 0.006) and minimum GCIPL thicknesses as well as GCIPL thickness in the superotemporal, superior, superonasal, and inferonasal sectors at baseline. Conclusions Our data suggest that macular GCIPL thickness represents a promising biomarker for monitoring the progression of MCI and AD. PMID:27598262

  9. High-throughput sequencing and clinical microbiology: progress, opportunities and challenges.

    PubMed

    Pallen, Mark J; Loman, Nicholas J; Penn, Charles W

    2010-10-01

    High-throughput sequencing is sweeping through clinical microbiology, transforming our discipline in its wake. It is already providing an enhanced view of pathogen biology through rapid and inexpensive whole-genome sequencing and more sophisticated applications such as RNA-seq. It also promises to deliver high-resolution genomic epidemiology as the ultimate typing method for bacteria. However, the most revolutionary effect of this 'disruptive technology' is likely to be creation of a novel sequence-based, culture-independent diagnostic microbiology that incorporates microbial community profiling, metagenomics and single-cell genomics. We should prepare for the coming 'technological singularity' in sequencing, when this technology becomes so fast and so cheap that it threatens to out-compete existing diagnostic and typing methods in microbiology. PMID:20843733

  10. [Research progress regarding the clinical evaluation on recombinant human papillomavirus vaccines].

    PubMed

    He, W G; Zhao, J; Huang, S J; Wu, T

    2016-06-01

    Human papillomavirus (HPV) is the main cause for cervical cancer, anogenital cancers and genital warts. Three HPV vaccines have been licensed abroad. Data from clinical trials showed high efficacy of the HPV vaccines in young women with 90%-100% vaccine-related HPV diseases prevented. Though efficacy of the vaccine appears lower in older women, this population can still benefit from vaccination. Immunobriging trials show that the two-dose schedule in 9-14 years old girls elicits non-inferior immune response than the three-dose one in young adults. In addition, HPV vaccines can reduce the recurrent rates in CIN2+ patients after therapeutic surgery and the vaccines have cross-protection aganist diseases caused by non-vaccine type HPV. Safety data on HPV vaccines are assuring. Thus HPV vaccine should be widely used in adolescent girls and women of appropriate age groups. PMID:27346126

  11. Clinical characteristics and long-term progression of young patients with acute coronary syndrome in Brazil

    PubMed Central

    Soeiro, Alexandre de Matos; Fernandes, Felipe Lourenço; Soeiro, Maria Carolina Feres de Almeida; Serrano, Carlos Vicente; de Oliveira, Múcio Tavares

    2015-01-01

    Objective In Brazil, there are few descriptions in the literature on the angiographic pattern and clinical characteristics of young patients with acute coronary syndrome, despite the evident number of cases in the population. The objective of this study was to evaluate which clinical characteristics are most closely related to the acute coronary syndrome in young patients, and what long-term outcomes are in this population. Methods This is a prospective observational study with 268 patients aged under 55 years with acute coronary syndrome, carried out between May 2010 and May 2013. Data were obtained on demographics, laboratory test and angiography results, and the coronary treatment adopted. Statistical analysis was presented as percentages and absolute values. Results Approximately 57% were men and the median age was 50 years (30 to 55). The main risk factors were arterial hypertension (68%), smoking (67%), and dyslipidemia (43%). Typical pain was present in 90% of patients. In young individuals, 25.7% showed ST segment elevation. Approximately 56.5% of patients presented with a single-vessel angiographic pattern. About 7.1% were submitted to coronary bypass surgery, and 42.1% to percutaneous coronary angioplasty. Intrahospital mortality was 1.5%, and the combined event rate (cerebrovascular accident/stroke, cardiogenic shock, reinfarction, and arrhythmias) was 13.8%. After a mean follow-up of 10 months, mortality was 9.8%, while 25.4% of the patients had new ischemic events, and 37.3% required readmission to hospital. Conclusion In the short-term, young patients presented with mortality rates below what was expected when compared to the rates noted in other studies. However, there was a significant increase in the number of events in the 10-month follow-up. PMID:26466059

  12. Hepatitis E Virus Superinfection and Clinical Progression in Hepatitis B Patients.

    PubMed

    Hoan, Nghiem Xuan; Tong, Hoang Van; Hecht, Nicole; Sy, Bui Tien; Marcinek, Patrick; Meyer, Christian G; Song, Le Huu; Toan, Nguyen Linh; Kurreck, Jens; Kremsner, Peter G; Bock, C-Thomas; Velavan, Thirumalaisamy P

    2015-12-01

    Hepatitis E virus (HEV) infection may cause acute hepatitis and lead to hepatic failure in developing and developed countries. We studied HEV seroprevalences in patients with hepatitis B virus (HBV) infection to understand the consequences of HEV superinfection in a Vietnamese population. This cross-sectional study was conducted from 2012 to 2013 and included 1318 Vietnamese patients with HBV-related liver diseases and 340 healthy controls. The case group included patients with acute (n = 26) and chronic hepatitis B (n = 744), liver cirrhosis (n = 160), hepatocellular carcinoma (n = 166) and patients with both liver cirrhosis and hepatocellular carcinoma (n = 222). Anti-HEV IgG and IgM antibodies were assessed in patients and controls by ELISA. HEV-RNA was identified by PCR assays and sequencing. Seroprevalences of anti-HEV IgG among hepatitis B patients and controls were 45% and 31%, respectively (adjusted P = 0.034). Anti-HEV IgM seroprevalences were 11.6% and 4.7% in patients and controls, respectively (adjusted P = 0.005). Seroprevalences were higher among the elder individuals. When stratifying for patient groups, those with liver cirrhosis had the highest anti-HEV IgG (52%) and anti-HEV IgM (19%) seroprevalences. Hepatitis B patients with current HEV infection had abnormal liver function tests compared to patients with past or without HEV infection. One HEV isolate was retrieved from a patient with both liver cirrhosis and hepatocellular carcinoma and identified as HEV genotype 3. This study indicates high prevalences of HEV infection in Vietnamese HBV patients and among healthy individuals and shows that HEV superinfection may influence the outcome and progression of HBV-related liver disease.

  13. Evidence, research, and clinical practice: a patient-centered framework for progress in wound care.

    PubMed

    van Rijswijk, Lia; Gray, Mikel

    2011-09-01

    Traditional criteria used in selecting wound care interventions are being slowly replaced with an evidence-based practice approach. The value of such an approach for providing optimal care has been established, but the definition of evidence- based care and the process used to generate evidence continue to evolve. For example, the role of studies developed to demonstrate efficacy, randomized controlled trials (RCT), the value of effectiveness studies designed to evaluate outcomes in real world practice, and the use of disease-oriented (interim) study outcomes for wound care research such as reduces wound fluid or improves granulation tissue formation have been topics of international conversations and consensus documents. In addition, the use in some clinical studies and most systematic study reviews of ingredient- or characteristic-based categories to group products that may not share a common operational definition of how they function has led to a high variability in outcomes, resulting in inconclusive or low-level evidence. These concerns and debates, along with their influence on practice, may cast doubt on the value of evidence-based practice guidelines for some clinicians, slowing their rate of implementation and extending the discussion about definitions of evidence-based care and the relative merits of various research designs. At the same time, amid growing concerns about medical device safety, clinicians must answer three questions about an intervention and its related products or devices in order to provide safe and effective care: 1) Can it work? 2) Does it work? 3) Is it worth it? Reviewing current knowledge about wound care, wound treatment modalities, and the basic principles of research within the existing framework of questions to be answered suggests a clear path toward obtaining much-needed evidence. In wound care, using clearly defined process- es to study patient-centered outcomes (eg, quality of life, complete healing) and

  14. Evidence, research, and clinical practice: a patient-centered framework for progress in wound care.

    PubMed

    van Rijswijk, Lia; Gray, Mikel

    2012-01-01

    Traditional criteria used in selecting wound care interventions are being slowly replaced with an evidence-based practice approach. The value of such an approach for providing optimal care has been established, but the definition of evidence-based care and the process used to generate evidence continue to evolve. For example, the role of studies developed to demonstrate efficacy, randomized controlled trials, the value of effectiveness studies designed to evaluate outcomes in real world practice, and the use of disease-oriented (interim) study outcomes for wound care research, such as reduces wound fluid or improves granulation tissue formation, have been topics of international conversations and consensus documents. In addition, the use in some clinical studies and most systematic study reviews of ingredient or characteristic-based categories to group products that may not share a common operational definition of how they function has led to a high variability in outcomes, resulting in inconclusive or low-level evidence. These concerns and debates, along with their influence on practice, may cast doubt on the value of evidence-based practice guidelines for some clinicians, slowing their rate of implementation, and extending the discussion about definitions of evidence-based care and the relative merits of various research designs. At the same time, amid growing concerns about medical device safety, clinicians must answer 3 questions about an intervention and its related products or devices in order to provide safe and effective care: (1) Can it work? (2) Does it work? (3) Is it worth it? Reviewing current knowledge about wound care, wound treatment modalities, and the basic principles of research within the existing framework of questions to be answered suggests a clear path toward obtaining much-needed evidence. In wound care, using clearly defined processes to study patient-centered outcomes (eg, quality of life, complete healing) and only product groupings that

  15. A clinical review on extreme hypofractionated stereotactic body radiation therapy for localized prostate cancer using nonrobotic linear accelerators.

    PubMed

    Macias, Victor A; Perez-Romasanta, Luis A

    2014-06-01

    Seven phase I-II studies fell within the inclusion criteria. Details on the radiotherapy technique, patient selection, fractionation scheme, exclusion criteria, treatment toxicity, quality-of-life, and tumor control were collected. The studies provide encouraging results of acute and late toxicity, with rare grade 3 events, that seem comparable to robotic SBRT. The biochemical disease-free survival rates look promising, but most patients belong to the low-risk group. The trials are limited by a short follow-up, small number of patients, and different approaches in prescribing dose and defining the acceptable dose heterogeneities. Currently, nonrobotic SBRT regimens should be used in the context of clinical trials.

  16. Distinct clinical patterns and immune infiltrates are observed at time of progression on targeted therapy versus immune checkpoint blockade for melanoma

    PubMed Central

    Cooper, Zachary A.; Reuben, Alexandre; Spencer, Christine N.; Prieto, Peter A.; Austin-Breneman, Jacob L.; Jiang, Hong; Haymaker, Cara; Gopalakrishnan, Vancheswaran; Tetzlaff, Michael T.; Frederick, Dennie T.; Sullivan, Ryan J.; Amaria, Rodabe N.; Patel, Sapna P.; Hwu, Patrick; Woodman, Scott E.; Glitza, Isabella C.; Diab, Adi; Vence, Luis M.; Rodriguez-Canales, Jaime; Parra, Edwin R.; Wistuba, Ignacio I.; Coussens, Lisa M.; Sharpe, Arlene H.; Flaherty, Keith T.; Gershenwald, Jeffrey E.; Chin, Lynda; Davies, Michael A.; Clise-Dwyer, Karen; Allison, James P.; Sharma, Padmanee; Wargo, Jennifer A.

    2016-01-01

    ABSTRACT We have made major advances in the treatment of melanoma through the use of targeted therapy and immune checkpoint blockade; however, clinicians are posed with therapeutic dilemmas regarding timing and sequence of therapy. There is a growing appreciation of the impact of antitumor immune responses to these therapies, and we performed studies to test the hypothesis that clinical patterns and immune infiltrates differ at progression on these treatments. We observed rapid clinical progression kinetics in patients on targeted therapy compared to immune checkpoint blockade. To gain insight into possible immune mechanisms behind these differences, we performed deep immune profiling in tumors of patients on therapy. We demonstrated low CD8+ T-cell infiltrate on targeted therapy and high CD8+ T-cell infiltrate on immune checkpoint blockade at clinical progression. These data have important implications, and suggest that antitumor immune responses should be assessed when considering therapeutic options for patients with melanoma. PMID:27141370

  17. Effects of acupressure on progress of labor and cesarean section rate: randomized clinical trial

    PubMed Central

    Mafetoni, Reginaldo Roque; Shimo, Antonieta Keiko Kakuda

    2015-01-01

    OBJECTIVE To analyze the effects of acupressure at the SP6 point on labor duration and cesarean section rates in parturients served in a public maternity hospital. METHODS This controlled, randomized, double-blind, pragmatic clinical trial involved 156 participants with gestational age ≥ 37 weeks, cervical dilation ≥ 4 cm, and ≥ 2 contractions in 10 min. The women were randomly divided into an acupressure, placebo, or control group at a university hospital in an inland city in the state of Sao Paulo, Brazil, in 2013. Acupressure was applied to the SP6 point during contractions for 20 min. RESULTS The average labor duration was significantly different between the SP6 acupressure group [221.5 min (SD = 162.4)] versus placebo [397.9 min (SD = 265.6)] and versus control [381.9 min (SD = 358.3)] (p = 0.0047); however, the groups were similar regarding the cesarean section rates (p = 0.2526) and Apgar scores in the first minute (p = 0.9542) and the fifth minute (p = 0.7218) of life of the neonate. CONCLUSIONS The SP6 acupressure point proved to be a complementary measure to induce labor and may shorten the labor duration without causing adverse effects to the mother or the newborn. However, it did not affect the cesarean section rate. PMID:25741644

  18. Effects of acupressure on progress of labor and cesarean section rate: randomized clinical trial.

    PubMed

    Mafetoni, Reginaldo Roque; Shimo, Antonieta Keiko Kakuda

    2015-01-01

    OBJECTIVE To analyze the effects of acupressure at the SP6 point on labor duration and cesarean section rates in parturients served in a public maternity hospital. METHODS This controlled, randomized, double-blind, pragmatic clinical trial involved 156 participants with gestational age ≥ 37 weeks, cervical dilation ≥ 4 cm, and ≥ 2 contractions in 10 min. The women were randomly divided into an acupressure, placebo, or control group at a university hospital in an inland city in the state of Sao Paulo, Brazil, in 2013. Acupressure was applied to the SP6 point during contractions for 20 min. RESULTS The average labor duration was significantly different between the SP6 acupressure group [221.5 min (SD = 162.4)] versus placebo [397.9 min (SD = 265.6)] and versus control [381.9 min (SD = 358.3)] (p = 0.0047); however, the groups were similar regarding the cesarean section rates (p = 0.2526) and Apgar scores in the first minute (p = 0.9542) and the fifth minute (p = 0.7218) of life of the neonate. CONCLUSIONS The SP6 acupressure point proved to be a complementary measure to induce labor and may shorten the labor duration without causing adverse effects to the mother or the newborn. However, it did not affect the cesarean section rate.

  19. Have Smartphones Contributed in the Clinical Progress of Oral and Maxillofacial Surgery?

    PubMed Central

    Dhuvad, Mukesh M.; Kshirsagar, Rajesh A.

    2015-01-01

    Background Dental surgeons who encounter complex situations, such as those in unscheduled care, often have limited resources to provide a structured and specialty care. Therefore, there is always a need for cost-effective, easy to handle, easy to carry “Smartphones”. Objective The purpose of this paper was to undertake a review of literature on “Smartphone in Oral and Maxillofacial Surgery” online data-base and discuss the case series with emphasis on the role of attending dental surgeon and the maxillofacial surgeon. Materials and Methods The available literature relevant to oral and maxillofacial surgery in online data-base of the United States National Library of Medicine: PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) was searched. The inclusion criterion was to review the published clinical papers, abstracts and evidence based reviews on ‘Uses of Smartphone in Oral and Maxillofacial Surgery’. Results Six articles were found with the search term “Smartphone in Oral and Maxillofacial Surgery” in the literature searched. Five articles met the inclusion criteria for the study. The relevant data was extracted, tabulated, and reviewed to draw evidence-based conclusions for uses of smartphone in oral and maxillofacial surgery. Conclusion Utilization of smartphones in oral and maxillofacial surgery facilitate in differential diagnosis, treatment, follow up, prevention of the disease further and thereby improve the quality of patient care without requiring the presence of the maxillofacial surgeon in remote areas. PMID:26501006

  20. A clinically applicable approach for detecting spontaneous action potential spikes in amyotrophic lateral sclerosis with a linear electrode array.

    PubMed

    Jahanmiri-Nezhad, Faezeh; Li, Xiaoyan; Barkhaus, Paul E; Rymer, William Z; Zhou, Ping

    2014-02-01

    Examination of spontaneous muscle activity is an important part of the routine electromyogram (EMG) in assessing neuromuscular diseases. The EMG is specifically valuable as a diagnostic test in supporting the diagnosis of amyotrophic lateral sclerosis. High-density surface EMG is a relatively new technique that has until now been used in research but has the potential for clinical application. This study presents a simple high-density surface EMG method for automatic detection of spontaneous action potentials from surface electrode array recordings of patients with amyotrophic lateral sclerosis. To reduce computational complexity while maintaining useful information from the electrode array recording, the multichannel high-density surface EMG was transferred to single-dimensional data by calculating the maximum difference across all channels of the electrode array. A spike detection threshold was then set in the single-dimensional domain to identify the firing times of each spontaneous action potential spike, whereas a spike extraction threshold was used to define the onset and offset of the spontaneous spikes. These data were used to extract the spontaneous spike waveforms from the electrode array EMG. A database of detected spontaneous spikes was thus obtained, including their waveforms, on all channels along with their corresponding firing times. This newly developed method makes use of the information from different channels of the electrode array EMG recording. It also has the primary feature of being simple and fast in implementation, with convenient parameter adjustment and user-computer interaction. Hence, it has good possibilities for clinical application.

  1. Linear association between social anxiety symptoms and neural activations to angry faces: from subclinical to clinical levels.

    PubMed

    Carré, Arnaud; Gierski, Fabien; Lemogne, Cédric; Tran, Eric; Raucher-Chéné, Delphine; Béra-Potelle, Céline; Portefaix, Christophe; Kaladjian, Arthur; Pierot, Laurent; Besche-Richard, Chrystel; Limosin, Frédéric

    2014-06-01

    Social anxiety disorder (SAD), which is characterized by the fear of being rejected and negatively evaluated, involves altered brain activation during the processing of negative emotions in a social context. Although associated temperament traits, such as shyness or behavioral inhibition, have been studied, there is still insufficient knowledge to support the dimensional approach, which assumes a continuum from subclinical to clinical levels of social anxiety symptoms. This study used functional magnetic resonance imaging (fMRI) to examine the neural bases of individual differences in social anxiety. Our sample included participants with both healthy/subclinical as well as clinical levels of social anxiety. Forty-six participants with a wide range of social anxiety levels performed a gender decision task with emotional facial expressions during fMRI scanning. Activation in the left anterior insula and right lateral prefrontal cortex in response to angry faces was positively correlated with the level of social anxiety in a regression analysis. The results substantiate, with a dimensional approach, those obtained in previous studies that involved SAD patients or healthy and subclinical participants. It may help to refine further therapeutic strategies based on markers of social anxiety.

  2. Plant-Derived Anti-Inflammatory Compounds: Hopes and Disappointments regarding the Translation of Preclinical Knowledge into Clinical Progress

    PubMed Central

    Fürst, Robert; Zündorf, Ilse

    2014-01-01

    Many diseases have been described to be associated with inflammatory processes. The currently available anti-inflammatory drug therapy is often not successful or causes intolerable side effects. Thus, new anti-inflammatory substances are still urgently needed. Plants were the first source of remedies in the history of mankind. Since their chemical characterization in the 19th century, herbal bioactive compounds have fueled drug development. Also, nowadays, new plant-derived agents continuously enrich our drug arsenal (e.g., vincristine, galantamine, and artemisinin). The number of new, pharmacologically active herbal ingredients, in particular that of anti-inflammatory compounds, rises continuously. The major obstacle in this field is the translation of preclinical knowledge into evidence-based clinical progress. Human trials of good quality are often missing or, when available, are frequently not suitable to really prove a therapeutical value. This minireview will summarize the current situation of 6 very prominent plant-derived anti-inflammatory compounds: curcumin, colchicine, resveratrol, capsaicin, epigallocatechin-3-gallate (EGCG), and quercetin. We will highlight their clinical potential and/or pinpoint an overestimation. Moreover, we will sum up the planned trials in order to provide insights into the inflammatory disorders that are hypothesized to be beneficially influenced by the compound. PMID:24987194

  3. Uncertainty of measurement and clinical value of semen analysis: has standardisation through professional guidelines helped or hindered progress?

    PubMed

    Tomlinson, M J

    2016-09-01

    This article suggests that diagnostic semen analysis has no more clinical value today than it had 25-30 years ago, and both the confusion surrounding its evidence base (in terms of relationship with conception) and the low level of confidence in the clinical setting is attributable to an associated high level of 'uncertainty'. Consideration of the concept of measurement uncertainty is mandatory for medical laboratories applying for the ISO15189 standard. It is evident that the entire semen analysis process is prone to error every step from specimen collection to the reporting of results and serves to compound uncertainty associated with diagnosis or prognosis. Perceived adherence to published guidelines for the assessment of sperm concentration, motility and morphology does not guarantee a reliable and reproducible test result. Moreover, the high level of uncertainty associated with manual sperm motility and morphology can be attributed to subjectivity and lack a traceable standard. This article describes where and why uncertainty exists and suggests that semen analysis will continue to be of limited value until it is more adequately considered and addressed. Although professional guidelines for good practice have provided the foundations for testing procedures for many years, the risk in following rather prescriptive guidance to the letter is that unless they are based on an overwhelmingly firm evidence base, the quality of semen analysis will remain poor and the progress towards the development of more innovative methods for investigating male infertility will be slow. PMID:27529487

  4. Recruitment and retention strategies in clinical studies with low-income and minority populations: Progress from 2004-2014.

    PubMed

    Nicholson, Lisa M; Schwirian, Patricia M; Groner, Judith A

    2015-11-01

    More than 20years have passed since the NIH 1993 Act was initiated, and while progress has been made toward better representation of minorities and women in clinical research studies, as this review will show, there is still tremendous room for improvement. The purpose of this review was to identify the current state of literature on recruitment and retention strategies in clinical studies of low-income and minority populations. We identified 165 studies published in English between 2004 and 2014. Data extracted included information on the study type (descriptive or analytical), study design, study focus (recruitment, retention, both recruitment and retention), health outcome, specific minority group, special population or age group, if specific recruitment/retention techniques were tested, and key research findings. Particular attention was given to articles that statistically analyzed the effectiveness of recruitment and retention strategies on enrollment/retention rates. Effective recruitment and retention strategies for low-income and minority groups, differential effectiveness across groups, and implications for future research are discussed.

  5. Uncertainty of measurement and clinical value of semen analysis: has standardisation through professional guidelines helped or hindered progress?

    PubMed

    Tomlinson, M J

    2016-09-01

    This article suggests that diagnostic semen analysis has no more clinical value today than it had 25-30 years ago, and both the confusion surrounding its evidence base (in terms of relationship with conception) and the low level of confidence in the clinical setting is attributable to an associated high level of 'uncertainty'. Consideration of the concept of measurement uncertainty is mandatory for medical laboratories applying for the ISO15189 standard. It is evident that the entire semen analysis process is prone to error every step from specimen collection to the reporting of results and serves to compound uncertainty associated with diagnosis or prognosis. Perceived adherence to published guidelines for the assessment of sperm concentration, motility and morphology does not guarantee a reliable and reproducible test result. Moreover, the high level of uncertainty associated with manual sperm motility and morphology can be attributed to subjectivity and lack a traceable standard. This article describes where and why uncertainty exists and suggests that semen analysis will continue to be of limited value until it is more adequately considered and addressed. Although professional guidelines for good practice have provided the foundations for testing procedures for many years, the risk in following rather prescriptive guidance to the letter is that unless they are based on an overwhelmingly firm evidence base, the quality of semen analysis will remain poor and the progress towards the development of more innovative methods for investigating male infertility will be slow.

  6. Plant-derived anti-inflammatory compounds: hopes and disappointments regarding the translation of preclinical knowledge into clinical progress.

    PubMed

    Fürst, Robert; Zündorf, Ilse

    2014-01-01

    Many diseases have been described to be associated with inflammatory processes. The currently available anti-inflammatory drug therapy is often not successful or causes intolerable side effects. Thus, new anti-inflammatory substances are still urgently needed. Plants were the first source of remedies in the history of mankind. Since their chemical characterization in the 19th century, herbal bioactive compounds have fueled drug development. Also, nowadays, new plant-derived agents continuously enrich our drug arsenal (e.g., vincristine, galantamine, and artemisinin). The number of new, pharmacologically active herbal ingredients, in particular that of anti-inflammatory compounds, rises continuously. The major obstacle in this field is the translation of preclinical knowledge into evidence-based clinical progress. Human trials of good quality are often missing or, when available, are frequently not suitable to really prove a therapeutical value. This minireview will summarize the current situation of 6 very prominent plant-derived anti-inflammatory compounds: curcumin, colchicine, resveratrol, capsaicin, epigallocatechin-3-gallate (EGCG), and quercetin. We will highlight their clinical potential and/or pinpoint an overestimation. Moreover, we will sum up the planned trials in order to provide insights into the inflammatory disorders that are hypothesized to be beneficially influenced by the compound. PMID:24987194

  7. The predictive distribution of the residual variability in the linear-fixed effects model for clinical cross-over trials.

    PubMed

    Bertsche, Anja; Nehmiz, Gerhard; Beyersmann, Jan; Grieve, Andrew P

    2016-07-01

    In the linear model for cross-over trials, with fixed subject effects and normal i.i.d. random errors, the residual variability corresponds to the intraindividual variability. While population variances are in general unknown, an estimate can be derived that follows a gamma distribution, where the scale parameter is based on the true unknown variability. This gamma distribution is often used for the sample size calculation for trial planning with the precision approach, where the aim is to achieve in the next trial a predefined precision with a given probability. But then the imprecision in the estimated residual variability or, from a Bayesian perspective, the uncertainty of the unknown variability is not taken into account. Here, we present the predictive distribution for the residual variability, and we investigate a link to the F distribution. The consequence is that in the precision approach more subjects will be necessary than with the conventional calculation. For values of the intraindividual variability that are typical of human pharmacokinetics, that is a gCV of 17-36%, we would need approximately a sixth more subjects. PMID:27003464

  8. Linear Energy Transfer Painting With Proton Therapy: A Means of Reducing Radiation Doses With Equivalent Clinical Effectiveness

    SciTech Connect

    Fager, Marcus; Toma-Dasu, Iuliana; Kirk, Maura; Dolney, Derek; Diffenderfer, Eric S.; Vapiwala, Neha; Carabe, Alejandro

    2015-04-01

    Purpose: The purpose of this study was to propose a proton treatment planning method that trades physical dose (D) for dose-averaged linear energy transfer (LET{sub d}) while keeping the radiobiologically weighted dose (D{sub RBE}) to the target the same. Methods and Materials: The target is painted with LET{sub d} by using 2, 4, and 7 fields aimed at the proximal segment of the target (split target planning [STP]). As the LET{sub d} within the target increases with increasing number of fields, D decreases to maintain the D{sub RBE} the same as the conventional treatment planning method by using beams treating the full target (full target planning [FTP]). Results: The LET{sub d} increased 61% for 2-field STP (2STP) compared to FTP, 72% for 4STP, and 82% for 7STP inside the target. This increase in LET{sub d} led to a decrease of D with 5.3 ± 0.6 Gy for 2STP, 4.4 ± 0.7 Gy for 4STP, and 5.3 ± 1.1 Gy for 7STP, keeping the DRBE at 90% of the volume (DRBE, 90) constant to FTP. Conclusions: LET{sub d} painting offers a method to reduce prescribed dose at no cost to the biological effectiveness of the treatment.

  9. The predictive distribution of the residual variability in the linear-fixed effects model for clinical cross-over trials.

    PubMed

    Bertsche, Anja; Nehmiz, Gerhard; Beyersmann, Jan; Grieve, Andrew P

    2016-07-01

    In the linear model for cross-over trials, with fixed subject effects and normal i.i.d. random errors, the residual variability corresponds to the intraindividual variability. While population variances are in general unknown, an estimate can be derived that follows a gamma distribution, where the scale parameter is based on the true unknown variability. This gamma distribution is often used for the sample size calculation for trial planning with the precision approach, where the aim is to achieve in the next trial a predefined precision with a given probability. But then the imprecision in the estimated residual variability or, from a Bayesian perspective, the uncertainty of the unknown variability is not taken into account. Here, we present the predictive distribution for the residual variability, and we investigate a link to the F distribution. The consequence is that in the precision approach more subjects will be necessary than with the conventional calculation. For values of the intraindividual variability that are typical of human pharmacokinetics, that is a gCV of 17-36%, we would need approximately a sixth more subjects.

  10. Merkel Cell Carcinoma: Recent Progress and Current Priorities on Etiology, Pathogenesis, and Clinical Management

    PubMed Central

    2009-01-01

    Purpose To expedite improved understanding, diagnosis, treatment, and prevention of Merkel cell carcinoma (MCC), a rare malignancy of cutaneous neuroendocrine cells that has a 28% 2-year mortality rate. Methods This article summarizes a workshop that discussed the state-of-the-art research and priorities for research on MCC and on a new human polyomavirus (ie, MCPyV) recently discovered in 80% of MCC tumors. Results Normal Merkel cells are widely distributed in the epidermis near the end of nerve axons and may function as mechanoreceptors or chemoreceptors. Malignant MCC cells typically stain for cytokeratin 20 as well as for other epithelial and neuroendocrine markers. MCC subtypes, which are based on histology, on cell line growth properties, and on gene expression profiles, have been reported but have not been linked to prognosis. Clinical management has been empiric. MCPyV is clonally integrated at various sites in the human genome of MCC tumors, with truncating mutations in the viral, large T antigen gene that interrupt viral replication. MCPyV seroprevalence may be high, as with previously known human polyomaviruses. MCC risk is increased 11-fold with AIDS and with other cell-mediated immune deficiencies, B-cell neoplasms, and ultraviolet radiation exposure. Conclusion Development and validation of a range quantitative polymerase chain reaction and serologic assays for detection of MCPyV, as well as an infectious clone of the virus, would clarify the fundamental biology, natural history, and epidemiology of the virus, of MCC, and of other diseases. Contingent on standardized histologic diagnosis and staging of MCC, consortia are needed to clarify the risks and benefits of sentinel lymph node biopsy, adjuvant radiation therapy, and salvage therapies; consortia are needed also for epidemiologic studies of MCC etiology. PMID:19597021

  11. An Autopsy Case of Anti-melanoma Differentiation-associated Gene-5 Antibody-positive Clinical Amyopathic Dermatomyositis Complicated by Rapidly Progressive Interstitial Lung Disease.

    PubMed

    Yoshida, Naomi; Kaieda, Shinjiro; Tomozoe, Kumi; Tajiri, Morihiro; Wakasugi, Daisuke; Okamoto, Masaki; Tominaga, Masaki; Ida, Hiroaki; Hoshino, Tomoaki

    2016-01-01

    A 62-year-old man presented with heliotrope rash, Gottron's sign, and mild muscle weakness. Both of his lung fields showed interstitial changes that worsened rapidly. He was diagnosed with clinical amyopathic dermatomyositis with rapidly progressive interstitial lung disease. The patient died of respiratory failure, despite the administration of immunosuppressive therapy. Autopsy revealed diffuse alveolar damage. An antibody analysis, which was performed postmortem, detected the presence of anti-melanoma differentiation-associated gene (MDA)-5 antibodies. Clinicians should note the clinical, radiologic, and serologic findings to predict anti-MDA-5 antibody-associated rapidly progressive interstitial lung disease. PMID:27301523

  12. Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer.

    PubMed

    Pang, Er-Jun; Yang, Rui; Fu, Xi-bo; Liu, Ye-fu

    2015-04-01

    Long non-coding RNAs (lncRNAs) have been proved to serve as a critical role in cancer development and progression. However, little is known about the pathological role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in pancreatic cancer patients. The aims of this study are to measure the expression of lncRNA MALAT1 in pancreatic cancer patients and to explore the clinical significance of the lncRNA MALAT1. Using qRT-PCR, the expression of lncRNA MALAT1 was measured in 126 pancreatic cancer tissues and 15 adjacent non-cancerous tissues. In the present study, our results indicated that lncRNA MALAT1 was highly expressed in pancreatic cancer compared with adjacent non-cancerous tissues (P < 0.001), and positively correlated with clinical stage (early stages vs. advanced stages, P < 0.001), tumor size (<2 vs. ≥2 cm, P = 0.004), lymph node metastasis (negative vs. positive, P < 0.001), and distant metastasis (absent vs. present, P = 0.001) in pancreatic cancer patients. Furthermore, we also found that lncRNA MALAT1 overexpression was an unfavorable prognostic factor in pancreatic cancer patients (P < 0.001), regardless of clinical stage, tumor size, lymph node metastasis, and distant metastasis. Finally, increased lncRNA MALAT1 expression was an independent poor prognostic factor for pancreatic patients through multivariate analysis (P = 0.018). In conclusion, overexpression of lncRNA MALAT1 serves as an unfavorable prognostic biomarker in pancreatic cancer patients.

  13. Young's modulus imaging based on axial and lateral strain estimation from ultrasound data using a clinical linear probe

    NASA Astrophysics Data System (ADS)

    Said, Ghada; Vray, Didier; Liebgott, Herve; Brusseau, Elisabeth; Basset, Olivier

    2005-04-01

    Strain imaging is useful for visualizing information related to tissue stiffness. However, strain is a parameter that depends on the boundary conditions, tissue connectivity and geometry. As a result, tissue hardness cannot be quantitatively evaluated from the strain distribution. Therefore, reconstruction of the elastic modulus (Young's Modulus) distribution has been investigated for quantitative evaluation of tissue hardness. A method has been recently proposed [NITT 00] to calculate locally the Young's modulus of tissues from the estimations of 3D displacement field within the medium. This approach requires a specific annular ultrasonic probe. The aim of our work, based on Nitta's approach, is to build a Young modulus mapping using clinical ultrasonic equipment. Results from finite-element simulations and a physical phantom are presented.

  14. Value of Baseline Clinical and CT Characteristics for Predicting the Progression of Persistent Pure Ground-glass Nodule 10 mm or Less in Diameter.

