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Sample records for applications proof-of-concept model

  1. Application of Multivariate Modeling for Radiation Injury Assessment: A Proof of Concept

    Directory of Open Access Journals (Sweden)

    David L. Bolduc

    2014-01-01

    Full Text Available Multivariate radiation injury estimation algorithms were formulated for estimating severe hematopoietic acute radiation syndrome (H-ARS injury (i.e., response category three or RC3 in a rhesus monkey total-body irradiation (TBI model. Classical CBC and serum chemistry blood parameters were examined prior to irradiation (d 0 and on d 7, 10, 14, 21, and 25 after irradiation involving 24 nonhuman primates (NHP (Macaca mulatta given 6.5-Gy 60Co Υ-rays (0.4 Gy min−1 TBI. A correlation matrix was formulated with the RC3 severity level designated as the “dependent variable” and independent variables down selected based on their radioresponsiveness and relatively low multicollinearity using stepwise-linear regression analyses. Final candidate independent variables included CBC counts (absolute number of neutrophils, lymphocytes, and platelets in formulating the “CBC” RC3 estimation algorithm. Additionally, the formulation of a diagnostic CBC and serum chemistry “CBC-SCHEM” RC3 algorithm expanded upon the CBC algorithm model with the addition of hematocrit and the serum enzyme levels of aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. Both algorithms estimated RC3 with over 90% predictive power. Only the CBC-SCHEM RC3 algorithm, however, met the critical three assumptions of linear least squares demonstrating slightly greater precision for radiation injury estimation, but with significantly decreased prediction error indicating increased statistical robustness.

  2. Integrated Workforce Planning Model: A Proof of Concept

    Science.gov (United States)

    Guruvadoo, Eranna K.

    2001-01-01

    Recently, the Workforce and Diversity Management Office at KSC have launched a major initiative to develop and implement a competency/skill approach to Human Resource management. As the competency/skill dictionary is being elaborated, the need for a competency-based workforce-planning model is recognized. A proof of concept for such a model is presented using a multidimensional data model that can provide the data infrastructure necessary to drive intelligent decision support systems for workforce planing. The components of competency-driven workforce planning model are explained. The data model is presented and several schemes that would support the workforce-planning model are presented. Some directions and recommendations for future work are given.

  3. Proof-of-Concept Application of Tier 2 Modeling Approach within the Training Range Environmental Evaluation And Characterization System

    Science.gov (United States)

    2011-08-01

    coefficient of the two metals for this soil. The percent for sand was reduced from 65 to 63.8, since the percentage of all components must sum to 100...model solves time-varying reactive transport assuming steady, uniform , one-dimensional horizontal flow and advection with three- dimensional...as discussed in the section titled “Site Dimensions and Physical Characteristics.” Surface water morphometry and hydrology information must be

  4. A Real-Time Open Access Platform Towards Proof of Concept for Smart Grid Applications

    DEFF Research Database (Denmark)

    Kemal, Mohammed Seifu; Petersen, Lennart; Iov, Florin

    2017-01-01

    This paper presents development of real time open access platform towards proof of concept of smart grid applications deployed at Smart Energy System Laboratory of Aalborg University. Discussed on the paper is the architecture and set-up of the platform by elaborating the three main layers...

  5. Integrated surface/subsurface permafrost thermal hydrology: Model formulation and proof-of-concept simulations

    Science.gov (United States)

    Painter, Scott L.; Coon, Ethan T.; Atchley, Adam L.; Berndt, Markus; Garimella, Rao; Moulton, J. David; Svyatskiy, Daniil; Wilson, Cathy J.

    2016-08-01

    The need to understand potential climate impacts and feedbacks in Arctic regions has prompted recent interest in modeling of permafrost dynamics in a warming climate. A new fine-scale integrated surface/subsurface thermal hydrology modeling capability is described and demonstrated in proof-of-concept simulations. The new modeling capability combines a surface energy balance model with recently developed three-dimensional subsurface thermal hydrology models and new models for nonisothermal surface water flows and snow distribution in the microtopography. Surface water flows are modeled using the diffusion wave equation extended to include energy transport and phase change of ponded water. Variation of snow depth in the microtopography, physically the result of wind scour, is modeled phenomenologically with a diffusion wave equation. The multiple surface and subsurface processes are implemented by leveraging highly parallel community software. Fully integrated thermal hydrology simulations on the tilted open book catchment, an important test case for integrated surface/subsurface flow modeling, are presented. Fine-scale 100 year projections of the integrated permafrost thermal hydrological system on an ice wedge polygon at Barrow Alaska in a warming climate are also presented. These simulations demonstrate the feasibility of microtopography-resolving, process-rich simulations as a tool to help understand possible future evolution of the carbon-rich Arctic tundra in a warming climate.

  6. Density and Flow-Velocity Measurement Technology for Dredging Applications - Proof of Concept Study

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, Margaret S.; Tucker, Brian J.; Diaz, Aaron A.

    2004-10-01

    This technical letter report provides the results of all PNNL managed activities on this project, and contains a description of the data acquisition configuration and testing protocols, results and conclusions from this work. This technical letter report constitutes the final deliverable to be submitted to the client for this proof-of-concept study.

  7. A simplified chemistry module for atmospheric transport and dispersion models: Proof-of-concept using SCIPUFF

    Science.gov (United States)

    Burns, Douglas S.; Rottmann, Shawn D.; Plitz, Angela B. L.; Wiseman, Floyd L.; Moore, William; Chynwat, Veeradej

    2012-09-01

    An atmospheric chemistry module was developed to predict the fate of environmentally hazardous compounds discharged into the atmosphere. The computationally efficient model captures the diurnal variation within the environment and in the degradation rates of the released compounds, follows the formation of toxic degradation products, runs rapidly, and in principle can be integrated with any atmospheric transport and dispersion model. To accomplish this, a detailed atmospheric chemistry mechanism for a target toxic industrial compound (TIC) was reduced to a simple empirical effective degradation rate term (keff). Empirically derived decay functions for keff were developed as a function of important meteorological parameters such as solar flux, temperature, humidity, and cloud cover for various land uses and locations by statistically analyzing data generated from a detailed chemistry mechanism run over a wide range of (typical) atmospheric conditions. 1-Butene and two degradation products (propanal and nitrooxybutanone) were used as representative chemicals in the algorithm development for this proof-of-concept demonstration of the capability of the model. The quality of the developed model was evaluated via comparison with experimental chamber data and the results (decay rates) compared favorably for ethene, propene, and 1-butene (within a factor of two 75% or more of the time).

  8. Validation, Proof-of-Concept, and Postaudit of the Groundwater Flow and Transport Model of the Project Shoal Area

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed Hassan

    2004-09-01

    The groundwater flow and radionuclide transport model characterizing the Shoal underground nuclear test has been accepted by the State of Nevada Division of Environmental Protection. According to the Federal Facility Agreement and Consent Order (FFACO) between DOE and the State of Nevada, the next steps in the closure process for the site are then model validation (or postaudit), the proof-of-concept, and the long-term monitoring stage. This report addresses the development of the validation strategy for the Shoal model, needed for preparing the subsurface Corrective Action Decision Document-Corrective Action Plan and the development of the proof-of-concept tools needed during the five-year monitoring/validation period. The approach builds on a previous model, but is adapted and modified to the site-specific conditions and challenges of the Shoal site.

  9. Proof-of-Concept Experiments on a Gallium-Based Ignitron for Pulsed Power Applications

    Science.gov (United States)

    Ali, H. K.; Hanson, V. S.; Polzin, K. A.; Pearson, J. B.

    2015-01-01

    ignitron designs have used mercury as the liquid metal cathode, owing to its presence as a liquid at room temperatures and a vapor pressure of 10 Pa (75 mtorr) at room temperature. While these are favorable properties, there are obvious environmental and personal safety concerns with the storage, handling, and use of mercury and its compounds. The purpose of the present work was to fabricate and test an ignitron that used as its cathode an alternate liquid metal that was safe to handle and store. To that end, an ignitron test article that used liquid gallium as the cathode material was developed and tested. Gallium is a metal that has a melting temperature of 29.76 C, which is slightly above room temperature, and a boiling point of over 2,300 C at atmospheric pressure. This property makes gallium the element with the largest relative difference between melting and boiling points. Gallium has a limited role in biology, and when ingested, it will be subsequently processed by the body and expelled rather than accumulating to toxic levels. The next section of this Technical Memorandum (TM) provides background information on the development of mercury-based ignitrons, which serves as the starting point for the development of the gallium-based variant. Afterwards, the experimental hardware and setup used in proof-of-concept testing of a basic gallium ignitron are presented. Experimental data, consisting of discharge voltage and current waveforms as well as high-speed imaging of the gallium arc discharge in the gallium ignitron test article, are presented to demonstrate the efficacy of the concept. Discussion of the data and suggestions on improvements for future iterations of the design are presented in the final two sections of this TM.

  10. Hyperbrain features of team mental models within a juggling paradigm: a proof of concept

    Directory of Open Access Journals (Sweden)

    Edson Filho

    2016-09-01

    Full Text Available Background Research on cooperative behavior and the social brain exists, but little research has focused on real-time motor cooperative behavior and its neural correlates. In this proof of concept study, we explored the conceptual notion of shared and complementary mental models through EEG mapping of two brains performing a real-world interactive motor task of increasing difficulty. We used the recently introduced participative “juggling paradigm,” and collected neuro-physiological and psycho-social data. We were interested in analyzing the between-brains coupling during a dyadic juggling task, and in exploring the relationship between the motor task execution, the jugglers’skill level and the task difficulty. We also investigated how this relationship could be mirrored in the coupled functional organization of the interacting brains. Methods To capture the neural schemas underlying the notion of shared and complementary mental models, we examined the functional connectivity patterns and hyperbrain features of a juggling dyad involved in cooperative motor tasks of increasing difficulty. Jugglers’ cortical activity was measured using two synchronized 32-channel EEG systems during dyadic juggling performed with 3, 4, 5 and 6 balls. Individual and hyperbrain functional connections were quantified through coherence maps calculated across all electrode pairs in the theta and alpha bands (4–8 and 8–12 Hz. Graph metrics were used to typify the global topology and efficiency of the functional networks for the four difficulty levels in the theta and alpha bands. Results Results indicated that, as task difficulty increased, the cortical functional organization of the more skilled juggler became progressively more segregated in both frequency bands, with a small-world organization in the theta band during easier tasks, indicative of a flow-like state in line with the neural efficiency hypothesis. Conversely, more integrated functional patterns

  11. Urban Form Energy Use and Emissions in China: Preliminary Findings and Model Proof of Concept

    Energy Technology Data Exchange (ETDEWEB)

    Aden, Nathaniel; Qin, Yining; Fridley, David

    2010-12-15

    Urbanization is reshaping China's economy, society, and energy system. Between 1990 and 2008 China added more than 300 million new urban residents, bringing the total urbanization rate to 46%. The ongoing population shift is spurring energy demand for new construction, as well as additional residential use with the replacement of rural biomass by urban commercial energy services. This project developed a modeling tool to quantify the full energy consequences of a particular form of urban residential development in order to identify energy- and carbon-efficient modes of neighborhood-level development and help mitigate resource and environmental implications of swelling cities. LBNL developed an integrated modeling tool that combines process-based lifecycle assessment with agent-based building operational energy use, personal transport, and consumption modeling. The lifecycle assessment approach was used to quantify energy and carbon emissions embodied in building materials production, construction, maintenance, and demolition. To provide more comprehensive analysis, LBNL developed an agent-based model as described below. The model was applied to LuJing, a residential development in Jinan, Shandong Province, to provide a case study and model proof of concept. This study produced results data that are unique by virtue of their scale, scope and type. Whereas most existing literature focuses on building-, city-, or national-level analysis, this study covers multi-building neighborhood-scale development. Likewise, while most existing studies focus exclusively on building operational energy use, this study also includes embodied energy related to personal consumption and buildings. Within the boundaries of this analysis, food is the single largest category of the building energy footprint, accounting for 23% of the total. On a policy level, the LCA approach can be useful for quantifying the energy and environmental benefits of longer average building lifespans. In

  12. Accelerating the commercialization of university technologies for military healthcare applications: the role of the proof of concept process

    Science.gov (United States)

    Ochoa, Rosibel; DeLong, Hal; Kenyon, Jessica; Wilson, Eli

    2011-06-01

    The von Liebig Center for Entrepreneurism and Technology Advancement at UC San Diego (vonliebig.ucsd.edu) is focused on accelerating technology transfer and commercialization through programs and education on entrepreneurism. Technology Acceleration Projects (TAPs) that offer pre-venture grants and extensive mentoring on technology commercialization are a key component of its model which has been developed over the past ten years with the support of a grant from the von Liebig Foundation. In 2010, the von Liebig Entrepreneurism Center partnered with the U.S. Army Telemedicine and Advanced Technology Research Center (TATRC), to develop a regional model of Technology Acceleration Program initially focused on military research to be deployed across the nation to increase awareness of military medical needs and to accelerate the commercialization of novel technologies to treat the patient. Participants to these challenges are multi-disciplinary teams of graduate students and faculty in engineering, medicine and business representing universities and research institutes in a region, selected via a competitive process, who receive commercialization assistance and funding grants to support translation of their research discoveries into products or services. To validate this model, a pilot program focused on commercialization of wireless healthcare technologies targeting campuses in Southern California has been conducted with the additional support of Qualcomm, Inc. Three projects representing three different universities in Southern California were selected out of forty five applications from ten different universities and research institutes. Over the next twelve months, these teams will conduct proof of concept studies, technology development and preliminary market research to determine the commercial feasibility of their technologies. This first regional program will help build the needed tools and processes to adapt and replicate this model across other regions in the

  13. Proof of Concept: Model Based Bionic Muscle with Hyperbolic Force-Velocity Relation

    Directory of Open Access Journals (Sweden)

    D. F. B. Haeufle

    2012-01-01

    Full Text Available Recently, the hyperbolic Hill-type force-velocity relation was derived from basic physical components. It was shown that a contractile element CE consisting of a mechanical energy source (active element AE, a parallel damper element (PDE, and a serial element (SE exhibits operating points with hyperbolic force-velocity dependency. In this paper, a technical proof of this concept was presented. AE and PDE were implemented as electric motors, SE as a mechanical spring. The force-velocity relation of this artificial CE was determined in quick release experiments. The CE exhibited hyperbolic force-velocity dependency. This proof of concept can be seen as a well-founded starting point for the development of Hill-type artificial muscles.

  14. Supercritical CO2 Foaming of Thermoplastic Materials Derived from Maize: Proof-of-Concept Use in Mammalian Cell Culture Applications

    Science.gov (United States)

    Trujillo-de Santiago, Grissel; Portales-Cabrera, Cynthia Guadalupe; Portillo-Lara, Roberto; Araiz-Hernández, Diana; Del Barone, Maria Cristina; García-López, Erika; Rojas-de Gante, Cecilia; de los Angeles De Santiago-Miramontes, María; Segoviano-Ramírez, Juan Carlos; García-Lara, Silverio; Rodríguez-González, Ciro Ángel; Alvarez, Mario Moisés; Di Maio, Ernesto; Iannace, Salvatore

    2015-01-01

    Background Foams are high porosity and low density materials. In nature, they are a common architecture. Some of their relevant technological applications include heat and sound insulation, lightweight materials, and tissue engineering scaffolds. Foams derived from natural polymers are particularly attractive for tissue culture due to their biodegradability and bio-compatibility. Here, the foaming potential of an extensive list of materials was assayed, including slabs elaborated from whole flour, the starch component only, or the protein fraction only of maize seeds. Methodology/Principal Findings We used supercritical CO2 to produce foams from thermoplasticized maize derived materials. Polyethylene-glycol, sorbitol/glycerol, or urea/formamide were used as plasticizers. We report expansion ratios, porosities, average pore sizes, pore morphologies, and pore size distributions for these materials. High porosity foams were obtained from zein thermoplasticized with polyethylene glycol, and from starch thermoplasticized with urea/formamide. Zein foams had a higher porosity than starch foams (88% and 85%, respectively) and a narrower and more evenly distributed pore size. Starch foams exhibited a wider span of pore sizes and a larger average pore size than zein (208.84 vs. 55.43 μm2, respectively). Proof-of-concept cell culture experiments confirmed that mouse fibroblasts (NIH 3T3) and two different prostate cancer cell lines (22RV1, DU145) attached to and proliferated on zein foams. Conclusions/Significance We conducted screening and proof-of-concept experiments on the fabrication of foams from cereal-based bioplastics. We propose that a key indicator of foamability is the strain at break of the materials to be foamed (as calculated from stress vs. strain rate curves). Zein foams exhibit attractive properties (average pore size, pore size distribution, and porosity) for cell culture applications; we were able to establish and sustain mammalian cell cultures on zein

  15. Supercritical CO2 foaming of thermoplastic materials derived from maize: proof-of-concept use in mammalian cell culture applications.

    Directory of Open Access Journals (Sweden)

    Grissel Trujillo-de Santiago

    Full Text Available Foams are high porosity and low density materials. In nature, they are a common architecture. Some of their relevant technological applications include heat and sound insulation, lightweight materials, and tissue engineering scaffolds. Foams derived from natural polymers are particularly attractive for tissue culture due to their biodegradability and bio-compatibility. Here, the foaming potential of an extensive list of materials was assayed, including slabs elaborated from whole flour, the starch component only, or the protein fraction only of maize seeds.We used supercritical CO2 to produce foams from thermoplasticized maize derived materials. Polyethylene-glycol, sorbitol/glycerol, or urea/formamide were used as plasticizers. We report expansion ratios, porosities, average pore sizes, pore morphologies, and pore size distributions for these materials. High porosity foams were obtained from zein thermoplasticized with polyethylene glycol, and from starch thermoplasticized with urea/formamide. Zein foams had a higher porosity than starch foams (88% and 85%, respectively and a narrower and more evenly distributed pore size. Starch foams exhibited a wider span of pore sizes and a larger average pore size than zein (208.84 vs. 55.43 μm2, respectively. Proof-of-concept cell culture experiments confirmed that mouse fibroblasts (NIH 3T3 and two different prostate cancer cell lines (22RV1, DU145 attached to and proliferated on zein foams.We conducted screening and proof-of-concept experiments on the fabrication of foams from cereal-based bioplastics. We propose that a key indicator of foamability is the strain at break of the materials to be foamed (as calculated from stress vs. strain rate curves. Zein foams exhibit attractive properties (average pore size, pore size distribution, and porosity for cell culture applications; we were able to establish and sustain mammalian cell cultures on zein foams for extended time periods.

  16. Hydrological modelling in a "big data" era: a proof of concept of hydrological models as web services

    Science.gov (United States)

    Buytaert, Wouter; Vitolo, Claudia

    2013-04-01

    Dealing with the massive increase in global data availability of all sorts is increasingly being known as "big data" science. Indeed, largely leveraged by the internet, a new resource of data sets emerges that are so large and heterogeneous that they become awkward to work with. New algorithms, methods and models are needed to filter such data to find trends, test hypotheses, make predictions and quantify uncertainties. As a considerable share of the data relate to environmental processes (e.g., satellite images, distributed sensor networks), this evolution provides exciting challenges for environmental sciences, and hydrology in particular. Web-enabled models are a promising approach to process large and distributed data sets, and to provide tailored products for a variety of end-users. It will also allow hydrological models to be used as building blocks in larger earth system simulation systems. However, in order to do so we need to reconsider the ways that hydrological models are built, results are made available, and uncertainties are quantified. We present the results of an experimental proof of concept of a hydrological modelling web-service to process heterogeneous hydrological data sets. The hydrological model itself consists of a set of conceptual model routines implemented with on a common platform. This framework is linked to global and local data sets through web standards provided by the Open Geospatial Consortium, as well as to a web interface that enables an end-user to request stream flow simulations from a self-defined location. In essence, the proof-of-concept can be seen as an implementation of the "Models of Everywhere" concept introduced by Beven in 2007. Although the setup is operational and effectively simulates stream flow, we identify several bottlenecks for optimal hydrological simulation in a web-context. The major challenges we identify are related to (1) model selection; (2) uncertainty quantification, and (3) user interaction and

  17. Stem cell-based treatments against stroke: observations from human proof-of-concept studies and considerations regarding clinical applicability

    Directory of Open Access Journals (Sweden)

    Thorsten Roland Doeppner

    2014-10-01

    Full Text Available Ischemic stroke remains a heavy burden for industrialized countries. The only causal therapy is the recanalization of occluded vessels via thrombolysis, which due to a narrow time window still can be offered only to a minority of patients. Since the majority of patients continues to exhibit neurological deficits even following successful thrombolysis, restorative therapies are urgently needed that promote brain remodeling and repair once stroke injury has occurred. Due to their unique properties of action, stem cell-based strategies gained increasing interest during recent years. Using various stroke models in both rodents and primates, the transplantation of stem cells, namely of bone marrow derived mesenchymal stem cells (MSCs or neural progenitor cells (NPCs, has been shown to promote neurological recovery most likely via indirect bystander actions. In view of promising observations, clinical proof-of-concept studies are currently under way, in which effects of stem and precursor cells are evaluated in human stroke patients. In this review we summarize already published studies, which due to the broad experience in other medical contexts mostly employed bone marrow-derived MSCs by means of intravenous transplantation. With the overall number of clinical trials limited in number, only a fraction of these studies used non-treated control groups, and only single studies were adequately blinded. Despite these limitations, first promising results justify the need for more elaborate clinical trials in order to make stem cell transplantation a success for stroke treatment in the future.

  18. Utilizing somatic mutation data from numerous studies for cancer research: proof of concept and applications.

    Science.gov (United States)

    Amar, D; Izraeli, S; Shamir, R

    2017-06-15

    Large cancer projects measure somatic mutations in thousands of samples, gradually assembling a catalog of recurring mutations in cancer. Many methods analyze these data jointly with auxiliary information with the aim of identifying subtype-specific results. Here, we show that somatic gene mutations alone can reliably and specifically predict cancer subtypes. Interpretation of the classifiers provides useful insights for several biomedical applications. We analyze the COSMIC database, which collects somatic mutations from The Cancer Genome Atlas (TCGA) as well as from many smaller scale studies. We use multi-label classification techniques and the Disease Ontology hierarchy in order to identify cancer subtype-specific biomarkers. Cancer subtype classifiers based on TCGA and the smaller studies have comparable performance, and the smaller studies add a substantial value in terms of validation, coverage of additional subtypes, and improved classification. The gene sets of the classifiers are used for threefold contribution. First, we refine the associations of genes to cancer subtypes and identify novel compelling candidate driver genes. Second, using our classifiers we successfully predict the primary site of metastatic samples. Third, we provide novel hypotheses regarding detection of subtype-specific synthetic lethality interactions. From the cancer research community perspective, our results suggest that curation efforts, such as COSMIC, have great added and complementary value even in the era of large international cancer projects.

  19. Efficiency of chlorophyll in gross primary productivity: A proof of concept and application in crops.

    Science.gov (United States)

    Gitelson, Anatoly A; Peng, Yi; Viña, Andrés; Arkebauer, Timothy; Schepers, James S

    2016-08-20

    One of the main factors affecting vegetation productivity is absorbed light, which is largely governed by chlorophyll. In this paper, we introduce the concept of chlorophyll efficiency, representing the amount of gross primary production per unit of canopy chlorophyll content (Chl) and incident PAR. We analyzed chlorophyll efficiency in two contrasting crops (soybean and maize). Given that they have different photosynthetic pathways (C3 vs. C4), leaf structures (dicot vs. monocot) and canopy architectures (a heliotrophic leaf angle distribution vs. a spherical leaf angle distribution), they cover a large spectrum of biophysical conditions. Our results show that chlorophyll efficiency in primary productivity is highly variable and responds to various physiological and phenological conditions, and water availability. Since Chl is accessible through non-destructive, remotely sensed techniques, the use of chlorophyll efficiency for modeling and monitoring plant optimization patterns is practical at different scales (e.g., leaf, canopy) and under widely-varying environmental conditions. Through this analysis, we directly related a functional characteristic, gross primary production with a structural characteristic, canopy chlorophyll content. Understanding the efficiency of the structural characteristic is of great interest as it allows explaining functional components of the plant system.

  20. Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model.

    Science.gov (United States)

    Linke, Lyndsey M; Wilusz, Jeffrey; Pabilonia, Kristy L; Fruehauf, Johannes; Magnuson, Roberta; Olea-Popelka, Francisco; Triantis, Joni; Landolt, Gabriele; Salman, Mo

    2016-03-01

    Influenza A viruses pose significant health and economic threats to humans and animals. Outbreaks of avian influenza virus (AIV) are a liability to the poultry industry and increase the risk for transmission to humans. There are limitations to using the AIV vaccine in poultry, creating barriers to controlling outbreaks and a need for alternative effective control measures. Application of RNA interference (RNAi) techniques hold potential; however, the delivery of RNAi-mediating agents is a well-known obstacle to harnessing its clinical application. We introduce a novel antiviral approach using bacterial vectors that target avian mucosal epithelial cells and deliver (small interfering RNA) siRNAs against two AIV genes, nucleoprotein (NP) and polymerase acidic protein (PA). Using a red fluorescent reporter, we first demonstrated vector delivery and intracellular expression in avian epithelial cells. Subsequently, we demonstrated significant reductions in AIV shedding when applying these anti-AIV vectors prophylactically. These antiviral vectors provided up to a 10,000-fold reduction in viral titers shed, demonstrating in vitro proof-of-concept for using these novel anti-AIV vectors to inhibit AIV shedding. Our results indicate this siRNA vector technology could represent a scalable and clinically applicable antiviral technology for avian and human influenza and a prototype for RNAi-based vectors against other viruses.

  1. Biomolecular structure manipulation using tailored electromagnetic radiation: a proof of concept on a simplified model of the active site of bacterial DNA topoisomerase.

    Science.gov (United States)

    Jarukanont, Daungruthai; Coimbra, João T S; Bauerhenne, Bernd; Fernandes, Pedro A; Patel, Shekhar; Ramos, Maria J; Garcia, Martin E

    2014-10-21

    We report on the viability of breaking selected bonds in biological systems using tailored electromagnetic radiation. We first demonstrate, by performing large-scale simulations, that pulsed electric fields cannot produce selective bond breaking. Then, we present a theoretical framework for describing selective energy concentration on particular bonds of biomolecules upon application of tailored electromagnetic radiation. The theory is based on the mapping of biomolecules to a set of coupled harmonic oscillators and on optimal control schemes to describe optimization of temporal shape, the phase and polarization of the external radiation. We have applied this theory to demonstrate the possibility of selective bond breaking in the active site of bacterial DNA topoisomerase. For this purpose, we have focused on a model that was built based on a case study. Results are given as a proof of concept.

  2. Semi-empirical models for chlorine activation and ozone depletion in the Antarctic stratosphere: proof of concept

    Science.gov (United States)

    Huck, P. E.; Bodeker, G. E.; Kremser, S.; McDonald, A. J.; Rex, M.; Struthers, H.

    2013-03-01

    Two semi-empirical models were developed for the Antarctic stratosphere to relate the shift of species within total chlorine (Cly = HCl + ClONO2 + HOCl + 2 × Cl2 + 2×Cl2O2 + ClO + Cl) into the active forms (here: ClOx = 2×Cl2O2 + ClO), and to relate the rate of ozone destruction to ClOx. These two models provide a fast and computationally inexpensive way to describe the inter- and intra-annual evolution of ClOx and ozone mass deficit (OMD) in the Antarctic spring. The models are based on the underlying physics/chemistry of the system and capture the key chemical and physical processes in the Antarctic stratosphere that determine the interaction between climate change and Antarctic ozone depletion. They were developed considering bulk effects of chemical mechanisms for the duration of the Antarctic vortex period and quantities averaged over the vortex area. The model equations were regressed against observations of daytime ClO and OMD providing a set of empirical fit coefficients. Both semi-empirical models are able to explain much of the intra- and inter-annual variability observed in daily ClOx and OMD time series. This proof-of-concept paper outlines the semi-empirical approach to describing the evolution of Antarctic chlorine activation and ozone depletion.

  3. Semi-empirical models for chlorine activation and ozone depletion in the Antarctic stratosphere: proof of concept

    Directory of Open Access Journals (Sweden)

    P. E. Huck

    2013-03-01

    Full Text Available Two semi-empirical models were developed for the Antarctic stratosphere to relate the shift of species within total chlorine (Cly = HCl + ClONO2 + HOCl + 2 × Cl2 + 2×Cl2O2 + ClO + Cl into the active forms (here: ClOx = 2×Cl2O2 + ClO, and to relate the rate of ozone destruction to ClOx. These two models provide a fast and computationally inexpensive way to describe the inter- and intra-annual evolution of ClOx and ozone mass deficit (OMD in the Antarctic spring. The models are based on the underlying physics/chemistry of the system and capture the key chemical and physical processes in the Antarctic stratosphere that determine the interaction between climate change and Antarctic ozone depletion. They were developed considering bulk effects of chemical mechanisms for the duration of the Antarctic vortex period and quantities averaged over the vortex area. The model equations were regressed against observations of daytime ClO and OMD providing a set of empirical fit coefficients. Both semi-empirical models are able to explain much of the intra- and inter-annual variability observed in daily ClOx and OMD time series. This proof-of-concept paper outlines the semi-empirical approach to describing the evolution of Antarctic chlorine activation and ozone depletion.

  4. Chimeric proteins combining phosphatase and cellulose-binding activities: proof-of-concept and application in the hydrolysis of paraoxon.

    Science.gov (United States)

    Gonçalves, Larissa M; Chaimovich, Hernan; Cuccovia, Iolanda M; Marana, Sandro R

    2014-05-01

    Phosphatases for organophosphate degradation and carbohydrate-binding domains (CBMs) have potential biotechnological applications. As a proof-of-concept, a soluble chimeric protein that combines acid phosphatase (AppA) from Escherichia coli and a CBM from Xanthomonas axonopodis pv. citri (AppA-CBM) was produced in E.coli. AppACBM adsorbed in microcrystalline cellulose Avicel PH101 catalyzed the hydrolysis of p-nitrophenyl phosphate (PNPP). The binding to microcrystalline cellulose displayed saturation behavior with an apparent binding constant (Kb) of 22 ± 5 mg and a maximum binding (Bmax) of 1.500 ± 0.001 enzyme units. Binding was highest at pH 2.5 and decreased above pH 6.5, as previously observed for family 2 CBMs. The Km values for PNPP of AppA-CBM and native AppA were identical (2.7 mM). To demonstrate that this strategy for protein engineering has practical applications and is largely functional, even for phosphatases exhibiting diverse folds, a chimeric protein combining human paraoxonase 1 (hPON1) and the CBM was produced. Both PON1-CBM and hPON1 had identical Km values for paraoxon (1.3 mM). Additionally, hPON1 bound to microcrystalline cellulose with a Kb of 27 ± 3 mg, the same as that observed for AppA-CBM. These data show that the phosphatase domains are as functional in both of the chimeric proteins as they are in the native enzymes and that the CBM domain maintains the same cellulose affinity. Therefore, the engineering of chimeric proteins combining domains of phosphatases and CBMs is fully feasible, resulting in chimeric enzymes that exhibit potential for OP detoxification.

  5. Computer modelling of anterior circulation stroke: Proof of concept in Cerebrovascular Occlusion

    Directory of Open Access Journals (Sweden)

    THANH G PHAN

    2014-09-01

    Full Text Available Background: Current literature emphasizes the role of the Circle of Willis (CoW in salvaging ischemic brain tissue but not that of leptomeningeal anastomoses (LA. We developed a computational model of the cerebral circulation to 1 evaluate the roles of the CoW and LA in restoring flow to the superficial compartment of the middle cerebral artery territory and 2 estimate the size of the LA required to maintain flow above the critical ischemic threshold (>30% of baseline under simulated occlusion. Methods: Cerebral vasculature was modelled as a network of junctions connected by cylindrical pipes. The experiments included occlusion of successive distal branches of the intracranial arteries while the diameters of LA were varied. Results: The model showed that the region of reduced flow became progressively smaller as the site of occlusion was moved from the large proximal to the smaller distal arteries. There was no improvement in flow in the MCA territory when the diameters of the inter-territorial LA were varied from 0.0625 mm to 0.5 mm while keeping the intra-territorial LA constant. By contrast, the diameter of the inter-territorial LA needed to be greater than 1.0 mm in order to provide adequate (>30% flow to selected arteries in the occluded MCA territory. Conclusions: The CoW and inter-territorial LA together play important supportive roles in intracranial artery occlusion. Computational modelling provides the ability to experimentally investigate the effect of arterial occlusion on CoW and LA function.

  6. Polydimethylsiloxane embedded mouse aorta ex vivo perfusion model: proof-of-concept study focusing on atherosclerosis.

    Science.gov (United States)

    Wang, Xueya; Wolf, Marc P; Keel, Rahel Bänziger; Lehner, Roman; Hunziker, Patrick R

    2012-07-01

    Existing mouse artery ex vivo perfusion models have utilized arteries such as carotid, uterine, and mesenteric arteries, but not the aorta. However, the aorta is the principal vessel analyzed for atherosclerosis studies in vivo. We have devised a mouse aorta ex vivo perfusion model that can bridge this gap. Aortas from apoE((-/-)) mice are embedded in a transparent, gas-permeable, and elastic polymer matrix [polydimethylsiloxane (PDMS)] and artificially perfused with cell culture medium under cell culture conditions. After 24 h of artificial ex vivo perfusion, no evidence of cellular apoptosis is detected. Utilizing a standard confocal microscope, it is possible to image specific receptor targeting of cells in atherosclerotic plaques during 24 h. Imaging motion artifacts are minimal due to the polymer matrix embedding. Re-embedding of the aorta enables tissue sectioning and immuno-histochemical analysis. The ex vivo data are validated by comparison with in vivo experiments. This model can save animal lives via production of multiple endpoints in a single experiment, is easy to apply, and enables straightforward comparability with pre-existing atherosclerosis in vivo data. It is suited to investigate atherosclerotic disease in particular and vascular biology in general.

  7. Risk assessment for job burnout with a mobile health web application using questionnaire data: a proof of concept study.

    Science.gov (United States)

    von Känel, Roland; van Nuffel, Marc; Fuchs, Walther J

    2016-01-01

    Job burnout has become a rampant epidemic in working societies, causing high productivity loss and healthcare costs. An easy accessible tool to detect clinically relevant risk may bear the potential to timely avert the dire sequelae of burnout. As a start, we performed a proof of concept study to test the utilization of a mobile health web application for a free and anonymous burnout risk assessment with established questionnaires. We designed a client-side javascript web application for users who filled out demographic and psychometric data forms over the internet. Users were recruited through social media, back links from hospital websites, and search engine optimization. Similar to population-based studies, we used the Maslach Burnout Inventory-General Survey (MBI-GS) to calculate a burnout risk index (BRIX). As additional mental health burden indices, users filled out the Perceived Stress Scale, Insomina Severity Index, and Profile of Mood States. Within six months, the MBI-GS was completed by 11,311 users (median age 33 years, 85 % women) of whom 20.0 % had no clinically relevant burnout risk, 54.7 % had mild-to-moderate risk, and 25.3 % had high risk. In the 2947 users completing all questionnaires, female sex (B = -0.03), cohabiting (B = -0.03), negative affect (B = 0.46), positive affect (B = -0.20), perceived stress (B = 0.18), and insomnia symptoms (B = 0.04) explained 56.2 % of the variance in the continuously scaled BRIX. The reliability was good to excellent for all psychometric scales. The weighting of the BRIX with mental health burden indices primarily modified the risk in users with mild-to-moderate burnout risk. A low-threshold web application can reliably assess the risk of job burnout. As the bulk of users had clinically relevant burnout scores, a web application may be useful to target employees at risk. The clinical value of the BRIX and its modification with coexistent/absent mental health burden awaits

  8. Semi-empirical models for chlorine activation and ozone depletion in the Antarctic stratosphere: proof of concept

    Directory of Open Access Journals (Sweden)

    P. E. Huck

    2012-10-01

    Full Text Available Two semi-empirical models were developed for the Antarctic stratosphere to relate the shift of species within total chlorine (Cly = HCl + ClONO2 + HOCl + 2 × Cl2 + 2 × Cl2O2 + ClO + Cl into the active forms (here: ClOx = 2 × Cl2O2 + ClO, and to relate the rate of ozone destruction to ClOx. These two models provide a fast and computationally inexpensive way to describe the inter- and intra-annual evolution of ClOx and ozone mass deficit (OMD in the Antarctic spring. The models are based on the underlying physics/chemistry of the system and capture the key chemical and physical processes in the Antarctic stratosphere that determine the interaction between climate change and Antarctic ozone depletion. They were developed considering bulk effects of chemical mechanisms for the duration of the Antarctic vortex period and quantities averaged over the vortex area. The model equations were regressed against observations of daytime ClO and OMD providing a set of empirical fit coefficients. Both semi-empirical models are able to explain much of the intra- and inter-annual variability observed in daily ClOx and OMD time series. This proof-of-concept paper outlines the semi-empirical approach to describing the evolution of Antarctic chlorine activation and ozone depletion.

  9. Selection of reliable biomarkers from PCR array analyses using relative distance computational model: methodology and proof-of-concept study.

    Directory of Open Access Journals (Sweden)

    Chunsheng Liu

    Full Text Available It is increasingly evident about the difficulty to monitor chemical exposure through biomarkers as almost all the biomarkers so far proposed are not specific for any individual chemical. In this proof-of-concept study, adult male zebrafish (Danio rerio were exposed to 5 or 25 µg/L 17β-estradiol (E2, 100 µg/L lindane, 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or 15 mg/L arsenic for 96 h, and the expression profiles of 59 genes involved in 7 pathways plus 2 well characterized biomarker genes, vtg1 (vitellogenin1 and cyp1a1 (cytochrome P450 1A1, were examined. Relative distance (RD computational model was developed to screen favorable genes and generate appropriate gene sets for the differentiation of chemicals/concentrations selected. Our results demonstrated that the known biomarker genes were not always good candidates for the differentiation of pair of chemicals/concentrations, and other genes had higher potentials in some cases. Furthermore, the differentiation of 5 chemicals/concentrations examined were attainable using expression data of various gene sets, and the best combination was the set consisting of 50 genes; however, as few as two genes (e.g. vtg1 and hspa5 [heat shock protein 5] were sufficient to differentiate the five chemical/concentration groups in the present test. These observations suggest that multi-parameter arrays should be more reliable for biomonitoring of chemical exposure than traditional biomarkers, and the RD computational model provides an effective tool for the selection of parameters and generation of parameter sets.

  10. Selection of reliable biomarkers from PCR array analyses using relative distance computational model: methodology and proof-of-concept study.

    Science.gov (United States)

    Liu, Chunsheng; Xu, Hongyan; Lam, Siew Hong; Gong, Zhiyuan

    2013-01-01

    It is increasingly evident about the difficulty to monitor chemical exposure through biomarkers as almost all the biomarkers so far proposed are not specific for any individual chemical. In this proof-of-concept study, adult male zebrafish (Danio rerio) were exposed to 5 or 25 µg/L 17β-estradiol (E2), 100 µg/L lindane, 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 15 mg/L arsenic for 96 h, and the expression profiles of 59 genes involved in 7 pathways plus 2 well characterized biomarker genes, vtg1 (vitellogenin1) and cyp1a1 (cytochrome P450 1A1), were examined. Relative distance (RD) computational model was developed to screen favorable genes and generate appropriate gene sets for the differentiation of chemicals/concentrations selected. Our results demonstrated that the known biomarker genes were not always good candidates for the differentiation of pair of chemicals/concentrations, and other genes had higher potentials in some cases. Furthermore, the differentiation of 5 chemicals/concentrations examined were attainable using expression data of various gene sets, and the best combination was the set consisting of 50 genes; however, as few as two genes (e.g. vtg1 and hspa5 [heat shock protein 5]) were sufficient to differentiate the five chemical/concentration groups in the present test. These observations suggest that multi-parameter arrays should be more reliable for biomonitoring of chemical exposure than traditional biomarkers, and the RD computational model provides an effective tool for the selection of parameters and generation of parameter sets.

  11. Use of CBCT Imaging, Open-Source Modeling Software, and Desktop Stereolithography 3D Printing to Duplicate a Removable Dental Prosthesis-A Proof of Concept.

    Science.gov (United States)

    Lin, Wei-Shao; Harris, Bryan T; Morton, Dean

    2017-09-01

    This article describes an alternative computer-aided design/computer-aided manufacturing (CAD/CAM) technique that uses cone-beam computed tomography (CBCT) imaging, open-source 3-dimensional (3D) modeling software, and a desktop stereolithography (SLA) 3D printer to duplicate an existing complete removable dental prosthesis (CRDP). Intended to offer a proof of concept, this proposed technique provides dental clinicians who have access to a CBCT imaging unit and a desktop SLA 3D printer an option to manufacture a duplicated prosthesis in-office. The 3D model of the CRDP can be preserved indefinitely, and the CAD/CAM process makes it possible to manufacture the CRDP multiple times with ease, when necessary. Different materials can be selected for the SLA 3D printer, and the duplicated prosthesis could be used for a variety of clinical and laboratory indications, such as a custom tray, a trial prosthesis, a reference record for a definitive prosthesis in laboratory procedures, or a radiographic template. Clinicians should select and use 3D software, printers, and materials with proper biocompatibility and classification and clearance from respective medical device regulatory bodies (such as US Food & Drug Administration) in different intended applications.

  12. Subject-specific cardiovascular system model-based identification and diagnosis of septic shock with a minimally invasive data set: animal experiments and proof of concept.

    Science.gov (United States)

    Chase, J Geoffrey; Lambermont, Bernard; Starfinger, Christina; Hann, Christopher E; Shaw, Geoffrey M; Ghuysen, Alexandre; Kolh, Philippe; Dauby, Pierre C; Desaive, Thomas

    2011-01-01

    process for validation. Importantly, all identified parameter trends match physiologically and clinically and experimentally expected changes, indicating that no diagnostic power is lost. This work represents a further with human subjects validation for this model-based approach to cardiovascular diagnosis and therapy guidance in monitoring endotoxic disease states. The results and methods obtained can be readily extended from this case study to the other animal model results presented previously. Overall, these results provide further support for prospective, proof of concept clinical testing with humans.

  13. Electrochemical degradation of PAH compounds in process water: A kinetic study on model solutions and a proof of concept study on runoff water from harbour sediment purification

    DEFF Research Database (Denmark)

    Muff, Jens; Søgaard, Erik Gydesen

    2010-01-01

    The present study has investigated the possibility to apply electrochemical oxidation in the treatment of polycyclic aromatic hydrocarbon (PAHs) pollutants in water. The reaction kinetics of naphthalene, fluoranthene, and pyrene oxidation have been studied in a batch recirculation experimental....... Decreased current densities from 200 to 15 mA cm-2 in the NaCl electrolyte also decreased the removal rates, but significantly enhanced the current efficiencies of the PAH oxidation, based on a defined current efficiency constant, kq. This observation is believed to be due to the suppression of the water...... oxidation side reaction at lower applied voltages. A proof of concept study in real polluted water demonstrated the applicability of the electrochemical oxidation technique for larger scale use, where especially the indirect chloride mediated oxidation approach was a promising technique. However, the risk...

  14. In vivo proof-of-concept of removal of the huntingtin caspase cleavage motif-encoding exon 12 approach in the YAC128 mouse model of Huntington's disease.

    Science.gov (United States)

    Casaca-Carreira, João; Toonen, Lodewijk J A; Evers, Melvin M; Jahanshahi, Ali; van-Roon-Mom, Willeke M C; Temel, Yasin

    2016-12-01

    Huntington's disease (HD) is a progressive autosomal dominant disease, caused by a CAG repeat expansion in the HTT gene, resulting in an expanded polyglutamine stretch at the N-terminal of the huntingtin protein. An important event in HD pathogenesis appears to be the proteolysis of the mutant protein, which forms N-terminal huntingtin fragments. These fragments form insoluble aggregates and are found in nuclei and cytoplasm of affected neurons where they interfere with normal cell functioning. Important cleavage sites are encoded by exon 12 of HTT. A novel approach is Htt protein modification through exon skipping, which has recently been proven effective both in vitro and in vivo. Here we report proof-of-concept of AON 12.1 in vivo using the YAC128 mouse model of HD. Our results support and encourage future longitudinal studies exploring the therapeutic effects of sustained infusions in the YAC128 mouse model.

  15. 'P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model'.

    Science.gov (United States)

    2016-05-01

    This article corrects: P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model Volume 229, Issue 5, 705–718, Article first published online: 24 January 2013. By Ana Sofia Ribeiro, Bárbara Sousa, Laura Carreto, Nuno Mendes, Ana Rita Nobre, Sara Ricardo, André Albergaria, Jorge F Cameselle-Teijeiro, Rene Gerhard, Ola Söderberg, Raquel Seruca, Manuel A Santos, Fernando Schmitt and Joana Paredes, J Pathol 2013; 229: 708–718. DOI: 10.1002/path.4143. The above article, published online on 24 January 2013 on Wiley Online Library (wileyonlinelibrary.com). The funding information, “This work was also funded by FEDER funds through the Operational Programme for Competitiveness Factors - COMPETE (FCOMP-01-0124-FEDER-021209).” was omitted from the Acknowledgements section. We apologise for any inconvenience caused.

  16. Proof-of-Concept Demonstrations for Computation-Based Human Reliability Analysis. Modeling Operator Performance During Flooding Scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Joe, Jeffrey Clark [Idaho National Lab. (INL), Idaho Falls, ID (United States); Boring, Ronald Laurids [Idaho National Lab. (INL), Idaho Falls, ID (United States); Herberger, Sarah Elizabeth Marie [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis Lee [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    The United States (U.S.) Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program has the overall objective to help sustain the existing commercial nuclear power plants (NPPs). To accomplish this program objective, there are multiple LWRS “pathways,” or research and development (R&D) focus areas. One LWRS focus area is called the Risk-Informed Safety Margin and Characterization (RISMC) pathway. Initial efforts under this pathway to combine probabilistic and plant multi-physics models to quantify safety margins and support business decisions also included HRA, but in a somewhat simplified manner. HRA experts at Idaho National Laboratory (INL) have been collaborating with other experts to develop a computational HRA approach, called the Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER), for inclusion into the RISMC framework. The basic premise of this research is to leverage applicable computational techniques, namely simulation and modeling, to develop and then, using RAVEN as a controller, seamlessly integrate virtual operator models (HUNTER) with 1) the dynamic computational MOOSE runtime environment that includes a full-scope plant model, and 2) the RISMC framework PRA models already in use. The HUNTER computational HRA approach is a hybrid approach that leverages past work from cognitive psychology, human performance modeling, and HRA, but it is also a significant departure from existing static and even dynamic HRA methods. This report is divided into five chapters that cover the development of an external flooding event test case and associated statistical modeling considerations.

  17. Bistatic SAR: Proof of Concept.

    Energy Technology Data Exchange (ETDEWEB)

    Yocky, David A.; Doren, Neall E.; Bacon, Terry A.; Wahl, Daniel E.; Eichel, Paul H.; Jakowatz, Charles V,; Delaplain, Gilbert G.; Dubbert, Dale F.; Tise, Bertice L.; White, Kyle R.

    2014-10-01

    Typical synthetic aperture RADAR (SAR) imaging employs a co-located RADAR transmitter and receiver. Bistatic SAR imaging separates the transmitter and receiver locations. A bistatic SAR configuration allows for the transmitter and receiver(s) to be in a variety of geometric alignments. Sandia National Laboratories (SNL) / New Mexico proposed the deployment of a ground-based RADAR receiver. This RADAR receiver was coupled with the capability of digitizing and recording the signal collected. SNL proposed the possibility of creating an image of targets the illuminating SAR observes. This document describes the developed hardware, software, bistatic SAR configuration, and its deployment to test the concept of a ground-based bistatic SAR. In the proof-of-concept experiments herein, the RADAR transmitter will be a commercial SAR satellite and the RADAR receiver will be deployed at ground level, observing and capturing RADAR ground/targets illuminated by the satellite system.

  18. Towards the sequential assimilation of SAR-derived water stages into hydraulic models using the Particle Filter: proof of concept

    Science.gov (United States)

    Matgen, P.; Montanari, M.; Hostache, R.; Pfister, L.; Hoffmann, L.; Plaza, D.; Pauwels, V. R. N.; de Lannoy, G. J. M.; de Keyser, R.; Savenije, H. H. G.

    2010-09-01

    With the onset of new satellite radar constellations (e.g. Sentinel-1) and advances in computational science (e.g. grid computing) enabling the supply and processing of multi-mission satellite data at a temporal frequency that is compatible with real-time flood forecasting requirements, this study presents a new concept for the sequential assimilation of Synthetic Aperture Radar (SAR)-derived water stages into coupled hydrologic-hydraulic models. The proposed methodology consists of adjusting storages and fluxes simulated by a coupled hydrologic-hydraulic model using a Particle Filter-based data assimilation scheme. Synthetic observations of water levels, representing satellite measurements, are assimilated into the coupled model in order to investigate the performance of the proposed assimilation scheme as a function of both accuracy and frequency of water level observations. The use of the Particle Filter provides flexibility regarding the form of the probability densities of both model simulations and remote sensing observations. We illustrate the potential of the proposed methodology using a twin experiment over a widely studied river reach located in the Grand-Duchy of Luxembourg. The study demonstrates that the Particle Filter algorithm leads to significant uncertainty reduction of water level and discharge at the time step of assimilation. However, updating the storages of the model only improves the model forecast over a very short time horizon. A more effective way of updating thus consists in adjusting both states and inputs. The proposed methodology, which consists in updating the biased forcing of the hydraulic model using information on model errors that is inferred from satellite observations, enables persistent model improvement. The present schedule of satellite radar missions is such that it is likely that there will be continuity for SAR-based operational water management services. This research contributes to evolve reactive flood management into

  19. Process-based modeling of species' responses to climate change - a proof of concept using western North American trees

    Science.gov (United States)

    Evans, M. E.; Merow, C.; Record, S.; Menlove, J.; Gray, A.; Cundiff, J.; McMahon, S.; Enquist, B. J.

    2013-12-01

    Current attempts to forecast how species' distributions will change in response to climate change suffer under a fundamental trade-off: between modeling many species superficially vs. few species in detail (between correlative vs. mechanistic models). The goals of this talk are two-fold: first, we present a Bayesian multilevel modeling framework, dynamic range modeling (DRM), for building process-based forecasts of many species' distributions at a time, designed to address the trade-off between detail and number of distribution forecasts. In contrast to 'species distribution modeling' or 'niche modeling', which uses only species' occurrence data and environmental data, DRMs draw upon demographic data, abundance data, trait data, occurrence data, and GIS layers of climate in a single framework to account for two processes known to influence range dynamics - demography and dispersal. The vision is to use extensive databases on plant demography, distributions, and traits - in the Botanical Information and Ecology Network, the Forest Inventory and Analysis database (FIA), and the International Tree Ring Data Bank - to develop DRMs for North American trees. Second, we present preliminary results from building the core submodel of a DRM - an integral projection model (IPM) - for a sample of dominant tree species in western North America. IPMs are used to infer demographic niches - i.e., the set of environmental conditions under which population growth rate is positive - and project population dynamics through time. Based on >550,000 data points derived from FIA for nine tree species in western North America, we show IPM-based models of their current and future distributions, and discuss how IPMs can be used to forecast future forest productivity, mortality patterns, and inform efforts at assisted migration.

  20. Continuous stroke volume estimation from aortic pressure using zero dimensional cardiovascular model: proof of concept study from porcine experiments.

    Directory of Open Access Journals (Sweden)

    Shun Kamoi

    Full Text Available Accurate, continuous, left ventricular stroke volume (SV measurements can convey large amounts of information about patient hemodynamic status and response to therapy. However, direct measurements are highly invasive in clinical practice, and current procedures for estimating SV require specialized devices and significant approximation.This study investigates the accuracy of a three element Windkessel model combined with an aortic pressure waveform to estimate SV. Aortic pressure is separated into two components capturing; 1 resistance and compliance, 2 characteristic impedance. This separation provides model-element relationships enabling SV to be estimated while requiring only one of the three element values to be known or estimated. Beat-to-beat SV estimation was performed using population-representative optimal values for each model element. This method was validated using measured SV data from porcine experiments (N = 3 female Pietrain pigs, 29-37 kg in which both ventricular volume and aortic pressure waveforms were measured simultaneously.The median difference between measured SV from left ventricle (LV output and estimated SV was 0.6 ml with a 90% range (5th-95th percentile -12.4 ml-14.3 ml. During periods when changes in SV were induced, cross correlations in between estimated and measured SV were above R = 0.65 for all cases.The method presented demonstrates that the magnitude and trends of SV can be accurately estimated from pressure waveforms alone, without the need for identification of complex physiological metrics where strength of correlations may vary significantly from patient to patient.

  1. Xenobiotic effects in cancer related pathways-high throughput screening and proof of concept in animal models

    Institute of Scientific and Technical Information of China (English)

    Ursula E. Schumacher

    2013-01-01

    Xenobiotic drugs and chemicals directly interact with DNA, proteins, or other biomolecules in cells. These direct interactions with molecular targets may trigger a series of downstream effects on metabolic-biochemical and regulatory-signaling networks that can invoke cellular consequences leading to adaptive homeostatic or adverse pathological responses. Regulators for drug and chemicals safety have therefore since long required the testing of toxicity in animal models before drugs and pesticides can enter the market. The US National Research Council of the National Academy of Sciences, in its report, Toxicity Testing in the 21st Century: a Vision and a Strategy[1], proposed that toxicity testing should become less reliant on apical endpoints from whole animal tests and eventually rely instead on quantitative, dose-response models based on information from in vitro assays and in vivo biomarkers, which can be used to screen large numbers of chemicals.The present paper reports about a combination of HTS in vitro assays that can be used to study the potential tumorigenic effect of xenobiotics (drug targets, environmental chemicals) via a set of "sentinel" genes[2] that are functionally interrelated based on evidence weighted functional linkage network (FLN) log-likelihood scores (Linghu et al[3]).

  2. A proof of concept: Airborne LIDAR-measured ellipsoidal heights of a lake surface correspond to a local geoid model

    Science.gov (United States)

    Zlinszky, András; Ressl, Camillo; Timár, Gábor; Weber, Robert; Székely, Balázs; Briese, Christian; Pfeifer, Norbert

    2013-04-01

    The geoid is the theoretical model of the Earth, defined as an equipotential surface. Typically it corresponds to a mean ocean surface and is extended through the continents. Elevations are measured above "sea level" based on the fact that the surface of water in equilibrium closely follows this equipotential surface. On dry land, the geoid can be determined from gravimetric measurements, and interpolation methods are used to represent variations of gravity in a regular grid model. For practical reasons, these are represented as geoid undulation, which is the difference of the ellipsoidal height and the height of the equipotential surface. In his work Principia, Isaac Newton proposed the thought experiment of connecting the North Pole and the Equator through a "canal" filled with water in order to determine gravitational flattening of the Earth. It was also Newton's idea to use the level of water in a global network of canals and wells to survey the geoid. Of course, these experiments are impossible at a global scale, but a sufficiently large lake and an accurate method for measuring elevation independently from the geoid can be used to prove the concept. Our objective was to measure the ellipsoidal water surface elevation of Lake Balaton in Hungary with high spatial resolution and accuracy and compare these measurements with the gravimetrically determined local geoid model. Airborne laser scanning (ALS, also known as airborne LIDAR) is a remote sensing technique capable of delivering a large number of points with elevations and horizontal positions accurate to a few centimetres. Laser pulses are emitted in a scan pattern from an airborne sensor, and are reflected from the illuminated terrain (or water) surface. Based on the position and orientation of the aircraft (typically observed by GNSS and an inertial navigation system), the scan angle and the travel time of the laser pulse, the exact position of each measurement point is calculated. In this particular case

  3. Quantifying reliability uncertainty : a proof of concept.

    Energy Technology Data Exchange (ETDEWEB)

    Diegert, Kathleen V.; Dvorack, Michael A.; Ringland, James T.; Mundt, Michael Joseph; Huzurbazar, Aparna (Los Alamos National Laboratory, Los Alamos, NM); Lorio, John F.; Fatherley, Quinn (Los Alamos National Laboratory, Los Alamos, NM); Anderson-Cook, Christine (Los Alamos National Laboratory, Los Alamos, NM); Wilson, Alyson G. (Los Alamos National Laboratory, Los Alamos, NM); Zurn, Rena M.

    2009-10-01

    This paper develops Classical and Bayesian methods for quantifying the uncertainty in reliability for a system of mixed series and parallel components for which both go/no-go and variables data are available. Classical methods focus on uncertainty due to sampling error. Bayesian methods can explore both sampling error and other knowledge-based uncertainties. To date, the reliability community has focused on qualitative statements about uncertainty because there was no consensus on how to quantify them. This paper provides a proof of concept that workable, meaningful quantification methods can be constructed. In addition, the application of the methods demonstrated that the results from the two fundamentally different approaches can be quite comparable. In both approaches, results are sensitive to the details of how one handles components for which no failures have been seen in relatively few tests.