    PubMed

    Wu, Fang; Cai, Zu-Long; Tian, Shu-Ping; Jin, Xin; Jing, Rui; Yang, Yue-Qing; Jin, Mei; Zhao, Shao-Hong

    2016-08-01

    Objective To explore the risk factors of the progression of persistent pure ground-glass nodule (pGGN) and make the risk stratification for pGGN 10 mm or less in diameter. Methods From June 2008 to April 2015,100 patients (108 lesions) with persistent pGGN≤10 mm in diameter were included in this study. Patients were followed up at least 1 year using thin-section computed tomography (CT). Patients' baseline clinical data and CT characteristics of pGGN were compared between progression group (size increased or/and solid component appeared) and non-progression group. Cox regression analysis was used to assess the relationship between clinical data,CT characteristics of pGGN,and lesion progression. The risk indices of lesion progression were calculated according to the results of Cox regression analysis and the relative factors of lung adenocarcinoma in previous studies. Logistic regression analysis was used to assess the relationship between risk indices and lesion progression. The optimal cutoff value was decided on receiver operating characteristic curve of risk indices and verified for predicting lesion progression. Results Fifteen of 108 lesions showed progression. The mean follow-up duration was (1016.36±486.00) days. There were statistically significant differences of lesion size,air bronchogram,and vessel changes between progression group and non-progression group (P=0.040,P=0.003,P=0.030,respectively).Lesion density (CT value≥-542.5 HU) and air bronchogram were the risk factors of lesion progression (P=0.003,P=0.021,respectively). The optimal cutoff value of total risk indices on predicting lesion progression was 4.25,with the sensitivity of 46.7%,specificity of 89.2%,and consistency of 83.3%. Conclusions CT value ≥-542.5 HU of pGGN and air bronchogram within lesion may predict lesion progression in persistent pGGN 10 mm or less in diameter. A risk index of less than 4.25 often suggests small probability of disease progression and thus a longer follow

  15. Changes in muscle activity determine progression of clinical symptoms in patients with chronic spine-related muscle pain. A complex clinical and neurophysiological approach.

    PubMed

    Wytrazek, Marcin; Huber, Juliusz; Lisinski, Przemyslaw

    2011-01-01

    Spine-related muscle pain can affect muscle strength and motor unit activity. This study was undertaken to investigate whether surface electromyographic (sEMG) recordings performed during relaxation and maximal contraction reveal differences in the activity of muscles with or without trigger points (TRPs). We also analyzed the possible coexistence of characteristic spontaneous activity in needle electromyographic (eEMG) recordings with the presence of TRPs. Thirty patients with non-specific cervical and back pain were evaluated using clinical, neuroimaging and electroneurographic examinations. Muscle pain was measured using a visual analog scale (VAS), and strength using Lovett's scale; trigger points were detected by palpation. EMG was used to examine motor unit activity. Trigger points were found mainly in the trapezius muscles in thirteen patients. Their presence was accompanied by increased pain intensity, decreased muscle strength, increased resting sEMG amplitude, and decreased sEMG amplitude during muscle contraction. eEMG revealed characteristic asynchronous discharges in TRPs. The results of EMG examinations point to a complexity of muscle pain that depends on progression of the myofascial syndrome.

  16. Changes in muscle activity determine progression of clinical symptoms in patients with chronic spine-related muscle pain. A complex clinical and neurophysiological approach

    PubMed Central

    Wytra̦żek, Marcin; Huber, Juliusz; Lisiński, Przemysław

    Summary Spine-related muscle pain can affect muscle strength and motor unit activity. This study was undertaken to investigate whether surface electromyographic (sEMG) recordings performed during relaxation and maximal contraction reveal differences in the activity of muscles with or without trigger points (TRPs). We also analyzed the possible coexistence of characteristic spontaneous activity in needle electromyographic (eEMG) recordings with the presence of TRPs. Thirty patients with non-specific cervical and back pain were evaluated using clinical, neuroimaging and electroneurographic examinations. Muscle pain was measured using a visual analog scale (VAS), and strength using Lovett’s scale; trigger points were detected by palpation. EMG was used to examine motor unit activity. Trigger points were found mainly in the trapezius muscles in thirteen patients. Their presence was accompanied by increased pain intensity, decreased muscle strength, increased resting sEMG amplitude, and decreased sEMG amplitude during muscle contraction. eEMG revealed characteristic asynchronous discharges in TRPs. The results of EMG examinations point to a complexity of muscle pain that depends on progression of the myofascial syndrome PMID:22152435

  17. X-Linked Hereditary Nephropathy in Navasota Dogs: Clinical Pathology, Morphology, and Gene Expression During Disease Progression.

    PubMed

    Benali, S L; Lees, G E; Nabity, M B; Aricò, A; Drigo, M; Gallo, E; Giantin, M; Aresu, L

    2016-07-01

    X-linked hereditary nephropathy (XLHN) in Navasota dogs is a spontaneously occurring disease caused by a mutation resulting in defective production of type IV collagen and juvenile-onset renal failure. The study was aimed at examining the evolution of renal damage and the expression of selected molecules potentially involved in the pathogenesis of XLHN. Clinical data and renal samples were obtained in 10 XLHN male dogs and 5 controls at 4 (T0), 6 (T1), and 9 (T2) months of age. Glomerular and tubulointerstitial lesions were scored by light microscopy, and the expression of 21 molecules was investigated by quantitative real-time polymerase chain reaction with selected proteins evaluated by immunohistochemistry. No significant histologic lesions or clinicopathologic abnormalities were identified in controls at any time-point. XLHN dogs had progressive proteinuria starting at T0. At T1, XLHN dogs had a mesangioproliferative glomerulopathy with glomerular loss, tubular necrosis, and interstitial fibrosis. At T2, glomerular and tubulointerstitial lesions were more severe, particularly glomerular loss, interstitial fibrosis, and inflammation. At T0, transforming growth factor β, connective tissue growth factor, and platelet-derived growth factor α mRNA were overexpressed in XLHN dogs compared with controls. Clusterin and TIMP1 transcripts were upregulated in later stages of the disease. Transforming growth factor β, connective tissue growth factor, and platelet-derived growth factor α should be considered as key players in the initial events of XHLN. Clusterin and TIMP1 appear to be more associated with the progression rather than initiation of tubulointerstitial damage in chronic renal disease. PMID:26917550

  18. Progressive Reduction in Cortical Thickness as Psychosis Develops: A Multisite Longitudinal Neuroimaging Study of Youth at Elevated Clinical Risk

    PubMed Central

    Cannon, Tyrone D.; Chung, Yoonho; He, George; Sun, Daqiang; Jacobson, Aron; van Erp, Theo G. M.; McEwen, Sarah; Addington, Jean; Bearden, Carrie E.; Cadenhead, Kristin; Cornblatt, Barbara; Mathalon, Daniel H.; McGlashan, Thomas; Perkins, Diana; Jeffries, Clark; Seidman, Larry J.; Tsuang, Ming; Walker, Elaine; Woods, Scott W.; Heinssen, Robert

    2014-01-01

    Background Individuals at clinical high-risk (CHR) who progress to fully psychotic symptoms have been observed to show a steeper rate of cortical gray matter reduction compared with those without symptomatic progression and with healthy controls. Whether such changes reflect processes associated with the pathophysiology of schizophrenia or exposure to antipsychotic drugs is unknown. Methods In this multisite study, 274 CHR cases, including 35 who converted to psychosis, and 135 healthy comparison subjects were scanned with MRI at baseline, 12-month follow-up, and/or the point of conversion for those who developed fully psychotic symptoms. Results In a traveling subjects sub-study, we observed excellent reliability for measures of cortical thickness and subcortical volumes. Controlling for multiple comparisons throughout the brain, CHR converters showed a steeper rate of gray matter loss in right superior frontal, middle frontal, and medial orbitofrontal cortical regions, as well as a greater rate of expansion of the third ventricle, compared with CHR non-converters and healthy controls. Differential tissue loss was present among cases who had not received antipsychotic medications during the inter-scan interval and was predicted by baseline levels of an aggregate measure of pro-inflammatory cytokines in plasma. Conclusions These findings demonstrate that the brain changes are not explained by exposure to antipsychotic drugs, but likely play a role in psychosis pathophysiology. Given that the cortical changes were more pronounced among cases with briefer durations of prodromal symptoms, contributing factors may predominantly play a role in acute-onset forms of psychosis. PMID:25034946

  19. Contemporary phase III clinical trial endpoints in advanced ovarian cancer: assessing the pros and cons of objective response rate, progression-free survival, and overall survival.

    PubMed

    Tate Thigpen, J

    2015-01-01

    Among gynecologic cancers, ovarian cancer provides the greatest challenge because 75% to 80% of patients present with stage III/IV disease. Over the last 40 years, a series of large trials conducted by the Gynecologic Oncology Group and other cooperative groups has produced striking improvements in patient outcome; but the majority still dies of their disease. Further research in both the laboratory and the clinic is essential to continued improvement in patient management. Clinical trials, however, have become a major challenge because of issues with trial endpoints. Historically, overall survival (OS) has been regarded as the "gold standard" of endpoints. Lack of effective treatment for patients who progressed on or recurred after front-line therapy allowed trials to avoid obfuscation of OS by post-progression therapy. More recently, studies have identified over 20 agents active against ovarian cancer. Reasonable evidence shows that effective post-progression therapy with multiple lines of active agents can render the survival endpoint uninterpretable. Two other endpoints avoid this problem. The objective response rate, assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), is an accepted endpoint for accelerated approval in ovarian cancer. More importantly, progression-free survival (PFS), measured from study entry to progression of disease, avoids post-progression therapy completely. Without effective post-progression therapy (prior to 1990), data show that PFS is a surrogate for OS. Recent experience with 4 large trials of bevacizumab shows that PFS can be accurately assessed if progression is clearly defined and if timing of assessments is consistent in all study arms. Acceptance of PFS as the optimal endpoint for ovarian cancer trials by investigators and regulatory agencies is crucial to further advances in management because effective post-progression therapy has rendered differences in OS virtually impossible to assess reliably.

  20. Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study

    PubMed Central

    2012-01-01

    Background Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression. Methods We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA. Results Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of −1.3% point/year for manual muscle testing and of −2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast. Conclusions Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function

  1. Linear and Nonlinear Growth Models for Value-Added Assessment: An Application to Spanish Primary and Secondary Schools' Progress in Reading Comprehension

    ERIC Educational Resources Information Center

    Lopez-Martin, Esther; Kuosmanen, Timo; Gaviria, Jose Luis

    2014-01-01

    Value-added models are considered one of the best alternatives not only for accountability purposes but also to improve the school system itself. The estimates provided by these models measure the contribution of schools to students' academic progress, once the effect of other factors outside school control are eliminated. The functional form…

  2. The Clinical Presentation of Mitochondrial Diseases in Children with Progressive Intellectual and Neurological Deterioration: A National, Prospective, Population-Based Study

    ERIC Educational Resources Information Center

    Verity, Christopher M.; Winstone, Anne Marie; Stellitano, Lesley; Krishnakumar, Deepa; Will, Robert; McFarland, Robert

    2010-01-01

    Aim: Our aim was to study the clinical presentation, mode of diagnosis, and epidemiology of mitochondrial disorders in children from the UK who have progressive intellectual and neurological deterioration (PIND). Method: Since April 1997, we have identified patients aged 16 years or younger with suspected PIND through the monthly notification card…

  3. Clinical and histological assessment of collagen-induced arthritis progression in the diabetes-resistant BB/Wor rat.

    PubMed

    Knoerzer, D B; Donovan, M G; Schwartz, B D; Mengle-Gaw, L J

    1997-01-01

    Collagen-induced arthritis in the diabetes-resistant BB (DR BB)/Wor rat is a severe, aggressive disease initiated by immunization with heterologous native Type II collagen. Onset of clinical symptoms reproducibly occurs in 100% of animals between days 10 and 12 following collagen immunization. Hypertrophy of the synovial lining is the first histological manifestation of the early inflammatory arthritis. A mild inflammatory infiltrate in the synovium rapidly becomes a fibrovascular pannus eroding articular cartilage and subchondral bone. Beginning at the joint margins, an active synovitis is present. Light microscopy and immunohistochemical staining show the infiltrate to be comprised of mononuclear (lymphocytes, macrophages) and polymorphonuclear inflammatory cells. In addition, there is histological evidence for chronic inflammatory nodules and necrotizing vasculitis in connective tissue from diseased joints, both morphologic features associated with rheumatoid arthritis in humans. Subchondral bone erosion appears to be mediated largely by the resorptive action of activated osteoclasts. These histological parameters of disease progression in the DR BB/Wor rat are similar to human rheumatoid arthritis. The extensive degree of similarity in the pathology of DR BB/Wor rat collagen-induced arthritis and human rheumatoid arthritis supports the role of this model as an in vivo disease model for human rheumatoid arthritis. PMID:9061845

  4. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals progression of erosions despite clinical improvement

    PubMed Central

    McQueen, F.; Stewart, N.; Crabbe, J.; Robinson, E.; Yeoman, S.; Tan, P.; McLean, L.

    1999-01-01

    OBJECTIVES—To investigate the progression of joint damage in early rheumatoid arthritis (RA) using magnetic resonance imaging (MRI) of the wrist and determine whether this technique can be used to predict prognosis.
METHODS—An inception cohort of 42 early patients has been followed up prospectively for one year. Gadolinium enhanced MRI scans of the dominant wrist were obtained at baseline and one year and scored for synovitis, tendonitis, bone marrow oedema, and erosions. Plain radiographs were performed concurrently and scored for erosions. Patients were assessed clinically for disease activity and HLA-DRB1 genotyping was performed.
RESULTS—At one year, MRI erosions were found in 74% of patients (31 of 42) compared with 45% at baseline. Twelve patients (28.6%) had radiographic erosions at one year. The total MRI score and MRI erosion score increased significantly from baseline to one year despite falls in clinical measures of inflammation including erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and swollen joint count (p < 0.01 for all). Baseline findings that predicted carpal MRI erosions at one year included a total MRI score of 6 or greater (sensitivity: 93.3%, specificity 81.8%, positive predictive value 93.3%, p = 0.000007), MRI bone oedema (OR = 6.47, p < 0.001), MRI synovitis (OR = 2.14, p = 0.003), and pain score (p = 0.01). Radiological erosions at one year were predicted by a total MRI score at baseline of greater than 13 (OR = 12.4, p = 0.002), the presence of MRI erosions (OR = 11.6, p = 0.005), and the ESR (p = 0.02). If MRI erosions were absent at baseline and the total MRI score was low, radiological erosions were highly unlikely to develop by one year (negative predictive value 0.91 and 0.92 respectively). No association was found between the shared epitope and erosions on MRI (p = 0.4) or radiography (p = 1.0) at one year.
CONCLUSIONS—MRI scans of the dominant wrist are useful

  5. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  6. Clinical stage of breast cancer by parity, age at birth, and time since birth: a progressive effect of pregnancy hormones?

    PubMed

    Albrektsen, Grethe; Heuch, Ivar; Thoresen, Steinar; Kvåle, Gunnar

    2006-01-01

    Breast cancer diagnosed during pregnancy or 1 to 2 years after birth often occurs at a late stage. Little is known about tumor characteristics in the high-risk period shortly after a childbirth. We here explore whether stage of disease differs according to timing of births. Results are based on 22,351 Norwegian breast cancer patients of parity 0 to 5, ages 20 to 74 years. The proportion of stage II to IV tumors was considerably higher among parous than nulliparous women at age <30 years (52.7% versus 36.8%, P=0.009), but similar or lower in other age groups (P(interaction)=0.029). In general, the largest proportion of stage II to IV tumors was found among women diagnosed during pregnancy or <2 years after birth. However, among women with late-age births (first or second birth >or=30 years, third birth >or=35 years), as well as women with an early second birth (<25 years), the proportion with advanced disease was rather similar or even higher among those diagnosed 2 to 6 years after birth (49.3-56.0%). The association between clinical stage and time since birth reached statistical significance among women with a late first or second birth and among all triparous women (P progressive effect on breast cancer tumors in addition to a possible promoting effect. A potential effect of prolactin is discussed.

  7. Mutant, wild type, or overall p53 expression: freedom from clinical progression in tumours of astrocytic lineage.

    PubMed

    Pardo, F S; Hsu, D W; Zeheb, R; Efird, J T; Okunieff, P G; Malkin, D M

    2004-11-01

    Abnormalities of the p53 tumor-suppressor gene are found in a significant proportion of astrocytic brain tumours. We studied tumour specimens from 74 patients evaluated over 20 years at the Massachusetts General Hospital, where clinical outcome could be determined and sufficient pathologic material was available for immunostaining. p53 expression studies employed an affinity-purified p53 monoclonal antibody, whose specificity was verified in absorption studies and, in a minority of cases, a second antibody recognising a different epitope of p53. Significant overexpression of p53 protein was found in 48% of the 74 tumours included in this series and high levels of expression were associated with higher mortality from astrocytic tumours (P<0.001, log rank). Multivariate analyses revealed that immunohistochemically detected p53 was an independent marker of shortened progression-free and overall actuarial survival in patients with astrocytic tumours, suggesting that increased expression of p53 plays an important role in the pathobiology of these tumours. In a subset of 36 cases, coding regions of the p53 gene were completely sequenced via SSCP and direct DNA sequencing, revealing that overexpression of p53 protein is not always associated with point mutations in conserved exons of the p53 gene. Finally, we confirmed p53 protein expression in early-passage human glioma cell lines of known p53 mutational status and immunostaining scores. Although grade continues to be the strongest prognostic variable, the use of p53 staining as a prognostic indicator, in contrast to mutational DNA analyses, may be a useful adjunct in identifying patients at higher risk of treatment failure.

  8. Progression and survival in prostatic adenocarcinoma: a comparison of clinical stage, Gleason grade, S-phase fraction and DNA ploidy.

    PubMed

    Vesalainen, S; Nordling, S; Lipponen, P; Talja, M; Syrjänen, K

    1994-08-01

    Clinical data were reviewed in 325 patients with prostatic adenocarcinoma followed up for a mean of 13 years. Paraffin-embedded tumour biopsy specimens from the primary tumours were available for flow cytometry (FCM) in 273 cases. Intra-tumour heterogeneity in DNA index (DI) was found in 4% of the tumours (54 cases were analysed). S-phase fraction (SPF) and DNA ploidy were significantly interrelated. Aneuploidy and high SPF were significantly related to both a high T category and high Gleason score. The progression in T1-2M0 tumours was related to Gleason score (P = 0.009), DNA ploidy (P = 0.006) and SPF (P = 0.007), while the Gleason score (P = 0.0013), DNA ploidy (P = 0.002) and SPF (P < 0.001) had prognostic value in univariate survival analysis. In the entire cohort, the T category (P < 0.001), M category (P < 0.001), Gleason score (P < 0.001), DNA ploidy (P < 0.001) and SPF (P < 0.001) were significant prognostic factors. In Cox's analysis, the M category (P < 0.001), Gleason score (P < 0.001), T category (P = 0.003), age (P = 0.001) and SPF (P = 0.087) were independently related to prognosis. In the T1-2M0 tumours, Gleason score (P < 0.001), T category (P = 0.022) and SPF (P = 0.058) were independent predictors. A novel classification system in which the DNA ploidy or SPF and the Gleason score were combined was found to be of significant prognostic value in all M0 tumours (P < 0.001). The results suggest that FCM can be used as an adjunct to conventional histological assessments for determination of the correct prognostic category in prostatic adenocarcinoma.

  9. Pre-cART Elevation of CRP and CD4+ T-cell Immune Activation Associated with HIV Clinical Progression in a Multinational Case-Cohort Study

    PubMed Central

    Balagopal, Ashwin; Asmuth, David M.; Yang, Wei-Teng; Campbell, Thomas B.; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R.; Lalloo, Umesh G.; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B.; Semba, Richard D.; Thomas, David L.; Bollinger, Robert C.; Gupta, Amita

    2015-01-01

    Background Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. Methods A case-cohort study (n=470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) clinical trial (1571 HIV treatment-naïve adults who initiated cART; CD4+ T cell count <300 cells/mm3; nine countries) was conducted. A subcohort of 30 participants/country was randomly selected; additional cases were added from the main cohort. Cases (n=236 [random subcohort–36; main cohort–200]) had clinical progression (incident WHO Stage 3/4 event or death) within 96 weeks following cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Results Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4+ T-cell count was 167 cells/mm3. In multivariate analysis, highest quartile CRP concentration (adjusted hazards ratio [aHR] 2.53, 95%CI 1.02-6.28) and CD4+ T-cell activation (aHR 5.18, 95CI 1.09-24.47) were associated with primary outcomes, compared to lowest quartiles. sCD14 had a trend towards association with clinical failure (aHR 2.24, 95%CI 0.96–5.21). Conclusions Measuring CRP and CD4+ T-cell activation may identify patients with CD4+ T cell counts < 300 cells/mm3 at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART. PMID:26017661

  10. Primary care of the patient with chronic obstructive pulmonary disease-part 4: understanding the clinical manifestations of a progressive disease.

    PubMed

    Cooper, Christopher B; Dransfield, Mark

    2008-07-01

    This article reviews the main factors influencing the pathophysiology, symptoms, and progression of chronic obstructive pulmonary disease (COPD), including dynamic hyperinflation, exacerbations, and comorbid illness. Key clinical trials and reviews were identified. After formal presentations to a panel of pulmonary specialists and primary care physicians, a series of concepts, studies, and practical clinical implications related to COPD progression were integrated into this article, the last in a 4-part mini-symposium. The main points of roundtable consensus were as follows: (1) COPD is characterized by declining pulmonary function as classically measured by forced expiratory volume in 1 second (FEV(1)), but the complex pathophysiology and the rationale for bronchodilator therapy are actually better understood in terms of progressive hyperinflation, both at rest (static) and worsening during exercise (dynamic) and exacerbations; (2) although COPD progression is often thought of as inevitable and continuous, the clinical course is actually quite variable and probably influenced by the frequency of exacerbations; (3) preventing exacerbations with pharmacologic and nonpharmacologic care can influence overall morbidity; (4) comorbidities such as lung cancer, cardiovascular disease, and skeletal muscle dysfunction also contribute to declining patient health; and (5) surgical lung volume reduction and lung transplantation should be considered for selected patients with very severe COPD. We conclude that the concept of COPD as a gradual but relentlessly progressive illness that is best monitored via FEV(1) is outdated and likely compromises patient care. Many patients now being managed in primary care settings will benefit from an earlier, broad-based, and aggressive approach to management.

  11. Isolated linear blaschkoid psoriasis.

    PubMed

    Nasimi, M; Abedini, R; Azizpour, A; Nikoo, A

    2016-10-01

    Linear psoriasis (LPs) is considered a rare clinical presentation of psoriasis, which is characterized by linear erythematous and scaly lesions along the lines of Blaschko. We report the case of a 20-year-old man who presented with asymptomatic linear and S-shaped erythematous, scaly plaques on right side of his trunk. The plaques were arranged along the lines of Blaschko with a sharp demarcation at the midline. Histological examination of a skin biopsy confirmed the diagnosis of psoriasis. Topical calcipotriol and betamethasone dipropionate ointments were prescribed for 2 months. A good clinical improvement was achieved, with reduction in lesion thickness and scaling. In patients with linear erythematous and scaly plaques along the lines of Blaschko, the diagnosis of LPs should be kept in mind, especially in patients with asymptomatic lesions of late onset. PMID:27663156

  12. Linear Collisions

    ERIC Educational Resources Information Center

    Walkiewicz, T. A.; Newby, N. D., Jr.

    1972-01-01

    A discussion of linear collisions between two or three objects is related to a junior-level course in analytical mechanics. The theoretical discussion uses a geometrical approach that treats elastic and inelastic collisions from a unified point of view. Experiments with a linear air track are described. (Author/TS)

  13. Frontal linear scieroderma (en Coup de Sabre): a case report.

    PubMed

    Pekiner, Filiz Namdar; Yücelten, Deniz; Gümrü, Birsay; Sinanoğlu, Enver Alper

    2006-01-01

    En coup de sabre is a type of linear scleroderma which presents on the frontal or frontoparietal scalp. En coup de sabre in children is associated with asymmetric growth and progressive facial disfigurement. The purpose of this report was to present the case of a 4-year-old girl with a 2-year history of en coup de sabre. The clinical presentation and radiographic findings are discussed.

  14. Prospective Study on the Incidence and Progression of Clinical Signs in Naïve Dogs Naturally Infected by Leishmania infantum

    PubMed Central

    Foglia Manzillo, Valentina; Di Muccio, Trentina; Cappiello, Sivia; Scalone, Aldo; Paparcone, Rosa; Fiorentino, Eleonora; Gizzarelli, Manuela; Gramiccia, Marina; Gradoni, Luigi; Oliva, Gaetano

    2013-01-01

    The incidence of clinical and clinicopathological signs associated with the progression of infection was evaluated prospectively in 329 naïve young dogs exposed to Leishmania infantum transmission and examined periodically during 22 months (M). The dogs were part of Leishmania vaccine investigations performed under natural conditions. Vaccinated groups were considered in the evaluation when the vaccine resulted non-protective and the appearance and progression of signs did not differ statistically from controls at each time point, otherwise only control groups were included. 115 beagles were part of 3 studies (A to C) performed in the same kennel; 214 owned dogs (29 breeds, 2.3% beagles) were included in a study (D) performed in 45 endemic sites. At M22 the prevalence of any Leishmania infection stage classified as subpatent, active asymptomatic, or symptomatic was 59.8% in studies A–C and 29.2% in study D. Despite different breed composition and infection incidence, the relative proportion of active infections and the progression and type of clinical and clinicopathological signs have been similar in both study sets. All asymptomatic active infections recorded have invariably progressed to full-blown disease, resulting in 56 sick dogs at M22. In these dogs, lymph nodes enlargement and weight loss — recorded from M12 — were the most common signs. Cutaneous signs were seen late (M18) and less frequently. Ocular signs appeared even later, being sporadically recorded at M22. Most clinicopathological alterations became evident from M12, although a few cases of thrombocytopenia or mild non-regenerative anemia were already observed at M6. Albumin/globulin inversions were recorded from M12 and urea/creatinine increase appeared mostly from M18. Altogether our findings indicate that any susceptible young dogs naturally infected by L. infantum present a common pattern of progression of signs during 2 years post infection, providing clues for medical and

  15. Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression

    PubMed Central

    Palmer, T. D.; Martínez, C. H.; Vasquez; Hebron, K.; Jones-Paris, C.; Arnold, S.A.; Chan, S.M.; Chalasani, V.; Gomez-Lemus, J.A.; Williams, A.K.; Chin, J.L.; Giannico, G.A.; Ketova, T.; Lewis, J.D.; Zijlstra, A.

    2013-01-01

    Normal physiology relies on the organization of transmembrane proteins by molecular scaffolds, such as tetraspanins. Oncogenesis frequently involves changes in their organization or expression. The tetraspanin CD151 is thought to contribute to cancer progression through direct interaction with the laminin-binding integrins α3β1 and α6β1. However, this interaction cannot explain the ability of CD151 to control migration in the absence of these integrins or on non-laminin substrates. We demonstrate that CD151 can regulate tumor cell migration without direct integrin binding and that integrin-free CD151 (CD151free) correlates clinically with tumor progression and metastasis. Clustering CD151free through its integrin-binding domain promotes accumulation in areas of cell-cell contact leading to enhanced adhesion and inhibition of tumor cell motility in vitro and in vivo. CD151free clustering is a strong regulator of motility even in the absence of α3 expression but requires PKCα, suggesting that CD151 can control migration independent of its integrin associations. The histological detection of CD151free in prostate cancer correlates with poor patient outcome. When CD151free is present, patients are more likely to recur after radical prostatectomy and progression to metastatic disease is accelerated. Multivariable analysis identifies CD151free as an independent predictor of survival. Moreover, the detection of CD151free can stratify survival among patients with elevated PSA. Cumulatively these studies demonstrate that a subpopulation of CD151 exists on the surface of tumor cells that can regulate migration independent of its integrin partner. The clinical correlation of CD151free with prostate cancer progression suggests that it may contribute to the disease and predict cancer progression. PMID:24220242

  16. Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group.

    PubMed

    Lin, Nancy U; Lee, Eudocia Q; Aoyama, Hidefumi; Barani, Igor J; Baumert, Brigitta G; Brown, Paul D; Camidge, D Ross; Chang, Susan M; Dancey, Janet; Gaspar, Laurie E; Harris, Gordon J; Hodi, F Stephen; Kalkanis, Steven N; Lamborn, Kathleen R; Linskey, Mark E; Macdonald, David R; Margolin, Kim; Mehta, Minesh P; Schiff, David; Soffietti, Riccardo; Suh, John H; van den Bent, Martin J; Vogelbaum, Michael A; Wefel, Jeffrey S; Wen, Patrick Y

    2013-09-01

    Therapeutic outcomes for patients with brain metastases need to improve. A critical review of trials specifically addressing brain metastases shows key issues that could prevent acceptance of results by regulatory agencies, including enrolment of heterogeneous groups of patients and varying definitions of clinical endpoints. Considerations specific to disease, modality, and treatment are not consistently addressed. Additionally, the schedule of CNS imaging and consequences of detection of new or progressive brain metastases in trials mainly exploring the extra-CNS activity of systemic drugs are highly variable. The Response Assessment in Neuro-Oncology (RANO) working group is an independent, international, collaborative effort to improve the design of trials in patients with brain tumours. In this two-part series, we review the state of clinical trials of brain metastases and suggest a consensus recommendation for the development of criteria for future clinical trials.

  17. Linear regression analysis of survival data with missing censoring indicators.

    PubMed

    Wang, Qihua; Dinse, Gregg E

    2011-04-01

    Linear regression analysis has been studied extensively in a random censorship setting, but typically all of the censoring indicators are assumed to be observed. In this paper, we develop synthetic data methods for estimating regression parameters in a linear model when some censoring indicators are missing. We define estimators based on regression calibration, imputation, and inverse probability weighting techniques, and we prove all three estimators are asymptotically normal. The finite-sample performance of each estimator is evaluated via simulation. We illustrate our methods by assessing the effects of sex and age on the time to non-ambulatory progression for patients in a brain cancer clinical trial. PMID:20559722

  18. Expression and clinical significance of estrogen-regulated long non-coding RNAs in estrogen receptor α-positive ovarian cancer progression.

    PubMed

    Qiu, Jun-Jun; Ye, Le-Chi; Ding, Jing-Xin; Feng, Wei-Wei; Jin, Hong-Yan; Zhang, Ying; Li, Qing; Hua, Ke-Qin

    2014-04-01

    Estrogen (E2) has long been implicated in epithelial ovarian cancer (EOC) progression. The effects of E2 on cancer progression can be mediated by numerous target genes, including coding RNAs and, more recently, non-coding RNAs (ncRNAs). Among the ncRNAs, long ncRNAs (lncRNAs) have emerged as new regulators in cancer progression; therefore, our aim was to determine whether the expression of any lncRNAs is regulated by E2 and, if so, whether a subset of these lncRNAs have some clinical significance in EOC progression. A microarray was performed to identify E2-regulated lncRNAs in E2 receptor (ER) α-positive EOC cells. Bioinformatics analyses of lncRNAs were conducted, focusing on gene ontology and pathway analyses. Quantitative real-time polymerase chain reactions were performed to confirm the expression of certain lncRNAs in ERα-positive EOC tissues. The correlation between certain lncRNA expression and clinicopathological factors as well as prognosis in ERα-positive EOC patients was then analyzed. We showed that 115 lncRNAs exhibited significant changes in E2-treated SKOV3 cells compared with untreated controls. Most of these lncRNAs were predicated to have potential to contribute to cancer progression. Notably, three candidates (TC0100223, TC0101686 and TC0101441) were aberrantly expressed in ERα-positive compared to ERα-negative EOC tissues, showing correlations with some malignant cancer phenotypes such as advanced FIGO stage and/or high histological grade. Furthermore, multivariate analysis indicated that TC0101441 was an independent prognostic factor for overall survival. Taken together, these results indicate for the first time that E2 can modulate lncRNA expression in ERα-positive EOC cells and that certain lncRNAs are correlated with advanced cancer progression and suggestive of a prognostic indicator in ERα-positive EOC patients. Knowledge of these E2-regulated lncRNAs could aid in the future understanding of the estrogenic effect on EOC progression

  19. LINEAR ACCELERATOR

    DOEpatents

    Christofilos, N.C.; Polk, I.J.

    1959-02-17

    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  20. A Randomized Clinical Trial of Acceptance and Commitment Therapy versus Progressive Relaxation Training for Obsessive-Compulsive Disorder

    ERIC Educational Resources Information Center

    Twohig, Michael P.; Hayes, Steven C.; Plumb, Jennifer C.; Pruitt, Larry D.; Collins, Angela B.; Hazlett-Stevens, Holly; Woidneck, Michelle R.

    2010-01-01

    Objective: Effective treatments for obsessive-compulsive disorder (OCD) exist, but additional treatment options are needed. The effectiveness of 8 sessions of acceptance and commitment therapy (ACT) for adult OCD was compared with progressive relaxation training (PRT). Method: Seventy-nine adults (61% female) diagnosed with OCD (mean age = 37…

  1. Assessing the Impact of Continuous Quality Improvement on Clinical Practice: What It Will Take to Accelerate Progress

    PubMed Central

    Shortell, Stephen M.; Bennett, Charles L.; Byck, Gayle R.

    1998-01-01

    The literature on continuous quality improvement (CQI) has produced some evidence, based on nonrandomized studies, that its clinical application can improve outcomes of care while reducing costs. Its effectiveness is enhanced by a nucleus of physician involvement, individual practitioner feedback, and a supportive organizational culture. The few randomized studies, however, suggest no impact of CQI on clinical outcomes and no evidence to date of organization-wide improvement in clinical performance. Further, most studies address misuse issues and avoid examining overuse or underuse of services. The clinical application of CQI is more likely to have a pervasive impact when it takes place within a supportive regulatory and competitive environment, when it is aligned with financial incentives, and when it is under the direction of an organizational leadership that is committed to integrating all aspects of the work. PMID:9879304

  2. A protocol for evaluating progressive levels of simulation fidelity in the development of technical skills, integrated performance and woman centred clinical assessment skills in undergraduate midwifery students

    PubMed Central

    2013-01-01

    Background Simulation as a pedagogical approach has been used in health professional education to address the need to safely develop effective clinical skills prior to undertaking clinical practice. However, evidence for the use of simulation in midwifery is largely anecdotal, and research evaluating the effectiveness of different levels of simulation fidelity are lacking. Woman centred care is a core premise of the midwifery profession and describes the behaviours of an individual midwife who demonstrates safe and effective care of the individual woman. Woman centred care occurs when the midwife modifies the care to ensure the needs of each individual woman are respected and addressed. However, a review of the literature demonstrates an absence of a valid and reliable tool to measure the development of woman centred care behaviours. This study aims to determine which level of fidelity in simulated learning experiences provides the most effective learning outcomes in the development of woman centred clinical assessment behaviors and skills in student midwives. Methods/Design Three-arm, randomised, intervention trial. In this research we plan to: a) trial three levels of simulation fidelity - low, medium and progressive, on student midwives performing the procedure of vaginal examination; b) measure clinical assessment skills using the Global Rating Scale (GRS) and Integrated Procedural Performance Instrument (IPPI); and c) pilot the newly developed Woman Centred Care Scale (WCCS) to measure clinical behaviors related to Woman-Centredness. Discussion This project aims to enhance knowledge in relation to the appropriate levels of fidelity in simulation that yield the best educational outcomes for the development of woman centred clinical assessment in student midwives. The outcomes of this project may contribute to improved woman centred clinical assessment for student midwives, and more broadly influence decision making regarding education resource allocation for

  3. Lung histopathological pattern in a survivor with rapidly progressive interstitial lung disease and anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis.