  4. Effects of the North Atlantic Oscillation and wind waves on salt marsh dynamics in the Danish Wadden Sea: a quantitative model as proof of concept

    Science.gov (United States)

    Kim, Daehyun; Grant, William E.; Cairns, David M.; Bartholdy, Jesper

    2013-08-01

    Long-term eustatic sea-level variation has been recognized as a primary factor affecting the hydrological and geomorphic dynamics of salt marshes. However, recent studies suggest that wind waves influenced by atmospheric oscillations also may play an important role in many coastal areas. Although this notion has been conceptually introduced for the Wadden Sea, no modeling attempts have been made yet. As a proof of concept, this study developed a simulation model using the commercially available STELLA® software, based on long-term data on water level and sedimentation collected at a back-barrier marsh on the Skallingen peninsula in Denmark. In the model, the frequency (number year-1) of wind-driven extreme high water level (HWL) events (>130 cm Danish Ordnance Zero) was simulated in terms of the North Atlantic Oscillation (NAO) index. Then, surface accretion (cm year-1) and submergence duration (h year-1) were simulated for the period 1933-2007. The model showed good performances: simulated rates of surface accretion and simulated durations of submergence decreased from 1950 to 1980, the point at which the NAO shifted from its negative to its positive phase, and increased thereafter. Despite continuous increases in surface elevation, increases in simulated submergence duration were apparently due to wind-driven HWL events, which generally increased in frequency after 1980. These findings for the Danish Wadden Sea add to the growing body of evidence that the role of atmospheric oscillations—e.g., the NAO—as drivers of wind-generated water level variations merits more attention in assessing the impact of climate change on coastal marshes.

  5. Proof of concept of the WOMED model of benign thyroid disease: Restitution of thyroid morphology after correction of physical and psychological stressors and magnesium supplementation

    Science.gov (United States)

    Moncayo, Roy; Moncayo, Helga

    2014-01-01

    Background The aim of this study was to investigate the influence of a combined supplementation with magnesium, selenium and coenzyme Q10 on the morphology of the thyroid in patients with benign diseases. The clinical examination and treatment approach aims additionally at treating musculoskeletal and psychological stress. Methods A group of 8 patients (5 with hyperthyroidism, 3 with hypothyroidism) who initially attended a public institution received additional treatment at our private institution. The basic pharmacological treatment, i.e. substitution or thyreostatic, was kept unchanged. The inclusion of patients required good quality ultrasound images to be available. Results Initially the changes of the musculoskeletal system were corrected. Following this, stress components were also treated. After a period of 2–4 years of supplementation we observed a normalization of thyroid morphology as evidenced on ultrasound while at the same time there was a reduction of perfusion intensity. Thyroid antibody titers decreased in the majority of cases. Failure of the treatment was seen in 2 cases of chronic thyroiditis that was present for more than 10 years. The ultrasound images of these patients suggest a possible fibrosis. Conclusions In spite of the limitation due to the small number of cases, our observational study has delivered proof of concept for our examination and treatment model for benign thyroid disease. General significance Our results challenge validity of the prevailing dogma of a destructive unstoppable “autoimmune” destructive process of the gland. At the same time it shows new therapeutic options for patients with thyroid disease. PMID:26672672

  6. A Numerical Proof of Concept for Thermal Flow Control

    Directory of Open Access Journals (Sweden)

    V. Dragan

    2017-02-01

    Full Text Available In this paper computational fluid dynamics is used to provide a proof of concept for controlled flow separation using thermal wall interactions with the velocity boundary layer. A 3D case study is presented, using a transition modeling Shear Stress Transport turbulence model. The highly loaded single slot flap airfoil was chosen to be representative for a light aircraft and the flow conditions were modeled after a typical landing speed. In the baseline case, adiabatic walls were considered while in the separation control case, the top surface of the flaps was heated to 500 K. This heating lead to flow separation on the flaps and a significant alteration of the flow pattern across all the elements of the wing. The findings indicate that this control method has potential, with implications in both aeronautical as well as sports and civil engineering applications.

  7. Direct Laser Ice Penetrator for Exploring Icy Ocean Worlds: Design, Modeling and Test Results of a Proof-of-Concept Prototype

    Science.gov (United States)

    Hogan, B.; Stone, W.; Bramall, N. E.; Siegel, V.; Lelievre, S.; Rothhammer, B.; Richmond, K.; Flesher, C.

    2016-12-01

    Subsurface exploration of icy ocean worlds requires an efficient method of penetrating ice to significant depths under extreme environment conditions. Searching for extant life dictates descent to a depth which is habitable or where biomarkers can survive and allow detection. It's anticipated that several meters to 10s of meters of shielding is required to prevent cosmic background radiation and other energetic particles from destroying biomarker evidence. We have devised, developed and demonstrated an entirely novel ice penetrating technology utilizing laser light carried by an optical fiber tether and emitted from a probe's optical nose cone and radiated directly into the volume of ice preceding the penetrator. We have termed it a "Direct Laser Penetrator" or DLP. We present design details, modeling, and test data from preliminary proof-of-concept experiments conducted at Stone Aerospace with results exceeding expectations and achieving the fastest reported thermal probe descent rate to date (> 12 m / hr). DLP has critical benefits over conventional "hot point" melt probes, which must generate large temperature gradients to force heat by conduction through the nose cone, and layers of ice and water. Additionally, hot point melt probes tested under vacuum have shown extreme difficulty initiating penetration, as virtually no thermal contact exists between the probe nose and rough ice surface. The ice simply sublimates and any transferred heat is quickly dissipated due to the low power density and extreme cold. DLP requires NO thermal contact between the probe nose and the ice surface since the laser energy is radiated directly into the volume (vs. surface) of ice preceding the penetrator. A proposed key element of the DLP is the fiber optic tether, coupled with a dedicated sensor fiber, enables "optical access" to the subsurface environment by a lander's shared or DLP dedicated on-board instruments (Raman / Fluorescence / fiber / UV / VIS / NIR spectroscopy, etc

  8. Digital TAcy: proof of concept

    Science.gov (United States)

    Bubel, Annie; Sylvain, Jean-François; Martin, François

    2009-06-01

    Anthocyanins are water soluble pigments in plants that are recognized for their antioxidant property. These pigments are found in high concentration in cranberries, which give their characteristic dark red color. The Total Anthocyanin concentration (TAcy) measurement process requires precious time, consumes chemical products and needs to be continuously repeated during the harvesting period. The idea of the digital TAcy system is to explore the possibility of estimating the TAcy based on analysing the color of the fruits. A calibrated color image capture set-up was developed and characterized, allowing calibrated color data capture from hundreds of samples over two harvesting years (fall of 2007 and 2008). The acquisition system was designed in such a way to avoid specular reflections and provide good resolution images with an extended range of color values representative of the different stages of fruit ripeness. The chemical TAcy value being known for every sample, a mathematical model was developed to predict the TAcy based on color information. This model, which also takes into account bruised and rotten fruits, shows a RMS error of less than 6% over the TAcy interest range [0-50].

  9. Proof-of-Concept Testing of the Passive Cooling System (T-CLIP™) for Solar Thermal Applications at an Elevated Temperature

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Jun [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Applied Engineering and Technology; Quintana, Donald L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Applied Engineering and Technology; Vigil, Gabrielle M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Applied Engineering and Technology; Perraglio, Martin Juan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Applied Engineering and Technology; Farley, Cory Wayne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Applied Engineering and Technology; Tafoya, Jose I. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Applied Engineering and Technology; Martinez, Adam L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Applied Engineering and Technology

    2015-11-30

    The Applied Engineering and Technology-1 group (AET-1) at Los Alamos National Laboratory (LANL) conducted the proof-of-concept tests of SolarSPOT LLC’s solar thermal Temperature- Clipper, or T-CLIP™ under controlled thermal conditions using a thermal conditioning unit (TCU) and a custom made environmental chamber. The passive T-CLIP™ is a plumbing apparatus that attaches to a solar thermal collector to limit working fluid temperature and to prevent overheating, since overheating may lead to various accident scenarios. The goal of the current research was to evaluate the ability of the T-CLIP™ to control the working fluid temperature by using its passive cooling mechanism (i.e. thermosiphon, or natural circulation) in a small-scale solar thermal system. The assembled environmental chamber that is thermally controlled with the TCU allows one to simulate the various possible weather conditions, which the solar system will encounter. The performance of the T-CLIP™ was tested at two different target temperatures: 1) room temperature (70 °F) and 2) an elevated temperature (130 °F). The current test campaign demonstrated that the T-CLIP™ was able to prevent overheating by thermosiphon induced cooling in a small-scale solar thermal system. This is an important safety feature in situations where the pump is turned off due to malfunction or power outages.

  10. Activity Monitoring and Heart Rate Variability as Indicators of Fall Risk: Proof-of-Concept for Application of Wearable Sensors in the Acute Care Setting.

    Science.gov (United States)

    Razjouyan, Javad; Grewal, Gurtej Singh; Rishel, Cindy; Parthasarathy, Sairam; Mohler, Jane; Najafi, Bijan

    2017-03-02

    Growing concern for falls in acute care settings could be addressed with objective evaluation of fall risk. The current proof-of-concept study evaluated the feasibility of using a chest-worn sensor during hospitalization to determine fall risk. Physical activity and heart rate variability (HRV) of 31 volunteers admitted to a 29-bed adult inpatient unit were recorded using a single chest-worn sensor. Sensor data during the first 24-hour recording were analyzed. Participants were stratified using the Hendrich II fall risk assessment into high and low fall risk groups. Univariate analysis revealed age, daytime activity, nighttime side lying posture, and HRV were significantly different between groups. Results suggest feasibility of wearable technology to consciously monitor physical activity, sleep postures, and HRV as potential markers of fall risk in the acute care setting. Further study is warranted to confirm the results and examine the efficacy of the proposed wearable technology to manage falls in hospitals. [Journal of Gerontological Nursing, xx(x), xx-xx.].

  11. The Application of Informatics in Delineating the Proof of Concept for Creating Knowledge of the Value Added by Interprofessional Practice and Education.

    Science.gov (United States)

    Cerra, Frank; Pacala, James; Brandt, Barbara F; Lutfiyya, May Nawal

    2015-11-12

    The resurgence of interest in the promise of interprofessional education and collaborative practice (IPECP) to positively impact health outcomes, requires the collection of appropriate data that can be analyzed and from which information and knowledge linking IPECP interventions to improved health outcomes might be produced and reported to stakeholders such as health systems, policy makers and regulators, payers, and accreditation agencies. To generate such knowledge the National Center for Interprofessional Practice and Education at the University of Minnesota has developed three strategies, the first two of which are: (1) creating an IPECP research agenda, and (2) a national Nexus Innovation Network (NIN) of intervention projects that are generating data that are being input and housed in a National Center Data Repository (NCDR). In this paper, the informatics platform supporting the work of these first two strategies is presented as the third interconnected strategy for knowledge generation. The proof of concept for the informatics strategy is developed in this paper by describing: data input from the NIN into the NCDR, the linking and merging of those data to produce analyzable data files that incorporate institutional and individual level data, and the production of meaningful analyses to create and provide relevant information and knowledge. This paper is organized around the concepts of data, information and knowledge-the three conceptual foundations of informatics.

  12. Automation of strategy using IDEF0 — A proof of concept

    National Research Council Canada - National Science Library

    Waissi, Gary R; Demir, Mustafa; Humble, Jane E; Lev, Benjamin

    2015-01-01

    ... to a model- and software-based approach. A sequence of examples, as a proof-of-concept, is shown to demonstrate the use of IDEF0 to translate document-based strategic plans to model-based plans...

  13. Application of Multivariate Modeling for Radiation Injury Assessment: A Proof of Concept (Radiation Injury Algorithms)

    Science.gov (United States)

    2014-01-01

    amylase , C - reactive protein (CRP), and hematological blood-cell counts measured at 1 - 4 d post-radiation exposure. A recent study by Moroni [19... food , etc.). The total body 6.5-Gy radiation dose was considered the equivalent of a METREPOL BM-ARS RC3 condition as outlined in the Medical Management...known to manifest in the prodromal and/or late ARS phases (Flt3 ligand, Citrulline, C-reactive protein, serum amylase IL-6) may contribute to our

  14. CIRCULATING MOVING BED COMBUSTION PROOF OF CONCEPT

    Energy Technology Data Exchange (ETDEWEB)

    Jukkola, Glen

    2010-06-30

    Circulating Moving Bed (CMB) combustion technology has its roots in traditional circulating fluidized bed technology and involves a novel method of solid fuel combustion and heat transfer. CMB technology represents a step change in improved performance and cost relative to conventional PC and FBC boilers. The CMB heat exchanger preheats the energy cycle working fluid, steam or air, to the high temperature levels required in systems for advanced power generation. Unique features of the CMB are the reduction of the heat transfer surfaces by about 60% as a result of the enhanced heat transfer rates, flexibility of operation, and about 30% lower cost over existing technology. The CMB Phase I project ran from July 2001 through March 2003. Its objective was to continue development of the CMB technology with a series of proof of concept tests. The tests were conducted at a scale that provided design data for scale up to a demonstration plant. These objectives were met by conducting a series of experiments in ALSTOM Power’s Multi-use Test Facility (MTF). The MTF was modified to operate under CMB conditions of commercial interest. The objective of the tests were to evaluate gas-to-solids heat transfer in the upper furnace, assess agglomeration in the high temperature CMB bubbling bed, and evaluate solids-to-tube heat transfer in the moving bed heat exchanger. The Phase I program results showed that there are still some significant technical uncertainties that needed to be resolved before the technology can be confidently scaled up for a successful demonstration plant design. Work remained in three primary areas: • scale up of gas to solid heat transfer • high temperature finned surface design • the overall requirements of mechanical and process design. The CMB Phase II workscope built upon the results of Phase I and specifically addressed the remaining technical uncertainties. It included a scaled MTF heat transfer test to provide the necessary data to scale up gas

  15. ATAC Process Proof of Concept Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Bri Rolston; Sarah Freeman

    2014-03-01

    Researchers at INL with funding from the Department of Energy’s Office of Electricity Delivery and Energy Reliability (DOE-OE) evaluated a novel approach for near real-time consumption of threat intelligence. Demonstration testing in an industry environment supported the development of this new process to assist the electric sector in securing their critical networks. This report provides the reader with an understanding of the methods used during this proof of concept project. The processes and templates were further advanced with an industry partner during an onsite assessment. This report concludes with lessons learned and a roadmap for final development of these materials for use by industry.

  16. The Versatile Transceiver Proof of Concept

    CERN Document Server

    Troska, J; Papadopoulos, S; Papakonstantinou, I; Rui Silva, S; Seif el Nasr, S; Sigaud, C; Stejskal,; Soos, C; Vasey, F

    2009-01-01

    SLHC experiment upgrades will make substantial use of optical links to enable high-speed data readout and control. The Versatile Link project will develop and assess optical link architectures and components suitable for deployment at SLHC. The on-detector element will be bidirectional optoelectronic module: the Versatile Transceiver that will be based on a commercially available module type minimally customized to meet the constraints of the SLHC on-detector environment in terms of mass, volume, power consumption, operational temperature and radiation environment. We report on the first proof of concept phase of the development, showing the steps towards customization and first results of the radiation resistance of candidate optoelectronic components.

  17. VAMP in Stellarium/VirGO: A Proof of Concept

    Science.gov (United States)

    Kapadia, Amit; Chéreau, Fabien; Christensen, Lars Lindberg; Nielsen, Lars Holm; Gauthier, Adrienne; Hurt, Robert; Wyatt, Ryan

    2008-06-01

    The Virtual Astronomy Multimedia Project (VAMP) and the Astronomy Visualization Metadata (AVM) standard will give observatories and astronomers an easy way to distribute their astronomical visualisation products. The CAP2007 demonstration which is described here is an early, although fully functioning, proof-of-concept for the VAMP project showing the capabilities and functionalities of the AVM. Our hope is to encourage people to begin applying the AVM standard to their Education and Public Outreach (EPO) images as they witness the spectacular end results that applications like Stellarium, World Wide Telescope, and Sky in Google Earth can bring to the future.

  18. Using the automata processor for fast pattern recognition in high energy physics experiments-A proof of concept

    Science.gov (United States)

    Wang, Michael H. L. S.; Cancelo, Gustavo; Green, Christopher; Guo, Deyuan; Wang, Ke; Zmuda, Ted

    2016-10-01

    We explore the Micron Automata Processor (AP) as a suitable commodity technology that can address the growing computational needs of pattern recognition in High Energy Physics (HEP) experiments. A toy detector model is developed for which an electron track confirmation trigger based on the Micron AP serves as a test case. Although primarily meant for high speed text-based searches, we demonstrate a proof of concept for the use of the Micron AP in a HEP trigger application.

  19. Using the automata processor for fast pattern recognition in high energy physics experiments—A proof of concept

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Michael H.L.S., E-mail: mwang@fnal.gov [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Cancelo, Gustavo; Green, Christopher [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Guo, Deyuan; Wang, Ke [University of Virginia, Charlottesville, VA 22904 (United States); Zmuda, Ted [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States)

    2016-10-01

    We explore the Micron Automata Processor (AP) as a suitable commodity technology that can address the growing computational needs of pattern recognition in High Energy Physics (HEP) experiments. A toy detector model is developed for which an electron track confirmation trigger based on the Micron AP serves as a test case. Although primarily meant for high speed text-based searches, we demonstrate a proof of concept for the use of the Micron AP in a HEP trigger application.

  20. Group online mindfulness training: proof of concept.

    Science.gov (United States)

    Kemper, Kathi J; Yun, Jonathan

    2015-01-01

    Mindfulness-based stress reduction training is attractive, but training with an expert teacher is often inconvenient and costly. This proof-of-concept project assessed the feasibility of providing a hybrid of free online mindfulness-based stress reduction training with small group peer facilitation. Six medical students asked a family medicine resident with 5 years of meditation experience but no formal training as a teacher to facilitate 8 weekly group sessions using a free online mindfulness-based stress reduction course. They completed pre- and posttraining questionnaires online. Six of the 7 trainees completed at least half the sessions. Completers and noncompleters had similar age (29 years), gender (about half male), and health status. Changes in the expected direction were observed for perceived stress, mindfulness, resilience, and confidence in providing calm, compassionate care. The hybrid of online mindfulness-based stress reduction training with peer support is feasible. Additional research is warranted to formally evaluate the impact of this approach.

  1. Scada Malware, a Proof of Concept

    Science.gov (United States)

    Carcano, Andrea; Fovino, Igor Nai; Masera, Marcelo; Trombetta, Alberto

    Critical Infrastructures are nowadays exposed to new kind of threats. The cause of such threats is related to the large number of new vulnerabilities and architectural weaknesses introduced by the extensive use of ICT and Network technologies into such complex critical systems. Of particular interest are the set of vulnerabilities related to the class of communication protocols normally known as “SCADA” protocols, under which fall all the communication protocols used to remotely control the RTU devices of an industrial system. In this paper we present a proof of concept of the potential effects of a set of computer malware specifically designed and created in order to impact, by taking advantage of some vulnerabilities of the ModBUS protocol, on a typical Supervisory Control and Data Acquisition system.

  2. The direct liquefaction proof of concept program

    Energy Technology Data Exchange (ETDEWEB)

    Comolli, A.G.; Lee, L.K.; Pradhan, V.R.; Stalzer, R.H. [New York & Puritan Avenues, Lawrenceville, NJ (United States)

    1995-12-31

    The goal of the Proof of Concept (POC) Program is to develop Direct Coal Liquefaction and associated transitional technologies towards commercial readiness for economically producing premium liquid fuels from coal in an environmentally acceptable manner. The program focuses on developing the two-stage liquefaction (TSL) process by utilizing geographically strategic feedstocks, commercially feasible catalysts, new prototype equipment, and testing co-processing or alternate feedstocks and improved process configurations. Other high priority objectives include dispersed catalyst studies, demonstrating low rank coal liquefaction without solids deposition, improving distillate yields on a unit reactor volume basis, demonstrating ebullated bed operations while obtaining scale-up data, demonstrating optimum catalyst consumption using new concepts (e.g. regeneration, cascading), producing premium products through on-line hydrotreating, demonstrating improved hydrogen utilization for low rank coals using novel heteroatom removal methods, defining and demonstrating two-stage product properties for upgrading; demonstrating efficient and economic solid separation methods, examining the merits of integrated coal cleaning, demonstrating co-processing, studying interactions between the preheater and first and second-stage reactors, improving process operability by testing and incorporating advanced equipment and instrumentation, and demonstrating operation with alternate coal feedstocks. During the past two years major PDU Proof of Concept runs were completed. POC-1 with Illinois No. 6 coal and POC-2 with Black Thunder sub-bituminous coal. Results from these operations are continuing under review and the products are being further refined and upgraded. This paper will update the results from these operations and discuss future plans for the POC program.

  3. S/G-1: an ab initio force-field blending frozen Hermite Gaussian densities and distributed multipoles. Proof of concept and first applications to metal cations.

    Science.gov (United States)

    Chaudret, Robin; Gresh, Nohad; Narth, Christophe; Lagardère, Louis; Darden, Thomas A; Cisneros, G Andrés; Piquemal, Jean-Philip

    2014-09-04

    We demonstrate as a proof of principle the capabilities of a novel hybrid MM'/MM polarizable force field to integrate short-range quantum effects in molecular mechanics (MM) through the use of Gaussian electrostatics. This lead to a further gain in accuracy in the representation of the first coordination shell of metal ions. It uses advanced electrostatics and couples two point dipole polarizable force fields, namely, the Gaussian electrostatic model (GEM), a model based on density fitting, which uses fitted electronic densities to evaluate nonbonded interactions, and SIBFA (sum of interactions between fragments ab initio computed), which resorts to distributed multipoles. To understand the benefits of the use of Gaussian electrostatics, we evaluate first the accuracy of GEM, which is a pure density-based Gaussian electrostatics model on a test Ca(II)-H2O complex. GEM is shown to further improve the agreement of MM polarization with ab initio reference results. Indeed, GEM introduces nonclassical effects by modeling the short-range quantum behavior of electric fields and therefore enables a straightforward (and selective) inclusion of the sole overlap-dependent exchange-polarization repulsive contribution by means of a Gaussian damping function acting on the GEM fields. The S/G-1 scheme is then introduced. Upon limiting the use of Gaussian electrostatics to metal centers only, it is shown to be able to capture the dominant quantum effects at play on the metal coordination sphere. S/G-1 is able to accurately reproduce ab initio total interaction energies within closed-shell metal complexes regarding each individual contribution including the separate contributions of induction, polarization, and charge-transfer. Applications of the method are provided for various systems including the HIV-1 NCp7-Zn(II) metalloprotein. S/G-1 is then extended to heavy metal complexes. Tested on Hg(II) water complexes, S/G-1 is shown to accurately model polarization up to quadrupolar

  4. Eliciting meta consent for future secondary research use of health data using a smartphone application - a proof of concept study in the Danish population.

    Science.gov (United States)

    Ploug, Thomas; Holm, Søren

    2017-08-15

    The increased use of information technology in every day health care creates vast amounts of stored health data that can be used for research. The secondary research use of routinely collected data raises questions about appropriate consent mechanisms for such use. One option is meta consent where individuals state their own consent preferences in relation to future use of their data, e.g. whether they want the data to be accessible to researchers under conditions of specific consent, broad consent, blanket consent or not at all. This study investigates whether meta consent preferences can be successfully elicited by a smartphone application in the adult Danish population. A smartphone app was developed for the elicitation of meta consent preferences. An invitation to use the app was distributed to a stratified, representative sample of the Danish adult population. The meta consent choices, the use of the app, user experience data, and demographic data were logged and analysed statistically using IBM SPSS version 20. Of 1000 potential respondents 221 used the app. One hundred eighty-eight of the respondents were female and 103 male. The age range was 19 to 79 years with an average of 51 years (SD 16). Most users indicate 1) that they find the choices they are asked to make easy to understand (>75% find it 'Easy' or 'Very easy'), 2) that the application is easy to use (>75% find it 'Easy' or 'Very easy'), and 3) that this kind of choice should be offered to people (89% find it 'Absolutely' or 'Somewhat' important). It is possible to collect meta consent preferences in the general, adult population using a smartphone app.

  5. Natural Tuning: Towards A Proof of Concept

    CERN Document Server

    Dubovsky, Sergei; Mirbabayi, Mehrdad

    2013-01-01

    The cosmological constant problem and the absence of new natural physics at the electroweak scale, if confirmed by the LHC, may either indicate that the nature is fine-tuned or that a refined notion of naturalness is required. We construct a family of toy UV complete quantum theories providing a proof of concept for the second possibility. Low energy physics is described by a tuned effective field theory, which exhibits relevant interactions not protected by any symmetries and separated by an arbitrary large mass gap from the new "gravitational" physics, represented by a set of irrelevant operators. Nevertheless, the only available language to describe dynamics at all energy scales does not require any fine-tuning. The interesting novel feature of this construction is that UV physics is not described by a fixed point, but rather exhibits asymptotic fragility. Observation of additional unprotected scalars at the LHC would be a smoking gun for this scenario. Natural tuning also favors TeV scale unification.

  6. Public health benefits of reducing air pollution in Shanghai: a proof-of-concept methodology with application to BenMAP.

    Science.gov (United States)

    Voorhees, A Scott; Wang, Jiandong; Wang, Cuicui; Zhao, Bin; Wang, Shuxiao; Kan, Haidong

    2014-07-01

    In recent years, levels of particulate matter (PM) air pollution in China have been relatively high, exceeding China's Class II standards in many cities and impacting public health. This analysis takes Chinese health impact functions and underlying health incidence, applies 2010-2012 modeled and monitored PM air quality data, and estimates avoided cases of mortality and morbidity in Shanghai, assuming achievement of China's Class II air quality standards. In Shanghai, the estimated avoided all cause mortality due to PM10 ranged from 13 to 55 cases per day and from 300 to 800 cases per year. The estimated avoided impact on hospital admissions due to PM10 ranged from 230 cases to 580 cases per day and from 5400 to 7900 per year. The estimated avoided impact on all cause mortality due to PM2.5 ranged from 6 to 26 cases per day and from 39 to 1400 per year. The estimated impact on all cause mortality of a year exposure to an annual or monthly mean PM2.5 concentration ranged from 180 to 3500 per year. In Shanghai, the avoided cases of all cause mortality had an estimated monetary value ranging from 170 million yuan (1 US dollar=4.2 yuan Purchasing Power Parity) to 1200 million yuan. Avoided hospital admissions had an estimated value from 20 to 43 million yuan. Avoided emergency department visits had an estimated value from 5.6 million to 15 million yuan. Avoided outpatient visits had an estimated value from 21 million to 31 million yuan. In this analysis, available data were adequate to estimate avoided health impacts and assign monetary value. Sufficient supporting documentation was available to construct and format data sets for use in the United States Environmental Protection Agency's health and environmental assessment model, known as the Environmental Benefits Mapping and Analysis Program - Community Edition ("BenMAP-CE").

  7. Progress toward Biomass and Coal-Derived Syngas Warm Cleanup: Proof-of-Concept Process Demonstration of Multicontaminant Removal for Biomass Application

    Energy Technology Data Exchange (ETDEWEB)

    Howard, Christopher J.; Dagle, Robert A.; Lebarbier, Vanessa MC; Rainbolt, James E.; Li, Liyu; King, David L.

    2013-06-19

    Systems comprising of multiple sorbent and catalytic beds have been developed for the warm syngas cleanup of coal- and biomass-derived syngas. Tailored specifically for biomass application the process described here consists of six primary unit operations: 1) Na2CO3 bed for HCl removal, 2) two regenerable ZnO beds for bulk H2S removal, 3) ZnO bed for H2S polishing, 4) NiCu/SBA-16 sorbent for trace metal (e.g. AsH3) removal, 5) steam reforming catalyst bed for tars and light hydrocarbons reformation and NH3 decomposition, and a 6) Cu-based LT-WGS catalyst bed. Simulated biomass-derived syngas containing a multitude of inorganic contaminants (H2S, AsH3, HCl, and NH3) and hydrocarbon additives (methane, ethylene, benzene, and naphthalene) was used to demonstrate process effectiveness. The efficiency of the process was demonstrated for a period of 175 hours, during which no signs of deactivation were observed. Post-run analysis revealed small levels of sulfur slipped through the sorbent bed train to the two downstream catalytic beds. Future improvements could be made to the trace metal polishing sorbent to ensure complete inorganic contaminant removal (to low ppb level) prior to the catalytic steps. However, dual, regenerating ZnO beds were effective for continuous removal for the vast majority of the sulfur present in the feed gas. The process was effective for complete AsH3 and HCl removal. The steam reforming catalyst completely reformed all the hydrocarbons present in the feed (methane, ethylene, benzene, and naphthalene) to additional syngas. However, post-run evaluation, under kinetically-controlled conditions, indicates deactivation of the steam reforming catalyst. Spent material characterization suggests this is attributed, in part, to coke formation, likely due to the presence of benzene and/or naphthalene in the feed. Future adaptation of this technology may require dual, regenerable steam reformers. The process and materials described in this report hold

  8. The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease

    Science.gov (United States)

    Serrano, Mari Paz; Herrero-Labrador, Raquel; Futch, Hunter S.; Serrano, Julia; Romero, Alejandro; Fernandez, Ana Patricia; Samadi, Abdelouahid; Unzeta, Mercedes; Marco-Contelles, Jose; Martínez-Murillo, Ricardo

    2017-01-01

    Background The heterogeneity of Alzheimer disease requires the development of multitarget drugs for treating the symptoms of the disease and its progression. Both cholinergic and monoamine oxidase dysfunctions are involved in the pathological process. Thus, we hypothesized that the development of therapies focused on these targets might be effective. We have developed and assessed a new product, coded ASS234, a multipotent acetyl and butyrylcholinesterase/monoamine oxidase A–B inhibitor with a potent inhibitory effect on amyloid-β aggregation as well as antioxidant and antiapoptotic properties. But there is a need to reliably correlate in vitro and in vivo drug release data. Methods We examined the effect of ASS234 on cognition in healthy adult C57BL/6J mice in a model of scopolamine-induced cognitive impairment that often accompanies normal and pathological aging. Also, in a characterized transgenic APPswe/PS1ΔE9 mouse model of Alzheimer disease, we examined the effects of short-term ASS234 treatment on plaque deposition and gliosis using immunohistochemistry. Toxicology of ASS234 was assessed using a quantitative high-throughput in vitro cytotoxicity screening assay following the MTT assay method in HepG2 liver cells. Results In vivo, ASS234 significantly decreased scopolamine-induced learning deficits in C57BL/6J mice. Also, reduction of amyloid plaque burden and gliosis in the cortex and hippocampus was assessed. In vitro, ASS234 exhibited lesser toxicity than donepezil and tacrine. Limitations The study was conducted in male mice only. Although the Alzheimer disease model does not recapitulate all features of the human disease, it exhibits progressive monoaminergic neurodegeneration. Conclusion ASS234 is a promising alternative drug of choice to treat the cognitive decline and neurodegeneration underlying Alzheimer disease. PMID:27636528

  9. Topical gene silencing by iontophoretic delivery of an antisense oligonucleotide-dendrimer nanocomplex: the proof of concept in a skin cancer mouse model

    Science.gov (United States)

    Venuganti, , Venkata Vamsi K.; Saraswathy, Manju; Dwivedi, Chandradhar; Kaushik, Radhey S.; Perumal, Omathanu P.

    2015-02-01

    The study was aimed at investigating the feasibility of using a poly (amidoamine) (PAMAM) dendrimer as a carrier for topical iontophoretic delivery of an antisense oligonucleotide (ASO). Bcl-2, an anti-apoptotic protein implicated in skin cancer, was used as the model target protein to demonstrate the topical gene silencing approach. Confocal laser scanning microscopy studies demonstrated that the iontophoretically delivered ASO-dendrimer complex can reach the viable epidermis in porcine skin. In contrast, passively delivered free or dendrimer complexed ASO was mainly localized to the stratum corneum. The cell uptake of ASO was significantly enhanced by the dendrimer complex and the complex suppressed Bcl-2 levels in the cell. In the skin cancer mouse model, the iontophoretically delivered ASO-dendrimer complex reduced the tumor volume by 45% and was consistent with the reduction in Bcl-2 protein levels. The iontophoretically delivered ASO-dendrimer complex caused significant apoptosis in skin tumor. Overall, the findings from this study demonstrate that dendrimers are promising nanocarriers for developing topical gene silencing approaches for skin diseases.The study was aimed at investigating the feasibility of using a poly (amidoamine) (PAMAM) dendrimer as a carrier for topical iontophoretic delivery of an antisense oligonucleotide (ASO). Bcl-2, an anti-apoptotic protein implicated in skin cancer, was used as the model target protein to demonstrate the topical gene silencing approach. Confocal laser scanning microscopy studies demonstrated that the iontophoretically delivered ASO-dendrimer complex can reach the viable epidermis in porcine skin. In contrast, passively delivered free or dendrimer complexed ASO was mainly localized to the stratum corneum. The cell uptake of ASO was significantly enhanced by the dendrimer complex and the complex suppressed Bcl-2 levels in the cell. In the skin cancer mouse model, the iontophoretically delivered ASO-dendrimer complex

  10. Model-Based Estimation of Forest Canopy Height in Red and Austrian Pine Stands Using Shuttle Radar Topography Mission and Ancillary Data: a Proof-of-Concept Study

    Energy Technology Data Exchange (ETDEWEB)

    Brown Jr., C G; Sarabandi, K; Pierce, L E

    2007-04-06

    In this paper, accurate tree stand height retrieval is demonstrated using C-band Shuttle Radar Topography Mission (SRTM) height and ancillary data. The tree height retrieval algorithm is based on modeling uniform tree stands with a single layer of randomly oriented vegetation particles. For such scattering media, the scattering phase center height, as measured by SRTM, is a function of tree height, incidence angle, and the extinction coefficient of the medium. The extinction coefficient for uniform tree stands is calculated as a function of tree height and density using allometric equations and a fractal tree model. The accuracy of the proposed algorithm is demonstrated using SRTM and TOPSAR data for 15 red pine and Austrian pine stands (TOPSAR is an airborne interferometric synthetic aperture radar). The algorithm yields root-mean-square (rms) errors of 2.5-3.6 m, which is a substantial improvement over the 6.8-8.3-m rms errors from the raw SRTM minus National Elevation Dataset Heights.

  11. Novel in vitro diagnosis of equine allergies using a protein array and mathematical modelling approach: a proof of concept using insect bite hypersensitivity.

    Science.gov (United States)

    Marti, E; Wang, X; Jambari, N N; Rhyner, C; Olzhausen, J; Pérez-Barea, J J; Figueredo, G P; Alcocer, M J C

    2015-10-15

    Insect bite hypersensitivity (IBH) is a seasonal recurrent skin allergy of horses caused by IgE-mediated reactions to allergens present in the saliva of biting insects of the genus Culicoides, and possibly also Simulium and Stomoxys species. In this work we show that protein microarrays containing complex extracts and pure proteins, including recombinant Culicoides allergens, can be used as a powerful technique for the diagnosis of IBH. Besides the obvious advantages such as general profiling and use of few microliters of samples, this microarray technique permits automation and allows the generation of mathematical models with the calculation of individual risk profiles that can support the clinical diagnosis of allergic diseases. After selection of variables on influence on the projection (VIP), the observed values of sensitivity and specificity were 1.0 and 0.967, respectively. This confirms the highly discriminatory power of this approach for IBH and made it possible to attain a robust predictive mathematical model for this disease. It also further demonstrates the specificity of the protein array method on identifying a particular IgE-mediated disease when the sensitising allergen group is known.

  12. A proof-of-concept model for the identification of the key events in the infection process with specific reference to Pseudomonas aeruginosa in corneal infections

    Directory of Open Access Journals (Sweden)

    Ilias Soumpasis

    2015-11-01

    Full Text Available Background: It is a common medical practice to characterise an infection based on the causative agent and to adopt therapeutic and prevention strategies targeting the agent itself. However, from an epidemiological perspective, exposure to a microbe can be harmless to a host as a result of low-level exposure or due to host immune response, with opportunistic infection only occurring as a result of changes in the host, pathogen, or surrounding environment. Methods: We have attempted to review systematically the key host, pathogen, and environmental factors that may significantly impact clinical outcomes of exposure to a pathogen, using Pseudomonas aeruginosa eye infection as a case study. Results and discussion: Extended contact lens wearing and compromised hygiene may predispose users to microbial keratitis, which can be a severe and vision-threatening infection. P. aeruginosa has a wide array of virulence-associated genes and sensing systems to initiate and maintain cell populations at the corneal surface and beyond. We have adapted the well-known concept of the epidemiological triangle in combination with the classic risk assessment framework (hazard identification, characterisation, and exposure to develop a conceptual pathway-based model that demonstrates the overlapping relationships between the host, the pathogen, and the environment; and to illustrate the key events in P. aeruginosa eye infection. Conclusion: This strategy differs from traditional approaches that consider potential risk factors in isolation, and hopefully will aid the identification of data and models to inform preventive and therapeutic measures in addition to risk assessment. Furthermore, this may facilitate the identification of knowledge gaps to direct research in areas of greatest impact to avert or mitigate adverse outcomes of infection.

  13. A proof-of-concept model for the identification of the key events in the infection process with specific reference to Pseudomonas aeruginosa in corneal infections

    Science.gov (United States)

    Soumpasis, Ilias; Knapp, Laura; Pitt, Tyrone

    2015-01-01

    Background It is a common medical practice to characterise an infection based on the causative agent and to adopt therapeutic and prevention strategies targeting the agent itself. However, from an epidemiological perspective, exposure to a microbe can be harmless to a host as a result of low-level exposure or due to host immune response, with opportunistic infection only occurring as a result of changes in the host, pathogen, or surrounding environment. Methods We have attempted to review systematically the key host, pathogen, and environmental factors that may significantly impact clinical outcomes of exposure to a pathogen, using Pseudomonas aeruginosa eye infection as a case study. Results and discussion Extended contact lens wearing and compromised hygiene may predispose users to microbial keratitis, which can be a severe and vision-threatening infection. P. aeruginosa has a wide array of virulence-associated genes and sensing systems to initiate and maintain cell populations at the corneal surface and beyond. We have adapted the well-known concept of the epidemiological triangle in combination with the classic risk assessment framework (hazard identification, characterisation, and exposure) to develop a conceptual pathway-based model that demonstrates the overlapping relationships between the host, the pathogen, and the environment; and to illustrate the key events in P. aeruginosa eye infection. Conclusion This strategy differs from traditional approaches that consider potential risk factors in isolation, and hopefully will aid the identification of data and models to inform preventive and therapeutic measures in addition to risk assessment. Furthermore, this may facilitate the identification of knowledge gaps to direct research in areas of greatest impact to avert or mitigate adverse outcomes of infection. PMID:26546946

  14. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

    Science.gov (United States)

    Emmert, Maximilian Y; Weber, Benedikt; Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P

    2013-01-01

    Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70-75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7-9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×10(5)-5×10(5) human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow

  15. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

    Directory of Open Access Journals (Sweden)

    Maximilian Y Emmert

    Full Text Available Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI, key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70-75 days were included. Ten animals either received an intra-uterine induction of MI only (n = 4 or MI+intra-myocardial injection (IMI;n = 6 using micron-sized, iron-oxide (MPIO labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3 or the bone-marrow (BMMSCs;n = 3. Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1. All procedures were performed successfully and follow-up was 7-9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×10(5-5×10(5 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow

  16. Hydrolytic Cleavage Products of Globin Adducts in Urine as Possible Biomarkers of Cumulative Dose: Proof of Concept Using Styrene Oxide as a Model Adduct-Forming Compound.

    Science.gov (United States)

    Mráz, Jaroslav; Hanzlíková, Iveta; Moulisová, Alena; Dušková, Šárka; Hejl, Kamil; Bednářová, Aneta; Dabrowská, Ludmila; Linhart, Igor

    2016-04-18

    A new experimental model was designed to study the fate of globin adducts with styrene 7,8-oxide (SO), a metabolic intermediate of styrene and a model electrophilic compound. Rat erythrocytes were incubated with SO at 7 or 22 °C. Levels of specific amino acid adducts in globin were determined by LC/MS analysis of the globin hydrolysate, and erythrocytes with known adduct content were administered intravenously to recipient rats. The course of adduct elimination from the rat blood was measured over the following 50 days. In the erythrocytes incubated at 22 °C, a rapid decline in the adduct levels on the first day post-transfusion followed by a slow phase of elimination was observed. In contrast, the adduct elimination in erythrocytes incubated at 7 °C was nearly linear, copying elimination of intact erythrocytes. In the urine of recipient rats, regioisomeric SO adducts at cysteine, valine, lysine, and histidine in the form of amino acid adducts and/or their acetylated metabolites as well as SO-dipeptide adducts were identified by LC/MS supported by synthesized reference standards. S-(2-Hydroxy-1-phenylethyl)cysteine and S-(2-hydroxy-2-phenylethyl)cysteine, the most abundant globin adducts, were excreted predominantly in the form of the corresponding urinary mercapturic acids (HPEMAs). Massive elimination of HPEMAs via urine occurred within the first day from the erythrocytes incubated at both 7 and 22 °C. However, erythrocytes incubated at 7 °C also showed a slow second phase of elimination such that HPEMAs were detected in urine up to 50 days post-transfusion. These results indicate for the first time that globin adducts can be cleaved in vivo to modified amino acids and dipeptides. The cleavage products and/or their predictable metabolites are excreted in urine over the whole life span of erythrocytes. Some of the urinary adducts may represent a new type of noninvasive biomarker for exposure to adduct-forming chemicals.

  17. Wavelet-based Gaussian-mixture hidden Markov model for the detection of multistage seizure dynamics: A proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Carlen Peter L

    2011-04-01

    Full Text Available Abstract Background Epilepsy is a common neurological disorder characterized by recurrent electrophysiological activities, known as seizures. Without the appropriate detection strategies, these seizure episodes can dramatically affect the quality of life for those afflicted. The rationale of this study is to develop an unsupervised algorithm for the detection of seizure states so that it may be implemented along with potential intervention strategies. Methods Hidden Markov model (HMM was developed to interpret the state transitions of the in vitro rat hippocampal slice local field potentials (LFPs during seizure episodes. It can be used to estimate the probability of state transitions and the corresponding characteristics of each state. Wavelet features were clustered and used to differentiate the electrophysiological characteristics at each corresponding HMM states. Using unsupervised training method, the HMM and the clustering parameters were obtained simultaneously. The HMM states were then assigned to the electrophysiological data using expert guided technique. Minimum redundancy maximum relevance (mRMR analysis and Akaike Information Criterion (AICc were applied to reduce the effect of over-fitting. The sensitivity, specificity and optimality index of chronic seizure detection were compared for various HMM topologies. The ability of distinguishing early and late tonic firing patterns prior to chronic seizures were also evaluated. Results Significant improvement in state detection performance was achieved when additional wavelet coefficient rates of change information were used as features. The final HMM topology obtained using mRMR and AICc was able to detect non-ictal (interictal, early and late tonic firing, chronic seizures and postictal activities. A mean sensitivity of 95.7%, mean specificity of 98.9% and optimality index of 0.995 in the detection of chronic seizures was achieved. The detection of early and late tonic firing was

  18. Proof-of-concept and advancement of the CellFlux concept

    Science.gov (United States)

    Odenthal, Christian; Steinmann, Wolf-Dieter

    2016-05-01

    The CellFlux storage system is a new concept for reducing the costs of medium to high temperature thermal energy storage. Initially designed for solar thermal power plants, the concept is suitable for industrial processes and power to heat applications as well. This paper gives first results of a new pilot scale plant set up at DLR in Stuttgart as a proof of concept. Experimental results are used for the validation of a simplified model. The model is apllied to calculate pareto optimal storage configurations in terms of necessary storage mass and exergetic efficiency, suitable for two types of solar thermal power plants. Particularly for applications having larger temperature differences, high exergetic efficiencies at low costs for the storage material can be achieved.

  19. Proof of Concept for an Approach to a Finer Resolution Inventory

    Science.gov (United States)

    Chris J. Cieszewski; Kim Iles; Roger C. Lowe; Michal Zasada

    2005-01-01

    This report presents a proof of concept for a statistical framework to develop a timely, accurate, and unbiased fiber supply assessment in the State of Georgia, U.S.A. The proposed approach is based on using various data sources and modeling techniques to calibrate satellite image-based statewide stand lists, which provide initial estimates for a State inventory on a...

  20. Reducing antimicrobial therapy for asymptomatic bacteriuria among noncatheterized inpatients: a proof-of-concept study.

    Science.gov (United States)

    Leis, Jerome A; Rebick, Gabriel W; Daneman, Nick; Gold, Wayne L; Poutanen, Susan M; Lo, Pauline; Larocque, Michael; Shojania, Kaveh G; McGeer, Allison

    2014-04-01

    This proof-of-concept study demonstrates that no longer routinely reporting urine culture results from noncatheterized medical and surgical inpatients can greatly reduce unnecessary antimicrobial therapy for asymptomatic bacteriuria without significant additional laboratory workload. Larger studies are needed to confirm the generalizability, safety, and sustainability of this model of care.

  1. Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes.

    Science.gov (United States)

    Justice, Jamie; Miller, Jordan D; Newman, John C; Hashmi, Shahrukh K; Halter, Jeffrey; Austad, Steve N; Barzilai, Nir; Kirkland, James L

    2016-11-01

    Therapies targeted at fundamental processes of aging may hold great promise for enhancing the health of a wide population by delaying or preventing a range of age-related diseases and conditions-a concept dubbed the "geroscience hypothesis." Early, proof-of-concept clinical trials will be a key step in the translation of therapies emerging from model organism and preclinical studies into clinical practice. This article summarizes the outcomes of an international meeting partly funded through the NIH R24 Geroscience Network, whose purpose was to generate concepts and frameworks for early, proof-of-concept clinical trials for therapeutic interventions that target fundamental processes of aging. The goals of proof-of-concept trials include generating preliminary signals of efficacy in an aging-related disease or outcome that will reduce the risk of conducting larger trials, contributing data and biological samples to support larger-scale research by strategic networks, and furthering a dialogue with regulatory agencies on appropriate registration indications. We describe three frameworks for proof-of-concept trials that target age-related chronic diseases, geriatric syndromes, or resilience to stressors. We propose strategic infrastructure and shared resources that could accelerate development of therapies that target fundamental aging processes. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

  2. US NDC Modernization: Service Oriented Architecture Proof of Concept

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Benjamin R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Encarnacao, Andre Villanova [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jackson, Keilan R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hays, Ian A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Barron, Nathan E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Simon, Luke B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Harris, James M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Young, Christopher J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-12-01

    This report is a progress update on the US NDC Modernization Service Oriented Architecture (SOA) study describing results from a proof of concept project completed from May through September 2013. Goals for this proof of concept are 1) gain experience configuring, using, and running an Enterprise Service Bus (ESB), 2) understand the implications of wrapping existing software in standardized interfaces for use as web services, and 3) gather performance metrics for a notional seismic event monitoring pipeline implemented using services with various data access and communication patterns. The proof of concept is a follow on to a previous SOA performance study. Work was performed by four undergraduate summer student interns under the guidance of Sandia staff.

  3. Global Combat Support System-Marine Corps Proof-of-Concept for Dashboard Analytics

    Science.gov (United States)

    2014-12-01

    applications within Oracle. JDeveloper integrates development features for Java, HTML5 , SOA, Web , Mobile, Database, XML, and Web services which...GCSS-MC. D. SCOPE AND METHODOLOGY 1. Scope This research is focused on the design and development of a dashboard environment proof-of-concept web ...description of the development methods used in the creation of our web -based application. It starts with a brief history of Oracle and Oracle

  4. Electronic Vehicle Identification Architecture and Proof of Concept

    NARCIS (Netherlands)

    Passchier, I.; Chevrollier, N.G.; Mulder,A.; Vliet,A.O.T.van

    2009-01-01

    An architecture and a proof of concept for Electronic Vehicle Identification have beendeveloped. The system has been successfully tested in a pilot with 23 participants over a period of three months and a total distance of 75.000 km travelled. The architecture consists of a functional definition, a

  5. Evaluation of TENCompetence proof of concept assessment tools

    NARCIS (Netherlands)

    Petrov, Milen; Aleksieva-Petrova, Adelina; Stefanov, Krassen; Schoonenboom, Judith; Miao, Yongwu

    2008-01-01

    Petrov, M., Aleksieva-Petrova, A., Stefanov, K., Schoonenboom, J., & Miao, Y. (2008). Evaluation of TENCompetence proof of concept assessment tools. In H. W. Sligte & R. Koper (Eds.). Proceedings of the 4th TENCompetence Open Workshop. Empowering Learners for Lifelong Competence Development: pedagog

  6. Electronic Vehicle Identification Architecture and Proof of Concept

    NARCIS (Netherlands)

    Passchier, I.; Chevrollier, N.G.; Mulder,A.; Vliet,A.O.T.van

    2009-01-01

    An architecture and a proof of concept for Electronic Vehicle Identification have beendeveloped. The system has been successfully tested in a pilot with 23 participants over a period of three months and a total distance of 75.000 km travelled. The architecture consists of a functional definition, a

  7. Evaluation of TENCompetence proof of concept assessment tools

    NARCIS (Netherlands)

    Petrov, Milen; Aleksieva-Petrova, Adelina; Stefanov, Krassen; Schoonenboom, Judith; Miao, Yongwu

    2008-01-01

    Petrov, M., Aleksieva-Petrova, A., Stefanov, K., Schoonenboom, J., & Miao, Y. (2008). Evaluation of TENCompetence proof of concept assessment tools. In H. W. Sligte & R. Koper (Eds.). Proceedings of the 4th TENCompetence Open Workshop. Empowering Learners for Lifelong Competence Development: pedagog

  8. Embedded ESD Protection Proof of Concept

    Science.gov (United States)

    Gerke, David; Herrmann, Bill

    2008-01-01

    The purpose of this project is to characterize and correlate Electrostatic Discharge (ESD) sensitivity levels of an Integrated Circuit (IC) package using Transmission Line Pulse (TLP) and Human Body Model (HBM) methods. This characterization will be used as a baseline ESD sensitivity level to demonstrate improvement to the ESD sensitivity of the IC package through the use of EPI-FLO(Trade Mark) Polymer Voltage Suppression (PVS) protection devices developed and manufactured by Electronic Polymers, Inc. (EPI).

  9. Embedded ESD Protection Proof of Concept

    Science.gov (United States)

    Gerke, David; Herrmann, Bill

    2008-01-01

    The purpose of this project is to characterize and correlate Electrostatic Discharge (ESD) sensitivity levels of an Integrated Circuit (IC) package using Transmission Line Pulse (TLP) and Human Body Model (HBM) methods. This characterization will be used as a baseline ESD sensitivity level to demonstrate improvement to the ESD sensitivity of the IC package through the use of EPI-FLO(Trade Mark) Polymer Voltage Suppression (PVS) protection devices developed and manufactured by Electronic Polymers, Inc. (EPI).

  10. Boolean network robotics: a proof of concept

    CERN Document Server

    Roli, Andrea; Pinciroli, Carlo; Birattari, Mauro

    2011-01-01

    Dynamical systems theory and complexity science provide powerful tools for analysing artificial agents and robots. Furthermore, they have been recently proposed also as a source of design principles and guidelines. Boolean networks are a prominent example of complex dynamical systems and they have been shown to effectively capture important phenomena in gene regulation. From an engineering perspective, these models are very compelling, because they can exhibit rich and complex behaviours, in spite of the compactness of their description. In this paper, we propose the use of Boolean networks for controlling robots' behaviour. The network is designed by means of an automatic procedure based on stochastic local search techniques. We show that this approach makes it possible to design a network which enables the robot to accomplish a task that requires the capability of navigating the space using a light stimulus, as well as the formation and use of an internal memory.

  11. A Bayesian paradigm for decision-making in proof-of-concept trials.

    Science.gov (United States)

    Pulkstenis, Erik; Patra, Kaushik; Zhang, Jianliang

    2017-01-01

    Decision-making is central to every phase of drug development, and especially at the proof of concept stage where risk and evidence must be weighed carefully, often in the presence of significant uncertainty. The decision to proceed or not to large expensive Phase 3 trials has significant implications to both patients and sponsors alike. Recent experience has shown that Phase 3 failure rates remain high. We present a flexible Bayesian quantitative decision-making paradigm that evaluates evidence relative to achieving a multilevel target product profile. A framework for operating characteristics is provided that allows the drug developer to design a proof-of-concept trial in light of its ability to support decision-making rather than merely achieve statistical significance. Operating characteristics are shown to be superior to traditional p-value-based methods. In addition, discussion related to sample size considerations, application to interim futility analysis and incorporation of prior historical information is evaluated.

  12. A Proof-of-Concept for Semantically Interoperable Federation of IoT Experimentation Facilities.

    Science.gov (United States)

    Lanza, Jorge; Sanchez, Luis; Gomez, David; Elsaleh, Tarek; Steinke, Ronald; Cirillo, Flavio

    2016-06-29

    The Internet-of-Things (IoT) is unanimously identified as one of the main pillars of future smart scenarios. The potential of IoT technologies and deployments has been already demonstrated in a number of different application areas, including transport, energy, safety and healthcare. However, despite the growing number of IoT deployments, the majority of IoT applications tend to be self-contained, thereby forming application silos. A lightweight data centric integration and combination of these silos presents several challenges that still need to be addressed. Indeed, the ability to combine and synthesize data streams and services from diverse IoT platforms and testbeds, holds the promise to increase the potentiality of smart applications in terms of size, scope and targeted business context. In this article, a proof-of-concept implementation that federates two different IoT experimentation facilities by means of semantic-based technologies will be described. The specification and design of the implemented system and information models will be described together with the practical details of the developments carried out and its integration with the existing IoT platforms supporting the aforementioned testbeds. Overall, the system described in this paper demonstrates that it is possible to open new horizons in the development of IoT applications and experiments at a global scale, that transcend the (silo) boundaries of individual deployments, based on the semantic interconnection and interoperability of diverse IoT platforms and testbeds.

  13. A Proof-of-Concept for Semantically Interoperable Federation of IoT Experimentation Facilities

    Directory of Open Access Journals (Sweden)

    Jorge Lanza

    2016-06-01

    Full Text Available The Internet-of-Things (IoT is unanimously identified as one of the main pillars of future smart scenarios. The potential of IoT technologies and deployments has been already demonstrated in a number of different application areas, including transport, energy, safety and healthcare. However, despite the growing number of IoT deployments, the majority of IoT applications tend to be self-contained, thereby forming application silos. A lightweight data centric integration and combination of these silos presents several challenges that still need to be addressed. Indeed, the ability to combine and synthesize data streams and services from diverse IoT platforms and testbeds, holds the promise to increase the potentiality of smart applications in terms of size, scope and targeted business context. In this article, a proof-of-concept implementation that federates two different IoT experimentation facilities by means of semantic-based technologies will be described. The specification and design of the implemented system and information models will be described together with the practical details of the developments carried out and its integration with the existing IoT platforms supporting the aforementioned testbeds. Overall, the system described in this paper demonstrates that it is possible to open new horizons in the development of IoT applications and experiments at a global scale, that transcend the (silo boundaries of individual deployments, based on the semantic interconnection and interoperability of diverse IoT platforms and testbeds.

  14. A Proof-of-Concept for Semantically Interoperable Federation of IoT Experimentation Facilities

    Science.gov (United States)

    Lanza, Jorge; Sanchez, Luis; Gomez, David; Elsaleh, Tarek; Steinke, Ronald; Cirillo, Flavio

    2016-01-01

    The Internet-of-Things (IoT) is unanimously identified as one of the main pillars of future smart scenarios. The potential of IoT technologies and deployments has been already demonstrated in a number of different application areas, including transport, energy, safety and healthcare. However, despite the growing number of IoT deployments, the majority of IoT applications tend to be self-contained, thereby forming application silos. A lightweight data centric integration and combination of these silos presents several challenges that still need to be addressed. Indeed, the ability to combine and synthesize data streams and services from diverse IoT platforms and testbeds, holds the promise to increase the potentiality of smart applications in terms of size, scope and targeted business context. In this article, a proof-of-concept implementation that federates two different IoT experimentation facilities by means of semantic-based technologies will be described. The specification and design of the implemented system and information models will be described together with the practical details of the developments carried out and its integration with the existing IoT platforms supporting the aforementioned testbeds. Overall, the system described in this paper demonstrates that it is possible to open new horizons in the development of IoT applications and experiments at a global scale, that transcend the (silo) boundaries of individual deployments, based on the semantic interconnection and interoperability of diverse IoT platforms and testbeds. PMID:27367695

  15. Automation of strategy using IDEF0 — A proof of concept

    Directory of Open Access Journals (Sweden)

    Gary R. Waissi

    2015-12-01

    Full Text Available The goal of this interdisciplinary paper is to show that an existing modeling language, Integration Definition for Function Modeling (IDEF0, is applicable for use in strategy modeling and for automation of strategic plan development and implementation. We will show how utilization of the systems modeling language IDEF0 simplifies strategic plan development, and moves strategic planning and management from a static, document-based approach to a model- and software-based approach. A sequence of examples, as a proof-of-concept, is shown to demonstrate the use of IDEF0 to translate document-based strategic plans to model-based plans. The advantages of IDEF0 include: a well-tested language, and comprehensive systems modeling technique. The resulting IDEF0 models are well-defined, well-structured, easy to understand, easy to modify and use, and can be extended to any depth of detail. It is noted, that while the paper focuses on small- and medium manufacturing enterprises (SME, the approach can be used for strategy development and strategy automation of any size company or organization.

  16. Proof of concept non-invasive estimation of peripheral venous oxygen saturation.

    Science.gov (United States)

    Khan, Musabbir; Pretty, Chris G; Amies, Alexander C; Balmer, Joel; Banna, Houda E; Shaw, Geoffrey M; Geoffrey Chase, J

    2017-05-19

    of this study is the proof of concept validation of a novel pulse oximeter sensor and calibration model to assess peripheral SvO2, and thus O2E, using the method used in this study. Further validation, improvement, and application of this model can aid in clinical diagnosis of microcirculation failures due to alterations in oxygen extraction.

  17. Visualizing Digital Forensic Datasets: A Proof of Concept.

    Science.gov (United States)

    Tassone, Christopher F R; Martini, Ben; Choo, Kim-Kwang Raymond

    2017-02-01

    Digital forensic visualization is an understudied area despite its potential to achieve significant improvements in the efficiency of an investigation, criminal or civil. In this study, a three-stage forensic data storage and visualization life cycle is presented. The first stage is the decoding of data, which involves preparing both structured and unstructured data for storage. In the storage stage, data are stored within our proposed database schema designed for ensuring data integrity and speed of storage and retrieval. The final stage is the visualization of stored data in a manner that facilitates user interaction. These functionalities are implemented in a proof of concept to demonstrate the utility of the proposed life cycle. The proof of concept demonstrates the utility of the proposed approach for the storage and visualization of digital forensic data. © 2017 American Academy of Forensic Sciences.

  18. High Altitude Venus Operational Concept (HAVOC): Proofs of Concept

    Science.gov (United States)

    Jones, Christopher A.; Arney, Dale C.; Bassett, George Z.; Clark, James R.; Hennig, Anthony I.; Snyder, Jessica C.

    2015-01-01

    The atmosphere of Venus is an exciting destination for both further scientific study and future human exploration. A recent internal NASA study of a High Altitude Venus Operational Concept (HAVOC) led to the development of an evolutionary program for the exploration of Venus, with focus on the mission architecture and vehicle concept for a 30-day crewed mission into Venus's atmosphere at 50 kilometers. Key technical challenges for the mission include performing the aerocapture maneuvers at Venus and Earth, inserting and inflating the airship at Venus during the entry sequence, and protecting the solar panels and structure from the sulfuric acid in the atmosphere. Two proofs of concept were identified that would aid in addressing some of the key technical challenges. To mitigate the threat posed by the sulfuric acid ambient in the atmosphere of Venus, a material was needed that could protect the systems while being lightweight and not inhibiting the performance of the solar panels. The first proof of concept identified candidate materials and evaluated them, finding FEP-Teflon (Fluorinated Ethylene Propylene-Teflon) to maintain 90 percent transmittance to relevant spectra even after 30 days of immersion in concentrated sulfuric acid. The second proof of concept developed and verified a packaging algorithm for the airship envelope to inform the entry, descent, and inflation analysis.

  19. Large-amplitude rotary induced-strain (LARIS) actuator proof-of-concept demonstrator

    Science.gov (United States)

    Giurgiutiu, Victor; Rogers, Craig A.; McNeil, Shane

    1997-06-01

    Induced-strain materials can produce very large forces and, hence, large energy density, but small actual displacements. A new concept for obtaining large-amplitude rotary displacements from small linear displacements generated by induced-strain material stacks is proposed. The concept utilizes the theory of twist-warping coupling in thin-wall open tubes. The theory of the proposed solid-state axial-to- rotary converter-amplifier, together with the appropriate bibliographical references, is given. A simple formula is generated for estimating the axial-to-rotary conversion- amplification coefficient from the geometrical length, L, and enclosed area, A, of the open tube. A large-displacement induced-strain rotary (LARIS) actuator proof-of-concept demonstrator was built and tested to verify and validate the theoretical developments. The LARIS actuator consisted of a 28 mm diameter, 1.2 m length open tube and a 120 micrometer, -1000 V PZT translator. The experimental set-up and the excitation and measuring equipment are fully described in the paper. A maximum rotary displacement of 8 degrees was measured, and the linear relationship between the rotation coefficient, the tube length, L, and the inverse of the enclosed area, A, was verified. An improved theoretical model, that accounts for the experimentally observed zero off-set, is also given. The theoretical developments and experimental tests presented in this paper show that the proposed LARIS actuator, based on a novel solid-state axial-to-rotary converter-amplifier utilizing the warping-torsion coupling of an open tube, is a viable design option, of great constructive simplicity and very low parts count. This concept can be successfully used in a series of aerospace and mechanical engineering applications, as for example in the actuation of adaptive control surfaces for aircraft wings and helicopter blades. The 8 degree rotary displacement capabilities measured on the proof-of-concept demonstrator can be easily

  20. Fuzzy logic inference-based Pavement Friction Management and real-time slippery warning systems: A proof of concept study.

    Science.gov (United States)

    Najafi, Shahriar; Flintsch, Gerardo W; Khaleghian, Seyedmeysam

    2016-05-01

    Minimizing roadway crashes and fatalities is one of the primary objectives of highway engineers, and can be achieved in part through appropriate maintenance practices. Maintaining an appropriate level of friction is a crucial maintenance practice, due to the effect it has on roadway safety. This paper presents a fuzzy logic inference system that predicts the rate of vehicle crashes based on traffic level, speed limit, and surface friction. Mamdani and Sugeno fuzzy controllers were used to develop the model. The application of the proposed fuzzy control system in a real-time slippery road warning system is demonstrated as a proof of concept. The results of this study provide a decision support model for highway agencies to monitor their network's friction and make appropriate judgments to correct deficiencies based on crash risk. Furthermore, this model can be implemented in the connected vehicle environment to warn drivers of potentially slippery locations.

  1. Machine learning methods to predict child posttraumatic stress: a proof of concept study.

    Science.gov (United States)

    Saxe, Glenn N; Ma, Sisi; Ren, Jiwen; Aliferis, Constantin

    2017-07-10

    The care of traumatized children would benefit significantly from accurate predictive models for Posttraumatic Stress Disorder (PTSD), using information available around the time of trauma. Machine Learning (ML) computational methods have yielded strong results in recent applications across many diseases and data types, yet they have not been previously applied to childhood PTSD. Since these methods have not been applied to this complex and debilitating disorder, there is a great deal that remains to be learned about their application. The first step is to prove the concept: Can ML methods - as applied in other fields - produce predictive classification models for childhood PTSD? Additionally, we seek to determine if specific variables can be identified - from the aforementioned predictive classification models - with putative causal relations to PTSD. ML predictive classification methods - with causal discovery feature selection - were applied to a data set of 163 children hospitalized with an injury and PTSD was determined three months after hospital discharge. At the time of hospitalization, 105 risk factor variables were collected spanning a range of biopsychosocial domains. Seven percent of subjects had a high level of PTSD symptoms. A predictive classification model was discovered with significant predictive accuracy. A predictive model constructed based on subsets of potentially causally relevant features achieves similar predictivity compared to the best predictive model constructed with all variables. Causal Discovery feature selection methods identified 58 variables of which 10 were identified as most stable. In this first proof-of-concept application of ML methods to predict childhood Posttraumatic Stress we were able to determine both predictive classification models for childhood PTSD and identify several causal variables. This set of techniques has great potential for enhancing the methodological toolkit in the field and future studies should seek to

  2. ReACT Methodology Proof of Concept Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Bri Rolston; Sarah Freeman

    2014-03-01

    The Department of Energy’s Office of Electricity Delivery and Energy Reliability (DOE-OE) funded INL Researchers to evaluate a novel process for assessing and mitigating cyber security risks. The proof of concept level of the method was tested in an industry environment. This case study, plus additional case studies will support the further development of the method into a tool to assist industry in securing their critical networks. This report provides an understanding of the process developed in the Response Analysis and Characterization Tool (ReACT) project. This report concludes with lessons learned and a roadmap for final development of these tools for use by industry.

  3. SSFF Health Management Analysis Report. Part 2: Proof of Concept

    Science.gov (United States)

    Wilson, L.; Spruill, J.; Hong, Y.

    1995-01-01

    In this Proof of Concept analysis on SSFF Health Management the following area was described: the Gas Distribution Subsystem (GDS) was studied and evaluated utilizing the PDR Configuration and with respect to the design features encompassing Health Management (HM) aspects outlined in the Generic Handbook. From the results of this study, it was found that there is a definite need for coordinating measurements within and between the subsystems that will ensure that Functional Failures are properly revealed and substantiated as valid by other measurements, even those from other interfacing subsystems.

  4. Phonetic compliance: a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Véronique eDelvaux

    2014-12-01

    Full Text Available In this paper, we introduce the concept of phonetic compliance, which is defined as the intrinsic individual ability to produce speech sounds that are unusual in the native language, and constitutes a part of the ability to acquire L2 phonetics and phonology. We argue that phonetic compliance represents a systematic source of variance that needs to be accounted for if one wants to improve the control over the independent variables manipulated in SLA experimental studies. We then present the results of a two-fold proof-of-concept study aimed at testing the feasibility of assessing phonetic compliance in terms of gradient. In study 1, a pilot data collection paradigm is implemented on an occasional sample of 10 native French speakers engaged in two reproduction tasks involving respectively vowels and aspirated stops, and data are analysed using descriptive statistics. In study 2, complementary data including L1-typical realizations are collected, resulting in the development of a first set of indicators that may be useful to appropriately assess, and further refine the concept of, phonetic compliance. Based on a critical analysis of the contributions and limitations of the proof-of-concept study, general discussion formulates the guidelines for the following stages of development of a reliable and valid test of phonetic compliance.

  5. Proof of Concept Study of Trade Space Configuration Tool for Spacecraft Design

    Science.gov (United States)

    Glidden, Geoffrey L.

    2009-01-01

    Spacecraft design is a very difficult and time consuming process because requirements and criteria are often changed or modified as the design is refined. Accounting for these adjustments in the design constraints plays a significant role in furthering the overall progress. There are numerous aspects and variables that hold significant influence on various characteristics of the design. This can be especially frustrating when attempting to conduct rapid trade space analysis on system configurations. Currently, the data and designs considered for trade space evaluations can only be displayed by using the traditional interfaces of Excel spreadsheets or CAD (Computer Aided Design) models. While helpful, these methods of analyzing the data from a systems engineering approach can be rather complicated and overwhelming. As a result, a proof of concept was conducted on a dynamic data visualization software called Thinkmap SDK (Software Developer Kit) to allow for better organization and understanding of the relationships between the various aspects that make up an entire design. The Orion Crew Module Aft Bay Subsystem was used as the test case for this study because the design and layout of many of the subsystem components will be significant in ensuring the overall center of gravity of the capsule is correct. A simplified model of this subsystem was created and programmed using Thinkmap SDK to create a preliminary prototype application of a Trade Space Configuration Tool. The completed application ensures that the core requirements for the Tool can be met. Further development is strongly suggested to produce a full prototype application to allow final evaluations and recommendations of the software capabilities.

  6. Pythia version 7-0.0 - a proof-of-concept version

    CERN Document Server

    Bertini, M; Sjöstrand, Torbjörn; Bertini, Marc; Lonnblad, Leif; Sjostrand, Torbjorn

    2001-01-01

    This document describes the first proof-of-concept version of the Pythia7 program. Pythia7 is a complete re-write of the Pythia program in C++. It is mainly intended to be a replacement for the `Lund' family of event generators, but is also a toolkit with a structure suitable for implementing any event generator model. In this document, the structure of the program is presented both from the user and the developer point of view. It is not intended to be a complete manual, but together with the documentation provided in the distribution, it should be sufficient to start working with the program.

  7. Towards soil property retrieval from space: Proof of concept using in situ observations

    Science.gov (United States)

    Bandara, Ranmalee; Walker, Jeffrey P.; Rüdiger, Christoph

    2014-05-01

    Soil moisture is a key variable that controls the exchange of water and energy fluxes between the land surface and the atmosphere. However, the temporal evolution of soil moisture is neither easy to measure nor monitor at large scales because of its high spatial variability. This is mainly a result of the local variation in soil properties and vegetation cover. Thus, land surface models are normally used to predict the evolution of soil moisture and yet, despite their importance, these models are based on low-resolution soil property information or typical values. Therefore, the availability of more accurate and detailed soil parameter data than are currently available is vital, if regional or global soil moisture predictions are to be made with the accuracy required for environmental applications. The proposed solution is to estimate the soil hydraulic properties via model calibration to remotely sensed soil moisture observation, with in situ observations used as a proxy in this proof of concept study. Consequently, the feasibility is assessed, and the level of accuracy that can be expected determined, for soil hydraulic property estimation of duplex soil profiles in a semi-arid environment using near-surface soil moisture observations under naturally occurring conditions. The retrieved soil hydraulic parameters were then assessed by their reliability to predict the root zone soil moisture using the Joint UK Land Environment Simulator model. When using parameters that were retrieved using soil moisture observations, the root zone soil moisture was predicted to within an accuracy of 0.04 m3/m3, which is an improvement of ∼0.025 m3/m3 on predictions that used published values or pedo-transfer functions.

  8. Design and evaluation of a hybrid radiofrequency applicator for magnetic resonance imaging and RF induced hyperthermia: electromagnetic field simulations up to 14.0 Tesla and proof-of-concept at 7.0 Tesla.

    Directory of Open Access Journals (Sweden)

    Lukas Winter

    Full Text Available This work demonstrates the feasibility of a hybrid radiofrequency (RF applicator that supports magnetic resonance (MR imaging and MR controlled targeted RF heating at ultrahigh magnetic fields (B0≥7.0T. For this purpose a virtual and an experimental configuration of an 8-channel transmit/receive (TX/RX hybrid RF applicator was designed. For TX/RX bow tie antenna electric dipoles were employed. Electromagnetic field simulations (EMF were performed to study RF heating versus RF wavelength (frequency range: 64 MHz (1.5T to 600 MHz (14.0T. The experimental version of the applicator was implemented at B0 = 7.0T. The applicators feasibility for targeted RF heating was evaluated in EMF simulations and in phantom studies. Temperature co-simulations were conducted in phantoms and in a human voxel model. Our results demonstrate that higher frequencies afford a reduction in the size of specific absorption rate (SAR hotspots. At 7T (298 MHz the hybrid applicator yielded a 50% iso-contour SAR (iso-SAR-50% hotspot with a diameter of 43 mm. At 600 MHz an iso-SAR-50% hotspot of 26 mm in diameter was observed. RF power deposition per RF input power was found to increase with B0 which makes targeted RF heating more efficient at higher frequencies. The applicator was capable of generating deep-seated temperature hotspots in phantoms. The feasibility of 2D steering of a SAR/temperature hotspot to a target location was demonstrated by the induction of a focal temperature increase (ΔT = 8.1 K in an off-center region of the phantom. Temperature simulations in the human brain performed at 298 MHz showed a maximum temperature increase to 48.6C for a deep-seated hotspot in the brain with a size of (19×23×32mm(3 iso-temperature-90%. The hybrid applicator provided imaging capabilities that facilitate high spatial resolution brain MRI. To conclude, this study outlines the technical underpinnings and demonstrates the basic feasibility of an 8-channel hybrid TX

  9. Design and evaluation of a hybrid radiofrequency applicator for magnetic resonance imaging and RF induced hyperthermia: electromagnetic field simulations up to 14.0 Tesla and proof-of-concept at 7.0 Tesla.

    Science.gov (United States)

    Winter, Lukas; Özerdem, Celal; Hoffmann, Werner; Santoro, Davide; Müller, Alexander; Waiczies, Helmar; Seemann, Reiner; Graessl, Andreas; Wust, Peter; Niendorf, Thoralf

    2013-01-01

    This work demonstrates the feasibility of a hybrid radiofrequency (RF) applicator that supports magnetic resonance (MR) imaging and MR controlled targeted RF heating at ultrahigh magnetic fields (B0≥7.0T). For this purpose a virtual and an experimental configuration of an 8-channel transmit/receive (TX/RX) hybrid RF applicator was designed. For TX/RX bow tie antenna electric dipoles were employed. Electromagnetic field simulations (EMF) were performed to study RF heating versus RF wavelength (frequency range: 64 MHz (1.5T) to 600 MHz (14.0T)). The experimental version of the applicator was implemented at B0 = 7.0T. The applicators feasibility for targeted RF heating was evaluated in EMF simulations and in phantom studies. Temperature co-simulations were conducted in phantoms and in a human voxel model. Our results demonstrate that higher frequencies afford a reduction in the size of specific absorption rate (SAR) hotspots. At 7T (298 MHz) the hybrid applicator yielded a 50% iso-contour SAR (iso-SAR-50%) hotspot with a diameter of 43 mm. At 600 MHz an iso-SAR-50% hotspot of 26 mm in diameter was observed. RF power deposition per RF input power was found to increase with B0 which makes targeted RF heating more efficient at higher frequencies. The applicator was capable of generating deep-seated temperature hotspots in phantoms. The feasibility of 2D steering of a SAR/temperature hotspot to a target location was demonstrated by the induction of a focal temperature increase (ΔT = 8.1 K) in an off-center region of the phantom. Temperature simulations in the human brain performed at 298 MHz showed a maximum temperature increase to 48.6C for a deep-seated hotspot in the brain with a size of (19×23×32)mm(3) iso-temperature-90%. The hybrid applicator provided imaging capabilities that facilitate high spatial resolution brain MRI. To conclude, this study outlines the technical underpinnings and demonstrates the basic feasibility of an 8-channel hybrid TX

  10. “概念证明中心”:美国研究型大学促进科研成果转化的新组织模式%"Proof of Concept Center":A New Organizational Model to Promote the Commercialization of Scientific Research in American Research Universities

    Institute of Scientific and Technical Information of China (English)

    卓泽林; 赵中建

    2015-01-01

    促进科研成果商业转化是激发区域和国家经济繁荣发展的重要渠道,但是基础研发活动与产品开发之间往往存在着一座“死亡之谷”。为了跨越“死亡之谷”、提高大学科研成果转化能力,美国兴起了一种新的组织模式———概念证明中心,旨在帮助解决大学研发成果与可市场化成果之间的空白。概念证明中心在美国已经取得明显的成效,它的成功经验对于我国科研成果转化有着重要启示。%Promoting the commercialization of scientific technology is an important way to stimulate regional and national economic prosperity and development. However, there tends to be a "valley of death" between basic research activities and product development. To cross the"valley of death"and enhance university's capability of commercialization of scientific research, there emerges a new kind of organizational model--proof of concept center in America, which mainly fills the gap between university research and marketable product. Proof of concept centers have made significant achievements in American research universities, and their successful experiences may shed light on the commercialization of scientific research in China.

  11. Effect of aerobic exercise on cancer-associated cognitive impairment: A proof-of-concept RCT.

    Science.gov (United States)

    Campbell, K L; Kam, J W Y; Neil-Sztramko, S E; Liu Ambrose, T; Handy, T C; Lim, H J; Hayden, S; Hsu, L; Kirkham, A A; Gotay, C C; McKenzie, D C; Boyd, L A

    2017-01-11

    Change in cognitive ability is a commonly reported adverse effect by breast cancer survivors. The underlying etiology of cognitive complaints is unclear and to date, there is limited evidence for effective intervention strategies. Exercise has been shown to improve cognitive function in older adults and animal models treated with chemotherapy. This proof-of-concept randomized controlled trial tested the effect of aerobic exercise versus usual lifestyle on cognitive function in postmenopausal breast cancer survivors. Women, aged 40 to 65 years, postmenopausal, stages I to IIIA breast cancer, and who self-reported cognitive dysfunction following chemotherapy treatment, were recruited and randomized to a 24-week aerobic exercise intervention (EX; n = 10) or usual lifestyle control (CON; n = 9). Participants completed self-report measures of the impact of cognitive issues on quality of life (Functional Assessment of Cancer Therapy-Cognitive version 3), objective neuropsychological testing, and functional magnetic resonance imaging at baseline and 24 weeks. Compared to CON, EX had a reduced time to complete a processing speed test (trail making test-A) (-14.2 seconds, P proof-of-concept results for the potential of aerobic exercise to improve cancer-related cognitive impairment and will serve to inform the development of future trials. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Computer-Supported Feedback Message Tailoring for Healthcare Providers in Malawi: Proof-of-Concept.

    Science.gov (United States)

    Landis-Lewis, Zach; Douglas, Gerald P; Hochheiser, Harry; Kam, Matthew; Gadabu, Oliver; Bwanali, Mwatha; Jacobson, Rebecca S

    2015-01-01

    Although performance feedback has the potential to help clinicians improve the quality and safety of care, healthcare organizations generally lack knowledge about how this guidance is best provided. In low-resource settings, tools for theory-informed feedback tailoring may enhance limited clinical supervision resources. Our objectives were to establish proof-of-concept for computer-supported feedback message tailoring in Malawi, Africa. We conducted this research in five stages: clinical performance measurement, modeling the influence of feedback on antiretroviral therapy (ART) performance, creating a rule-based message tailoring process, generating tailored messages for recipients, and finally analysis of performance and message tailoring data. We retrospectively generated tailored messages for 7,448 monthly performance reports from 11 ART clinics. We found that tailored feedback could be routinely generated for four guideline-based performance indicators, with 35% of reports having messages prioritized to optimize the effect of feedback. This research establishes proof-of-concept for a novel approach to improving the use of clinical performance feedback in low-resource settings and suggests possible directions for prospective evaluations comparing alternative designs of feedback messages.

  13. SPARCLE: Electrostatic Dust Control Tool Proof of Concept

    Science.gov (United States)

    Clark, P. E.; Curtis, S. A.; Minetto, F.; Marshall, J.; Nuth, J.; Calle, C.

    2010-01-01

    Successful exploration of most planetary surfaces, with their impact-generated dusty regoliths, will depend on the capabilities to keep surfaces free of the performance-compromising dust. Once in contact with surfaces, whether set in motion by natural or mechanical means, regolith fines, or dust, behave like abrasive Velcro, coating surfaces, clogging mechanisms, making movement progressively more difticult, and being almost impossible to remove by mechanical mcans (brushing). The successful dust removal strategy will deal with dust dynamics resulting from interaction between Van der Waals and Coulombic forces. Here, proof of concept for an electrostatically-based concept for dust control tool is described and demonstrated. A low power focused electron beam is used in the presence of a small electrical field to increase the negative charge to mass ratio of a dusty surface until dust repulsion and attraction to a lower potential surface, acting as a dust collector, occurred. Our goal is a compact device of less than 5 kg mass and using less than 5 watts of power to be operational in less than 5 years with heritage from ionic sweepers for active spacecraft potential control (e.g ., on POLAR). Rovers could be fitted with devices that could hamess the removal of dust for sampling as part of the extended exploration process on Mercury, Mars, asteroids or outer solar system satellites, as well as the Moon.

  14. The paperless labeling initiative: a proof-of-concept study.

    Science.gov (United States)

    Ruchalski, Charles

    2004-01-01

    Traditional paper professional package inserts (PPIs) are used on a daily basis by a variety of healthcare providers to locate and disseminate drug information. Unfortunately, paper PPIs are sometimes not accessible to the healthcare provider, appear unreadable due to varied font sizes, and are often considered not to be user-friendly. In December 2000, the Food and Drug Administration proposed regulations that would revise the format of PPIs. To determine whether electronic delivery of PPI information is achievable in community pharmacy practice settings. Electronic PPIs are an alternative means of delivering this information. This 12-week proof-of-concept study evaluated the Health Information Designs/Thomson Healthcare and Etreby Computer Company for electronic delivery of PPIs in 6 chain and 4 independent community pharmacies, with 5 pharmacies evaluating each system. Participating pharmacists were asked 9 questions designed to determine the feasibility of implementing electronic PPI delivery, as well as pharmacist satisfaction with each system. Pharmacists deemed both systems to be accessible and user-friendly. Pharmacists from both groups felt that the electronic PPIs were challenging to read and that printing took too long. Future studies in a more diverse selection of dispensing sites, including pharmacies (community and hospital based), clinics, and physician practices, need to be performed to maximize the use of electronic PPIs.

  15. SPARCLE: Electrostatic Dust Control Tool Proof of Concept

    Science.gov (United States)

    Clark, P. E.; Curtis, S. A.; Minetto, F.; Marshall, J.; Nuth, J.; Calle, C.

    2010-01-01

    Successful exploration of most planetary surfaces, with their impact-generated dusty regoliths, will depend on the capabilities to keep surfaces free of the performance-compromising dust. Once in contact with surfaces, whether set in motion by natural or mechanical means, regolith fines, or dust, behave like abrasive Velcro, coating surfaces, clogging mechanisms, making movement progressively more difticult, and being almost impossible to remove by mechanical mcans (brushing). The successful dust removal strategy will deal with dust dynamics resulting from interaction between Van der Waals and Coulombic forces. Here, proof of concept for an electrostatically-based concept for dust control tool is described and demonstrated. A low power focused electron beam is used in the presence of a small electrical field to increase the negative charge to mass ratio of a dusty surface until dust repulsion and attraction to a lower potential surface, acting as a dust collector, occurred. Our goal is a compact device of less than 5 kg mass and using less than 5 watts of power to be operational in less than 5 years with heritage from ionic sweepers for active spacecraft potential control (e.g ., on POLAR). Rovers could be fitted with devices that could hamess the removal of dust for sampling as part of the extended exploration process on Mercury, Mars, asteroids or outer solar system satellites, as well as the Moon.

  16. 76 FR 36919 - Proof of Concept Demonstration for Electronic Reporting of Clean Water Act Compliance Monitoring...

    Science.gov (United States)

    2011-06-23

    ... commercial products or services of any third-party software providers. Proof of Concept Demonstration for... software provider selected for participating in the technical proof of concept demonstration by EPA must... concept by the software provider are: Ability of the software provider's electronic reporting software...

  17. Proton-minibeam radiation therapy: A proof of concept

    Energy Technology Data Exchange (ETDEWEB)

    Prezado, Y. [IMNC-UMR 8165, CNRS, Paris 7 and Paris 11 Universities, 15 rue Georges Clemenceau, 91406 Orsay Cedex (France); Fois, G. R. [Dipartimento di Fisica, Universita degli Studi di Cagliari, Strada provinciale Monserrato Sestu km 0.700, Monserrato, Cagliari 09042 (Italy)

    2013-03-15

    Purpose: This Monte Carlo simulation work aims at studying a new radiotherapy approach called proton-minibeam radiation therapy (pMBRT). The main objective of this proof of concept was the evaluation of the possible gain in tissue sparing, thanks to the spatial fractionation of the dose, which could be used to deposit higher and potentially curative doses in clinical cases where tissue tolerances are a limit for conventional methods. Methods: Monte Carlo simulations (GATE v.6) have been used as a method to calculate the ratio of the peak-to-valley doses (PVDR) for arrays of proton minibeams of 0.7 mm width and several center-to-center distances, at different depths in a water phantom. The beam penumbras were also evaluated as an important parameter for tissue sparing, for example, in the treatment of non-cancer diseases like epilepsy. Two proton energies were considered in this study: a clinically relevant energy (105 MeV) and a very high energy (1 GeV), to benefit from a reduced lateral scattering. For the latter case, an interlaced geometry was also evaluated. Results: Higher or similar PVDR than the ones obtained in x-rays minibeam radiation therapy were achieved in several pMBRT configurations. In addition, for the two energies studied, the beam penumbras are smaller than in the case of Gamma Knife radiosurgery. Conclusions: The high PVDR obtained for some configurations and the small penumbras in comparison with existing radiosurgery techniques, suggest a potential gain in healthy tissue sparing in this new technique. Biological studies are warranted to assess the effects of pMBRT on both normal and tumoral tissues.

  18. Wireless Roadside Inspection Proof of Concept Test Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Capps, Gary J [ORNL; Franzese, Oscar [ORNL; Knee, Helmut E [ORNL; Plate, Randall S [ORNL; Lascurain, Mary Beth [ORNL

    2009-03-01

    The U.S. Department of Transportation (DOT) FMCSA commissioned the Wireless Roadside Inspection (WRI) Program to validate technologies and methodologies that can improve safety through inspections using wireless technologies that convey real-time identification of commercial vehicles, drivers, and carriers, as well as information about the condition of the vehicles and their drivers. It is hypothesized that these inspections will: -- Increase safety -- Decrease the number of unsafe commercial vehicles on the road; -- Increase efficiency -- Speed up the inspection process, enabling more inspections to occur, at least on par with the number of weight inspections; -- Improve effectiveness -- Reduce the probability of drivers bypassing CMV inspection stations and increase the likelihood that fleets will attempt to meet the safety regulations; and -- Benefit industry -- Reduce fleet costs, provide good return-on-investment, minimize wait times, and level the playing field. The WRI Program is defined in three phases which are: Phase 1: Proof of Concept Test (POC) Testing of commercially available off-the-shelf (COTS) or near-COTS technology to validate the wireless inspection concept. Phase 2: Pilot Test Safety technology maturation and back office system integration Phase 3: Field Operational Test Multi-vehicle testing over a multi-state instrumented corridor This report focuses on Phase 1 efforts that were initiated in March, 2006. Technical efforts dealt with the ability of a Universal Wireless Inspection System (UWIS) to collect driver, vehicle, and carrier information; format a Safety Data Message Set from this information; and wirelessly transmit a Safety Data Message Set to a roadside receiver unit or mobile enforcement vehicle.

  19. Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation: proof of concept and application to the pyramidal tract side effect induced by pallidal stimulation.

    Science.gov (United States)

    Baumgarten, Clement; Zhao, Yulong; Sauleau, Paul; Malrain, Cecile; Jannin, Pierre; Haegelen, Claire

    2016-04-01

    Deep brain stimulation of the medial globus pallidus (GPm) is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning-based method called PyMAN (PTSE model based on artificial neural network) accounting for the current used in stimulation, the three-dimensional electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the GPm have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was 0.78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

  20. Design and Control of a Proof-of-Concept Active Jet Engine Intake Using Shape Memory Alloy Actuators

    Science.gov (United States)

    Song, Gangbing; Ma, Ning; Penney, Nicholas; Barr, Todd; Lee, Ho-Jun; Arnold, Steven M.

    2004-01-01

    The design and control of a novel proof-of-concept active jet engine intake using Nickel-Titanium (Ni-Ti or Nitinol) shape memory alloy (SMA) wire actuators is used to demonstrate the potential of an adaptive intake to improve the fuel efficiency of a jet engine. The Nitinol SMA material is selected for this research due to the material's ability to generate large strains of up to 5 percent for repeated operations, a high power-to-weight ratio, electrical resistive actuation, and easy fabrication into a variety of shapes. The proof-of-concept engine intake employs an overlapping leaf design arranged in a concentric configuration. Each leaf is mounted on a supporting bar that rotates upon actuation by SMA wires electrical resistive heating. Feedback control is enabled through the use of a laser range sensor to detect the movement of a leaf and determine the radius of the intake area. Due to the hysteresis behavior inherent in SMAs, a nonlinear robust controller is used to direct the SMA wire actuation. The controller design utilizes the sliding-mode approach to compensate for the nonlinearities associated with the SMA actuator. Feedback control experiments conducted on a fabricated proof-of-concept model have demonstrated the capability to precisely control the intake area and achieve up to a 25 percent reduction in intake area. The experiments demonstrate the feasibility of engine intake area control using the proposed design.

  1. Therapeutic NOTCH3 cysteine correction in CADASIL using exon skipping: in vitro proof of concept.

    Science.gov (United States)

    Rutten, Julie W; Dauwerse, Hans G; Peters, Dorien J M; Goldfarb, Andrew; Venselaar, Hanka; Haffner, Christof; van Ommen, Gert-Jan B; Aartsma-Rus, Annemieke M; Lesnik Oberstein, Saskia A J

    2016-04-01

    . Transfection of these antisense oligonucleotides into CADASIL patient-derived cerebral vascular smooth muscle cells resulted in successful exon skipping, without abrogating NOTCH3 signalling. Combined, these data provide proof of concept for this novel application of exon skipping, and are a first step towards the development of a rational therapeutic approach applicable to up to 94% of CADASIL-causing mutations.

  2. Three-dimensional modeling of oxidized-LDL accumulation and HDL mass transport in a coronary artery: a proof-of-concept study for predicting the region of atherosclerotic plaque development.

    Science.gov (United States)

    Sakellarios, Antonis I; Siogkas, Panagiotis K; Athanasiou, Lambros S; Exarchos, Themis P; Papafaklis, Michail I; Bourantas, Christos V; Naka, Katerina K; Michalis, Lampros K; Filipovic, Nenad; Parodi, Oberdan; Fotiadis, Dimitrios I

    2013-01-01

    Low density lipoprotein (LDL) has a significant role on the atherosclerotic plaque development, while the concentration of high density lipoproteins (HDL) is considered to play an atheroprotective role according to several biochemical mechanisms. In this work, it is the first time that both LDL and HDL concentrations are taken into account in order to predict the regions prone for plaque development. Our modeling approach is based on the use of a realistic three-dimensional reconstructed pig coronary artery in two time points. Biochemical data measured in the pig were also included in order to develop a more customized model. We modeled coronary blood flow by solving the Navier-Stokes equations in the arterial lumen and plasma filtration in the arterial wall using Darcy's Law. HDL transport was modeled only in the arterial lumen using the convection-diffusion equation, while LDL transport was modeled both in the lumen and the arterial wall. An additional novelty of this work is that we model the oxidation of LDL taking into account the atheroprotective role of HDL. The results of our model were in good agreement with histological findings demonstrating that increased oxidized LDL is found near regions of advanced plaques, while non-oxidized LDL is found in regions of early plaque types.

  3. Helistroke: neurointerventionalist helicopter transport for interventional stroke treatment: proof of concept and rationale.

    Science.gov (United States)

    Hui, Ferdinand K; El Mekabaty, Amgad; Schultz, Jacky; Hong, Kelvin; Horton, Karen; Urrutia, Victor; Naqvi, Imama; Brast, Shawn; Lynch, John K; Nadareishvili, Zurab

    2017-05-02

    It is increasingly recognized that time is one of the key determinants in acute stroke outcome when interventional stroke therapy is applied. With increasing device efficacy and understanding of imaging triage options, reducing pre-treatment time loss may be a critical component of improving interventional stroke outcomes for the population at large. Time sensitive procedures such as organ harvest have transported physicians to the patient site to improve time to procedure. Applying this same principle to interventional stroke management may be a valid paradigm. Previous logistical deliberation with hospital and Medevac companies was carried out to provide the rationale and funding for helicopter transfer of a neurointerventionalist to an in-network hospital with an on-site angiographic suite. An appropriate patient with large vessel occlusion and an NIH Stroke Scale score >8 was identified. MRI was performed, then the Medevac transport system was activated and the intervention was carried out. Times were collected during the case and assessed for time efficiency. The proof of concept case was identified and Medevac was consulted at 12:13 after verifying that no in-house emergencies would prevent physician departure. Weather clearance was obtained and stroke intervention confirmed as a go at 12:24. Groin puncture occurred at 13:07 and the intervention was completed at 13:41. The total time from decision-to-treat to groin puncture was 43 min and groin closure was completed at 77 min from decision-to-treat. This proof of concept case is presented for logistical, financial and use-case analysis. As it is a first case, times can likely be improved. We assert that this model may be another option in the spoke-and-hub design of stroke systems of care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Remarkable phylogenetic resolution of the most complex clade of Cyprinidae (Teleostei: Cypriniformes): a proof of concept of homology assessment and partitioning sequence data integrated with mixed model Bayesian analyses.

    Science.gov (United States)

    Tao, Wenjing; Mayden, Richard L; He, Shunping

    2013-03-01

    Despite many efforts to resolve evolutionary relationships among major clades of Cyprinidae, some nodes have been especially problematic and remain unresolved. In this study, we employ four nuclear gene fragments (3.3kb) to infer interrelationships of the Cyprinidae. A reconstruction of the phylogenetic relationships within the family using maximum parsimony, maximum likelihood, and Bayesian analyses is presented. Among the taxa within the monophyletic Cyprinidae, Rasborinae is the basal-most lineage; Cyprinine is sister to Leuciscine. The monophyly for the subfamilies Gobioninae, Leuciscinae and Acheilognathinae were resolved with high nodal support. Although our results do not completely resolve relationships within Cyprinidae, this study presents novel and significant findings having major implications for a highly diverse and enigmatic clade of East-Asian cyprinids. Within this monophyletic group five closely-related subgroups are identified. Tinca tinca, one of the most phylogenetically enigmatic genera in the family, is strongly supported as having evolutionary affinities with this East-Asian clade; an established yet remarkable association because of the natural variation in phenotypes and generalized ecological niches occupied by these taxa. Our results clearly argue that the choice of partitioning strategies has significant impacts on the phylogenetic reconstructions, especially when multiple genes are being considered. The most highly partitioned model (partitioned by codon positions within genes) extracts the strongest phylogenetic signals and performs better than any other partitioning schemes supported by the strongest 2Δln Bayes factor. Future studies should include higher levels of taxon sampling and partitioned, model-based analyses.

  5. A proof-of-concept implementation of a unit-based advanced practice registered nurse (APRN) role: structural empowerment, role clarity and team effectiveness.

    Science.gov (United States)

    Feistritzer, Nancye R; Jones, Pam O

    2014-03-01

    The quest for decreased cost of care and improved outcomes has created the need for highly effective clinical roles and teams. This article describes the role of a unit-based advanced practice registered nurse (APRN) within a proof-of-concept implementation of a new care delivery model, the Vanderbilt Anticipatory Care Team. Role clarity is central to both structural empowerment of the APRN and team effectiveness. A modified PeaceHealth Team Development Measure tool measured baseline role clarity as a component of overall team effectiveness. A role description for the unit-based APRN based on a comprehensive assessment of the proof-of-concept unit is provided.

  6. Strategies for Determining Correct Cytochrome P450 Contributions in Hepatic Clearance Predictions: In Vitro-In Vivo Extrapolation as Modelling Approach and Tramadol as Proof-of Concept Compound.

    Science.gov (United States)

    T'jollyn, Huybrecht; Snoeys, Jan; Van Bocxlaer, Jan; De Bock, Lies; Annaert, Pieter; Van Peer, Achiel; Allegaert, Karel; Mannens, Geert; Vermeulen, An; Boussery, Koen

    2017-06-01

    Although the measurement of cytochrome P450 (CYP) contributions in metabolism assays is straightforward, determination of actual in vivo contributions might be challenging. How representative are in vitro for in vivo CYP contributions? This article proposes an improved strategy for the determination of in vivo CYP enzyme-specific metabolic contributions, based on in vitro data, using an in vitro-in vivo extrapolation (IVIVE) approach. Approaches are exemplified using tramadol as model compound, and CYP2D6 and CYP3A4 as involved enzymes. Metabolism data for tramadol and for the probe substrates midazolam (CYP3A4) and dextromethorphan (CYP2D6) were gathered in human liver microsomes (HLM) and recombinant human enzyme systems (rhCYP). From these probe substrates, an activity-adjustment factor (AAF) was calculated per CYP enzyme, for the determination of correct hepatic clearance contributions. As a reference, tramadol CYP contributions were scaled-back from in vivo data (retrograde approach) and were compared with the ones derived in vitro. In this view, the AAF is an enzyme-specific factor, calculated from reference probe activity measurements in vitro and in vivo, that allows appropriate scaling of a test drug's in vitro activity to the 'healthy volunteer' population level. Calculation of an AAF, thus accounts for any 'experimental' or 'batch-specific' activity difference between in vitro HLM and in vivo derived activity. In this specific HLM batch, for CYP3A4 and CYP2D6, an AAF of 0.91 and 1.97 was calculated, respectively. This implies that, in this batch, the in vitro CYP3A4 activity is 1.10-fold higher and the CYP2D6 activity 1.97-fold lower, compared to in vivo derived CYP activities. This study shows that, in cases where the HLM pool does not represent the typical mean population CYP activities, AAF correction of in vitro metabolism data, optimizes CYP contributions in the prediction of hepatic clearance. Therefore, in vitro parameters for any test compound

  7. Dose fractionated gamma knife radiosurgery for large arteriovenous malformations on daily or alternate day schedule outside the linear quadratic model: Proof of concept and early results. A substitute to volume fractionation.

    Science.gov (United States)

    Mukherjee, Kanchan Kumar; Kumar, Narendra; Tripathi, Manjul; Oinam, Arun S; Ahuja, Chirag K; Dhandapani, Sivashanmugam; Kapoor, Rakesh; Ghoshal, Sushmita; Kaur, Rupinder; Bhatt, Sandeep

    2017-01-01

    To evaluate the feasibility, safety and efficacy of dose fractionated gamma knife radiosurgery (DFGKRS) on a daily schedule beyond the linear quadratic (LQ) model, for large volume arteriovenous malformations (AVMs). Between 2012-16, 14 patients of large AVMs (median volume 26.5 cc) unsuitable for surgery or embolization were treated in 2-3 of DFGKRS sessions. The Leksell G frame was kept in situ during the whole procedure. 86% (n = 12) patients had radiologic evidence of bleed, and 43% (n = 6) had presented with a history of seizures. 57% (n = 8) patients received a daily treatment for 3 days and 43% (n = 6) were on an alternate day (2 fractions) regimen. The marginal dose was split into 2 or 3 fractions of the ideal prescription dose of a single fraction of 23-25 Gy. The median follow up period was 35.6 months (8-57 months). In the three-fraction scheme, the marginal dose ranged from 8.9-11.5 Gy, while in the two-fraction scheme, the marginal dose ranged from 11.3-15 Gy at 50% per fraction. Headache (43%, n = 6) was the most common early postoperative complication, which was controlled with short course steroids. Follow up evaluation of at least three years was achieved in seven patients, who have shown complete nidus obliteration in 43% patients while the obliteration has been in the range of 50-99% in rest of the patients. Overall, there was a 67.8% reduction in the AVM volume at 3 years. Nidus obliteration at 3 years showed a significant rank order correlation with the cumulative prescription dose (p 0.95, P value 0.01), with attainment of near-total (more than 95%) obliteration rates beyond 29 Gy of the cumulative prescription dose. No patient receiving a cumulative prescription dose of less than 31 Gy had any severe adverse reaction. In co-variate adjusted ordinal regression, only the cumulative prescription dose had a significant correlation with common terminology criteria for adverse events (CTCAE) severity (P value 0.04), independent of age, AVM volume

  8. Quantification of coffee blends for authentication of Asian palm civet coffee (Kopi Luwak) via metabolomics: A proof of concept.

    Science.gov (United States)

    Jumhawan, Udi; Putri, Sastia Prama; Yusianto; Bamba, Takeshi; Fukusaki, Eiichiro

    2016-07-01

    Asian palm civet coffee (Kopi Luwak), an animal-digested coffee with an exotic feature, carries a notorious reputation of being the rarest and most expensive coffee beverage in the world. Considering that illegal mixture of cheap coffee into civet coffee is a growing concern among consumers, we evaluated the use of metabolomics approach and orthogonal projection to latent structures (OPLS) prediction technique to quantify the degree of coffee adulteration. Two prediction sets, consisting of certified and commercial coffee, were made from a blend of civet and regular coffee with eleven mixing percentages. The prediction model exhibited accurate estimation of coffee blend percentage thus, successfully validating the prediction and quantification of the mixing composition of known-unknown samples. This work highlighted proof of concept of metabolomics application to predict degree of coffee adulteration by determining the civet coffee fraction in blends.

  9. SALT DAMAGE CRITERION PROOF-OF-CONCEPT RESEARCH

    Energy Technology Data Exchange (ETDEWEB)

    Kerry L. DeVries; Kirby D. Mellegard; Gary D. Callahan

    2002-11-01

    The purpose of this study was to conduct a field-scale application demonstrating the use of continuum damage mechanics to determine the minimum allowable operating pressure of compressed natural gas storage caverns in salt formations. A geomechanical study was performed of two natural gas storage caverns (one existing and one planned) utilizing state-of-the-art salt mechanics to assess the potential for cavern instability and collapse. The geomechanical study consisted primarily of laboratory testing, theoretical development, and analytical/numerical tasks. A total of 50 laboratory tests was performed on salt specimens to aid in the development and definition of the material model used to predict the behavior of rock salt. Material model refinement was performed that improved the predictive capability of modeling salt during damage healing, recovery of work-hardened salt, and the behavior of salt at stress states other than triaxial compression. Results of this study showed that the working gas capacity of the existing cavern could be increased by 18 percent and the planned cavern could be increased by 8 percent using the proposed method compared to a conventional stress-based method. Further refinement of the continuum damage model is recommended to account for known behavior of salt at stress conditions other than triaxial compression that is not characterized accurately by the existing model.

  10. A Probabilistic Framework for Risk Analysis of Widespread Flood Events: A Proof-of-Concept Study.

    Science.gov (United States)

    Schneeberger, Klaus; Huttenlau, Matthias; Winter, Benjamin; Steinberger, Thomas; Achleitner, Stefan; Stötter, Johann

    2017-07-27

    This article presents a flood risk analysis model that considers the spatially heterogeneous nature of flood events. The basic concept of this approach is to generate a large sample of flood events that can be regarded as temporal extrapolation of flood events. These are combined with cumulative flood impact indicators, such as building damages, to finally derive time series of damages for risk estimation. Therefore, a multivariate modeling procedure that is able to take into account the spatial characteristics of flooding, the regionalization method top-kriging, and three different impact indicators are combined in a model chain. Eventually, the expected annual flood impact (e.g., expected annual damages) and the flood impact associated with a low probability of occurrence are determined for a study area. The risk model has the potential to augment the understanding of flood risk in a region and thereby contribute to enhanced risk management of, for example, risk analysts and policymakers or insurance companies. The modeling framework was successfully applied in a proof-of-concept exercise in Vorarlberg (Austria). The results of the case study show that risk analysis has to be based on spatially heterogeneous flood events in order to estimate flood risk adequately. © 2017 Society for Risk Analysis.

  11. Can openEHR archetypes be used in a national context? The Danish archetype proof-of-concept project.

    Science.gov (United States)

    Bernstein, Knut; Tvede, Ida; Petersen, Jan; Bredegaard, Kirsten

    2009-01-01

    Semantic interoperability and secondary use of data are important informatics challenges in modern healthcare. Connected Digital Health Denmark is investigating if the openEHR reference model, archetypes and templates could be used for representing and exchanging clinical content specification and could become a candidate for a national logical infrastructure for semantic interoperability. The Danish archetype proof-of-concept project has tried out some elements of the openEHR methodology in cooperation with regions and vendors. The project has pointed out benefits and challenges using archetypes, and has identified barriers that need to be addressed in the next steps.

  12. Technical Note: Motion-perturbation method applied to dosimetry of dynamic MLC target tracking—A proof-of-concept

    Energy Technology Data Exchange (ETDEWEB)

    Feygelman, Vladimir, E-mail: vladimir.feygelman@moffitt.org; Tonner, Brian; Hunt, Dylan; Zhang, Geoffrey; Moros, Eduardo [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida 33612 (United States); Stambaugh, Cassandra [Department of Physics, University of South Florida, Tampa, Florida 33612 (United States); Nelms, Benjamin E. [Canis Lupus LLC, Merrimac, Wisconsin 53561 (United States)

    2015-11-15

    Purpose: Previous studies show that dose to a moving target can be estimated using 4D measurement-guided dose reconstruction based on a process called virtual motion simulation, or VMS. A potential extension of VMS is to estimate dose during dynamic multileaf collimator (MLC)-tracking treatments. The authors introduce a modified VMS method and quantify its performance as proof-of-concept for tracking applications. Methods: Direct measurements with a moving biplanar diode array were used to verify accuracy of the VMS dose estimates. A tracking environment for variably sized circular MLC apertures was simulated by sending preprogrammed control points to the MLC while simultaneously moving the accelerator treatment table. Sensitivity of the method to simulated tracking latency (0–700 ms) was also studied. Potential applicability of VMS to fast changing beam apertures was evaluated by modeling, based on the demonstrated dependence of the cumulative dose on the temporal dose gradient. Results: When physical and virtual latencies were matched, the agreement rates (2% global/2 mm gamma) between the VMS and the biplanar dosimeter were above 96%. When compared to their own reference dose (0 induced latency), the agreement rates for VMS and biplanar array track closely up to 200 ms of induced latency with 10% low-dose cutoff threshold and 300 ms with 50% cutoff. Time-resolved measurements suggest that even in the modulated beams, the error in the cumulative dose introduced by the 200 ms VMS time resolution is not likely to exceed 0.5%. Conclusions: Based on current results and prior benchmarks of VMS accuracy, the authors postulate that this approach should be applicable to any MLC-tracking treatments where leaf speeds do not exceed those of the current Varian accelerators.

  13. Technical Note: Motion-perturbation method applied to dosimetry of dynamic MLC target tracking--A proof-of-concept.

    Science.gov (United States)

    Feygelman, Vladimir; Tonner, Brian; Stambaugh, Cassandra; Hunt, Dylan; Zhang, Geoffrey; Moros, Eduardo; Nelms, Benjamin E

    2015-11-01

    Previous studies show that dose to a moving target can be estimated using 4D measurement-guided dose reconstruction based on a process called virtual motion simulation, or VMS. A potential extension of VMS is to estimate dose during dynamic multileaf collimator (MLC)-tracking treatments. The authors introduce a modified VMS method and quantify its performance as proof-of-concept for tracking applications. Direct measurements with a moving biplanar diode array were used to verify accuracy of the VMS dose estimates. A tracking environment for variably sized circular MLC apertures was simulated by sending preprogrammed control points to the MLC while simultaneously moving the accelerator treatment table. Sensitivity of the method to simulated tracking latency (0-700 ms) was also studied. Potential applicability of VMS to fast changing beam apertures was evaluated by modeling, based on the demonstrated dependence of the cumulative dose on the temporal dose gradient. When physical and virtual latencies were matched, the agreement rates (2% global/2 mm gamma) between the VMS and the biplanar dosimeter were above 96%. When compared to their own reference dose (0 induced latency), the agreement rates for VMS and biplanar array track closely up to 200 ms of induced latency with 10% low-dose cutoff threshold and 300 ms with 50% cutoff. Time-resolved measurements suggest that even in the modulated beams, the error in the cumulative dose introduced by the 200 ms VMS time resolution is not likely to exceed 0.5%. Based on current results and prior benchmarks of VMS accuracy, the authors postulate that this approach should be applicable to any MLC-tracking treatments where leaf speeds do not exceed those of the current Varian accelerators.

  14. Reservoir Cannulas for Pediatric Oxygen Therapy: A Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Grace Wu

    2016-01-01

    Full Text Available Hypoxemia is a complication of pneumonia—the leading infectious cause of death in children worldwide. Treatment generally requires oxygen-enriched air, but access in low-resource settings is expensive and unreliable. We explored use of reservoir cannulas (RCs, which yield oxygen savings in adults but have not been examined in children. Toddler, small child, and adolescent breathing profiles were simulated with artificial lung and airway models. An oxygen concentrator provided flow rates of 0 to 5 L/min via a standard nasal cannula (NC or RC, and delivered oxygen fraction (FdO2 was measured. The oxygen savings ratio (SR and absolute flow savings (AFS were calculated, comparing NC and RC. We demonstrated proof-of-concept that pendant RCs could conserve oxygen during pediatric therapy. SR mean and standard deviation were 1.1±0.2 to 1.4±0.4, 1.1±0.1 to 1.7±0.3, and 1.3±0.1 to 2.4±0.3 for toddler, small child, and adolescent models, respectively. Maximum AFS observed were 0.3±0.3, 0.2±0.1, and 1.4±0.3 L/min for the same models. RCs have the potential to reduce oxygen consumption during treatment of hypoxemia in children; however, further evaluation of products is needed, followed by clinical analysis in patients.

  15. Engineering of Saccharomyces cerevisiae for the production of dihydroxyacetone (DHA) from sugars: a proof of concept.

    Science.gov (United States)

    Nguyen, H T T; Nevoigt, E

    2009-11-01

    Dihydroxyacetone (DHA) has numerous industrial applications. In this work, we pursue the idea to produce DHA from sugars in the yeast Saccharomyces cerevisiae, via glycerol as an intermediate. Firstly, three glycerol dehydrogenase (GDH) genes from different microbial sources were expressed in yeast. Among them, the NAD(+)-dependent GDH of Hansenula polymorpha showed the highest glycerol-oxidizing activity. DHA concentration in shake-flask experiments was roughly 100mg/lDHA from 20g/l glucose, i.e. five times the wild-type level. This level was achieved only when cultures were subjected to osmotic stress, known to enhance glycerol production and accumulation in S. cerevisiae. Secondly, DHA kinase activity was abolished to prevent conversion of DHA to dihydroxyacetone phosphate (DHAP). The dak1Deltadak2Delta double-deletion mutant overexpressing H. polymorpha gdh produced 700mg/l DHA under the same conditions. Although current DHA yield and titer still need to be optimized, our approach provides the proof of concept for producing DHA from sugars in yeast.

  16. Microwave bone imaging: a preliminary scanning system for proof-of-concept.

    Science.gov (United States)

    Ruvio, Giuseppe; Cuccaro, Antonio; Solimene, Raffaele; Brancaccio, Adriana; Basile, Bruno; Ammann, Max J

    2016-09-01

    This Letter introduces a feasibility study of a scanning system for applications in biomedical bone imaging operating in the microwave range 0.5-4 GHz. Mechanical uncertainties and data acquisition time are minimised by using a fully automated scanner that controls two antipodal Vivaldi antennas. Accurate antenna positioning and synchronisation with data acquisition enables a rigorous proof-of-concept for the microwave imaging procedure of a multi-layer phantom including skin, fat, muscle and bone tissues. The presence of a suitable coupling medium enables antenna miniaturisation and mitigates the impedance mismatch between antennas and phantom. The three-dimensional image of tibia and fibula is successfully reconstructed by scanning the multi-layer phantom due to the distinctive dielectric contrast between target and surrounding tissues. These results show the viability of a microwave bone imaging technology which is low cost, portable, non-ionising, and does not require specially trained personnel. In fact, as no a-priori characterisation of the antenna is required, the image formation procedure is very conveniently simplified.

  17. Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Proof of Concept Study

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2013-01-01

    Full Text Available Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7. Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT scan recorded objective changes. Out of 32 patients, a total of 29 (91% patients improved on total ISAA scores and 20 patients (62% showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P<0.001 on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism.

  18. Photodynamic therapy in neurosurgery: a proof of concept of treatment planning system

    Science.gov (United States)

    Dupont, C.; Reyns, N.; Mordon, S.; Vermandel, M.

    2017-02-01

    Glioblastoma (GBM) is the most common primary brain tumor. PhotoDynamic Therapy (PDT) appears as an interesting research field to improve GBM treatment. Nevertheless, PDT cannot fit into the current therapeutic modalities according to several reasons: the lack of reliable and reproducible therapy schemes (devices, light delivery system), the lack of consensus on a photosensitizer and the absence of randomized and controlled multicenter clinical trial. The main objective of this study is to bring a common support for PDT planning. Here, we describe a proof of concept of Treatment Planning System (TPS) dedicated to interstitial PDT for GBM treatment. The TPS was developed with the integrated development environment C++ Builder XE8 and the environment ArtiMED, developed in our laboratory. This software enables stereotactic registration of DICOM images, light sources insertion and an accelerated CUDA GPU dosimetry modeling. Although, Monte-Carlo is more robust to describe light diffusion in biological tissue, analytical model accelerated by GPU remains relevant for dose preview or fast reverse planning processes. Finally, this preliminary work proposes a new tool to plan interstitial or intraoperative PDT treatment and might be included in the design of future clinical trials in order to deliver PDT straightforwardly and homogenously in investigator centers.

  19. Big Data, Predictive Analytics, and Quality Improvement in Kidney Transplantation: A Proof of Concept.

    Science.gov (United States)

    Srinivas, T R; Taber, D J; Su, Z; Zhang, J; Mour, G; Northrup, D; Tripathi, A; Marsden, J E; Moran, W P; Mauldin, P D

    2017-03-01

    We sought proof of concept of a Big Data Solution incorporating longitudinal structured and unstructured patient-level data from electronic health records (EHR) to predict graft loss (GL) and mortality. For a quality improvement initiative, GL and mortality prediction models were constructed using baseline and follow-up data (0-90 days posttransplant; structured and unstructured for 1-year models; data up to 1 year for 3-year models) on adult solitary kidney transplant recipients transplanted during 2007-2015 as follows: Model 1: United Network for Organ Sharing (UNOS) data; Model 2: UNOS & Transplant Database (Tx Database) data; Model 3: UNOS, Tx Database & EHR comorbidity data; and Model 4: UNOS, Tx Database, EHR data, Posttransplant trajectory data, and unstructured data. A 10% 3-year GL rate was observed among 891 patients (2007-2015). Layering of data sources improved model performance; Model 1: area under the curve (AUC), 0.66; (95% confidence interval [CI]: 0.60, 0.72); Model 2: AUC, 0.68; (95% CI: 0.61-0.74); Model 3: AUC, 0.72; (95% CI: 0.66-077); Model 4: AUC, 0.84, (95 % CI: 0.79-0.89). One-year GL (AUC, 0.87; Model 4) and 3-year mortality (AUC, 0.84; Model 4) models performed similarly. A Big Data approach significantly adds efficacy to GL and mortality prediction models and is EHR deployable to optimize outcomes. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. Passive soil heating using an inexpensive infrared mirror design - a proof of concept

    Science.gov (United States)

    Rasmussen, C.; Gallery, R. E.; Fehmi, J. S.