    PubMed

    Suzuki, Atsushi; Kondoh, Yasuhiro; Taniguchi, Hiroyuki; Tabata, Kazuhiko; Kimura, Tomoki; Kataoka, Kensuke; Ono, Kenzo; Hashisako, Mikiko; Fukuoka, Junya

    2016-01-01

    Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are specific indicators of patients with dermatomyositis, particularly clinically amyopathic dermatomyositis (CADM). CADM is occasionally accompanied by fatal, treatment-resistant, rapidly-progressive interstitial lung disease (RP-ILD). All previous reports showed that histopathological findings in RP-ILD with anti-MDA5 antibody-positive CADM indicated diffuse alveolar damage (DAD). This is the first report describing a non-DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM, which was improved by immunosuppressive therapy. This case may be a milder clinical phenotype than a typical DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM. PMID:27354955

  4. Defocus Incorporated Soft Contact (DISC) lens slows myopia progression in Hong Kong Chinese schoolchildren: a 2-year randomised clinical trial

    PubMed Central

    Lam, Carly Siu Yin; Tang, Wing Chun; Tse, Dennis Yan-Yin; Tang, Ying Yung; To, Chi Ho

    2014-01-01

    Aims To determine if ‘Defocus Incorporated Soft Contact’ (DISC) lens wear slows childhood myopia progression. Methods A 2-year double-blind randomised controlled trial was carried out in 221 children aged 8–13 years, with myopia between −1.00 and −5.00 Dioptres (D) and astigmatism ≤1.00 D. Subjects were randomly assigned to the DISC (n=111) or single vision (SV; n=110) contact lens group. DISC lenses incorporated concentric rings, which provided an addition of +2.50 D, alternating with the normal distance correction. Refractive error (cycloplegic autorefraction) and axial length were measured at 6-month intervals. Differences between groups were analysed using unpaired t test. Results In total, 128 children completed the study, n=65 in the DISC group and n=63 in the SV group. Myopia progressed 25% more slowly for children in the DISC group compared with those in the control group (0.30 D/year; 95% CI −0.71 to −0.47 vs 0.4 D/year; 95% CI −0.93 to −0.65, p=0.031). Likewise, there was less axial elongation for children in the DISC versus SV groups (0.13 mm/year; 95% CI 0.20 to 0.31 vs 0.18 mm/year; 95% CI 0.30 to 0.43, p=0.009). Treatment effect correlated positively with DISC lens wearing time (r=0.342; p=0.005). Indeed, myopia in children who wore the DISC lenses for five or more hours/day progressed 46% (mean difference=−0.382 D, p=0.001; 95% CI −0.59 to −0.17) less than those in the SV group. Conclusions The daily wearing of DISC lens significantly slowed myopia progression and axial elongation in Hong Kong schoolchildren. The findings demonstrated that simultaneous clear vision with constant myopic defocus can retard myopia progression. PMID:24169657

  5. The International Linear Collider Progress Report 2015

    SciTech Connect

    Yamamoto, Akira

    2015-07-15

    The ILC technical design is now being adapted to the preferred candidate site. Changes in layout are being managed by a rigorous change-control procedure. Series production of cavities for the European XFEL has shown that cavities can be mass-produced in industry with a performance well above XFEL requirements and close to that needed for the ILC. A number of technical developments are under way with a view to further reducing the ILC cost. This work must continue through the preparatory stage for ILC construction once resources become available. A summary of the design updates and of the further preparatory work needed is summarized in tabular form in the Appendix.

  6. Lack of age-related clinical progression in PGC-1α-deficient mice - implications for mitochondrial encephalopathies.

    PubMed

    Szalardy, Levente; Molnar, Mate; Torok, Rita; Zadori, Denes; Kovacs, Gabor G; Vecsei, Laszlo; Klivenyi, Peter

    2016-10-15

    Impaired peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) function has been demonstrated in several neurodegenerative diseases, and murine whole-body knockouts of PGC-1α have been considered as models for Huntington's disease. Recent neuropathological studies, however, rather propose these animals to be morphological models of mitochondrial encephalopathies, with special reminiscence of Kearns-Sayre syndrome. PGC-1α-deficient animals have already been subjected to behavioral assessments; however, the contradictory findings and the paucity of data assessing long-term progression necessitated further examinations. This study provides a comprehensive neurological phenotypic profiling of full-length-(FL-)PGC-1α-deficient mice in a broad age spectrum, with special focus on previously controversial findings, the issue of long-term phenotypic progression, the histopathological assessment of previously non-characterized tissues of potential clinicopathological relevance, and the gene expression profile of novel brain-specific isoforms of PGC-1α. Our findings demonstrate moderate hypomotility with signs of gait and trunk ataxia in addition to severe impairments in coordination and muscle strength in FL-PGC-1α-deficient mice, phenotypic features consistent of a mitochondrial disease. Intriguingly, however, these early alterations did not progress with age, the understanding of which may unveil mechanisms of potential therapeutic relevance, as discussed. The observed phenotype did not associate with retinal or spinal cord alterations, and was accompanied by mild myopathic changes. Based on these, FL-PGC-1α-deficient mice can be regarded not only as morphological but behavioral models of mitochondrial encephalopathies, with an important temporal limitation that has now been clarified. The mechanisms capable of halting a potentially lethal phenotype are to be unveiled, as they may hold therapeutic value for mitochondrial diseases.

  7. Lack of age-related clinical progression in PGC-1α-deficient mice - implications for mitochondrial encephalopathies.

    PubMed

    Szalardy, Levente; Molnar, Mate; Torok, Rita; Zadori, Denes; Kovacs, Gabor G; Vecsei, Laszlo; Klivenyi, Peter

    2016-10-15

    Impaired peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) function has been demonstrated in several neurodegenerative diseases, and murine whole-body knockouts of PGC-1α have been considered as models for Huntington's disease. Recent neuropathological studies, however, rather propose these animals to be morphological models of mitochondrial encephalopathies, with special reminiscence of Kearns-Sayre syndrome. PGC-1α-deficient animals have already been subjected to behavioral assessments; however, the contradictory findings and the paucity of data assessing long-term progression necessitated further examinations. This study provides a comprehensive neurological phenotypic profiling of full-length-(FL-)PGC-1α-deficient mice in a broad age spectrum, with special focus on previously controversial findings, the issue of long-term phenotypic progression, the histopathological assessment of previously non-characterized tissues of potential clinicopathological relevance, and the gene expression profile of novel brain-specific isoforms of PGC-1α. Our findings demonstrate moderate hypomotility with signs of gait and trunk ataxia in addition to severe impairments in coordination and muscle strength in FL-PGC-1α-deficient mice, phenotypic features consistent of a mitochondrial disease. Intriguingly, however, these early alterations did not progress with age, the understanding of which may unveil mechanisms of potential therapeutic relevance, as discussed. The observed phenotype did not associate with retinal or spinal cord alterations, and was accompanied by mild myopathic changes. Based on these, FL-PGC-1α-deficient mice can be regarded not only as morphological but behavioral models of mitochondrial encephalopathies, with an important temporal limitation that has now been clarified. The mechanisms capable of halting a potentially lethal phenotype are to be unveiled, as they may hold therapeutic value for mitochondrial diseases. PMID

  8. [Progress of Clinical Trials on Bone Marrow Mesenchymal Stem Cells for Prevention and Therapy of Graft-Versus-Host Disease].

    PubMed

    Zhong, Dan-Li; Tu, San-Fang; Li, Yu-Hua

    2015-12-01

    Graft-versus-host disease (GVHD) is a major complication following allogenetic hematopoietic stem cell transplantation, which shows a great threat to patients' survival and life quality. Along with multiple differentiation potential to various types of progenitor cells, bone marrow mesenchymal stem cells (BMMSC) have been confirmed to possess low immunogenicity and exert favorable immunomodulation. The recent studies show that the safety and high efficiency of BMMSC to prevent and cure GVHD greatly improved survival rate of the hosts. The most recent progress on prevention and therapy of GVHD is summarized in this review based on biology of BMMSC and pathogenesis of GVHD, so as to provide the effective evidence for further research.

  9. Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives

    PubMed Central

    Napp, Joanna; Mathejczyk, Julia E.

    2011-01-01

    To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue. PMID:21221568

  10. International Union of Basic and Clinical Pharmacology. LXXXIII: classification of prostanoid receptors, updating 15 years of progress.

    PubMed

    Woodward, D F; Jones, R L; Narumiya, S

    2011-09-01

    It is now more than 15 years since the molecular structures of the major prostanoid receptors were elucidated. Since then, substantial progress has been achieved with respect to distribution and function, signal transduction mechanisms, and the design of agonists and antagonists (http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=58). This review systematically details these advances. More recent developments in prostanoid receptor research are included. The DP(2) receptor, also termed CRTH2, has little structural resemblance to DP(1) and other receptors described in the original prostanoid receptor classification. DP(2) receptors are more closely related to chemoattractant receptors. Prostanoid receptors have also been found to heterodimerize with other prostanoid receptor subtypes and nonprostanoids. This may extend signal transduction pathways and create new ligand recognition sites: prostacyclin/thromboxane A(2) heterodimeric receptors for 8-epi-prostaglandin E(2), wild-type/alternative (alt4) heterodimers for the prostaglandin FP receptor for bimatoprost and the prostamides. It is anticipated that the 15 years of research progress described herein will lead to novel therapeutic entities. PMID:21752876

  11. Radioiostope studies utilizing a low level whole body counter and clinical application of activation analysis. Progress report

    SciTech Connect

    Brill, A. B.; Price, R. R.

    1980-01-16

    The main emphasis of these studies is the development of methods (hardware and software) for the quantitation of body and specific organ burdens of radioactivity. Current work is directed toward the evaluation of radiation dose distributions in human beings from new radioactive tracers and new procedures used in nuclear medicine. Dosimetry and clinical studies will be carried out on patients using new radiopharmaceuticals where dosimetry data are lacking. Future efforts will be directed toward the development of systems that will facilitate the collection of dosimetry data using less specialized facilities. The availability of instrumentation and analytic techniques that provide clinical images as well as dosimetry data should enhance the rate of collection of data on human exposures in medicine and assist in the optimization of diagnostic strategies. In parallel with these efforts, we are developing a new computer assisted technique for diagnostic decision making. The basic aim is to utilize efficiently all the available data to maximize information gain while minimizing cost factors.

  12. Sharing raw data from clinical trials: what progress since we first asked "Whose data set is it anyway?".

    PubMed

    Vickers, Andrew J

    2016-05-04

    Ten years ago, one of the first papers published in Trials was a commentary entitled "Whose data set is it anyway?" The commentary pointed out that trialists routinely refused requests for data sharing and argued that this attitude was a community standard that had no rational basis. At the time, there had been few calls for clinical trial data sharing and certainly no institutional support. Today the situation could not be more different. Numerous organizations now recommend or require raw data to be made available, including the International Committee of Medical Journal Editors, which recently proposed that clinical trial data sharing be a "condition of … publication." Furthermore, the literature is replete with papers covering an enormously wide variety of topics on data sharing. But despite a tectonic shift in attitudes, we are yet to see clinical trial data sharing become an unquestioned norm, where a researcher can readily download a data set from a trial almost as easily as they can now download a copy of the published paper. The battle over the next few years is to go beyond changing minds to ensuring that real data sets are routinely made available.

  13. [The clinical and forensic psychiatric assessment of attack-like progressive schizophrenia with the Kandinsky-Clérambault syndrome].

    PubMed

    Vasil'ev, V D

    1992-01-01

    Overall 200 patients suffering from attack-like progressive schizophrenia associated with Kandinsky-Clérambault syndrome were examined. All the patients underwent compulsory treatment at the psychiatric hospitals. Two varieties of schizophrenia associated with Kandinsky-Clérambault syndrome were distinguished: psychotic (127 persons) and psychopath-like (73 persons). The psychotic variety is characterized by the growth of personality disintegration because of changes to a greater degree in the thinking sphere, whereas the psychopath-like variety is marked by alterations in the affective volitional sphere. The psychopathological mechanisms of socially dangerous action of the patients at the preproductive and productive stages of endogenous process are described depending on the varieties distinguished.

  14. LINEAR ACCELERATOR

    DOEpatents

    Colgate, S.A.

    1958-05-27

    An improvement is presented in linear accelerators for charged particles with respect to the stable focusing of the particle beam. The improvement consists of providing a radial electric field transverse to the accelerating electric fields and angularly introducing the beam of particles in the field. The results of the foregoing is to achieve a beam which spirals about the axis of the acceleration path. The combination of the electric fields and angular motion of the particles cooperate to provide a stable and focused particle beam.

  15. Linear Clouds

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Context image for PIA03667 Linear Clouds

    These clouds are located near the edge of the south polar region. The cloud tops are the puffy white features in the bottom half of the image.

    Image information: VIS instrument. Latitude -80.1N, Longitude 52.1E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  16. Tissue non-linearity.

    PubMed

    Duck, F

    2010-01-01

    The propagation of acoustic waves is a fundamentally non-linear process, and only waves with infinitesimally small amplitudes may be described by linear expressions. In practice, all ultrasound propagation is associated with a progressive distortion in the acoustic waveform and the generation of frequency harmonics. At the frequencies and amplitudes used for medical diagnostic scanning, the waveform distortion can result in the formation of acoustic shocks, excess deposition of energy, and acoustic saturation. These effects occur most strongly when ultrasound propagates within liquids with comparatively low acoustic attenuation, such as water, amniotic fluid, or urine. Attenuation by soft tissues limits but does not extinguish these non-linear effects. Harmonics may be used to create tissue harmonic images. These offer improvements over conventional B-mode images in spatial resolution and, more significantly, in the suppression of acoustic clutter and side-lobe artefacts. The quantity B/A has promise as a parameter for tissue characterization, but methods for imaging B/A have shown only limited success. Standard methods for the prediction of tissue in-situ exposure from acoustic measurements in water, whether for regulatory purposes, for safety assessment, or for planning therapeutic regimes, may be in error because of unaccounted non-linear losses. Biological effects mechanisms are altered by finite-amplitude effects. PMID:20349813

  17. [The Weaver syndrome in cattle. Clinical, biochemical and pathologico-anatomic studies in a Braunvieh/Brown Swiss cow with bovine progressive degenerative myeloencephalopathy].

    PubMed

    Braun, U; Ehrensperger, F; Bracher, V

    1987-01-01

    The clinical signs and pathological lesions, consistent with Bovine Progressive Degenerative Myeloencephalopathy (BPDME), are described in a heifer. The animal was an 18-month-old Braunvieh-/Brown Swiss crossbreed with 50% Brown Swiss. Both the sire as well as the dam were related to the bull "B.". The only neurological signs were a posterior ataxia. Mobility and coordination of the front legs were normal. The CK activity of the cerebrospinal fluid was enhanced. There was a moderate to severe degeneration of the white matter consisting of marked axonal degradation and distension and degradation of myelin sheats in all parts of the spinal cord as well as in the medulla oblongata. The lesions were more severe in the descending than in the ascending tracts.

  18. A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma.

    PubMed

    Stanojevic, Ivan; Miller, Karolina; Kandolf-Sekulovic, Lidija; Mijuskovic, Zeljko; Zolotarevski, Lidija; Jovic, Milena; Gacevic, Milomir; Djukic, Mirjana; Arsenijevic, Nebojsa; Vojvodic, Danilo

    2016-02-01

    Seventy-eight melanoma patients and 10 healthy individuals were examined. Follow-up examinations of all melanoma patients were performed regularly every three months. Myeloid-derived suppressor cells (MDSC) were defined as lineage negative (CD3(-), CD19(-), CD56(-)), HLA-DR(-/low), CD11b(+) and CD33(+). Classification of granulocytic (GrMDSC) and monocytic (MoMDSC) subsets was based on the CD15 and CD14 expression, respectively. Unlike the MoMDSC, that were present in 60% of healthy controls and 15% of melanoma patients, the GrMDSC were present in all examined participants, and the melanoma patients were found to have statistically higher frequencies compared with healthy controls. Accordingly, we kept focused on GrMDSC frequencies in relation to the melanoma stages and course of the disease. The GrMDSC values are highest in stage IV melanoma patients, with statistical significance compared with stages IA, IB, IIA and IIB. Patients with progression had statistically higher GrMDSC counts comparing with those with stable disease (P = 0.0079). Patients who had progression-free interval (PFI) < 12 months showed significantly higher GrMDSC values compared with those with PFI > 12 months (P = 0.0333). GrMDSC showed significant negative correlation with PFI intervals (P = 0.0095). The GrMDSC subset was predominant in all our patients. We confirmed that GrMDSC do accumulate early in the peripheral blood of melanoma patients and their frequencies correlate narrowly with the clinical stage and the spread of the disease. The increase in GrMDSC frequencies correlates well with a progressive disease and could be considered a potential predictive biomarker of high-risk melanoma cases that are more likely to have a shorter PFI. PMID:26391013

  19. Familial Amyloid Polyneuropathy Type IV (FINNISH) with Rapid Clinical Progression in an Iranian Woman: A Case Report

    PubMed Central

    Babaei-Ghazani, Arash; Eftekharsadat, Bina

    2016-01-01

    Familial amyloid polyneuropathy (FAP) type IV (FINNISH) is a rare clinical entity with challenging neuropathy and cosmetic deficits. Amyloidosis can affect peripheral sensory, motor, or autonomic nerves. Nerve lesions are induced by deposits of amyloid fibrils and treatment approaches for neuropathy are challenging. Involvement of cranial nerves and atrophy in facial muscles is a real concern in daily life of such patients. Currently, diagnosis of neuropathy can be made by electrodiagnostic studies and diagnosis of amyloidosis can be made by genetic testing or by detection of amyloid deposition in abdominal fat pad, rectal, or nerve biopsies. It is preferable to consider FAP as one of the differential diagnosis of a case presented with multiple cranial nerves symptoms. The authors present a case of familial amyloid polyneuropathy (FAP) type IV with severe involvement of multiple cranial nerves, peripheral limb neuropathy, and orthostatic hypotension. PMID:27217609

  20. Familial Amyloid Polyneuropathy Type IV (FINNISH) with Rapid Clinical Progression in an Iranian Woman: A Case Report.

    PubMed

    Babaei-Ghazani, Arash; Eftekharsadat, Bina

    2016-05-01

    Familial amyloid polyneuropathy (FAP) type IV (FINNISH) is a rare clinical entity with challenging neuropathy and cosmetic deficits. Amyloidosis can affect peripheral sensory, motor, or autonomic nerves. Nerve lesions are induced by deposits of amyloid fibrils and treatment approaches for neuropathy are challenging. Involvement of cranial nerves and atrophy in facial muscles is a real concern in daily life of such patients. Currently, diagnosis of neuropathy can be made by electrodiagnostic studies and diagnosis of amyloidosis can be made by genetic testing or by detection of amyloid deposition in abdominal fat pad, rectal, or nerve biopsies. It is preferable to consider FAP as one of the differential diagnosis of a case presented with multiple cranial nerves symptoms. The authors present a case of familial amyloid polyneuropathy (FAP) type IV with severe involvement of multiple cranial nerves, peripheral limb neuropathy, and orthostatic hypotension. PMID:27217609

  1. Clinical significance of Anoctamin-1 gene at 11q13 in the development and progression of head and neck squamous cell carcinomas

    PubMed Central

    Rodrigo, Juan P.; Menéndez, Sofía Tirados; Hermida-Prado, Francisco; Álvarez-Teijeiro, Saúl; Villaronga, M. Ángeles; Alonso-Durán, Laura; Vallina, Aitana; Martínez-Camblor, Pablo; Astudillo, Aurora; Suárez, Carlos; María García-Pedrero, Juana

    2015-01-01

    This study investigates the clinical significance of Anoctamin-1 gene mapping at 11q13 amplicon in both the development and progression of head and neck squamous cell carcinomas (HNSCC). ANO1 protein expression was evaluated by immunohistochemistry in a cohort of 372 surgically treated HNSCC patients and also in 35 laryngeal precancerous lesions. ANO1 gene amplification was determined by real-time PCR in all the laryngeal premalignancies and 60 of the HNSCCs, and molecular data correlated with clinical outcome. ANO1 gene amplification was frequently detected in both premalignant lesions (63%) and HNSCC tumours (58%), whereas concomitant ANO1 expression occurred at a much lower frequency (20 and 22%). Interestingly, laryngeal dysplasias harbouring ANO1 gene amplification showed a higher risk of malignant transformation (HR = 3.62; 95% CI 0.79–16.57; P = 0.097; Cox regression). ANO1 expression and gene amplification showed no significant associations with clinicopathological parameters in HNSCC. However, remarkably ANO1 expression differentially influenced patient survival depending on the tumour site. Collectively, this study provides original evidence demonstrating the distinctive impact of ANO1 expression on HNSCC prognosis depending on the tumour site. PMID:26498851

  2. Do HIV-1 non-B subtypes differentially impact resistance mutations and clinical disease progression in treated populations? Evidence from a systematic review.

    PubMed

    Bhargava, Madhavi; Cajas, Jorge Martinez; Wainberg, Mark A; Klein, Marina B; Pant Pai, Nitika

    2014-01-01

    There are 31 million adults living with HIV-1 non-B subtypes globally, and about 10 million are on antiretroviral therapy (ART). Global evidence to guide clinical practice on ART response in HIV-1 non-B subtypes remains limited. We systematically searched 11 databases for the period 1996 to 2013 for evidence. Outcomes documented included time to development of AIDS and/or death, resistance mutations, opportunistic infections, and changes in CD4 cell counts and viral load. A lack of consistent reporting of all clinical end points precluded a meta-analysis. In sum, genetic diversity that precipitated differences in disease progression in ART-naïve populations was minimized in ART-experienced populations, although variability in resistance mutations persisted across non-B subtypes. To improve the quality of patient care in global settings, recording HIV genotypes at baseline and at virologic failure with targeted non-B subtype-based point-of-care resistance assays and timely phasing out of resistance-inducing ART regimens is recommended.

  3. SU-E-T-78: Comparison of Dose-Averaged Linear Energy Transfer Calculation Methods Used in Monte Carlo Simulations of Clinical Proton Beams

    SciTech Connect

    Cortes-Giraldo, M A; Carabe-Fernandez, A

    2014-06-01

    Purpose: To evaluate the differences in dose-averaged linear energy transfer (LETd) maps calculated in water by means of different strategies found in the literature in proton therapy Monte Carlo simulations and to compare their values with dose-mean lineal energy microdosimetry calculations. Methods: The Geant4 toolkit (version 9.6.2) was used. Dose and LETd maps in water were scored for primary protons with cylindrical voxels defined around the beam axis. Three LETd calculation methods were implemented. First, the LETd values were computed by calculating the unrestricted linear energy transfer (LET) associated to each single step weighted by the energy deposition (including delta-rays) along the step. Second, the LETd was obtained for each voxel by computing the LET along all the steps simulated for each proton track within the voxel, weighted by the energy deposition of those steps. Third, the LETd was scored as the quotient between the second momentum of the LET distribution, calculated per proton track, over the first momentum. These calculations were made with various voxel thicknesses (0.2 – 2.0 mm) for a 160 MeV proton beamlet and spread-out Bragg Peaks (SOBP). The dose-mean lineal energy was calculated in a uniformly-irradiated water sphere, 0.005 mm radius. Results: The value of the LETd changed systematically with the voxel thickness due to delta-ray emission and the enlargement of the LET distribution spread, especially at shallow depths. Differences of up to a factor 1.8 were found at the depth of maximum dose, leading to similar differences at the central and distal depths of the SOBPs. The third LETd calculation method gave better agreement with microdosimetry calculations around the Bragg Peak. Conclusion: Significant differences were found between LETd map Monte Carlo calculations due to both the calculation strategy and the voxel thickness used. This could have a significant impact in radiobiologically-optimized proton therapy treatments.

  4. The MRI-Linear Accelerator Consortium: Evidence-Based Clinical Introduction of an Innovation in Radiation Oncology Connecting Researchers, Methodology, Data Collection, Quality Assurance, and Technical Development

    PubMed Central

    Kerkmeijer, Linda G. W.; Fuller, Clifton D.; Verkooijen, Helena M.; Verheij, Marcel; Choudhury, Ananya; Harrington, Kevin J.; Schultz, Chris; Sahgal, Arjun; Frank, Steven J.; Goldwein, Joel; Brown, Kevin J.; Minsky, Bruce D.; van Vulpen, Marco

    2016-01-01

    An international research consortium has been formed to facilitate evidence-based introduction of MR-guided radiotherapy (MR-linac) and to address how the MR-linac could be used to achieve an optimized radiation treatment approach to improve patients’ survival, local, and regional tumor control and quality of life. The present paper describes the organizational structure of the clinical part of the MR-linac consortium. Furthermore, it elucidates why collaboration on this large project is necessary, and how a central data registry program will be implemented. PMID:27790408

  5. [Congenital linear nevus sebaceus].

    PubMed

    Linnemann, Anders; Bygum, Anette; Fenger-Grøn, Jesper

    2011-09-01

    An unusual case of nevus sebaceous is described. Nevus sebaceous is a congenital epidermal hamartoma of the skin and the predilection site is the head or neck. In this case the nevus followed the lines of Blaschko along the back of the left lower extremity. The linear lesion seemed papulovesicular which caused suspicion of incontinentia pigmenti or infection, and the boy received antimicrobial treatment until a biopsy revealed the correct diagnosis. We wish to emphasize this clinical picture to spare the patient and relatives from unnecessary tests, treatment and concern. PMID:21893006

  6. Progressive multiple sclerosis

    PubMed Central

    Ontaneda, Daniel; Fox, Robert J.

    2015-01-01

    Purpose to Review To highlight the pathological features and clinical aspects of progressive multiple sclerosis (PMS). To highlight results of clinical trial experience to date and review ongoing clinical trials and perspective new treatment options. Explain the challenges of clinical trial design in PMS. Recent Findings MS has been identified as a chronic immune mediated disease, and the progressive phase of the disease appears to have significant neurodegenerative mechanisms. The classification of the course of PMS has been re-organized into categories of active vs. inactive inflammatory disease and the presence vs. absence of gradual disease progression. This differentiation allows clearer conceptualization of PMS and possibly even more efficient recruitment of PMS subjects into clinical trials. Clinical trial experience to date in PMS has been negative with anti-inflammatory medications used in relapsing MS. Simvastatin was recently tested in a phase II trial and showed a 43% reduction on annualized atrophy progression in secondary progressive MS. Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod, and anti-B-cell therapy ocrelizumab. Several efforts for development of outcome measures in PMS are ongoing. Summary PMS represents a significant challenge, as the pathogenesis of the disease is not well understood, no validated outcome metrics have been established, and clinical trial experience to date has been disappointing. Advances in the understanding of the disease and lessons learned in previous clinical trials are paving the way for successful development of disease modifying agents for this disease. PMID:25887766

  7. FTLD-TDP with motor neuron disease, visuospatial impairment and a progressive supranuclear palsy-like syndrome: broadening the clinical phenotype of TDP-43 proteinopathies. A report of three cases

    PubMed Central

    2011-01-01

    Background Frontotemporal lobar degeneration with ubiquitin and TDP-43 positive neuronal inclusions represents a novel entity (FTLD-TDP) that may be associated with motor neuron disease (FTLD-MND); involvement of extrapyramidal and other systems has also been reported. Case presentation We present three cases with similar clinical symptoms, including Parkinsonism, supranuclear gaze palsy, visuospatial impairment and a behavioral variant of frontotemporal dementia, associated with either clinically possible or definite MND. Neuropathological examination revealed hallmarks of FTLD-TDP with major involvement of subcortical and, in particular, mesencephalic structures. These cases differed in onset and progression of clinical manifestations as well as distribution of histopathological changes in the brain and spinal cord. Two cases were sporadic, whereas the third case had a pathological variation in the progranulin gene 102 delC. Conclusions Association of a "progressive supranuclear palsy-like" syndrome with marked visuospatial impairment, motor neuron disease and early behavioral disturbances may represent a clinically distinct phenotype of FTLD-TDP. Our observations further support the concept that TDP-43 proteinopathies represent a spectrum of disorders, where preferential localization of pathogenetic inclusions and neuronal cell loss defines clinical phenotypes ranging from frontotemporal dementia with or without motor neuron disease, to corticobasal syndrome and to a progressive supranuclear palsy-like syndrome. PMID:21569259

  8. A critical study of different Monte Carlo scoring methods of dose average linear-energy-transfer maps calculated in voxelized geometries irradiated with clinical proton beams.

    PubMed

    Cortés-Giraldo, M A; Carabe, A

    2015-04-01

    We compare unrestricted dose average linear energy transfer (LET) maps calculated with three different Monte Carlo scoring methods in voxelized geometries irradiated with proton therapy beams with three different Monte Carlo scoring methods. Simulations were done with the Geant4 (Geometry ANd Tracking) toolkit. The first method corresponds to a step-by-step computation of LET which has been reported previously in the literature. We found that this scoring strategy is influenced by spurious high LET components, which relative contribution in the dose average LET calculations significantly increases as the voxel size becomes smaller. Dose average LET values calculated for primary protons in water with voxel size of 0.2 mm were a factor ~1.8 higher than those obtained with a size of 2.0 mm at the plateau region for a 160 MeV beam. Such high LET components are a consequence of proton steps in which the condensed-history algorithm determines an energy transfer to an electron of the material close to the maximum value, while the step length remains limited due to voxel boundary crossing. Two alternative methods were derived to overcome this problem. The second scores LET along the entire path described by each proton within the voxel. The third followed the same approach of the first method, but the LET was evaluated at each step from stopping power tables according to the proton kinetic energy value. We carried out microdosimetry calculations with the aim of deriving reference dose average LET values from microdosimetric quantities. Significant differences between the methods were reported either with pristine or spread-out Bragg peaks (SOBPs). The first method reported values systematically higher than the other two at depths proximal to SOBP by about 15% for a 5.9 cm wide SOBP and about 30% for a 11.0 cm one. At distal SOBP, the second method gave values about 15% lower than the others. Overall, we found that the third method gave the most consistent

  9. The accuracy of linear measurements of maxillary and mandibular edentulous sites in cone-beam computed tomography images with different fields of view and voxel sizes under simulated clinical conditions

    PubMed Central

    Ramesh, Aruna; Pagni, Sarah

    2016-01-01

    Purpose The objective of this study was to investigate the effect of varying resolutions of cone-beam computed tomography images on the accuracy of linear measurements of edentulous areas in human cadaver heads. Intact cadaver heads were used to simulate a clinical situation. Materials and Methods Fiduciary markers were placed in the edentulous areas of 4 intact embalmed cadaver heads. The heads were scanned with two different CBCT units using a large field of view (13 cm×16 cm) and small field of view (5 cm×8 cm) at varying voxel sizes (0.3 mm, 0.2 mm, and 0.16 mm). The ground truth was established with digital caliper measurements. The imaging measurements were then compared with caliper measurements to determine accuracy. Results The Wilcoxon signed rank test revealed no statistically significant difference between the medians of the physical measurements obtained with calipers and the medians of the CBCT measurements. A comparison of accuracy among the different imaging protocols revealed no significant differences as determined by the Friedman test. The intraclass correlation coefficient was 0.961, indicating excellent reproducibility. Inter-observer variability was determined graphically with a Bland-Altman plot and by calculating the intraclass correlation coefficient. The Bland-Altman plot indicated very good reproducibility for smaller measurements but larger discrepancies with larger measurements. Conclusion The CBCT-based linear measurements in the edentulous sites using different voxel sizes and FOVs are accurate compared with the direct caliper measurements of these sites. Higher resolution CBCT images with smaller voxel size did not result in greater accuracy of the linear measurements. PMID:27358816

  10. Evaluating the Role of Corticosteroid Pulse Therapy in Patients With Secondary Progressive Multiple Sclerosis Receiving Mitoxantrone: A Double Blind Randomized Controlled Clinical Trial

    PubMed Central

    Rahimdel, Abolghasem; Zeinali, Ahmad; Mellat, Ali

    2015-01-01

    Background: Multiple sclerosis (MS) is a central nervous system disorder with periods of recurrence and recovery. Mitoxantrone has been approved for secondary progressive MS (SPMS) treatment but data lacks the role of corticosteroid pulse therapy in SPMS. Objectives: To evaluate the role of corticosteroid pulse therapy in patients with SPMS receiving mitoxantrone. Patients and Methods: A double blind randomized controlled clinical trial was performed on 71 patients with SPMS referred to Shahid Sadoughi Hospital (Yazd, Iran) for receiving mitoxantrone in two groups. The first group (35 patients) received 20 mg mitoxantrone plus 500 mg methylprednisolone monthly for six months. The second group (36 patients) received the same dosage of mitoxantrone plus 100 CC of 5% dextrose water monthly for six months. Expanded disability status scale (EDSS), MRI plaques in both groups before and after the treatment completion and six months after the end of trial were compared together. Results: 28 men and 43 women enrolled in the study. MRI plaques number reduced in groups significantly (2.29 vs. 2.17) without significant difference between the groups (P = 0.782). Six months after trial completion, plaques number increased in groups without significantly difference (0.72 vs. 0.77, P = 0.611). The mean value of EDSS showed significant reduction at the end of treatment in groups (0.79 and 0.53) without significant difference between the groups (P = 0.953). Six months after trial completion, EDSS increased in groups without significant difference (0.35 vs. 0.43, P = 0.624). Conclusions: Corticosteroid pulse therapy in SPMS was effective in inflammatory process, but could not postpone or decline the neurodegenerative process and besides the imposing side effects could not result in significant improvement in EDSS and MRI plaques number in long term. PMID:26566454

  11. Breastfeeding Progression in Preterm Infants Is Influenced by Factors in Infants, Mothers and Clinical Practice: The Results of a National Cohort Study with High Breastfeeding Initiation Rates

    PubMed Central

    Maastrup, Ragnhild; Hansen, Bo Moelholm; Kronborg, Hanne; Bojesen, Susanne Norby; Hallum, Karin; Frandsen, Annemi; Kyhnaeb, Anne; Svarer, Inge; Hallström, Inger

    2014-01-01

    Background and Aim Many preterm infants are not capable of exclusive breastfeeding from birth. To guide mothers in breastfeeding, it is important to know when preterm infants can initiate breastfeeding and progress. The aim was to analyse postmenstrual age (PMA) at breastfeeding milestones in different preterm gestational age (GA) groups, to describe rates of breastfeeding duration at pre-defined times, as well as analyse factors associated with PMA at the establishment of exclusive breastfeeding. Methods The study was part of a prospective survey of a national Danish cohort of preterm infants based on questionnaires and structured telephone interviews, including 1,221 mothers and their 1,488 preterm infants with GA of 24–36 weeks. Results Of the preterm infants, 99% initiated breastfeeding and 68% were discharged exclusively breastfed. Breastfeeding milestones were generally reached at different PMAs for different GA groups, but preterm infants were able to initiate breastfeeding at early times, with some delay in infants less than GA 32 weeks. Very preterm infants had lowest mean PMA (35.5 weeks) at first complete breastfeed, and moderate preterm infants had lowest mean PMA at the establishment of exclusive breastfeeding (36.4 weeks). Admitting mothers to the NICU together with the infant and minimising the use of a pacifier during breastfeeding transition were associated with 1.6 (95% CI 0.4–2.8) and 1.2 days (95% CI 0.1–2.3) earlier establishment of exclusive breastfeeding respectively. Infants that were small for gestational age were associated with 5.6 days (95% CI 4.1–7.0) later establishment of exclusive breastfeeding. Conclusion Breastfeeding competence is not developed at a fixed PMA, but is influenced by multiple factors in infants, mothers and clinical practice. Admitting mothers together with their infants to the NICU and minimising the use of pacifiers may contribute to earlier establishment of exclusive breastfeeding. PMID:25251690

  12. N-methyl-d-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes

    PubMed Central

    Irani, Sarosh R.; Bera, Katarzyna; Waters, Patrick; Zuliani, Luigi; Maxwell, Susan; Zandi, Michael S.; Friese, Manuel A.; Galea, Ian; Kullmann, Dimitri M.; Beeson, David; Lang, Bethan; Bien, Christian G.