    2015-09-01

    There is a need to understand the soil system response to warming in order to model the soil process response to predicted climate change. Current methods for soil warming include expensive and difficult to implement active and passive techniques. Here we test a simple, inexpensive in situ passive soil heating approach, based on easy to construct infrared mirrors that do not require automation or enclosures. The infrared mirrors consisted of 61 × 61 cm glass panels coated with infrared reflecting film. The mirrors as constructed are effective for soil heating in environments typified by an open vegetation canopy. Mirror tests were performed on three soils of varying texture, organic matter content, and heat capacity in a warm semi-arid environment. Results indicated that the infrared mirrors yielded significant heating and drying of soil surface and shallow subsurface relative to unwarmed control treatments, and that warming and drying effects were soil specific with greater potential warming on soils with lower volumetric heat capacity. Partial shading from the mirror frame did produce periods of relative cooling at specific times of the day but overall the mirrors yielded a net soil warming. The results demonstrate proof of concept that the infrared mirrors may be used to passively heat the near soil surface, providing an inexpensive, low-maintenance alternative to other passive and active soil heating technologies.

  1. Development of a proof of concept low temperature 4He Superfluid Magnetic Pump

    Science.gov (United States)

    Jahromi, Amir E.; Miller, Franklin K.

    2017-03-01

    We describe the development and experimental results of a proof of concept Superfluid Magnetic Pump in this work. This novel low temperature, no moving part pump can replace the existing bellows-piston driven 4He or 3He-4He mixture compressor/circulators used in various sub Kelvin refrigeration systems such as dilution, Superfluid pulse tube, Stirling, or active magnetic regenerative refrigerators. Due to the superior thermal transport properties of sub-Lambda 4He this pump can also be used as a simple circulator to distribute cooling over large surface areas. Our pump was experimentally shown to produce a maximum flow rate of 440 mg/s (averaged over cycle), 665 mg/s (peak) and produced a maximum pressure difference of 2323 Pa using only the more common isotope of helium, 4He. This pump worked in an ;ideal; thermodynamic state: The experimental results matched with the theoretical values predicted by a computer model. Pump curves were developed to map the performance of this pump. This successful demonstration will enable this novel pump to be implemented in suitable sub Kelvin refrigeration systems.

  2. Asymptotic approximation method of force reconstruction: Proof of concept

    Science.gov (United States)

    Sanchez, J.; Benaroya, H.

    2017-08-01

    An important problem in engineering is the determination of the system input based on the system response. This type of problem is difficult to solve as it is often ill-defined, and produces inaccurate or non-unique results. Current reconstruction techniques typically involve the employment of optimization methods or additional constraints to regularize the problem, but these methods are not without their flaws as they may be sub-optimally applied and produce inadequate results. An alternative approach is developed that draws upon concepts from control systems theory, the equilibrium analysis of linear dynamical systems with time-dependent inputs, and asymptotic approximation analysis. This paper presents the theoretical development of the proposed method. A simple application of the method is presented to demonstrate the procedure. A more complex application to a continuous system is performed to demonstrate the applicability of the method.

  3. OTF Proof of Concept: CCSDS Mission Operations Alert Services

    Science.gov (United States)

    Reynolds, Walt; Lucord, Steven A.; Stevens, John E.

    2009-01-01

    Conclusions: Use of multiple vendor frameworks within a component creates thread lockups and fragility conflicts over the control of the main thread. Avoid closed vendor messaging frameworks. The MAL layer does isolate the data elements from the messaging framework but application work dispatch is heavily dominated by the framework chosen. API Language is a major factor in implementation. Message APIs with timeouts seem unavoidable in some environments (GUI). Language environment needs to support callbacks (or threads) from the messaging framework to deal with pub/sub management messages and status. Statusing of application communications demand a local broker agent per physical system or else the use of the AMSstyle registrar heartbeat.

  4. Real-Time Dynamic Brake Assessment Proof of Concept Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Lascurain, Mary Beth [ORNL; Franzese, Oscar [ORNL; Capps, Gary J [ORNL

    2011-11-01

    This proof-of-concept research was performed to explore the feasibility of using real-world braking data from commercial motor vehicles to make a diagnosis of brake condition similar to that of the performance-based brake tester (PBBT). This was done by determining the relationship between pressure and brake force (P-BF), compensating for the gross vehicle weight (GVW). The nature of this P-BF relationship (e.g., low braking force for a given brake application pressure) may indicate brake system problems. In order to determine the relationship between brake force and brake application pressure, a few key parameters of duty cycle information were collected. Because braking events are often brief, spanning only a few seconds, a sample rate of 10 Hz was needed. The algorithm under development required brake application pressure and speed (from which deceleration was calculated). Accurate weight estimation was also needed to properly derive the braking force from the deceleration. In order to ensure that braking force was the predominant factor in deceleration for the segments of data used in analysis, the data was screened for grade as well. Also, the analysis needed to be based on pressures above the crack pressure. The crack pressure is the pressure below which the individual brakes are not applied due the nature of the mechanical system. This value, which may vary somewhat from one wheel end to another, is approximately 10 psi. Therefore, only pressures 15 psi and above were used in the analysis. The Department of Energy s Medium Truck Duty Cycle research has indicated that under the real-world circumstances of the test vehicle brake pressures of up to approximately 30 psi can be expected. Several different types of data were collected during the testing task of this project. Constant-pressure stopping tests were conducted at several combinations of brake application pressure (15, 20, 25, and 30 psi), load conditions (moderately and fully laden), and speeds (20 and

  5. Gold Nanotheranostics: Proof-of-Concept or Clinical Tool?

    Directory of Open Access Journals (Sweden)

    Pedro Pedrosa

    2015-11-01

    Full Text Available Nanoparticles have been making their way in biomedical applications and personalized medicine, allowing for the coupling of diagnostics and therapeutics into a single nanomaterial—nanotheranostics. Gold nanoparticles, in particular, have unique features that make them excellent nanomaterials for theranostics, enabling the integration of targeting, imaging and therapeutics in a single platform, with proven applicability in the management of heterogeneous diseases, such as cancer. In this review, we focus on gold nanoparticle-based theranostics at the lab bench, through pre-clinical and clinical stages. With few products facing clinical trials, much remains to be done to effectively assess the real benefits of nanotheranostics at the clinical level. Hence, we also discuss the efforts currently being made to translate nanotheranostics into the market, as well as their commercial impact.

  6. Relaxing the cosmological constant: a proof of concept

    Energy Technology Data Exchange (ETDEWEB)

    Alberte, Lasma [SISSA,Via Bonomea 265, 34136 Trieste (Italy); INFN - Sezione di Trieste,Via Valerio 2, 34127 Trieste (Italy); Creminelli, Paolo; Khmelnitsky, Andrei [Abdus Salam International Centre for Theoretical Physics (ICTP),Strada Costiera 11, 34151, Trieste (Italy); Pirtskhalava, David [Institute of Physics, École Polytechnique Fédérale de Lausanne,CH-1015, Lausanne (Switzerland); Trincherini, Enrico [Scuola Normale Superiore,Piazza dei Cavalieri 7, 56126, Pisa (Italy); INFN - Sezione di Pisa,56200, Pisa (Italy)

    2016-12-06

    We propose a technically natural scenario whereby an initially large cosmological constant (c.c.) is relaxed down to the observed value due to the dynamics of a scalar evolving on a very shallow potential. The model crucially relies on a sector that violates the null energy condition (NEC) and gets activated only when the Hubble rate becomes sufficiently small — of the order of the present one. As a result of NEC violation, this low-energy universe evolves into inflation, followed by reheating and the standard Big Bang cosmology. The symmetries of the theory force the c.c. to be the same before and after the NEC-violating phase, so that a late-time observer sees an effective c.c. of the correct magnitude. Importantly, our model allows neither for eternal inflation nor for a set of possible values of dark energy, the latter fixed by the parameters of the theory.

  7. Relaxing the Cosmological Constant: a Proof of Concept

    CERN Document Server

    Alberte, Lasma; Khmelnitsky, Andrei; Pirtskhalava, David; Trincherini, Enrico

    2016-01-01

    We propose a technically natural scenario whereby an initially large cosmological constant (c.c.) is relaxed down to the observed value due to the dynamics of a scalar evolving on a very shallow potential. The model crucially relies on a sector that violates the null energy condition (NEC) and gets activated only when the Hubble rate becomes sufficiently small --- of the order of the present one. As a result of NEC violation, this low-energy universe evolves into inflation, followed by reheating and the standard Big Bang cosmology. The symmetries of the theory force the c.c. to be the same before and after the NEC-violating phase, so that a late-time observer sees an effective c.c. of the correct magnitude. Importantly, our model allows neither for eternal inflation nor for a set of possible values of dark energy, the latter fixed by the parameters of the theory.

  8. Sequential Data Assimilation for Seismicity: a Proof of Concept

    Science.gov (United States)

    van Dinther, Ylona; Fichtner, Andreas; Kuensch, Hansruedi

    2016-04-01

    Our probabilistic forecasting ability and physical understanding of earthquakes is significantly hampered by limited indications on the current and evolving state of stress and strength on faults. This information is typically thought to be beyond our resolution capabilities based on surface data. We show that the state of stress and strength are actually obtainable for settings with one dominant fault. State variables and their uncertainties are obtained using Ensemble Kalman Filtering, a sequential data assimilation technique extensively developed for weather forecasting purposes. Through the least-squares solution of Bayes theorem erroneous data is for the first time assimilated to update a Partial Differential Equation-driven seismic cycle model. This visco-elasto-plastic continuum forward model solves Navier-Stokes equations with a rate-dependent friction coefficient (van Dinther et al., JGR, 2013). To prove the concept of this weather - earthquake forecasting bridge we perform a perfect model test. Synthetic numerical data from a single analogue borehole is assimilated into 20 ensemble models over 14 cycles of analogue earthquakes. Since we know the true state of the numerical data model, a quantitative and qualitative evaluation shows that meaningful information on the stress and strength of the unobserved fault is typically already available, once data from a single, shallow borehole is assimilated over part of a seismic cycle. This is possible, since the sampled error covariance matrix contains prior information on the physics that relates velocities, stresses, and pressures at the surface to those at the fault. During the analysis step stress and strength distributions are thus reconstructed in such a way that fault coupling can be updated to either inhibit or trigger events. In the subsequent forward propagation step the physical equations are solved to propagate the updated states forward in time and thus provide probabilistic information on the

  9. Moving Denitrifying Bioreactors beyond Proof of Concept: Introduction to the Special Section.

    Science.gov (United States)

    Christianson, Laura E; Schipper, Louis A

    2016-05-01

    Denitrifying bioreactors are organic carbon-filled excavations designed to enhance the natural process of denitrification for the simple, passive treatment of nitrate-nitrogen. Research on and installation of these bioreactors has accelerated within the past 10 years, particularly in watersheds concerned about high nonpoint-source nitrate loads and also for tertiary wastewater treatment. This special section, inspired by the meeting of the Managing Denitrification in Agronomic Systems Community at the 2014 Annual Meeting of the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, aims to firmly establish that denitrifying bioreactors for treatment of nitrate in drainage waters, groundwater, and some wastewaters have moved beyond the proof of concept. This collection of 14 papers expands the peer-reviewed literature of denitrifying bioreactors into new locations, applications, and environmental conditions. There is momentum behind the pairing of wood-based bioreactors with other media (biochar, corn cobs) and in novel designs (e.g., use within treatment trains or use of baffles) to broaden applicability into new kinds of waters and pollutants and to improve performance under challenging field conditions such as cool early season agricultural drainage. Concerns about negative bioreactor by-products (nitrous oxide and hydrogen sulfide emissions, start-up nutrient flushing) are ongoing, but this translates into a significant research opportunity to develop more advanced designs and to fine tune management strategies. Future research must think more broadly to address bioreactor impacts on holistic watershed health and greenhouse gas balances and to facilitate collaborations that allow investigation of mechanisms within the bioreactor "black box."

  10. Bioassays for bomb-makers: proof of concept.

    Science.gov (United States)

    Bell, Suzanne C; Gayton-Ely, Melissa; Nida, Corey M

    2009-09-01

    Clandestine bomb-makers are exposed to significant amounts of explosives and allied materials. As with any ingested xenobiotic substance, these compounds are subject to biotransformation. As such, the potential exists that characteristic suites of biomarkers may be produced and deposited in matrices that can be exploited for forensic and investigative purposes. However, before such assays can be developed, foundational data must be gathered regarding the toxicokinetics, fate, and transport of the resulting biomarkers within the body and in matrices such as urine, hair, nails, sweat, feces, and saliva. This report presents an in vitro method for simulation of human metabolic transformations using human liver microsomes and an assay applicable to representative nitro-explosives. Control and metabolized samples of TNT, RDX, HMX, and tetryl were analyzed using high-performance liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) and biomarkers identified for each. The challenges associated with this method arise from solubility issues and limitations imposed by instrumentation, specifically, modes of ionization.

  11. Proof-of-Concept Oil Shale Facility Environmental Analysis Program

    Energy Technology Data Exchange (ETDEWEB)

    1990-11-01

    The objectives of the Project are to demonstrate: (1) the Modified In- Situ (MIS) shale oil extraction process and (2) the application of CFBC technology using oil shale, coal and waste gas streams as fuels. The project will focus on evaluating and improving the efficiency and environmental performance of these technologies. The project will be modest by commercial standards. A 17-retort MIS system is planned in which two retorts will be processed simultaneously. Production of 1206-barrels per calendar day of raw shale oil and 46-megawatts of electricity is anticipated. West Virginia University coordinated an Environmental Analysis Program for the Project. Experts from around the country were retained by WVU to prepare individual sections of the report. These experts were exposed to all of OOSI`s archives and toured Tract C-b and Logan Wash. Their findings were incorporated into this report. In summary, no environmental obstacles were revealed that would preclude proceeding with the Project. One of the most important objectives of the Project was to verify the environmental acceptability of the technologies being employed. Consequently, special attention will be given to monitoring environmental factors and providing state of the art mitigation measures. Extensive environmental and socioeconomic background information has been compiled for the Tract over the last 15 years and permits were obtained for the large scale operations contemplated in the late 1970`s and early 1980`s. Those permits have been reviewed and are being modified so that all required permits can be obtained in a timely manner.

  12. Audiomotor Integration in Minimally Conscious State: Proof of Concept!

    Science.gov (United States)

    Naro, Antonino; Leo, Antonino; Cannavò, Antonino; Buda, Antonio; Bruno, Rocco; Salviera, Carlo; Bramanti, Placido; Calabrò, Rocco Salvatore

    2015-01-01

    Patients suffering from chronic disorders of consciousness (DOC) are characterized by profound unawareness and an impairment of large-scale cortical and subcortical connectivity. In this study, we applied an electrophysiological approach aimed at identifying the residual audiomotor connectivity patterns that are thought to be linked to awareness. We measured some markers of audiomotor integration (AMI) in 20 patients affected by DOC, before and after the application of a repetitive transcranial magnetic stimulation protocol (rTMS) delivered over the left primary motor area (M1), paired to a transauricular alternating current stimulation. Our protocol induced potentiating of the electrophysiological markers of AMI and M1 excitability, paired to a clinical improvement, in all of the patients with minimally conscious state (MCS) but in none of those suffering from unresponsive wakefulness syndrome (UWS). Our protocol could be a promising approach to potentiate the functional connectivity within large-scale audiomotor networks, thus allowing clinicians to differentiate patients affected by MCS from UWS, besides the clinical assessment. PMID:26425370

  13. Audiomotor Integration in Minimally Conscious State: Proof of Concept!

    Directory of Open Access Journals (Sweden)

    Antonino Naro

    2015-01-01

    Full Text Available Patients suffering from chronic disorders of consciousness (DOC are characterized by profound unawareness and an impairment of large-scale cortical and subcortical connectivity. In this study, we applied an electrophysiological approach aimed at identifying the residual audiomotor connectivity patterns that are thought to be linked to awareness. We measured some markers of audiomotor integration (AMI in 20 patients affected by DOC, before and after the application of a repetitive transcranial magnetic stimulation protocol (rTMS delivered over the left primary motor area (M1, paired to a transauricular alternating current stimulation. Our protocol induced potentiating of the electrophysiological markers of AMI and M1 excitability, paired to a clinical improvement, in all of the patients with minimally conscious state (MCS but in none of those suffering from unresponsive wakefulness syndrome (UWS. Our protocol could be a promising approach to potentiate the functional connectivity within large-scale audiomotor networks, thus allowing clinicians to differentiate patients affected by MCS from UWS, besides the clinical assessment.

  14. Proof-of-Concept Oil Shale Facility Environmental Analysis Program

    Energy Technology Data Exchange (ETDEWEB)

    1990-11-01

    The objectives of the Project are to demonstrate: (1) the Modified In- Situ (MIS) shale oil extraction process and (2) the application of CFBC technology using oil shale, coal and waste gas streams as fuels. The project will focus on evaluating and improving the efficiency and environmental performance of these technologies. The project will be modest by commercial standards. A 17-retort MIS system is planned in which two retorts will be processed simultaneously. Production of 1206-barrels per calendar day of raw shale oil and 46-megawatts of electricity is anticipated. West Virginia University coordinated an Environmental Analysis Program for the Project. Experts from around the country were retained by WVU to prepare individual sections of the report. These experts were exposed to all of OOSI's archives and toured Tract C-b and Logan Wash. Their findings were incorporated into this report. In summary, no environmental obstacles were revealed that would preclude proceeding with the Project. One of the most important objectives of the Project was to verify the environmental acceptability of the technologies being employed. Consequently, special attention will be given to monitoring environmental factors and providing state of the art mitigation measures. Extensive environmental and socioeconomic background information has been compiled for the Tract over the last 15 years and permits were obtained for the large scale operations contemplated in the late 1970's and early 1980's. Those permits have been reviewed and are being modified so that all required permits can be obtained in a timely manner.

  15. Electrophysiological biomarkers in spinal muscular atrophy: proof of concept

    Science.gov (United States)

    David Arnold, W; Porensky, Paul N; McGovern, Vicki L; Iyer, Chitra C; Duque, Sandra; Li, Xiaobai; Meyer, Kathrin; Schmelzer, Leah; Kaspar, Brian K; Kolb, Stephen J; Kissel, John T; Burghes, Arthur H M

    2014-01-01

    Objective Preclinical therapies that restore survival motor neuron (SMN) protein levels can dramatically extend survival in spinal muscular atrophy (SMA) mouse models. Biomarkers are needed to effectively translate these promising therapies to clinical trials. Our objective was to investigate electrophysiological biomarkers of compound muscle action potential (CMAP), motor unit number estimation (MUNE) and electromyography (EMG) using an SMA mouse model. Methods Sciatic CMAP, MUNE, and EMG were obtained in SMNΔ7 mice at ages 3–13 days and at 21 days in mice with SMN selectively reduced in motor neurons (ChATCre). To investigate these measures as biomarkers of treatment response, measurements were obtained in SMNΔ7 mice treated with antisense oligonucleotide (ASO) or gene therapy. Results CMAP was significantly reduced in SMNΔ7 mice at days 6–13 (P < 0.01), and MUNE was reduced at days 7–13 (P < 0.01). Fibrillations were present on EMG in SMNΔ7 mice but not controls (P = 0.02). Similar findings were seen at 21 days in ChATCre mice. MUNE in ASO-treated SMNΔ7 mice were similar to controls at day 12 and 30. CMAP reduction persisted in ASO-treated SMNΔ7 mice at day 12 but was corrected at day 30. Similarly, CMAP and MUNE responses were corrected with gene therapy to restore SMN. Interpretation These studies confirm features of preserved neuromuscular function in the early postnatal period and subsequent motor unit loss in SMNΔ7 mice. SMN restoring therapies result in preserved MUNE and gradual repair of CMAP responses. This provides preclinical evidence for the utilization of CMAP and MUNE as biomarkers in future SMA clinical trials. PMID:24511555

  16. Green IT Readiness: A Framework and Preliminary Proof of Concept

    Directory of Open Access Journals (Sweden)

    Alemayehu Molla

    2010-01-01

    Full Text Available Businesses are under increasing pressure from customers, competitors, regulators and community groups to implement sustainable business practices. Balancing economic and environmental performance to be green and competitive is therefore a key strategic issue. The information technology (IT sector is one of the pioneer sectors which started working on the sustainable development model. However, it is only lately that researchers and organisations have begun to consider the role of IT, not only in contributing to a businesses environmental footprint but also in tackling climate change problems. Usually coined as, “Green Information Technology”, the role of IT in causing and resolving ecological sustainability, in maintaining low cost IT shops, in building green reputation capital and in supporting corporate green strategies has hardly been researched. This paper identifies four main areas of Green IT capability and describes the main pillars of a G-readiness framework to help organisations evaluate their maturity for Green IT. The utility of the framework is demonstrated through a desk-based research case study of seven organisations. The paper argues that just as e-readiness has been, and continues to be, a critical capability in the digital economy, G-readiness is an equally critical capability in the low carbon digital economy. Without a clear understanding of G-readiness, organisations would approach Green IT initiatives on an ad hoc and somewhat reactive basis, which is undesirable.

  17. Electrochemical Disinfection of Dental Implants – a Proof of Concept

    Science.gov (United States)

    Mohn, Dirk; Zehnder, Matthias; Stark, Wendelin J.; Imfeld, Thomas

    2011-01-01

    Background Peri-implantitis has gained significant clinical attention in recent years. This disease is an inflammatory reaction to microorganisms around dental implants. Due to the limited accessibility, non-invasive antimicrobial strategies are of high interest. An unexpected approach to implant disinfection may evolve from electrolysis. Given the electrical conductivity of titanium implants, alkalinity or active oxidants can be generated in body fluids. We investigated the use of dental titanium implants as electrodes for the local generation of disinfectants. Our hypothesis was that electrolysis can reduce viable counts of adhering bacteria, and that this reduction should be greater if active oxidative species are generated. Methodology/Principal Findings As model systems, dental implants, covered with a mono-species biofilm of Escherichia coli C43, were placed in photographic gelatin prepared with physiological saline. Implants were treated by a continuous current of 0 - 10 mA for 15 minutes. The reduction of viable counts was investigated on cathodes and anodes. In separate experiments, the local change in pH was visualized using color indicators embedded in the gelatin. Oxidative species were qualitatively detected by potassium iodide-starch paper. The in situ generated alkaline environment around cathodic implants caused a reduction of up to 2 orders of magnitude in viable E. coli counts. On anodic implants, in contrast to cathodic counterparts, oxidative species were detected. Here, a current of merely 7.5 mA caused complete kill of the bacteria. Conclusions/Significance This laboratory study shows that electrochemical treatment may provide access to a new way to decontaminate dental implants in situ. PMID:21264247

  18. Comparative spatial genetics and epigenetics of plant populations: heuristic value and a proof of concept.

    Science.gov (United States)

    Herrera, Carlos M; Medrano, Mónica; Bazaga, Pilar

    2016-04-01

    Despite the recent upsurge of interest on natural epigenetic variation of nonmodel organisms, factors conditioning the spatial structure of epigenetic diversity in wild plant populations remain virtually unexplored. We propose that information on processes shaping natural epigenetic variation can be gained using the spatial structure of genetic diversity as null model. Departures of epigenetic isolation-by-distance (IBD) patterns from genetic IBD patterns for the same sample, particularly differences in slope of similarity-distance regressions, will reflect the action of factors that operate specifically on epigenetic variation, including imperfect transgenerational inheritance and responsiveness to environmental factors of epigenetic marks. As a proof of concept, we provide a comparative analysis of spatial genetic and epigenetic structure of 200 mapped individuals of the perennial herb Helleborus foetidus. Plants were fingerprinted using nuclear microsatellites, amplified fragment length polymorphisms (AFLP) and methylation-sensitive AFLP markers. Expectations from individual-level IBD patterns were tested by means of kinship-distance regressions. Both genetic and epigenetic similarity between H. foetidus individuals conformed to theoretical expectations under individual-level IBD models. Irrespective of marker type, there were significant negative linear relationships between the kinship coefficient for plant pairs and their spatial separation. Regression slopes were significantly steeper for epigenetic markers. Epigenetic similarity between individuals was much greater than genetic similarity at shortest distances, such epigenetic 'kinship excess' tending to decrease as plant separation increased. Results suggest that moderate-to-high heritability and responsiveness to local environments are major drivers of epigenetic spatial structure in H. foetidus, and illustrate the heuristic value of comparing genetic and epigenetic spatial structure for formulating

  19. Feasibility of Telementoring for Microneurosurgical Procedures Using a Microscope: A Proof-of-Concept Study.

    Science.gov (United States)

    Ladd, Bryan M; Tackla, Ryan D; Gupte, Akshay; Darrow, David; Sorenson, Jeffery; Zuccarello, Mario; Grande, Andrew W

    2017-03-01

    Our pilot study evaluated the effectiveness of our telementoring-telescripting model to facilitate seamless communication between surgeons while the operating surgeon is using a microscope. As a first proof of concept, 4 students identified 20 anatomic landmarks on a dry human skull with or without telementoring guidance. To assess the ability to communicate operative information, a senior neurosurgery resident evaluated the student's ability and timing to complete a stepwise craniotomy on a cadaveric head, with and without telementoring guidance; a second portion included exposure of the anterior circulation. The mentor was able to annotate directly onto the operator's visual field, which was visible to the operator without looking away from the binocular view. The students showed that they were familiar with half (50% ± 10%) of the structures for identification and none was familiar with the steps to complete a craniotomy before using our system. With the guidance of a remote surgeon projected into the visual field of the microscope, the students were able to correctly identify 100% of the structures and complete a craniotomy. Our system also proved effective in guiding a more experienced neurosurgery resident through complex operative steps associated with exposure of the anterior circulation. Our pilot study showed a platform feasible in providing effective operative direction to inexperienced operators while operating using a microscope. A remote mentor was able to view the visual field of the microscope, annotate on the visual stream, and have the annotated stream appear in the binocular view for the operating mentee. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Proof of Concept of Integrated Load Measurement in 3D Printed Structures

    Science.gov (United States)

    Hinderdael, Michaël; Jardon, Zoé; Lison, Margot; De Baere, Dieter; Devesse, Wim; Strantza, Maria; Guillaume, Patrick

    2017-01-01

    Currently, research on structural health monitoring systems is focused on direct integration of the system into a component or structure. The latter results in a so-called smart structure. One example of a smart structure is a component with integrated strain sensing for continuous load monitoring. Additive manufacturing, or 3D printing, now also enables such integration of functions inside components. As a proof-of-concept, the Fused Deposition Modeling (FDM) technique was used to integrate a strain sensing element inside polymer (ABS) tensile test samples. The strain sensing element consisted of a closed capillary filled with a fluid and connected to an externally mounted pressure sensor. The volumetric deformation of the integrated capillary resulted in pressure changes in the fluid. The obtained pressure measurements during tensile testing are reported in this paper and compared to state-of-the-art extensometer measurements. The sensitivity of the 3D printed pressure-based strain sensor is primarily a function of the compressibility of the capillary fluid. Air- and watertightness are of critical importance for the proper functioning of the 3D printed pressure-based strain sensor. Therefore, the best after-treatment procedure was selected on basis of a comparative analysis. The obtained pressure measurements are linear with respect to the extensometer readings, and the uncertainty on the strain measurement of a capillary filled with water (incompressible fluid) is ±3.1 µstrain, which is approximately three times less sensitive than conventional strain gauges (±1 µstrain), but 32 times more sensitive than the same sensor based on air (compressible fluid) (±101 µstrain). PMID:28208779

  1. A small molecule (pluripotin as a tool for studying cancer stem cell biology: proof of concept.

    Directory of Open Access Journals (Sweden)

    Susan D Mertins

    Full Text Available BACKGROUND: Cancer stem cells (CSC are thought to be responsible for tumor maintenance and heterogeneity. Bona fide CSC purified from tumor biopsies are limited in supply and this hampers study of CSC biology. Furthermore, purified stem-like CSC subpopulations from existing tumor lines are unstable in culture. Finding a means to overcome these technical challenges would be a useful goal. In a first effort towards this, we examined whether a chemical probe that promotes survival of murine embryonic stem cells without added exogenous factors can alter functional characteristics in extant tumor lines in a fashion consistent with a CSC phenotype. METHODOLOGY/PRINCIPAL FINDINGS: The seven tumor lines of the NCI60 colon subpanel were exposed to SC-1 (pluripotin, a dual kinase and GTPase inhibitor that promotes self-renewal, and then examined for tumorigenicity under limiting dilution conditions and clonogenic activity in soft agar. A statistically significant increase in tumor formation following SC-1 treatment was observed (p<0.04. Cloning efficiencies and expression of putative CSC surface antigens (CD133 and CD44 were also increased. SC-1 treatment led to sphere formation in some colon tumor lines. Finally, SC-1 inhibited in vitro kinase activity of RSK2, and another RSK2 inhibitor increased colony formation implicating a role for this kinase in eliciting a CSC phenotype. CONCLUSIONS/SIGNIFICANCE: These findings validate a proof of concept study exposure of extant tumor lines to a small molecule may provide a tractable in vitro model for understanding CSC biology.

  2. Proof of Concept of Integrated Load Measurement in 3D Printed Structures.

    Science.gov (United States)

    Hinderdael, Michaël; Jardon, Zoé; Lison, Margot; De Baere, Dieter; Devesse, Wim; Strantza, Maria; Guillaume, Patrick

    2017-02-09

    Currently, research on structural health monitoring systems is focused on direct integration of the system into a component or structure. The latter results in a so-called smart structure. One example of a smart structure is a component with integrated strain sensing for continuous load monitoring. Additive manufacturing, or 3D printing, now also enables such integration of functions inside components. As a proof-of-concept, the Fused Deposition Modeling (FDM) technique was used to integrate a strain sensing element inside polymer (ABS) tensile test samples. The strain sensing element consisted of a closed capillary filled with a fluid and connected to an externally mounted pressure sensor. The volumetric deformation of the integrated capillary resulted in pressure changes in the fluid. The obtained pressure measurements during tensile testing are reported in this paper and compared to state-of-the-art extensometer measurements. The sensitivity of the 3D printed pressure-based strain sensor is primarily a function of the compressibility of the capillary fluid. Air- and watertightness are of critical importance for the proper functioning of the 3D printed pressure-based strain sensor. Therefore, the best after-treatment procedure was selected on basis of a comparative analysis. The obtained pressure measurements are linear with respect to the extensometer readings, and the uncertainty on the strain measurement of a capillary filled with water (incompressible fluid) is ±3.1 µstrain, which is approximately three times less sensitive than conventional strain gauges (±1 µstrain), but 32 times more sensitive than the same sensor based on air (compressible fluid) (±101 µstrain).

  3. Toward proof of concept of a one health approach to disease prediction and control.

    Science.gov (United States)

    Rabinowitz, Peter M; Kock, Richard; Kachani, Malika; Kunkel, Rebekah; Thomas, Jason; Gilbert, Jeffrey; Wallace, Robert; Blackmore, Carina; Wong, David; Karesh, William; Natterson, Barbara; Dugas, Raymond; Rubin, Carol

    2013-12-01

    A One Health approach considers the role of changing environments with regard to infectious and chronic disease risks affecting humans and nonhuman animals. Recent disease emergence events have lent support to a One Health approach. In 2010, the Stone Mountain Working Group on One Health Proof of Concept assembled and evaluated the evidence regarding proof of concept of the One Health approach to disease prediction and control. Aspects examined included the feasibility of integrating human, animal, and environmental health and whether such integration could improve disease prediction and control efforts. They found evidence to support each of these concepts but also identified the need for greater incorporation of environmental and ecosystem factors into disease assessments and interventions. The findings of the Working Group argue for larger controlled studies to evaluate the comparative effectiveness of the One Health approach.

  4. Nutrition, Exercise, and Wellness Treatment in bipolar disorder: proof of concept for a consolidated intervention

    OpenAIRE

    Sylvia, Louisa G; Salcedo, Stephanie; Bernstein, Emily E; Baek, Ji Hyun; Nierenberg, Andrew A.; Deckersbach, Thilo

    2013-01-01

    Background This pilot study examines the proof of concept of a consolidated Nutrition, Exercise, and Wellness Treatment (NEW Tx) for overweight individuals with bipolar disorder. Findings Five participants completed NEW Tx, a 20-week individual cognitive behavioral therapy-based treatment comprising three modules: Nutrition teaches appropriate serving sizes and balanced diet; Exercise emphasizes increasing weekly physical activity; Wellness focuses on skills for healthy decision-making. Parti...

  5. Nutrition, Exercise, and Wellness Treatment in bipolar disorder: proof of concept for a consolidated intervention

    OpenAIRE

    Sylvia, Louisa G; Salcedo, Stephanie; Bernstein, Emily E; Baek, Ji Hyun; Nierenberg, Andrew A.; Deckersbach, Thilo

    2013-01-01

    Background: This pilot study examines the proof of concept of a consolidated Nutrition, Exercise, and Wellness Treatment (NEW Tx) for overweight individuals with bipolar disorder. Findings: Five participants completed NEW Tx, a 20-week individual cognitive behavioral therapy-based treatment comprising three modules: Nutrition teaches appropriate serving sizes and balanced diet; Exercise emphasizes increasing weekly physical activity; Wellness focuses on skills for healthy decision-making. Par...

  6. Flow-Control Systems Proof of Concept for Snowmelt Runoff at McMurdo Station, Antarctica

    Science.gov (United States)

    2017-01-01

    ER D C/ CR RE L TR -1 7- 1 Engineering for Polar Operations , Logistics, and Research (EPOLAR) Flow-Control Systems Proof of Concept for...online library at http://acwc.sdp.sirsi.net/client/default. Engineering for Polar Operations , Logistics, and Research (EPOLAR) ERDC/CRREL TR-17-1...Antarctic Infrastructure and Logistics Arlington, VA 22230 Under Engineering for Polar Operations , Logistics, and Research (EPOLAR) EP-ANT-15-04

  7. Development of an Ontology Based Forensic Search Mechanism: Proof of Concept

    Directory of Open Access Journals (Sweden)

    Jill Slay

    2006-03-01

    Full Text Available This paper examines the problems faced by Law Enforcement in searching large quantities of electronic evidence. It examines the use of ontologies as the basis for new forensic software filters and provides a proof of concept tool based on an ontological design. It demonstrates that efficient searching is produced through the use of such a design and points to further work that might be carried out to extend this concept.

  8. Reconstruction of 3D Shapes of Opaque Cumulus Clouds from Airborne Multiangle Imaging: A Proof-of-Concept

    Science.gov (United States)

    Davis, A. B.; Bal, G.; Chen, J.

    2015-12-01

    Operational remote sensing of microphysical and optical cloud properties is invariably predicated on the assumption of plane-parallel slab geometry for the targeted cloud. The sole benefit of this often-questionable assumption about the cloud is that it leads to one-dimensional (1D) radiative transfer (RT)---a textbook, computationally tractable model. We present new results as evidence that, thanks to converging advances in 3D RT, inverse problem theory, algorithm implementation, and computer hardware, we are at the dawn of a new era in cloud remote sensing where we can finally go beyond the plane-parallel paradigm. Granted, the plane-parallel/1D RT assumption is reasonable for spatially extended stratiform cloud layers, as well as the smoothly distributed background aerosol layers. However, these 1D RT-friendly scenarios exclude cases that are critically important for climate physics. 1D RT---whence operational cloud remote sensing---fails catastrophically for cumuliform clouds that have fully 3D outer shapes and internal structures driven by shallow or deep convection. For these situations, the first order of business in a robust characterization by remote sensing is to abandon the slab geometry framework and determine the 3D geometry of the cloud, as a first step toward bone fide 3D cloud tomography. With this specific goal in mind, we deliver a proof-of-concept for an entirely new kind of remote sensing applicable to 3D clouds. It is based on highly simplified 3D RT and exploits multi-angular suites of cloud images at high spatial resolution. Airborne sensors like AirMSPI readily acquire such data. The key element of the reconstruction algorithm is a sophisticated solution of the nonlinear inverse problem via linearization of the forward model and an iteration scheme supported, where necessary, by adaptive regularization. Currently, the demo uses a 2D setting to show how either vertical profiles or horizontal slices of the cloud can be accurately reconstructed

  9. Protecting an island nation from extreme pandemic threats: Proof-of-concept around border closure as an intervention.

    Science.gov (United States)

    Boyd, Matt; Baker, Michael G; Mansoor, Osman D; Kvizhinadze, Giorgi; Wilson, Nick

    2017-01-01

    Countries are well advised to prepare for future pandemic risks (e.g., pandemic influenza, novel emerging agents or synthetic bioweapons). These preparations do not typically include planning for complete border closure. Even though border closure may not be instituted in time, and can fail, there might still plausible chances of success for well organized island nations. To estimate costs and benefits of complete border closure in response to new pandemic threats, at an initial proof-of-concept level. New Zealand was used as a case-study for an island country. An Excel spreadsheet model was developed to estimate costs and benefits. Case-study specific epidemiological data was sourced from past influenza pandemics. Country-specific healthcare cost data, valuation of life, and lost tourism revenue were imputed (with lost trade also in scenario analyses). For a new pandemic equivalent to the 1918 influenza pandemic (albeit with half the mortality rate, "Scenario A"), it was estimated that successful border closure for 26 weeks provided a net societal benefit (e.g., of NZ$11.0 billion, USD$7.3 billion). Even in the face of a complete end to trade, a net benefit was estimated for scenarios where the mortality rate was high (e.g., at 10 times the mortality impact of "Scenario A", or 2.75% of the country's population dying) giving a net benefit of NZ$54 billion (USD$36 billion). But for some other pandemic scenarios where trade ceased, border closure resulted in a net negative societal value (e.g., for "Scenario A" times three for 26 weeks of border closure-but not for only 12 weeks of closure when it would still be beneficial). This "proof-of-concept" work indicates that more detailed cost-benefit analysis of border closure in very severe pandemic situations for some island nations is probably warranted, as this course of action might sometimes be worthwhile from a societal perspective.

  10. A Proof of Concept Experiment for Reducing Skin Friction by Using a Micro-Blowing Technique

    Science.gov (United States)

    Hwang, Danny P.

    1996-01-01

    A proof of concept experiment for reducing skin friction has been conducted in the Advanced Nozzle and Engine Components Test Facility at the NASA Lewis Research Center. In this unique concept, called the micro-blowing technique (MBT), an extremely small amount of air was blown vertically through very small holes to reduce the surface roughness and to control the gradient of the flow velocity profile on the surface thereby reducing skin friction. Research revealed that the skin was the most important factor to make this concept achievable. The proposed skin consisted of two layers. The inner layer was a low permeable porous skin for distributing the blowing air evenly while the outer layer with small holes controlled the vertical or nearly vertical blowing air. Preliminary experimental results showed that the MBT has the potential of a very large reduction in skin friction below the skin friction of a nonporous plain flat plate. Of the skins tested, three have been identified as the MBT skins. They provided very low unblown skin friction such that a large skin friction reduction, below a flat plate value, was achieved with very small amounts of blowing air. The reduction in skin friction of 55 percent was achieved at the Mach number of 0.3 for the exhaust pressure of 0.85 atm, and 60 percent reduction was obtained for the exhaust pressure of 0.24 atm (corresponding to 10 700-m altitude) at the same Mach number. A significant reduction in skin friction of over 25 percent was achieved for the exhaust pressure of 0.24 atm at the Mach number of 0.7. This implied that the MBT could be applied to a wide range of flight conditions. It is also believed that additional 10 percent reduction could be obtained by eliminating the gap between the inner layer and the outer layer. The aspect ratio of the vertical small holes for the outer layer of the MBT skin should be larger than 4 based on the preliminary conclusion from this test. Many experiments are needed to find out the

  11. mHealth medication and blood pressure self-management program in Hispanic hypertensives: a proof of concept trial

    Directory of Open Access Journals (Sweden)

    Sieverdes JC

    2013-10-01

    Full Text Available John C Sieverdes,1 Mathew Gregoski,1 Sachin Patel,1 Deborah Williamson,1 Brenda Brunner-Jackson,1 Judith Rundbaken,1 Eveline Treiber,1 Lydia Davidson,1 Frank A Treiber1,21Technology Applications Center for Healthful Lifestyles, College of Nursing, 2College of Medicine, Medical University of South Carolina, Charleston, SC, USAAbstract: Patient nonadherence to medication regimens and provider therapeutic inertia (failure to respond in timely manner to clinical data are two primary contributors to ineffective chronic disease management. This 3-month proof of concept trial used an iterative design approach guided by self-determination theory and the technology acceptance model to develop a culturally sensitive, patient-centered, and provider-centered mobile health medication and blood pressure self-management program. Cellular connected electronic medication trays provided reminder signals for patients to take medications and smartphone messaging reminded patients to take at-home blood pressures using a Bluetooth-enabled monitor. Providers were given bimonthly feedback. Motivational and reinforcement text and audio messages were sent based upon medication adherence rates and blood pressure levels. Ten Hispanics with uncontrolled essential hypertension were randomized to standard care and Smartphone Medication Adherence Stops Hypertension (SMASH intervention groups. Primary outcomes of provider and patient acceptability of the program were found to be high. Retention rates for the 3-month program were 100%, with mean ± standard deviation overall medication adherence for the SMASH group at 97.2% ± 2.8%, with all strongly believing the program helped them remember to take their medication. SMASH participants measured their blood pressure every 3 days 83.2% ± 6.0% of the time and completed 89.2% ± 19.06% of the expected readings. Nonparametric tests showed statistical significance for resting blood pressure changes between groups at months 2 (P = 0

  12. Ultra-high gradient channeling acceleration in nanostructures: Design/progress of proof-of-concept (POC) experiments

    Science.gov (United States)

    Shin, Y. M.; Green, A.; Lumpkin, A. H.; Thurman-Keup, R. M.; Shiltsev, V.; Zhang, X.; Farinella, D. M.-A.; Taborek, P.; Tajima, T.; Wheeler, J. A.; Mourou, G.

    2017-03-01

    A short bunch of relativistic particles, or a short-pulse laser, perturb the density state of conduction electrons in a solid crystal and excite wakefields along atomic lattices in a crystal. Under a coupling condition between a driver and plasma, the wakes, if excited, can accelerate channeling particles with TeV/m acceleration gradients [1], in principle, since the density of charge carriers (conduction electrons) in solids n0 = 1020 - 1023 cm-3 is significantly higher than what was considered above in gaseous plasma. Nanostructures have some advantages over crystals for channeling applications of high power beams. The de-channeling rate can be reduced and the beam acceptance increased by the large size of the channels. For beam-driven acceleration, a bunch length with a sufficient charge density would need to be in the range of the plasma wavelength to properly excite plasma wakefields, and channeled particle acceleration with the wakefields must occur before the ions in the lattices move beyond the restoring threshold. In the case of the excitation by short laser pulses, the dephasing length is appreciably increased with the larger channel, which enables channeled particles to gain sufficient amounts of energy. This paper describes simulation analyses on beam- and laser (X-ray)-driven accelerations in effective nanotube models obtained from the Vsim and EPOCH codes. Experimental setups to detect wakefields are also outlined with accelerator facilities at Fermilab and Northern Illinois University (NIU). In the FAST facility, the electron beamline was successfully commissioned at 50 MeV, and it is being upgraded toward higher energies for electron accelerator R&D. The 50 MeV injector beamline of the facility is used for X-ray crystal-channeling radiation with a diamond target. It has been proposed to utilize the same diamond crystal for a channeling acceleration proof-of-concept (POC). Another POC experiment is also designed for the NIU accelerator lab with time

  13. Application of chemicals to substrates without the use of liquids: Proof of concepts for powder spray gun and fluidized bed solid-on- solid (SOS) processing of textiles, and continued research in textile xerography printing, solid shade coloration and electrostatic liquid spray SOS finishing of fabrics

    Energy Technology Data Exchange (ETDEWEB)

    Cook, F.L.; Carr, W.W.; Tincher, W.C.; Sikorski, M.

    1990-09-28

    The first two years of research under DOE Contract No. FG05-84CE40702 were devoted toward developing processes whereby certain chemicals could be applied to textiles without the use of water, mainly concentrating on powder deposition techniques. The approach was to identify powder-based processes in other industry sectors (mainly the metals and paper industries) that possessed the potential to be adapted to continuous textile manufacturing lines. The adapted textile processes were classified under the general category of solid-on-solid (SOS) processes, since no liquid water was required, and 100% of the chemical materials applied to the substrate remained with it into final product manufacture. The current research focused on several areas of chemical treatment: yarn slashing, textile xerography printing, binding of nonwovens, fluoropolymer barrier finishing, and liquid spray and finishing. Several of these areas were sufficiently developed in the first phase to allow full-scale, proof-of-concept trials to be conducted at industrial sites in the third and fourth years of the project. Other areas were identified and preliminary investigations conducted in the first phase, but were largely left for full development in the reported phase, e.g., liquid spray finishing of 100% solids formulations. This report discusses work in each area of chemical treatment.

  14. Structure of proof of concept studies that precede a nonalcoholic steatohepatitis development program

    Science.gov (United States)

    Filozof, C; Goldstein, BJ; Cusi, K

    2016-01-01

    Surrogate endpoints for clinical proof of concept (POC) trials in nonalcoholic steatohepatitis (NASH) are based upon expert pathological review of liver biopsies. During early development, these long‐term POC studies (≥48 weeks) add cost and time to the “Go/No Go” decision process. However, it is possible to conduct short‐term noninvasive POC studies utilizing biomarkers and magnetic resonance imaging. Here, we discuss the use of shorter noninvasive POC studies relative to biopsy‐driven studies for drug development in NASH. PMID:28032901

  15. Supply Chain Based Solution to Prevent Fuel Tax Evasion: Proof of Concept Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Capps, Gary J [ORNL; Lascurain, Mary Beth [ORNL; Franzese, Oscar [ORNL; Earl, Dennis Duncan [ORNL; West, David L [ORNL; McIntyre, Timothy J [ORNL; Chin, Shih-Miao [ORNL; Hwang, Ho-Ling [ORNL; Connatser, Raynella M [ORNL; Lewis Sr, Samuel Arthur [ORNL; Moore, Sheila A [ORNL

    2011-12-01

    The goal of this research was to provide a proof-of-concept (POC) system for preventing non-taxable (non-highway diesel use) or low-taxable (jet fuel) petrochemical products from being blended with taxable fuel products and preventing taxable fuel products from cross-jurisdiction evasion. The research worked to fill the need to validate the legitimacy of individual loads, offloads, and movements by integrating and validating, on a near-real-time basis, information from global positioning system (GPS), valve sensors, level sensors, and fuel-marker sensors.

  16. Robot-assisted shopping for the visually impaired: proof-of-concept design and feasibility evaluation.

    Science.gov (United States)

    Kulyukin, Vladimir; Gharpure, Chaitanya; Coster, Daniel

    2008-01-01

    This article presents RoboCart, a proof-of-concept prototype of a robotic shopping cart for the visually impaired in supermarkets. RoboCart autonomously leads shoppers to required locations and cues them through synthetic speech and a portable barcode reader to the salient features of the environment sufficient for product retrieval. In a longitudinal pilot feasibility study, visually impaired shoppers (n = 10) used the device to retrieve products in Lee's MarketPlace, a supermarket in Logan, Utah. The main finding is that RoboCart enables visually impaired shoppers to reliably and independently navigate to and retrieve products in a real supermarket.

  17. The proof of concept for 3-cm Altimetry using the Paris Interferometric Technique

    OpenAIRE

    Nogues-Correig, Oleguer; Ribó Vedrilla, Serni; Arco, Juan Carlos; Cardellach, Estel; Rius Jordán, Antonio; Valencia, Enric; Tarongí, José Miguel; Camps, Adriano; Van der Marel, Hans; Martín-Neira, Manuel

    2010-01-01

    © 2010 IEEE. Reprinted, with permission, from Nogués, O., Ribó, S., Arco, J. C., Cardellach, E., Rius, A., València, E., A. Camps, van der Marel, H., Martín-Neira, M., The proof of concept for 3-cm altimetry using the PARIS interferometric technique, Proceedings of IEEE International Geoscience and Remote Sensing Symposium (IEEE IGARSS), and july/2010. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endo...

  18. Proof-of-Concept Studies for a Local Tie Monitoring System

    Science.gov (United States)

    Schmeing, Benno; Behrend, Dirk; Gipson, John; Nothnagel, Axel

    2010-01-01

    We present preliminary results of proof-of-concept studies for an automatic monitoring system of local site ties. The system is based on the usage of robotic total stations. A set of tests were performed with a Leica TCA2003 total station on the local network of Goddard s Geophysical and Astronomical Observatory (GGAO) and the 5-m VLBI antenna at this site. Both the TCA2003 and the VLBI antenna are controlled from a Matlab-coded control program. Running specific observational programs, data were collected that indicate that the reference point of the VLBI antenna can be automatically determined with an accuracy of 1 mm or better.

  19. Development of a Flexible Laser Hardening & Machining Center and Proof of Concept on C-45 Steel

    Science.gov (United States)

    Bouquet, Jan; Van Camp, Dries; Vanhove, Hans; Clijsters, Stijn; Amirahmad, Mohammadi; Lauwers, Bert

    The production of hardened precision parts is conventionally done in 3 steps. Rough machining of a workpiece in soft stage is followed by a hardening step, usually a batch process, and finalized by a hard machining finishing step. To omit the inevitable time delay and loss of accuracy because of part re-clamping, these steps should be incorporated within one flexible machining center. This paper describes the development of this machining center which allowsmachining and laser hardening in one setup, followed by a proof of concept for hardening C45 steel on this setup.

  20. A novel topical agent in the treatment of seborrheic keratoses: A proof of concept study by clinical and dermoscopic evaluation.

    Science.gov (United States)

    Lacarrubba, Francesco; Nasca, Maria Rita; Verzì, Anna Elisa; Micali, Giuseppe

    2017-08-10

    In this proof of concept study, 50 lesions from 15 patients with multiple seborrheic keratoses (SKs) were treated with a novel aqueous solution containing nitric acid, zinc and copper salts, and organic acids (acetic, lactic, and oxalic acid). Treatment consisted in the application of an amount of the solution sufficient to obtain a whitening/yellowish reaction. Application of the nitric-zinc solution was performed every other week until clinical and dermoscopic clearance or crust formation, for a maximum of 4 applications. Efficacy evaluation was performed at 8 weeks (T1) and 6 months (T2). All subjects, who reported no or minimal discomfort during and after the application of the solution, completed the study. At T1, a complete clinical and dermoscopic resolution was observed in 37 lesions after an average of 3 applications/lesion (range 2-4). A partial response, with minimal persistent residual spots, was detected in the remaining 13 lesions. All patients with complete clearance showed no relapses at a 6-month follow-up (T2). The positive preliminary results indicate that this novel solution may represent a promising alternative option for SKs especially in patients not keen or eligible to undergo invasive tissue-destructive procedures. © 2017 Wiley Periodicals, Inc.

  1. Stone/tissue differentiation for Holmium laser lithotripsy using autofluorescence: Clinical proof of concept study.

    Science.gov (United States)

    Lange, Birgit; Jocham, Dieter; Brinkmann, Ralf; Cordes, Jens

    2017-04-01

    Holmium laser lithotripsy is the gold standard for intracorporeal fragmentation of urinary calculi. Usually, a visible beam is superimposed on the IR treatment laser as an aiming beam to guide the surgeon. In vitro tests showed that this aiming beam (532 nm, power proof of concept study with eight patients. For this, a modulated excitation/detection scheme (lock-in technique) was implemented. A frequency-doubled, diode-pumped solid-state laser module (532 nm, modulation frequency 66 Hz, average power 0.3 mW) was coupled via a dichroic mirror with the Holmium lithotripsy laser into the treatment fiber. The fluorescence signal entering the treatment fiber was detected via another dichroic mirror with a photodiode and a lock-in amplifier. In most instances (94%), the calculus of a patient gave a signal which was at least twice the maximum signal of ureteral tissue. The results of our proof of concept study indicate that measuring the fluorescence signal of a green aiming beam could be used to implement a feedback loop for Holmium laser lithotripsy. Preventing the laser being fired on tissue, this would increase the safety of the procedure. Lasers Surg. Med. 49:361-365, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. The Glacier and Land Ice Surface Topography Interferometer: An Airborne Proof-of-concept Mapping Sensor

    Science.gov (United States)

    Moller, D.; Hensley, S.; Chuang, C.; Fisher, C.; Muellerschoen, R.; Milligan, L.; Sadowy, G.; Rignot, E. J.

    2009-12-01

    In May 2009 a new radar technique for mapping ice surface topography was demonstrated in a Greenland campaign as part of the NASA International Polar Year activities. This was achieved by integrating a Ka-band single-pass interferometric synthetic radar on the NASA Dryden Gulfstream III for a coordinated deployment. Although the technique of using radar interferometry for mapping terrain has been demonstrated before, this is the first such application at millimeter-wave frequencies. This proof-of-concept demonstration was motivated by the Glacier and Land Ice Surface Topography Interferometer (GLISTIN) Instrument Incubator Program and furthermore, highly leveraged existing ESTO hardware and software assets (the Unmanned Airborne Vehicle Synthetic Aperture Radar (UAVSAR) and processor and the PR2 (precipitation radar 2) RF assembly and power amplifier). Initial Ka-band test flights occurred in March and April of 2009 followed by the Greenland deployment. Instrument performance indicates swath widths over the ice between 5-7km, with height precisions ranging from 30cm-3m at a posting of 3m x 3m. However, for this application the electromagnetic wave will penetrate an unknown amount into the snow cover thus producing an effective bias that must be calibrated. This penetration will be characterized as part of this program and is expected to vary as a function of snow wetness and radar incidence angle. To evaluate this, we flew a coordinated collection with the NASA Wallops Airborne Topographic Mapper on a transect from Greenland’s Summit its West coast. This flight included two field calibration sites at Colorado Institute for Research in Environmental Science’s Swiss Camp and the National Science Foundation’s Summit station. Additional collections entailed flying a grid over Jakobshavn glacier which were repeated after 6 days to reveal surface dynamics. In this time frame we were able to observe horizontal motion of over 1km on the glacier. While developed for

  3. Design trade-off and proof of concept for LOUPE, the Lunar Observatory for Unresolved Polarimetry of Earth.

    Science.gov (United States)

    Hoeijmakers, H J; Arts, M L J; Snik, F; Keller, C U; Kuiper, J M

    2016-09-19

    We provide a proof of the technical feasibility of LOUPE, the first integral-field snapshot spectropolarimeter, designed to monitor the reflected flux and polarization spectrum of Earth. These are to be used as benchmark data for the retrieval of biomarkers and atmospheric and surface characteristics from future direct observations of exoplanets. We perform a design trade-off for an implementation in which LOUPE performs snapshot integral-field spectropolarimetry at visible wavelengths. We used off-the-shelf optics to construct a polarization modulator, in which polarization information is encoded into the spectrum as a wavelength-dependent modulation, while spatial resolution is maintained using a micro-lens array. The performance of this design concept is validated in a laboratory setup. Our proof-of-concept is capable of measuring a grid of 50 × 50 polarization spectra between 610 and 780 nm of a mock target planet - proving the merit of this design. The measurements are affected by systematic noise on the percent level, and we discuss how to mitigate this in future iterations. We conclude that LOUPE can be small and robust while meeting the science goals of this particular space application, and note the many potential applications that may benefit from our concept for doing snapshot integral-field spectropolarimetry.