    2010-01-01

    Antibodies to the N-methyl-d-aspartate subtype of glutamate receptor have been associated with a newly-described encephalopathy that has been mainly identified in young females with ovarian tumours. However, the full clinical spectrum and treatment responses are not yet clear. We established a sensitive cell-based assay for detection of N-methyl-d-aspartate receptor antibodies in serum or cerebrospinal fluid, and a quantitative fluorescent immunoprecipitation assay for serial studies. Although there was marked intrathecal synthesis of N-methyl-d-aspartate receptor antibodies, the absolute levels of N-methyl-d-aspartate receptor antibodies were higher in serum than in cerebrospinal fluid. N-methyl-d-aspartate receptor antibodies were of the immunoglobulin G1 subclass and were able to activate complement on N-methyl d-aspartate receptor-expressing human embryonic kidney cells. From questionnaires returned on 44 N-methyl-d-aspartate receptor antibody-positive patients, we identified a high proportion without a detected tumour (35/44, 80%: follow-up 3.6–121 months, median 16 months). Among the latter were 15 adult females (43%), 10 adult males (29%) and 10 children (29%), with four in the first decade of life. Overall, there was a high proportion (29%) of non-Caucasians. Good clinical outcomes, as defined by reductions in modified Rankin scores, correlated with decreased N-methyl-d-aspartate receptor antibody levels and were associated with early (<40 days) administration of immunotherapies in non-paraneoplastic patients (P < 0.0001) and earlier tumour removal in paraneoplastic patients (P = 0.02). Ten patients (23%) who were first diagnosed during relapses had no evidence of tumours but had received minimal or no immunotherapy during earlier episodes. Temporal analysis of the onset of the neurological features suggested progression through two main stages. The time of onset of the early features, characterized by neuropsychiatric symptoms and seizures preceded by a

  13. Global Linear Instability

    NASA Astrophysics Data System (ADS)

    Theofilis, Vassilios

    2011-01-01

    This article reviews linear instability analysis of flows over or through complex two-dimensional (2D) and 3D geometries. In the three decades since it first appeared in the literature, global instability analysis, based on the solution of the multidimensional eigenvalue and/or initial value problem, is continuously broadening both in scope and in depth. To date it has dealt successfully with a wide range of applications arising in aerospace engineering, physiological flows, food processing, and nuclear-reactor safety. In recent years, nonmodal analysis has complemented the more traditional modal approach and increased knowledge of flow instability physics. Recent highlights delivered by the application of either modal or nonmodal global analysis are briefly discussed. A conscious effort is made to demystify both the tools currently utilized and the jargon employed to describe them, demonstrating the simplicity of the analysis. Hopefully this will provide new impulses for the creation of next-generation algorithms capable of coping with the main open research areas in which step-change progress can be expected by the application of the theory: instability analysis of fully inhomogeneous, 3D flows and control thereof.

  14. [Clinical features of the patients with "secondary infection" of Mycobacterium avium complex--Radiographic pattern of progressions in the patients with and without underlying pulmonary conditions].

    PubMed

    Tanaka, E; Amitani, R; Kuze, F

    1993-01-01

    We reviewed the radiographic features of 42 patients with Mycobacterium avium complex (MAC) infection. Six cases were definite "primary", 20 were "secondary", and 15 were indeterminate (probably "primary"). In the definite and probable "primary" cases, and some of the "secondary" cases, pulmonary lesions slowly progressed following a common and characteristic sequence from a cluster of small nodules or fibro-productive nodules to those with subpleural thickening, or with thickening of the draining bronchi, or with both subpleural and bronchial thickening, and to cystic bronchiectatic changes associated with collapse of the segment or the lobe, in the final stage. Cases of airspace pneumonia appeared rarely. In these cases, neither apical-subapical region prevalence, pleural effusion, nor mediastinal lymphadenopathy were found. On the contrary, in five cases of "secondary" infection, MAC lesions located at the same place with the predisposing lung disease and did not progress during more than five years of observation. In the progressive cases of "secondary" infection, however, the appearance of new lesions and the progressions thereafter showed the same pattern as in "primary" infection. These features would suggest that MAC infection would occur and progress slowly among patients who had unknown pathogenetical factor, whether they had underlying predisposing lung conditions or not.

  15. Removing Malmquist bias from linear regressions

    NASA Technical Reports Server (NTRS)

    Verter, Frances

    1993-01-01

    Malmquist bias is present in all astronomical surveys where sources are observed above an apparent brightness threshold. Those sources which can be detected at progressively larger distances are progressively more limited to the intrinsically luminous portion of the true distribution. This bias does not distort any of the measurements, but distorts the sample composition. We have developed the first treatment to correct for Malmquist bias in linear regressions of astronomical data. A demonstration of the corrected linear regression that is computed in four steps is presented.

  16. Learning from data: recognizing glaucomatous defect patterns and detecting progression from visual field measurements.

    PubMed

    Yousefi, Siamak; Goldbaum, Michael H; Balasubramanian, Madhusudhanan; Medeiros, Felipe A; Zangwill, Linda M; Liebmann, Jeffrey M; Girkin, Christopher A; Weinreb, Robert N; Bowd, Christopher

    2014-07-01

    A hierarchical approach to learn from visual field data was adopted to identify glaucomatous visual field defect patterns and to detect glaucomatous progression. The analysis pipeline included three stages, namely, clustering, glaucoma boundary limit detection, and glaucoma progression detection testing. First, cross-sectional visual field tests collected from each subject were clustered using a mixture of Gaussians and model parameters were estimated using expectation maximization. The visual field clusters were further estimated to recognize glaucomatous visual field defect patterns by decomposing each cluster into several axes. The glaucoma visual field defect patterns along each axis then were identified. To derive a definition of progression, the longitudinal visual fields of stable glaucoma eyes on the abnormal cluster axes were projected and the slope was approximated using linear regression (LR) to determine the confidence limit of each axis. For glaucoma progression detection, the longitudinal visual fields of each eye on the abnormal cluster axes were projected and the slope was approximated by LR. Progression was assigned if the progression rate was greater than the boundary limit of the stable eyes; otherwise, stability was assumed. The proposed method was compared to a recently developed progression detection method and to clinically available glaucoma progression detection software. The clinical accuracy of the proposed pipeline was as good as or better than the currently available methods.

  17. Learning from data: recognizing glaucomatous defect patterns and detecting progression from visual field measurements.

    PubMed

    Yousefi, Siamak; Goldbaum, Michael H; Balasubramanian, Madhusudhanan; Medeiros, Felipe A; Zangwill, Linda M; Liebmann, Jeffrey M; Girkin, Christopher A; Weinreb, Robert N; Bowd, Christopher

    2014-07-01

    A hierarchical approach to learn from visual field data was adopted to identify glaucomatous visual field defect patterns and to detect glaucomatous progression. The analysis pipeline included three stages, namely, clustering, glaucoma boundary limit detection, and glaucoma progression detection testing. First, cross-sectional visual field tests collected from each subject were clustered using a mixture of Gaussians and model parameters were estimated using expectation maximization. The visual field clusters were further estimated to recognize glaucomatous visual field defect patterns by decomposing each cluster into several axes. The glaucoma visual field defect patterns along each axis then were identified. To derive a definition of progression, the longitudinal visual fields of stable glaucoma eyes on the abnormal cluster axes were projected and the slope was approximated using linear regression (LR) to determine the confidence limit of each axis. For glaucoma progression detection, the longitudinal visual fields of each eye on the abnormal cluster axes were projected and the slope was approximated by LR. Progression was assigned if the progression rate was greater than the boundary limit of the stable eyes; otherwise, stability was assumed. The proposed method was compared to a recently developed progression detection method and to clinically available glaucoma progression detection software. The clinical accuracy of the proposed pipeline was as good as or better than the currently available methods. PMID:24710816

  18. Effect of Sitagliptin and Metformin on Prediabetes Progression to Type 2 Diabetes - A Randomized, Double-Blind, Double-Arm, Multicenter Clinical Trial: Protocol for the Sitagliptin and Metformin in PreDiabetes (SiMePreD) Study

    PubMed Central

    2016-01-01

    Background The high prevalence and incidence of type 2 diabetes mellitus (DM), and its associated morbidity and mortality, has prompted growing international interest and effort in the primary prevention of this disease. Primary prevention is possible since type 2 DM is preceded by prediabetes, offering a window opportunity to treat patients, and prevent the emergence of advanced disease. Sitagliptin is an oral dipeptidyl peptidase-IV inhibitor that preserves existing beta cell function and increases beta cell mass. These two effects have been demonstrated both in vitro and in animal studies, and current clinical data show that sitagliptin is safe. Metformin, a biguanide, reduces insulin resistance and inhibits hepatic gluconeogenesis, and has an excellent safety profile. The combination of metformin and sitagliptin, targeting both characteristics of prediabetes (insulin resistance and progressive beta cell degeneration), may potentially slow or halt the progression from prediabetes to type 2 DM. This paper describes the rationale and design of the Sitagliptin and Metformin in PreDiabetes (SiMePreD) study. Objective The aim of this study is to determine the effect of sitagliptin and metformin on progression from prediabetes to type 2 DM. The objectives of the study are to determine the effects of metformin and placebo on glycemic endpoints, the effects of sitagliptin and metformin on glycemic endpoints, the effects of metformin and placebo on incidence of cardiovascular disease and death, and the effects of sitagliptin and metformin on incidence of cardiovascular disease and death. Methods This is a randomized, double-blind, multicenter clinical study that will determine if the combination of metformin and sitagliptin is effective in preventing the progression from prediabetes to type 2 DM. The study will contain two arms (metformin/sitagliptin and metformin/placebo). Primary endpoints include the number of subjects progressing from prediabetes to type 2 DM, the

  19. Electrothermal linear actuator

    NASA Technical Reports Server (NTRS)

    Derr, L. J.; Tobias, R. A.

    1969-01-01

    Converting electric power into powerful linear thrust without generation of magnetic fields is accomplished with an electrothermal linear actuator. When treated by an energized filament, a stack of bimetallic washers expands and drives the end of the shaft upward.

  20. A linear programming manual

    NASA Technical Reports Server (NTRS)

    Tuey, R. C.

    1972-01-01

    Computer solutions of linear programming problems are outlined. Information covers vector spaces, convex sets, and matrix algebra elements for solving simultaneous linear equations. Dual problems, reduced cost analysis, ranges, and error analysis are illustrated.

  1. Linear-Algebra Programs

    NASA Technical Reports Server (NTRS)

    Lawson, C. L.; Krogh, F. T.; Gold, S. S.; Kincaid, D. R.; Sullivan, J.; Williams, E.; Hanson, R. J.; Haskell, K.; Dongarra, J.; Moler, C. B.

    1982-01-01

    The Basic Linear Algebra Subprograms (BLAS) library is a collection of 38 FORTRAN-callable routines for performing basic operations of numerical linear algebra. BLAS library is portable and efficient source of basic operations for designers of programs involving linear algebriac computations. BLAS library is supplied in portable FORTRAN and Assembler code versions for IBM 370, UNIVAC 1100 and CDC 6000 series computers.

  2. A boosted optimal linear learner for retinal vessel segmentation

    NASA Astrophysics Data System (ADS)

    Poletti, E.; Grisan, E.

    2014-03-01

    Ocular fundus images provide important information about retinal degeneration, which may be related to acute pathologies or to early signs of systemic diseases. An automatic and quantitative assessment of vessel morphological features, such as diameters and tortuosity, can improve clinical diagnosis and evaluation of retinopathy. At variance with available methods, we propose a data-driven approach, in which the system learns a set of optimal discriminative convolution kernels (linear learner). The set is progressively built based on an ADA-boost sample weighting scheme, providing seamless integration between linear learner estimation and classification. In order to capture the vessel appearance changes at different scales, the kernels are estimated on a pyramidal decomposition of the training samples. The set is employed as a rotating bank of matched filters, whose response is used by the boosted linear classifier to provide a classification of each image pixel into the two classes of interest (vessel/background). We tested the approach fundus images available from the DRIVE dataset. We show that the segmentation performance yields an accuracy of 0.94.

  3. Phosphorylated human tau associates with mouse prion protein amyloid in scrapie-infected mice but does not increase progression of clinical disease.

    PubMed

    Race, Brent; Phillips, Katie; Kraus, Allison; Chesebro, Bruce

    2016-07-01

    Tauopathies are a family of neurodegenerative diseases in which fibrils of human hyperphosphorylated tau (P-tau) are believed to cause neuropathology. In Alzheimer disease, P-tau associates with A-beta amyloid and contributes to disease pathogenesis. In familial human prion diseases and variant CJD, P-tau often co-associates with prion protein amyloid, and might also accelerate disease progression. To test this latter possibility, here we compared progression of amyloid prion disease in vivo after scrapie infection of mice with and without expression of human tau. The mice used expressed both anchorless prion protein (PrP) and membrane-anchored PrP, that generate disease associated amyloid and non-amyloid PrP (PrPSc) after scrapie infection. Human P-tau induced by scrapie infection was only rarely associated with non-amyloid PrPSc, but abundant human P-tau was detected at extracellular, perivascular and axonal deposits associated with amyloid PrPSc. This pathology was quite similar to that seen in familial prion diseases. However, association of human and mouse P-tau with amyloid PrPSc did not diminish survival time following prion infection in these mice. By analogy, human P-tau may not affect prion disease progression in humans. Alternatively, these results might be due to other factors, including rapidity of disease, blocking effects by mouse tau, or low toxicity of human P-tau in this model.

  4. Phosphorylated human tau associates with mouse prion protein amyloid in scrapie-infected mice but does not increase progression of clinical disease.

    PubMed

    Race, Brent; Phillips, Katie; Kraus, Allison; Chesebro, Bruce

    2016-07-01

    Tauopathies are a family of neurodegenerative diseases in which fibrils of human hyperphosphorylated tau (P-tau) are believed to cause neuropathology. In Alzheimer disease, P-tau associates with A-beta amyloid and contributes to disease pathogenesis. In familial human prion diseases and variant CJD, P-tau often co-associates with prion protein amyloid, and might also accelerate disease progression. To test this latter possibility, here we compared progression of amyloid prion disease in vivo after scrapie infection of mice with and without expression of human tau. The mice used expressed both anchorless prion protein (PrP) and membrane-anchored PrP, that generate disease associated amyloid and non-amyloid PrP (PrPSc) after scrapie infection. Human P-tau induced by scrapie infection was only rarely associated with non-amyloid PrPSc, but abundant human P-tau was detected at extracellular, perivascular and axonal deposits associated with amyloid PrPSc. This pathology was quite similar to that seen in familial prion diseases. However, association of human and mouse P-tau with amyloid PrPSc did not diminish survival time following prion infection in these mice. By analogy, human P-tau may not affect prion disease progression in humans. Alternatively, these results might be due to other factors, including rapidity of disease, blocking effects by mouse tau, or low toxicity of human P-tau in this model. PMID:27463540

  5. Progressive hemifacial atrophy

    PubMed Central

    Sande, Abhijeet; Risbud, Mukund; Kshar, Avinash; Paranjpe, Arati Oka

    2013-01-01

    Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative and poorly understood condition. It is characterized by a slow and progressive but self-limited atrophy affecting one side of the face. The incidence and the cause of this alteration are unknown. A cerebral disturbance of fat metabolism has been proposed as a primary cause. Possible factors that are involved in the pathogenesis include trauma, viral infections, heredity, endocrine disturbances and auto-immunity. The most common complications that appear in association to this disorder are: trigeminal neuralgia, facial paresthesia, severe headache and epilepsy. Characteristically, the atrophy progresses slowly for several years and, it becomes stable. The objective of this work is, through the presentation of a clinical case, to accomplish a literature review concerning general characteristics, etiology, physiopathology and treatment of progressive hemifacial atrophy. PMID:23878573

  6. [Progress on the cause and mechanism of a separation of clinical symptoms and signs and imaging features in lumbar disk herniation].

    PubMed

    Hu, Xing-xin; Liu, Li-min

    2015-10-01

    A few of patients with lumbar disk herniation having a separation of clinical symptoms and signs and imaging features, can be found in clinic, but the traditional theory of direct mechanical compression of nerve roots by herniated nucleus pulposus can't be used to explain this abnormal protrusion of lumbar intervertebral disc. The clinical symptoms and signs of the atypical lumbar disk herniation are affected by multiple factors. The indirect mechanical compression and distraction effect of spinal nerve roots may play an important role in the occurrence of the separation, and the appearance of abnormal clinical symptoms and signs is closely related to the migration of herniated nucleus pulposus tissue, transmission of injury information in the nervous system, and the complex interactions among the nucleus pulposus, dural sac and nerve roots. Moreover,the changes of microcirculation and inflammation secondary to the herniated nucleus pulposus tissue, the hyperosteogeny in the corresponding segment of the lumbar vertebrae and the posture changes all results in a diversity of symptoms and signs in patients with lumbar intervertebral disc herniation. Besides, there exist congenital variation of lumbosacral nerve roots and vertebral bodies in some patients, and the misdiagnosis or missed diagnosis of imaging finding may occur in some cases. However, the appearance of a separation of clinical symptoms and signs and imaging examination in patients may be caused by a variety of reasons in clinic. The exact mechanism involved in the interaction among nucleus pulposus tissue, dural sac and nerve root, secondary changes of pathophysiology and biomechanics around the nucleus pulposus, the determination of lesioned responsible segments, and how to overcome the limitations of imaging all need the further researches. PMID:26727796

  7. The Emerging Role of PI3K Inhibitors in the Treatment of Hematological Malignancies: Preclinical Data and Clinical Progress to Date.

    PubMed

    Seiler, Till; Hutter, Grit; Dreyling, Martin

    2016-04-01

    The phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway is implicated in the pathogenesis of lymphoma. Deeper understanding of the diversity and biological impact of this pathway has led to the development of specific inhibitors to this pathway. Preclinical data in cell lines, patient samples and disease models have broadened our understanding of PI3K inhibition. Several PI3K inhibitors are currently in advanced stages of clinical development. Idelalisib is the first agent of this new substance class to be approved in chronic lymphocytic leukemia and follicular lymphoma. Other agents specifically target different PI3K isoforms and show promising clinical efficacy. PMID:27052260

  8. A phase 2 trial of lenvatinib (E7080) in advanced progressive radioiodine-refractory differentiated thyroid cancer: a clinical outcomes and biomarker assessment

    PubMed Central

    Cabanillas, Maria E.; Schlumberger, Martin; Jarzab, Barbara; Martins, Renato G.; Pacini, Furio; Robinson, Bruce; McCaffrey, Judith C.; Shah, Manisha H.; Bodenner, Donald L.; Topliss, Duncan; Andresen, Corina; O'Brien, James P.; Ren, Min; Funahashi, Yasuhiro; Allison, Roger; Elisei, Rossella; Newbold, Kate; Licitra, Lisa F.; Sherman, Steven I.; Ball, Douglas W.

    2016-01-01

    Background Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT signaling networks implicated in tumor angiogenesis. Positive phase 1 results in solid tumors prompted a phase 2 trial in advanced radioiodine-refractory differentiated thyroid cancer (RR-DTC). Methods Fifty-eight patients with RR-DTC and disease progression during the prior 12 months were administered lenvatinib 24-mg once daily in 28-day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Prior VEGFR-targeted therapy was permitted. The primary endpoint was objective response rate (ORR) based upon independent imaging review (IIR). Secondary endpoints included progression-free survival (PFS) and safety. Serum levels of 51 circulating cytokines and angiogenic factors were also assessed. Results After ≥14 months of follow-up, patients had ORR of 50% (95% confidence interval [CI] 37–63) with only partial responses reported. Median time to response was 3.6 months; median duration of response was 12.7 months; median PFS was 12.6 months (95% CI 9.9–16.1). ORR for patients with prior VEGF therapy (n=17) was 59% (95% CI 33–82). Lower baseline levels of angiopoietin-2 were suggestive of tumor response and longer PFS. Grade 3/4 treatment-emergent adverse events regardless of relation to treatment occurred in 72% of patients, most frequently weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%). Conclusion In patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in a phase 3 trial. PMID:25913680

  9. Encouraging Early Clinical Outcomes With Helical Tomotherapy-Based Image-Guided Intensity-Modulated Radiation Therapy for Residual, Recurrent, and/or Progressive Benign/Low-Grade Intracranial Tumors: A Comprehensive Evaluation

    SciTech Connect

    Gupta, Tejpal

    2012-02-01

    Purpose: To report early clinical outcomes of helical tomotherapy (HT)-based image-guided intensity-modulated radiation therapy (IMRT) in brain tumors of varying shape, size, and location. Materials and Methods: Patients with residual, recurrent, and/or progressive low-grade intracranial and skull-base tumors were treated on a prospective protocol of HT-based IMRT and followed clinicoradiologically. Standardized metrics were used for plan evaluation and outcome analysis. Results: Twenty-seven patients with 30 lesions were treated to a median radiotherapy dose of 54 Gy in 30 fractions. All HT plans resulted in excellent target volume coverage with steep dose-gradients. The mean (standard deviation) dose homogeneity index and conformity index was 0.07 (0.05) and 0.71 (0.08) respectively. At first response assessment, 20 of 30 lesions were stable, whereas 9 showed partial regression. One patient with a recurrent clival chordoma though neurologically stable showed imaging-defined progression, whereas another patient with stable disease on serial imaging had sustained neurologic worsening. With a median follow-up of 19 months (interquartile range, 11-26 months), the 2-year clinicoradiological progression-free survival and overall survival was 93.3% and 100% respectively. Conclusions: Careful selection of radiotherapy technique is warranted for benign/low-grade brain tumors to achieve durable local control with minimum long-term morbidity. Large or complex-shaped tumors benefit most from IMRT. Our early clinical experience of HT-based IMRT for brain tumors has been encouraging.

  10. Towards a Future Linear Collider and The Linear Collider Studies at CERN

    ScienceCinema

    None

    2016-07-12

    During the week 18-22 October, more than 400 physicists will meet at CERN and in the CICG (International Conference Centre Geneva) to review the global progress towards a future linear collider. The 2010 International Workshop on Linear Colliders will study the physics, detectors and accelerator complex of a linear collider covering both the CLIC and ILC options. Among the topics presented and discussed will be the progress towards the CLIC Conceptual Design Report in 2011, the ILC Technical Design Report in 2012, physics and detector studies linked to these reports, and an increasing numbers of common working group activities. The seminar will give an overview of these topics and also CERN’s linear collider studies, focusing on current activities and initial plans for the period 2011-16. n.b: The Council Chamber is also reserved for this colloquium with a live transmission from the Main Auditorium.

  11. THE FIRST GRADE CLINIC--A MEDIUM FOR EARLY IDENTIFICATION OF PHYSICAL, SOCIAL, EMOTIONAL, AND MENTAL DEVELOPMENT FACTOR THAT MAY TEND TO BLOCK OR IMPEDE SCHOOL PROGRESS.

    ERIC Educational Resources Information Center

    MCGAHAN, F.E.

    DURING A 5-YEAR PERIOD, A FIRST GRADE CLINIC IDENTIFIED, AT THE START OF EACH SCHOOL YEAR, CHILDREN WITH DEVIATIONS IN BEHAVIOR, SOCIAL AND EMOTIONAL ADJUSTMENT, AND MENTAL MATURATION THAT MIGHT BLOCK OR RETARD SUCCESS IN SCHOOL. THESE CHILDREN WERE REFERRED FOR FURTHER DIAGNOSTIC EVALUATIONS. THE PROGRAM WAS FIRST TRIED IN ONE CLASSROOM. A 3-YEAR…

  12. Progress in the prognosis of adult Hodgkin's lymphoma in the past 35 years through clinical trials in Argentina: a GATLA experience.

    PubMed

    Pavlovsky, Santiago; Lastiri, Francisco

    2004-09-01

    The purpose of this study was to evaluate the trends in complete remission (CR) rate, disease-free survival (DFS), and overall survival (OS) through 35 years of Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) clinical trials. A total of 1,254 adult patients with Hodgkin's Lymphoma were evaluated according to seven consecutive protocols. This 35-year study was divided into three phases. The patients in the first phase (1968-1985) were treated with CVPP (cyclophosphamide/vinblastine/procarbazine/prednisone) plus involved-field radiotherapy (IFRT). In the CVPP regimen, cyclophosphamide and vinblastine were administered intravenously on day 1 and prednisone and procarbazine were administered orally on days 1-14 every 28 days. The second phase (1986-1996) used mainly reinforced CVPP with cyclophosphamide and vinblastine on days 1-8 plus IFRT. The third phase (1997-2003) used ABVD(doxorubicin/bleomycin/vinblastine/dacarbazine) plus IFRT. In clinical stage I/II, the CR rate was 86% in 252 patients treated in the first phase and DFS and OS were 57% and 78% at 5 years and 50% and 71% at 10 years. The second phase had 148 patients with clinical stage I/II disease, and the CR rate was 91%, 5-year DFS and OS were 78% and 90%, and 10-year DFS and OS were 70% and 83%. The third phase had 182 patients with clinical stage I/II disease, and the CR rate was 95%, 5-year DFS and OS were 87% and 96%, and 10-year DFS and OS were not reached. The statistical difference was P = 0.016 in terms of CR and P < 0.001 in terms of DFS and OS. In the first phase of 394 patients with clinical stage III/IV disease, the CR rate was 71%, DFS and OS at 5 years were 37% and 62%, and DFS and OS at 10 years were 32% and 53%. In the second phase of 164 patients with clinical stage III/IV disease, the CR rate was 84%, DFS and OS at 5 years were 66% and 80%, and DFS and OS at 10 years were 60% and 75%. In the third phase of 114 patients with clinical stage III/IV disease, the CR rate was 88% and

  13. Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on progression of diabetic neuropathy and other microvascular complications: multivariate epidemiological analysis based on patient background factors and severity of diabetic neuropathy

    PubMed Central

    Hotta, N; Kawamori, R; Fukuda, M; Shigeta, Y

    2012-01-01

    Abstract Aims The goal of the study was to evaluate the efficacy of epalrestat, an aldose reductase inhibitor, on diabetic retinopathy and diabetic nephropathy, based on analysis of the results of the Aldose Reductase Inhibitor–Diabetes Complications Trial, a 3-year multicentre comparative clinical trial of conventional therapy (control group) and epalrestat therapy (epalrestat group) in Japanese patients with mild diabetic neuropathy. Methods The subjects of the study were patients enrolled in the Aldose Reductase Inhibitor–Diabetes Complications Trial for whom data for major patient characteristics, severity of diabetic neuropathy at the end of the study and time-courses of diabetic retinopathy and diabetic nephropathy were available (57 and 52 patients from the control and epalrestat groups, respectively). Progression of diabetic retinopathy/nephropathy (a primary endpoint) in relation to major patient characteristics, severity of diabetic neuropathy at the end of the study (assessed from the mean of z-scores in four neurological function tests) and epalrestat treatment were analysed using univariate analysis and multiple logistic regression analysis. Results Progression of diabetic retinopathy/nephropathy was significantly inhibited in the epalrestat group compared with the control group (odds ratio = 0.323, P = 0.014) and was dependent on the severity of diabetic neuropathy at the end of the study (odds ratio = 2.131, P = 0.025). Conclusions Epalrestat prevented progression of diabetic neuropathy and retinopathy/nephropathy. The effect on diabetic retinopathy/nephropathy may have occurred indirectly because of the prevention of progression of diabetic neuropathy, in addition to the inhibitory action of epalrestat on aldose reductase. PMID:22507139

  14. Linear collider: a preview

    SciTech Connect

    Wiedemann, H.

    1981-11-01

    Since no linear colliders have been built yet it is difficult to know at what energy the linear cost scaling of linear colliders drops below the quadratic scaling of storage rings. There is, however, no doubt that a linear collider facility for a center of mass energy above say 500 GeV is significantly cheaper than an equivalent storage ring. In order to make the linear collider principle feasible at very high energies a number of problems have to be solved. There are two kinds of problems: one which is related to the feasibility of the principle and the other kind of problems is associated with minimizing the cost of constructing and operating such a facility. This lecture series describes the problems and possible solutions. Since the real test of a principle requires the construction of a prototype I will in the last chapter describe the SLC project at the Stanford Linear Accelerator Center.

  15. Linear mass actuator

    NASA Technical Reports Server (NTRS)

    Holloway, Sidney E., III (Inventor); Crossley, Edward A., Jr. (Inventor); Jones, Irby W. (Inventor); Miller, James B. (Inventor); Davis, C. Calvin (Inventor); Behun, Vaughn D. (Inventor); Goodrich, Lewis R., Sr. (Inventor)

    1992-01-01

    A linear mass actuator includes an upper housing and a lower housing connectable to each other and having a central passageway passing axially through a mass that is linearly movable in the central passageway. Rollers mounted in the upper and lower housings in frictional engagement with the mass translate the mass linearly in the central passageway and drive motors operatively coupled to the roller means, for rotating the rollers and driving the mass axially in the central passageway.

  16. Linear phase compressive filter

    DOEpatents

    McEwan, Thomas E.

    1995-01-01

    A phase linear filter for soliton suppression is in the form of a laddered series of stages of non-commensurate low pass filters with each low pass filter having a series coupled inductance (L) and a reverse biased, voltage dependent varactor diode, to ground which acts as a variable capacitance (C). L and C values are set to levels which correspond to a linear or conventional phase linear filter. Inductance is mapped directly from that of an equivalent nonlinear transmission line and capacitance is mapped from the linear case using a large signal equivalent of a nonlinear transmission line.

  17. Linear phase compressive filter

    DOEpatents

    McEwan, T.E.

    1995-06-06

    A phase linear filter for soliton suppression is in the form of a laddered series of stages of non-commensurate low pass filters with each low pass filter having a series coupled inductance (L) and a reverse biased, voltage dependent varactor diode, to ground which acts as a variable capacitance (C). L and C values are set to levels which correspond to a linear or conventional phase linear filter. Inductance is mapped directly from that of an equivalent nonlinear transmission line and capacitance is mapped from the linear case using a large signal equivalent of a nonlinear transmission line. 2 figs.

  18. Fault tolerant linear actuator

    DOEpatents

    Tesar, Delbert

    2004-09-14

    In varying embodiments, the fault tolerant linear actuator of the present invention is a new and improved linear actuator with fault tolerance and positional control that may incorporate velocity summing, force summing, or a combination of the two. In one embodiment, the invention offers a velocity summing arrangement with a differential gear between two prime movers driving a cage, which then drives a linear spindle screw transmission. Other embodiments feature two prime movers driving separate linear spindle screw transmissions, one internal and one external, in a totally concentric and compact integrated module.

  19. Sauer's non-linear voltage division.

    PubMed

    Schwan, H P; McAdams, E T; Jossinet, J

    2002-09-01

    The non-linearity of the electrode-tissue interface impedance gives rise to harmonics and thus degrades the accuracy of impedance measurements. Also, electrodes are often driven into the non-linear range of their polarisation impedance. This is particularly true in clinical applications. Techniques to correct for electrode effects are usually based on linear electrode impedance data. However, these data can be very different from the non-linear values needed. Non-linear electrode data suggested a model based on simple assumptions. It is useful in predicting the frequency dependence of non-linear effects from linear properties. Sauer's treatment is a first attempt to provide a more general and rigorous basis for modelling the non-linear state. The paper reports Sauer's treatment of the non-linear case and points out its limitations. The paper considers Sauer's treatment of a series arrangement of two impedances. The tissue impedance is represented by a linear voltage-current characteristic. The interface impedance is represented by a Volterra expansion. The response of this network to periodic signals is calculated up to the second-order term of the series expansion. The resultant, time-dependent current is found to contain a DC term (rectification), as well as frequency-dependent terms. Sauer's treatment assumes a voltage clamp across the impedances and neglects higher-order terms in the series expansion. As a consequence, it fails adequately to represent some experimentally observed phenomena. It is therefore suggested that Sauer's expressions for the voltage divider should be combined with the non-linear treatments previously published by the co-authors. Although Sauer's work on the non-linear voltage divider was originally applied to the study of the non-linear behaviour of the electrode-electrolyte interface and biological tissues, it is stressed, however, that the work is applicable to a wide range of research areas.

  20. Clinical impact of post-progression survival on overall survival in patients with limited-stage disease small cell lung cancer after first-line chemoradiotherapy

    PubMed Central

    Kasahara, Norimitsu; Imai, Hisao; Kaira, Kyoichi; Mori, Keita; Wakuda, Kazushige; Ono, Akira; Taira, Tetsuhiko; Kenmotsu, Hirotsugu; Harada, Hideyuki; Naito, Tateaki; Murakami, Haruyasu; Endo, Masahiro; Nakajima, Takashi; Yamada, Masanobu; Takahashi, Toshiaki

    2015-01-01

    Background The effects of first-line chemoradiotherapy on overall survival (OS) may be confounded by subsequent lines of therapy in patients with limited-stage disease small cell lung cancer (LD-SCLC). Therefore, we aimed to determine the relationships between progression-free survival (PFS), post-progression survival (PPS) and OS after first-line chemoradiotherapy in LD-SCLC patients. Patients and methods. We retrospectively analyzed 71 LD-SCLC patients with performance status (PS) 0–2 who received first-line chemoradiotherapy and had disease recurrence between September 2002 and March 2013 at Shizuoka Cancer Center (Shizuoka, Japan). We determined the correlation between PFS and OS and between PPS and OS at the individual level. In addition, we performed univariate and multivariate analyses to identify significant prognostic factors of PPS. Results OS is more strongly correlated with PPS (Spearman’s r = 0.86, R2 = 0.72, p < 0.05) than PFS (Spearman’s r = 0.46, R2 = 0.38, p < 0.05). In addition, the response to second-line treatments, the presence of distant metastases at recurrence and the number of additional regimens after first-line chemoradiotherapy were significant independent prognostic factors for PPS. Conclusions PPS has more impact on OS than PFS in recurrent LD-SCLC patients with good PS at beginning of the treatment. Moreover, treatments administered after first-line chemoradiotherapy may affect their OS. However, larger multicenter studies are needed to validate these findings. PMID:26834529

  1. Linearly polarized fiber amplifier

    SciTech Connect

    Kliner, Dahv A.; Koplow, Jeffery P.

    2004-11-30

    Optically pumped rare-earth-doped polarizing fibers exhibit significantly higher gain for one linear polarization state than for the orthogonal state. Such a fiber can be used to construct a single-polarization fiber laser, amplifier, or amplified-spontaneous-emission (ASE) source without the need for additional optical components to obtain stable, linearly polarized operation.

  2. The Use of Per Session Clinical Assessment with Clients in a Mental Health Delivery System: An Investigation into How Clinical Mental Health Counseling Practicum Students and Practicum Instructors Use Routine Client Progress Feedback

    ERIC Educational Resources Information Center

    Yates, Chad Michael

    2012-01-01

    The purpose of this study was to investigate how clinical mental health counseling practicum students and practicum instructors use per session assessment feedback with clients they served at a university counseling center. Per session assessment and feedback has been shown to increase the treatment outcomes that counselors achieve while treating…

  3. Linear force device

    NASA Technical Reports Server (NTRS)

    Clancy, John P.

    1988-01-01

    The object of the invention is to provide a mechanical force actuator which is lightweight and manipulatable and utilizes linear motion for push or pull forces while maintaining a constant overall length. The mechanical force producing mechanism comprises a linear actuator mechanism and a linear motion shaft mounted parallel to one another. The linear motion shaft is connected to a stationary or fixed housing and to a movable housing where the movable housing is mechanically actuated through actuator mechanism by either manual means or motor means. The housings are adapted to releasably receive a variety of jaw or pulling elements adapted for clamping or prying action. The stationary housing is adapted to be pivotally mounted to permit an angular position of the housing to allow the tool to adapt to skewed interfaces. The actuator mechanisms is operated by a gear train to obtain linear motion of the actuator mechanism.

  4. Linear models: permutation methods

    USGS Publications Warehouse

    Cade, B.S.; Everitt, B.S.; Howell, D.C.

    2005-01-01

    Permutation tests (see Permutation Based Inference) for the linear model have applications in behavioral studies when traditional parametric assumptions about the error term in a linear model are not tenable. Improved validity of Type I error rates can be achieved with properly constructed permutation tests. Perhaps more importantly, increased statistical power, improved robustness to effects of outliers, and detection of alternative distributional differences can be achieved by coupling permutation inference with alternative linear model estimators. For example, it is well-known that estimates of the mean in linear model are extremely sensitive to even a single outlying value of the dependent variable compared to estimates of the median [7, 19]. Traditionally, linear modeling focused on estimating changes in the center of distributions (means or medians). However, quantile regression allows distributional changes to be estimated in all or any selected part of a distribution or responses, providing a more complete statistical picture that has relevance to many biological questions [6]...

  5. Myositis autoantibodies in Korean patients with inflammatory myositis: Anti-140-kDa polypeptide antibody is primarily associated with rapidly progressive interstitial lung disease independent of clinically amyopathic dermatomyositis

    PubMed Central

    2010-01-01

    Background To investigate the association between myositis autoantibodies and clinical subsets of inflammatory myositis in Korean patients. Methods Immunoprecipitation was performed using the sera of classic polymyositis (PM) (n = 11) and dermatomyositis (DM) (n = 38) patients who met the Bohan and Peter criteria for definite inflammatory myositis. A panel of defined myositis autoantibodies was surveyed to investigate the association between each autoantibody and clinical subsets of inflammatory myositis. Results Either MSAs, anti-p140, or anti-p155/140 antibodies were found in 63.3% (31/49) of the study subjects. Anti-140-kDa-polypeptide (anti-p140) (18.4%, 9/49) and anti-155/140-kDa polypeptide (anti-p155/140) (16.3%, 8/49) antibodies were the most common, followed by anti-Mi2 (14.3%, 7/49), anti-ARS (12.2%, 6/49) and anti-SRP (2.0%, 1/49) antibodies. All MSAs and anti-p140 and anti-p155/140 antibodies were mutually exclusive. Anti-p140 (23.7%, 9/38), anti-p155/140 (21.1%, 8/38), and anti-Mi2 (18.4%, 3/38) antibodies were found exclusively in DM patients. Anti-p140 antibody was associated with rapidly progressive interstitial lung disease (ILD) (p = 0.001), with a sensitivity of 100.0% (4/4) and a specificity of 85.3% (29/34) in DM patients. Anti-p155/140 antibody was associated with cancer-associated DM (p = 0.009), with a sensitivity of 55.6% (5/9) and a specificity of 89.7% (26/29). Cancer-associated survival was significantly worse when anti-p155/140 antibody was present (19.2 ± 7.6 vs. 65.0 ± 3.5 months, p = 0.032). Finally, anti-ARS antibodies were associated with stable or slowly progressive ILD in PM and DM patients (p = 0.005). Conclusions Anti-p140 and anti-p155/140 antibodies were commonly found autoantibodies in Korean patients with inflammatory myositis. Despite the lack of clinically amyopathic DM patients in the study subjects, a strong association was observed between anti-p140 antibody and rapidly progressive ILD. Anti-p155/140 antibody was

  6. Data on alteration of hormone and growth factor receptor profiles over progressive passages of breast cancer cell lines representing different clinical subtypes.

    PubMed

    Nair, Madhumathy G; Desai, Krisha; Prabhu, Jyothi S; Hari, P S; Remacle, Jose; Sridhar, T S

    2016-09-01

    Human breast cancers are a highly heterogeneous group of tumours consisting of several molecular subtypes with a variable profile of hormone, growth factor receptors and cytokeratins [1]. Here, the data shows immunofluorescence profiling of four different cell lines belonging to distinct clinical subtypes of breast cancer. Post revival, the cell lines were passaged in culture and immunophenotyping was done for ER, HER-2, AR and EGFR. Data for the markers from early passage (5th) through passages as late as 25 for the different cell lines is presented. PMID:27508248

  7. [Effect of triamcinolone acetonide, montelukast, nedocromil sodium and formoterol on eosinophil blood counts, ECP serum levels and clinical progression of asthma in children].

    PubMed

    Stelmach, Iwona; Grzelewski, Tomasz; Stelmach, Włodzimierz; Majak, Paweł; Jerzyńska, Joanna; Górski, Paweł; Kuna, Piotr

    2002-03-01

    Eosinophil-mediated damage to the respiratory epithelium is a major pathogenetic mechanism in asthma. Glucocorticoids have confirmed antiinflammatory properties and effect of formoterol, montelukast and nedocromil on markers of inflammation has been studied. Eosinophil blood counts and eosinophil cation protein (ECP) serum level are often use as markers of clinical monitoring of the disease activity. To evaluate the effect of treatment on allergic inflammation, we measured eosinophil blood counts and ECP serum level, and clinical parameters before and after 4 weeks treatment with triamcinolon, montelukast, nedocromil, formoterol. It was 8 week, placebo-controlled and randomized, double blind trial of 154 children with moderate atopic asthma. Patients were randomly allocated to receive 400 mg triamcinolon (n = 28), 5 or 10 mg (according to age) montelukast (n = 27), 16 mg nedocromil (n = 26), 24 micrograms formoterol (n = 28) or placebo (n = 45). 140 children completed the study. After treatment with triamcinolon and montelukast eosinophil blood counts significantly decreased, after treatment with triamcinolon, montelukast and nedocromil ECP serum level significantly decreased; all clinical parameters improved after treatment with each drug; treatment with triamcinolon had the strongest effect on most parameters (except of FEV1). Mean eosinophil blood counts before and after treatment with triamcinolon were 277.4 and 187.2 cells/mm3 respectively (p < 0.001); with montelukast were 279.6 and 250.7 cells/mm3 respectively (p = 0.002); with nedocromil were 181.7 and 170.1 cells/mm3 respectively (p < 0.183); with formoterol were 276.4 and 264.1 cells/mm3 respectively (p = 0.2). Mean ECP serum levels before and after treatment with triamcinolon were 94.3 and 63.5 micrograms/l respectively (p < 0.001); with montelukast were 85.1 micrograms/l and 71.2 micrograms/l respectively (p < 0.001); with nedocromil were 92.6 and 80.1 micrograms/l respectively (p < 0.001); with

  8. Embodied, Symbolic and Formal Thinking in Linear Algebra

    ERIC Educational Resources Information Center

    Stewart, Sepideh; Thomas, Michael O. J.

    2007-01-01

    Students often find their first university linear algebra experience very challenging. While coping with procedural aspects of the subject, solving linear systems and manipulating matrices, they may struggle with crucial conceptual ideas underpinning them, making it very difficult to progress in more advanced courses. This research has sought to…

  9. How Much Progress Has Been Made in Minimally Invasive Surgery for Gastric Cancer in Korea?: A Viewpoint From Korean Prospective Clinical Trials

    PubMed Central

    Kim, Ki-Han; Kim, Sung-Heun; Kim, Min-Chan

    2014-01-01

    Abstract Gastric cancer is the most common cancer in Korea. Because the incidence of gastric cancer is still high even with early detection and because of developments in surgical instruments and technological advances, minimally invasive surgery has rapidly become an accepted treatment for gastric cancer in Korea. Many Korean gastric surgeons have contributed to the rapid adaptation of minimally invasive surgery for gastric cancer: not only the Korean Laparoscopic Gastrointestinal Surgery Study (KLASS) group, but also other expert surgeons after the 2000s. Thanks to their vigorous efforts involving active learning, education, workshops, academic communications, and international communications with active laparoscopic gastric surgeons in Korea, numerous results and well-designed large-scale clinical studies have been published or are actively ongoing, thus increasing its wide acceptance as an option for gastric cancer. Now, Korea has become one of the leading countries using minimally invasive surgery for the treatment of gastric cancer. This review article will summarize the current status and issues, as well as the clinical trials that have finished or are ongoing, regarding minimally invasive surgery for gastric cancer in Korea. PMID:25526443

  10. Auricular Acupuncture Versus Progressive Muscle Relaxation in Patients with Anxiety Disorders or Major Depressive Disorder: A Prospective Parallel Group Clinical Trial.

    PubMed

    de Lorent, Lukas; Agorastos, Agorastos; Yassouridis, Alexander; Kellner, Michael; Muhtz, Christoph

    2016-08-01

    Although acupuncture treatment is increasingly in demand among psychiatric patients, to date no studies have investigated the effectiveness of auricular acupuncture (AA) in treating anxiety disorders or major depressive disorder. Thus, this study aimed to compare the effectiveness of AA versus progressive muscle relaxation (PMR), a standardized and accepted relaxation method. We examined 162 patients with a primary diagnosis of anxiety disorder or major depressive disorder, and each patient chose between treatment with AA, executed according to the National Acupuncture Detoxification Association protocol, and treatment with PMR. Each group had treatments twice a week for 4 weeks. Before and after treatment, each participant rated four items on a visual analog scale: anxiety, tension, anger/aggression, and mood. Statistical analyses were performed with the original visual analog scale scores and the Change-Intensity Index, an appropriate indicator of the difference between two values of a variable. Our results show that treatment with AA significantly decreased tension, anxiety, and anger/aggression throughout the 4 weeks, but did not elevate mood. Between AA and PMR, no statistically significant differences were found at any time. Thus, we suggest that both AA and PMR may be useful, equally-effective additional interventions in the treatment of the above-mentioned disorders. PMID:27555224

  11. Linear magnetic bearing

    NASA Technical Reports Server (NTRS)

    Studer, P. A. (Inventor)

    1983-01-01

    A linear magnetic bearing system having electromagnetic vernier flux paths in shunt relation with permanent magnets, so that the vernier flux does not traverse the permanent magnet, is described. Novelty is believed to reside in providing a linear magnetic bearing having electromagnetic flux paths that bypass high reluctance permanent magnets. Particular novelty is believed to reside in providing a linear magnetic bearing with a pair of axially spaced elements having electromagnets for establishing vernier x and y axis control. The magnetic bearing system has possible use in connection with a long life reciprocating cryogenic refrigerator that may be used on the space shuttle.

  12. Student Learning of Basis, Span and Linear Independence in Linear Algebra

    ERIC Educational Resources Information Center

    Stewart, Sepideh; Thomas, Michael O. J.

    2010-01-01

    One of the earlier, more challenging concepts in linear algebra at university is that of basis. Students are often taught procedurally how to find a basis for a subspace using matrix manipulation, but may struggle with understanding the construct of basis, making further progress harder. We believe one reason for this is because students have…

  13. Progressive cerebral atrophy in neuromyelitis optica.

    PubMed

    Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

    2015-12-01

    We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients.

  14. Linear Accelerator (LINAC)

    MedlinePlus

    ... is the device most commonly used for external beam radiation treatments for patients with cancer. The linear ... shape of the patient's tumor and the customized beam is directed to the patient's tumor. The beam ...

  15. Inertial Linear Actuators

    NASA Technical Reports Server (NTRS)

    Laughlin, Darren

    1995-01-01

    Inertial linear actuators developed to suppress residual accelerations of nominally stationary or steadily moving platforms. Function like long-stroke version of voice coil in conventional loudspeaker, with superimposed linear variable-differential transformer. Basic concept also applicable to suppression of vibrations of terrestrial platforms. For example, laboratory table equipped with such actuators plus suitable vibration sensors and control circuits made to vibrate much less in presence of seismic, vehicular, and other environmental vibrational disturbances.

  16. Linear Alopecia Areata.

    PubMed

    Shetty, Shricharith; Rao, Raghavendra; Kudva, R Ranjini; Subramanian, Kumudhini

    2016-01-01

    Alopecia areata (AA) over scalp is known to present in various shapes and extents of hair loss. Typically it presents as circumscribed patches of alopecia with underlying skin remaining normal. We describe a rare variant of AA presenting in linear band-like form. Only four cases of linear alopecia have been reported in medical literature till today, all four being diagnosed as lupus erythematosus profundus. PMID:27625568

  17. Linear Alopecia Areata

    PubMed Central

    Shetty, Shricharith; Rao, Raghavendra; Kudva, R Ranjini; Subramanian, Kumudhini

    2016-01-01

    Alopecia areata (AA) over scalp is known to present in various shapes and extents of hair loss. Typically it presents as circumscribed patches of alopecia with underlying skin remaining normal. We describe a rare variant of AA presenting in linear band-like form. Only four cases of linear alopecia have been reported in medical literature till today, all four being diagnosed as lupus erythematosus profundus.

  18. Linear Alopecia Areata

    PubMed Central

    Shetty, Shricharith; Rao, Raghavendra; Kudva, R Ranjini; Subramanian, Kumudhini

    2016-01-01

    Alopecia areata (AA) over scalp is known to present in various shapes and extents of hair loss. Typically it presents as circumscribed patches of alopecia with underlying skin remaining normal. We describe a rare variant of AA presenting in linear band-like form. Only four cases of linear alopecia have been reported in medical literature till today, all four being diagnosed as lupus erythematosus profundus. PMID:27625568

  19. Primary Progressive Aphasia and Apraxia of Speech

    PubMed Central

    Jung, Youngsin; Duffy, Joseph R.; Josephs, Keith A.

    2014-01-01

    Primary progressive aphasia is a neurodegenerative syndrome characterized by progressive language dysfunction. The majority of primary progressive aphasia cases can be classified into three subtypes: non-fluent/agrammatic, semantic, and logopenic variants of primary progressive aphasia. Each variant presents with unique clinical features, and is associated with distinctive underlying pathology and neuroimaging findings. Unlike primary progressive aphasia, apraxia of speech is a disorder that involves inaccurate production of sounds secondary to impaired planning or programming of speech movements. Primary progressive apraxia of speech is a neurodegenerative form of apraxia of speech, and it should be distinguished from primary progressive aphasia given its discrete clinicopathological presentation. Recently, there have been substantial advances in our understanding of these speech and language disorders. Here, we review clinical, neuroimaging, and histopathological features of primary progressive aphasia and apraxia of speech. The distinctions among these disorders will be crucial since accurate diagnosis will be important from a prognostic and therapeutic standpoint. PMID:24234355

  20. Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

    PubMed Central

    Tremblay, Gabriel; Livings, Christopher; Crowe, Lydia; Kapetanakis, Venediktos; Briggs, Andrew

    2016-01-01

    Background Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. Objectives This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Methods Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. Results A piecewise model, in which the Kaplan–Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. Conclusion In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses. PMID:27418847

  1. Relation between clinical findings and progression of cerebral cortical pathology in MM1-type sporadic Creutzfeldt-Jakob disease: proposed staging of cerebral cortical pathology.

    PubMed

    Iwasaki, Yasushi; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Hashizume, Yoshio; Yoshida, Mari

    2014-06-15

    In our pathologic observation of the cerebral cortex including the neocortex, hippocampus, and limbic cortex in 43 Japanese patients with MM1-type sporadic Creutzfeldt-Jakob disease, the earliest pathologic finding was spongiform change and next was gliosis. Subsequently, neuropil rarefaction appeared, followed by neuron loss. On the basis of these observations, we propose the following cortical pathologic staging: Stage I, spongiform change; Stage II, hypertrophic astrocytosis; Stage III, neuropil rarefaction; Stage IV, neuron loss; Stage V, status spongiosus; and Stage VI, large cavity formation. We also suggest a more simple staging classification: Stages I and II, mild; Stages III and IV, moderate; and Stages V and VI, severe involvement. Based on statistical analysis of the cases, strong correlation coefficients were obtained between the neocortical and limbic pathologic stage and both total disease duration and brain weight. We estimated that the first observation times of cortical hyperintensity on diffusion-weighted images of magnetic resonance imaging, myoclonus, and periodic sharp wave complexes on the electroencephalogram approximately correspond to the early phase of Stage II of the neocortex. The time to reach the akinetic mutism state approximately corresponds to the middle phase of Stage II of the neocortex. Therefore, we think that approximate clinical manifestations at death, total disease duration, and brain weight can be estimated according to the pathologic stage of the neocortex or limbic cortex. Panencephalopathic-type pathology appeared approximately 12 months after disease onset, and this time approximately corresponds to the middle phase of Stage III of the neocortex.

  2. Superconducting linear actuator

    NASA Technical Reports Server (NTRS)

    Johnson, Bruce; Hockney, Richard

    1993-01-01

    Special actuators are needed to control the orientation of large structures in space-based precision pointing systems. Electromagnetic actuators that presently exist are too large in size and their bandwidth is too low. Hydraulic fluid actuation also presents problems for many space-based applications. Hydraulic oil can escape in space and contaminate the environment around the spacecraft. A research study was performed that selected an electrically-powered linear actuator that can be used to control the orientation of a large pointed structure. This research surveyed available products, analyzed the capabilities of conventional linear actuators, and designed a first-cut candidate superconducting linear actuator. The study first examined theoretical capabilities of electrical actuators and determined their problems with respect to the application and then determined if any presently available actuators or any modifications to available actuator designs would meet the required performance. The best actuator was then selected based on available design, modified design, or new design for this application. The last task was to proceed with a conceptual design. No commercially-available linear actuator or modification capable of meeting the specifications was found. A conventional moving-coil dc linear actuator would meet the specification, but the back-iron for this actuator would weigh approximately 12,000 lbs. A superconducting field coil, however, eliminates the need for back iron, resulting in an actuator weight of approximately 1000 lbs.

  3. Test facilities for future linear colliders

    SciTech Connect

    Ruth, R.D.

    1995-12-01

    During the past several years there has been a tremendous amount of progress on Linear Collider technology world wide. This research has led to the construction of the test facilities described in this report. Some of the facilities will be complete as early as the end of 1996, while others will be finishing up around the end 1997. Even now there are extensive tests ongoing for the enabling technologies for all of the test facilities. At the same time the Linear Collider designs are quite mature now and the SLC is providing the key experience base that can only come from a working collider. All this taken together indicates that the technology and accelerator physics will be ready for a future Linear Collider project to begin in the last half of the 1990s.

  4. Designing linear systolic arrays

    SciTech Connect

    Kumar, V.K.P.; Tsai, Y.C. . Dept. of Electrical Engineering)

    1989-12-01

    The authors develop a simple mapping technique to design linear systolic arrays. The basic idea of the technique is to map the computations of a certain class of two-dimensional systolic arrays onto one-dimensional arrays. Using this technique, systolic algorithms are derived for problems such as matrix multiplication and transitive closure on linearly connected arrays of PEs with constant I/O bandwidth. Compared to known designs in the literature, the technique leads to modular systolic arrays with constant hardware in each PE, few control lines, lexicographic data input/output, and improved delay time. The unidirectional flow of control and data in this design assures implementation of the linear array in the known fault models of wafer scale integration.

  5. Linear encoding device

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B. (Inventor)

    1993-01-01

    A Linear Motion Encoding device for measuring the linear motion of a moving object is disclosed in which a light source is mounted on the moving object and a position sensitive detector such as an array photodetector is mounted on a nearby stationary object. The light source emits a light beam directed towards the array photodetector such that a light spot is created on the array. An analog-to-digital converter, connected to the array photodetector is used for reading the position of the spot on the array photodetector. A microprocessor and memory is connected to the analog-to-digital converter to hold and manipulate data provided by the analog-to-digital converter on the position of the spot and to compute the linear displacement of the moving object based upon the data from the analog-to-digital converter.

  6. Linearly Adjustable International Portfolios

    NASA Astrophysics Data System (ADS)

    Fonseca, R. J.; Kuhn, D.; Rustem, B.

    2010-09-01

    We present an approach to multi-stage international portfolio optimization based on the imposition of a linear structure on the recourse decisions. Multiperiod decision problems are traditionally formulated as stochastic programs. Scenario tree based solutions however can become intractable as the number of stages increases. By restricting the space of decision policies to linear rules, we obtain a conservative tractable approximation to the original problem. Local asset prices and foreign exchange rates are modelled separately, which allows for a direct measure of their impact on the final portfolio value.

  7. Targeting ECM Disrupts Cancer Progression

    PubMed Central

    Venning, Freja A.; Wullkopf, Lena; Erler, Janine T.

    2015-01-01

    Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression. PMID:26539408

  8. Improved Electrohydraulic Linear Actuators

    NASA Technical Reports Server (NTRS)

    Hamtil, James

    2004-01-01

    A product line of improved electrohydraulic linear actuators has been developed. These actuators are designed especially for use in actuating valves in rocket-engine test facilities. They are also adaptable to many industrial uses, such as steam turbines, process control valves, dampers, motion control, etc. The advantageous features of the improved electrohydraulic linear actuators are best described with respect to shortcomings of prior electrohydraulic linear actuators that the improved ones are intended to supplant. The flow of hydraulic fluid to the two ports of the actuator cylinder is controlled by a servo valve that is controlled by a signal from a servo amplifier that, in turn, receives an analog position-command signal (a current having a value between 4 and 20 mA) from a supervisory control system of the facility. As the position command changes, the servo valve shifts, causing a greater flow of hydraulic fluid to one side of the cylinder and thereby causing the actuator piston to move to extend or retract a piston rod from the actuator body. A linear variable differential transformer (LVDT) directly linked to the piston provides a position-feedback signal, which is compared with the position-command signal in the servo amplifier. When the position-feedback and position-command signals match, the servo valve moves to its null position, in which it holds the actuator piston at a steady position.

  9. Linear motion valve

    NASA Technical Reports Server (NTRS)

    Chandler, J. A. (Inventor)

    1985-01-01

    The linear motion valve is described. The valve spool employs magnetically permeable rings, spaced apart axially, which engage a sealing assembly having magnetically permeable pole pieces in magnetic relationship with a magnet. The gap between the ring and the pole pieces is sealed with a ferrofluid. Depletion of the ferrofluid is minimized.

  10. Resistors Improve Ramp Linearity

    NASA Technical Reports Server (NTRS)

    Kleinberg, L. L.

    1982-01-01

    Simple modification to bootstrap ramp generator gives more linear output over longer sweep times. New circuit adds just two resistors, one of which is adjustable. Modification cancels nonlinearities due to variations in load on charging capacitor and due to changes in charging current as the voltage across capacitor increases.

  11. On Solving Linear Recurrences

    ERIC Educational Resources Information Center

    Dobbs, David E.

    2013-01-01

    A direct method is given for solving first-order linear recurrences with constant coefficients. The limiting value of that solution is studied as "n to infinity." This classroom note could serve as enrichment material for the typical introductory course on discrete mathematics that follows a calculus course.

  12. Myositis ossificans progressive: case report

    PubMed Central

    Talbi, Sofia; Aradoini, Nassira; Mezouar, Iman El; Abourazzak, Fatima Ezzahra; Harzy, Taoufik

    2016-01-01

    Myositis ossificans progressiva (MOP) is an autosomal dominant disorder. There is a progressive ectopic ossification and skeletal malformation, mainly in the connective tissue of muscle. The diagnosis is based on the clinical findings and radiological demonstration of the skeletal malformations. A 38-year-old female patient was admitted to our department with progressive increase of the thigh. Results of laboratory studies were normal. The radiography of the right thigh showed multiple intramuscular calcifications. Myositis ossificans progressiva should be diagnosed as early as possible and non-invasively, based upon history, clinical and radiological findings. Early and correct diagnosis is fundamental for indication of proper management of the disease. PMID:27800117

  13. Comparison of Standard Automated Perimetry, Short-Wavelength Automated Perimetry, and Frequency-Doubling Technology Perimetry to Monitor Glaucoma Progression

    PubMed Central

    Hu, Rongrong; Wang, Chenkun; Gu, Yangshun; Racette, Lyne

    2016-01-01

    Abstract Detection of progression is paramount to the clinical management of glaucoma. Our goal is to compare the performance of standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology (FDT) perimetry in monitoring glaucoma progression. Longitudinal data of paired SAP, SWAP, and FDT from 113 eyes with primary open-angle glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. Data from all tests were expressed in comparable units by converting the sensitivity from decibels to unitless contrast sensitivity and by expressing sensitivity values in percent of mean normal based on an independent dataset of 207 healthy eyes with aging deterioration taken into consideration. Pointwise linear regression analysis was performed and 3 criteria (conservative, moderate, and liberal) were used to define progression and improvement. Global mean sensitivity (MS) was fitted with linear mixed models. No statistically significant difference in the proportion of progressing and improving eyes was observed across tests using the conservative criterion. Fewer eyes showed improvement on SAP compared to SWAP and FDT using the moderate criterion; and FDT detected less progressing eyes than SAP and SWAP using the liberal criterion. The agreement between these test types was poor. The linear mixed model showed a progressing trend of global MS overtime for SAP and SWAP, but not for FDT. The baseline estimate of SWAP MS was significantly lower than SAP MS by 21.59% of mean normal. FDT showed comparable estimation of baseline MS with SAP. SWAP and FDT do not appear to have significant benefits over SAP in monitoring glaucoma progression. SAP, SWAP, and FDT may, however, detect progression in different glaucoma eyes. PMID:26886602

  14. Clinical ethics revisited

    PubMed Central

    Singer, Peter A; Pellegrino, Edmund D; Siegler, Mark

    2001-01-01

    A decade ago, we reviewed the field of clinical ethics; assessed its progress in research, education, and ethics committees and consultation; and made predictions about the future of the field. In this article, we revisit clinical ethics to examine our earlier observations, highlight key developments, and discuss remaining challenges for clinical ethics, including the need to develop a global perspective on clinical ethics problems. PMID:11346456

  15. Linear Lumbar Localized Lysis of Elastic Fibers

    PubMed Central

    Tschen, Jaime A.

    2013-01-01

    Background: The absence or loss of elastic fibers in the skin is referred to as dermal elastolysis. Purpose: This paper describes a woman with a distinctive clinical presentation of mid-dermal elastolysis characterized morphologically by multiple horizontal raised bands on the lower back. Methods: A 20-year-old Filipino woman presented with multiple asymptomatic, flesh-colored, raised, firm, linear, cord-like bands on the lumbar area of her back. There were neither similar lesions elsewhere nor a family member with this condition. Results: Microscopic examination of the raised band showed nearly complete absence of elastic fibers in the mid dermis. In contrast, a biopsy of symmetrically located normal-appearing skin showed a uniform distribution of elastic fibers throughout the dermis. Linear lumbar localized elastolysis is a descriptive designation that accurately reflects a correlation of the clinical and pathological changes of this condition. Conclusion: The clinical differential of raised horizontal cord-like bands on the lower back (without a family history of an inherited elastic fiber disorder, a prior history of trauma, or a significant change in weight or exercise habit) includes linear focal elastosis and linear lumbar localized elastolysis. Microscopic evaluation of a Verhoeff-van Gieson stained lesion specimen (which may be accompanied by a biopsy of normal-appearing skin for comparison) will readily differentiate these conditions. The former is usually characterized by increased elastic fibers, whereas the latter, as in this patient, shows a paucity or absence of elastic fibers in the mid dermis. PMID:23882313

  16. Reciprocating linear motor

    NASA Technical Reports Server (NTRS)

    Goldowsky, Michael P. (Inventor)

    1987-01-01

    A reciprocating linear motor is formed with a pair of ring-shaped permanent magnets having opposite radial polarizations, held axially apart by a nonmagnetic yoke, which serves as an axially displaceable armature assembly. A pair of annularly wound coils having axial lengths which differ from the axial lengths of the permanent magnets are serially coupled together in mutual opposition and positioned with an outer cylindrical core in axial symmetry about the armature assembly. One embodiment includes a second pair of annularly wound coils serially coupled together in mutual opposition and an inner cylindrical core positioned in axial symmetry inside the armature radially opposite to the first pair of coils. Application of a potential difference across a serial connection of the two pairs of coils creates a current flow perpendicular to the magnetic field created by the armature magnets, thereby causing limited linear displacement of the magnets relative to the coils.

  17. General linear chirplet transform

    NASA Astrophysics Data System (ADS)

    Yu, Gang; Zhou, Yiqi

    2016-03-01

    Time-frequency (TF) analysis (TFA) method is an effective tool to characterize the time-varying feature of a signal, which has drawn many attentions in a fairly long period. With the development of TFA, many advanced methods are proposed, which can provide more precise TF results. However, some restrictions are introduced inevitably. In this paper, we introduce a novel TFA method, termed as general linear chirplet transform (GLCT), which can overcome some limitations existed in current TFA methods. In numerical and experimental validations, by comparing with current TFA methods, some advantages of GLCT are demonstrated, which consist of well-characterizing the signal of multi-component with distinct non-linear features, being independent to the mathematical model and initial TFA method, allowing for the reconstruction of the interested component, and being non-sensitivity to noise.

  18. Heart failure: a complex clinical process interpreted by systems biology approach and network medicine.

    PubMed

    Louridas, George E; Lourida, Katerina G

    2014-03-01

    Systems biology is founded on the principles of integrative computational analysis and on the data from genetic and molecular components. The integration of biological components produces interacting networks, modules and phenotypes with remarkable applications in the field of clinical medicine. The evolving concept of network medicine gives a more precise picture of the intrinsic complexity of failing myocardium and its clinical consequences. The present review is focused on the impact of network cardiology in explaining the progressive nature of the clinical syndrome of heart failure. The failing myocardium and the subsequent clinical syndrome of heart failure disclose a dynamical and non-linear system with a progressive picture of clinical deterioration. The classical description of heart failure is based on tissue pathology and clinical presentation, and lately on specific genetic and molecular modifications. This characterization of heart failure has significant limitations to recognize preclinical disease features and to explain the progressive nature of the syndrome. Systems biology detects and evaluates specific networks from molecular, cellular and tissue elements, and assesses their influence on the appearance of clinical phenotypes. The classical reductive concept of heart failure is inadequate to provide data for molecular dysfunctions or defective coordination of the interconnected network components that are central to the genesis and clinical deterioration of heart failure. In heart failure, the recognition of molecular targets within the complex networks will increase the conceptual basis of pharmacology and the identification of novel biomarkers and at the same time will accelerate the discovery of new drugs.

  19. Electrostatic Linear Actuator

    NASA Technical Reports Server (NTRS)

    Collins, Earl R., Jr.; Curry, Kenneth C.

    1990-01-01

    Electrically charged helices attract or repel each other. Proposed electrostatic linear actuator made with intertwined dual helices, which holds charge-bearing surfaces. Dual-helix configuration provides relatively large unbroken facing charged surfaces (relatively large electrostatic force) within small volume. Inner helix slides axially in outer helix in response to voltages applied to conductors. Spiral form also makes components more rigid. Actuator conceived to have few moving parts and to be operable after long intervals of inactivity.

  20. Linear induction accelerator

    DOEpatents

    Buttram, M.T.; Ginn, J.W.

    1988-06-21

    A linear induction accelerator includes a plurality of adder cavities arranged in a series and provided in a structure which is evacuated so that a vacuum inductance is provided between each adder cavity and the structure. An energy storage system for the adder cavities includes a pulsed current source and a respective plurality of bipolar converting networks connected thereto. The bipolar high-voltage, high-repetition-rate square pulse train sets and resets the cavities. 4 figs.

  1. Relativistic Linear Restoring Force

    ERIC Educational Resources Information Center

    Clark, D.; Franklin, J.; Mann, N.

    2012-01-01

    We consider two different forms for a relativistic version of a linear restoring force. The pair comes from taking Hooke's law to be the force appearing on the right-hand side of the relativistic expressions: d"p"/d"t" or d"p"/d["tau"]. Either formulation recovers Hooke's law in the non-relativistic limit. In addition to these two forces, we…

  2. Combustion powered linear actuator

    DOEpatents

    Fischer, Gary J.

    2007-09-04

    The present invention provides robotic vehicles having wheeled and hopping mobilities that are capable of traversing (e.g. by hopping over) obstacles that are large in size relative to the robot and, are capable of operation in unpredictable terrain over long range. The present invention further provides combustion powered linear actuators, which can include latching mechanisms to facilitate pressurized fueling of the actuators, as can be used to provide wheeled vehicles with a hopping mobility.

  3. Representation of linear orders.

    PubMed

    Taylor, D A; Kim, J O; Sudevan, P

    1984-01-01

    Two binary classification tasks were used to explore the associative structure of linear orders. In Experiment 1, college students classified English letters as targets or nontargets, the targets being consecutive letters of the alphabet. The time to reject nontargets was a decreasing function of the distance from the target set, suggesting response interference mediated by automatic associations from the target to the nontarget letters. The way in which this interference effect depended on the placement of the boundaries between the target and nontarget sets revealed the relative strengths of individual interletter associations. In Experiment 2, students were assigned novel linear orders composed of letterlike symbols and asked to classify pairs of symbols as being adjacent or nonadjacent in the assigned sequence. Reaction time was found to be a joint function of the distance between any pair of symbols and the relative positions of those symbols within the sequence. The effects of both distance and position decreased systematically over 6 days of practice with a particular order, beginning at a level typical of unfamiliar orders and converging on a level characteristic of familiar orders such as letters and digits. These results provide an empirical unification of two previously disparate sets of findings in the literature on linear orders, those concerning familiar and unfamiliar orders, and the systematic transition between the two patterns of results suggests the gradual integration of a new associative structure.