  4. Development of a lozenge for oral transmucosal delivery of trans-resveratrol in humans: proof of concept.

    Directory of Open Access Journals (Sweden)

    Otis L Blanchard

    Full Text Available Resveratrol provides multiple physiologic benefits which promote healthspan in various model species and clinical trials support continued exploration of resveratrol treatment in humans. However, there remains concern regarding low bioavailability and wide inter-individual differences in absorption and metabolism in humans, which suggests a great need to develop novel methods for resveratrol delivery. We hypothesized that oral transmucosal delivery, using a lozenge composed of a resveratrol-excipient matrix, would allow resveratrol to be absorbed rapidly into the bloodstream. We pursued proof of concept through two experiments. In the first experiment, the solubility of trans-resveratrol (tRES in water and 2.0 M solutions of dextrose, fructose, ribose, sucrose, and xylitol was determined using HPLC. Independent t-tests with a Bonferroni correction were used to compare the solubility of tRES in each of the solutions to that in water. tRES was significantly more soluble in the ribose solution (p = 0.0013 than in the other four solutions. Given the enhanced solubility of tRES in a ribose solution, a resveratrol-ribose matrix was developed into a lozenge suitable for human consumption. Lozenges were prepared, each containing 146±5.5 mg tRES per 2000 mg of lozenge mass. Two healthy human participants consumed one of the prepared lozenges following an overnight fast. Venipuncture was performed immediately before and 15, 30, 45, and 60 minutes following lozenge administration. Maximal plasma concentrations (Cmax for tRES alone (i.e., resveratrol metabolites not included were 325 and 332 ng⋅mL(-1 for the two participants at 15 minute post-administration for both individuals. These results suggest a resveratrol-ribose matrix lozenge can achieve greater Cmax and enter the bloodstream faster than previously reported dosage forms for gastrointestinal absorption. While this study is limited by small sample size and only one method of resveratrol

  5. Collection, synthesis, and interpretation of evidence: a proof-of-concept study in COPD.

    Science.gov (United States)

    Di Scala, L; Kerman, J; Neuenschwander, B

    2013-05-10

    We present a clinical proof-of-concept (PoC) study in chronic obstructive pulmonary disease with the objective of assessing the bronchodilatory effect of an experimental drug as compared with an active control treatment. In such an exploratory Phase II setting, we discuss the formal inclusion of relevant historical information and tailored PoC criteria for the purpose of a more efficient use of the available evidence to support clinical decision making. We provide guidance with regard to practical and methodological aspects for assessing the relevance of the historical data, synthesizing the evidence via a meta-analytic-predictive approach, and defining transparent statistical PoC decision criteria that are aligned with the clinical context. The case study was implemented using the Bayesian approach, which offers an ideal framework for the early phases of drug development. Copyright © 2013 John Wiley & Sons, Ltd.

  6. Development of a pseudo/anonymised primary care research database: Proof-of-concept study.

    Science.gov (United States)

    MacRury, Sandra; Finlayson, Jim; Hussey-Wilson, Susan; Holden, Samantha

    2016-06-01

    General practice records present a comprehensive source of data that could form a variety of anonymised or pseudonymised research databases to aid identification of potential research participants regardless of location. A proof-of-concept study was undertaken to extract data from general practice systems in 15 practices across the region to form pseudo and anonymised research data sets. Two feasibility studies and a disease surveillance study compared numbers of potential study participants and accuracy of disease prevalence, respectively. There was a marked reduction in screening time and increase in numbers of potential study participants identified with the research repository compared with conventional methods. Accurate disease prevalence was established and enhanced with the addition of selective text mining. This study confirms the potential for development of national anonymised research database from general practice records in addition to improving data collection for local or national audits and epidemiological projects.

  7. Development and testing of the Perseus proof-of-concept aircraft. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Langford, J.S. [Aurora Flight Sciences Corp., Manassas, VA (United States)

    1993-02-26

    Many areas of global climate change research could benefit from a flexible, affordable, and near-term platform that could provide in situ measurements in the upper troposphere and lower stratosphere. To provide such a capability, the Perseus unmanned science research aircraft was proposed in 1989. As a first step toward the development of Perseus, a proof-of-concept (POC) demonstrator was constructed and tested during 1990 and 1991. The POC was a full scale Perseus airframe intended to validate the structural, aerodynamic, and flight control technologies for the Perseus within a total budget of about $1.5 million. Advanced propulsion systems needed for the operational Perseus were not covered in the POC program due to funding limitations. This report documents the design, development, and testing of the Perseus POC.

  8. Approach Bias Modification in Food Craving-A Proof-of-Concept Study.

    Science.gov (United States)

    Brockmeyer, Timo; Hahn, Carolyn; Reetz, Christina; Schmidt, Ulrike; Friederich, Hans-Christoph

    2015-09-01

    The aim of the present proof-of-concept study was to test a novel cognitive bias modification (CBM) programme in an analogue sample of people with subclinical bulimic eating disorder (ED) psychopathology. Thirty participants with high levels of trait food craving were trained to make avoidance movements in response to visual food stimuli in an implicit learning paradigm. The intervention comprised ten 15-minute sessions over a 5-week course. At baseline, participants showed approach and attentional biases towards high-caloric palatable food that were both significantly reduced and turned into avoidance biases after the training. Participants also reported pronounced reductions in both trait and cue-elicited food craving and in ED symptoms as well. The overall evaluation of the training by the participants was positive. The specific CBM programme tested in this pilot trial promises to be an effective and feasible way to alter automatic action tendencies towards food in people suffering from bulimic ED psychopathology.

  9. Similarity-based disease risk assessment for personal genomes: proof of concept.

    Science.gov (United States)

    Woo, Jung Hoon; Lai, Albert M; Chung, Wendy K; Weng, Chunhua

    2011-01-01

    The increasing availability of personal genome data has led to escalating needs by consumers to understand the implications of their gene sequences. At present, poorly integrated genetic knowledge has not met these needs. This proof-of-concept study proposes a similarity-based approach to assess the disease risk predisposition for personal genomes. We hypothesize that the semantic similarity between a personal genome and a disease can indicate the disease risks in the person. We developed a knowledge network that integrates existing knowledge of genes, diseases, and symptoms from six sources using the Semantic Web standard, Resource Description Framework (RDF). We then used latent relationships between genes and diseases derived from our knowledge network to measure the semantic similarity between a personal genome and a genetic disease. For demonstration, we showed the feasibility of assessing the disease risks in one personal genome and discussed related methodology issues.

  10. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.

    Science.gov (United States)

    Franke, Barbara; Stein, Jason L; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Yao, Yin; Ho, Yvonne Y W; Martin, Nicholas G; Wright, Margaret J; O'Donovan, Michael C; Thompson, Paul M; Neale, Benjamin M; Medland, Sarah E; Sullivan, Patrick F

    2016-03-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

  11. Early recognition of coeliac disease through community pharmacies: a proof of concept study.

    Science.gov (United States)

    Urwin, Heidi; Wright, David; Twigg, Michael; McGough, Norma

    2016-10-01

    Setting Fifteen community pharmacies in the UK. Objective Proof of concept study to test the use of community pharmacies for active case finding of patients with coeliac disease. Methods Customers accessing over-the counter and prescription medicines indicated in the treatment of possible symptoms of coeliac disease over a 6 month period were offered a free point of care test. All patients were given advice regarding the test results and those who tested positive were advised to make an appointment with their general practitioner. Patients and pharmacists involved in service provision were asked to complete a satisfaction survey. Pharmacists were additionally invited to undertake interviews to better understand their views on the service. Main outcome measures Feasibility of service, acceptability to stakeholders and proportion testing positive for coeliac disease. Results Of the 551 individuals tested, 52 (9.4 %) tested positive. 277 (50.3 %) were tested for accessing irritable bowel syndrome treatment, 142 (25.8 %) due to presenting for diarrhoea. The proportion of patients testing positive with different symptoms or for different treatments were similar. Of 43 customers who returned the satisfaction survey, all would recommend the service to others, believing the community pharmacy to be a suitable location. Community pharmacists believed that it enabled them to improve relationships with their customers and that medical practices were receptive to the service. Conclusion This proof of concept study has shown that community pharmacies using a point of care test can effectively recognise and refer patients for confirmatory coeliac disease testing with high levels of customer and service provider satisfaction.

  12. Support vector machines for automated snoring detection: proof-of-concept.

    Science.gov (United States)

    Samuelsson, Laura B; Rangarajan, Anusha A; Shimada, Kenji; Krafty, Robert T; Buysse, Daniel J; Strollo, Patrick J; Kravitz, Howard M; Zheng, Huiyong; Hall, Martica H

    2017-03-01

    Snoring has been shown to be associated with adverse physical and mental health, independent of the effects of sleep disordered breathing. Despite increasing evidence for the risks of snoring, few studies on sleep and health include objective measures of snoring. One reason for this methodological limitation is the difficulty of quantifying snoring. Conventional methods may rely on manual scoring of snore events by trained human scorers, but this process is both time- and labor-intensive, making the measurement of objective snoring impractical for large or multi-night studies. The current study is a proof-of-concept to validate the use of support vector machines (SVM), a form of machine learning, for the automated scoring of an objective snoring signal. An SVM algorithm was trained and tested on a set of approximately 150,000 snoring and non-snoring data segments, and F-scores for SVM performance compared to visual scoring performance were calculated using the Wilcoxon signed rank test for paired data. The ability of the SVM algorithm to discriminate snore from non-snore segments of data did not differ statistically from visual scorer performance (SVM F-score = 82.46 ± 7.93 versus average visual F-score = 88.35 ± 4.61, p = 0.2786), supporting SVM snore classification ability comparable to visual scorers. In this proof-of-concept, we established that the SVM algorithm performs comparably to trained visual scorers, supporting the use of SVM for automated snoring detection in future studies.

  13. Kaiser Permanente Northern California pregnancy database: Description and proof of concept study.

    Science.gov (United States)

    Zerbo, Ousseny; Chan, Berwick; Goddard, Kristin; Lewis, Ned; Bok, Karin; Klein, Nicola P; Baxter, Roger

    2016-11-04

    We describe the establishment of a dynamic database linking mothers to newborns with the goal of studying vaccine safety in both pregnant women and their children and provide results of a study utilizing this database as a proof of concept. All Kaiser Permanente Northern California (KPNC) live births and their mothers were eligible for inclusion in the pregnancy database. We used the medical record number (MRN), a unique identifier, to retrieve information about events that occurred during the pregnancy and at delivery and linked this same MRN to newborns for post-partum follow up. We conducted a retrospective cohort study to evaluate the association between receipt of tetanus, diphtheria and acellular pertussis (Tdap) vaccine during pregnancy and fever 0-3days after the first dose of diphtheria tetanus and acellular pertussis (DTaP) vaccine in the infant. The study included infants who were born at ⩾37weeks gestation from January 1, 2009 - October 1, 2015 and who received their first DTaP vaccine between 6 and 10weeks of age. We utilized diagnostic codes from inpatient, emergency department, outpatient clinics, and telephone calls. We identified fever using ICD 9 code 780.6, recorded temperature ⩾101 degree Fahrenheit, or parental report. The database contained the starting and ending date of each pregnancy and basic demographic characteristics of mothers and infants. There were 859,699 women and 873,753 children in the database as of January 2016. The proof of concept study included 148,699 infants. In a multivariable logistic regression analysis, Tdap vaccination during pregnancy was not associated with infant fever 0-3daysafter first dose of DTaP (adjusted odds ratio=0.92, 95% CI 0.82-1.04). The KPNC pregnancy database can be used for studies investigating exposure during pregnancy and outcomes in mothers and/or infants, particularly monitoring vaccine safety and effectiveness. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Proof of concept of the ability of the kinect to quantify upper extremity function in dystrophinopathy.

    Science.gov (United States)

    Lowes, Linda P; Alfano, Lindsay N; Yetter, Brent A; Worthen-Chaudhari, Lise; Hinchman, William; Savage, Jordan; Samona, Patrick; Flanigan, Kevin M; Mendell, Jerry R

    2013-03-14

    Individuals with dystrophinopathy lose upper extremity strength in proximal muscles followed by those more distal. Current upper extremity evaluation tools fail to fully capture changes in upper extremity strength and function across the disease spectrum as they tend to focus solely on distal ability. The Kinect by Microsoft is a gaming interface that can gather positional information about an individual's upper extremity movement which can be used to determine functional reaching volume, velocity of movement, and rate of fatigue while playing an engaging video game. The purpose of this study was to determine the feasibility of using the Kinect platform to assess upper extremity function in individuals with dystrophinopathy across the spectrum of abilities. Investigators developed a proof-of-concept device, ACTIVE (Abilities Captured Through Interactive Video Evaluation), to measure functional reaching volume, movement velocity, and rate of fatigue. Five subjects with dystrophinopathy and 5 normal controls were tested using ACTIVE during one testing session. A single subject with dystrophinopathy was simultaneously tested with ACTIVE and a marker-based motion analysis system to establish preliminary validity of measurements. ACTIVE proof-of-concept ranked the upper extremity abilities of subjects with dystrophinopathy by Brooke score, and also differentiated them from performance of normal controls for the functional reaching volume and velocity tests. Preliminary test-retest reliability of the ACTIVE for 2 sequential trials was excellent for functional reaching volume (ICC=0.986, pproof-of-concept demonstrates that newly available gaming technology has potential to be used to create a low-cost, widely-accessible and functional upper extremity outcome measure for use with children and adults with dystrophinopathy.

  15. External Vision Systems (XVS) proof-of-concept flight test evaluation

    Science.gov (United States)

    Shelton, Kevin J.; Williams, Steven P.; Kramer, Lynda J.; Arthur, Jarvis J.; Prinzel, Lawrence; Bailey, Randall E.

    2014-06-01

    NASA's Fundamental Aeronautics Program, High Speed Project is performing research, development, test and evaluation of flight deck and related technologies to support future low-boom, supersonic configurations (without forward-facing windows) by use of an eXternal Vision System (XVS). The challenge of XVS is to determine a combination of sensor and display technologies which can provide an equivalent level of safety and performance to that provided by forward-facing windows in today's aircraft. This flight test was conducted with the goal of obtaining performance data on see-and-avoid and see-to-follow traffic using a proof-of-concept XVS design in actual flight conditions. Six data collection flights were flown in four traffic scenarios against two different sized participating traffic aircraft. This test utilized a 3x1 array of High Definition (HD) cameras, with a fixed forward field-of-view, mounted on NASA Langley's UC-12 test aircraft. Test scenarios, with participating NASA aircraft serving as traffic, were presented to two evaluation pilots per flight - one using the proof-of-concept (POC) XVS and the other looking out the forward windows. The camera images were presented on the XVS display in the aft cabin with Head-Up Display (HUD)-like flight symbology overlaying the real-time imagery. The test generated XVS performance data, including comparisons to natural vision, and post-run subjective acceptability data were also collected. This paper discusses the flight test activities, its operational challenges, and summarizes the findings to date.

  16. Proof of concept in cardiovascular risk: the paradoxical findings in blood pressure and lipid abnormalities

    Directory of Open Access Journals (Sweden)

    Fuchs FD

    2012-07-01

    Full Text Available Flavio Danni Fuchs, Sandra Costa Fuchs, Leila Beltrami Moreira, Miguel GusDivision of Cardiology and Postgraduate Studies Program in Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilAbstract: High blood pressure and lipoprotein abnormalities were identified by many cohort studies as the major risk factors for cardiovascular disease. Laboratory experiments apparently confirmed their role in the causation of atherosclerosis, but a proof of concept requires the corroboration by clinical trials in human beings. The size of benefit in clinical trials regarding the control of high blood pressure was within the estimations of risk provided by cohort studies. For a reduction of 10 mmHg in systolic blood pressure or 5 mmHg in diastolic blood pressure, the relative risk reduction of coronary heart disease was 22% (95% confidence interval 27%–17% in a meta-analysis of clinical trials, close to the estimation of reduction of 25% (95% confidence interval 23%–27% provided by a meta-analysis of cohort studies. The corresponding values for stroke were 41% (95% confidence interval 33%–48% in clinical trials compared to a cohort risk prediction of 36% (95% confidence interval 34%–38%. This efficacy was shared by all blood pressure-lowering drugs. The same figure has not paradoxically happened with drugs that act over abnormalities of cholesterol and lipoproteins. Only statins, which have other beneficial actions as well, have consistently lowered the incidence of cardiovascular diseases, an efficacy that was not reproduced by older and newer quite potent lipid drugs. The adverse effects of these drugs may nullify their beneficial effects over lipoproteins and abnormalities of lipoproteins may only be surrogate markers of the underlying real risks.Keywords: proof of concept, hypertension, lipoproteins, clinical trials

  17. External Vision Systems (XVS) Proof-of-Concept Flight Test Evaluation

    Science.gov (United States)

    Shelton, Kevin J.; Williams, Steven P.; Kramer, Lynda J.; Arthur, Jarvis J.; Prinzel, Lawrence, III; Bailey, Randall E.

    2014-01-01

    NASA's Fundamental Aeronautics Program, High Speed Project is performing research, development, test and evaluation of flight deck and related technologies to support future low-boom, supersonic configurations (without forward-facing windows) by use of an eXternal Vision System (XVS). The challenge of XVS is to determine a combination of sensor and display technologies which can provide an equivalent level of safety and performance to that provided by forward-facing windows in today's aircraft. This flight test was conducted with the goal of obtaining performance data on see-and-avoid and see-to-follow traffic using a proof-of-concept XVS design in actual flight conditions. Six data collection flights were flown in four traffic scenarios against two different sized participating traffic aircraft. This test utilized a 3x1 array of High Definition (HD) cameras, with a fixed forward field-of-view, mounted on NASA Langley's UC-12 test aircraft. Test scenarios, with participating NASA aircraft serving as traffic, were presented to two evaluation pilots per flight - one using the proof-of-concept (POC) XVS and the other looking out the forward windows. The camera images were presented on the XVS display in the aft cabin with Head-Up Display (HUD)-like flight symbology overlaying the real-time imagery. The test generated XVS performance data, including comparisons to natural vision, and post-run subjective acceptability data were also collected. This paper discusses the flight test activities, its operational challenges, and summarizes the findings to date.

  18. Non-Invasive Intra-cardiac Pressure Measurements Using Subharmonic-Aided Pressure Estimation: Proof of Concept in Humans.

    Science.gov (United States)

    Dave, Jaydev K; Kulkarni, Sushmita V; Pangaonkar, Purva P; Stanczak, Maria; McDonald, Maureen E; Cohen, Ira S; Mehrotra, Praveen; Savage, Michael P; Walinsky, Paul; Ruggiero, Nicholas J; Fischman, David L; Ogilby, David; VanWhy, Carolyn; Lombardi, Matthew; Forsberg, Flemming

    2017-08-11

    This study evaluated the feasibility of employing non-invasive intra-cardiac pressure estimation using subharmonic signals from ultrasound contrast agents in humans. This institutional review board-approved proof-of-concept study included 15 consenting patients scheduled for left and right heart catheterization. During the catheterization procedure, Definity was infused intra-venously at 4-10 mL/min. Ultrasound scanning was performed with a Sonix RP using pulse inversion, three incident acoustic output levels and 2.5-MHz transmit frequency. Radiofrequency data were processed and subharmonic amplitudes were compared with the pressure catheter data. The correlation coefficient between subharmonic signals and pressure catheter data ranged from -0.3 to -0.9. For acquisitions with optimum acoustic output, pressure errors between the subharmonic technique and catheter were as low as 2.6 mmHg. However, automatically determining optimum acoustic output during scanning for each patient remains to be addressed before clinical applicability can be decided. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  19. Metformin and Melatonin in Adrenocortical Carcinoma: Morphoproteomics and Biomedical Analytics Provide Proof of Concept in a Case Study.

    Science.gov (United States)

    Brown, Robert E; Buryanek, Jamie; McGuire, Mary F

    2017-08-01

    Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli's recent preclinical studies that 1. "in vitro" metformin modulates the ACC cell model H295R and 2. "in vivo" metformin inhibits tumor growth in a xenograft model as confirmed by a significant reduction of Ki67 [1]. Here we report on our prior clinical case study that provides proof of concept for Poli's studies. We were requested to perform morphoproteomic analysis to further define the biology of, and raise targeted therapeutic options, for a case of post-treatment and chemoresistant ACC metastatic to the liver and the lung. Profiling the patient's ACC from the liver resulted in the recommendation of metformin as a maintenance therapy, which was supported by biomedical data analysis. The patient remains on maintenance therapy with metformin and melatonin and is free of disease some 7 years post diagnosis, thus underscoring the recommendation for clinical trials employing these therapeutic agents. © 2017 by the Association of Clinical Scientists, Inc.

  20. Climate change-related temperature impacts on warm season heat mortality: a proof-of-concept methodology using BenMAP.

    Science.gov (United States)

    Voorhees, A Scott; Fann, Neal; Fulcher, Charles; Dolwick, Patrick; Hubbell, Bryan; Bierwagen, Britta; Morefield, Philip

    2011-02-15

    Climate change is anticipated to raise overall temperatures and is likely to increase heat-related human health morbidity and mortality risks. The objective of this work was to develop a proof-of-concept approach for estimating excess heat-related premature deaths in the continental United States resulting from potential changes in future temperature using the BenMAP model. In this approach we adapt the methods and tools that the US Environmental Protection Agency uses to assess air pollution health impacts by incorporating temperature modeling and heat mortality health impact functions. This new method demonstrates the ability to apply the existing temperature-health literature to quantify prospective changes in climate-sensitive heat-related mortality. We compared estimates of future temperature with and without climate change and applied heat-mortality health functions to estimate relative changes in heat-related premature mortality. Using the A1B emissions scenario, we applied the GISS-II global circulation model downscaled to 36-km using MM5 and formatted using the Meteorology-Chemistry Interface Processor. For averaged temperatures derived from the 5 years 2048-2052 relative to 1999-2003 we estimated for the warm season May-September a national U.S. estimate of annual incidence of heat-related mortality to be 3700-3800 from all causes, 3500 from cardiovascular disease, and 21 000-27 000 from nonaccidental death, applying various health impact functions. Our estimates of mortality, produced to validate the application of a new methodology, suggest the importance of quantifying heat impacts in economic assessments of climate change.

  1. Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Frankwich Karen

    2012-10-01

    Full Text Available Abstract Background Obesity is a state of subclinical inflammation resulting in loss of function of insulin receptors and decreased insulin sensitivity. Inhibition of the inflammatory enzymes, matrix metalloproteinases (MMPs, for 6 months in rodent models restores insulin receptor function and insulin sensitivity. Methods This 12-week double-blind, randomized, placebo (PL-controlled proof-of-concept study was performed to determine if the MMP inhibitor (MMPI, doxycycline, decreased global markers of inflammation and enhanced muscle insulin sensitivity in obese people with type 2 diabetes (DM2. The study included non-DM2 controls (n = 15, and DM2 subjects randomized to PL (n = 13 or doxycycline 100 mg twice daily (MMPI; n = 11. All participants were evaluated on Day 1; MMPI and PL groups were also evaluated after 84 days of treatment. Results There was a significant decrease in inflammatory markers C-reactive protein (P  Conclusions This study demonstrated short term treatment of people with diabetes with an MMPI resulted in decreased inflammation and improved insulin sensitivity. Larger, longer studies are warranted to determine if doxycycline can improve glucose control in people with diabetes. Trial Registration Clinicaltrials.gov NCT01375491

  2. Proof-of-concept Design and Development of an EN13606-based Electronic Health Care Record Service

    Science.gov (United States)

    Muñoz, Adolfo; Somolinos, Roberto; Pascual, Mario; Fragua, Juan A.; González, Miguel A.; Monteagudo, Jose Luis; Salvador, Carlos H.

    2007-01-01

    Objective The authors present an Electronic Healthcare Record (EHR) server, designed and developed as a proof of concept of the revised prEN13606:2005 European standard concerning EHR communications. Methods The development of the server includes five modules: the libraries for the management of the standard reference model, for the demographic package and for the data types; the permanent storage module, built on a relational database; two communication interfaces through which the clients can send information or make queries; the XML (eXtensible Markup Language) process module; and the tools for the validation of the extracts managed, implemented on a defined XML-Schema. Results The server was subjected to four phases of trials, the first three with ad hoc test data and processes to ensure that each of the modules complied with its specifications and that the interaction between them provided the expected functionalities. The fourth used real extracts generated by other research groups for the additional purpose of testing the validity of the standard in real-world scenarios. Conclusion The acceptable performance of the server has made it possible to include it as a middleware service in a platform for the out-of-hospital follow-up and monitoring of patients with chronic heart disease which, at the present time, supports pilot projects and clinical trials for the evaluation of eHealth services. PMID:17068357

  3. Peptide Nucleic Acid-Fluorescence In Situ Hybridization for Detection of Staphylococci From Endophthalmitis Isolates: A Proof-of-Concept Study.

    Science.gov (United States)

    Patel, Nimesh; Miller, Darlene; Relhan, Nidhi; Flynn, Harry W

    2017-08-01

    Rapid identification of pathogens causing endophthalmitis may improve treatment outcomes through early administration of species-specific medication. The current study reports a new molecular application of peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) with Staphylococcus-specific molecular PNA probes for the potential rapid detection of common pathogens causing endophthalmitis. An experimental study was designed to evaluate the proof of concept at the microbiology laboratory of the Bascom Palmer Eye Institute. Stored culture-positive staphylococci endophthalmitis isolates obtained from prior vitreous samples (n = 15), along with broth as negative controls (n = 5) were used. Inoculum was prepared to a final concentration of 1 × 105 colony-forming units/mL to ensure that the isolates were viable. Smears of samples were fixed and hybridized using QuickFISH protocol with probes for Staphylococcus. With PNA-FISH technique, Staphylococcus aureus was identified in 9 of 10 samples and coagulase-negative staphylococci were identified in 10 of 10 samples. Detection time was 20 minutes. This study serves a proof of concept using a new microbial detection system with FISH probes, and may have the potential for clinical use in the rapid and accurate identification of isolates from patients with endophthalmitis.

  4. In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept.

    Science.gov (United States)

    Rodriguez, Carolyn I; Kegeles, Lawrence S; Levinson, Amanda; Ogden, R Todd; Mao, Xiangling; Milak, Matthew S; Vermes, Donna; Xie, Shan; Hunter, Liane; Flood, Pamela; Moore, Holly; Shungu, Dikoma C; Simpson, Helen B

    2015-08-30

    We previously reported the rapid and robust clinical effects of ketamine versus saline infusions in a proof-of-concept crossover trial in unmedicated adults with obsessive-compulsive disorder (OCD). This study examined the concurrent neurochemical effects of ketamine versus saline infusions using proton magnetic resonance spectroscopy ((1)H MRS) during the clinical proof-of-concept crossover trial. Levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurochemicals glutamate+glutamine (Glx) were acquired in the medial prefrontal cortex (MPFC), a region implicated in OCD pathology. Seventeen unmedicated OCD adults received two intravenous infusions at least 1 week apart, one of saline and one of ketamine, while lying supine in a 3.0 T GE MR scanner. The order of each infusion pair was randomized. Levels of GABA and Glx were measured in the MPFC before, during, and after each infusion and normalized to water (W). A mixed effects model found that MPFC GABA/W significantly increased over time in the ketamine compared with the saline infusion. In contrast, there were no significant differences in Glx/W between the ketamine and saline infusions. Together with earlier evidence of low cortical GABA in OCD, our findings suggest that models of OCD pathology should consider the role of GABAergic abnormalities in OCD symptomatology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Permutation criteria to evaluate multiple clinical endpoints in a proof-of-concept study : lessons from Pre-RELAX-AHF

    NARCIS (Netherlands)

    Davison, Beth A.; Cotter, Gad; Sun, Hengrui; Chen, Li; Teerlink, John R.; Metra, Marco; Felker, G. Michael; Voors, Adriaan A.; Ponikowski, Piotr; Filippatos, Gerasimos; Greenberg, Barry; Teichman, Sam L.; Unemori, Elaine; Koch, Gary G.

    2011-01-01

    Clinically relevant endpoints cannot be routinely targeted with reasonable power in a small study. Hence, proof-of-concept studies are often powered to a primary surrogate endpoint. However, in acute heart failure (AHF) effects on surrogates have not translated into clinical benefit in confirmatory

  6. A proof-of-concept study with the tyrosine kinase inhibitor nilotinib in spondyloarthritis.

    Science.gov (United States)

    Paramarta, Jacqueline E; Turina, Maureen C; Noordenbos, Troy; Heijda, Tanja F; Blijdorp, Iris C; Yeremenko, Nataliya; Baeten, Dominique

    2016-10-27

    To evaluate the immunomodulating and clinical effects of nilotinib, a tyrosine kinase inhibitor, in a proof-of-concept study in spondyloarthritis (SpA) assessing the mast cell as potential novel therapeutic target in this disease. Twenty eight patients with active peripheral (pSpA) and/or axial SpA (axSpA) were included in a randomized, double-blind, placebo-controlled clinical trial (Trial registration: Trialregister.nl NTR2834). Patients were treated 1:1 with nilotinib or placebo for 12 weeks, followed by an open label extension for another 12 weeks. Paired synovial tissue biopsies, serum sampling and assessment of clinical symptoms were performed serially. In pSpA (n = 13) synovial inflammation appeared to diminish after 12 weeks of nilotinib treatment as evidenced by histopathology (decrease in number of infiltrating CD68+ and CD163+ macrophages and mast cells). Compared to placebo mRNA expression of c-Kit as mast cell marker (p = 0.037) and of pro-inflammatory cytokines such as IL-6 (p = 0.024) were reduced. The reduction of synovial inflammation was paralleled by a decrease in serum biomarkers of inflammation such as C-reactive protein (p = 0.024) and calprotectin (p = 0.055). Also clinical parameters such as patient's global assessment of disease activity (p = 0.031) and ankylosing spondylitis disease activity score (p = 0.031) showed improvement upon 12 weeks of nilotinib but not placebo treatment. This improvement was further augmented at week 24. In contrast to pSpA, neither serum biomarkers of inflammation nor clinical parameters improved upon nilotinib treatment in axSpA. During the trial one serious adverse event occurred, which was considered unrelated to the study drug. This small proof-of-concept study suggests that nilotinib treatment modulates inflammation and clinical symptoms in pSpA. A similar effect was not seen in axSpA. trialregister.nl registration code NTR2834 registered 31 March 2011.

  7. Monolithic glass block lasercom terminal: hardware proof of concept and test results

    Science.gov (United States)

    Carlson, Robert T.; Drake, Marvin D.; Jaeger, Jerold L.

    1995-04-01

    We summarize a compact lasercom terminal implementation based on a previously described system concept, and report on measurements made on a prototype optical system built on internal MITRE funds. This paper discusses the fabrication and test of an innovative hardware proof-of-concept for an advanced satellite lasercom terminal with a ten-fold size, weight, and production cost reduction over current practice. We have built and tested a proof-of-concept of the optics portion of a full duplex `monolithic glass block' (MGB) lasercom terminal. The complete MGB optical system is only 6' X 4' X 0.5' and weighs less than a pound. A complete terminal which includes a 3 - 4 inch telescope and gimbal could be implemented for as little as 15 - 30 pounds. The optical system test results are reported. Our approach uses emerging technologies and a highly integrated system design, based on representative system requirements for satellite crosslinks. Technology evaluation and system trades led to a novel optics design for a lasercom terminal, based on thin film coatings and half-inch glass cubes. The emerging photonic technologies employed include liquid crystals for solid state switching, automatic gain control, and microradian alignment; multi-layer dielectric films for optical bandpass filters, dichroic separation, and polarization control; semiconductor lasers with microlens optics; and an original design where all the optics are realized in planar thin films incorporated on small glass substrates, nominally one-half inch in size. These glass cubes are permanently bonded together to form a monolithic ensemble. Hence, we have coined this implementation the monolithic glass block (MGB) approach. Fused silica is used throughout for reasons of superb radiation resistance and thermal stability. The thin film filters, switches, and polarizers perform all the necessary functions in collimated light. This approach is feasible because the optical paths have been dramatically reduced to

  8. Innovative Power Wheelchair Control Interface: A Proof-of-Concept Study.

    Science.gov (United States)

    Winkler, Sandra L; Romero, Sergio; Prather, Emily; Ramroop, Marisa; Slaibe, Emmy; Christensen, Matthew

    2016-01-01

    Some people without independent mobility are candidates for powered mobility but are unable to use a traditional power wheelchair joystick. This proof-of-concept study tested and further developed an innovative method of driving power wheelchairs for people whose impairments prevent them from operating commercial wheelchair controls. Our concept, Self-referenced Personal Orthotic Omni-purpose Control Interface (SPOOCI), is distinguished by referencing the control sensor not to the wheelchair frame but instead to the adjacent proximal lower-extremity segment via a custom-formed orthosis. Using a descriptive case-series design, we compared the pre-post functional power wheelchair driving skill data of 4 participants, measured by the Power Mobility Program, using descriptive analyses. The intervention consisted of standard-care power wheelchair training during 12 outpatient occupational or physical therapy sessions. All 4 participants who completed the 12-wk intervention improved their functional power wheelchair driving skills using SPOOCI, but only 3 were deemed safe to continue with power wheelchair driving.

  9. Transcranial Direct Current Stimulation Effects on Athletes’ Cognitive Performance: An Exploratory Proof of Concept Trial

    Directory of Open Access Journals (Sweden)

    Davimar Borduchi

    2016-11-01

    Full Text Available Among the 2016 Olympic and Paralympic Games unforgettable moments, one could not overlook performances by Phelps and Bolt, which challenge old premises about the maximum extension of individual supremacism in ultracompetitive modalities and the doping scandals. Different media channels resonated these two trends, with an unseen rise on discussions about traits and practices that may set ultrahigh performance athletes apart from the more ordinary ones. Yet, some key issues remain undebated. This paper aims to add to this debate, with a proof of concept trial, which investigates whether tDCS may serve as an aid for professional athletes. Ten professional athletes of three different modalities of (judo, N=4 athletes, swimming, N=3 athletes and rhythmic gymnastics, N=3 athletes received anodal stimulation (2mA for 20 minutes on the left dorsolateral prefrontal cortex for ten consecutive weekdays. We observed a positive effect of tDCS in their cognitive performance, including a significant improvement in alternated, sustained and divided attention and in memory scores. We also observed a decrease in Beck Depression Inventory scores (4.50 points in this non-clinical population. These preliminary results suggest that tDCS sessions may translate into competitive advantages for professional athletes and recommend the deepening of the discussion on its ethical use in sports, which is ultimately tied to the wider debate around the risks and opportunities that neuromodulation brings to the table.

  10. Proof-of-Concept Demonstration Results for Robotic Visual Servo Controllers

    Energy Technology Data Exchange (ETDEWEB)

    Chawda, P.V.

    2004-09-22

    There is significant motivation to provide robotic systems with improved autonomy as a means to significantly accelerate deactivation and decommissioning operations while also reducing the associated costs, removing human operators from hazardous environments, and reducing the required burden and skill of human operators. To achieve improved autonomy, fundamental research is focused on the challenges of developing visual servo controllers. The challenge in developing these controllers is that a camera provides 2-dimensional image information about the 3-dimensional Euclidean-space through a perspective (range dependent) projection that can be corrupted by uncertainty in the camera calibration matrix. Disturbances in this relationship (i.e., corruption in the sensor information) propagate erroneous information to the feedback controller of the robot, leading to potentially unpredictable task execution. This technical manual describes 3 proof-of-concept demonstrations of visual servo controllers developed from fundamental research aimed at these challenges. Specifically, one section describes the implementation of a cooperative visual servo control scheme with a camera-in-hand and a fixed camera to track a moving target despite uncertainty in the camera calibration and the unknown constant distance from the camera to a target where the camera is mounted on the end-effector of a 6 degrees-of-freedom hydraulic robot manipulator. The next section describes the implementation of 2 homography-based visual servo tracking and regulation controllers for a mobile robot with a calibrated camera despite an unknown time-varying distance from the camera to a target.

  11. Performance evaluation of a proof-of-concept 70 W internal reforming methanol fuel cell system

    Science.gov (United States)

    Avgouropoulos, G.; Schlicker, S.; Schelhaas, K.-P.; Papavasiliou, J.; Papadimitriou, K. D.; Theodorakopoulou, E.; Gourdoupi, N.; Machocki, A.; Ioannides, T.; Kallitsis, J. K.; Kolb, G.; Neophytides, S.

    2016-03-01

    A proof-of-concept 70 W Internal Reforming Methanol Fuel Cell (IRMFC) stack including Balance-of-Plant (BoP) was designed, assembled and tested. Advent TPS® high-temperature, polymer electrolyte membrane electrode assemblies were employed for fuel cell operation at 200 °C. In order to avoid phosphoric acid poisoning of the reformer, the anode electrocatalyst of each cell was indirectly adjoined, via a separation plate, to a highly active CuMnAlOx catalyst coated onto copper foam, which served as methanol reforming layer. The reformer was in-situ converting the methanol/steam feed to the required hydrogen (internal reforming concept) at 200 °C, which was readily oxidized at the anode electrodes. The operation of the IRMFC was supported through a number of BoP components consisting of a start-up subsystem (air blower, evaporator and monolithic burner), a combined afterburner/evaporator device, methanol/water supply and data acquisition units (reactants/products analysis, temperature control, flow control, system load/output control). Depending on the composition of the liquid MeOH/H2O feed streams, current densities up to 0.18 A cm-2 and power output up to 70 W could be obtained with remarkable repeatability. Specific targets for improvement of the efficiency were identified.

  12. Proof of Concept of Automated Collision Detection Technology in Rugby Sevens.

    Science.gov (United States)

    Clarke, Anthea C; Anson, Judith M; Pyne, David B

    2017-04-01

    Clarke, AC, Anson, JM, and Pyne, DB. Proof of concept of automated collision detection technology in rugby sevens. J Strength Cond Res 31(4): 1116-1120, 2017-Developments in microsensor technology allow for automated detection of collisions in various codes of football, removing the need for time-consuming postprocessing of video footage. However, little research is available on the ability of microsensor technology to be used across various sports or genders. Game video footage was matched with microsensor-detected collisions (GPSports) in one men's (n = 12 players) and one women's (n = 12) rugby sevens match. True-positive, false-positive, and false-negative events between video and microsensor-detected collisions were used to calculate recall (ability to detect a collision) and precision (accurately identify a collision). The precision was similar between the men's and women's rugby sevens game (∼0.72; scale 0.00-1.00); however, the recall in the women's game (0.45) was less than that for the men's game (0.69). This resulted in 45% of collisions for men and 62% of collisions for women being incorrectly labeled. Currently, the automated collision detection system in GPSports microtechnology units has only modest utility in rugby sevens, and it seems that a rugby sevens-specific algorithm is needed. Differences in measures between the men's and women's game may be a result of physical size, and strength, and physicality, as well as technical and tactical factors.

  13. Loving-Kindness Meditation to Target Affect in Mood Disorders: A Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Stefan G. Hofmann

    2015-01-01

    Full Text Available Conventional treatments for mood disorders primarily focus on reducing negative affect, but little on enhancing positive affect. Loving-kindness meditation (LKM is a traditional meditation practice directly oriented toward enhancing unconditional and positive emotional states of kindness towards oneself and others. We report here two independent and uncontrolled studies carried out at different centers, one in Boston, USA (n = 10, and one in Frankfurt, Germany (n = 8, to examine the potential therapeutic utility of a brief LKM group intervention for symptoms of dysthymia and depression. Results at both centers suggest that LKM was associated with large-sized effects on self-reported symptoms of depression (d = 3.33 and 1.90, negative affect (d = 1.98 and 0.92, and positive affect (d = 1.63 and 0.94. Large effects were also found for clinician-reported changes in depression, rumination and specific positive emotions, and moderate effects for changes in adaptive emotion regulation strategies. The qualitative data analyses provide additional support for the potential clinical utility of the intervention. This proof-of-concept evaluation of LKM as a clinical strategy warrants further investigation.

  14. Coupled anaerobic-aerobic treatment of whey wastewater in a sequencing batch reactor: proof of concept.

    Science.gov (United States)

    Frigon, J C; Bruneau, T; Moletta, R; Guiot, S R

    2007-01-01

    A proof of concept was performed in order to verify if the coupling of anaerobic and aerobic conditions inside the same digester could efficiently treat a reconstituted whey wastewater at 21 degrees C. The sequencing batch reactor (SBR) cycles combined initial anaerobic phase and final aerobic phase with reduced aeration. A series of 24 h cycles in 0.5 L digesters, with four different levels of oxygenation (none, 54, 108 and 182 mgO2 per gram of chemical oxygen demand (COD)), showed residual soluble chemical oxygen demand (sCOD) of 683 +/- 46, 720 +/- 33, 581 +/- 45, 1239 +/- 15 mg L(-1), respectively. Acetate and hydrogen specific activities were maintained for the anaerobic digester, but decreased by 10-25% for the acetate and by 20-50% for the hydrogen, in the coupled digesters. The experiment was repeated using 48 h cycles with limited aeration during 6 or 16 hours at 54 and 108 mgO2gCODinitial(-1), displaying residual sCOD of 177 +/- 43, 137 +/- 38, 104 +/- 22 and 112 +/- 9 mgL(-1) for the anaerobic and the coupled digesters, respectively. The coupled digesters recovered after a pH shock with residual sCOD as low as 132 mg L(-1) compared to 636 mg L(-1) for the anaerobic digester. With regard to the obtained results, the feasibility of the anaerobic-aerobic coupling in SBR digesters for the treatment of whey wastewater was demonstrated.

  15. Integrative Medical Care Plus Mindfulness Training for Patients With Congestive Heart Failure: Proof of Concept.

    Science.gov (United States)

    Kemper, Kathi J; Carmin, Cheryl; Mehta, Bella; Binkley, Phillip

    2016-10-01

    Congestive heart failure (CHF) has a high rate of morbidity and mortality. It is often accompanied by other medical and psychosocial comorbidities that complicate treatment and adherence. We conducted a proof of concept pilot project to determine the feasibility of providing integrative group medical visits plus mindfulness training for patients recently discharged with CHF. Patients were eligible if they had been discharged from an inpatient stay for CHF within the 12 months prior to the new program. The Compassionate Approach to Lifestyle and Mind-Body (CALM) Skills for Patients with CHF consisted of 8 weekly visits focusing on patient education about medications, diet, exercise, sleep, and stress management; group support; and training in mind-body skills such as mindfulness, self-compassion, and loving-kindness. Over two 8-week sessions, 8/11 (73%) patients completed at least 4 visits. The patients had an average age of 57 years. The most common comorbidities were weight gain, sleep problems, and fatigue. After the sessions, 100% of patients planned to make changes to their diet, exercise, and stress management practices. Over half of the patients who met with a pharmacist had a medication-related problem. Improvements were observed in depression, fatigue, and satisfaction with life. Integrative group visits focusing on healthy lifestyle, support, and skill-building are feasible even among CHF patients and should be evaluated in controlled trials as a patient-centered approach to improving outcomes related to improving medication management, depression, fatigue, and quality of life.

  16. Automated disposable small scale reactor for high throughput bioprocess development: a proof of concept study.

    Science.gov (United States)

    Bareither, Rachel; Bargh, Neil; Oakeshott, Robert; Watts, Kathryn; Pollard, David

    2013-12-01

    The acceleration of bioprocess development for biologics and vaccines can be enabled by automated high throughput technologies. This will alleviate the significant resource burden from the multi-factorial statistical experimentation required for controlling product quality attributes of complex biologics. Recent technology advances have improved clone evaluation and screening, but have struggled to combine the scale down criteria required for both high cell density cell culture and microbial processes, with sufficient automation and disposable technologies to accelerate process development. This article describes the proof of concept evaluations of an automated disposable small scale reactor for high throughput upstream process development. Characterization studies established the small scale stirred tank disposable 250 mL reactor as similar to those of lab and pilot scale. The reactor generated equivalent process performance for industrial biologics processes for therapeutic protein and monoclonal antibody production using CHO cell culture, Pichia pastoris and E. coli. This included similar growth, cell viability, product titer, and product quality. The technology was shown to be robust across multiple runs and met the requirements for the ability to run high cell density processes (>400 g/L wet cell weight) with exponential feeds and sophisticated event triggered processes. Combining this reactor into an automated array of reactors will ultimately be part of a high throughput process development strategy. This will combine upstream, small scale purification with rapid analytics that will dramatically shorten timelines and costs of developing biological processes.

  17. Proof of concept demonstration of novel technologies for lunar spacesuit dust mitigation

    Science.gov (United States)

    Manyapu, Kavya K.; De Leon, Pablo; Peltz, Leora; Gaier, James R.; Waters, Deborah

    2017-08-01

    A recent report by NASA identified dust/particulate mitigation techniques as a highly relevant study for future long-term planetary exploration missions (NASA, 2015). The deleterious effects of lunar dust on spacesuits discovered during the Apollo missions has compelled NASA to identify dust mitigation as a critical path for potential future lunar, asteroid and Mars missions. The complexity of spacesuit design has however constrained integrating existing dust cleaning technologies, formerly demonstrated on rigid surfaces, into the spacesuit system. Accordingly, this research is investigating novel methods to integrate dust mitigation technologies for use on spacesuits. We examine utilizing a novel combination of active and passive technologies integrated into the spacesuit outerlayer to alleviate dust contamination. Leveraging two specific technologies, the Electrodynamics Dust Shield (EDS) active technology and Work Function Matching Coating (WFM) passive technology, developed by NASA for rigid surfaces, we apply new high performance materials such as the Carbon Nanotube (CNT) flexible fibers to develop a spacesuit-integrated dust cleaning system. Through experiments conducted using JSC-1A lunar dust simulant on coupons made of spacesuit outerlayer material, feasibility of integrating the proposed dust cleaning system and its performance were assessed. Results from these preliminary experiments show that the integrated dust cleaning system is capable of removing 80-95% of dust from the spacesuit material demonstrating proof of concept. This paper describes the techniques and results from the experiments. Future challenges of implementing the proposed approach into fight suits are identified.

  18. Counter-ion complexes for enhanced drug loading in nanocarriers: Proof-of-concept and beyond.

    Science.gov (United States)

    Günday Türeli, Nazende; Türeli, Akif E; Schneider, Marc

    2016-09-25

    Enhanced drug loading is an important prerequisite of nanomedicines, to reach administration dose while reducing the amount of excipient. Considering biocompatible and biodegradable polymers such as PLGA, pH dependent solubility characteristics along with limited organic solvent solubility of the drug hampers nanoparticle (NP) preparation. To improve loading of such molecules, a method based on using counter ions for complex formation is proposed. Formed complex alters the intrinsic solubility of active substance via electrostatic interaction without chemical modification. A proof-of-concept study was conducted with sodium dodecyl sulfate as counter-ion to fluoroquinolone antibiotic ciprofloxacin. Complex formation resulted in suppressed pH dependent solubility over pH 1.2-9.0 and an additional -80 fold increase in organic solubility was achieved. In consequence, NPs prepared by microjet reactor technology have shown enhanced drug loading efficiencies (-78%) and drug loading of 14%. Moreover, the counter-ion concept was also demonstrated with another class of antibiotics, water soluble aminoglycosides gentamycin and tobramycin. In addition, the counter ion was substituted by degradable excipients such as phosphatidic acid derivatives. Successful implementation has proven the counter-ion concept to be a platform concept that can be successfully implemented for a variety of active substances and counter-ions to enhance drug loading in nanocarriers. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Online support groups for young women with breast cancer: a proof-of-concept study.

    Science.gov (United States)

    Stephen, Joanne; Rojubally, Adina; Linden, Wolfgang; Zhong, Lihong; Mackenzie, Gina; Mahmoud, Sahar; Giese-Davis, Janine

    2017-07-01

    This initial study examined a therapist-led, synchronous, online support group (OSG) with psycho-education (OSG + E) compared to self-help psycho-education (E). The study aims were to examine proof of concept-feasibility, acceptability, and usefulness-and to hone methods for a formal RCT. One hundred five young breast cancer survivors (<50 years) post-treatment were randomized either to OSG + E or E. OSG + E received a therapist-led 10-week synchronous online intervention. E received a self-help workbook. Assessments were at baseline, 10 weeks, and 3 months, with willing OSG + E members completing post-study interviews. Researchers used inductive analysis, generating qualitative themes for feasibility, acceptability, and usefulness. We examined trajectories for one primary and two secondary quantitative outcomes and a combined moderator to discover who preferentially benefitted from the intervention. Qualitative analyses revealed that synchronous chat was at times challenging, but minimal technical coaching, structure, set topics, and professional facilitation enabled conversations that were focused and meaningful. A combined moderator indicated that generally more women benefitted from OSG + E relative to E and particularly those women in semi-rural and rural areas. This study suggests that therapist-led synchronous OSGs are feasible, acceptable, and useful for young breast cancer survivors and that a future RCT with a larger sample size, perhaps more focused on non-urban areas, is needed to establish its effectiveness.

  20. Adaptation of the global frameworks for community based rehabilitation in southern Africa: a proof of concept.

    Science.gov (United States)

    M'kumbuzi, Vyvienne Rp; Myezwa, Hellen

    2017-01-01

    Community based rehabilitation (CBR) has evolved over the last 30 years and now focuses on empowering persons with disabilities to access and benefit from a wide range of services. The essence and ethos of CBR is captured in several global frameworks, such as the UN Convention on the Rights of People with Disabilities (2006) and the CBR guidelines (2010). The latter contains the CBR matrix. All 15 countries in southern Africa are implementing CBR mostly in rural areas, but the policy framework to guide CBR in the region is unknown. The purpose of the study was to determine to what extent countries in southern Africa have adapted the global frameworks available for CBR. A CBR policy analysis using proof-of-concept methodology was undertaken. Policy documents on CBR were sought from relevant government departments or agencies. Multiple methods and media, including web searches, searches for grey literature, social media and contact through an elaborate network of colleagues working in the region, were employed to execute the search strategy. Data were organized using NVivo software, and three independent raters coded the emergent themes using the CBR matrix. Only Namibia, South Africa, Tanzania and Zimbabwe have specific policy content for CBR. These, however, lacked structure; the content was predominantly aligned to health. Inclusion of key international concepts such as mainstreaming and empowerment were superfluous when present. The CBR policy environment in southern Africa appears inadequate. Contingent factors that preclude adaptation of the global frameworks available for CBR appear to be at play. These warrant further investigation.

  1. Proof of concept in cardiovascular risk: the paradoxical findings in blood pressure and lipid abnormalities

    Science.gov (United States)

    Fuchs, Flavio Danni; Fuchs, Sandra Costa; Moreira, Leila Beltrami; Gus, Miguel

    2012-01-01

    High blood pressure and lipoprotein abnormalities were identified by many cohort studies as the major risk factors for cardiovascular disease. Laboratory experiments apparently confirmed their role in the causation of atherosclerosis, but a proof of concept requires the corroboration by clinical trials in human beings. The size of benefit in clinical trials regarding the control of high blood pressure was within the estimations of risk provided by cohort studies. For a reduction of 10 mmHg in systolic blood pressure or 5 mmHg in diastolic blood pressure, the relative risk reduction of coronary heart disease was 22% (95% confidence interval 27%–17%) in a meta-analysis of clinical trials, close to the estimation of reduction of 25% (95% confidence interval 23%–27%) provided by a meta-analysis of cohort studies. The corresponding values for stroke were 41% (95% confidence interval 33%–48%) in clinical trials compared to a cohort risk prediction of 36% (95% confidence interval 34%–38%). This efficacy was shared by all blood pressure-lowering drugs. The same figure has not paradoxically happened with drugs that act over abnormalities of cholesterol and lipoproteins. Only statins, which have other beneficial actions as well, have consistently lowered the incidence of cardiovascular diseases, an efficacy that was not reproduced by older and newer quite potent lipid drugs. The adverse effects of these drugs may nullify their beneficial effects over lipoproteins and abnormalities of lipoproteins may only be surrogate markers of the underlying real risks. PMID:22870036

  2. Fluorescent particle tracers in surface hydrology: a proof of concept in a semi-natural hillslope

    Directory of Open Access Journals (Sweden)

    F. Tauro

    2012-08-01

    Full Text Available In this paper, a proof of concept experiment is conducted to assess the feasibility of tracing overland flow on an experimental hillslope plot via a novel fluorescent particle tracer. Experiments are performed by using beads of diameters ranging from 75 to 1180 μm. Particles are sensed through an experimental apparatus comprising a light source and a video acquisition unit. Runoff on the experimental plot is artificially simulated by using a custom-built rainfall system. Particle transits are detected through supervised methodologies requiring the presence of operators and unsupervised procedures based on image analysis techniques. Average flow velocity estimations are executed based on travel time measurements of the particles as they are dragged by the overland flow on the hillslope. Velocities are compared to flow measurements obtained using rhodamine dye. Experimental findings demonstrate the potential of the methodology for understanding overland flow dynamics in complex natural settings. In addition, insights on the optimization of particle size are presented based on the visibility of the beads and their accuracy in flow tracing.

  3. Automated point-of-care testing for ABO agglutination test: proof of concept and validation.

    Science.gov (United States)

    El Kenz, H; Corazza, F

    2015-07-01

    ABO-incompatible red blood cell transfusions still represent an important hazard in transfusion medicine. Therefore, some countries have introduced a systematic bedside ABO agglutination test checking that the right blood is given to the right patient. However, this strategy requires an extremely time-consuming learning programme and relies on a subjective interpretation of ABO test cards agglutination. We developed a prototype of a fully automated device performing the bedside agglutination test that could be completed by reading of a barcoded wristband. This POCT checks the ABO compatibility between the patient and the blood bag. Proof of concept and analytical validation of the prototype has been completed on 451 blood samples: 238 donor packed red blood cells, 137 consecutive unselected patients for whom a blood group determination had been ordered and on 76 patient samples selected with pathology that could possibly interfere with or impair performances of the assay. We observed 100% concordance for ABO blood groups between the POCT and the laboratory instrument. These preliminary results demonstrate the feasibility of ABO determination with a simple POCT device eliminating manipulation and subjective interpretation responsible for transfusion errors. This device should be linked to the blood bank system allowing all cross-check of the results. © 2015 International Society of Blood Transfusion.

  4. RB-ARD: A proof of concept rule-based abort

    Science.gov (United States)

    Smith, Richard; Marinuzzi, John

    1987-01-01

    The Abort Region Determinator (ARD) is a console program in the space shuttle mission control center. During shuttle ascent, the Flight Dynamics Officer (FDO) uses the ARD to determine the possible abort modes and make abort calls for the crew. The goal of the Rule-based Abort region Determinator (RB/ARD) project was to test the concept of providing an onboard ARD for the shuttle or an automated ARD for the mission control center (MCC). A proof of concept rule-based system was developed on a LMI Lambda computer using PICON, a knowdedge-based system shell. Knowdedge derived from documented flight rules and ARD operation procedures was coded in PICON rules. These rules, in conjunction with modules of conventional code, enable the RB-ARD to carry out key parts of the ARD task. Current capabilities of the RB-ARD include: continuous updating of the available abort mode, recognition of a limited number of main engine faults and recommendation of safing actions. Safing actions recommended by the RB-ARD concern the Space Shuttle Main Engine (SSME) limit shutdown system and powerdown of the SSME Ac buses.

  5. Proof-of-Concept of a Millimeter-Wave Integrated Heterogeneous Network for 5G Cellular.

    Science.gov (United States)

    Okasaka, Shozo; Weiler, Richard J; Keusgen, Wilhelm; Pudeyev, Andrey; Maltsev, Alexander; Karls, Ingolf; Sakaguchi, Kei

    2016-08-25

    The fifth-generation mobile networks (5G) will not only enhance mobile broadband services, but also enable connectivity for a massive number of Internet-of-Things devices, such as wireless sensors, meters or actuators. Thus, 5G is expected to achieve a 1000-fold or more increase in capacity over 4G. The use of the millimeter-wave (mmWave) spectrum is a key enabler to allowing 5G to achieve such enhancement in capacity. To fully utilize the mmWave spectrum, 5G is expected to adopt a heterogeneous network (HetNet) architecture, wherein mmWave small cells are overlaid onto a conventional macro-cellular network. In the mmWave-integrated HetNet, splitting of the control plane (CP) and user plane (UP) will allow continuous connectivity and increase the capacity of the mmWave small cells. mmWave communication can be used not only for access linking, but also for wireless backhaul linking, which will facilitate the installation of mmWave small cells. In this study, a proof-of-concept (PoC) was conducted to demonstrate the practicality of a prototype mmWave-integrated HetNet, using mmWave technologies for both backhaul and access.

  6. Proof-of-Concept of a Millimeter-Wave Integrated Heterogeneous Network for 5G Cellular

    Directory of Open Access Journals (Sweden)

    Shozo Okasaka

    2016-08-01

    Full Text Available The fifth-generation mobile networks (5G will not only enhance mobile broadband services, but also enable connectivity for a massive number of Internet-of-Things devices, such as wireless sensors, meters or actuators. Thus, 5G is expected to achieve a 1000-fold or more increase in capacity over 4G. The use of the millimeter-wave (mmWave spectrum is a key enabler to allowing 5G to achieve such enhancement in capacity. To fully utilize the mmWave spectrum, 5G is expected to adopt a heterogeneous network (HetNet architecture, wherein mmWave small cells are overlaid onto a conventional macro-cellular network. In the mmWave-integrated HetNet, splitting of the control plane (CP and user plane (UP will allow continuous connectivity and increase the capacity of the mmWave small cells. mmWave communication can be used not only for access linking, but also for wireless backhaul linking, which will facilitate the installation of mmWave small cells. In this study, a proof-of-concept (PoC was conducted to demonstrate the practicality of a prototype mmWave-integrated HetNet, using mmWave technologies for both backhaul and access.