  4. Anti- (conjugate) linearity

    NASA Astrophysics Data System (ADS)

    Uhlmann, Armin

    2016-03-01

    This is an introduction to antilinear operators. In following Wigner the terminus antilinear is used as it is standard in Physics. Mathematicians prefer to say conjugate linear. By restricting to finite-dimensional complex-linear spaces, the exposition becomes elementary in the functional analytic sense. Nevertheless it shows the amazing differences to the linear case. Basics of antilinearity is explained in sects. 2, 3, 4, 7 and in sect. 1.2: Spectrum, canonical Hermitian form, antilinear rank one and two operators, the Hermitian adjoint, classification of antilinear normal operators, (skew) conjugations, involutions, and acq-lines, the antilinear counterparts of 1-parameter operator groups. Applications include the representation of the Lagrangian Grassmannian by conjugations, its covering by acq-lines. As well as results on equivalence relations. After remembering elementary Tomita-Takesaki theory, antilinear maps, associated to a vector of a two-partite quantum system, are defined. By allowing to write modular objects as twisted products of pairs of them, they open some new ways to express EPR and teleportation tasks. The appendix presents a look onto the rich structure of antilinear operator spaces.

  5. Linearized Kernel Dictionary Learning

    NASA Astrophysics Data System (ADS)

    Golts, Alona; Elad, Michael

    2016-06-01

    In this paper we present a new approach of incorporating kernels into dictionary learning. The kernel K-SVD algorithm (KKSVD), which has been introduced recently, shows an improvement in classification performance, with relation to its linear counterpart K-SVD. However, this algorithm requires the storage and handling of a very large kernel matrix, which leads to high computational cost, while also limiting its use to setups with small number of training examples. We address these problems by combining two ideas: first we approximate the kernel matrix using a cleverly sampled subset of its columns using the Nystr\\"{o}m method; secondly, as we wish to avoid using this matrix altogether, we decompose it by SVD to form new "virtual samples," on which any linear dictionary learning can be employed. Our method, termed "Linearized Kernel Dictionary Learning" (LKDL) can be seamlessly applied as a pre-processing stage on top of any efficient off-the-shelf dictionary learning scheme, effectively "kernelizing" it. We demonstrate the effectiveness of our method on several tasks of both supervised and unsupervised classification and show the efficiency of the proposed scheme, its easy integration and performance boosting properties.

  6. The Stanford Linear Collider

    SciTech Connect

    Rees, J.R.

    1989-10-01

    April, 1989, the first Z zero particle was observed at the Stanford Linear Collider (SLC). The SLC collides high-energy beams of electrons and positrons into each other. In break with tradition the SLC aims two linear beams at each other. Strong motives impelled the Stanford team to choose the route of innovation. One reason being that linear colliders promise to be less expensive to build and operate than storage ring colliders. An equally powerful motive was the desire to build an Z zero factory, a facility at which the Z zero particle can be studied in detail. More than 200 Z zero particles have been detected at the SLC and more continue to be churned out regularly. It is in measuring the properties of the Z zero that the SLC has a seminal contribution to make. One of the primary goals of the SLC experimental program is to determine the mass of the Z zero as precisely as possible.In the end, the SLC's greatest significance will be in having proved a new accelerator technology. 7 figs.

  7. Progressive Ratio Schedules of Reinforcement

    PubMed Central

    Killeen, Peter R.; Posadas-Sanchez, Diana; Johansen, Espen Borgå; Thrailkill, Eric A.

    2009-01-01

    Pigeons’ pecks produced grain under progressive ratio (PR) schedules, whose response requirements increased systematically within sessions. Experiment 1 compared arithmetic (AP) and geometric (GP) progressions. Response rates increased as a function of the component ratio requirement, then decreased linearly (AP) or asymptotically (GP). Experiment 2 found the linear decrease in AP rates to be relatively independent of step size. Experiment 3 showed pausing to be controlled by the prior component length, which predicted the differences between PR and regressive ratio schedules found in Experiment 4. When the longest component ratios were signaled by different key colors, rates at moderate ratios increased, demonstrating control by forthcoming context. Models for response rate and pause duration described performance on AP schedules; GP schedules required an additional parameter representing the contextual reinforcement. PMID:19159161

  8. Thematic Progression in a Cardiologist's Text: Context, Frames and Progression.

    ERIC Educational Resources Information Center

    Salter, Robert T.

    Thematic progression (TP) is examined in the text of a communication between a cardiologist and a general practitioner concerning a patient, offering a clinical diagnosis of the patient's condition. Analysis of the discourse looks at the field, tenor, and mode of the communication as a context for TP. The methods of analysis are first described,…

  9. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD.

    PubMed

    Tramutola, Antonella; Triplett, Judy C; Di Domenico, Fabio; Niedowicz, Dana M; Murphy, Michael P; Coccia, Raffaella; Perluigi, Marzia; Butterfield, D Allan

    2015-06-01

    The clinical symptoms of Alzheimer disease (AD) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis. The current study investigated the status of the PI3K/Akt/mTOR pathway in post-mortem tissue from the inferior parietal lobule (IPL) at three different stages of AD: late AD, amnestic mild cognitive impairment (MCI) and pre-clinical AD (PCAD). Our findings suggest that the alteration of mTOR signaling and autophagy occurs at early stages of AD. We found a significant increase in Aβ (1-42) levels, associated with reduction in autophagy (Beclin-1 and LC-3) observed in PCAD, MCI, and AD subjects. Related to the autophagy impairment, we found a hyperactivation of PI3K/Akt/mTOR pathway in IPL of MCI and AD subjects, but not in PCAD, along with a significant decrease in phosphatase and tensin homolog. An increase in two mTOR downstream targets, p70S6K and 4EBP1, occurred in AD and MCI subjects. Both AD and MCI subjects showed increased, insulin receptor substrate 1, a candidate biomarker of brain insulin resistance, and GSK-3β, a kinase targeting tau phosphorylation. Nevertheless, tau phosphorylation was increased in the clinical groups. The results hint at a link between Aβ and the PI3K/Akt/mTOR axis and provide further insights into the relationship between AD pathology and insulin resistance. In addition, we speculate that the alteration of mTOR signaling in the IPL of AD and MCI subjects, but not in PCAD, is due to the lack of substantial increase in oxidative stress. The figure represents the three different stages of Alzheimer Disease: Preclinical Alzheimer Disease (PCAD), Mild cognitive impairment (MCI

  10. Predicting time to prostate cancer recurrence based on joint models for non-linear longitudinal biomarkers and event time outcomes.

    PubMed

    Pauler, Donna K; Finkelstein, Dianne M

    2002-12-30

    Biological markers that are both sensitive and specific for tumour regrowth or metastasis are increasingly becoming available and routinely monitored during the regular follow-up of patients treated for cancer. Obtained by a simple blood test, these markers provide an inexpensive non-invasive means for the early detection of recurrence (or progression). Currently, the longitudinal behaviour of the marker is viewed as an indicator of early disease progression, and is applied by a physician in making clinical decisions. One marker that has been studied for use in both population screening for early disease and for detection of recurrence in prostate cancer patients is PSA. The elevation of PSA levels is known to precede clinically detectable recurrence by 2 to 5 years, and current clinical practice often relies partially on multiple recent rises in PSA to trigger a change in treatment. However, the longitudinal trajectory for individual markers is often non-linear; in many cases there is a decline immediately following radiation therapy or surgery, a plateau during remission, followed by an exponential rise following the recurrence of the cancer. The aim of this article is to determine the multiple aspects of the longitudinal PSA biomarker trajectory that can be most sensitive for predicting time to clinical recurrence. Joint Bayesian models for the longitudinal measures and event times are utilized based on non-linear hierarchical models, implied by unknown change-points, for the longitudinal trajectories, and a Cox proportional hazard model for progression times, with functionals of the longitudinal parameters as covariates in the Cox model. Using Markov chain Monte Carlo sampling schemes, the joint model is fit to longitudinal PSA measures from 676 patients treated at Massachusetts General Hospital between the years 1988 and 1995 with follow-up to 1999. Based on these data, predictive schemes for detecting cancer recurrence in new patients based on their

  11. Oligonucleotide therapeutics: chemistry, delivery and clinical progress.

    PubMed

    Sharma, Vivek K; Watts, Jonathan K

    2015-01-01

    Oligonucleotide therapeutics have the potential to become a third pillar of drug development after small molecules and protein therapeutics. However, the three approved oligonucleotide drugs over the past 17 years have not proven to be highly successful in a commercial sense. These trailblazer drugs have nonetheless laid the foundations for entire classes of drug candidates to follow. This review will examine further advances in chemistry that are earlier in the pipeline of oligonucleotide drug candidates. Finally, we consider the possible effect of delivery systems that may provide extra footholds to improve the potency and specificity of oligonucleotide drugs. Our overview focuses on strategies to imbue antisense oligonucleotides with more drug-like properties and their applicability to other nucleic acid therapeutics.

  12. Linear IgA Bullous Dermatosis

    PubMed Central

    Chaudhari, Soham

    2015-01-01

    Linear immunoglobulin A bullous dermatosis is a rare autoimmune mucocutaneous disorder caused by immunoglobulin A autoantibodies produced against several different antigens in the basement membrane zone. Clinically, it is characterized by tense vesicles or bullae, which on histopathological exam demonstrate subepidermal blister with a predominantly neutrophilic infiltrate. A smooth, linear pattern of immunoglobulin A deposition in the basement membrane zone on direct immunofluorescence is considered the gold standard for establishing a diagnosis. Treatment consists of dapsone or sulfapyridine. The authors report a 60-year-old woman who presented with pruritic erythematous patches and plaques on her trunk, back, and legs without blisters, who was diagnosed with eczema for several months with no response to prior treatments. A biopsy was performed, which was consistent with linear immunoglobulin A bullous dermatosis and later confirmed by direct immunofluorescence studies. The authors present this case to increase awareness of this rare disease, which could manifest in a nonclassical, nonblistering fashion. PMID:26557220

  13. Sparse linear programming subprogram

    SciTech Connect

    Hanson, R.J.; Hiebert, K.L.

    1981-12-01

    This report describes a subprogram, SPLP(), for solving linear programming problems. The package of subprogram units comprising SPLP() is written in Fortran 77. The subprogram SPLP() is intended for problems involving at most a few thousand constraints and variables. The subprograms are written to take advantage of sparsity in the constraint matrix. A very general problem statement is accepted by SPLP(). It allows upper, lower, or no bounds on the variables. Both the primal and dual solutions are returned as output parameters. The package has many optional features. Among them is the ability to save partial results and then use them to continue the computation at a later time.

  14. Ultrasonic linear measurement system

    NASA Technical Reports Server (NTRS)

    Marshall, Scot H. (Inventor)

    1991-01-01

    An ultrasonic linear measurement system uses the travel time of surface waves along the perimeter of a three-dimensional curvilinear body to determine the perimeter of the curvilinear body. The system can also be used piece-wise to measure distances along plane surfaces. The system can be used to measure perimeters where use of laser light, optical means or steel tape would be extremely difficult, time consuming or impossible. It can also be used to determine discontinuities in surfaces of known perimeter or dimension.

  15. Lead screw linear actuator

    NASA Technical Reports Server (NTRS)

    Perkins, Gerald S. (Inventor)

    1980-01-01

    A linear actuator which can apply high forces is described, which includes a reciprocating rod having a threaded portion engaged by a nut that is directly coupled to the rotor of an electric motor. The nut is connected to the rotor in a manner that minimizes loading on the rotor, by the use of a coupling that transmits torque to the nut but permits it to shift axially and radially with respect to the rotor. The nut has a threaded hydrostatic bearing for engaging the threaded rod portion, with an oilcarrying groove in the nut being interrupted.

  16. A Zeno-like paradox in linear interaction

    NASA Astrophysics Data System (ADS)

    Weiss, J.

    1998-08-01

    The so-called Zeno-like paradox of infinite regressions and progressions connected by light cones, typical to particle dynamics of direct-interaction (AAD) theory, is examined for linear AAD interaction. It is shown that the paradox is resolved via convenient evaluating integral expressions which determine conserved quantities of Lorentz group to exhibit integral-free forms. As a result the formalism is also permitted to emerge the field confinement as one of substantial properties of linear interaction.

  17. Induction linear accelerators

    NASA Astrophysics Data System (ADS)

    Birx, Daniel

    1992-03-01

    Among the family of particle accelerators, the Induction Linear Accelerator is the best suited for the acceleration of high current electron beams. Because the electromagnetic radiation used to accelerate the electron beam is not stored in the cavities but is supplied by transmission lines during the beam pulse it is possible to utilize very low Q (typically<10) structures and very large beam pipes. This combination increases the beam breakup limited maximum currents to of order kiloamperes. The micropulse lengths of these machines are measured in 10's of nanoseconds and duty factors as high as 10-4 have been achieved. Until recently the major problem with these machines has been associated with the pulse power drive. Beam currents of kiloamperes and accelerating potentials of megavolts require peak power drives of gigawatts since no energy is stored in the structure. The marriage of liner accelerator technology and nonlinear magnetic compressors has produced some unique capabilities. It now appears possible to produce electron beams with average currents measured in amperes, peak currents in kiloamperes and gradients exceeding 1 MeV/meter, with power efficiencies approaching 50%. The nonlinear magnetic compression technology has replaced the spark gap drivers used on earlier accelerators with state-of-the-art all-solid-state SCR commutated compression chains. The reliability of these machines is now approaching 1010 shot MTBF. In the following paper we will briefly review the historical development of induction linear accelerators and then discuss the design considerations.

  18. Pseudo Linear Gyro Calibration

    NASA Technical Reports Server (NTRS)

    Harman, Richard; Bar-Itzhack, Itzhack Y.

    2003-01-01

    Previous high fidelity onboard attitude algorithms estimated only the spacecraft attitude and gyro bias. The desire to promote spacecraft and ground autonomy and improvements in onboard computing power has spurred development of more sophisticated calibration algorithms. Namely, there is a desire to provide for sensor calibration through calibration parameter estimation onboard the spacecraft as well as autonomous estimation on the ground. Gyro calibration is a particularly challenging area of research. There are a variety of gyro devices available for any prospective mission ranging from inexpensive low fidelity gyros with potentially unstable scale factors to much more expensive extremely stable high fidelity units. Much research has been devoted to designing dedicated estimators such as particular Extended Kalman Filter (EKF) algorithms or Square Root Information Filters. This paper builds upon previous attitude, rate, and specialized gyro parameter estimation work performed with Pseudo Linear Kalman Filter (PSELIKA). The PSELIKA advantage is the use of the standard linear Kalman Filter algorithm. A PSELIKA algorithm for an orthogonal gyro set which includes estimates of attitude, rate, gyro misalignments, gyro scale factors, and gyro bias is developed and tested using simulated and flight data. The measurements PSELIKA uses include gyro and quaternion tracker data.

  19. Comet LINEAR Splits Further

    NASA Astrophysics Data System (ADS)

    2001-05-01

    Third Nucleus Observed with the VLT Summary New images from the VLT show that one of the two nuclei of Comet LINEAR (C/2001 A2), now about 100 million km from the Earth, has just split into at least two pieces . The three fragments are now moving through space in nearly parallel orbits while they slowly drift apart. This comet will pass through its perihelion (nearest point to the Sun) on May 25, 2001, at a distance of about 116 million kilometres. It has brightened considerably due to the splitting of its "dirty snowball" nucleus and can now be seen with the unaided eye by observers in the southern hemisphere as a faint object in the southern constellation of Lepus (The Hare). PR Photo 18a/01 : Three nuclei of Comet LINEAR . PR Photo 18b/01 : The break-up of Comet LINEAR (false-colour). Comet LINEAR splits and brightens ESO PR Photo 18a/01 ESO PR Photo 18a/01 [Preview - JPEG: 400 x 438 pix - 55k] [Normal - JPEG: 800 x 875 pix - 136k] ESO PR Photo 18b/01 ESO PR Photo 18b/01 [Preview - JPEG: 367 x 400 pix - 112k] [Normal - JPEG: 734 x 800 pix - 272k] Caption : ESO PR Photo 18a/01 shows the three nuclei of Comet LINEAR (C/2001 A2). It is a reproduction of a 1-min exposure in red light, obtained in the early evening of May 16, 2001, with the 8.2-m VLT YEPUN (UT4) telescope at Paranal. ESO PR Photo 18b/01 shows the same image, but in a false-colour rendering for more clarity. The cometary fragment "B" (right) has split into "B1" and "B2" (separation about 1 arcsec, or 500 km) while fragment "A" (upper left) is considerably fainter. Technical information about these photos is available below. Comet LINEAR was discovered on January 3, 2001, and designated by the International Astronomical Union (IAU) as C/2001 A2 (see IAU Circular 7564 [1]). Six weeks ago, it was suddenly observed to brighten (IAUC 7605 [1]). Amateurs all over the world saw the comparatively faint comet reaching naked-eye magnitude and soon thereafter, observations with professional telescopes indicated

  20. Linear and whorled nevoid hypermelanosis complicated with inflammatory linear verrucous epidermal nevus and ichthyosis vulgaris.

    PubMed

    Lu, Yan; Zhu, Wen-Yuan

    2007-11-01

    We report a 17-year-old girl who presented with linear and whorled melanosis following Blaschko lines mainly on her trunk. Ichthyosiform lesions and linear scaling erythemas were observed respectively on her lower limbs and the dorsa of her hands, left knee, ankle and foot. No abnormality was found in systemic examination and blood tests. A biopsy specimen of pigmentation of her back showed there was increased pigmentation within the basal keratinocytes, with focal incontinentia pigmenti. Notable lymphangiectasis could also be seen in the mid part of dermis, which had never previously been described. The biopsy of scaling erythemas of her hand showed dominant hyperkeratosis with focal parakeratosis, acanthosis and papillomatous hyperplasia in the epidermis. The diagnosis of linear and whorled nevoid hypermelanosis (LWNH) complicated with inflammatory linear verrucous epidermal nevus and ichthyosis vulgaris was made in accordance with clinical and pathological manifestations. LWNH ought to be differentiated from incontinentia pigmenti and hypomelanosis of Ito.

  1. On the linear programming bound for linear Lee codes.

    PubMed

    Astola, Helena; Tabus, Ioan

    2016-01-01

    Based on an invariance-type property of the Lee-compositions of a linear Lee code, additional equality constraints can be introduced to the linear programming problem of linear Lee codes. In this paper, we formulate this property in terms of an action of the multiplicative group of the field [Formula: see text] on the set of Lee-compositions. We show some useful properties of certain sums of Lee-numbers, which are the eigenvalues of the Lee association scheme, appearing in the linear programming problem of linear Lee codes. Using the additional equality constraints, we formulate the linear programming problem of linear Lee codes in a very compact form, leading to a fast execution, which allows to efficiently compute the bounds for large parameter values of the linear codes.

  2. On unitary reconstruction of linear optical networks

    NASA Astrophysics Data System (ADS)

    Tillmann, Max; Schmidt, Christian; Walther, Philip

    2016-11-01

    Linear optical elements are pivotal instruments in the manipulation of classical and quantum states of light. Recent progress in integrated quantum photonic technology enabled the implementation of large numbers of such elements on chip, in particular passively stable interferometers. However, it is a challenge to characterize the optical transformation of such a device as the individual optical elements are not directly accessible. Thus only an effective overall transformation can be recovered. Here we present a reconstruction approach based on a global optimization of element parameters and compare it to two prominently used approaches. We numerically evaluate their performance for networks up to 14 modes and various levels of error on the primary data.

  3. Micro-Miniature Split Stirling Linear Crycooler

    NASA Astrophysics Data System (ADS)

    Veprik, A.; Zehtzer, S.; Vilenchik, H.; Pundak, N.

    2010-04-01

    Novel tactics for rescue, surveillance, reconnaissance, force protection, perimeter security, navigation and targeting often involve the use of miniature infrared imagers, where the cooled imaging systems are known to be superior to their uncooled rivals in terms of working range, resolution and ability to distinguish/track fast moving objects in dynamic infrared scenes. The latest technological advances in industrial applications of high-temperature infrared detectors have spurred the development of linearly driven, long life, dynamically quiet and aurally undetectable micro-miniature split Stirling linear cryogenic coolers. Recent progress in designing highly efficient "moving magnet" resonant linear actuators and dedicated smart electronics have enabled further improvements to the cooler's size, weight, power consumption, cooldown time and ownership costs. The authors report on the development of a novel micro-miniature split Stirling linear cryogenic cooler, where, by means of increasing the driving frequency up to 90 Hz, it appeared possible to shorten the cold finger to 19 mm. The cooler was specifically designed to cool a new generation of 130 K infrared detectors for portable infrared imagers, where compactness, low steady-state power consumption, fast cool-down time, vibration export and aural stealth are of primary concern.

  4. A phase I clinical trial of dose escalation of lobaplatin in combination with fixed-dose docetaxel for the treatment of human solid tumours that had progressed following chemotherapy.

    PubMed

    Peng, Yu; Liu, Yue-E; Ren, Xiao-Can; Chen, Xue-Ji; Su, Hui-Ling; Zong, Jie; Feng, Zeng-Li; Wang, Dong-Ying; Lin, Qiang; Gao, Xian-Shu

    2015-01-01

    In this study, the maximum tolerated dose (MTD) of lobaplatin (LBP) when it was combined with docetaxel (TXT) for the treatment of solid tumours that had progressed following chemotherapy was determined, and toxicities to this regimen were evaluated. A modified Fibonacci method was used for the dose escalation of LBP. The patients received TXT (at a fixed dose of 60 mg/m(2)) on day one (d1) and LBP (at an initial tested dose of 30 mg/m(2)) on day two (d2) of a treatment cycle that was repeated every 21 days. Each dose group consisted of at least three cases. In the absence of dose-limiting toxicity (DLT), we proceeded to the next dose group, with a dose increment of 5 mg/m(2) between groups, until DLT occurred. The dose immediately below the dose that produced DLT was regarded as the MTD. The 17 patients examined in this study completed a total of 58 cycles of chemotherapy, and a total of three dose-escalation groups (30 mg/m(2) LBP, 35 mg/m(2) LBP, and 40 mg/m(2) LBP) were established. The main adverse event that was observed was myelosuppression. DLT occurred in four patients, including three patients in the 40 mg/m(2) LBP group and one patient in the 35 mg/m(2) LBP group. In total, three out of the four patients in the 40 mg/m(2) LBP group exhibited DLT. We determined that the treatment administered to the 35 mg/m(2) LBP group represented the MTD. Thus, our phase I trial revealed that the MTD for the tested LBP combination regimen was 35 mg/m(2) LBP and 60 mg/m(2) TXT. This regimen resulted in mild adverse reactions and favourable patient tolerance. Therefore, we recommend the use of these dosages in phase II clinical trials. PMID:25435935

  5. [IgA linear dermatosis (author's transl)].

    PubMed

    Jablonska, S; Chorzelski, T

    1979-09-01

    Besides the typical forms of dermatitis herpetiformis (DH) and bullous pemphigoid (BP) of adults and children, there are cases combining clinical, histological and electronmicroscopic features of both. Linear continuous IgA deposits along basement membrane zone (BMZ) are a most characteristic finding. They differ from the granular IgA deposits in DH, even if these are also distributed along the BMZ (however, preserving as a rule their granular pattern). IgG circulating anti-BMZ antibodies are absent, whereas in some cases IgA anti-BMZ antibodies may be found. In contrast to DH, there is no gluten-sensitive enteropathy, and the gluten-free diet is ineffective. The recognition of this bullous disease as a distinct entity is of practical significance because these cases respond well to combined treatment with sulfones and corticosteroids, all in small doses. Because of diagnostic importance of linear IgA deposits at BMZ we have proposed the name IgA linear dermatosis. In children a counterpart of IgA linear dermatosis of adults is chronic bullous disease of childhood (CBDC), which we propose to call IgA linear dermatosis of childhood.

  6. Positrons for linear colliders

    SciTech Connect

    Ecklund, S.

    1987-11-01

    The requirements of a positron source for a linear collider are briefly reviewed, followed by methods of positron production and production of photons by electromagnetic cascade showers. Cross sections for the electromagnetic cascade shower processes of positron-electron pair production and Compton scattering are compared. A program used for Monte Carlo analysis of electromagnetic cascades is briefly discussed, and positron distributions obtained from several runs of the program are discussed. Photons from synchrotron radiation and from channeling are also mentioned briefly, as well as positron collection, transverse focusing techniques, and longitudinal capture. Computer ray tracing is then briefly discussed, followed by space-charge effects and thermal heating and stress due to showers. (LEW)

  7. Non Linear Conjugate Gradient

    2006-11-17

    Software that simulates and inverts electromagnetic field data for subsurface electrical properties (electrical conductivity) of geological media. The software treats data produced by a time harmonic source field excitation arising from the following antenna geometery: loops and grounded bipoles, as well as point electric and magnetic dioples. The inversion process is carried out using a non-linear conjugate gradient optimization scheme, which minimizes the misfit between field data and model data using a least squares criteria.more » The software is an upgrade from the code NLCGCS_MP ver 1.0. The upgrade includes the following components: Incorporation of new 1 D field sourcing routines to more accurately simulate the 3D electromagnetic field for arbitrary geologic& media, treatment for generalized finite length transmitting antenna geometry (antennas with vertical and horizontal component directions). In addition, the software has been upgraded to treat transverse anisotropy in electrical conductivity.« less

  8. Linear response at criticality

    NASA Astrophysics Data System (ADS)

    Svenkeson, Adam; Bologna, Mauro; Grigolini, Paolo

    2012-10-01

    We study a set of cooperatively interacting units at criticality, and we prove with analytical and numerical arguments that they generate the same renewal non-Poisson intermittency as that produced by blinking quantum dots, thereby giving a stronger support to the results of earlier investigation. By analyzing how this out-of-equilibrium system responds to harmonic perturbations, we find that the response can be described only using a new form of linear response theory that accounts for aging and the nonergodic behavior of the underlying process. We connect the undamped response of the system at criticality to the decaying response predicted by the recently established nonergodic fluctuation-dissipation theorem for dichotomous processes using information about the second moment of the fluctuations. We demonstrate that over a wide range of perturbation frequencies the response of the cooperative system is greatest when at criticality.

  9. HEAVY ION LINEAR ACCELERATOR

    DOEpatents

    Van Atta, C.M.; Beringer, R.; Smith, L.

    1959-01-01

    A linear accelerator of heavy ions is described. The basic contributions of the invention consist of a method and apparatus for obtaining high energy particles of an element with an increased charge-to-mass ratio. The method comprises the steps of ionizing the atoms of an element, accelerating the resultant ions to an energy substantially equal to one Mev per nucleon, stripping orbital electrons from the accelerated ions by passing the ions through a curtain of elemental vapor disposed transversely of the path of the ions to provide a second charge-to-mass ratio, and finally accelerating the resultant stripped ions to a final energy of at least ten Mev per nucleon.

  10. Linear Proof Mass Actuator

    NASA Technical Reports Server (NTRS)

    Holloway, Sidney E., III

    1994-01-01

    This paper describes the mechanical design, analysis, fabrication, testing, and lessons learned by developing a uniquely designed spaceflight-like actuator. The linear proof mass actuator (LPMA) was designed to attach to both a large space structure and a ground test model without modification. Previous designs lacked the power to perform in a terrestrial environment while other designs failed to produce the desired accelerations or frequency range for spaceflight applications. Thus, the design for a unique actuator was conceived and developed at NASA Langley Research Center. The basic design consists of four large mechanical parts (mass, upper housing, lower housing, and center support) and numerous smaller supporting components including an accelerometer, encoder, and four drive motors. Fabrication personnel were included early in the design phase of the LPMA as part of an integrated manufacturing process to alleviate potential difficulties in machining an already challenging design. Operating testing of the LPMA demonstrated that the actuator is capable of various types of load functions.

  11. Linear Proof Mass Actuator

    NASA Technical Reports Server (NTRS)

    Holloway, S. E., III

    1995-01-01

    This paper describes the mechanical design, analysis, fabrication, testing, and lessons learned by developing a uniquely designed spaceflight-like actuator. The Linear Proof Mass Actuator (LPMA) was designed to attach to both a large space structure and a ground test model without modification. Previous designs lacked the power to perform in a terrestrial environment while other designs failed to produce the desired accelerations or frequency range for spaceflight applications. Thus, the design for a unique actuator was conceived and developed at NASA Langley Research Center. The basic design consists of four large mechanical parts (Mass, Upper Housing, Lower Housing, and Center Support) and numerous smaller supporting components including an accelerometer, encoder, and four drive motors. Fabrication personnel were included early in the design phase of the LPMA as part of an integrated manufacturing process to alleviate potential difficulties in machining an already challenging design. Operational testing of the LPMA demonstrated that the actuator is capable of various types of load functions.

  12. Computer Program For Linear Algebra

    NASA Technical Reports Server (NTRS)

    Krogh, F. T.; Hanson, R. J.

    1987-01-01

    Collection of routines provided for basic vector operations. Basic Linear Algebra Subprogram (BLAS) library is collection from FORTRAN-callable routines for employing standard techniques to perform basic operations of numerical linear algebra.

  13. Medical Progress

    PubMed Central

    Starzl, Thomas E.; Demetris, Anthony J.; Van Thiel, David

    2010-01-01

    Advances in the management of both chronic and acute hepatic disease have been made possible and even mandated by the development of liver transplantation. The clinical use of transplantation has proceeded at a rapid pace since a Consensus Development Conference of the National Institutes of Health concluded in June 1983 that liver transplantation had become a service and not simply an experimental procedure.1 The liver can be transplanted as an extra (auxiliary) organ at an ectopic site, or in the orthotopic location after the removal of the host liver (Fig. 1). This article will focus primarily on the orthotopic procedure. However, there has been renewed interest in the auxiliary operation, which will be discussed separately. PMID:2674716

  14. Frontal linear scleroderma en coup de sabre associated with epileptic seizure.

    PubMed

    Inci, Rahime; Inci, Mehmet Fatih; Ozkan, Fuat; Oztürk, Perihan

    2012-12-10

    Linear scleroderma is a rare variant of localised scleroderma, which is usually seen in childhood and during the adolescent period, and can cause severe functional morbidity as well as cosmetic and psychological problems. Although its ethiopathogenesis is yet obscure, autoimmunity, local ischaemia and injuries, vaccination, irradiation, vitamin K injections, Borrelia burgdorferi and Varicella infections have been incriminated. A 4-year-old girl who had been followed up for about 18 months with diagnosis of epilepsy had a colour discolouration and depression that first appeared 1 year ago and then progressed on her left frontal region. Her CT scan showed a thinning in the frontal bone and depression in the frontal region. These findings are described as 'en coup de sabre' a rare form of linear scleroderma localised at the frontal region of the scalp. In this paper, we present clinical and radiological findings of a 4-year-old girl with epileptic seizures that started 1 year before the onset of the lesion of linear scleroderma.

  15. Frontal linear scleroderma en coup de sabre associated with epileptic seizure

    PubMed Central

    Inci, Rahime; Inci, Mehmet Fatih; Ozkan, Fuat; Oztürk, Perihan

    2012-01-01

    Linear scleroderma is a rare variant of localised scleroderma, which is usually seen in childhood and during the adolescent period, and can cause severe functional morbidity as well as cosmetic and psychological problems. Although its ethiopathogenesis is yet obscure, autoimmunity, local ischaemia and injuries, vaccination, irradiation, vitamin K injections, Borrelia burgdorferi and Varicella infections have been incriminated. A 4-year-old girl who had been followed up for about 18 months with diagnosis of epilepsy had a colour discolouration and depression that first appeared 1 year ago and then progressed on her left frontal region. Her CT scan showed a thinning in the frontal bone and depression in the frontal region. These findings are described as ‘en coup de sabre’ a rare form of linear scleroderma localised at the frontal region of the scalp. In this paper, we present clinical and radiological findings of a 4-year-old girl with epileptic seizures that started 1 year before the onset of the lesion of linear scleroderma. PMID:23230261

  16. Learning oncogenetic networks by reducing to mixed integer linear programming.

    PubMed

    Shahrabi Farahani, Hossein; Lagergren, Jens

    2013-01-01

    Cancer can be a result of accumulation of different types of genetic mutations such as copy number aberrations. The data from tumors are cross-sectional and do not contain the temporal order of the genetic events. Finding the order in which the genetic events have occurred and progression pathways are of vital importance in understanding the disease. In order to model cancer progression, we propose Progression Networks, a special case of Bayesian networks, that are tailored to model disease progression. Progression networks have similarities with Conjunctive Bayesian Networks (CBNs) [1],a variation of Bayesian networks also proposed for modeling disease progression. We also describe a learning algorithm for learning Bayesian networks in general and progression networks in particular. We reduce the hard problem of learning the Bayesian and progression networks to Mixed Integer Linear Programming (MILP). MILP is a Non-deterministic Polynomial-time complete (NP-complete) problem for which very good heuristics exists. We tested our algorithm on synthetic and real cytogenetic data from renal cell carcinoma. We also compared our learned progression networks with the networks proposed in earlier publications. The software is available on the website https://bitbucket.org/farahani/diprog.

  17. Non-linear Systems and Educational Development in Europe.

    ERIC Educational Resources Information Center

    Reilly, David H.

    1999-01-01

    European educational systems are under immense pressure to change, develop, improve, and satisfy many conflicting demands. Educational development and improvement in these countries is unlikely to progress in a neat, orderly, and linear fashion. Applying nonlinear (chaos) theory to development theory may aid understanding of educational…

  18. LINEAR - DERIVATION AND DEFINITION OF A LINEAR AIRCRAFT MODEL

    NASA Technical Reports Server (NTRS)

    Duke, E. L.

    1994-01-01

    The Derivation and Definition of a Linear Model program, LINEAR, provides the user with a powerful and flexible tool for the linearization of aircraft aerodynamic models. LINEAR was developed to provide a standard, documented, and verified tool to derive linear models for aircraft stability analysis and control law design. Linear system models define the aircraft system in the neighborhood of an analysis point and are determined by the linearization of the nonlinear equations defining vehicle dynamics and sensors. LINEAR numerically determines a linear system model using nonlinear equations of motion and a user supplied linear or nonlinear aerodynamic model. The nonlinear equations of motion used are six-degree-of-freedom equations with stationary atmosphere and flat, nonrotating earth assumptions. LINEAR is capable of extracting both linearized engine effects, such as net thrust, torque, and gyroscopic effects and including these effects in the linear system model. The point at which this linear model is defined is determined either by completely specifying the state and control variables, or by specifying an analysis point on a trajectory and directing the program to determine the control variables and the remaining state variables. The system model determined by LINEAR consists of matrices for both the state and observation equations. The program has been designed to provide easy selection of state, control, and observation variables to be used in a particular model. Thus, the order of the system model is completely under user control. Further, the program provides the flexibility of allowing alternate formulations of both the state and observation equations. Data describing the aircraft and the test case is input to the program through a terminal or formatted data files. All data can be modified interactively from case to case. The aerodynamic model can be defined in two ways: a set of nondimensional stability and control derivatives for the flight point of

  19. Generalized Linear Covariance Analysis

    NASA Astrophysics Data System (ADS)

    Markley, F. Landis; Carpenter, J. Russell

    2009-01-01

    This paper presents a comprehensive approach to filter modeling for generalized covariance analysis of both batch least-squares and sequential estimators. We review and extend in two directions the results of prior work that allowed for partitioning of the state space into "solve-for" and "consider" parameters, accounted for differences between the formal values and the true values of the measurement noise, process noise, and a priori solve-for and consider covariances, and explicitly partitioned the errors into subspaces containing only the influence of the measurement noise, process noise, and a priori solve-for and consider covariances. In this work, we explicitly add sensitivity analysis to this prior work, and relax an implicit assumption that the batch estimator's epoch time occurs prior to the definitive span. We also apply the method to an integrated orbit and attitude problem, in which gyro and accelerometer errors, though not estimated, influence the orbit determination performance. We illustrate our results using two graphical presentations, which we call the "variance sandpile" and the "sensitivity mosaic," and we compare the linear covariance results to confidence intervals associated with ensemble statistics from a Monte Carlo analysis.

  20. Generalized Linear Covariance Analysis

    NASA Technical Reports Server (NTRS)

    Carpenter, James R.; Markley, F. Landis

    2014-01-01

    This talk presents a comprehensive approach to filter modeling for generalized covariance analysis of both batch least-squares and sequential estimators. We review and extend in two directions the results of prior work that allowed for partitioning of the state space into solve-for'' and consider'' parameters, accounted for differences between the formal values and the true values of the measurement noise, process noise, and textita priori solve-for and consider covariances, and explicitly partitioned the errors into subspaces containing only the influence of the measurement noise, process noise, and solve-for and consider covariances. In this work, we explicitly add sensitivity analysis to this prior work, and relax an implicit assumption that the batch estimator's epoch time occurs prior to the definitive span. We also apply the method to an integrated orbit and attitude problem, in which gyro and accelerometer errors, though not estimated, influence the orbit determination performance. We illustrate our results using two graphical presentations, which we call the variance sandpile'' and the sensitivity mosaic,'' and we compare the linear covariance results to confidence intervals associated with ensemble statistics from a Monte Carlo analysis.

  1. Winding for linear pump

    DOEpatents

    Kliman, Gerald B.; Brynsvold, Glen V.; Jahns, Thomas M.

    1989-01-01

    A winding and method of winding for a submersible linear pump for pumping liquid sodium is disclosed. The pump includes a stator having a central cylindrical duct preferably vertically aligned. The central vertical duct is surrounded by a system of coils in slots. These slots are interleaved with magnetic flux conducting elements, these magnetic flux conducting elements forming a continuous magnetic field conduction path along the stator. The central duct has placed therein a cylindrical magnetic conducting core, this core having a cylindrical diameter less than the diameter of the cylindrical duct. The core once placed to the duct defines a cylindrical interstitial pumping volume of the pump. This cylindrical interstitial pumping volume preferably defines an inlet at the bottom of the pump, and an outlet at the top of the pump. Pump operation occurs by static windings in the outer stator sequentially conveying toroidal fields from the pump inlet at the bottom of the pump to the pump outlet at the top of the pump. The winding apparatus and method of winding disclosed uses multiple slots per pole per phase with parallel winding legs on each phase equal to or less than the number of slots per pole per phase. The slot sequence per pole per phase is chosen to equalize the variations in flux density of the pump sodium as it passes into the pump at the pump inlet with little or no flux and acquires magnetic flux in passage through the pump to the pump outlet.

  2. Winding for linear pump

    DOEpatents

    Kliman, G.B.; Brynsvold, G.V.; Jahns, T.M.

    1989-08-22

    A winding and method of winding for a submersible linear pump for pumping liquid sodium are disclosed. The pump includes a stator having a central cylindrical duct preferably vertically aligned. The central vertical duct is surrounded by a system of coils in slots. These slots are interleaved with magnetic flux conducting elements, these magnetic flux conducting elements forming a continuous magnetic field conduction path along the stator. The central duct has placed therein a cylindrical magnetic conducting core, this core having a cylindrical diameter less than the diameter of the cylindrical duct. The core once placed to the duct defines a cylindrical interstitial pumping volume of the pump. This cylindrical interstitial pumping volume preferably defines an inlet at the bottom of the pump, and an outlet at the top of the pump. Pump operation occurs by static windings in the outer stator sequentially conveying toroidal fields from the pump inlet at the bottom of the pump to the pump outlet at the top of the pump. The winding apparatus and method of winding disclosed uses multiple slots per pole per phase with parallel winding legs on each phase equal to or less than the number of slots per pole per phase. The slot sequence per pole per phase is chosen to equalize the variations in flux density of the pump sodium as it passes into the pump at the pump inlet with little or no flux and acquires magnetic flux in passage through the pump to the pump outlet. 4 figs.

  3. Linear induction pump

    DOEpatents

    Meisner, John W.; Moore, Robert M.; Bienvenue, Louis L.

    1985-03-19

    Electromagnetic linear induction pump for liquid metal which includes a unitary pump duct. The duct comprises two substantially flat parallel spaced-apart wall members, one being located above the other and two parallel opposing side members interconnecting the wall members. Located within the duct are a plurality of web members interconnecting the wall members and extending parallel to the side members whereby the wall members, side members and web members define a plurality of fluid passageways, each of the fluid passageways having substantially the same cross-sectional flow area. Attached to an outer surface of each side member is an electrically conductive end bar for the passage of an induced current therethrough. A multi-phase, electrical stator is located adjacent each of the wall members. The duct, stators, and end bars are enclosed in a housing which is provided with an inlet and outlet in fluid communication with opposite ends of the fluid passageways in the pump duct. In accordance with a preferred embodiment, the inlet and outlet includes a transition means which provides for a transition from a round cross-sectional flow path to a substantially rectangular cross-sectional flow path defined by the pump duct.

  4. Generalized Linear Covariance Analysis

    NASA Technical Reports Server (NTRS)

    Carpenter, J. Russell; Markley, F. Landis

    2008-01-01

    We review and extend in two directions the results of prior work on generalized covariance analysis methods. This prior work allowed for partitioning of the state space into "solve-for" and "consider" parameters, allowed for differences between the formal values and the true values of the measurement noise, process noise, and a priori solve-for and consider covariances, and explicitly partitioned the errors into subspaces containing only the influence of the measurement noise, process noise, and a priori solve-for and consider covariances. In this work, we explicitly add sensitivity analysis to this prior work, and relax an implicit assumption that the batch estimator s anchor time occurs prior to the definitive span. We also apply the method to an integrated orbit and attitude problem, in which gyro and accelerometer errors, though not estimated, influence the orbit determination performance. We illustrate our results using two graphical presentations, which we call the "variance sandpile" and the "sensitivity mosaic," and we compare the linear covariance results to confidence intervals associated with ensemble statistics from a Monte Carlo analysis.

  5. Berkeley Proton Linear Accelerator

    DOE R&D Accomplishments Database

    Alvarez, L. W.; Bradner, H.; Franck, J.; Gordon, H.; Gow, J. D.; Marshall, L. C.; Oppenheimer, F. F.; Panofsky, W. K. H.; Richman, C.; Woodyard, J. R.

    1953-10-13

    A linear accelerator, which increases the energy of protons from a 4 Mev Van de Graaff injector, to a final energy of 31.5 Mev, has been constructed. The accelerator consists of a cavity 40 feet long and 39 inches in diameter, excited at resonance in a longitudinal electric mode with a radio-frequency power of about 2.2 x 10{sup 6} watts peak at 202.5 mc. Acceleration is made possible by the introduction of 46 axial "drift tubes" into the cavity, which is designed such that the particles traverse the distance between the centers of successive tubes in one cycle of the r.f. power. The protons are longitudinally stable as in the synchrotron, and are stabilized transversely by the action of converging fields produced by focusing grids. The electrical cavity is constructed like an inverted airplane fuselage and is supported in a vacuum tank. Power is supplied by 9 high powered oscillators fed from a pulse generator of the artificial transmission line type.

  6. EDITORIAL: Catalysing progress Catalysing progress

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  7. EDITORIAL: Catalysing progress Catalysing progress

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  8. Cancer progression modeling using static sample data.

    PubMed

    Sun, Yijun; Yao, Jin; Nowak, Norma J; Goodison, Steve

    2014-01-01

    As molecular profiling data continues to accumulate, the design of integrative computational analyses that can provide insights into the dynamic aspects of cancer progression becomes feasible. Here, we present a novel computational method for the construction of cancer progression models based on the analysis of static tumor samples. We demonstrate the reliability of the method with simulated data, and describe the application to breast cancer data. Our findings support a linear, branching model for breast cancer progression. An interactive model facilitates the identification of key molecular events in the advance of disease to malignancy.

  9. Varieties of progressive non-fluent aphasia.

    PubMed

    Cappa, S F; Perani, D; Messa, C; Miozzo, A; Fazio, F

    1996-01-17

    We report four patients with progressive aphasia of the non-fluent type as the presenting clinical manifestation. The patients were included in a longitudinal study of focal progressive neuropsychological syndromes, and were periodically submitted to neuropsychological evaluations and neuroimaging studies (TC, MRI, SPET or PET). The pattern of neuropsychological impairment was in good agreement with the results of functional imaging studies, which indicated involvement of the anterior regions of the left hemisphere. The evolution of the clinical picture was extremely heterogeneous in the four patients, ranging from a relatively stable picture of transcortical motor aphasia to a severe progressive frontal lobe syndrome. Progressive non-fluent aphasia appears to be a reliable clinical marker of the localization of the pathological process; whether this is related to specific neuropathological conditions, such as Pick's disease, remains for the moment a matter of speculation.

  10. Linear Algebraic Method for Non-Linear Map Analysis

    SciTech Connect

    Yu,L.; Nash, B.

    2009-05-04

    We present a newly developed method to analyze some non-linear dynamics problems such as the Henon map using a matrix analysis method from linear algebra. Choosing the Henon map as an example, we analyze the spectral structure, the tune-amplitude dependence, the variation of tune and amplitude during the particle motion, etc., using the method of Jordan decomposition which is widely used in conventional linear algebra.

  11. Progress and Potential

    PubMed Central

    Haspel, Richard L.; Olsen, Randall J.; Berry, Anna; Hill, Charles E.; Pfeifer, John D.; Schrijver, Iris; Kaul, Karen L.

    2014-01-01

    Context Genomic medicine is revolutionizing patient care. Physicians in areas as diverse as oncology, obstetrics, and infectious disease have begun using next-generation sequencing assays as standard diagnostic tools. Objective To review the role of pathologists in genomic testing as well as current educational programs and future training needs in genomic pathology. Data Sources Published literature as well as personal experience based on committee membership and genomic pathology curricular design. Conclusion Pathologists, as the directors of the clinical laboratories, must be prepared to integrate genomic testing into their practice. The pathology community has made significant progress in genomics-related education. A continued coordinated and proactive effort will ensure a future vital role for pathologists in the evolving health care system and also the best possible patient care. PMID:24678680

  12. Turbulence Spreading into Linearly Stable Zone and Transport Scaling

    SciTech Connect

    T.S. Hahm; P.H. Diamond; Z. Lin; K. Itoh; S.-I. Itoh

    2003-10-20

    We study the simplest problem of turbulence spreading corresponding to the spatio-temporal propagation of a patch of turbulence from a region where it is locally excited to a region of weaker excitation, or even local damping. A single model equation for the local turbulence intensity I(x, t) includes the effects of local linear growth and damping, spatially local nonlinear coupling to dissipation and spatial scattering of turbulence energy induced by nonlinear coupling. In the absence of dissipation, the front propagation into the linearly stable zone occurs with the property of rapid progression at small t, followed by slower subdiffusive progression at late times. The turbulence radial spreading into the linearly stable zone reduces the turbulent intensity in the linearly unstable zone, and introduces an additional dependence on the rho* is always equal to rho i/a to the turbulent intensity and the transport scaling. These are in broad, semi-quantitative agreements with a number of global gyrokinetic simulation results with zonal flows and without zonal flows. The front propagation stops when the radial flux of fluctuation energy from the linearly unstable region is balanced by local dissipation in the linearly stable region.

  13. Clinical and Translational Epidemiology Branch (CTEB)

    Cancer.gov

    The Clinical and Translational Epidemiology Branch focuses on factors that influence cancer progression, recurrence, survival, and other treatment outcomes, and factors associated with cancer development.

  14. A prototype piecewise-linear dynamic attenuator

    NASA Astrophysics Data System (ADS)

    Hsieh, Scott S.; Peng, Mark V.; May, Christopher A.; Shunhavanich, Picha; Fleischmann, Dominik; Pelc, Norbert J.

    2016-07-01

    The piecewise-linear dynamic attenuator has been proposed as a mechanism in CT scanning for personalizing the x-ray illumination on a patient- and application-specific basis. Previous simulations have shown benefits in image quality, scatter, and dose objectives. We report on the first prototype implementation. This prototype is reduced in scale and speed and is integrated into a tabletop CT system with a smaller field of view (25 cm) and longer scan time (42 s) compared to a clinical system. Stainless steel wedges were machined and affixed to linear actuators, which were in turn held secure by a frame built using rapid prototyping technologies. The actuators were computer-controlled, with characteristic noise of about 100 microns. Simulations suggest that in a clinical setting, the impact of actuator noise could lead to artifacts of only 1 HU. Ring artifacts were minimized by careful design of the wedges. A water beam hardening correction was applied and the scan was collimated to reduce scatter. We scanned a 16 cm water cylinder phantom as well as an anthropomorphic pediatric phantom. The artifacts present in reconstructed images are comparable to artifacts normally seen with this tabletop system. Compared to a flat-field reference scan, increased detectability at reduced dose is shown and streaking is reduced. Artifacts are modest in our images and further refinement is possible. Issues of mechanical speed and stability in the challenging clinical CT environment will be addressed in a future design.

  15. A prototype piecewise-linear dynamic attenuator.

    PubMed

    Hsieh, Scott S; Peng, Mark V; May, Christopher A; Shunhavanich, Picha; Fleischmann, Dominik; Pelc, Norbert J

    2016-07-01

    The piecewise-linear dynamic attenuator has been proposed as a mechanism in CT scanning for personalizing the x-ray illumination on a patient- and application-specific basis. Previous simulations have shown benefits in image quality, scatter, and dose objectives. We report on the first prototype implementation. This prototype is reduced in scale and speed and is integrated into a tabletop CT system with a smaller field of view (25 cm) and longer scan time (42 s) compared to a clinical system. Stainless steel wedges were machined and affixed to linear actuators, which were in turn held secure by a frame built using rapid prototyping technologies. The actuators were computer-controlled, with characteristic noise of about 100 microns. Simulations suggest that in a clinical setting, the impact of actuator noise could lead to artifacts of only 1 HU. Ring artifacts were minimized by careful design of the wedges. A water beam hardening correction was applied and the scan was collimated to reduce scatter. We scanned a 16 cm water cylinder phantom as well as an anthropomorphic pediatric phantom. The artifacts present in reconstructed images are comparable to artifacts normally seen with this tabletop system. Compared to a flat-field reference scan, increased detectability at reduced dose is shown and streaking is reduced. Artifacts are modest in our images and further refinement is possible. Issues of mechanical speed and stability in the challenging clinical CT environment will be addressed in a future design. PMID:27284705

  16. Linear Proof-Mass Actuator

    NASA Technical Reports Server (NTRS)

    Holloway, Sidney E., III; Crossley, Edward A.; Miller, James B.; Jones, Irby W.; Davis, C. Calvin; Behun, Vaughn D.; Goodrich, Lewis R., Sr.

    1995-01-01

    Linear proof-mass actuator (LPMA) is friction-driven linear mass actuator capable of applying controlled force to structure in outer space to damp out oscillations. Capable of high accelerations and provides smooth, bidirectional travel of mass. Design eliminates gears and belts. LPMA strong enough to be used terrestrially where linear actuators needed to excite or damp out oscillations. High flexibility designed into LPMA by varying size of motors, mass, and length of stroke, and by modifying control software.

  17. Progress in acute myeloid leukemia.

    PubMed

    Kadia, Tapan M; Ravandi, Farhad; O'Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M

    2015-03-01

    Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

  18. Progress in breast cancer: overview.

    PubMed

    Arteaga, Carlos L

    2013-12-01

    This edition of CCR Focus titled Research in Breast Cancer: Frontiers in Genomics, Biology, and Clinical Investigation reviews six topics that cover areas of translational research of high impact in breast cancer. These topics represent areas of breast cancer research where significant progress has occurred but also where very important challenges remain. The papers in this CCR Focus section are contributed by experts in the respective areas of investigation. Herein, key aspects of these contributions and the research directions they propose are reviewed.

  19. Learning numerical progressions.

    PubMed

    Vitz, P C; Hazan, D N

    1974-01-01

    Learning of simple numerical progressions and compound progressions formed by combining two or three simple progressions is investigated. In two experiments, time to solution was greater for compound vs simple progressions; greater the higher the progression's solution level; and greater if the progression consisted of large vs small numbers. A set of strategies is proposed to account for progression learning based on the assumption S computes differences between integers, differences between differences, etc., in a hierarchical fashion. Two measures of progression difficulty, each a summary of the strategies, are proposed; C1 is a count of the number of differences needed to solve a progression; C2 is the same count with higher level differences given more weight. The measures accurately predict in both experiments the mean time to solve 16 different progressions with C2 being somewhat superior. The measures also predict the learning difficulty of 10 other progressions reported by Bjork (1968).

  20. Linear collider development at SLAC

    SciTech Connect

    Irwin, J.

    1993-08-01

    Linear collider R&D at SLAC comprises work on the present Stanford Linear Collider (SLC) and work toward the next linear collider (NLC). Recent SLC developments are summarized. NLC studies are divided into hardware-based and theoretical. We report on the status of the NLC Test Accelerator (NLCTA) and the final focus test beam (FFTB), describe plans for ASSET, an installation to measure accelerator structure wakefields, and mention IR design developments. Finally we review recent NLC theoretical studies, ending with the author`s view of next linear collider parameter sets.

  1. Quantization of general linear electrodynamics

    SciTech Connect

    Rivera, Sergio; Schuller, Frederic P.

    2011-03-15

    General linear electrodynamics allow for an arbitrary linear constitutive relation between the field strength 2-form and induction 2-form density if crucial hyperbolicity and energy conditions are satisfied, which render the theory predictive and physically interpretable. Taking into account the higher-order polynomial dispersion relation and associated causal structure of general linear electrodynamics, we carefully develop its Hamiltonian formulation from first principles. Canonical quantization of the resulting constrained system then results in a quantum vacuum which is sensitive to the constitutive tensor of the classical theory. As an application we calculate the Casimir effect in a birefringent linear optical medium.

  2. A Young Man With Progressive Vision and Hearing Loss.

    PubMed

    Kung, Nathan H; Bucelli, Robert C; Van Stavern, Renee B; Goebel, Joel A; Van Stavern, Gregory P

    2016-07-01

    A 37-year-old man with a history of progressive bilateral sensorineural hearing loss presented to a neuro-ophthalmology clinic with an acute left homonymous hemianopsia. In this article, we discuss the clinical approach and differential diagnosis of progressive combined vision and hearing loss and guide the reader to discover the patient's ultimate diagnosis. PMID:27213952

  3. Nocturnal Systemic Hypotension Increases the Risk of Glaucoma Progression

    PubMed Central

    Charlson, Mary E.; de Moraes, Carlos Gustavo; Link, Alissa; Wells, Martin T.; Harmon, Gregory; Peterson, Janey C.; Ritch, Robert; Liebmann, Jeffrey M.

    2015-01-01

    Objective The objective of this prospective, longitudinal study of patients with normal-tension glaucoma (NTG) was to determine whether patients with nocturnal hypotension are at greater risk for visual field (VF) loss over 12 months than those without nocturnal hypotension. Design Prospective, longitudinal study. Participants Consecutive patients with NTG with at least 5 prior VF tests were screened for eligibility. Methods The baseline evaluation assessed demographic and clinical characteristics, covering systemic comorbid conditions, including systemic hypertension. All oral and ophthalmologic medications were recorded. A complete ophthalmological examination was performed at baseline and follow-up. Patients had their blood pressure (BP) monitored every 30 minutes for 48 hours with an ambulatory recording device at baseline and 6 and 12 months. Main Outcome Measures The primary outcome was based on the global rates of VF progression by linear regression of the mean VF threshold sensitivity over time (decibels/year). Results Eighty-five patients with NTG (166 eyes; mean age, 65 years; 67% were women) were included. Of the 85 patients, 29% had progressed in the 5 VFs collected before study enrollment. The nocturnal mean arterial pressure (MAP) was compared with the daytime MAP. Multivariate analysis showed that the total time that sleep MAP was 10 mmHg below the daytime MAP was a significant predictor of subsequent VF progression (P<0.02). Conclusions Cumulative nocturnal hypotension predicted VF loss in this cohort. Our data suggest that the duration and magnitude of decrease in nocturnal blood pressure below the daytime MAP, especially pressures that are 10 mmHg lower than daytime MAP, predict progression of NTG. Low nocturnal blood pressure, whether occurring spontaneously or as a result of medications, may lead to worsening of VF defects. PMID:24869467

  4. Linear equality constraints in the general linear mixed model.

    PubMed

    Edwards, L J; Stewart, P W; Muller, K E; Helms, R W

    2001-12-01

    Scientists may wish to analyze correlated outcome data with constraints among the responses. For example, piecewise linear regression in a longitudinal data analysis can require use of a general linear mixed model combined with linear parameter constraints. Although well developed for standard univariate models, there are no general results that allow a data analyst to specify a mixed model equation in conjunction with a set of constraints on the parameters. We resolve the difficulty by precisely describing conditions that allow specifying linear parameter constraints that insure the validity of estimates and tests in a general linear mixed model. The recommended approach requires only straightforward and noniterative calculations to implement. We illustrate the convenience and advantages of the methods with a comparison of cognitive developmental patterns in a study of individuals from infancy to early adulthood for children from low-income families.

  5. Student learning of basis, span and linear independence in linear algebra

    NASA Astrophysics Data System (ADS)

    Stewart, Sepideh; Thomas, Michael O. J.

    2010-03-01

    One of the earlier, more challenging concepts in linear algebra at university is that of basis. Students are often taught procedurally how to find a basis for a subspace using matrix manipulation, but may struggle with understanding the construct of basis, making further progress harder. We believe one reason for this is because students have major difficulties with concepts of span and linear independence which form the requirements for a set of vectors to form a basis. In this research we applied a theoretical framework based on Tall's three worlds of mathematics learning and action-process-object-schema (APOS) theory to the learning of the concept of basis by a group of second year university students. The results suggest that an emphasis on matrix processes may not help students understand the concept, and embodied, visual ideas that could be valuable were usually lacking.

  6. Overview of NASA Magnet and Linear Alternator Research Efforts

    NASA Technical Reports Server (NTRS)

    Geng, Steven M.; Niedra, Janis M.; Schwarze, Gene E.

    2005-01-01

    The Department of Energy, Lockheed Martin, Stirling Technology Company, and NASA Glenn Research Center are developing a high-efficiency, 110 watt Stirling Radioisotope Generator (SRG110) for NASA Space Science missions. NASA Glenn is conducting in-house research on rare earth permanent magnets and on linear alternators to assist in developing a free-piston Stirling convertor for the SRG110 and for developing advanced technology. The permanent magnet research efforts include magnet characterization, short-term magnet aging tests, and long-term magnet aging tests. Linear alternator research efforts have begun just recently at GRC with the characterization of a moving iron type linear alternator using GRC's alternator test rig. This paper reports on the progress and future plans of GRC's magnet and linear alternator research efforts.

  7. Linear Algebra and Image Processing

    ERIC Educational Resources Information Center

    Allali, Mohamed

    2010-01-01

    We use the computing technology digital image processing (DIP) to enhance the teaching of linear algebra so as to make the course more visual and interesting. Certainly, this visual approach by using technology to link linear algebra to DIP is interesting and unexpected to both students as well as many faculty. (Contains 2 tables and 11 figures.)

  8. Linear algebra and image processing

    NASA Astrophysics Data System (ADS)

    Allali, Mohamed

    2010-09-01

    We use the computing technology digital image processing (DIP) to enhance the teaching of linear algebra so as to make the course more visual and interesting. Certainly, this visual approach by using technology to link linear algebra to DIP is interesting and unexpected to both students as well as many faculty.

  9. Linear Programming across the Curriculum

    ERIC Educational Resources Information Center

    Yoder, S. Elizabeth; Kurz, M. Elizabeth

    2015-01-01

    Linear programming (LP) is taught in different departments across college campuses with engineering and management curricula. Modeling an LP problem is taught in every linear programming class. As faculty teaching in Engineering and Management departments, the depth to which teachers should expect students to master this particular type of…

  10. Passive linearization of nonlinear resonances

    NASA Astrophysics Data System (ADS)

    Habib, G.; Grappasonni, C.; Kerschen, G.

    2016-07-01

    The objective of this paper is to demonstrate that the addition of properly tuned nonlinearities to a nonlinear system can increase the range over which a specific resonance responds linearly. Specifically, we seek to enforce two important properties of linear systems, namely, the force-displacement proportionality and the invariance of resonance frequencies. Numerical simulations and experiments are used to validate the theoretical findings.

  11. Spatial Processes in Linear Ordering

    ERIC Educational Resources Information Center

    von Hecker, Ulrich; Klauer, Karl Christoph; Wolf, Lukas; Fazilat-Pour, Masoud

    2016-01-01

    Memory performance in linear order reasoning tasks (A > B, B > C, C > D, etc.) shows quicker, and more accurate responses to queries on wider (AD) than narrower (AB) pairs on a hypothetical linear mental model (A -- B -- C -- D). While indicative of an analogue representation, research so far did not provide positive evidence for spatial…

  12. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    sclerosis based on the Expanded Disability Status Scale and information about preceding relapses provides a tool for a reproducible, accurate and timely diagnosis that requires a very short confirmation period. If applied broadly, the definition has the potential to strengthen the design and improve comparability of clinical trials and observational studies in secondary progressive multiple sclerosis.

  13. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    sclerosis based on the Expanded Disability Status Scale and information about preceding relapses provides a tool for a reproducible, accurate and timely diagnosis that requires a very short confirmation period. If applied broadly, the definition has the potential to strengthen the design and improve comparability of clinical trials and observational studies in secondary progressive multiple sclerosis. PMID:27401521

  14. Simulation of a medical linear accelerator for teaching purposes.

    PubMed

    Anderson, Rhys; Lamey, Michael; MacPherson, Miller; Carlone, Marco

    2015-01-01

    Simulation software for medical linear accelerators that can be used in a teaching environment was developed. The components of linear accelerators were modeled to first order accuracy using analytical expressions taken from the literature. The expressions used constants that were empirically set such that realistic response could be expected. These expressions were programmed in a MATLAB environment with a graphical user interface in order to produce an environment similar to that of linear accelerator service mode. The program was evaluated in a systematic fashion, where parameters affecting the clinical properties of medical linear accelerator beams were adjusted independently, and the effects on beam energy and dose rate recorded. These results confirmed that beam tuning adjustments could be simulated in a simple environment. Further, adjustment of service parameters over a large range was possible, and this allows the demonstration of linear accelerator physics in an environment accessible to both medical physicists and linear accelerator service engineers. In conclusion, a software tool, named SIMAC, was developed to improve the teaching of linear accelerator physics in a simulated environment. SIMAC performed in a similar manner to medical linear accelerators. The authors hope that this tool will be valuable as a teaching tool for medical physicists and linear accelerator service engineers.

  15. Heritable unilateral clinical anophthalmia.

    PubMed

    Griepentrog, Gregory J; Lucarelli, Mark J

    2004-03-01

    We examined a newborn child with unilateral right-sided clinical anophthalmos born to a mother with unilateral left-sided anophthalmos. Although rare, isolated nonsyndromic heritable unilateral anophthalmia and microphthalmia have been reported in the literature. We briefly review the genetics of such anomalies and discuss the importance of a full clinical genetics evaluation. Treatment of this patient's anophthalmic socket consists of progressive conformer expansion to be followed by placement of a self-inflating polymer expander.

  16. Non-linear characterisation of the physical model of an ancient masonry bridge

    NASA Astrophysics Data System (ADS)

    Zanotti Fragonara, L.; Ceravolo, R.; Matta, E.; Quattrone, A.; De Stefano, A.; Pecorelli, M.

    2012-08-01

    This paper presents the non-linear investigations carried out on a scaled model of a two-span masonry arch bridge. The model has been built in order to study the effect of the central pile settlement due to riverbank erosion. Progressive damage was induced in several steps by applying increasing settlements at the central pier. For each settlement step, harmonic shaker tests were conducted under different excitation levels, this allowing for the non-linear identification of the progressively damaged system. The shaker tests have been performed at resonance with the modal frequency of the structure, which were determined from a previous linear identification. Estimated non-linearity parameters, which result from the systematic application of restoring force based identification algorithms, can corroborate models to be used in the reassessment of existing structures. The method used for non-linear identification allows monitoring the evolution of non-linear parameters or indicators which can be used in damage and safety assessment.

  17. Clinical Preceptors' Perspectives on Clinical Education in Post-Professional Athletic Training Education Programs

    ERIC Educational Resources Information Center

    Phan, Kelvin; McCarty, Cailee W.; Mutchler, Jessica M.; Van Lunen, Bonnie

    2012-01-01

    Context: Clinical education is the interaction between a clinical preceptor and student within the clinical setting to help the student progress as a clinician. Post-professional athletic training clinical education is especially important to improve these students' clinical knowledge and skills. However, little research has been conducted to…

  18. ALPS: A Linear Program Solver

    NASA Technical Reports Server (NTRS)

    Ferencz, Donald C.; Viterna, Larry A.

    1991-01-01

    ALPS is a computer program which can be used to solve general linear program (optimization) problems. ALPS was designed for those who have minimal linear programming (LP) knowledge and features a menu-driven scheme to guide the user through the process of creating and solving LP formulations. Once created, the problems can be edited and stored in standard DOS ASCII files to provide portability to various word processors or even other linear programming packages. Unlike many math-oriented LP solvers, ALPS contains an LP parser that reads through the LP formulation and reports several types of errors to the user. ALPS provides a large amount of solution data which is often useful in problem solving. In addition to pure linear programs, ALPS can solve for integer, mixed integer, and binary type problems. Pure linear programs are solved with the revised simplex method. Integer or mixed integer programs are solved initially with the revised simplex, and the completed using the branch-and-bound technique. Binary programs are solved with the method of implicit enumeration. This manual describes how to use ALPS to create, edit, and solve linear programming problems. Instructions for installing ALPS on a PC compatible computer are included in the appendices along with a general introduction to linear programming. A programmers guide is also included for assistance in modifying and maintaining the program.

  19. Putaminal Diffusivity Correlates With Disease Progression in Parkinson's Disease

    PubMed Central

    Chan, Ling-Ling; Ng, Kia-Min; Yeoh, Chooi-Sum; Rumpel, H.; Li, Hui-Hua; Tan, Eng-King

    2016-01-01

    Abstract Diffusion tensor imaging (DTI) is an increasingly used noninvasive imaging tool. However its long-term clinical utility is unclear. Parkinson's disease (PD) is a common neurodegenerative disease. We prospectively examined a cohort of 46 Parkinson's disease (PD) patients who underwent diffusion tensor imaging (DTI) of the brain at baseline and 6 years later on a 1.5 Tesla scanner using a standardized protocol. DTI parameters of mean diffusivity (MD) and fractional anisotrophy (FA) were extracted using regions-of-interest (ROIs) analysis from various brain regions. Compared to the baseline scan, MD increased in all brain regions (P < 0.0001). FA increased in the substantia nigra and posterior putamen, but decreased in the frontal white matter (P < 0.0001). Linear regression analysis demonstrated that the MD in the anterior putamen increased 11.6 units (95% CI = [4.71, 18.43]) (P = 0.0003) for every unit increase of United PD Rating Scale (UPDRS). Our 6-year prospective longitudinal study demonstrated increased diffusivity in all brain regions and that in the anterior putamen correlated with disease progression. Serial diffusion data may be useful as an additional objective in vivo biomarker for motor progression in PD. PMID:26871779

  20. LDRD final report : autotuning for scalable linear algebra.

    SciTech Connect

    Heroux, Michael Allen; Marker, Bryan

    2011-09-01

    This report summarizes the progress made as part of a one year lab-directed research and development (LDRD) project to fund the research efforts of Bryan Marker at the University of Texas at Austin. The goal of the project was to develop new techniques for automatically tuning the performance of dense linear algebra kernels. These kernels often represent the majority of computational time in an application. The primary outcome from this work is a demonstration of the value of model driven engineering as an approach to accurately predict and study performance trade-offs for dense linear algebra computations.

  1. Linearization algorithms for line transfer

    SciTech Connect

    Scott, H.A.

    1990-11-06

    Complete linearization is a very powerful technique for solving multi-line transfer problems that can be used efficiently with a variety of transfer formalisms. The linearization algorithm we describe is computationally very similar to ETLA, but allows an effective treatment of strongly-interacting lines. This algorithm has been implemented (in several codes) with two different transfer formalisms in all three one-dimensional geometries. We also describe a variation of the algorithm that handles saturable laser transport. Finally, we present a combination of linearization with a local approximate operator formalism, which has been implemented in two dimensions and is being developed in three dimensions. 11 refs.

  2. Precision magnetic suspension linear bearing

    NASA Technical Reports Server (NTRS)

    Trumper, David L.; Queen, Michael A.

    1992-01-01

    We have shown the design and analyzed the electromechanics of a linear motor suitable for independently controlling two suspension degrees of freedom. This motor, at least on paper, meets the requirements for driving an X-Y stage of 10 Kg mass with about 4 m/sq sec acceleration, with travel of several hundred millimeters in X and Y, and with reasonable power dissipation. A conceptual design for such a stage is presented. The theoretical feasibility of linear and planar bearings using single or multiple magnetic suspension linear motors is demonstrated.

  3. Characterizations of linear sufficient statistics

    NASA Technical Reports Server (NTRS)

    Peters, B. C., Jr.; Redner, R.; Decell, H. P., Jr.

    1976-01-01

    A necessary and sufficient condition is developed such that there exists a continous linear sufficient statistic T for a dominated collection of totally finite measures defined on the Borel field generated by the open sets of a Banach space X. In particular, corollary necessary and sufficient conditions are given so that there exists a rank K linear sufficient statistic T for any finite collection of probability measures having n-variate normal densities. In this case a simple calculation, involving only the population means and covariances, determines the smallest integer K for which there exists a rank K linear sufficient statistic T (as well as an associated statistic T itself).

  4. Practical Session: Simple Linear Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

    Two exercises are proposed to illustrate the simple linear regression. The first one is based on the famous Galton's data set on heredity. We use the lm R command and get coefficients estimates, standard error of the error, R2, residuals …In the second example, devoted to data related to the vapor tension of mercury, we fit a simple linear regression, predict values, and anticipate on multiple linear regression. This pratical session is an excerpt from practical exercises proposed by A. Dalalyan at EPNC (see Exercises 1 and 2 of http://certis.enpc.fr/~dalalyan/Download/TP_ENPC_4.pdf).