  7. Polyamine inhibitors for treatment of feline oral squamous cell carcinoma: a proof-of-concept study.

    Science.gov (United States)

    Lewis, John R; O'Brien, Thomas G; Skorupski, Katherine A; Krick, Erika L; Reiter, Alexander M; Jennings, Michael W; Jurney, Carrie H; Shofer, F S

    2013-01-01

    This study assessed proof-of-concept for use of polyamine inhibitor 2-diluoromethylornithine (DFMO) as a treatment for oral squamous cell carcinoma (SCC) in client-owned cats. Polyamine levels in tumor tissue and normal oral mucosa were quantified before and after treatment. DFMO was administered orally to 14 client-owned cats with histologically confirmed oral SCC. Patients were monitored for gastrointestinal, dermatologic, auditory, hematological, and biochemical abnormalities. Total polyamine levels in tumor tissue decreased after treatment, as did the specific polyamine putrescine in both tumor tissue and normal mucosa. Ototoxicity was observed in 5 of 6 cats receiving pre- and post-treatment brainstem auditory evoked potential tests. Subclinical thrombocytopenia was observed in 6 of 14 cats. One cat showed mild post-anesthetic tremors that resolved without treatment. Oral administration of DFMO at doses used in this study resulted in significantly decreased tumor polyamine levels without life-threatening clinical or hematological toxicities. Further studies are warranted to explore pathophysiology of polyamine biochemistry and use of polyamine inhibitors in treatment of cats with oral SCC.

  8. Investigations on hydrogen isotope ratios of endogenous urinary steroids: reference-population-based thresholds and proof-of-concept.

    Science.gov (United States)

    Piper, Thomas; Thomas, Andreas; Thevis, Mario; Saugy, Martial

    2012-09-01

    Carbon isotope ratio (CIR) analysis has been routinely and successfully used in sports drug testing for many years to uncover the misuse of endogenous steroids. One limitation of the method is the availability of steroid preparations exhibiting CIRs equal to endogenous steroids. To overcome this problem, hydrogen isotope ratios (HIR) of endogenous urinary steroids were investigated as a potential complement; results obtained from a reference population of 67 individuals are presented herein. An established sample preparation method was modified and improved to enable separate measurements of each analyte of interest where possible. From the fraction of glucuronidated steroids; pregnanediol, 16-androstenol, 11-ketoetiocholanolone, androsterone (A), etiocholanolone (E), dehydroepiandrosterone (D), 5α- and 5β-androstanediol, testosterone and epitestosterone were included. In addition, sulfate conjugates of A, E, D, epiandrosterone and 17α- and 17β-androstenediol were considered and analyzed after acidic solvolysis. The obtained results enabled the calculation of the first reference-population-based thresholds for HIR of urinary steroids that can readily be applied to routine doping control samples. Proof-of-concept was accomplished by investigating urine specimens collected after a single oral application of testosterone-undecanoate. The HIR of most testosterone metabolites were found to be significantly influenced by the exogenous steroid beyond the established threshold values. Additionally, one regular doping control sample with an extraordinary testosterone/epitestosterone ratio of 100 without suspicious CIR was subjected to the complementary methodology of HIR analysis. The HIR data eventually provided evidence for the exogenous origin of urinary testosterone metabolites. Despite further investigations on HIR being advisable to corroborate the presented reference-population-based thresholds, the developed method proved to be a new tool supporting modern

  9. Direct liquefaction proof-of-concept program: POC bench option run 01 (227-90). Final report

    Energy Technology Data Exchange (ETDEWEB)

    Comolli, A.G.; Pradhan, V.R.; Lee, T.L.K.; Karolkiewicz, W.F.; Popper, G.

    1996-05-01

    This report presents the results of bench-scale work, Bench Run PB-01, conducted under the DOE Proof of Concept-Bench Option Program in direct coal liquefaction at Hydrocarbon Technologies, Inc. in Lawrenceville, New Jersey. The Bench Run PB-01 was the first of nine runs planned under the POC Bench Option Contract between the US DOE and Hydrocarbon Technologies, Inc. The primary goal of this bench run was to evaluate the most successful of the process improvements concepts, evolving out of the earlier CMSL Project, for conventional direct liquefaction as well as coprocessing of a sub-bituminous Black Thunder mine coal with waste organics such as waste plastics and heavy resid. The interstage separation of light ends and gases was indeed found to reduce the overall light gas-make from the liquefaction process. The organic waste feeds such as mixed plastics and vacuum resid, employed during Bench Run PB-01, in combined processing with coal, resulted in making the overall process more hydrogen efficient by virtue of reducing the light gas make and also decreasing the hydrogen consumption from the process, while at the same time improving the yields and quality of the distillate products. A definite synergy was found during the combined processing of coal with mixtures of vacuum resid and mixed waste plastics. The application of an all dispersed catalyst conversion reactor resulted in higher feed throughput at equivalent process performance, but also necessitated the use of an in-line hydrotreater for improving the quality of IBP-400{degrees}C distillate products. The combination of HTI`s iron gel catalyst and Molyvan-A was found very effective in achieving high levels of process performance; although, in recycled form, these catalysts were not as effective as the freshly added precursors.

  10. Noninvasive referencing of intraocular tumors for external beam radiation therapy using optical coherence tomography: A proof of concept

    Energy Technology Data Exchange (ETDEWEB)

    Rüegsegger, Michael B.; Steiner, Patrick; Kowal, Jens H., E-mail: jens.kowal@artorg.unibe.ch [ARTORG Center for Biomedical Engineering Research, University of Bern, Bern 3010 (Switzerland); Geiser, Dominik [Berne University of Applied Sciences, HuCE OptoLab, 2501 (Switzerland); Pica, Alessia; Aebersold, Daniel M. [Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern 3010 (Switzerland)

    2014-08-15

    Purpose: External beam radiation therapy is currently considered the most common treatment modality for intraocular tumors. Localization of the tumor and efficient compensation of tumor misalignment with respect to the radiation beam are crucial. According to the state of the art procedure, localization of the target volume is indirectly performed by the invasive surgical implantation of radiopaque clips or is limited to positioning the head using stereoscopic radiographies. This work represents a proof-of-concept for direct and noninvasive tumor referencing based on anterior eye topography acquired using optical coherence tomography (OCT). Methods: A prototype of a head-mounted device has been developed for automatic monitoring of tumor position and orientation in the isocentric reference frame for LINAC based treatment of intraocular tumors. Noninvasive tumor referencing is performed with six degrees of freedom based on anterior eye topography acquired using OCT and registration of a statistical eye model. The proposed prototype was tested based on enucleated pig eyes and registration accuracy was measured by comparison of the resulting transformation with tilt and torsion angles manually induced using a custom-made test bench. Results: Validation based on 12 enucleated pig eyes revealed an overall average registration error of 0.26 ± 0.08° in 87 ± 0.7 ms for tilting and 0.52 ± 0.03° in 94 ± 1.4 ms for torsion. Furthermore, dependency of sampling density on mean registration error was quantitatively assessed. Conclusions: The tumor referencing method presented in combination with the statistical eye model introduced in the past has the potential to enable noninvasive treatment and may improve quality, efficacy, and flexibility of external beam radiotherapy of intraocular tumors.

  11. Integrating health education and physical activity programming for cardiovascular health promotion among female inmates: A proof of concept study.

    Science.gov (United States)

    Nair, Uma S; Jordan, Jeremy S; Funk, Daniel; Gavin, Kristin; Tibbetts, Erica; Collins, Bradley N

    2016-05-01

    Female inmate populations in the United States tend to be overweight, physically inactive, experience high stress, and have a history of nicotine and other drug dependence. Thus, they bear an elevated risk of cardiovascular (CV) disease than the general population. However, few evidence-based health interventions exist for this population. This study will test proof of concept, feasibility, and potential efficacy of a multiple health behavior change intervention that integrates CV-health promotion education delivered during a physical activity (PA) program (indoor cycling) tailored to this population. This study uses a quasi-experimental 2-group design with two measurement time-points: baseline and 8-week end of treatment. N=120 incarcerated women (18-59years of age) who are medically cleared for participation in PA will be enrolled. Indoor cycling instructors will be trained to deliver five health education topics over an 8-week period during twice-weekly cycling classes. Topics match the American Heart Association recommendations for CV health: (a) nutrition, (b) PA promotion, (c) weight management, (d) stress management, and (e) smoking cessation and relapse prevention. Modes of intervention include instructor advice, written materials and audio/video clips reviewed during class. CV-related and mental health measures will be assessed at both time-points. Results will guide a full scale efficacy study. Future research in this area has potential to impact the health of female inmates, a high-risk population. Moreover, this multiple health behavior change intervention model represents a community approach to health promotion that could generalize to other underserved populations who may benefit most from similar intervention efforts.

  12. A proof-of-concept study on the combination of repetitive transcranial magnetic stimulation and relaxation techniques in chronic tinnitus.

    Science.gov (United States)

    Kreuzer, Peter M; Poeppl, Timm B; Bulla, Jan; Schlee, Winfried; Lehner, Astrid; Langguth, Berthold; Schecklmann, Martin

    2016-10-01

    Interference of ongoing neuronal activity and brain stimulation motivated this study to combine repetitive transcranial magnetic stimulation (rTMS) and relaxation techniques in tinnitus patients. Forty-two patients were enrolled in this one-arm proof-of-concept study to receive ten sessions of rTMS applied to the left dorsolateral prefrontal cortex and temporo-parietal cortex. During stimulation, patients listened to five different kinds of relaxation audios. Variables of interest were tinnitus questionnaires, tinnitus numeric rating scales, depressivity, and quality of life. Results were compared to results of historical control groups having received the same rTMS protocol (active control) and sham treatment (placebo) without relaxation techniques. Thirty-eight patients completed the treatment, drop-out rates and adverse events were low. Responder rates (reduction in tinnitus questionnaire (TQ) score ≥5 points 10 weeks after treatment) were 44.7 % in the study, 27.8 % in the active control group, and 21.7 % in the placebo group, differing between groups on a near significant level. For the tinnitus handicap inventory (THI), the main effect of group was not significant. However, linear mixed model analyses showed that the relaxation/rTMS group differed significantly from the active control group showing steeper negative THI trend for the relaxation/rTMS group indicating better amelioration over the course of the trial. Deepness of relaxation during rTMS and selection of active relaxation vs. passive listening to music predicted larger TQ. All remaining secondary outcomes turned out non-significant. This combined treatment proved to be a safe, feasible and promising approach to enhance rTMS treatment effects in chronic tinnitus.

  13. Ecologically sustainable weed management: How do we get from proof-of-concept to adoption?

    Science.gov (United States)

    Liebman, Matt; Baraibar, Bàrbara; Buckley, Yvonne; Childs, Dylan; Christensen, Svend; Cousens, Roger; Eizenberg, Hanan; Heijting, Sanne; Loddo, Donato; Merotto, Aldo; Renton, Michael; Riemens, Marleen

    2016-07-01

    Weed management is a critically important activity on both agricultural and non-agricultural lands, but it is faced with a daunting set of challenges: environmental damage caused by control practices, weed resistance to herbicides, accelerated rates of weed dispersal through global trade, and greater weed impacts due to changes in climate and land use. Broad-scale use of new approaches is needed if weed management is to be successful in the coming era. We examine three approaches likely to prove useful for addressing current and future challenges from weeds: diversifying weed management strategies with multiple complementary tactics, developing crop genotypes for enhanced weed suppression, and tailoring management strategies to better accommodate variability in weed spatial distributions. In all three cases, proof-of-concept has long been demonstrated and considerable scientific innovations have been made, but uptake by farmers and land managers has been extremely limited. Impediments to employing these and other ecologically based approaches include inadequate or inappropriate government policy instruments, a lack of market mechanisms, and a paucity of social infrastructure with which to influence learning, decision-making, and actions by farmers and land managers. We offer examples of how these impediments are being addressed in different parts of the world, but note that there is no clear formula for determining which sets of policies, market mechanisms, and educational activities will be effective in various locations. Implementing new approaches for weed management will require multidisciplinary teams comprised of scientists, engineers, economists, sociologists, educators, farmers, land managers, industry personnel, policy makers, and others willing to focus on weeds within whole farming systems and land management units. © 2016 by the Ecological Society of America.

  14. A field proof-of-concept of tomographic slug tests in an anisotropic littoral aquifer

    Science.gov (United States)

    Paradis, Daniel; Gloaguen, Erwan; Lefebvre, René; Giroux, Bernard

    2016-05-01

    Hydraulic tomography is increasingly recognized as a characterization approach that can image pathways or barriers to flow as well as their connectivity. In this study, we assess the performance of a transient analysis of tomographic slug test head data in estimating heterogeneity in horizontal hydraulic conductivity (Kh), hydraulic conductivity anisotropy (the ratio between vertical and horizontal hydraulic conductivity - Kv/Kh) and specific storage (Ss) under actual field conditions. The tomographic experiment was carried out between two wells in a moderately heterogeneous and highly anisotropic silt and sand littoral aquifer. In this field proof-of-concept, the inversion of the two-dimensional (2D) head dataset was computed with a 2D radial flow algorithm that considers Kh, Kv/Kh, Ss and wellbore storage effects. This study demonstrated that a transient analysis of tomographic slug tests is able to capture the key features of the littoral environment of the test: the vertical profiles of Kh and Kv are indeed in agreement with those from other field and laboratory tests, and Ss values exhibit physically plausible profiles. Furthermore, the simulation of independent inter-well hydraulic tests (slug and pumping tests screened over the entire aquifer) using resolved Kh, Kv/Kh and Ss tomograms produce responses very close to field observations. This study demonstrates that the effects of fine scale heterogeneity that induces K-anisotropy at larger scales can be captured through a transient analysis of tomographic slug tests, which are very difficult to quantify otherwise with conventional hydraulic tests, thus allowing a better representation of properties controlling flow and transport in aquifer systems.

  15. Multidimensional cognitive evaluation of patients with disorders of consciousness using EEG: A proof of concept study

    Directory of Open Access Journals (Sweden)

    Claire Sergent

    2017-01-01

    In the present study we built a unique EEG protocol that probed 8 dimensions of cognitive processing in a single 1.5 h session. This protocol probed variants of classical markers together with new markers of spatial attention, which has not yet been studied in these patients. The eight dimensions were: (1 own name recognition, (2 temporal attention, (3 spatial attention, (4 detection of spatial incongruence (5 motor planning, and (6,7,8 modulations of these effects by the global context, reflecting higher-level functions. This protocol was tested in 15 healthy control subjects and in 17 patients with various etiologies, among which 13 could be included in the analysis. The results in the control group allowed a validation and a specific description of the cognitive levels probed by each marker. At the single-subject level, this combined protocol allowed assessing the presence of both classical and newly introduced markers for each patient and control, and revealed that the combination of several markers increased diagnostic sensitivity. The presence of a high-level effect in any of the three tested domains distinguished between minimally conscious and vegetative patients, while the presence of low-level effects was similar in both groups. In summary, this study constitutes a validated proof of concept in favor of probing multiple cognitive dimensions to improve the evaluation of non-communicating patients. At a more conceptual level, this EEG tool can help achieve a better understanding of disorders of consciousness by exploring consciousness in its multiple cognitive facets.

  16. Design and proof of concept of an innovative very high temperature ceramic solar absorber

    Science.gov (United States)

    Leray, Cédric; Ferriere, Alain; Toutant, Adrien; Olalde, Gabriel; Peroy, Jean-Yves; Chéreau, Patrick; Ferrato, Marc

    2017-06-01

    Hybrid solar gas-turbine (HSGT) is an attractive technology to foster market penetration of CSP. HSGT offers some major advantages like for example high solar-to-electric conversion efficiency, reduced water requirement and low capital cost. A very high temperature solar receiver is needed when elevated solar share is claimed. A few research works, as reported by Karni et al. [8] and by Buck et al. [1], have been dedicated to solar receiver technologies able to deliver pressurized air at temperature above 750°C. The present work focuses on research aiming at developing an efficient and reliable solar absorber able to provide pressurized air at temperature up to 1000°C and more. A surface absorber technology is selected and a modular design of receiver is proposed in which each absorber module is made of BOOSTEC® SiC ceramic (silicon carbide) as bulk material with straight air channels inside. Early stage experimental works done at CNRS/PROMES on lab-scale absorbers showed that the thermo-mechanical behavior of this material is a critical issue, resulting in elevated probability of failure under severe conditions like large temperature gradient or steep variation of solar flux density in situations of cloud covering. This paper reports on recent progress made at CNRS/PROMES to address this critical issue. The design of the absorber has been revised and optimized according to thermo-mechanical numerical simulations, and an experimental proof of concept has been done on a pilot-scale absorber module at Themis solar tower facility.

  17. Tele-pharmacy in rural Scotland: a proof of concept study.

    Science.gov (United States)

    Inch, Jackie; Notman, Frances; Watson, Margaret; Green, David; Baird, Robert; Ferguson, James; Hind, Caroline; McKinstry, Brian; Strath, Alison; Bond, Christine

    2017-06-01

    Technology enables medical services to be provided to rural communities. This proof of concept study assessed the feasibility and acceptability of delivering community pharmacy services (CPS; including advice, sale of over-the-counter products and dispensing of prescriptions) by tele-technology (the Telepharmacy Robotic Supply Service (TPRSS)) to a rural population in Scotland. Data collection included the following: postal surveys to local residents; focus groups/ interviews with pharmacists, other healthcare professionals (HCPs) and service users, at baseline and follow-up; TPRSS logs. Interviews/focus groups were audio-recorded, transcribed and thematically analysed. Descriptive statistics were reported for survey data. Qualitative results: Pre-installation: residents expressed satisfaction with current pharmacy access. HCPs believed the TPRSS would improve pharmacy access and reduce pressure on GPs. Concerns included costs, confidentiality, patient safety and 'fear' of technology. Post-installation: residents and pharmacy staff were positive, finding the service easy to use. Quantitative results: Pre-installation: almost half the respondents received regular prescription medicines and a third used an over-the-counter (OTC) medicine at least monthly. More than 80% (124/156) reported they would use the TPRSS. There was low awareness of the minor ailment service (MAS; 38%; 59/156). Post-installation: prescription ordering and OTC medicine purchase were used most frequently; the video link was used infrequently. Reasons for non-use were lack of need (36%; 40/112) and linkage to only one pharmacy (31%; 35/112). Community pharmacy services delivered remotely using tele-technology are feasible and acceptable. A larger study should be undertaken to confirm the potential of the TPRSS to reduce health inequalities in rural areas. © 2017 Royal Pharmaceutical Society.

  18. A TASER conducted electrical weapon with cardiac biomonitoring capability: Proof of concept and initial human trial.

    Science.gov (United States)

    Stopyra, Jason P; Ritter, Samuel I; Beatty, Jennifer; Johnson, James C; Kleiner, Douglas M; Winslow, James E; Gardner, Alison R; Bozeman, William P

    2016-10-01

    Despite research demonstrating the overall safety of Conducted Electrical Weapons (CEWs), commonly known by the brand name TASER(®), concerns remain regarding cardiac safety. The addition of cardiac biomonitoring capability to a CEW could prove useful and even lifesaving in the rare event of a medical crisis by detecting and analyzing cardiac rhythms during the period immediately after CEW discharge. To combine an electrocardiogram (ECG) device with a CEW to detect and store ECG signals while still allowing the CEW to perform its primary function of delivering an incapacitating electrical discharge. This work was performed in three phases. In Phase 1 standard law enforcement issue CEW cartridges were modified to demonstrate transmission of ECG signals. In Phase 2, a miniaturized ECG recorder was combined with a standard issue CEW and tested. In Phase 3, a prototype CEW with on-board cardiac biomonitoring was tested on human volunteers to assess its ability to perform its primary function of electrical incapacitation. Bench testing demonstrated that slightly modified CEW cartridge wires transmitted simulated ECG signals produced by an ECG rhythm generator and from a human volunteer. Ultimately, a modified CEW incorporating ECG monitoring successfully delivered incapacitating current to human volunteers and successfully recorded ECG signals from subcutaneous CEW probes after firing. An ECG recording device was successfully incorporated into a standard issue CEW without impeding the functioning of the device. This serves as proof-of-concept that safety measures such as cardiac biomonitoring can be incorporated into CEWs and possibly other law enforcement devices. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  19. Minimally Invasive Direct Lateral Interbody Fusion (MIS-DLIF): Proof of Concept and Perioperative Results.

    Science.gov (United States)

    Abbasi, Hamid; Abbasi, Ali

    2017-01-14

    Minimally invasive direct lateral interbody fusion (MIS-DLIF) is a novel approach for fusions of the lumbar spine. In this proof of concept study, we describe the surgical technique and report our experience and the perioperative outcomes of the first nine patients who underwent this procedure. In this study we establish the safety and efficacy of this approach. MIS-DLIF was performed on 15 spinal levels in nine patients who failed to respond to conservative therapy for the treatment of a re-herniated disk, spondylolisthesis, or other severe disk disease of the lumbar spine. We recorded surgery time, blood loss, fluoroscopy time, patient-reported pain, and complications. Throughout the MIS-DLIF procedure, the surgeon is aided by biplanar fluoroscopic imaging to place an interbody graft or cage into the disc space through the interpleural space. A discectomy is performed in the same minimally invasive fashion. The procedure is usually completed with posterior pedicle screw fixation. MIS-DLIF took 44/85 minutes, on average, for 1/2 levels, with 54/112 ml of blood loss, and 0.3/1.7 days of hospital stay. Four of nine patients did not require overnight hospitalization and were discharged two to four hours after surgery. We did not encounter any clinically significant complications. At more than ninety days post surgery, the patients reported a statistically significant reduction of 4.5 points on a 10-point sliding pain scale. MIS-DLIF with pedicle screw fixation is a safe and clinically effective procedure for fusions of the lumbar spine. The procedure overcomes many of the limitations of the current minimally invasive approaches to the lumbar spine and is technically straightforward. MIS-DLIF has the potential to improve patient outcomes and reduce costs relative to the current standard of care and therefore warrants further investigation. We are currently expanding this study to a larger cohort and documenting long-term outcome data.

  20. Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer's disease.

    Science.gov (United States)

    Koronyo, Yosef; Biggs, David; Barron, Ernesto; Boyer, David S; Pearlman, Joel A; Au, William J; Kile, Shawn J; Blanco, Austin; Fuchs, Dieu-Trang; Ashfaq, Adeel; Frautschy, Sally; Cole, Gregory M; Miller, Carol A; Hinton, David R; Verdooner, Steven R; Black, Keith L; Koronyo-Hamaoui, Maya

    2017-08-17

    Noninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD patients exhibit a myriad of retinal pathologies, including hallmark amyloid β-protein (Aβ) deposits. Burden, distribution, cellular layer, and structure of retinal Aβ plaques were analyzed in flat mounts and cross sections of definite AD patients and controls (n = 37). In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients. Histological examination uncovered classical and neuritic-like Aβ deposits with increased retinal Aβ42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aβ plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson's r = 0.84-0.91). Retinal deposits often associated with blood vessels and occurred in hot spot peripheral regions of the superior quadrant and innermost retinal layers. Transmission electron microscopy revealed retinal Aβ assembled into protofibrils and fibrils. Moreover, the ability to image retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope was demonstrated in live patients. A fully automated calculation of the retinal amyloid index (RAI), a quantitative measure of increased curcumin fluorescence, was constructed. Analysis of RAI scores showed a 2.1-fold increase in AD patients versus controls (P = 0.0031). The geometric distribution and increased burden of retinal amyloid pathology in AD, together with the feasibility to noninvasively detect discrete retinal amyloid deposits in living patients, may lead to a practical approach for large-scale AD diagnosis and monitoring. National Institute on Aging award (AG044897) and The Saban and The Marciano Family

  1. Improving ethanol productivity through self-cycling fermentation of yeast: a proof of concept.

    Science.gov (United States)

    Wang, Jie; Chae, Michael; Sauvageau, Dominic; Bressler, David C

    2017-01-01

    The cellulosic ethanol industry has developed efficient strategies for converting sugars obtained from various cellulosic feedstocks to bioethanol. However, any further major improvements in ethanol productivity will require development of novel and innovative fermentation strategies that enhance incumbent technologies in a cost-effective manner. The present study investigates the feasibility of applying self-cycling fermentation (SCF) to cellulosic ethanol production to elevate productivity. SCF is a semi-continuous cycling process that employs the following strategy: once the onset of stationary phase is detected, half of the broth volume is automatically harvested and replaced with fresh medium to initiate the next cycle. SCF has been shown to increase product yield and/or productivity in many types of microbial cultivation. To test whether this cycling process could increase productivity during ethanol fermentations, we mimicked the process by manually cycling the fermentation for five cycles in shake flasks, and then compared the results to batch operation. Mimicking SCF for five cycles resulted in regular patterns with regards to glucose consumption, ethanol titer, pH, and biomass production. Compared to batch fermentation, our cycling strategy displayed improved ethanol volumetric productivity (the titer of ethanol produced in a given cycle per corresponding cycle time) and specific productivity (the amount of ethanol produced per cellular biomass) by 43.1 ± 11.6 and 42.7 ± 9.8%, respectively. Five successive cycles contributed to an improvement of overall productivity (the aggregate amount of ethanol produced at the end of a given cycle per total processing time) and the estimated annual ethanol productivity (the amount of ethanol produced per year) by 64.4 ± 3.3 and 33.1 ± 7.2%, respectively. This study provides proof of concept that applying SCF to ethanol production could significantly increase productivities, which will help strengthen the

  2. Development of Proof-of-Concept Units for the Advanced Medium-Sized Mobile Power Sources (AMMPS) Program

    Energy Technology Data Exchange (ETDEWEB)

    Andriulli, JB

    2002-04-03

    The purpose of this report is to document the development of the proof-of-concept units within the Advanced Medium-sized Mobile Power Sources (AMMPS) program. The design used a small, lightweight diesel engine, a permanent magnet alternator, power electronics and digital controls as outlined in the philosophy detailed previously. One small proof-of-concept unit was completed and delivered to the military. The unit functioned well but was not optimized at the time of delivery to the military. A tremendous amount of experience was gained during this phase that can be used in the development of any follow-on AMMPS production systems. Lessons learned and recommendations for follow-on specifications are provided. The unit demonstrated that significant benefits are possible with the new design philosophy. Trade-offs will have to be made but many of the advantages appear to be within the technical grasp of the market.

  3. The Development of a Glucose Dehydrogenase 3D-Printed Glucose Sensor: A Proof-of-Concept Study.

    Science.gov (United States)

    Adams, Anngela; Malkoc, Aldin; La Belle, Jeffrey T

    2017-06-01

    This work represents a preliminary proof-of-concept design and verification of a 3D-printed glucose biosensor. The proof of concept presented is the first example of glucose dehydrogenase sensor fabricated by a 3D-printer while maintaining similar features to current lab-industry standards. The sensor was verified to detect physiological glucose concentrations between 0 and 400 mg/dL with a linear coefficient as high as .97. This study showed that it was possible to use 3D-printed technology to create a biosensor sensitive to glucose detection. As availability and functionality of 3D-printers expands, this technology has the potential to be an option for diabetes management. This preliminary study shows that the 3D-printed sensor platform holds promise for sensitive glucose detection.

  4. Impact of responder definition on the enriched enrollment randomized withdrawal trial design for establishing proof of concept in neuropathic pain.

    Science.gov (United States)

    Hewitt, David J; Ho, Tony W; Galer, Bradley; Backonja, Miroslav; Markovitz, Paul; Gammaitoni, Arnold; Michelson, David; Bolognese, James; Alon, Achilles; Rosenberg, Elizabeth; Herman, Gary; Wang, Hao

    2011-03-01

    The objective of this study was to evaluate how enrichment for responders increases assay sensitivity in an enriched enrollment randomized withdrawal (EERW) proof-of-concept (POC) study in neuropathic pain. Adults with moderate to severe peripheral neuropathic pain entered a 3- to 4-day screening period, followed by a 12-day titration to the highest tolerated dose that provided pain control (pregabalin 50-200mg t.i.d.), and then a 9-day maintenance period. Subjects were stratified as primary responders (⩾30%), secondary responders (⩾10% to proof-of-concept study to optimize assay sensitivity and efficiently determine the analgesic potential of a new treatment for neuropathic pain. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Virtual Reality-Based Attention Bias Modification Training for Social Anxiety: A Feasibility and Proof of Concept Study

    OpenAIRE

    Urech, Antoine; Krieger, Tobias; Chesham, Alvin; Mast, Fred W.; Berger, Thomas

    2015-01-01

    Attention bias modification (ABM) programs have been considered as a promising new approach for the treatment of various disorders, including social anxiety disorder (SAD). However, previous studies yielded ambiguous results regarding the efficacy of ABM in SAD. The present proof-of-concept study investigates the feasibility of a newly developed virtual reality (VR)-based dot-probe training paradigm. It was designed to facilitate attentional disengagement from threatening stimuli in socially ...

  6. Targeting pain catastrophization in patients with fibromyalgia using virtual reality exposure therapy: a proof-of-concept study

    OpenAIRE

    Morris, Linzette Deidrè; Louw, Quinette Abegail; Grimmer, Karen Anne; Meintjes, Ernesta

    2015-01-01

    [Purpose] Pain catastrophizing is a key predictor of poor compliance to exercises among patients with fibromyalgia syndrome. Alteration of pain catastrophizing in this group is thus warranted. This study aimed to provide proof-of-concept of a novel virtual reality exposure therapy program as treatment for exercise-related pain catastrophizing in patients with fibromyalgia syndrome. [Subjects and Methods] An exploratory, case-controlled study was conducted (fibromyalgia syndrome group and matc...

  7. Advanced Information Processing System (AIPS) proof-of-concept system functional design I/O network system services

    Science.gov (United States)

    1985-01-01

    The function design of the Input/Output (I/O) services for the Advanced Information Processing System (AIPS) proof of concept system is described. The data flow diagrams, which show the functional processes in I/O services and the data that flows among them, are contained. A complete list of the data identified on the data flow diagrams and in the process descriptions are provided.

  8. Pharmaceutical development of an amorphous solid dispersion formulation of elacridar hydrochloride for proof-of-concept clinical studies.

    Science.gov (United States)

    Sawicki, E; Schellens, J H M; Beijnen, J H; Nuijen, B

    2017-04-01

    A novel tablet formulation containing an amorphous solid dispersion (ASD) of elacridar hydrochloride was developed with the purpose to resolve the drug's low solubility in water and to conduct proof-of-concept clinical studies. Elacridar is highly demanded for proof-of-concept clinical trials that study the drug's suitability to boost brain penetration and bioavailability of numerous anticancer agents. Previously, clinical trials with elacridar were performed with a tablet containing elacridar hydrochloride. However, this tablet formulation resulted in poor and unpredictable absorption which was caused by the low aqueous solubility of elacridar hydrochloride. Twenty four different ASDs were produced and dissolution was compared to crystalline elacridar hydrochloride and a crystalline physical mixture. The formulation with highest dissolution was characterized for amorphicity. Subsequently, a tablet was developed and monitored for chemical/physical stability for 12 months at +15-25 °C, +2-8 °C and -20 °C. The ASD powder was composed of freeze dried elacridar hydrochloride-povidone K30-sodium dodecyl sulfate (1:6:1, w/w/w), appeared fully amorphous and resulted in complete dissolution whereas crystalline elacridar hydrochloride resulted in only 1% dissolution. The ASD tablets contained 25 mg elacridar hydrochloride and were stable for at least 12 months at -20 °C. The ASD tablet was considered feasible for proof-of-concept clinical studies and is now used as such.

  9. What is Proof of Concept Research and how does it Generate Epistemic and Ethical Categories for Future Scientific Practice?

    Science.gov (United States)

    Kendig, Catherine Elizabeth

    2016-06-01

    "Proof of concept" is a phrase frequently used in descriptions of research sought in program announcements, in experimental studies, and in the marketing of new technologies. It is often coupled with either a short definition or none at all, its meaning assumed to be fully understood. This is problematic. As a phrase with potential implications for research and technology, its assumed meaning requires some analysis to avoid it becoming a descriptive category that refers to all things scientifically exciting. I provide a short analysis of proof of concept research and offer an example of it within synthetic biology. I suggest that not only are there activities that circumscribe new epistemological categories but there are also associated normative ethical categories or principles linked to the research. I examine these and provide an outline for an alternative ethical account to describe these activities that I refer to as "extended agency ethics". This view is used to explain how the type of research described as proof of concept also provides an attendant proof of principle that is the result of decision-making that extends across practitioners, their tools, techniques, and the problem solving activities of other research groups.

  10. Multidimensional cognitive evaluation of patients with disorders of consciousness using EEG: A proof of concept study.

    Science.gov (United States)

    Sergent, Claire; Faugeras, Frédéric; Rohaut, Benjamin; Perrin, Fabien; Valente, Mélanie; Tallon-Baudry, Catherine; Cohen, Laurent; Naccache, Lionel

    2017-01-01

    sensitivity. The presence of a high-level effect in any of the three tested domains distinguished between minimally conscious and vegetative patients, while the presence of low-level effects was similar in both groups. In summary, this study constitutes a validated proof of concept in favor of probing multiple cognitive dimensions to improve the evaluation of non-communicating patients. At a more conceptual level, this EEG tool can help achieve a better understanding of disorders of consciousness by exploring consciousness in its multiple cognitive facets.

  11. Minimally Invasive Direct Lateral Interbody Fusion (MIS-DLIF): Proof of Concept and Perioperative Results

    Science.gov (United States)

    Abbasi, Hamid

    2017-01-01

    Background Minimally invasive direct lateral interbody fusion (MIS-DLIF) is a novel approach for fusions of the lumbar spine. In this proof of concept study, we describe the surgical technique and report our experience and the perioperative outcomes of the first nine patients who underwent this procedure. Study design/setting In this study we establish the safety and efficacy of this approach. MIS-DLIF was performed on 15 spinal levels in nine patients who failed to respond to conservative therapy for the treatment of a re-herniated disk, spondylolisthesis, or other severe disk disease of the lumbar spine. We recorded surgery time, blood loss, fluoroscopy time, patient-reported pain, and complications. Methods Throughout the MIS-DLIF procedure, the surgeon is aided by biplanar fluoroscopic imaging to place an interbody graft or cage into the disc space through the interpleural space. A discectomy is performed in the same minimally invasive fashion. The procedure is usually completed with posterior pedicle screw fixation. Results MIS-DLIF took 44/85 minutes, on average, for 1/2 levels, with 54/112 ml of blood loss, and 0.3/1.7 days of hospital stay. Four of nine patients did not require overnight hospitalization and were discharged two to four hours after surgery. We did not encounter any clinically significant complications. At more than ninety days post surgery, the patients reported a statistically significant reduction of 4.5 points on a 10-point sliding pain scale. Conclusions MIS-DLIF with pedicle screw fixation is a safe and clinically effective procedure for fusions of the lumbar spine. The procedure overcomes many of the limitations of the current minimally invasive approaches to the lumbar spine and is technically straightforward. MIS-DLIF has the potential to improve patient outcomes and reduce costs relative to the current standard of care and therefore warrants further investigation. We are currently expanding this study to a larger cohort and

  12. Exploration of chromatic aberration for multiplanar imaging: proof of concept with implications for fast, efficient autofocus.

    Science.gov (United States)

    Weinigel, Martin; Kellner, Albert L; Price, Jeffrey H

    2009-12-01

    Image-based autofocus determines focus directly from the specimen (as opposed to reflective surface positioning with an offset), but sequential acquisition of a stack of images to measure resolution/sharpness and find best focus is slower than reflective positioning. Simultaneous imaging of multiple focal planes, which is also useful for 3D imaging of live cells, is faster but requires complicated optics. With color CCD cameras and white light sources commonly available, we asked if axial chromatic aberration can be utilized to acquire multiple focal planes simultaneously, and if it can be controlled through a range sufficient for practical use. For proof of concept, we theoretically and experimentally explored the focal differences between three narrow wavelength bands on a 3-chip color CCD camera with and without glass inserts of various thicknesses and dispersions. Ray tracing yielded changes in foci of 0.65-0.9 microm upon insertion of 12.5-mm thick glass samples for green (G, 522 nm) vs. blue (B, 462 nm) and green vs. red (G-R, 604 nm). On a microscope: (1) With no glass inserts, the differences in foci were 2.15 microm (G-B) and 0.43 microm (G-R); (2) With glass inserts, the maximum change in foci for G vs. B was 0.44 microm and for G vs. R was 0.26 microm; and (3) An 11.3 mm thick N-BK7 glass insert shifted the foci 0.9 microm (R), 0.6 microm (G), and 0.35 microm (B), such that the B and R foci were farther apart (2.1 microm vs. 1.7 microm) and the R and G foci were closer together (0.25 microm vs. 0.45 microm). The slopes of the differences in foci were dependent on thickness, index of refraction, and dispersion. The measured differences in foci are comparable to the axial steps of 0.1-0.24 microm commonly used for autofocus, and focal plane separation can be altered by inserting optical elements of various dispersions and thicknesses. By enabling acquisition of multiple, axially offset images simultaneously, chromatic aberration, normally an imaging pariah

  13. Preparation for the Proof of Concept Flight of the Veggie Plant Growth Chamber

    Science.gov (United States)

    Massa, Gioia; Morrow, Robert; Hummerick, Mary; Newsham, Gerard; Wheeler, Raymond

    2012-01-01

    Veggie is a small plant growth chamber designed and built by ORBITEC that will fly to the International Space Station on SpaceX-3, scheduled for the summer of 2013. Ultimately Veggie will be used for research, education and outreach, and crew recreation. We want to demonstrate the functionality of this hardware by testing a scenario that could allow the crew to grow and consume fresh vegetables. Veggie will be collapsed and transported flat in a cargo transfer bag, and deployed on orbit, where it will be installed in an EXPRESS rack. The chamber consists of three subsystems: an LED light cap, a transparent bellows, and a root mat reservoir assembly. The bellows and flexible support arms allow the distance between plants and light cap to be adjusted for different ages and types of plants. Researchers at Kennedy Space Center and ORBITEC have been working to develop the plant growth interfaces for the proof of concept flight. We have developed a rooting pillow, consisting of a small bag containing media, time release fertilizer, seeds, and a wicking surface to conduct water from the root mat reservoir. Prototype pillows have been tested and results have influenced the design of flight pillows, which will be modified for microgravity from flight-approved materials. Several studies have been conducted selecting species and comparing media types in analog systems. Water content seems to be the most important factor differentiating media types in these small growth volumes (100 mL). Media type also influenced microbial levels on plants. Since produce sanitizing agents are not currently approved for growing food crops on orbit, plants and media types having very low microbial levels are being selected. Lettuce, mizuna, and other salad greens typically have microbial counts less than 10(exp 4) colony forming units and thus are good candidates for spaceflight. As we approach flight verification testing, we will finalize species, media selection, harvesting, and microbial

  14. RNA interference technology to control pest sea lampreys--a proof-of-concept.

    Directory of Open Access Journals (Sweden)

    George Heath

    Full Text Available The parasitic sea lamprey (Petromyzon marinus has caused extensive losses to commercial fish stocks of the upper Great Lakes of North America. Methods of controlling the sea lamprey include trapping, barriers to prevent migration, and use of a chemical lampricide (3-trifluoromethyl-4-nitrophenol to kill the filter-feeding larvae. Concerns about the non-specificity of these methods have prompted continued development of species-specific methods to control lampreys outside their native range. In this study, we considered the utility of RNA interference to develop a sea lamprey-specific lampricide. Injection of six different short interfering, double-stranded RNAs (siRNAs into lamprey embryos first confirmed that the siRNAs could reduce the targeted transcript levels by more than 50%. Two size classes of lamprey larvae were then fed the siRNAs complexed with liposomes, and three of the siRNAs (targeting elongation factor 1α, calmodulin, and α-actinin reduced transcript levels 2.5, 3.6, and 5.0-fold, respectively, within the lamprey midsections. This is not only the first demonstration of RNAi in lampreys, but it is also the first example of delivery of siRNAs to a non-mammalian vertebrate through feeding formulations. One of the siRNA treatments also caused increased mortality of the larvae following a single feeding of siRNAs, which suggests that prolonged or multiple feedings of siRNAs could be used to kill filter-feeding larvae within streams, following development of a slow-release formulation. The genes targeted in this study are highly conserved across many species, and only serve as a proof-of-concept demonstration that siRNAs can be used in lampreys. Given that RNA interference is a sequence-specific phenomenon, it should be possible to design siRNAs that selectively target gene sequences that are unique to sea lampreys, and thus develop a technology to control these pests without adversely affecting non-target species.

  15. Fatigue design of a mechanically biocompatible lattice for a proof-of-concept femoral stem.

    Science.gov (United States)

    Arabnejad Khanoki, Sajad; Pasini, Damiano

    2013-06-01

    A methodology is proposed to design a spatially periodic microarchitectured material for a two-dimensional femoral implant under walking gait conditions. The material is composed of a graded lattice with controlled property distribution that minimizes concurrently bone resorption and interface failure. The periodic microstructure of the material is designed for fatigue fracture caused by cyclic loadings on the hip joint as a result of walking. The bulk material of the lattice is Ti6AL4V and its microstructure is assumed free of defects. The Soderberg diagram is used for the fatigue design under multiaxial loadings. Two cell topologies, square and Kagome, are chosen to obtain optimized property gradients for a two-dimensional implant. Asymptotic homogenization (AH) theory is used to address the multiscale mechanics of the implant as well as to capture the stress and strain distribution at both the macro and the microscale. The microstress distribution found with AH is also compared with that obtained from a detailed finite element analysis. For the maximum value of the von Mises stress, we observe a deviation of 18.6% in unit cells close to the implant boundary, where the AH assumption of spatial periodicity of the fluctuating fields ceases to hold. In the second part of the paper, the metrics of bone resorption and interface shear stress are used to benchmark the graded cellular implant with existing prostheses made of fully dense titanium implant. The results show that the amount of initial postoperative bone loss for square and Kagome lattice implants decreases, respectively, by 53.8% and 58%. In addition, the maximum shear interface failure at the distal end is significantly reduced by about 79%. A set of proof-of-concepts of planar implants have been fabricated via Electron Beam Melting (EBM) to demonstrate the manufacturability of Ti6AL4V into graded lattices with alternative cell size. Optical microscopy has been used to measure the morphological parameters

  16. A Virtual Reality avatar interaction (VRai) platform to assess residual executive dysfunction in active military personnel with previous mild traumatic brain injury: proof of concept.

    Science.gov (United States)

    Robitaille, Nicolas; Jackson, Philip L; Hébert, Luc J; Mercier, Catherine; Bouyer, Laurent J; Fecteau, Shirley; Richards, Carol L; McFadyen, Bradford J

    2017-10-01

    This proof of concept study tested the ability of a dual task walking protocol using a recently developed avatar-based virtual reality (VR) platform to detect differences between military personnel post mild traumatic brain injury (mTBI) and healthy controls. The VR platform coordinated motion capture, an interaction and rendering system, and a projection system to present first (participant-controlled) and third person avatars within the context of a specific military patrol scene. A divided attention task was also added. A healthy control group was compared to a group with previous mTBI (both groups comprised of six military personnel) and a repeated measures ANOVA tested for differences between conditions and groups based on recognition errors, walking speed and fluidity and obstacle clearance. The VR platform was well tolerated by both groups. Walking fluidity was degraded for the control group within the more complex navigational dual tasking involving avatars, and appeared greatest in the dual tasking with the interacting avatar. This navigational behaviour was not seen in the mTBI group. The present findings show proof of concept for using avatars, particularly more interactive avatars, to expose differences in executive functioning when applying context-specific protocols (here for the military). Implications for rehabilitation Virtual reality provides a means to control context-specific factors for assessment and intervention. Adding human interaction and agency through avatars increases the ecologic nature of the virtual environment. Avatars in the present application of the Virtual Reality avatar interaction platform appear to provide a better ability to reveal differences between trained, military personal with and without mTBI.

  17. A Randomized, Controlled Proof-of-Concept Trial of an Internet-Based, Therapist-Assisted Self-Management Treatment for Posttraumatic Stress Disorder

    National Research Council Canada - National Science Library

    Bryant, Richard A; Engel, Charles C; Litz, Brett T; Papa, Anthony

    2007-01-01

    Objective: The authors report an 8-week randomized, controlled proof-of-concept trial of a new therapist-assisted, Internet-based, self-management cognitive behavior therapy versus Internet-based supportive...

  18. Proof of concept of an imaging system demonstrator for PET applications with SiPM

    Science.gov (United States)

    Morrocchi, Matteo; Marcatili, Sara; Belcari, Nicola; Giuseppina Bisogni, Maria; Collazuol, Gianmaria; Ambrosi, Giovanni; Santoni, Cristiano; Corsi, Francesco; Foresta, Maurizio; Marzocca, Cristoforo; Matarrese, Gianvito; Sportelli, Giancarlo; Guerra, Pedro; Santos, Andres; Del Guerra, Alberto

    2013-08-01

    A PET imaging system demonstrator based on LYSO crystal arrays coupled to SiPM matrices is under construction at the University and INFN of Pisa. Two SiPM matrices, composed of 8×8 SiPM pixels, and 1,5 mm pitch, have been coupled one to one to a LYSO crystals array and read out by a custom electronics system. front-end ASICs were used to read 8 channels of each matrix. Data from each front-end were multiplexed and sent to a DAQ board for the digital conversion; a motherboard collects the data and communicates with a host computer through a USB port for the storage and off-line data processing. In this paper we show the first preliminary tomographic image of a point-like radioactive source acquired with part of the two detection heads in time coincidence.

  19. Proof of concept of an imaging system demonstrator for PET applications with SiPM

    Energy Technology Data Exchange (ETDEWEB)

    Morrocchi, Matteo, E-mail: matteo.morrocchi@pi.infn.it [University of Pisa and INFN Sezione di Pisa, Pisa 56127 (Italy); Marcatili, Sara; Belcari, Nicola; Giuseppina Bisogni, Maria [University of Pisa and INFN Sezione di Pisa, Pisa 56127 (Italy); Collazuol, Gianmaria [INFN Sezione di Pisa, Pisa 56127 (Italy); Ambrosi, Giovanni; Santoni, Cristiano [INFN Sezione di Perugia, Perugia 06100 (Italy); Corsi, Francesco; Foresta, Maurizio; Marzocca, Cristoforo; Matarrese, Gianvito [Politecnico di Bari and INFN Sezione di Bari, Bari 70100 (Italy); Sportelli, Giancarlo [University of Pisa and INFN Sezione di Pisa, Pisa 56127 (Italy); Guerra, Pedro; Santos, Andres [Universidad Politecnica de Madrid, E 28040 Madrid (Spain); Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Del Guerra, Alberto [University of Pisa and INFN Sezione di Pisa, Pisa 56127 (Italy)

    2013-08-21

    A PET imaging system demonstrator based on LYSO crystal arrays coupled to SiPM matrices is under construction at the University and INFN of Pisa. Two SiPM matrices, composed of 8×8 SiPM pixels, and 1,5 mm pitch, have been coupled one to one to a LYSO crystals array and read out by a custom electronics system. front-end ASICs were used to read 8 channels of each matrix. Data from each front-end were multiplexed and sent to a DAQ board for the digital conversion; a motherboard collects the data and communicates with a host computer through a USB port for the storage and off-line data processing. In this paper we show the first preliminary tomographic image of a point-like radioactive source acquired with part of the two detection heads in time coincidence.

  20. Life cycle Prognostic Model Development and Initial Application Results

    Energy Technology Data Exchange (ETDEWEB)

    Jeffries, Brien; Hines, Wesley; Nam, Alan; Sharp, Michael; Upadhyaya, Belle [The University of Tennessee, Knoxville (United States)

    2014-08-15

    In order to obtain more accurate Remaining Useful Life (RUL) estimates based on empirical modeling, a Lifecycle Prognostics algorithm was developed that integrates various prognostic models. These models can be categorized into three types based on the type of data they process. The application of multiple models takes advantage of the most useful information available as the system or component operates through its lifecycle. The Lifecycle Prognostics is applied to an impeller test bed, and the initial results serve as a proof of concept.

  1. A Positive Psychology Intervention for Patients with an Acute Coronary Syndrome: Treatment Development and Proof-of-Concept Trial.

    Science.gov (United States)

    Huffman, Jeff C; Millstein, Rachel A; Mastromauro, Carol A; Moore, Shannon V; Celano, Christopher M; Bedoya, C Andres; Suarez, Laura; Boehm, Julia K; Januzzi, James L

    2016-10-01

    Positive psychological constructs are associated with superior outcomes in cardiac patients, but there has been minimal study of positive psychology (PP) interventions in this population. Our objective was to describe the intervention development and pilot testing of an 8-week phone-based PP intervention for patients following an acute coronary syndrome (ACS). Initial intervention development and single-arm proof-of-concept trial, plus comparison of the PP intervention to a subsequently-recruited treatment as usual (TAU) cohort. PP development utilized existing literature, expert input, and qualitative interview data in ACS patients. In the proof-of-concept trial, the primary outcomes were feasibility and acceptability, measured by rates of exercise completion and participant ratings of exercise ease/utility. Secondary outcomes were pre-post changes in psychological outcomes and TAU comparisons, measured using effect sizes (Cohen's d). The PP intervention and treatment manual were successfully created. In the proof-of-concept trial, 17/23 PP participants (74 %) completed at least 5 of 8 exercises. Participants rated the ease (M = 7.4/10; SD = 2.1) and utility (M = 8.1/10, SD = 1.6) of PP exercises highly. There were moderate pre-post improvements (ds = .46-.69) in positive affect, anxiety, and depression, but minimal effects on dispositional optimism (d = .08). Compared to TAU participants (n = 22), PP participants demonstrated greater improvements in positive affect, anxiety, and depression (ds = . 47-.71), but not optimism. A PP intervention was feasible, well-accepted, and associated with improvements in most psychological measures among cardiac patients. These results provide support for a larger trial focusing on behavioral outcomes.

  2. Combined cognitive–behavioural and mindfulness programme for people living with dystonia : a proof-of-concept study

    OpenAIRE

    Sandhu, Harbinder; Bernstein, C. J.; Davies, G.(Imperial College, London, UK); Tang, Nicole K. Y.; Belhag, M; Tingle, A.; Field, M; Foss, Jonathan G. K.; Lindahl, A; Underwood, M. (Martin) M.D.; Ellard, David R.

    2016-01-01

    Objectives To design and test the delivery of an intervention targeting the non-motor symptoms of dystonia and pilot key health and well-being questionnaires in this population.\\ud \\ud Design A proof-of-concept study to test the delivery, acceptability, relevance, structure and content for a 3-day group residential programme for the management of dystonia.\\ud \\ud Setting Participants were recruited from a single botulinum toxin clinic. The intervention was delivered in the community.\\ud \\ud P...

  3. Full 3-dimensional digital workflow for multicomponent dental appliances A proof of concept

    NARCIS (Netherlands)

    Meer, van der Joerd; Vissink, Arjan; Ren, Yijin

    Background. The authors used a 3-dimensional (3D) printer and a bending robot to produce a multicomponent dental appliance to assess whether 3D digital models of the dentition are applicable for a full digital workflow. Methods. The authors scanned a volunteer's dentition with an intraoral scanner

  4. Full 3-dimensional digital workflow for multicomponent dental appliances A proof of concept

    NARCIS (Netherlands)

    Meer, van der Joerd; Vissink, Arjan; Ren, Yijin

    2016-01-01

    Background. The authors used a 3-dimensional (3D) printer and a bending robot to produce a multicomponent dental appliance to assess whether 3D digital models of the dentition are applicable for a full digital workflow. Methods. The authors scanned a volunteer's dentition with an intraoral scanner (

  5. Flipping the classroom to teach Millennial residents medical leadership: a proof of concept.

    Science.gov (United States)

    Lucardie, Alicia T; Berkenbosch, Lizanne; van den Berg, Jochem; Busari, Jamiu O

    2017-01-01

    The ongoing changes in health care delivery have resulted in the reform of educational content and methods of training in postgraduate medical leadership education. Health care law and medical errors are domains in medical leadership where medical residents desire training. However, the potential value of the flipped classroom as a pedagogical tool for leadership training within postgraduate medical education has not been fully explored. Therefore, we designed a learning module for this purpose and made use of the flipped classroom model to deliver the training. The flipped classroom model reverses the order of learning: basic concepts are learned individually outside of class so that more time is spent applying knowledge to discussions and practical scenarios during class. Advantages include high levels of interaction, optimal utilization of student and expert time and direct application to the practice setting. Disadvantages include the need for high levels of self-motivation and time constraints within the clinical setting. Educational needs and expectations vary within various generations and call for novel teaching modalities. Hence, the choice of instructional methods should be driven not only by their intrinsic values but also by their alignment with the learners' preference. The flipped classroom model is an educational modality that resonates with Millennial students. It helps them to progress quickly beyond the mere understanding of theory to higher order cognitive skills such as evaluation and application of knowledge in practice. Hence, the successful application of this model would allow the translation of highly theoretical topics to the practice setting within postgraduate medical education.

  6. An Evaluation of a Factor Xa-Based Clotting Time Test for Enoxaparin: A Proof-of-Concept Study.

    Science.gov (United States)

    Ng, Deborah P J; Duffull, Stephen B; Faed, James M; Isbister, Geoffrey K; Gulati, Abhishek

    2017-01-01

    A well-accepted test for monitoring anticoagulation by enoxaparin is not currently available. As inadequate dosing may result in thrombosis or bleeding, a clinical need exists for a suitable test. Previous in silico and in vitro studies have identified factor Xa as an appropriate activating agent, and the phospholipid Actin FS as a cofactor for a Xa clotting time (TenaCT) test. A proof-of-concept study was designed to (1) explore the reproducibility of the TenaCT test and (2) explore factors that could affect the performance of the test. In vitro clotting time tests were carried out using plasma from 20 healthy volunteers. The effect of enoxaparin was determined at concentrations of 0.25, 0.5, and 1.0 IU/mL. Clotting times for the volunteers were significantly prolonged with increasing enoxaparin concentrations. Clotting times were significantly shortened for frozen plasma samples. No significant differences in prolongation of clotting times were observed between male and female volunteers or between the 2 evaluated age groups. The clotting times were consistent between 2 separate occasions. The TenaCT test was able to distinguish between the subtherapeutic and therapeutic concentrations of enoxaparin. Plasma should not be frozen prior to performing the test, without defining a frozen plasma reference range. This study provided proof-of-concept for a Xa-based test that can detect enoxaparin dose effects, but additional studies are needed to further develop the test.

  7. Vasodilation and Exercise Capacity in Patients with End-Stage Renal Disease: A Prospective Proof-of-Concept Study.

    Science.gov (United States)

    Habedank, Dirk; Schefold, Joerg C; Bernhardt, Carolin; Karhausen, Tim; Doehner, Wolfram; Anker, Stefan D; Reinke, Petra

    2016-11-01

    Previous data have pointed to the fact that vascular function is significantly impaired in patients with end-stage renal disease (ESRD). We aimed to better characterise vasodilation and exercise capacity in both ESRD and chronic heart failure (CHF) patients. A total of 30 ESRD patients (23 male; mean age 45.7 ± 9.9 years) were included in a prospective proof-of-concept study at a tertiary care academic centre. The patients underwent forearm venous plethysmography with post-ischaemic peak blood flow (PF) and flow-dependent flow (FDF) testing as well as cardiopulmonary exercise testing during the morning of the day following the last haemodialysis. After matching for age, gender, and body mass index, the data were compared to 30 patients with CHF and 20 age-matched healthy controls. PF in ESRD patients was reduced when compared to that in CHF patients (12.5 ± 4.2 vs. 15.6 ± 6.9 ml/100 ml/min; p = 0.048) and healthy controls (26.4 ± 9.3 ml/100 ml/min; p proof-of-concept study, exercise capacity was relatively preserved, while vasodilative capacity was substantially impaired in ESRD patients. Additional studies are warranted to examine the underlying mechanisms and potential clinical implications of our findings.

  8. Deterrence Impact Modeling Environment (DIME) Proof-of-Concept Test Evaluations and Findings

    Science.gov (United States)

    2016-06-01

    participants use facial expressions , physical actions, and the way that words are expressed to judge the trustworthiness of the others involved. 2...adoption and their manifestation in beliefs, behaviors and attitudes expressed not only in the tactical and operational maritime environments but...Within communities, instrumental, social, and normative sanctions continue to be expressed and experienced, but often in ways totally unknown and

  9. Modelling Public Security Operations: Evaluation of the Holistic Security Ecosystem (HSE) Proof-of-Concept

    Science.gov (United States)

    2012-12-01

    Ulieru Adaptive Risk Management Lab Faculty of Computer Science University of New Brunswick Scientific authority: Paul Chouinard DRDC...l’information qui minent la capacité de l’organisation à jauger la situation à mesure qu’elle évolue. Le projet FIT, la modélisation des opérations de sécurité...Nouveau-Brunswick (UNB) dans le contexte du projet de modélisation des opérations de sécurité publique du RDDC, qui vise à étudier la prise de

  10. Scripting approach in hybrid organic-inorganic condensation simulation: the GPTMS proof-of-concept

    OpenAIRE

    Maly, Marek; Posocco, Paola; Fermeglia, Maurizio; Pricl, Sabrina

    2008-01-01

    Abstract Silica-based hybrid organic-inorganic materials prepared by sol-gel chemistry exhibit unique chemical and physical properties by virtue of their anisotropic organization. (3-glycidoxypropyl)trimethoxysilane (GPTMS)-based networks represent an archetype of this class of substances, with a vast range of applications. In the present study, a new computational recipe has been developed within Materials Studio software platform to generate atomistic models of GPTMS crosslinked ...