  5. The next linear collider damping ring complex

    SciTech Connect

    Corlett,J.; Atkinson,D.; De Santis,S.; Hartman, N.; Kennedy, K.; Li, D.; Marks, S.; Minamihara, Y.; Nishimura, H.; Pivi, M.; Reavill, D.; Rimmer, R.; Schlueter, R.; Wolski, A.; Anderson,S.; McKee,B.; Raubenheimer, T.; Ross, M.; Sheppard, J.C.

    2001-06-12

    We report progress on the design of the Next Linear Collider (NLC) Damping Rings complexes. The purpose of the damping rings is to provide low emittance electron and positron bunch trains to the NLC linacs, at a rate of 120 Hz. As an option to operate at the higher rate of 180 Hz, two 1.98 GeV main damping rings per beam are proposed, and one positron pre-damping ring. The main damping rings store up to 0.8 amp in 3 trains of 190 bunches each and have normalized extracted beam emittances {gamma}{var_epsilon}x = 3 mm-mrad and {gamma}{var_epsilon}y = 0.02 mm-mrad. The optical designs, based on a theoretical minimum emittance lattice (TME), are described, with an analysis of dynamic aperture and non-linear effects. Key subsystems and components are described, including the wiggler, the vacuum systems and photon stop design, and the higher-order-mode damped RF cavities. Impedance and instabilities are discussed.

  6. Overdetermined Systems of Linear Equations.

    ERIC Educational Resources Information Center

    Williams, Gareth

    1990-01-01

    Explored is an overdetermined system of linear equations to find an appropriate least squares solution. A geometrical interpretation of this solution is given. Included is a least squares point discussion. (KR)

  7. Acoustic emission linear pulse holography

    DOEpatents

    Collins, H.D.; Busse, L.J.; Lemon, D.K.

    1983-10-25

    This device relates to the concept of and means for performing Acoustic Emission Linear Pulse Holography, which combines the advantages of linear holographic imaging and Acoustic Emission into a single non-destructive inspection system. This unique system produces a chronological, linear holographic image of a flaw by utilizing the acoustic energy emitted during crack growth. The innovation is the concept of utilizing the crack-generated acoustic emission energy to generate a chronological series of images of a growing crack by applying linear, pulse holographic processing to the acoustic emission data. The process is implemented by placing on a structure an array of piezoelectric sensors (typically 16 or 32 of them) near the defect location. A reference sensor is placed between the defect and the array.

  8. Ada Linear-Algebra Program

    NASA Technical Reports Server (NTRS)

    Klumpp, A. R.; Lawson, C. L.

    1988-01-01

    Routines provided for common scalar, vector, matrix, and quaternion operations. Computer program extends Ada programming language to include linear-algebra capabilities similar to HAS/S programming language. Designed for such avionics applications as software for Space Station.

  9. Optimal piecewise locally linear modeling

    NASA Astrophysics Data System (ADS)

    Harris, Chris J.; Hong, Xia; Feng, M.

    1999-03-01

    Associative memory networks such as Radial Basis Functions, Neurofuzzy and Fuzzy Logic used for modelling nonlinear processes suffer from the curse of dimensionality (COD), in that as the input dimension increases the parameterization, computation cost, training data requirements, etc. increase exponentially. Here a new algorithm is introduced for the construction of a Delaunay input space partitioned optimal piecewise locally linear models to overcome the COD as well as generate locally linear models directly amenable to linear control and estimation algorithms. The training of the model is configured as a new mixture of experts network with a new fast decision rule derived using convex set theory. A very fast simulated reannealing (VFSR) algorithm is utilized to search a global optimal solution of the Delaunay input space partition. A benchmark non-linear time series is used to demonstrate the new approach.

  10. SLC: The first linear collider

    NASA Astrophysics Data System (ADS)

    Phinney, Nan

    The Stanford Linear Collider (SLC) was built in the 1980s at the Stanford Linear Accelerator Center (SLAC) in California. Like LEP, it was designed to study the properties of the Z boson at a center-of-mass energy of about 91 GeV. The SLC was also a prototype for an entirely new approach to electron-positron colliders. The development of a new technology was motivated by the fact that in an electron storage ring, the electrons radiate synchrotron radiation as they are bent around the ring. To avoid excessive energy loss from this radiation, the circumference of the ring has to increase as the square of the desired energy, making very high energy rings prohibitively large and expensive. With a linear accelerator, the electrons do not need to bend and the tunnel length only grows linearly with energy...

  11. Spacetime metric from linear electrodynamics

    NASA Astrophysics Data System (ADS)

    Obukhov, Yuri N.; Hehl, Friedrich W.

    1999-07-01

    The Maxwell equations are formulated on an arbitrary (1+3)-dimensional manifold. Then, imposing a (constrained) linear constitutive relation between electromagnetic field (E,B) and excitation (D,ℌ), we derive the metric of spacetime therefrom.

  12. Linear Back-Drive Differentials

    NASA Technical Reports Server (NTRS)

    Waydo, Peter

    2003-01-01

    Linear back-drive differentials have been proposed as alternatives to conventional gear differentials for applications in which there is only limited rotational motion (e.g., oscillation). The finite nature of the rotation makes it possible to optimize a linear back-drive differential in ways that would not be possible for gear differentials or other differentials that are required to be capable of unlimited rotation. As a result, relative to gear differentials, linear back-drive differentials could be more compact and less massive, could contain fewer complex parts, and could be less sensitive to variations in the viscosities of lubricants. Linear back-drive differentials would operate according to established principles of power ball screws and linear-motion drives, but would utilize these principles in an innovative way. One major characteristic of such mechanisms that would be exploited in linear back-drive differentials is the possibility of designing them to drive or back-drive with similar efficiency and energy input: in other words, such a mechanism can be designed so that a rotating screw can drive a nut linearly or the linear motion of the nut can cause the screw to rotate. A linear back-drive differential (see figure) would include two collinear shafts connected to two parts that are intended to engage in limited opposing rotations. The linear back-drive differential would also include a nut that would be free to translate along its axis but not to rotate. The inner surface of the nut would be right-hand threaded at one end and left-hand threaded at the opposite end to engage corresponding right- and left-handed threads on the shafts. A rotation and torque introduced into the system via one shaft would drive the nut in linear motion. The nut, in turn, would back-drive the other shaft, creating a reaction torque. Balls would reduce friction, making it possible for the shaft/nut coupling on each side to operate with 90 percent efficiency.

  13. Surrogate Markers of Abdominal Aortic Aneurysm Progression.

    PubMed

    Wanhainen, Anders; Mani, Kevin; Golledge, Jonathan

    2016-02-01

    The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Standardized reporting of reproducible methods of measuring AAA diameter is essential. Newer imaging assessments, such as volume measurements, biomechanical analyses, and functional and molecular imaging, as well as circulating biomarkers, have potential to add important information about AAA progression. Currently, however, there is insufficient evidence to recommend their routine use in clinical practice. PMID:26715680

  14. Polarized Electrons for Linear Colliders

    NASA Astrophysics Data System (ADS)

    Clendenin, J. E.; Brachmann, A.; Garwin, E. L.; Kirby, R. E.; Luh, D.-A.; Maruyama, T.; Prescott, C. Y.; Sheppard, J. C.; Turner, J.; Prepost, R.

    2005-08-01

    Future electron-positron linear colliders require a highly polarized electron beam with a pulse structure that depends primarily on whether the acceleration utilizes warm or superconducting RF structures. The International Linear Collider (ILC) will use cold structures for the main linac. It is shown that a DC-biased polarized photoelectron source such as successfully used for the SLC can meet the charge requirements for the ILC micropulse with a polarization approaching 90%.

  15. Polarized Electrons for Linear Colliders

    SciTech Connect

    Clendenin, J.

    2004-11-19

    Future electron-positron linear colliders require a highly polarized electron beam with a pulse structure that depends primarily on whether the acceleration utilizes warm or superconducting rf structures. The International Linear Collider (ILC) will use cold structures for the main linac. It is shown that a dc-biased polarized photoelectron source such as successfully used for the SLC can meet the charge requirements for the ILC micropulse with a polarization approaching 90%.

  16. Linear superposition in nonlinear equations.

    PubMed

    Khare, Avinash; Sukhatme, Uday

    2002-06-17

    Several nonlinear systems such as the Korteweg-de Vries (KdV) and modified KdV equations and lambda phi(4) theory possess periodic traveling wave solutions involving Jacobi elliptic functions. We show that suitable linear combinations of these known periodic solutions yield many additional solutions with different periods and velocities. This linear superposition procedure works by virtue of some remarkable new identities involving elliptic functions. PMID:12059300

  17. Progressive Pigmentary Purpura

    MedlinePlus

    ... Category: Share: Yes No, Keep Private Progressive Pigmentary Purpura Share | Progressive pigmentary purpura (we will call it PPP) is a group ... conditions ( Schamberg's disease , Lichenoid dermatitis of Gourgerot-Blum, purpura annularis telangiectodes of Majocchi and Lichen aureus). Schamberg's ...

  18. Transformation matrices between non-linear and linear differential equations

    NASA Technical Reports Server (NTRS)

    Sartain, R. L.

    1983-01-01

    In the linearization of systems of non-linear differential equations, those systems which can be exactly transformed into the second order linear differential equation Y"-AY'-BY=0 where Y, Y', and Y" are n x 1 vectors and A and B are constant n x n matrices of real numbers were considered. The 2n x 2n matrix was used to transform the above matrix equation into the first order matrix equation X' = MX. Specially the matrix M and the conditions which will diagonalize or triangularize M were studied. Transformation matrices P and P sub -1 were used to accomplish this diagonalization or triangularization to return to the solution of the second order matrix differential equation system from the first order system.

  19. Microparticles in tumor progression.

    PubMed

    Falanga, Anna; Tartari, Carmen Julia; Marchetti, Marina

    2012-04-01

    Microparticles (MP) are shed from the surface of activated or apoptotic blood cells and their levels in plasma reflect a balance between cell stimulation, proliferation, and death. MP production occurs through vesiculation of cell membranes, and involves cytoskeletal changes and a shift in the normal phospholipid asymmetry. The expression on the majority of MP of the anionic phosphatidylserine (PS) is responsible for the capacity of MP to support blood coagulation activation. In some cases, PS expression is also associated, in the same MP, with the presence of active Tissue Factor, the main activator of blood coagulation. Elevation in plasma levels of MP have been described in numerous clinical conditions, most of which also associated with an increased thrombotic risk. Particularly, MP have been found to be increased in both solid and hematological malignancies, including myeloproliferative neoplasms. A role of MP in tumor progression has been suggested by both in vitro and in vivo studies. Evidence exists that MP of platelet origin are the main players in this process, being rich in pro-angiogenic factors. The utility of measuring MP as a diagnostic and prognostic marker is currently a subject of intense investigation. The possibility to inhibit MP production by pharmacological interventions represents a future challenge. PMID:22682124

  20. A nanoscale linear-to-linear motion converter of graphene.

    PubMed

    Dai, Chunchun; Guo, Zhengrong; Zhang, Hongwei; Chang, Tienchong

    2016-08-14

    Motion conversion plays an irreplaceable role in a variety of machinery. Although many macroscopic motion converters have been widely used, it remains a challenge to convert motion at the nanoscale. Here we propose a nanoscale linear-to-linear motion converter, made of a flake-substrate system of graphene, which can convert the out-of-plane motion of the substrate into the in-plane motion of the flake. The curvature gradient induced van der Waals potential gradient between the flake and the substrate provides the driving force to achieve motion conversion. The proposed motion converter may have general implications for the design of nanomachinery and nanosensors.

  1. Polyaniline-graphene based α-amylase biosensor with a linear dynamic range in excess of 6 orders of magnitude.

    PubMed

    Teixeira, Sofia Rodrigues; Lloyd, Catherine; Yao, Seydou; Andrea Salvatore Gazze; Whitaker, Iain S; Francis, Lewis; Conlan, R Steven; Azzopardi, Ernest

    2016-11-15

    α-amylase is an established marker for diagnosis of pancreatic and salivary disease, and recent research has seen a substantial expansion of its use in therapeutic and diagnostic applications for infection, cancer and wound healing. The lack of bedside monitoring devices for α-amylase detection has hitherto restricted the clinical progress of such applications. We have developed a highly sensitive α-amylase immunosensor platform, produced via in situ electropolymerization of aniline onto a screen-printed graphene support (SPE). Covalently binding an α-amylase specific antibody to a polyaniline (PANI) layer and controlling device assembly using electrochemical impedance spectroscopy (EIS), we have achieved a highly linear response against α-amylase concentration. Each stage of the assembly was characterized using a suite of high-resolution topographical, chemical and mechanical techniques. Quantitative, highly sensitive detection was demonstrated using an artificially spiked human blood plasma samples. The device has a remarkably wide limit of quantification (0.025-1000IU/L) compared to α-amylase assays in current clinical use. With potential for simple scale up to volume manufacturing though standard semiconductor production techniques and subsequently clinical application, this biosensor will enable clinical benefit through early disease detection, and better informed administration of correct therapeutic dose of drugs used to treat α-amylase related diseases. PMID:27196256

  2. Polyaniline-graphene based α-amylase biosensor with a linear dynamic range in excess of 6 orders of magnitude.

    PubMed

    Teixeira, Sofia Rodrigues; Lloyd, Catherine; Yao, Seydou; Andrea Salvatore Gazze; Whitaker, Iain S; Francis, Lewis; Conlan, R Steven; Azzopardi, Ernest

    2016-11-15

    α-amylase is an established marker for diagnosis of pancreatic and salivary disease, and recent research has seen a substantial expansion of its use in therapeutic and diagnostic applications for infection, cancer and wound healing. The lack of bedside monitoring devices for α-amylase detection has hitherto restricted the clinical progress of such applications. We have developed a highly sensitive α-amylase immunosensor platform, produced via in situ electropolymerization of aniline onto a screen-printed graphene support (SPE). Covalently binding an α-amylase specific antibody to a polyaniline (PANI) layer and controlling device assembly using electrochemical impedance spectroscopy (EIS), we have achieved a highly linear response against α-amylase concentration. Each stage of the assembly was characterized using a suite of high-resolution topographical, chemical and mechanical techniques. Quantitative, highly sensitive detection was demonstrated using an artificially spiked human blood plasma samples. The device has a remarkably wide limit of quantification (0.025-1000IU/L) compared to α-amylase assays in current clinical use. With potential for simple scale up to volume manufacturing though standard semiconductor production techniques and subsequently clinical application, this biosensor will enable clinical benefit through early disease detection, and better informed administration of correct therapeutic dose of drugs used to treat α-amylase related diseases.

  3. LINEAR COUNT-RATE METER

    DOEpatents

    Henry, J.J.

    1961-09-01

    A linear count-rate meter is designed to provide a highly linear output while receiving counting rates from one cycle per second to 100,000 cycles per second. Input pulses enter a linear discriminator and then are fed to a trigger circuit which produces positive pulses of uniform width and amplitude. The trigger circuit is connected to a one-shot multivibrator. The multivibrator output pulses have a selected width. Feedback means are provided for preventing transistor saturation in the multivibrator which improves the rise and decay times of the output pulses. The multivibrator is connected to a diode-switched, constant current metering circuit. A selected constant current is switched to an averaging circuit for each pulse received, and for a time determined by the received pulse width. The average output meter current is proportional to the product of the counting rate, the constant current, and the multivibrator output pulse width.

  4. Belos Block Linear Solvers Package

    2004-03-01

    Belos is an extensible and interoperable framework for large-scale, iterative methods for solving systems of linear equations with multiple right-hand sides. The motivation for this framework is to provide a generic interface to a collection of algorithms for solving large-scale linear systems. Belos is interoperable because both the matrix and vectors are considered to be opaque objects--only knowledge of the matrix and vectors via elementary operations is necessary. An implementation of Balos is accomplished viamore » the use of interfaces. One of the goals of Belos is to allow the user flexibility in specifying the data representation for the matrix and vectors and so leverage any existing software investment. The algorithms that will be included in package are Krylov-based linear solvers, like Block GMRES (Generalized Minimal RESidual) and Block CG (Conjugate-Gradient).« less

  5. QUANTUM OPTICS. Universal linear optics.

    PubMed

    Carolan, Jacques; Harrold, Christopher; Sparrow, Chris; Martín-López, Enrique; Russell, Nicholas J; Silverstone, Joshua W; Shadbolt, Peter J; Matsuda, Nobuyuki; Oguma, Manabu; Itoh, Mikitaka; Marshall, Graham D; Thompson, Mark G; Matthews, Jonathan C F; Hashimoto, Toshikazu; O'Brien, Jeremy L; Laing, Anthony

    2015-08-14

    Linear optics underpins fundamental tests of quantum mechanics and quantum technologies. We demonstrate a single reprogrammable optical circuit that is sufficient to implement all possible linear optical protocols up to the size of that circuit. Our six-mode universal system consists of a cascade of 15 Mach-Zehnder interferometers with 30 thermo-optic phase shifters integrated into a single photonic chip that is electrically and optically interfaced for arbitrary setting of all phase shifters, input of up to six photons, and their measurement with a 12-single-photon detector system. We programmed this system to implement heralded quantum logic and entangling gates, boson sampling with verification tests, and six-dimensional complex Hadamards. We implemented 100 Haar random unitaries with an average fidelity of 0.999 ± 0.001. Our system can be rapidly reprogrammed to implement these and any other linear optical protocol, pointing the way to applications across fundamental science and quantum technologies. PMID:26160375

  6. Interventions in progressive supranuclear palsy.

    PubMed

    Koros, Christos; Stamelou, Maria

    2016-01-01

    Progressive supranuclear palsy (PSP) an atypical parkinsonian with a common phenotype comprising early falls, the characteristic slowing of vertical saccades and a frontal syndrome with marked apathy (Richardson's syndrome). Currently, no effective symptomatic or neuroprotective treatment is available for PSP. Current medical have a limited role in PSP. Novel experimental treatments include davunetide or tideglusib, both inhibitors of glycogen synthase kinase-3 (GSK-3) that failed to improve the clinical outcome of PSP patients in two recent studies. Future interventions aiming at tau dysfunction and passive or active immunization are ongoing or underway.

  7. Permafrost Hazards and Linear Infrastructure

    NASA Astrophysics Data System (ADS)

    Stanilovskaya, Julia; Sergeev, Dmitry

    2014-05-01

    The international experience of linear infrastructure planning, construction and exploitation in permafrost zone is being directly tied to the permafrost hazard assessment. That procedure should also consider the factors of climate impact and infrastructure protection. The current global climate change hotspots are currently polar and mountain areas. Temperature rise, precipitation and land ice conditions change, early springs occur more often. The big linear infrastructure objects cross the territories with different permafrost conditions which are sensitive to the changes in air temperature, hydrology, and snow accumulation which are connected to climatic dynamics. One of the most extensive linear structures built on permafrost worldwide are Trans Alaskan Pipeline (USA), Alaska Highway (Canada), Qinghai-Xizang Railway (China) and Eastern Siberia - Pacific Ocean Oil Pipeline (Russia). Those are currently being influenced by the regional climate change and permafrost impact which may act differently from place to place. Thermokarst is deemed to be the most dangerous process for linear engineering structures. Its formation and development depend on the linear structure type: road or pipeline, elevated or buried one. Zonal climate and geocryological conditions are also of the determining importance here. All the projects are of the different age and some of them were implemented under different climatic conditions. The effects of permafrost thawing have been recorded every year since then. The exploration and transportation companies from different countries maintain the linear infrastructure from permafrost degradation in different ways. The highways in Alaska are in a good condition due to governmental expenses on annual reconstructions. The Chara-China Railroad in Russia is under non-standard condition due to intensive permafrost response. Standards for engineering and construction should be reviewed and updated to account for permafrost hazards caused by the

  8. Preface: Introductory Remarks: Linear Scaling Methods

    NASA Astrophysics Data System (ADS)

    Bowler, D. R.; Fattebert, J.-L.; Gillan, M. J.; Haynes, P. D.; Skylaris, C.-K.

    2008-07-01

    It has been just over twenty years since the publication of the seminal paper on molecular dynamics with ab initio methods by Car and Parrinello [1], and the contribution of density functional theory (DFT) and the related techniques to physics, chemistry, materials science, earth science and biochemistry has been huge. Nevertheless, significant improvements are still being made to the performance of these standard techniques; recent work suggests that speed improvements of one or even two orders of magnitude are possible [2]. One of the areas where major progress has long been expected is in O(N), or linear scaling, DFT, in which the computer effort is proportional to the number of atoms. Linear scaling DFT methods have been in development for over ten years [3] but we are now in an exciting period where more and more research groups are working on these methods. Naturally there is a strong and continuing effort to improve the efficiency of the methods and to make them more robust. But there is also a growing ambition to apply them to challenging real-life problems. This special issue contains papers submitted following the CECAM Workshop 'Linear-scaling ab initio calculations: applications and future directions', held in Lyon from 3-6 September 2007. A noteworthy feature of the workshop is that it included a significant number of presentations involving real applications of O(N) methods, as well as work to extend O(N) methods into areas of greater accuracy (correlated wavefunction methods, quantum Monte Carlo, TDDFT) and large scale computer architectures. As well as explicitly linear scaling methods, the conference included presentations on techniques designed to accelerate and improve the efficiency of standard (that is non-linear-scaling) methods; this highlights the important question of crossover—that is, at what size of system does it become more efficient to use a linear-scaling method? As well as fundamental algorithmic questions, this brings up

  9. Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study

    PubMed Central

    Lu, Ching-Hua; Petzold, Axel; Topping, Jo; Allen, Kezia; Macdonald-Wallis, Corrie; Clarke, Jan; Pearce, Neil; Kuhle, Jens; Giovannoni, Gavin; Fratta, Pietro; Sidle, Katie; Fish, Mark; Orrell, Richard; Howard, Robin; Greensmith, Linda; Malaspina, Andrea

    2015-01-01

    Objective To investigate the role of longitudinal plasma neurofilament heavy chain protein (NfH) levels as an indicator of clinical progression and survival in amyotrophic lateral sclerosis (ALS). Methods A cross-sectional study involving 136 clinically heterogeneous patients with ALS and 104 healthy and neurological controls was extended to include a prospective analysis of 74 of these ALS cases, with samplings at approximately 3-month intervals in a follow-up period of up to 3 years. We analysed the correlation between longitudinal NfH-phosphoform levels and disease progression. Temporal patterns of NfH changes were evaluated using multilevel linear regression. Results Baseline plasma NfH levels were higher than controls only in patients with ALS with short disease duration to baseline sampling. Compared with controls, fast-progressing patients with ALS, particularly those with a short diagnostic latency and disease duration, had higher plasma NfH levels at an early stage and lower levels closer to end-stage disease. Lower NfH levels between visits were associated with rapid functional deterioration. We also detected antibodies against NfH, NfH aggregates and NfH cleavage products. Conclusions Disease progression in ALS involves defined trajectories of plasma NfH levels, reflecting speed of neurological decline and survival. Intervisit plasma NfH changes are also indicative of disease progression. This study confirms that longitudinal measurements of NfH plasma levels are more informative than cross-sectional studies, where the time of sampling may represent a bias in the interpretation of the results. Autoantibodies against NfH aggregates and NfH cleavage products may explain the variable expression of plasma NfH with disease progression. Trail registration number NIHRID6160. PMID:25009280

  10. Vanilla technicolor at linear colliders

    NASA Astrophysics Data System (ADS)

    Frandsen, Mads T.; Järvinen, Matti; Sannino, Francesco

    2011-08-01

    We analyze the reach of linear colliders for models of dynamical electroweak symmetry breaking. We show that linear colliders can efficiently test the compositeness scale, identified with the mass of the new spin-one resonances, until the maximum energy in the center of mass of the colliding leptons. In particular we analyze the Drell-Yan processes involving spin-one intermediate heavy bosons decaying either leptonically or into two standard model gauge bosons. We also analyze the light Higgs production in association with a standard model gauge boson stemming also from an intermediate spin-one heavy vector.

  11. Characterizations of linear sufficient statistics

    NASA Technical Reports Server (NTRS)

    Peters, B. C., Jr.; Reoner, R.; Decell, H. P., Jr.

    1977-01-01

    A surjective bounded linear operator T from a Banach space X to a Banach space Y must be a sufficient statistic for a dominated family of probability measures defined on the Borel sets of X. These results were applied, so that they characterize linear sufficient statistics for families of the exponential type, including as special cases the Wishart and multivariate normal distributions. The latter result was used to establish precisely which procedures for sampling from a normal population had the property that the sample mean was a sufficient statistic.

  12. Linear Corrugating - Final Technical Report

    SciTech Connect

    Lloyd Chapman

    2000-05-23

    Linear Corrugating is a process for the manufacture of corrugated containers in which the flutes of the corrugated medium are oriented in the Machine Direction (MD) of the several layers of paper used. Conversely, in the conventional corrugating process the flutes are oriented at right angles to the MD in the Cross Machine Direction (CD). Paper is stronger in MD than in CD. Therefore, boxes made using the Linear Corrugating process are significantly stronger-in the prime strength criteria, Box Compression Test (BCT) than boxes made conventionally. This means that using Linear Corrugating boxes can be manufactured to BCT equaling conventional boxes but containing 30% less fiber. The corrugated container industry is a large part of the U.S. economy, producing over 40 million tons annually. For such a large industry, the potential savings of Linear Corrugating are enormous. The grant for this project covered three phases in the development of the Linear Corrugating process: (1) Production and evaluation of corrugated boxes on commercial equipment to verify that boxes so manufactured would have enhanced BCT as proposed in the application; (2) Production and evaluation of corrugated boxes made on laboratory equipment using combined board from (1) above but having dual manufactures joints (glue joints). This box manufacturing method (Dual Joint) is proposed to overcome box perimeter limitations of the Linear Corrugating process; (3) Design, Construction, Operation and Evaluation of an engineering prototype machine to form flutes in corrugating medium in the MD of the paper. This operation is the central requirement of the Linear Corrugating process. Items I and II were successfully completed, showing predicted BCT increases from the Linear Corrugated boxes and significant strength improvement in the Dual Joint boxes. The Former was constructed and operated successfully using kraft linerboard as the forming medium. It was found that tensile strength and stretch

  13. [Aspiration biopsy, puncture and neurolysis of coeliac plexus with guided linear endoscopic ultrasonography--personal experience].

    PubMed

    Milinić, N

    2005-01-01

    Endoscopic ultrasonography, as relatively new diagnostic procedure, has made a significant progress in detection and presentation of small lesions of digestive tract, as well as in other organs. By introducing linear ultrasonography in clinical practice, the possibilities of this procedure became even more apparent, anabling even more precise diagnosis and various therapeutic procedures. With endoscopic ultrasound (EUS) guided aspiration biopsy it is possible to obtain samples in specific, well defined layer of gastrointestinal tract wall, and also from different parts of other organs and formations, which finaly enables establishing definite patohystologic diagnosis. First linear EUS procedure in this part of south-east Europe, was performed in University Clinical Center "Bezanijska Kosa" (N. Milinic, M. Petrovic) in 1999, and first EUS guided aspiration biopsy was performed on July 4th 2000 (N. Milinic--biopsy of pancreas). Using "Pentax" FG-36UX linear echo-endoscope, until now, 40 pancreas biopsies, 34 stomach biopsies, 9 biopsies of mediastinal lymph nodes, cysts and tumors, 22 biopsies of masses in retroperitoneal region, 7 biopsies of papilla Vateri, 4 biopsies of left suprarenal gland, 2 punctures of renal cysts, 14 biopsies of focal liver lesions, 2 punctures of liver cysts, and 5 neurolyses of coeliac plexus was performed. From 134 EUS guided biopsy samples, 114 was, according to pathologist, adequate for patohystologic evaluation, and in 96 cases obtained samples was essential for obtaining definite diagnosis. The major problem in this issue was a lack of well trained and expirienced cytologist, as also is the current problem in Western countires with more expirience and practice in this field. EUS guided aspiration biopsy, as the procedure itself, was successful in all cases. There were no major complications during the procedures, mainly because of using Colour-Doppler technique in defferentiating vascular from other structures. Results so far are

  14. Preface: Introductory Remarks: Linear Scaling Methods

    NASA Astrophysics Data System (ADS)

    Bowler, D. R.; Fattebert, J.-L.; Gillan, M. J.; Haynes, P. D.; Skylaris, C.-K.

    2008-07-01

    It has been just over twenty years since the publication of the seminal paper on molecular dynamics with ab initio methods by Car and Parrinello [1], and the contribution of density functional theory (DFT) and the related techniques to physics, chemistry, materials science, earth science and biochemistry has been huge. Nevertheless, significant improvements are still being made to the performance of these standard techniques; recent work suggests that speed improvements of one or even two orders of magnitude are possible [2]. One of the areas where major progress has long been expected is in O(N), or linear scaling, DFT, in which the computer effort is proportional to the number of atoms. Linear scaling DFT methods have been in development for over ten years [3] but we are now in an exciting period where more and more research groups are working on these methods. Naturally there is a strong and continuing effort to improve the efficiency of the methods and to make them more robust. But there is also a growing ambition to apply them to challenging real-life problems. This special issue contains papers submitted following the CECAM Workshop 'Linear-scaling ab initio calculations: applications and future directions', held in Lyon from 3-6 September 2007. A noteworthy feature of the workshop is that it included a significant number of presentations involving real applications of O(N) methods, as well as work to extend O(N) methods into areas of greater accuracy (correlated wavefunction methods, quantum Monte Carlo, TDDFT) and large scale computer architectures. As well as explicitly linear scaling methods, the conference included presentations on techniques designed to accelerate and improve the efficiency of standard (that is non-linear-scaling) methods; this highlights the important question of crossover—that is, at what size of system does it become more efficient to use a linear-scaling method? As well as fundamental algorithmic questions, this brings up

  15. Parkinson's disease showing progressive conduction aphasia.

    PubMed

    Sakai, Kenji; Ono, Kenjiro; Harada, Hiromi; Shima, Keisuke; Notoya, Masako; Yamada, Masahito

    2012-04-01

    Patients with Parkinson's disease (PD) may develop progressive dementia late in their clinical course. Dementia in PD is mostly related to neuropathological findings of extensive Lewy bodies (LBs), with or without the coexistence of Alzheimer's disease (AD) pathology. Aphasia has been reported in patients with LB diseases with AD pathology; however, there have been no reports of typical PD patients developing progressive aphasia during their clinical course. We describe a female PD patient who later developed progressive conduction aphasia characterized by phonemic paraphasia and disturbance in repetition of short sentences without disturbance in writing or auditory comprehension. No episodes of fluctuations of attention, memory complaints, or planning errors were observed. She experienced episodes of visual hallucination. Her low scores on the Mini-Mental State Examination suggested impairment of orientation and attention, and her scores on Raven's Coloured Progressive Matrices test indicated impaired visuospatial functions. However, her cognitive deficits were not sufficiently severe to impair her daily life. Brain magnetic resonance images revealed atrophy of the left superior temporal gyrus and widening of the left sylvian fissure. [(18)F]-fluorodeoxyglucose positron emission tomography revealed glucose hypometabolism in the left cerebral hemisphere. These findings may be related to conduction aphasia. During the progression of PD lesions, the brainstem LB is assumed to take an upward course, extend to the limbic system, and then extend to the neocortex. Conduction aphasia observed in our patient may be associated with an unusual progression of the LB pathology from the brainstem to the left temporoparietal lobe. PMID:21879327

  16. Research Progress on Vertebrobasilar Dolichoectasia

    PubMed Central

    Yuan, Yong-Jie; Xu, Kan; Luo, Qi; Yu, Jin-Lu

    2014-01-01

    Vertebrobasilar dolichoectasia (VBD) is a rare disease characterized by significant expansion, elongation, and tortuosity of the vertebrobasilar arteries. Current data regarding VBD are very limited. Here we systematically review VBD incidence, etiology, characteristics, clinical manifestations, treatment strategies, and prognosis. The exact incidence rate of VBD remains unclear, but is estimated to be 1.3% of the population. The occurrence of VBD is thought to be due to the cooperation of multiple factors, including congenital factors, infections and immune status, and degenerative diseases. The VBD clinical manifestations are complex with ischemic stroke as the most common, followed by progressive compression of cranial nerves and the brain stem, cerebral hemorrhage, and hydrocephalus. Treatment of VBD remains difficult. Currently, there are no precise and effective treatments, and available treatments mainly target the complications of VBD. With the development of stent technology, however, it may become an effective treatment for VBD. PMID:25136259

  17. Gene therapy: progress and predictions

    PubMed Central

    Collins, Mary; Thrasher, Adrian

    2015-01-01

    The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of viral vectors. There are also a number of promising gene therapy approaches for cancer and infectious disease. We predict that the next 25 years will see improvements in safety, efficacy and manufacture of gene delivery vectors and introduction of gene-editing technologies to the clinic. Gene delivery may also prove a cost-effective method for the delivery of biological medicines. PMID:26702034

  18. Insulin-like growth factor-binding protein 2-driven glioma progression is prevented by blocking a clinically significant integrin, integrin-linked kinase, and NF-κB network

    PubMed Central

    Holmes, Kristen M.; Annala, Matti; Chua, Corrine Y. X.; Dunlap, Sarah M.; Liu, Yuexin; Hugen, Niek; Moore, Lynette M.; Cogdell, David; Hu, Limei; Nykter, Matti; Hess, Kenneth; Fuller, Gregory N.; Zhang, Wei

    2012-01-01

    Insulin-like growth factor-binding protein 2 (IGFBP2) is increasingly recognized as a glioma oncogene, emerging as a target for therapeutic intervention. In this study, we used an integrative approach to characterizing the IGFBP2 network, combining transcriptional profiling of human glioma with validation in glial cells and the replication-competent ASLV long terminal repeat with a splice acceptor/tv-a glioma mouse system. We demonstrated that IGFBP2 expression is closely linked to genes in the integrin and integrin-linked kinase (ILK) pathways and that these genes are associated with prognosis. We further showed that IGFBP2 activates integrin β1 and downstream invasion pathways, requires ILK to induce cell motility, and activates NF-κB. Most significantly, the IGFBP2/integrin/ILK/NF-κB network functions as a physiologically active signaling pathway in vivo by driving glioma progression; interfering with any point in the pathway markedly inhibits progression. The results of this study reveal a signaling pathway that is both targetable and highly relevant to improving the survival of glioma patients. PMID:22345562

  19. Progress in Understanding Autism: 2007-2010

    ERIC Educational Resources Information Center

    Rutter, Michael L.

    2011-01-01

    Scientific progress is discussed in relation to clinical issues; genetic issues; environmental issues; and the state of play on psychological treatments. It is concluded that substantial gains in knowledge have been achieved during the last 3 years, and there have been some unexpected findings, but major puzzles remain. We should be hopeful of…

  20. Linear Programming Applied to a Simple Circuit.

    ERIC Educational Resources Information Center

    Boyd, J. N.; Raychowdhury, P. N.

    1980-01-01

    Discusses what is meant by a linear program and states and illustrates two of the theorems upon which the methods of linear programing rest. This description is intended as an introduction to linear programing of physics students. (HM)