  11. Flipping the classroom to teach Millennial residents medical leadership: a proof of concept

    Science.gov (United States)

    Lucardie, Alicia T; Berkenbosch, Lizanne; van den Berg, Jochem; Busari, Jamiu O

    2017-01-01

    Introduction The ongoing changes in health care delivery have resulted in the reform of educational content and methods of training in postgraduate medical leadership education. Health care law and medical errors are domains in medical leadership where medical residents desire training. However, the potential value of the flipped classroom as a pedagogical tool for leadership training within postgraduate medical education has not been fully explored. Therefore, we designed a learning module for this purpose and made use of the flipped classroom model to deliver the training. Evidence The flipped classroom model reverses the order of learning: basic concepts are learned individually outside of class so that more time is spent applying knowledge to discussions and practical scenarios during class. Advantages include high levels of interaction, optimal utilization of student and expert time and direct application to the practice setting. Disadvantages include the need for high levels of self-motivation and time constraints within the clinical setting. Discussion Educational needs and expectations vary within various generations and call for novel teaching modalities. Hence, the choice of instructional methods should be driven not only by their intrinsic values but also by their alignment with the learners’ preference. The flipped classroom model is an educational modality that resonates with Millennial students. It helps them to progress quickly beyond the mere understanding of theory to higher order cognitive skills such as evaluation and application of knowledge in practice. Hence, the successful application of this model would allow the translation of highly theoretical topics to the practice setting within postgraduate medical education. PMID:28144170

  12. Topical, Non-Medicated LOYON(®) in Facilitating the Removal of Scaling in Infants and Children with Cradle Cap: a Proof-of-Concept Pilot Study.

    Science.gov (United States)

    Hengge, Ulrich R

    2014-12-01

    Cradle cap is a very common condition in infants that presents as greasy, scaly patches on the scalp within the first weeks of life. Although usually disappearing by itself, the condition worries parents because of its appearance. When removing the scales, it is crucial to prevent spot bleedings to avoid infections. The investigational medical device LOYON(®) (Cetiol(®) CC, dimethicone) solution (G. Pohl-Boskamp GmbH & Co. KG, Hohenlockstedt, Germany) has the potential to meet these needs since it removes scales gently. It was, therefore, the aim of this proof-of-concept study to assess the efficacy and safety of topically applied, non-medicated LOYON(®) in facilitating the removal of scaling in infants and children with cradle cap without inducing spot bleedings. This single-center, open, proof-of-concept, pilot study was conducted in 20 male or female infants/children aged 3-36 months with clinically diagnosed cradle cap. The 8-day study period included one to three applications of LOYON(®). Clinical assessment of scaling and secondary parameters was performed at baseline and after treatment. Adverse events were recorded. A questionnaire on subjective efficacy and usability was handed out to the parents. With a maximum of three applications of LOYON(®) applied to 20 subjects, a reduction in scaling intensity from moderate or severe to very mild or mild was achieved in 80% of the subjects. Treatment success, defined as the reduction of the scaling baseline score by at least two points, was achieved in 50% of subjects. Results of this study do not indicate any safety concern. No spot bleedings were observed. LOYON(®) was generally well tolerated and overall treatment was rated as "good" by the parents/legal guardians. This study suggests that LOYON(®) is well tolerated, safe and effective in facilitating the removal of scaling in infants and children with cradle cap. With its gentle approach and rapid effect, LOYON(®) thus represents a good alternative to

  13. The influence of amniotic membrane extracts on cell growth depends on the part of membrane and childbirth mode selected: a proof-of-concept study.

    Science.gov (United States)

    Litwiniuk, M; Radowicka, M; Krejner, A; Grzela, T

    2017-08-02

    The amniotic membrane (AM) is a rich source of biologically active factors, important for wound healing and is widely used in various clinical applications, including tissue engineering, reconstructive surgery and wound management. The aim of the present proof-of-concept study was to assess the influence of amniotic membrane extracts on in vitro proliferation of main cells involved in tissue regeneration. The assessment was done in regards to the content of selected biologically active factors in amniotic membrane extracts. The quantitative analysis of EGF, TGF-β and TIMP-1 in tested samples was assayed by enzyme-linked immunosorbent assay (ELISA) tests. The influence of amniotic membrane extracts on proliferation of keratinocytes (HaCaT), fibroblasts (Wi-38) and endothelial cell lines (HECa-10) was assessed using a colorimetric tetrazolium salt reduction assay. In all of the amnion samples high amounts of EGF, TGF-β and TIMP-1 were detected. However, the content of these factors varied between placental and cervical portions of the same membrane. Moreover, various concentrations of biologically active factors between physiological at-term delivery and caesarean section-derived membranes were also observed. All of the assessed amnion extracts stimulated proliferation of HaCaT and Wi-38 cells, although samples prepared from caesarean section-derived cervical portion of amniotic membrane stimulated more proliferation of keratinocytes than of fibroblasts. In contrast to HaCaT and Wi-38 cells, proliferation of HECa-10 cell line was inhibited by all tested extracts. The results of our proof-of-concept study confirm that biological dressings prepared from amniotic membrane, especially its placental portion, since they stimulated both fibroblasts and keratinocytes, may provide relevant support for wound healing. On the other hand, dressings prepared from caesarean section-derived cervical portion of amniotic membrane, since they stimulate mainly epidermal cells, may be

  14. Flipping the classroom to teach Millennial residents medical leadership: a proof of concept

    Directory of Open Access Journals (Sweden)

    Lucardie AT

    2017-01-01

    Full Text Available Alicia T Lucardie,1 Lizanne Berkenbosch,2 Jochem van den Berg,3 Jamiu O Busari3,4 1Faculty of Health, Medicine and Life Sciences, Maastricht University, 2Department of Pediatrics, Maastricht University Medical Centre, Maastricht, 3Department of Pediatrics, Zuyderland Medical Center, Heerlen, 4Department of Educational Development and Research, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands Introduction: The ongoing changes in health care delivery have resulted in the reform of educational content and methods of training in postgraduate medical leadership education. Health care law and medical errors are domains in medical leadership where medical residents desire training. However, the potential value of the flipped classroom as a pedagogical tool for leadership training within postgraduate medical education has not been fully explored. Therefore, we designed a learning module for this purpose and made use of the flipped classroom model to deliver the training. Evidence: The flipped classroom model reverses the order of learning: basic concepts are learned individually outside of class so that more time is spent applying knowledge to discussions and practical scenarios during class. Advantages include high levels of interaction, optimal utilization of student and expert time and direct application to the practice setting. Disadvantages include the need for high levels of self-motivation and time constraints within the clinical setting. Discussion: Educational needs and expectations vary within various generations and call for novel teaching modalities. Hence, the choice of instructional methods should be driven not only by their intrinsic values but also by their alignment with the learners’ preference. The flipped classroom model is an educational modality that resonates with Millennial students. It helps them to progress quickly beyond the mere understanding of theory to higher order

  15. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study.

    Directory of Open Access Journals (Sweden)

    Christopher Vollmers

    2015-10-01

    Full Text Available It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation.In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412 that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without. We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient's net state of immunosuppression (correlation with tacrolimus level, r = -0.867, 95% CI -0.968 to -0.523, p = 0.0014, as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9% and a specificity of 82.0% (95% CI 72.1% to 89.1% (cell-free donor-derived DNA as noninvasive gold standard. To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several criteria including the

  16. Monitoring Pharmacologically Induced Immunosuppression by Immune Repertoire Sequencing to Detect Acute Allograft Rejection in Heart Transplant Patients: A Proof-of-Concept Diagnostic Accuracy Study

    Science.gov (United States)

    Valantine, Hannah A.; Penland, Lolita; Luikart, Helen; Strehl, Calvin; Cohen, Garrett; Khush, Kiran K.; Quake, Stephen R.

    2015-01-01

    Background It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation. Methods and Findings In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412) that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without). We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient’s net state of immunosuppression (correlation with tacrolimus level, r = −0.867, 95% CI −0.968 to −0.523, p = 0.0014), as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9%) and a specificity of 82.0% (95% CI 72.1% to 89.1%) (cell-free donor-derived DNA as noninvasive gold standard). To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several

  17. Proof of concept for AAV2/5-mediated gene therapy in iPSC-derived retinal pigment epithelium of a choroideremia patient.

    Science.gov (United States)

    Cereso, Nicolas; Pequignot, Marie O; Robert, Lorenne; Becker, Fabienne; De Luca, Valerie; Nabholz, Nicolas; Rigau, Valerie; De Vos, John; Hamel, Christian P; Kalatzis, Vasiliki

    2014-01-01

    Inherited retinal dystrophies (IRDs) comprise a large group of genetically and clinically heterogeneous diseases that lead to progressive vision loss, for which a paucity of disease-mimicking animal models renders preclinical studies difficult. We sought to develop pertinent human cellular IRD models, beginning with choroideremia, caused by mutations in the CHM gene encoding Rab escort protein 1 (REP1). We reprogrammed REP1-deficient fibroblasts from a CHM (-/y) patient into induced pluripotent stem cells (iPSCs), which we differentiated into retinal pigment epithelium (RPE). This iPSC-derived RPE is a polarized monolayer with a classic morphology, expresses characteristic markers, is functional for fluid transport and phagocytosis, and mimics the biochemical phenotype of patients. We assayed a panel of adeno-associated virus (AAV) vector serotypes and showed that AAV2/5 is the most efficient at transducing the iPSC-derived RPE and that CHM gene transfer normalizes the biochemical phenotype. The high, and unmatched, in vitro transduction efficiency is likely aided by phagocytosis and mimics the scenario that an AAV vector encounters in vivo in the subretinal space. We demonstrate the superiority of AAV2/5 in the human RPE and address the potential of patient iPSC-derived RPE to provide a proof-of-concept model for gene replacement in the absence of an appropriate animal model.

  18. Rapid quantification of Staphylococcus aureus from endotracheal aspirates of ventilated patients: a proof-of-concept study.

    Science.gov (United States)

    Lacroix, Morgane; Barraud, Olivier; Clavel, Marc; Filiputti, Delphine; Prudent, Sandrine; François, Bruno; Ploy, Marie Cécile; Jestin, Marie-Astrid; Rodrigue, Marc; Pachot, Alexandre; Yugueros-Marcos, Javier; Moucadel, Virginie

    2015-10-01

    Major concern for intubated patients is ventilator-associated pneumonia (VAP). Early detection of VAP and its causative microorganism(s) is a key challenge for clinicians. Diagnosis is based on clinical, radiological, and microbiological elements, the latter being provided 24-48h after sampling. According to practices, clinicians can sample endotracheal aspirates (ETAs) so as to check for patient colonization or perform ETA in case of VAP suspicion. In this proof-of-concept study, we report the evaluation of a semiautomated molecular method to rapidly quantify Staphylococcus aureus, one of the most involved microorganisms in VAP, directly from raw ETA samples. After evaluation using artificial ETA samples, our method was applied on 40 clinical ETA samples. All S. aureus-positive samples were successfully detected and quantified. Our method can provide an efficient sample preparation protocol for all raw ETA samples, combined with an accurate quantification of the bacterial load, in less than 3h 30min.

  19. Catalytic conversion of light alkanes-proof-of-concept stage -- Phase 6. Final report, February 1--October 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    During the course of the first three years of the Cooperative Agreement, the authors uncovered a family of metal perhaloporphyrin complexes which had unprecedented activity for the selective air-oxidation of light alkanes to alcohols. The reactivity of light hydrocarbon substrates with air or oxygen was in the order: isobutane > propane > ethane > methane, in accord with their homolytic bond dissociation energies. Isobutane was so reactive that the proof-of-concept stage of a process for producing tert-butyl alcohol from isobutane was begun (Phase 5). It was proposed that as more active catalytic systems were developed (Phases 4, 6), propane, then ethane and finally methane oxidations will move into this stage (Phases 7 through 9). As of this writing, however, the program has been terminated during the later stages of Phase 5 and 6 so that further work is not anticipated. 72 refs.

  20. Construction of Extended 3D Field of Views of the Internal Bladder Wall Surface: A Proof of Concept

    Science.gov (United States)

    Ben-Hamadou, Achraf; Daul, Christian; Soussen, Charles

    2016-09-01

    3D extended field of views (FOVs) of the internal bladder wall facilitate lesion diagnosis, patient follow-up and treatment traceability. In this paper, we propose a 3D image mosaicing algorithm guided by 2D cystoscopic video-image registration for obtaining textured FOV mosaics. In this feasibility study, the registration makes use of data from a 3D cystoscope prototype providing, in addition to each small FOV image, some 3D points located on the surface. This proof of concept shows that textured surfaces can be constructed with minimally modified cystoscopes. The potential of the method is demonstrated on numerical and real phantoms reproducing various surface shapes. Pig and human bladder textures are superimposed on phantoms with known shape and dimensions. These data allow for quantitative assessment of the 3D mosaicing algorithm based on the registration of images simulating bladder textures.

  1. Teaching geriatrics using an innovative, individual-centered educational game: students and educators win. A proof-of-concept study.

    Science.gov (United States)

    van de Pol, Marjolein H J; Lagro, Joep; Fluit, Lia R M G; Lagro-Janssen, Toine L M; Olde Rikkert, Marcel G M

    2014-10-01

    Given the increasingly aging population, nearly every doctor will encounter elderly adults who present with multiple complex comorbidities that can challenge even experienced physicians. This may explain why many medical students do not have a positive attitude toward elderly adults and find the complexity of their problems overwhelming. It was hypothesized that a recently developed medical school geriatrics course, based on the game GeriatriX and designed specifically to address the complexities associated with decision-making in geriatrics, can have a positive effect on attitudes toward geriatrics and on perceived knowledge of geriatrics. The effects of this game-based course were evaluated as a proof of concept. The assessment was based on the Aging Semantic Differential (ASD) and a validated self-perceived knowledge scale of geriatric topics. The usability of (and satisfaction with) GeriatriX was also assessed using a 5-point Likert scale. After completion of the course, the ASD changed significantly in the geriatrics course group (n = 29; P = .02) but not in a control group that took a neuroscience course (n = 24; P = .30). Moreover, the geriatrics course group had a significant increase in self-perceived knowledge for 12 of the 18 topics (P = .002), whereas in the control group self-perceived knowledge increased significantly for one topic only (sensory impairment) (P = .04). Finally, the geriatrics students reported enjoying GeriatriX. This proof-of-concept study clearly supports the hypothesis that a 4-week course using a modern educational approach such as GeriatriX can improve students' self-perceived knowledge of geriatrics and their attitudes toward elderly adults. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  2. Virtual reality exposure therapy as treatment for pain catastrophizing in fibromyalgia patients: proof-of-concept study (Study Protocol).

    Science.gov (United States)

    Morris, Linzette D; Grimmer-Somers, Karen A; Spottiswoode, Bruce; Louw, Quinette A

    2011-04-30

    Albeit exercise is currently advocated as one of the most effective management strategies for fibromyalgia syndrome (FMS); the implementation of exercise as a FMS treatment in reality is significantly hampered by patients' poor compliance. The inference that pain catastrophizing is a key predictor of poor compliance in FMS patients, justifies considering the alteration of pain catastrophizing in improving compliance towards exercises in FMS patients. The aim of this study is to provide proof-of-concept for the development and testing of a novel virtual reality exposure therapy (VRET) program as treatment for exercise-related pain catastrophizing in FMS patients. Two interlinked experimental studies will be conducted. Study 1 aims to objectively ascertain if neurophysiological changes occur in the functional brain areas associated with pain catastrophizing, when catastrophizing FMS subjects are exposed to visuals of exercise activities. Study 2 aims to ascertain the preliminary efficacy and feasibility of exposure to visuals of exercise activities as a treatment for exercise-related pain catastrophizing in FMS subjects. Twenty subjects will be selected from a group of FMS patients attending the Tygerberg Hospital in Cape Town, South Africa and randomly allocated to either the VRET (intervention) group or waiting list (control) group. Baseline neurophysiological activity for subjects will be collected in study 1 using functional magnetic resonance imaging (fMRI). In study 2, clinical improvement in pain catastrophizing will be measured using fMRI (objective) and the pain catastrophizing scale (subjective). The premise is if exposing FMS patients to visuals of various exercise activities trigger the functional brain areas associated with pain catastrophizing; then as a treatment, repeated exposure to visuals of the exercise activities using a VRET program could possibly decrease exercise-related pain catastrophizing in FMS patients. Proof-of-concept will either be

  3. The Use of Screen-Printed Electrodes in a Proof of Concept Electrochemical Estimation of Homocysteine and Glutathione in the Presence of Cysteine Using Catechol

    Directory of Open Access Journals (Sweden)

    Patricia T. Lee

    2014-06-01

    Full Text Available Screen printed electrodes were employed in a proof of concept determination of homocysteine and glutathione using electrochemically oxidized catechol via a 1,4-Michael addition reaction in the absence and presence of cysteine, and each other. Using cyclic voltammetry, the Michael reaction introduces a new adduct peak which is analytically useful in detecting thiols. The proposed procedure relies on the different rates of reaction of glutathione and homocysteine with oxidized catechol so that at fast voltage scan rates only homocysteine is detected in cyclic voltammetry. At slower scan rates, both glutathione and homocysteine are detected. The combination of the two sets of data provides quantification for homocysteine and glutathione. The presence of cysteine is shown not to interfere provided sufficient high concentrations of catechol are used. Calibration curves were determined for each homocysteine and glutathione detection; where the sensitivities are 0.019 µA·µM−1 and 0.0019 µA·µM−1 and limit of detections are ca. 1.2 µM and 0.11 µM for homocysteine and glutathione, respectively, within the linear range. This work presents results with potential and beneficial use in re-useable and/or disposable point-of-use sensors for biological and medical applications.

  4. The Use of Screen-Printed Electrodes in a Proof of Concept Electrochemical Estimation of Homocysteine and Glutathione in the Presence of Cysteine Using Catechol

    Science.gov (United States)

    Lee, Patricia T.; Lowinsohn, Denise; Compton, Richard G.

    2014-01-01

    Screen printed electrodes were employed in a proof of concept determination of homocysteine and glutathione using electrochemically oxidized catechol via a 1,4-Michael addition reaction in the absence and presence of cysteine, and each other. Using cyclic voltammetry, the Michael reaction introduces a new adduct peak which is analytically useful in detecting thiols. The proposed procedure relies on the different rates of reaction of glutathione and homocysteine with oxidized catechol so that at fast voltage scan rates only homocysteine is detected in cyclic voltammetry. At slower scan rates, both glutathione and homocysteine are detected. The combination of the two sets of data provides quantification for homocysteine and glutathione. The presence of cysteine is shown not to interfere provided sufficient high concentrations of catechol are used. Calibration curves were determined for each homocysteine and glutathione detection; where the sensitivities are 0.019 μA·μM−1 and 0.0019 μA·μM−1 and limit of detections are ca. 1.2 μM and 0.11 μM for homocysteine and glutathione, respectively, within the linear range. This work presents results with potential and beneficial use in re-useable and/or disposable point-of-use sensors for biological and medical applications. PMID:24926695

  5. Medication eluting devices for the field of OBGYN (MEDOBGYN): 3D printed biodegradable hormone eluting constructs, a proof of concept study.

    Science.gov (United States)

    Tappa, Karthik; Jammalamadaka, Udayabhanu; Ballard, David H; Bruno, Todd; Israel, Marissa R; Vemula, Harika; Meacham, J Mark; Mills, David K; Woodard, Pamela K; Weisman, Jeffery A

    2017-01-01

    3D printing has the potential to deliver personalized implants and devices for obstetric and gynecologic applications. The aim of this study is to engineer customizable and biodegradable 3D printed implant materials that can elute estrogen and/or progesterone. All 3D constructs were printed using polycaprolactone (PCL) biodegradable polymer laden with estrogen or progesterone and were subjected to hormone-release profile studies using ELISA kits. Material thermal properties were tested using thermogravimetric analysis and differential scanning calorimetry. The 3D printed constructs showed extended hormonal release over a one week period. Cytocompatibility and bioactivity were assessed using a luciferase assay. The hormone-laden 3D printed constructs demonstrated an increase in luciferase activity and without any deleterious effects. Thermal properties of the PCL and hormones showed degradation temperatures above that of the temperature used in the additive manufacturing process-suggesting that 3D printing can be achieved below the degradation temperatures of the hormones. Sample constructs in the shape of surgical meshes, subdermal rods, intrauterine devices and pessaries were designed and printed. 3D printing of estrogen and progesterone-eluting constructs was feasible in this proof of concept study. These custom designs have the potential to act as a form of personalized medicine for drug delivery and optimized fit based on patient-specific anatomy.

  6. A quantitative framework to group nanoscale and microscale particles by hazard potency to derive occupational exposure limits: Proof of concept evaluation.

    Science.gov (United States)

    Drew, Nathan M; Kuempel, Eileen D; Pei, Ying; Yang, Feng

    2017-08-05

    The large and rapidly growing number of engineered nanomaterials (ENMs) presents a challenge to assessing the potential occupational health risks. An initial database of 25 rodent studies including 1929 animals across various experimental designs and material types was constructed to identify materials that are similar with respect to their potency in eliciting neutrophilic pulmonary inflammation, a response relevant to workers. Doses were normalized across rodent species, strain, and sex as the estimated deposited particle mass dose per gram of lung. Doses associated with specific measures of pulmonary inflammation were estimated by modeling the continuous dose-response relationships using benchmark dose modeling. Hierarchical clustering was used to identify similar materials. The 18 nanoscale and microscale particles were classified into four potency groups, which varied by factors of approximately two to 100. Benchmark particles microscale TiO2 and crystalline silica were in the lowest and highest potency groups, respectively. Random forest methods were used to identify the important physicochemical predictors of pulmonary toxicity, and group assignments were correctly predicted for five of six new ENMs. Proof-of-concept was demonstrated for this framework. More comprehensive data are needed for further development and validation for use in deriving categorical occupational exposure limits. Published by Elsevier Inc.

  7. Engineering of benzylglucosinolate in tobacco provides proof-of-concept for dead-end trap crops genetically modified to attract Plutella xylostella (diamondback moth).

    Science.gov (United States)

    Møldrup, Morten E; Geu-Flores, Fernando; de Vos, Martin; Olsen, Carl E; Sun, Joel; Jander, Georg; Halkier, Barbara A

    2012-05-01

    Glucosinolates are biologically active natural products characteristic of crucifers, including oilseed rape, cabbage vegetables and the model plant Arabidopsis thaliana. Crucifer-specialist insect herbivores, like the economically important pest Plutella xylostella (diamondback moth), frequently use glucosinolates as oviposition stimuli. This suggests that the transfer of a glucosinolate biosynthetic pathway to a non-crucifer would stimulate oviposition on an otherwise non-attractive plant. Here, we demonstrate that stable genetic transfer of the six-step benzylglucosinolate pathway from A. thaliana to Nicotiana tabacum (tobacco) results in the production of benzylglucosinolate without causing morphological alterations. Benzylglucosinolate-producing tobacco plants were more attractive for oviposition by female P. xylostella moths than wild-type tobacco plants. As newly hatched P. xylostella larvae were unable to survive on tobacco, these results represent a proof-of-concept strategy for rendering non-host plants attractive for oviposition by specialist herbivores with the long-term goal of generating efficient dead-end trap crops for agriculturally important pests.

  8. Use of Google Glass to Enhance Surgical Education of Neurosurgery Residents: "Proof-of-Concept" Study.

    Science.gov (United States)

    Nakhla, Jonathan; Kobets, Andrew; De la Garza Ramos, Rafeal; Haranhalli, Neil; Gelfand, Yaroslav; Ammar, Adam; Echt, Murray; Scoco, Aleka; Kinon, Merritt; Yassari, Reza

    2017-02-01

    The relatively decreased time spent in the operating room and overall reduction in cases performed by neurosurgical trainees as a result of duty-hour restrictions demands that the pedagogical content within each surgical encounter be maximized and crafted toward the specific talents and shortcomings of the individual. It is imperative to future generations that the quality of training adapts to the changing administrative infrastructures and compensates for anything that may compromise the technical abilities of trainees. Neurosurgeons in teaching hospitals continue to experiment with various emerging technologies-such as simulators and virtual presence-to supplement and improve surgical training. The authors participated in the Google Glass Explorer Program in order to assess the applicability of Google Glass as a tool to enhance the operative education of neurosurgical residents. Google Glass is a type of wearable technology in the form of eyeglasses that employs a high-definition camera and allows the user to interact using voice commands. Google Glass was able to effectively capture video segments of various lengths for residents to review in a variety of clinical settings within a large, tertiary care university hospital, as well as during a surgical mission to a developing country. The resolution and quality of the video were adequate to review and use as a teaching tool. While Google Glass harbors the potential to dramatically improve both neurosurgical education and practice in a variety of ways, certain technical drawbacks of the current model limit its effectiveness as a teaching tool. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Collimator design for a dedicated molecular breast imaging-guided biopsy system: Proof-of-concept

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, Amanda L.; Hruska, Carrie B.; Conners, Amy L.; O' Connor, Michael K. [Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905 (United States)

    2013-01-15

    acquired with the current parallel-hole collimator. Sensitivity was increased via more vertical cone slant angles, larger annular areas, thinner cone walls, shorter cone heights, and thinner radiating septa. Full width at half maximum trended in the opposite direction as sensitivity for all parameters. There was less error in the depth estimates for less vertical slant angles, smaller annular areas, thinner cone walls, cone heights near 1 cm, and generally thinner radiating septa. Conclusions: A Monte Carlo model was used to demonstrate the feasibility of a CSH collimator design for rapid biopsy application in molecular breast imaging. Specifically, lesion depth of a 1-cm diameter lesion positioned in the center of a typical breast can be estimated with error of less than 2 mm using circumferential count profiles of images acquired in 1 min.

  10. Proof-of-Concept Studies in Novel Guided Wave Methods for Metallic Structural Condition

    Science.gov (United States)

    2009-03-01

    honeycomb sandwich panel. In this work, experimental results will be shown to demonstrate the applicability of this approach to a more realist...originally developed at NASA Langley Research Center for low-frequency structural control (Wilkie et al. 2000, Sodano et al. 2004), are recently

  11. Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data

    National Research Council Canada - National Science Library

    Accurso, Frank J; Van Goor, Fredrick; Zha, Jiuhong; Stone, Anne J; Dong, Qunming; Ordonez, Claudia L; Rowe, Steven M; Clancy, John Paul; Konstan, Michael W; Hoch, Heather E; Heltshe, Sonya L; Ramsey, Bonnie W; Campbell, Preston W; Ashlock, Melissa A

    2014-01-01

    ...) were integrated into a model of CFTR activity. Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects...

  12. Forecasting of wet snow avalanche activity: Proof of concept and operational implementation

    Science.gov (United States)

    Gobiet, Andreas; Jöbstl, Lisa; Rieder, Hannes; Bellaire, Sascha; Mitterer, Christoph

    2017-04-01

    State-of-the-art tools for the operational assessment of avalanche danger include field observations, recordings from automatic weather stations, meteorological analyses and forecasts, and recently also indices derived from snowpack models. In particular, an index for identifying the onset of wet-snow avalanche cycles (LWCindex), has been demonstrated to be useful. However, its value for operational avalanche forecasting is currently limited, since detailed, physically based snowpack models are usually driven by meteorological data from automatic weather stations only and have therefore no prognostic ability. Since avalanche risk management heavily relies on timely information and early warnings, many avalanche services in Europe nowadays start issuing forecasts for the following days, instead of the traditional assessment of the current avalanche danger. In this context, the prognostic operation of detailed snowpack models has recently been objective of extensive research. In this study a new, observationally constrained setup for forecasting the onset of wet-snow avalanche cycles with the detailed snow cover model SNOWPACK is presented and evaluated. Based on data from weather stations and different numerical weather prediction models, we demonstrate that forecasts of the LWCindex as indicator for wet-snow avalanche cycles can be useful for operational warning services, but is so far not reliable enough to be used as single warning tool without considering other factors. Therefore, further development currently focuses on the improvement of the forecasts by applying ensemble techniques and suitable post processing approaches to the output of numerical weather prediction models. In parallel, the prognostic meteo-snow model chain is operationally used by two regional avalanche warning services in Austria since winter 2016/2017 for the first time. Experiences from the first operational season and first results from current model developments will be reported.

  13. Exploring Normalized Systems Potential for Dutch MoD’s Agility: A Proof of Concept on Flexibility, Time-to-market, Productivity and Quality

    NARCIS (Netherlands)

    Op 't Land, M.; Krouwel, M.R.; Van Dipten, E.G.; Verelst, J.

    2011-01-01

    Both the Command and Control Support Centre (C2SC) of the Dutch Ministry of Defense, and Capgemini are constantly exploring better ways of building and maintaining information systems which ef- fectively support strategy and operations of an enterprise. In a Proof of Concept conducted in March and A

  14. 68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies

    National Research Council Canada - National Science Library

    Weineisen, Martina; Schottelius, Margret; Simecek, Jakub; Baum, Richard P; Yildiz, Akin; Beykan, Seval; Kulkarni, Harshad R; Lassmann, Michael; Klette, Ingo; Eiber, Matthias; Schwaiger, Markus; Wester, Hans-Jürgen

    2015-01-01

    ...) in metastatic prostate cancer (PC), the goal of this study was the development, preclinical evaluation, and first proof-of-concept investigation of a PSMA inhibitor for imaging and therapy (PSMA I&T) for (68)Ga-based PET and (177...

  15. Exploring Normalized Systems Potential for Dutch MoD’s Agility: A Proof of Concept on Flexibility, Time-to-market, Productivity and Quality

    NARCIS (Netherlands)

    Op 't Land, M.; Krouwel, M.R.; Van Dipten, E.G.; Verelst, J.

    2011-01-01

    Both the Command and Control Support Centre (C2SC) of the Dutch Ministry of Defense, and Capgemini are constantly exploring better ways of building and maintaining information systems which ef- fectively support strategy and operations of an enterprise. In a Proof of Concept conducted in March and

  16. Exploring Normalized Systems Potential for Dutch MoD’s Agility: A Proof of Concept on Flexibility, Time-to-market, Productivity and Quality

    NARCIS (Netherlands)

    Op 't Land, M.; Krouwel, M.R.; Van Dipten, E.G.; Verelst, J.

    2011-01-01

    Both the Command and Control Support Centre (C2SC) of the Dutch Ministry of Defense, and Capgemini are constantly exploring better ways of building and maintaining information systems which ef- fectively support strategy and operations of an enterprise. In a Proof of Concept conducted in March and A

  17. Virtual reality exposure therapy as treatment for pain catastrophizing in fibromyalgia patients: proof-of-concept study (Study Protocol

    Directory of Open Access Journals (Sweden)

    Spottiswoode Bruce

    2011-04-01

    Full Text Available Abstract Background Albeit exercise is currently advocated as one of the most effective management strategies for fibromyalgia syndrome (FMS; the implementation of exercise as a FMS treatment in reality is significantly hampered by patients' poor compliance. The inference that pain catastrophizing is a key predictor of poor compliance in FMS patients, justifies considering the alteration of pain catastrophizing in improving compliance towards exercises in FMS patients. The aim of this study is to provide proof-of-concept for the development and testing of a novel virtual reality exposure therapy (VRET program as treatment for exercise-related pain catastrophizing in FMS patients. Methods Two interlinked experimental studies will be conducted. Study 1 aims to objectively ascertain if neurophysiological changes occur in the functional brain areas associated with pain catastrophizing, when catastrophizing FMS subjects are exposed to visuals of exercise activities. Study 2 aims to ascertain the preliminary efficacy and feasibility of exposure to visuals of exercise activities as a treatment for exercise-related pain catastrophizing in FMS subjects. Twenty subjects will be selected from a group of FMS patients attending the Tygerberg Hospital in Cape Town, South Africa and randomly allocated to either the VRET (intervention group or waiting list (control group. Baseline neurophysiological activity for subjects will be collected in study 1 using functional magnetic resonance imaging (fMRI. In study 2, clinical improvement in pain catastrophizing will be measured using fMRI (objective and the pain catastrophizing scale (subjective. Discussion The premise is if exposing FMS patients to visuals of various exercise activities trigger the functional brain areas associated with pain catastrophizing; then as a treatment, repeated exposure to visuals of the exercise activities using a VRET program could possibly decrease exercise-related pain catastrophizing

  18. Meteorological Sensor Array (MSA) - Phase I Volume 1 (Proof of Concept Overview)

    Science.gov (United States)

    2014-09-01

    ARL). These decision aids are based on atmospheric models, which are, in turn, based on algorithms. Physical science gleans these algorithms from...ambient temperature. Combining the local ambient warmth with the equipment-generated heat, there is a high likelihood that the data logger operating

  19. Feasibility of Storing Latent Heat with Liquid Crystals. Proof of Concept at Lab Scale

    Directory of Open Access Journals (Sweden)

    Rocío Bayón

    2016-04-01

    Full Text Available In this work, the first experimental results of thermotropic liquid crystals used as phase change materials for thermal storage are presented. For that purpose, the n = 10 derivative from the family of 4′-n-alkoxybiphenyl-4-carboxylic acids has been prepared. Different techniques like polarized-light microscopy, differential scanning calorimetry, thermogravimetric analysis and rheological measurements have been applied for its characterization. Having a mesophase/isotropic transition temperature around 251 °C, a clearing enthalpy of 55 kJ/kg, a thermal heat capacity of around 2.4 kJ/kg and a dynamic viscosity lower than 0.6 Pas, this compound fulfills the main requirements for being considered as latent heat storage material. Although further studies on thermal stability are necessary, the results already obtained are both promising and encouraging since they demonstrate de viability of this new application of liquid crystals as thermal storage media.

  20. Research designs for proof-of-concept chronic pain clinical trials

    DEFF Research Database (Denmark)

    Gewandter, Jennifer S; Dworkin, Robert H; Turk, Dennis C

    2014-01-01

    indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner. An IMMPACT...... consensus meeting was convened to discuss design considerations for POC trials in analgesia, with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic......-pharmacodynamic relationships, and minimization of missing data. Efficiency of single-dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and crossover designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages...

  1. CwicStart - a proof-of-concept client for the CEOSWGISS Integrated Catalog (CWIC)

    Science.gov (United States)

    Newman, D. J.; Mitchell, A. E.

    2012-12-01

    Keywords - Earth Science, data discovery, agile development, ruby on rails, catalog, OGC Audience - Earth Science application developers What is CwicStart CwicStart is a prototypical earth science data discovery web application designed, developed and hosted by NASA's Earth Observing System (EOS) Clearinghouse (ECHO). CwicStart searches the CEOS WGISS Integrated Catalog (CWIC) to provide users with dataset and granule level metadata from sources as diverse as NASA, NOAA, INPE and AOE. CwicStart demonstrates the ease of which it is possible to stand up a functioning client against the CWIC. From start to finish, CwicStart was designed, developed and deployed in one month. Built from OGC getCapabilities document of CWIC The CwicStart application takes the OGC getCapabilities (http://www.opengeospatial.org/standards/is) document describing CWIC, as it's starting point for providing a user interface suitable for interrogating CWIC. Consequently, it can allow the user to constrain their search by the following criteria, - Generic search terms - Spatial bounding box - Start date/time and end date/time - ISO-queryable key-value pairs User Interface inspired by Reverb ECHO's state-of-the-art earth science discovery tool, Reverb (http://reverb.echo.nasa.gov) was used as a guideline for the user interface components of CwicStart. It incorporates OpenLayers to provide point-and-click spatial constraint specification and calendar input for temporal constraints. Discovery involves two phases: dataset discovery and granule discovery with full pagination support for large results sets. CwicStart supports 'graceful degradation' of support for multiple browsers and accessibility requirements. Implemented in Ruby on Rails for Agile Development CwicStart is implemented in Ruby on Rails, a dynamic, rapid development language and environment that facilitates Agile development and is resilient to changing requirements. Using an Agile development methodology ECHO was able to stand up the

  2. Proof-of-concept of a laser mounted endoscope for touch-less navigated procedures.

    Science.gov (United States)

    Kral, Florian; Gueler, Oezguer; Perwoeg, Martina; Bardosi, Zoltan; Puschban, Elisabeth J; Riechelmann, Herbert; Freysinger, Wolfgang

    2013-08-01

    During navigated procedures a tracked pointing device is used to define target structures in the patient to visualize its position in a registered radiologic data set. When working with endoscopes in minimal invasive procedures, the target region is often difficult to reach and changing instruments is disturbing in a challenging, crucial moment of the procedure. We developed a device for touch less navigation during navigated endoscopic procedures. A laser beam is delivered to the tip of a tracked endoscope angled to its axis. Thereby the position of the laser spot in the video-endoscopic images changes according to the distance between the tip of the endoscope and the target structure. A mathematical function is defined by a calibration process and is used to calculate the distance between the tip of the endoscope and the target. The tracked tip of the endoscope and the calculated distance is used to visualize the laser spot in the registered radiologic data set. In comparison to the tracked instrument, the touch less target definition with the laser spot yielded in an over and above error of 0.12 mm. The overall application error in this experimental setup with a plastic head was 0.61 ± 0.97 mm (95% CI -1.3 to +2.5 mm). Integrating a laser in an endoscope and then calculating the distance to a target structure by image processing of the video endoscopic images is accurate. This technology eliminates the need for tracked probes intraoperatively and therefore allows navigation to be integrated seamlessly in clinical routine. However, it is an additional chain link in the sequence of computer-assisted surgery thus influencing the application error. Copyright © 2013 Wiley Periodicals, Inc.

  3. Passive soil heating using an inexpensive infrared mirror design – a proof of concept

    OpenAIRE

    Rasmussen, C; Gallery, R. E.; J. S. Fehmi

    2015-01-01

    There is a need to understand the soil system response to warming in order to model the soil process response to predicted climate change. Current methods for soil warming include expensive and difficult to implement active and passive techniques. Here we test a simple, inexpensive in situ passive soil heating approach, based on easy to construct infrared mirrors that do not require automation or enclosures. The infrared mirrors consisted of 61 × 61 cm glass panels coated with ...

  4. Reservoir Cannulas for Pediatric Oxygen Therapy: A Proof-of-Concept Study

    OpenAIRE

    Grace Wu; Alec Wollen; Robert M. DiBlasi; Stephen Himley; Eugene Saxon; Glenn Austin; Jaclyn Delarosa; Rasa Izadnegahdar; Amy Sarah Ginsburg; Darin Zehrung

    2016-01-01

    Hypoxemia is a complication of pneumonia—the leading infectious cause of death in children worldwide. Treatment generally requires oxygen-enriched air, but access in low-resource settings is expensive and unreliable. We explored use of reservoir cannulas (RCs), which yield oxygen savings in adults but have not been examined in children. Toddler, small child, and adolescent breathing profiles were simulated with artificial lung and airway models. An oxygen concentrator provided flow rates of 0...

  5. Pilot proof of concept clinical trials of Stochastic Targeted (STAR) glycemic control

    OpenAIRE

    Evans, Alicia; Shaw, Geoffrey M; Le Compte, Aaron; Tan, Chia*-Siong; Ward, Logan; Steel, James,; Pretty, Christopher G; Pfeifer, Leesa; Penning, Sophie; Suhaimi, Fatanah; Signal, Matthew; Desaive, Thomas; Chase, J. Geoffrey

    2011-01-01

    ABSTRACT: INTRODUCTION: Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach directly accounting for intra- and inter- patient variability with a stochastically derived maximum 5% risk of blood glucose (BG) < 4.0 mmol/L. This research assesses the safety, efficacy, and clinical burden of a STAR TGC controller modulating both insulin and nutrition inputs in pilot trials. METHODS: Seven...

  6. Proof-of-Concept Part Task Trainer for Close Air Support Procedures

    Science.gov (United States)

    2016-06-01

    using only their hands (Salamin et al. 2006). The analysis of study results collected through the questionnaires suggested that first-person...examined in the light of helping the users build mental models. Bowman et al. suggest that virtual environments could be used to help with education ...Bowman et al. 1999). In that article, the authors discuss the importance of direct experience and how it relates to education . They comment that

  7. Paleohydraulic Reconstruction of Modern Large Floods at Subcritical Speed in a Confined Valley: Proof of Concept

    Directory of Open Access Journals (Sweden)

    Patricio Bohorquez

    2016-12-01

    Full Text Available The present study aims to show the accuracy of paleoflood reconstruction techniques based on two-dimensional (2D hydraulic modelling of a large flood. Using this reconstruction technique, we determined trends in flood stages over time in a regulated river. A stretch of the Guadalquivir River (Southern Spain was selected as the study site. High-resolution orthophotos and LiDAR (Light Detection and Ranging elevations were acquired just after modern floods. They were used for the identification and location of stage indicators. In addition, water gradients were estimated from gauging records, documentary information and paleostage indicators (PSIs in two situations: (i pre-vegetation encroachment; and (ii post-vegetation encroachment due to upstream impoundment. Standard two-dimensional, flow depth-averaged equations over fixed beds were used in the hydraulic modelling. In a first stage, long records of instrumental data at gauging stations and documentary evidence of flood levels served to calibrate the input parameters of the hydraulic model. In a second stage, paleoflood signatures within sedimentary and botanical sequences served to verify the flood stages in the numerical simulations not only at the river reach where instrumental data exist but also in the downstream river reach. Interestingly, the rating curve obtained from the combined use of documentary information and imagery was nearly as accurate as gauging measurements. The thoughtful comparison of 2D modelled hydraulic variables against inferred values from PSIs and instrumental data supports the paleoflood reconstruction method over fixed beds. Vegetation encroachment provoked 10% deeper floods at the water discharge of 2000 m3 · s−1, which implied an increase of Manning’s roughness coefficient from 0.04 to 0.055 s · m−1/3 in less than 15 years.

  8. Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study.

    Science.gov (United States)

    Aschbacher, Kirstin; Adam, Emma K; Crofford, Leslie J; Kemeny, Margaret E; Demitrack, Mark A; Ben-Zvi, Amos

    2012-10-01

    A dynamic systems model was used to generate parameters describing a phenotype of Hypothalamic-Pituitary-Adrenal (HPA) behavior in a sample of 36 patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) and 36 case-matched healthy controls. Altered neuroendocrine function, particularly in relation to somatic symptoms and poor sleep quality, may contribute to the pathophysiology of these disorders. Blood plasma was assayed for cortisol and ACTH every 10 min for 24h. The dynamic model was specified with an ordinary differential equation using three parameters: (1) ACTH-adrenal signaling, (2) inhibitory feedback, and (3) non-ACTH influences. The model was "personalized" by estimating an individualized set of parameters from each participant's data. Day and nighttime parameters were assessed separately. Two nocturnal parameters (ACTH-adrenal signaling and inhibitory feedback) significantly differentiated the two patient subgroups ("fatigue-predominant" patients with CFS only versus "pain-predominant" patients with FM and comorbid chronic fatigue) from controls (all p'sdecreased when more cortisol was produced per unit ACTH, is consistent with cortisol's anti-inflammatory and sleep-modulatory effects. Patients' HPA systems may compensate by promoting more rapid or sustained cortisol production. Mapping "behavioral phenotypes" of stress-arousal systems onto symptom clusters may help disentangle the pathophysiology of complex disorders with frequent comorbidity.

  9. Synergistic Cytotoxicity from Drugs and Cytokines In Vitro as an Approach to Classify Drugs According to Their Potential to Cause Idiosyncratic Hepatotoxicity: A Proof-of-Concept Study.

    Science.gov (United States)

    Maiuri, Ashley R; Wassink, Bronlyn; Turkus, Jonathan D; Breier, Anna B; Lansdell, Theresa; Kaur, Gurpreet; Hession, Sarah L; Ganey, Patricia E; Roth, Robert A

    2017-09-01

    Idiosyncratic drug-induced liver injury (IDILI) typically occurs in a small fraction of patients and has resulted in removal of otherwise efficacious drugs from the market. Current preclinical testing methods are ineffective in predicting which drug candidates have IDILI liability. Recent results suggest that immune mediators such as tumor necrosis factor-α (TNF) and interferon-γ (IFN) interact with drugs that cause IDILI to kill hepatocytes. This proof-of-concept study was designed to test the hypothesis that drugs can be classified according to their ability to cause IDILI in humans using classification modeling with covariates derived from concentration-response relationships that describe cytotoxic interaction with cytokines. Human hepatoma (HepG2) cells were treated with drugs associated with IDILI or with drugs lacking IDILI liability and cotreated with TNF and/or IFN. Detailed concentration-response relationships were determined for calculation of parameters such as the maximal cytotoxic effect, slope, and EC50 for use as covariates for classification modeling using logistic regression. These parameters were incorporated into multiple classification models to identify combinations of covariates that most accurately classified the drugs according to their association with human IDILI. Of 14 drugs associated with IDILI, almost all synergized with TNF to kill HepG2 cells and were successfully classified by statistical modeling. IFN enhanced the toxicity mediated by some IDILI-associated drugs in the presence of TNF. In contrast, of 10 drugs with little or no IDILI liability, none synergized with inflammatory cytokines to kill HepG2 cells and were classified accordingly. The resulting optimal model classified the drugs with extraordinary selectivity and specificity. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  10. FLEX-TOPO: Proof of concept in a central European landscape

    Science.gov (United States)

    Gharari, Shervan; Hrachowitz, Markus; Fenicia, Fabrizio; Gao, Hongkai; Euser, Tanja; Savenije, Huub

    2013-04-01

    Landscape classification into meaningful hydrological units has important implications for hydrological modeling. Conceptual hydrological models, such as HBV-type models, are most commonly designed to represent catchments in a lumped or semi-distributed way at best, i.e. treating them as single entities or sometimes accounting for topographical and land cover variability by introducing some level of stratification. Moreover, such models often combine different dominant runoff mechanisms (such as Hortonian overland flow, saturation overland flow and rapid subsurface flow) into one mechanism, so as to avoid large numbers of parameters. These oversimplifications can frequently lead to substantial misrepresentations of flow generating processes in the catchments in question, as feedback processes between topography, land cover and hydrology in different landscape units can arguably lead to distinct hydrological patterns. By making use of readily available topographical information, hydrological units can be identified based on the concept of "Height above Nearest Drainage" (HAND; Rennó et al., 2008; Nobre et al., 2011). These hydrological units are characterized by different hydrological behavior with different dominant runoff generating mechanisms and can thus be assigned different model structures (Savenije, 2010). In this study we classified the Wark Catchment in Grand Duchy of Luxembourg into three distinct landscape units: plateau, wetland and hillslope, on the basis of a 5×5 m2 DEM. A revised and extended version of HAND gave preliminary estimates of uncertainty in the landscape unit identification as they were implemented in a stochastic framework. As the transition thresholds between the landscape units are a priori unknown, they were calibrated against landscape units observed in the field using a single probability based objective function. As a result, each grid cell of the DEM was characterized by a certain probability of being a certain landscape unit

  11. First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced (44)Sc-DOTATOC: A Proof-of-Concept Study.

    Science.gov (United States)

    Singh, Aviral; van der Meulen, Nicholas P; Müller, Cristina; Klette, Ingo; Kulkarni, Harshad R; Türler, Andreas; Schibli, Roger; Baum, Richard P

    2017-05-01

    (44)Sc is a promising positron emission tomography (PET) radionuclide (T1/2 = 4.04 hours, Eβ+average = 632 keV) and can be made available, using a cyclotron production route, in substantial quantities as a highly pure product. Herein, the authors report on a first-in-human PET/CT study using (44)Sc-DOTATOC prepared with cyclotron-produced (44)Sc. The production of (44)Sc was carried out through the (44)Ca(p,n)(44)Sc nuclear reaction at Paul Scherrer Institut, Switzerland. After separation, (44)Sc was shipped to Zentralklinik Bad Berka, Germany, where radiolabeling was performed, yielding radiochemically pure (44)Sc-DOTATOC. Two patients, currently followed up after peptide receptor radionuclide therapy of metastatic neuroendocrine neoplasms, participated in this proof-of-concept study. Blood sampling was performed before and after application of (44)Sc-DOTATOC. PET/CT acquisitions, performed at different time points after injection of (44)Sc-DOTATOC, allowed detection of even very small lesions on delayed scans. No clinical adverse effects were observed and the laboratory hematological, renal, and hepatic profiles remained unchanged. In this study, cyclotron-produced (44)Sc was used in the clinic for the first time. It is attractive for theranostic application with (177)Lu, (90)Y, or (47)Sc as therapeutic counterparts. (44)Sc-based radiopharmaceuticals will be of particular value for PET facilities without radiopharmacy, to which they can be shipped from a centralized production site.

  12. A proof-of-concept evaluation of a cloud-based store-and-forward telemedicine app for screening for oral diseases.

    Science.gov (United States)

    Estai, Mohamed; Kanagasingam, Yogesan; Xiao, Di; Vignarajan, Janardhan; Huang, Boyan; Kruger, Estie; Tennant, Marc

    2016-09-01

    It is widely considered that telemedicine can make positive contributions to dental practice. This study aimed to evaluate a cloud-based telemedicine application for screening for oral diseases. A telemedicine system, based on a store-and-forward method, was developed to work as a platform for data storage. An Android application was developed to facilitate entering demographic details and capturing oral photos. As a proof-of-concept, six volunteers were enrolled in a trial to obtain oral images using smartphone cameras. Following an onsite oral examination, images of participants' teeth were obtained by a trained dental assistant. Oral images were directly uploaded from the smartphone to a cloud-based server via broadband network. The assessments of oral images by offsite dentists were compared with those carried out via face-to-face oral examinations. A complete set of 30 oral images was obtained from all six participants. Out of 192 teeth reviewed, the proportion of ungradable teeth was 8%. Sensitivity and specificity of teledental screening were 57% and 100% respectively. The inter-grader agreement estimated for two examination modalities and between two teledental graders was 70% and 62% respectively. Findings indicate that the proposed system for screening of oral diseases can be implemented to provide a valid and reliable alternative to traditional oral screening. This study provided evidence that a robust system for store-and-forward screening for dental problems can be developed, and leads to the need for further testing of its robustness to confirm the accuracy and reliability of the teledentistry system. © The Author(s) 2015.

  13. Axono-cortical evoked potentials: A proof-of-concept study.

    Science.gov (United States)

    Mandonnet, E; Dadoun, Y; Poisson, I; Madadaki, C; Froelich, S; Lozeron, P

    2016-04-01

    Awake surgery is currently considered the best method to tailor intraparenchymatous resections according to functional boundaries. However, the exact mechanisms by which electrical stimulation disturbs behavior remain largely unknown. In this case report, we describe a new method to explore the propagation toward cortical sites of a brief pulse applied to an eloquent white matter pathway. We present a patient, operated on in awake condition for removal of a cavernoma of the left ventral premotor cortex. At the end of the resection, the application of 60Hz stimulation in the white matter of the operculum induced anomia. Stimulating the same site at a frequency of 1Hz during 70seconds allowed to record responses on electrodes put over Broca's area and around the inferior part of central sulcus. Axono-cortical evoked potentials were then obtained by averaging unitary responses, time-locked to the stimulus. We then discuss the origin of these evoked axono-cortical potentials and the likely pathway connecting the stimulation site to the recorded cortical sites.

  14. Proof-of-concept development of PXAMS (projectile x-ray accelerator mass spectrometry)

    Energy Technology Data Exchange (ETDEWEB)

    Proctor, I.D.; Roberts, M.L.; McAninch, J.E.; Bench, G.S.

    1996-03-01

    Prior to the current work, accelerator mass spectrometry (AMS) was limited to a set of {approximately}8--10 isotopes. This limitation is caused primarily by the inability to discriminate against stable atomic isobars. An analysis scheme that combines the isotopic sensitivity of AMS with similar isobar selectivity would open a large new class of isotope applications. This project was undertaken to explore the use of characteristic x rays as a method for the detection and identification of ions,and to allow the post-spectrometer rejection of isobaric interferences for isotopes previously inaccessible to AMS. During the second half of FY94 (with Advanced Concepts funding from the Office of Non-Proliferation and National Security), we examined the feasability of this technique, which we are referring to as PXAMS (Projectile X ray AMS), to the detection of several isotopes at Lawrence Livermore National Laboratory (LLNL). In our first exploratory work, we measured the x ray yield vs energy for {sup 80}Se ions stopped in a thick Y target. These results, demonstrated that useful detection efficiencies could be obtained for Se ions at energies accessible with our accelerator, and that the count rate from target x rays is small compared to the Se K{alpha} rate. We followed these measurements with a survey of x ray yields for Z = 14-46.

  15. Proof-of-Concept of the Phytoimmobilization Technology for TNX Outfall Delta: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, D.I.

    2001-06-04

    A series of proof-of-principle studies was initiated to evaluate the soil remediation technology, phytoimmobilization, for application at the TNX Outfall Delta (TNX OD) operable unit. Phytoimmobilization involves two steps. The first step is entitled phytoextraction, and it takes place mostly during the spring and summer. During this step the plants extract contaminants from the sediment into the roots and then translocate the contaminants to the aboveground plant parts. The second step is referred to as sequestration and it takes place largely during the autumn and winter when annual plants senesce or deciduous trees drop their leaves. This step involves the immobilization of the contaminant once it leaches form the fallen leaves into a ''geomat,'' a geotextile embedded with mineral sequestering agents. This final report describes the results to date, including those reported in the status report (Kaplan et al. 2000a), those completed since the report was issued, and the preliminary calculations of the phytoimmobilization effectiveness.

  16. Reversing Antisense Oligonucleotide Activity with a Sense Oligonucleotide Antidote: Proof of Concept Targeting Prothrombin.

    Science.gov (United States)

    Crosby, Jeff R; Zhao, Chenguang; Zhang, Hong; MacLeod, A Robert; Guo, Shuling; Monia, Brett P

    2015-12-01

    The tissue half-life of second-generation antisense oligonucleotide drugs (ASOs) is generally longer than traditional small molecule therapeutics. Thus, a strategy to reverse the activity of antisense drugs is warranted in certain settings. In this study, we describe a strategy employing the administration of a complementary sense oligonucleotide antidote (SOA). As a model system we have chosen to target the coagulation factor and antithrombotic drug target, prothrombin, to assess the feasibility of this approach. ASO targeting mouse prothrombin specifically suppressed >90% hepatic prothrombin mRNA levels and circulating prothrombin protein in mice. These effects were dose- and time-dependent, and as expected produced predictable increases in anticoagulation activity [prothrombin time/activated partial thromboplastin time (PT/aPTT)]. Treatment with prothrombin SOAs resulted in a dose-dependent reversal of ASO activity, as measured by a return in prothrombin mRNA levels and thrombin activity, and normalization of aPTT and PT. The antithrombotic activity of prothrombin ASOs was demonstrated in a FeCl3-induced thrombosis mouse model, and as predicted for this target, the doses required for antithrombotic activity were also associated with increased bleeding. Treatment with SOA was able to prevent prothrombin ASO-induced bleeding in a dose-dependent manner. These studies demonstrate for the first time the utility of SOAs to selectively and specifically reverse the intracellular effects of an antisense therapy.

  17. Closed Crawl Space Performance: Proof of Concept in the Production Builder Marketplace

    Energy Technology Data Exchange (ETDEWEB)

    Malkin-Weber, Melissa; Dastur, Cyrus; Mauceri, Maria; Hannas, Benjamin

    2008-10-30

    performance characteristics with regard to infiltration and duct leakage. Researchers settled on two closed crawl space designs, one with insulation located in the framed floor structure above the crawl space and one with insulation on the crawl space perimeter wall, as the designs with the most widespread potential for application. Researchers based this assessment not only on the field performance, but also on input from residential builders, pest control professionals, code officials, installers, and building scientists active in the region. The key findings from the field demonstration were that (1) closed crawl spaces stay substantially drier than traditional wall-vented crawl spaces during humid climate conditions, and (2) the houses built on the closed crawl space foundations saved, on average, 15% or more on annual energy used for space heating and cooling. A comparison of the actual energy performance of the homes versus the performance predicted by a popular HERS software application showed that the software was unable to predict the demonstrated savings, in some cases predicting an energy penalty. Findings from the 2005 project were summarized in a publication titled Closed Crawl Spaces: An Introduction to Design, Construction and Performance. Since its release, the publication has received widespread use by builders, homeowners, installers and code officials concerned about crawl space construction. The findings were also used to create major revisions to the NC Residential Code, which were adopted in 2004 and immediately began to reduce the regulatory barriers to widespread commercialization of the technology in NC, particularly in new residential construction. Full project details are located at www.crawlspaces.org.

  18. Inductive heating kills cells that contribute to plaque: a proof-of-concept

    Directory of Open Access Journals (Sweden)

    Angelo Gaitas

    2015-04-01

    Full Text Available Inducing cell death by heating targeted particles shows promise in cancer treatment. Here, we aim to demonstrate the feasibility of extending the use of this technique to treat and remove vascular deposits and thrombosis. We used induction heating of macrophages, which are key contributors to atherosclerosis and have demonstrated clear feasibility for heating and destroying these cells using ferromagnetic and pure iron particles. Specifically, iron particles achieved maximum temperatures of 51 ± 0.5 °C and spherical particles achieved a maximum temperature of 43.9 ± 0.2 °C (N = 6 after 30 min of inductive heating. Two days of subsequent observation demonstrated that inductive heating led to a significant reduction in cell number. Prior to induction heating, cell density was 105,000 ± 20,820 cells/ml (N = 3. This number was reduced to 6,666 ± 4,410 cells/ml for the spherical particles and 16,666 ± 9,280 cells/ml for the iron particles 24 h after inductive heating. Though cell density increased on the second day following inductive heating, the growth was minimal. Cells grew to 26,667 ± 6,670 cells/ml and 30,000 ± 15,280 cells/ml respectively. Compared to cell cultures with iron and spherical particles that were not subjected to induction heating, we observed a 97% reduction in cell count for the spherical particles and a 91% reduction for the iron particles after the first 24 h. After 48 h we observed a 95% reduction in cell growth for both spherical and iron particles. Induction heating of microparticles was thus highly effective in reducing the macrophage population and preventing their growth. These results demonstrate the feasibility of targeting cells involved in atherosclerosis and warrant further research into potential clinical applications.

  19. Inductive heating kills cells that contribute to plaque: a proof-of-concept.

    Science.gov (United States)

    Gaitas, Angelo; Kim, Gwangseong

    2015-01-01

    Inducing cell death by heating targeted particles shows promise in cancer treatment. Here, we aim to demonstrate the feasibility of extending the use of this technique to treat and remove vascular deposits and thrombosis. We used induction heating of macrophages, which are key contributors to atherosclerosis and have demonstrated clear feasibility for heating and destroying these cells using ferromagnetic and pure iron particles. Specifically, iron particles achieved maximum temperatures of 51 ± 0.5 °C and spherical particles achieved a maximum temperature of 43.9 ± 0.2 °C (N = 6) after 30 min of inductive heating. Two days of subsequent observation demonstrated that inductive heating led to a significant reduction in cell number. Prior to induction heating, cell density was 105,000 ± 20,820 cells/ml (N = 3). This number was reduced to 6,666 ± 4,410 cells/ml for the spherical particles and 16,666 ± 9,280 cells/ml for the iron particles 24 h after inductive heating. Though cell density increased on the second day following inductive heating, the growth was minimal. Cells grew to 26,667 ± 6,670 cells/ml and 30,000 ± 15,280 cells/ml respectively. Compared to cell cultures with iron and spherical particles that were not subjected to induction heating, we observed a 97% reduction in cell count for the spherical particles and a 91% reduction for the iron particles after the first 24 h. After 48 h we observed a 95% reduction in cell growth for both spherical and iron particles. Induction heating of microparticles was thus highly effective in reducing the macrophage population and preventing their growth. These results demonstrate the feasibility of targeting cells involved in atherosclerosis and warrant further research into potential clinical applications.

  20. Design of sEMG assembly to detect external anal sphincter activity: a proof of concept.

    Science.gov (United States)

    Shiraz, Arsam; Leaker, Brian; Mosse, Charles Alexander; Solomon, Eskinder; Craggs, Michael; Demosthenous, Andreas

    2017-09-13

    Conditional trans-rectal stimulation of the pudendal nerve could provide a viable solution to treat hyperreflexive bladder in spinal cord injury. A set threshold of the amplitude estimate of the external anal sphincter surface electromyography (sEMG) may be used as the trigger signal. The efficacy of such a device should be tested in a large scale clinical trial. As such a probe should remain in situ for several hours while patients attend to their daily routine, the recording electrodes should be designed to be large enough to maintain good contact while observing design constraints. The objective of this study was to arrive at a design for intra-anal sEMG recording electrodes for the subsequent clinical trials while deriving the possible recording and processing parameters. Approach: Having in mind existing solutions and based on theoretical and anatomical considerations, a set of four multi-electrode probes were designed and developed. These were tested in a healthy subject and the measured sEMG traces were recorded and appropriately processed. Main results: It was shown that while comparatively large electrodes record sEMG traces that are not sufficiently correlated with the external anal sphincter contractions, smaller electrodes may not maintain a stable electrode tissue contact. It was shown that 3 mm wide and 1 cm long electrodes with 5 mm inter-electrode spacing, in agreement with Nyquist sampling, placed 1 cm from the orifice may intra-anally record a sEMG trace sufficiently correlated with external anal sphincter activity. Significance: The outcome of this study can be used in any biofeedback, treatment or diagnostic application where the activity of the external anal sphincter sEMG should be detected for an extended period of time. . © 2017 Institute of Physics and Engineering in Medicine.

  1. A composite autonomic index as unitary metric for heart rate variability: a proof of concept.

    Science.gov (United States)

    Sala, Roberto; Malacarne, Mara; Solaro, Nadia; Pagani, Massimo; Lucini, Daniela

    2017-03-01

    This study addresses whether a unitary cardiac autonomic nervous system index (ANSI), obtained combining multiple metrics from heart rate variability (HRV) into a radar plot could provide an easy appreciation of autonomic performance in a clinical setting. Data are standardized using percentile ranking of autonomic proxies from a relatively large reference population (n = 1593, age 39 ± 13 years). Autonomic indices are obtained from autoregressive spectral analysis of (ECG derived) HRV at rest and during standing up. A reduced ANSI (using RR, RR variance and rest-stand difference of LFnu) is then constructed as a radar plot, quantified according to its combined area and tested against different risk subgroups. With growing risk profile, there is a marked reduction of the rank value of ANSI, quantified individually by the radar plot area. The practical usefulness of the approach was tested in small groups of additional subjects putatively characterized by elevated or poor autonomic performance. Data show that elite endurance athletes are characterized by elevated values of ANSI (80·6 ± 14·9, P values (DM1 = 37·0 ± 18·9 and DM2 = 26·8 ± 23·3, P = 0·002), and patients with coronary artery disease (CAD) represent a nadir (17 ± 20, P < 0·001). This observational study shows the feasibility of testing simpler metrics of cardiac autonomic regulation based on a multivariate unitary index in a preventive setting. This simple approach might foster a wider application of HRV in the clinical arena, and permit an easier appreciation of autonomic performance. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  2. Physics-based gene identification: proof of concept for Plasmodium falciparum.

    Science.gov (United States)

    Yeramian, Edouard; Bonnefoy, Serge; Langsley, Gordon

    2002-01-01

    The ab initio prediction of new genes in eukaryotic genomes represents a difficult task, notably for the identification of complex split genes. A Physics-Based Gene Identification (PBGI) method was formulated recently (Yeramian, Gene, 255, 139-150, 151-168, 2000a,b) to address this problem, taking as a model the Plasmodium falciparum genome. Here, the predictive power of this method is put under experimental test for this genome. The presented results demonstrate the usefulness of the PBGI as a gene-identification tool for P. falciparum, notably for the discovery of new genes with no homology to known genes. Perspectives opened by this new method for other eukaryotic genomes are also mentioned.

  3. ESRD special needs plans: a proof of concept for integrated care.

    Science.gov (United States)

    Krishnan, Mahesh; Franco, Eric; McMurray, Stephen; Petra, Eugene; Nissenson, Allen R

    2014-11-01

    Since the completion of the Centers for Medicare and Medicaid Services' end-stage renal disease (ESRD) demonstration projects, passage of the Affordable Care Act, and announcement of ESRD Seamless Care Organizations (ESCOs) by CMS' Innovation Center, it seems that ESRD-centered accountable care organizations will be the future model for kidney care of Medicare beneficiaries. Regardless of what you call it--managed care organization, special needs plan, ESCO--balancing quality of health care with costs of health care will continue to be the primary directive for physicians and institutions using integrated care management (ICM) strategies to manage their ESRD patients' health. The renal community has had previous success with ICM, and these experiences could help to guide our way.

  4. Inferring regional vertical crustal velocities from averaged relative sea level trends: A proof of concept

    Science.gov (United States)

    Bâki Iz, H.; Shum, C. K.; Zhang, C.; Kuo, C. Y.

    2017-02-01

    This study demonstrates that relative sea level trends calculated from long-term tide gauge records can be used to estimate relative vertical crustal velocities in a region with high accuracy. A comparison of the weighted averages of the relative sea level trends estimated at six tide gauge stations in two clusters along the Eastern coast of United States, in Florida and in Maryland, reveals a statistically significant regional vertical crustal motion of Maryland with respect to Florida with a subsidence rate of -1.15±0.15 mm/yr identified predominantly due to the ongoing glacial isostatic adjustment process. The estimate is a consilience value to validate vertical crustal velocities calculated from GPS time series as well as towards constraining predictive GIA models in these regions.

  5. Catalytic conversion of light alkanes-proof-of-concept stage - Phase IV. Topical report, February 1, 1994--January 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-31

    This report details the research performed on Phase IV of the extended Cooperative Agreement. This Phase, entitled C{sub 1}-C{sub 4} Research, provides the research support which accompanies the C{sub 4} Proof-of-Concept Phase (Phase V) as the two major activities of the Cooperative Agreement during calendar 1993. It is the objective of this phase to understand the nature of the catalysts and catalytic activity of perhaloporphyrin complexes uncovered during Phases I-III in order that superior catalytic materials can be made and tested which meet commercial criteria for the oxidation of the C{sub 1}-C{sub 4} light alkane gases found in natural gas and other available hydrocarbon streams. During Phase IV, we have examined the physical and electronic structures of the very active perhaloporphyrin catalysts which we have developed, and have gained an understanding of the properties which make them active. This has led us to design and synthesize materials which are cheaper, more active, more robust and, in general superior for carrying out practical catalysis. Our early generation perhaloporphyrin catalysts, while exhibiting unprecedented catalytic activity, were far too expensive for use in converting natural gas or its C{sub 1}-C{sub 4} components.

  6. Virtual Reality-Based Attention Bias Modification Training for Social Anxiety: A Feasibility and Proof of Concept Study

    Directory of Open Access Journals (Sweden)

    Antoine eUrech

    2015-10-01

    Full Text Available Attention bias modification (ABM programs have been considered as a promising new approach for the treatment of various disorders, including social anxiety disorder (SAD. However, previous studies yielded ambiguous results regarding the efficacy of ABM in SAD. The present proof-of-concept study investigates the feasibility of a newly developed virtual reality (VR-based dot-probe training paradigm. It was designed to facilitate attentional disengagement from threatening stimuli in socially anxious individuals (N=15. The following outcomes were examined: (a self-reports of enjoyment, motivation, flow and presence, (b attentional bias for social stimuli, and (c social anxiety symptoms. Results showed that ABM training is associated with high scores in enjoyment, motivation, flow and presence. Furthermore, significant improvements in terms of attention bias and social anxiety symptoms were observed from pre- to follow-up assessment. The study suggests that VR is a feasible and presumably a promising new medium for ABM trainings. Controlled studies will need to be carried out.

  7. Multivariate Analysis As a Support for Diagnostic Flowcharts in Allergic Bronchopulmonary Aspergillosis: A Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Joana Vitte

    2017-08-01

    Full Text Available Molecular-based allergy diagnosis yields multiple biomarker datasets. The classical diagnostic score for allergic bronchopulmonary aspergillosis (ABPA, a severe disease usually occurring in asthmatic patients and people with cystic fibrosis, comprises succinct immunological criteria formulated in 1977: total IgE, anti-Aspergillus fumigatus (Af IgE, anti-Af “precipitins,” and anti-Af IgG. Progress achieved over the last four decades led to multiple IgE and IgG(4 Af biomarkers available with quantitative, standardized, molecular-level reports. These newly available biomarkers have not been included in the current diagnostic criteria, either individually or in algorithms, despite persistent underdiagnosis of ABPA. Large numbers of individual biomarkers may hinder their use in clinical practice. Conversely, multivariate analysis using new tools may bring about a better chance of less diagnostic mistakes. We report here a proof-of-concept work consisting of a three-step multivariate analysis of Af IgE, IgG, and IgG4 biomarkers through a combination of principal component analysis, hierarchical ascendant classification, and classification and regression tree multivariate analysis. The resulting diagnostic algorithms might show the way for novel criteria and improved diagnostic efficiency in Af-sensitized patients at risk for ABPA.

  8. Using Expectancy Value Theory as a Framework to Reduce Student Resistance to Active Learning: A Proof of Concept.

    Science.gov (United States)

    Cooper, Katelyn M; Ashley, Michael; Brownell, Sara E

    2017-01-01

    There has been a national movement to transition college science courses from passive lectures to active learning environments. Active learning has been shown to be a more effective way for students to learn, yet there is concern that some students are resistant to active learning approaches. Although there is much discussion about student resistance to active learning, few studies have explored this topic. Furthermore, a limited number of studies have applied theoretical frameworks to student engagement in active learning. We propose using a theoretical lens of expectancy value theory to understand student resistance to active learning. In this study, we examined student perceptions of active learning after participating in 40 hours of active learning. We used the principal components of expectancy value theory to probe student experience in active learning: student perceived self-efficacy in active learning, value of active learning, and potential cost of participating in active learning. We found that students showed positive changes in the components of expectancy value theory and reported high levels of engagement in active learning, which provide proof of concept that expectancy value theory can be used to boost student perceptions of active learning and their engagement in active learning classrooms. From these findings, we have built a theoretical framework of expectancy value theory applied to active learning.

  9. Using Drainage Slots in Permeable Paving Blocks to Delay the Effects of Clogging: Proof of Concept Study

    Directory of Open Access Journals (Sweden)

    Terry Lucke

    2014-09-01

    Full Text Available Permeable interlocking concrete pavements (PICP are specifically designed to remove sediment and other pollutants from stormwater runoff. Over time, this can lead to clogging of the PICP system. Previous research has shown that much of the clogging occurs on the bedding aggregate directly below the paving joints, while the remainder of the aggregate is unaffected. This paper describes a proof of concept study to delay the effects of clogging by making more efficient use of the bedding aggregate used in PICP systems. Lateral drainage slots were cut into the underside of PICP blocks to allow sediment-laden stormwater to access, and be filtered by, a greater surface area of bedding aggregate. Eight different slot designs were trialed in the study to determine which of the slot designs made the most efficient use of the bedding aggregate to filter the sediment from the stormwater. The study results demonstrated that the eight drainage slot designs deposited between 25% and 366% more sediment (by weight beneath the pavers than the control pavement. The results of the study suggest that PICP systems with drainage slots cast into their bases would take much longer to clog than unmodified pavers, thereby proving the concept of this study.

  10. Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers

    Science.gov (United States)

    Modabbernia, A.; Velthorst, E.; Gennings, C.; De Haan, L.; Austin, C.; Sutterland, A.; Mollon, J.; Frangou, S.; Wright, R.; Arora, M.; Reichenberg, A.

    2016-01-01

    Background Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia. Methods We analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb2+), manganese (Mn2+), cadmium (Cd2+), copper (Cu2+), magnesium (Mg2+), and zinc (Zn2+), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry. Results We found higher early-life Pb2+ exposure among patients with schizophrenia than controls. The differences in log Mn2+ and log Cu2+ changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb2+ levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb2+ levels and adult IQ. Conclusions In our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis. PMID:27311101

  11. Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man.

    Science.gov (United States)

    Bukara, Katarina; Schueller, Laurent; Rosier, Jan; Martens, Mark A; Daems, Tinne; Verheyden, Loes; Eelen, Siemon; Van Speybroeck, Michiel; Libanati, Cristian; Martens, Johan A; Van Den Mooter, Guy; Frérart, Françoise; Jolling, Koen; De Gieter, Marjan; Bugarski, Branko; Kiekens, Filip

    2016-11-01

    Formulating poorly water soluble drugs using ordered mesoporous silica materials is an emerging approach to tackle solubility-related bioavailability problems. The current study was conducted to assess the bioavailability-enhancing potential of ordered mesoporous silica in man. In this open-label, randomized, two-way cross-over study, 12 overnight fasted healthy volunteers received a single dose of fenofibrate formulated with ordered mesoporous silica or a marketed product based on micronized fenofibrate. Plasma concentrations of fenofibric acid, the pharmacologically active metabolite of fenofibrate, were monitored up to 96h post-dose. The rate (Cmax/dose increased by 77%; tmax reduced by 0.75h) and extent of absorption (AUC0-24h/dose increased by 54%) of fenofibrate were significantly enhanced following administration of the ordered mesoporous silica based formulation. The results of this study serve as a proof of concept in man for this novel formulation approach. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Knowledge management in secondary pharmaceutical manufacturing by mining of data historians-A proof-of-concept study.

    Science.gov (United States)

    Meneghetti, Natascia; Facco, Pierantonio; Bezzo, Fabrizio; Himawan, Chrismono; Zomer, Simeone; Barolo, Massimiliano

    2016-05-30

    In this proof-of-concept study, a methodology is proposed to systematically analyze large data historians of secondary pharmaceutical manufacturing systems using data mining techniques. The objective is to develop an approach enabling to automatically retrieve operation-relevant information that can assist the management in the periodic review of a manufactory system. The proposed methodology allows one to automatically perform three tasks: the identification of single batches within the entire data-sequence of the historical dataset, the identification of distinct operating phases within each batch, and the characterization of a batch with respect to an assigned multivariate set of operating characteristics. The approach is tested on a six-month dataset of a commercial-scale granulation/drying system, where several millions of data entries are recorded. The quality of results and the generality of the approach indicate that there is a strong potential for extending the method to even larger historical datasets and to different operations, thus making it an advanced PAT tool that can assist the implementation of continual improvement paradigms within a quality-by-design framework.

  13. A label-free detector for liquid chromatography systems using mm-wave technology: First proof of concept.

    Science.gov (United States)

    Zhang, Y; Declerck, S; Mangelings, D; He, G; Matvejev, V; Vander Heyden, Y; Stiens, J

    2017-08-08

    The development of millimeter-wave (mm-wave) technology has enabled the study of bio-molecular interactions by means of electromagnetic waves with frequencies between 30 and 300GHz. In this study, an attempt has been made to exploit the possibility of mm-wave technology as alternative detection technique for liquid chromatographic (LC) systems. The goal is to design and fabricate a label-free mm-wave detector that is compatible with LC systems. As proof-of-concept experiments, the UV absorbing compounds praziquantel and trans-stilbene-oxide as well as a non-UV absorbing compound sorbitol are injected in an open capillary as well as a capillary with stationary phase and measured by both mm-wave and UV detectors. The in-house developed mm-wave detector is capable of detecting all compounds without the need for labelling. Although the detection limit of such detector still needs to be verified and occasionally improved in the future, it already shows great potential as an additional detection technique for LC systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Multivariate Analysis As a Support for Diagnostic Flowcharts in Allergic Bronchopulmonary Aspergillosis: A Proof-of-Concept Study.

    Science.gov (United States)

    Vitte, Joana; Ranque, Stéphane; Carsin, Ania; Gomez, Carine; Romain, Thomas; Cassagne, Carole; Gouitaa, Marion; Baravalle-Einaudi, Mélisande; Bel, Nathalie Stremler-Le; Reynaud-Gaubert, Martine; Dubus, Jean-Christophe; Mège, Jean-Louis; Gaudart, Jean

    2017-01-01

    Molecular-based allergy diagnosis yields multiple biomarker datasets. The classical diagnostic score for allergic bronchopulmonary aspergillosis (ABPA), a severe disease usually occurring in asthmatic patients and people with cystic fibrosis, comprises succinct immunological criteria formulated in 1977: total IgE, anti-Aspergillus fumigatus (Af) IgE, anti-Af "precipitins," and anti-Af IgG. Progress achieved over the last four decades led to multiple IgE and IgG(4) Af biomarkers available with quantitative, standardized, molecular-level reports. These newly available biomarkers have not been included in the current diagnostic criteria, either individually or in algorithms, despite persistent underdiagnosis of ABPA. Large numbers of individual biomarkers may hinder their use in clinical practice. Conversely, multivariate analysis using new tools may bring about a better chance of less diagnostic mistakes. We report here a proof-of-concept work consisting of a three-step multivariate analysis of Af IgE, IgG, and IgG4 biomarkers through a combination of principal component analysis, hierarchical ascendant classification, and classification and regression tree multivariate analysis. The resulting diagnostic algorithms might show the way for novel criteria and improved diagnostic efficiency in Af-sensitized patients at risk for ABPA.

  15. Polymeric microcapsules with switchable mechanical properties for self-healing concrete: synthesis, characterisation and proof of concept

    Science.gov (United States)

    Kanellopoulos, A.; Giannaros, P.; Palmer, D.; Kerr, A.; Al-Tabbaa, A.

    2017-04-01

    Microcapsules, with sodium silicate solution as core, were produced using complex coacervation in a double, oil-in-water-in oil, emulsion system. The shell material was a gelatin-acacia gum crosslinked coacervate and the produced microcapsules had diameters ranging from 300 to 700 μm. The shell material designed with switchable mechanical properties. When it is hydrated exhibits soft and ‘rubbery’ behaviour and, when dried, transitions to a stiff and ‘glassy’ material. The microcapsules survived drying and rehydrating cycles and preserved their structural integrity when exposed to highly alkaline solutions that mimic the pH environment of concrete. Microscopy revealed that the shell thickness of the microcapsules varies across their perimeter from 5 to 20 μm. Thermal analysis showed that the produced microcapsules were very stable up to 190 °C. Proof of concept investigation has demonstrated that the microcapsules successfully survive and function when exposed to a cement-based matrix. Observations showed that the microcapsules survive mixing with cement and rupture successfully upon crack formation releasing the encapsulated sodium silicate solution.

  16. Targeting pain catastrophization in patients with fibromyalgia using virtual reality exposure therapy: a proof-of-concept study.

    Science.gov (United States)

    Morris, Linzette Deidrè; Louw, Quinette Abegail; Grimmer, Karen Anne; Meintjes, Ernesta

    2015-11-01

    [Purpose] Pain catastrophizing is a key predictor of poor compliance to exercises among patients with fibromyalgia syndrome. Alteration of pain catastrophizing in this group is thus warranted. This study aimed to provide proof-of-concept of a novel virtual reality exposure therapy program as treatment for exercise-related pain catastrophizing in patients with fibromyalgia syndrome. [Subjects and Methods] An exploratory, case-controlled study was conducted (fibromyalgia syndrome group and matched control group). Functional magnetic resonance imaging was used to acquire neural correlates. The functional magnetic resonance imaging task consisted of two stimuli: active (exercise activity visuals) and passive (relaxing visuals). Structural images and blood-oxygenation-level-dependent contrasts were acquired for the conditions and compared within subjects/groups and between groups. Statistic images were thresholded using corrected clusters (determined by Z>2.3; level of significance: 0.05). [Results] Thirteen fibromyalgia syndrome subjects and nine healthy matched controls were included. The right inferior frontal gyrus, right middle frontal gyrus, right posterior cerebellum, left thalamus, and left supramarginal gyrus were activated in the fibromyalgia syndrome subjects. [Conclusion] The study results provide preliminary proof indicating that exposing patients with fibromyalgia syndrome to visuals of exercises elicits neurophysiological changes in functional brain areas associated with pain catastrophization and add to the current body of knowledge regarding the possibility of objectively identifying cognitive behavioral strategies like pain catastrophization.

  17. Virtual Reality-Based Attention Bias Modification Training for Social Anxiety: A Feasibility and Proof of Concept Study.

    Science.gov (United States)

    Urech, Antoine; Krieger, Tobias; Chesham, Alvin; Mast, Fred W; Berger, Thomas

    2015-01-01

    Attention bias modification (ABM) programs have been considered as a promising new approach for the treatment of various disorders, including social anxiety disorder (SAD). However, previous studies yielded ambiguous results regarding the efficacy of ABM in SAD. The present proof-of-concept study investigates the feasibility of a newly developed virtual reality (VR)-based dot-probe training paradigm. It was designed to facilitate attentional disengagement from threatening stimuli in socially anxious individuals (N = 15). The following outcomes were examined: (a) self-reports of enjoyment, motivation, flow, and presence; (b) attentional bias for social stimuli; and (c) social anxiety symptoms. Results showed that ABM training is associated with high scores in enjoyment, motivation, flow, and presence. Furthermore, significant improvements in terms of attention bias and social anxiety symptoms were observed from pre- to follow-up assessment. The study suggests that VR is a feasible and presumably a promising new medium for ABM trainings. Controlled studies will need to be carried out.

  18. Transpapillary (Nipple) Delivery of Macromolecules to the Breast: Proof of Concept Study.

    Science.gov (United States)

    Dave, Kaushalkumar; Alsharif, Fahd M; Perumal, Omathanu

    2016-11-07

    Localized drug delivery to the breast can maximize drug concentration at the target site and minimize systemic drug distribution. To this end, the study explored the feasibility of delivering macromolecules to the breast through mammary papilla (nipple). The in vitro penetration of model macromolecules (inulin, dextran, ovalbumin, and bovine serum albumin) varying in molecular weight from 5 to 67 kDa was studied using excised porcine and human mammary papilla. The penetration of macromolecules decreased with increase in molecular weight. The penetration of the macromolecules was significantly higher through the mammary papilla in comparison to breast skin. In vitro penetration of the macromolecules was similar in human and porcine mammary papilla. Iontophoresis was used to enhance the transport of bovine serum albumin (BSA) through the mammary papilla. The flux and cumulative amount permeated was increased by 2- to 4-fold by iontophoresis. The macromolecules were transported through the ducts and the surrounding connective tissue in the mammary papilla. Overall, the results from this study for the first time demonstrate the feasibility of delivering macromolecules through the mammary papilla. These findings have implications for developing safe and effective localized therapeutic approaches for breast cancer.

  19. Proof of Concept of a Tracheoesophageal Voice Prosthesis Insufflator for Speech Production After Total Laryngectomy.

    Science.gov (United States)

    Starmer, Heather; Taylor, Russell H; Noureldine, Salem I; Richmon, Jeremy D

    2017-07-01

    There may have a variety of reasons why patients are unable to produce tracheoesophageal speech after total laryngectomy (TL) including poor pulmonary reserve or other comorbidities that prevent adequate stoma occlusion and intratracheal pressure to voice. Other patients find it difficult, uncomfortable, or socially awkward to manually occlude the stoma with the finger or thumb. The study aimed to assess the feasibility of achieving TE speech with a prototype TE voice prosthesis insufflator (TEVPI). We prospectively assessed the feasibility of achieving TE speech with a commercially available continuous positive airway pressure device in six TL patients. The intervention is the use of a prototype TEVPI. A battery of acoustic and perceptual metrics were obtained and compared between TEVPI speech and standard tracheoesophageal voice prosthesis (TEVP) speech. Voicing was accomplished with the TEVPI in five of six participants. On average, the duration of phonation with TEVPI was shorter, not as loud, and perceived to be more difficult to produce compared to TEVP speech. The TEVPI is a feasible, hands-free solution for restoring speech after TL. Although the current model produced inferior acoustic metrics compared with standard TEVP speech, further modification and refinement of the device has the potential to produce much improved speech. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  20. Point-of-care vertical flow allergen microarray assay: proof of concept.

    Science.gov (United States)

    Chinnasamy, Thiruppathiraja; Segerink, Loes I; Nystrand, Mats; Gantelius, Jesper; Andersson Svahn, Helene

    2014-09-01

    Sophisticated equipment, lengthy protocols, and skilled operators are required to perform protein microarray-based affinity assays. Consequently, novel tools are needed to bring biomarkers and biomarker panels into clinical use in different settings. Here, we describe a novel paper-based vertical flow microarray (VFM) system with a multiplexing capacity of at least 1480 microspot binding sites, colorimetric readout, high sensitivity, and assay time of Affinity binders were deposited on nitrocellulose membranes by conventional microarray printing. Buffers and reagents were applied vertically by use of a flow controlled syringe pump. As a clinical model system, we analyzed 31 precharacterized human serum samples using the array system with 10 allergen components to detect specific IgE reactivities. We detected bound analytes using gold nanoparticle conjugates with assay time of ≤10 min. Microarray images were captured by a consumer-grade flatbed scanner. A sensitivity of 1 ng/mL was demonstrated with the VFM assay with colorimetric readout. The reproducibility (CV) of the system was affinity point-of-care testing. © 2014 American Association for Clinical Chemistry.

  1. Proof-of-Concept Demonstrations of a Flight Adjustment Logging and Communication Network

    Science.gov (United States)

    Underwood, Matthew C.; Merlino, Daniel K.; Carboneau, Lindsey M.; Wilson, C. Logan; Wilder, Andrew J.

    2016-01-01

    The National Airspace System is a highly complex system of systems within which a number of participants with widely varying business and operating models exist. From the airspace user's perspective, a means by which to operate flights in a more flexible and efficient manner is highly desired to meet their business objectives. From the air navigation service provider's viewpoint, there is a need for increasing the capacity of the airspace, while maintaining or increasing the levels of efficiency and safety that currently exist in order to meet the charter under which they operate. Enhancing the communication between airspace operators and users is essential in order to meet these demands. In the spring of 2015, a prototype system that implemented an airborne tool to optimize en-route flight paths for fuel and time savings was designed and tested. The system utilized in-flight Internet as a high-bandwidth data link to facilitate collaborative decision making between the flight deck and an airline dispatcher. The system was tested and demonstrated in a laboratory environment, as well as in-situ. Initial results from these tests indicate that this system is not only feasible, but could also serve as a growth path and testbed for future air traffic management concepts that rely on shared situational awareness through data exchange and electronic negotiation between multiple entities operating within the National Airspace System.

  2. A rod type linear ultrasonic motor utilizing longitudinal traveling waves: proof of concept

    Science.gov (United States)

    Wang, Liang; Wielert, Tim; Twiefel, Jens; Jin, Jiamei; Wallaschek, Jörg

    2017-08-01

    This paper proposes a non-resonant linear ultrasonic motor utilizing longitudinal traveling waves. The longitudinal traveling waves in the rod type stator are generated by inducing longitudinal vibrations at one end of the waveguide and eliminating reflections at the opposite end by a passive damper. Considering the Poisson’s effect, the stator surface points move on elliptic trajectories and the slider is driven forward by friction. In contrast to many other flexural traveling wave linear ultrasonic motors, the driving direction of the proposed motor is identical to the wave propagation direction. The feasibility of the motor concept is demonstrated theoretically and experimentally. First, the design and operation principle of the motor are presented in detail. Then, the stator is modeled utilizing the transfer matrix method and verified by experimental studies. In addition, experimental parameter studies are carried out to identify the motor characteristics. Finally, the performance of the proposed motor is investigated. Overall, the results indicate very dynamic drive characteristics. The motor prototype achieves a maximum mean velocity of 115 mm s-1 and a maximum load of 0.25 N. Thereby, the start-up and shutdown times from the maximum speed are lower than 5 ms.

  3. Development and proof-of-concept of three-dimensional lung histology volumes

    Science.gov (United States)

    Mathew, Lindsay; Alabousi, Mostafa; Wheatley, Andrew; Aladl, Usaf; Slipetz, Deborah; Hogg, James C.; Fenster, Aaron; Parraga, Grace

    2012-03-01

    Most medical imaging is inherently three-dimensional (3D) but for validation of pathological findings, histopathology is commonly used and typically histopathology images are acquired as twodimensional slices with quantitative analysis performed in a single dimension. Histopathology is invasive, labour-intensive, and the analysis cannot be performed in real time, yet it remains the gold standard for the pathological diagnosis and validation of clinical or radiological diagnoses of disease. A major goal worldwide is to improve medical imaging resolution, sensitivity and specificity to better guide therapy and biopsy and to one day delay or replace biopsy. A key limitation however is the lack of tools to directly compare 3D macroscopic imaging acquired in patients with histopathology findings, typically provided in a single dimension (1D) or in two dimensions (2D). To directly address this, we developed methods for 2D histology slice visualization/registration to generate 3D volumes and quantified tissue components in the 3D volume for direct comparison to volumetric micro-CT and clinical CT. We used the elastase-instilled mouse emphysema lung model to evaluate our methods with murine lungs sectioned (5 μm thickness/10 μm gap) and digitized with 2μm in-plane resolution. 3D volumes were generated for wildtype and elastase mouse lung sections after semi-automated registration of all tissue slices. The 1D mean linear intercept (Lm) for wildtype (WT) (47.1 μm +/- 9.8 μm) and elastase mouse lung (64.5 μm +/- 14.0 μm) was significantly different (p<.001). We also generated 3D measurements based on tissue and airspace morphometry from the 3D volumes and all of these were significantly different (p<.0001) when comparing elastase and WT mouse lung. The ratio of the airspace-to-lung volume for the entire lung volume was also significantly and strongly correlated with Lm.

  4. SSRI Augmentation by 5-Hydroxytryptophan Slow Release: Mouse Pharmacodynamic Proof of Concept

    Science.gov (United States)

    Jacobsen, Jacob PR; Rudder, Meghan L; Roberts, Wendy; Royer, Elizabeth L; Robinson, Taylor J; Oh, Adrianna; Spasojevic, Ivan; Sachs, Benjamin D; Caron, Marc G

    2016-01-01

    Drugs, notably SSRIs, that elevate brain extracellular 5-HT (5-HTExt) are antidepressants. Unfortunately, most patients fail to remit. Multipronged clinical evidence suggests that elevating 5-HTExt beyond the SSRI effect enhances antidepressant efficacy, but previous such drug strategies had prohibitive limitations. In humans, adjunct treatment with the 5-HT precursor 5-hydroxytryptophan (5-HTP) elevates 5-HTExt beyond the SSRI effect. Small pilot trials suggest that adjunct 5-HTP can confer antidepressant response in treatment-resistant depression (TRD). However, sustained, stable 5-HTExt elevation is required for antidepressant effect; therefore, the rapid absorption and elimination of standard 5-HTP immediate release (IR) likely curtail 5-HTP IR's antidepressant potential. Slow-release (SR) drug delivery can crucially improve efficacy and safety of rapidly absorbed and eliminated compounds. Here we tested in mice the hypothesis that SR delivery will substantially improve 5-HTP's drug properties, by minimizing adverse effects and securing sustained 5-HTExt elevation beyond the SSRI effect. We modeled 5-HTP SR with minipumps, 5-HTP IR with injections, and chronic SSRI with dietary fluoxetine. We tested adjunct 5-HTP SR in wild-type mice and in mice with low brain 5-HT owing to expression of a mutant form of the brain 5-HT synthesis enzyme, tryptophan hydroxylase 2. In both lines of mice, adjunct 5-HTP SR synergized with SSRI to elevate 5-HTExt beyond the SSRI effect. We observed no adverse effect. Adjunct 5-HTP IR could not produce this therapy-like profile, producing transient 5-HTExt spikes and marked adverse effects. Integrated with a body of clinical data, our mouse data suggest that an adjunct 5-HTP SR drug could safely and effectively elevate 5-HTExt beyond the SSRI effect and represent a novel treatment for TRD. PMID:26932820

  5. Evaluation of a novel multi-articulated endoscope: proof of concept through a virtual simulation.

    Science.gov (United States)

    Karvonen, Tuukka; Muranishi, Yusuke; Yamamoto, Goshiro; Kuroda, Tomohiro; Sato, Toshihiko

    2017-07-01

    In endoscopic surgery such as video-assisted thoracoscopic surgery and laparoscopic surgery, providing the surgeon a good view of the target is important. Rigid endoscope has for years been the go-to tool for this purpose, but it has certain limitations like the inability to work around obstacles. To improve on current tools, a novel multi-articulated endoscope (MAE) is currently under development. To investigate its feasibility and possible value, we performed a user test using virtual prototype of the MAE with the intent to show that it outperforms the conventional endoscope while bringing minimal additional burden to the operator. To evaluate the prototype, we built a virtual model of the MAE and a rigid oblique-viewing endoscope. Through a comparative user study we evaluate the ability of each device to visualize certain targets placed inside the virtual chest cavity by the angle between the visual axis of the scope and the normal of the plane of the target, while accounting for the usability of each endoscope by recording the time taken for each task. In addition, we collected a questionnaire from each participant to obtain feedback. The angles obtained using the MAE were smaller on average ([Formula: see text]), indicating that better visualization can be achieved through the proposed method. A nonsignificant difference in mean time taken for each task in favor of the rigid endoscope was also found ([Formula: see text]). We have demonstrated that better visualization for endoscopic surgery can be achieved through our novel MAE. The scope may bring about a paradigm shift in the field of minimally invasive surgery by providing more freedom in viewpoint selection, enabling surgeons to perform more elaborate procedures in minimally invasive settings.

  6. An ex vivo approach to botanical-drug interactions: A proof of concept study

    Science.gov (United States)

    Wang, Xinwen; Zhu, Hao-Jie; Munoz, Juliana; Gurley, Bill J.; Markowitz, John S.

    2015-01-01

    Ethnopharmacological relevance Botanical medicines are frequently used in combination with therapeutic drugs, imposing a risk for harmful botanical-drug interactions (BDIs). Among the existing BDI evaluation methods, clinical studies are the most desirable, but due to their expense and protracted time-line for completion, conventional in vitro methodologies remain the most frequently used BDI assessment tools. However, many predictions generated from in vitro studies are inconsistent with clinical findings. Accordingly, the present study aimed to develop a novel ex vivo approach for BDI assessment and expand the safety evaluation methodoloy in applied ethnopharmacological research. Materials and Methods This approach differs from conventional in vitro methods in that rather than botanical extracts or individual phytochemicals being prepared in artificial buffers, human plasma/serum collected from a limited number of subjects administered botanical supplements was utilized to assess BDIs. To validate the methodology, human plasma/serum samples collected from healthy subjects administered either milk thistle or goldenseal extracts were utilized in incubation studies to determine their potential inhibitory effects on CYP2C9 and CYP3A4/5, respectively. Silybin A and B, two principal milk thistle phytochemicals, and hydrastine and berberine, the purported active constituents in goldenseal, were evaluated in both phosphate buffer and human plasma based in vitro incubation systems. Results Ex vivo study results were consistent with formal clinical study findings for the effect of milk thistle on the disposition of tolbutamide, a CYP2C9 substrate, and for goldenseal’s influence on the pharmacokinetics of midazolam, a widely accepted CYP3A4/5 substrate. Compared to conventional in vitro BDI methodologies of assessment, the introduction of human plasma into the in vitro study model changed the observed inhibitory effect of silybinA, silybin B and hydrastine and berberine

  7. The problem of 2,4,6-trichloroanisole in cork planks studied by attenuated total reflection infrared spectroscopy: proof of concept.

    Science.gov (United States)

    Garcia, Ana R; Lopes, Luís F; Brito de Barros, Ricardo; Ilharco, Laura M

    2015-01-14

    Attenuated total reflection infrared spectroscopy (ATR-IR) proved to be a promising detection technique for 2,4,6-trichloroanisole (TCA), which confers organoleptic defects to bottled alcoholic beverages, allowing the proposal of a criterion for cork plank acceptance when meant for stopper production. By analysis of a significant number of samples, it was proved that the presence of TCA, even in very low concentrations, imparts subtle changes to the cork spectra, namely, the growth of two new bands at ∼1417 (νC═C of TCA ring) and 1314 cm–1 (a shifted νCC of TCA) and an increase in the relative intensities of the bands at ∼1039 cm–1 (δCO of polysaccharides) and ∼813 cm–1 (τCH of suberin), the latter by overlapping with intense bands of TCA. These relative intensities were evaluated in comparison to a fingerprint of suberin (νasC–O–C), at 1161 cm–1. On the basis of those spectral variables, a multivariate statistics linear analysis (LDA) was performed to obtain a discriminant function that allows classifying the samples according to whether they contain or not TCA. The methodology proposed consists of a demanding acceptance criterion for cork planks destined for stopper production (with the guarantee of nonexistence of TCA) that results from combining the quantitative results with the absence of the two TCA correlated bands. ATR infrared spectroscopy is a nondestructive and easy to apply technique, both on cork planks and on stoppers, and has proven more restrictive than other techniques used in the cork industry that analyze the cleaning solutions. At the level of proof of concept, the method here proposed is appealing for high-value stopper applications.

  8. Proof of Concept

    DEFF Research Database (Denmark)

    Margheritini, Lucia; Parmeggiani, Stefano; Kofoed, Jens Peter

    it is needed. In the following paragraphs, the desk study on the WEBAP concept is presented in terms of overtopping flow rates for different configurations. Investigations on different drafts, slope angles and crest levels have been completed. Calculations on the pipe discharge have been made in order......The Wave Energized Baltic Aeration Pump (WEBAP) is a concept that proposes to find a solution to the low level of oxygenation of the Baltic Sea by bringing the surface sea water to the depth where the oxygen is needed. It proposes to do so by using the rich in oxygen overtopping water collected...... in a reservoir floating on the sea. The stored water, after overtopping the ramp leading to the reservoir, will be at a higher level than mean water level and therefore will have a potential energy. This potential energy is indeed used to pump down to the sea bed the oxygenated water right there where...

  9. A non-axial superconducting magnet design for optimized patient access and minimal SAD for use in a Linac-MR hybrid: proof of concept

    Science.gov (United States)

    Yaghoobpour Tari, Shima; Wachowicz, Keith; Fallone, B. Gino

    2017-04-01

    A prototype rotating hybrid magnetic resonance imaging system and linac has been developed to allow for simultaneous imaging and radiation delivery parallel to B 0. However, the design of a compact magnet capable of rotation in a small vault with sufficient patient access and a typical clinical source-to-axis distance (SAD) is challenging. This work presents a novel superconducting magnet design as a proof of concept that allows for a reduced SAD and ample patient access by moving the superconducting coils to the side of the yoke. The yoke and pole-plate structures are shaped to direct the magnetic flux appropriately. The outer surface of the pole plate is optimized subject to the minimization of a cost function, which evaluates the uniformity of the magnetic field over an ellipsoid. The magnetic field calculations required in this work are performed with the 3D finite element method software package Opera-3D. Each tentative design strategy is virtually modeled in this software package, which is externally controlled by MATLAB, with its key geometries defined as variables. The optimization variables are the thickness of the pole plate at control points distributed over the pole plate surface. A novel design concept as a superconducting non-axial magnet is introduced, which could create a large uniform B 0 magnetic field with fewer geometric restriction. This non-axial 0.5 T superconducting magnet has a moderately reduced SAD of 123 cm and a vertical patient opening of 68 cm. This work is presented as a proof of principle to investigate the feasibility of a non-axial magnet with the coils located around the yoke, and the results encourage future design optimizations to maximize the benefits of this non-axial design.

  10. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study.

    Science.gov (United States)

    Rapaport, M H; Nierenberg, A A; Schettler, P J; Kinkead, B; Cardoos, A; Walker, R; Mischoulon, D

    2016-01-01

    This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 (n-3) fatty acids in subjects with major depressive disorder (MDD). One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD, a baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) score ⩾ 15 and baseline biomarker data (interleukin (IL)-1ra, IL-6, high-sensitivity C-reactive protein (hs-CRP), leptin and adiponectin) were randomized between 18 May 2006 and 30 June 2011 to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA)-enriched n-3 1060 mg day(-1), docosahexaenoic acid (DHA)-enriched n-3 900 mg day(-1) or placebo. Outcomes were determined using mixed model repeated measures analysis for 'high' and 'low' inflammation groups based on individual and combined biomarkers. Results are presented in terms of standardized treatment effect size (ES) for change in HAM-D-17 from baseline to treatment week 8. Although overall treatment group differences were negligible (ES=-0.13 to +0.04), subjects with any 'high' inflammation improved more on EPA than placebo (ES=-0.39) or DHA (ES=-0.60) and less on DHA than placebo (ES=+0.21); furthermore, EPA-placebo separation increased with increasing numbers of markers of high inflammation. Subjects randomized to EPA with 'high' IL-1ra or hs-CRP or low adiponectin ('high' inflammation) had medium ES decreases in HAM-D-17 scores vs subjects 'low' on these biomarkers. Subjects with 'high' hs-CRP, IL-6 or leptin were less placebo-responsive than subjects with low levels of these biomarkers (medium to large ES differences). Employing multiple markers of inflammation facilitated identification of a more homogeneous cohort of subjects with MDD responding to EPA vs placebo in our cohort. Studies are needed to replicate and extend this proof-of-concept work.

  11. A non-axial superconducting magnet design for optimized patient access and minimal SAD for use in a Linac-MR hybrid: proof of concept.

    Science.gov (United States)

    Yaghoobpour Tari, Shima; Wachowicz, Keith; Gino Fallone, B

    2017-04-21

    A prototype rotating hybrid magnetic resonance imaging system and linac has been developed to allow for simultaneous imaging and radiation delivery parallel to B 0. However, the design of a compact magnet capable of rotation in a small vault with sufficient patient access and a typical clinical source-to-axis distance (SAD) is challenging. This work presents a novel superconducting magnet design as a proof of concept that allows for a reduced SAD and ample patient access by moving the superconducting coils to the side of the yoke. The yoke and pole-plate structures are shaped to direct the magnetic flux appropriately. The outer surface of the pole plate is optimized subject to the minimization of a cost function, which evaluates the uniformity of the magnetic field over an ellipsoid. The magnetic field calculations required in this work are performed with the 3D finite element method software package Opera-3D. Each tentative design strategy is virtually modeled in this software package, which is externally controlled by MATLAB, with its key geometries defined as variables. The optimization variables are the thickness of the pole plate at control points distributed over the pole plate surface. A novel design concept as a superconducting non-axial magnet is introduced, which could create a large uniform B 0 magnetic field with fewer geometric restriction. This non-axial 0.5 T superconducting magnet has a moderately reduced SAD of 123 cm and a vertical patient opening of 68 cm. This work is presented as a proof of principle to investigate the feasibility of a non-axial magnet with the coils located around the yoke, and the results encourage future design optimizations to maximize the benefits of this non-axial design.

  12. Quantitative Tracking of Salmonella Enteritidis Transmission Routes Using Barcode-Tagged Isogenic Strains in Chickens: Proof-of-Concept Study

    Science.gov (United States)

    Yang, Yichao; Ricke, Steven C.; Tellez, Guillermo; Kwon, Young Min

    2017-01-01

    Salmonella is an important foodborne bacterial pathogen, however, a fundamental understanding on Salmonella transmission routes within a poultry flock remains unclear. In this study, a series of barcode-tagged strains were constructed by inserting six random nucleotides into a functionally neutral region on the chromosome of S. Enteritidis as a tool for quantitative tracking of Salmonella transmission in chickens. Six distinct barcode-tagged strains were used for infection or contamination at either low dose (103 CFUs; three strains) or high dose (105 CFUs; three strains) in three independent experiments (Experiment 1 oral gavage; Experiment 2 contaminated feed; Experiment 3 contaminated water). For all chick experiments, cecal and foot-wash samples were collected from a subset of the chickens at days 7 or/and 14, from which genomic DNA was extracted and used to amplify the barcode regions. After the resulting PCR amplicons were pooled and analyzed by MiSeq sequencing, a total of approximately 1.5 million reads containing the barcode sequences were analyzed to determine the relative frequency of every barcode-tagged strain in each sample. In Experiment 1, the high dose of oral infection was correlated with greater dominance of the strains in the ceca of the respective seeder chickens and also in the contact chickens yet at lesser degrees. When chicks were exposed to contaminated feed (Experiment 2) or water (Experiment 3), there were no clear patterns of the barcode-tagged strains in relation to the dosage, except that the strains introduced at low dose required a longer time to colonize the ceca with contaminated feed. Most foot-wash samples contained only one to three strains for the majority of the samples, suggesting potential existence of an unknown mechanism(s) for strain exclusion. These results demonstrated the proof of concept of using barcode tagged to investigate transmission dynamics of Salmonella in chickens in a quantitative manner. PMID:28261587

  13. Proof-of-Concept of a Networked Validation Environment for Distributed Air/Ground NextGen Concepts

    Science.gov (United States)

    Grisham, James; Larson, Natalie; Nelson, Justin; Reed, Joshua; Suggs, Marvin; Underwood, Matthew; Papelis, Yiannis; Ballin, Mark G.

    2013-01-01

    The National Airspace System (NAS) must be improved to increase capacity, reduce flight delays, and minimize environmental impacts of air travel. NASA has been tasked with aiding the Federal Aviation Administration (FAA) in NAS modernization. Automatic Dependent Surveillance-Broadcast (ADS-B) is an enabling technology that is fundamental to realization of the Next Generation Air Transportation System (NextGen). Despite the 2020 FAA mandate requiring ADS-B Out equipage, airspace users are lacking incentives to equip with the requisite ADS-B avionics. A need exists to validate in flight tests advanced concepts of operation (ConOps) that rely on ADS-B and other data links without requiring costly equipage. A potential solution is presented in this paper. It is possible to emulate future data link capabilities using the existing in-flight Internet and reduced-cost test equipment. To establish proof-of-concept, a high-fidelity traffic operations simulation was modified to include a module that simulated Internet transmission of ADS-B messages. An advanced NASA ConOp, Flight Deck Interval Management (FIM), was used to evaluate technical feasibility. A preliminary assessment of the effects of latency and dropout rate on FIM was performed. Flight hardware that would be used by proposed test environment was connected to the simulation so that data transfer from aircraft systems to test equipment could be verified. The results indicate that the FIM ConOp, and therefore, many other advanced ConOps with equal or lesser response characteristics and data requirements, can be evaluated in flight using the proposed concept.

  14. Using ambulatory virtual environments for the assessment of functional gait impairment: a proof-of-concept study.

    Science.gov (United States)

    Gérin-Lajoie, Martin; Ciombor, Deborah McK; Warren, William H; Aaron, Roy K

    2010-04-01

    This study aimed to demonstrate the sensitivity of virtual reality (VR)/motion tracking to detect global functional gait impairment resulting from an emulated knee disability as a prelude to describing mobility changes following lower limb injury/treatment. Participants walked in a figure-8 around two virtual posts placed 6m apart while viewing the computer-generated environment in a helmet-mounted display. Three-dimensional position and orientation of the participant's head were tracked and used to update the virtual scenes, measure walking path and speed, and control task parameters with real-time feedback. Participants walked with/without an emulated lower extremity disability (splint preventing normal knee flexion). Participants performed the task at self-selected Natural (NAT) speed providing a baseline measure of their turning speed and area. Turning speed and area were then in turn maintained fixed (controlled speed, CS; controlled path, CP) while the other variable was measured as a gait impairment indicator. Different adaptive strategies were used to cope with the emulated deficit during the NAT scenario: maintaining turning speed while altering path geometry; decreasing turning speed while maintaining path geometry; and combining the previous two strategies. This resulted, on average, in decreased turning speeds and increased turning areas. The CS and CP manipulations respectively generated even greater turning areas and more consistent speed decreases. The three subtests acted as intertwined filters enabling the detection of functional gait impairment in all subjects regardless of their adaptive strategies. This proof-of-concept study demonstrated how VR/motion tracking technology can be used to detect and quantitatively characterize global functional mobility impairment.

  15. Photodynamic Therapy treatment of onychomycosis with Aluminium-Phthalocyanine Chloride nanoemulsions: A proof of concept clinical trial.

    Science.gov (United States)

    Morgado, Luciano Ferreira; Trávolo, Ana Regina Franchi; Muehlmann, Luís Alexandre; Narcizo, Paulo Souza; Nunes, Rodrigo Barbosa; Pereira, Pedro Alencar Gomes; Py-Daniel, Karen Rapp; Jiang, Cheng-Shi; Gu, Jinsong; Azevedo, Ricardo Bentes; Longo, João Paulo Figueiró

    2017-08-01

    The conventional treatment of onychomycosis, a common fungal infection, consists in the use of local and systemic drugs for 4-6 months. This long protocol is often ineffective due to patient compliance, and usually promotes important collateral effects such as liver and kidney failure. As the alternative, Photodynamic Therapy (PDT) has been used as a noninvasive alternative local treatment for onychomycosis due to the reduction of systemic side effects, fact indicates their use for patients undergoing other systemic treatments. In the present article, we evaluated the effectiveness, as well as the safety of PDT mediated by Aluminium-Phthalocyanine Chloride, entrapped in nanoemulsions, as a drug carrier, to treat onychomycosis in a proof of concept clinical trial. To the date, this is the first published clinical trial that uses PDT mediated by nanomedicines to treat onychomycosis. As main results, we can highlight the safety of the clinical protocol and the antifungal effectiveness similar to the conventional treatments. We observed the (1) clinical cure of 60% of treated lesions; (2) the absence of local and systemic adverse effects; (3) from these clinically healed lesions, 40% were negative for fungal infection in laboratorial exams; and (4) nails that presented negative fungal culture were kept without fungal infection for at least four weeks. The innovation of this approach is the absence of collateral effects, due to the local therapeutically treatment, and the possibility to repeat the treatment without inducing fungal resistance, a fact that indicates this approach as a possible alternative protocol for onychomycosis management. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Working with parents to treat anxiety-disordered children: A proof of concept RCT evaluating Fear-less Triple P.

    Science.gov (United States)

    Cobham, Vanessa E; Filus, Ania; Sanders, Matthew R

    2017-08-01

    Little is known about the efficacy of parent-only interventions and the maintenance of gains over time with anxiety-disordered children and adolescents. The current study aimed to evaluate the efficacy of a 6-session parent-focused intervention (Fear-less Triple P) in reducing children's anxiety symptomatology. The parents of 61 anxiety-disordered children (7-14 years) were randomly assigned to either the 6-session parent-only group CBT intervention or a wait-list control (WL) group. Diagnostic and questionnaire measures were administered at post-treatment; as well as 3-, 6- and 12 months following the completion of treatment. Families in the WL group were re-assessed after 6 weeks (the duration of the active intervention) and were then offered the intervention. The parent-only intervention produced superior outcomes for children on diagnostic and questionnaire measures. The percentages of children free of any anxiety diagnosis following the intervention were 38.7% (post-treatment); 58.6% (3-mth); 69.2% (6-mth); and 84% (12-mth). At the post-treatment assessment point, 3.4% of children in the WL group were free of any anxiety diagnosis. Mother and child questionnaire measures demonstrated gains from pre to post-treatment that were maintained over time. This proof of concept study suggests that the brief, parent-only intervention evaluated is an efficacious treatment approach for child anxiety disorders. A parent-only, group CBT intervention such as the one described here offers a cost-effective, low intensity alternative to traditional child-focused interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Determining the adenoma detection rate and adenomas per colonoscopy by photography alone: proof-of-concept study.

    Science.gov (United States)

    Rex, Douglas K; Hardacker, Kyle; MacPhail, Margaret; Rahmani, Farrah; Vemulapalli, Krishna C; Kahi, Charles J

    2015-03-01

    The adenoma detection rate (ADR) and adenomas detected per colonoscopy (APC) are measures of the quality of mucosal inspection during colonoscopy. In a resect and discard policy, pathologic assessment for calculation of ADR and APC would not be available. The aim of this study was to determine whether ADR and APC calculation based on photography alone is adequate compared with the pathology-based gold standard. A prospective, observational, proof-of-concept study was performed in an academic endoscopy unit. High definition photographs of consecutive polyps were taken, and pathology was estimated by the colonoscopist. Among 121 consecutive patients aged ≥ 50 years who underwent colonoscopy, 268 polyps were removed from 97 patients. Photographs of consecutive polyps were reviewed by a second endoscopist. The resect and discard policy applied to lesions that were ≤ 5 mm in size. When only photographs of lesions that were ultimately proven to be adenomas were included, the reviewer assessed ADR and APC to be lower than that determined by pathology (absolute reductions of 6.6 % and 0.17, and relative reductions of 12.6 % and 13.1 % in ADR and APC, respectively). When all photographs were included for calculation of ADR and APC, the reviewer determined the ADR to be 3.3 % lower (absolute reduction) and the APC to be the same as the rates determined by pathology. In a simulated resect and discard strategy, a high-level detector can document adequate ADR and APC by photography alone. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Mindfulness and Metta-based Trauma Therapy (MMTT): Initial Development and Proof-of-Concept of an Internet Resource.

    Science.gov (United States)

    Frewen, Paul; Rogers, Nicholas; Flodrowski, Les; Lanius, Ruth

    Trauma and stressor-related disorders, including post-traumatic stress disorder (PTSD) and related comorbid disorders such as anxiety, depression, and dissociative disorders, are difficult to treat. Mindfulness-based clinical interventions have proven efficacy for mental health treatment in face-to-face individual and group modalities, although the feasibility and efficacy of delivering these interventions via the internet has not been evaluated. The present research developed mindfulness and metta-based trauma therapy (MMTT) as an internet resource to support the practice of mindfulness and metta (lovingkindness) meditations for self-regulation and healing from trauma and stressor-related disorders. In the present "proof-of-concept" study, research participants (n = 177) recruited online practiced mindfulness and metta meditations and related therapeutic exercises available via the website and rated their perceived credibility as interventions for improving self-regulation and well-being and reducing PTSD symptoms, anxiety, depressive, and dissociative experiences, as well as their experienced ease, helpfulness, and informational value. Results suggest that, independent of level of self-reported current and past psychiatric history and PTSD symptoms, participants considered the MMTT website as a credible and helpful therapeutic intervention for improving self-regulation and well-being and reducing PTSD, anxiety, depression, and dissociation. Overall, participants considered guided and non-guided meditation practices more helpful than a journaling exercise, and participants with increased PTSD symptoms preferred metta (lovingkindness) meditations less than other participants. We conclude that MMTT should be piloted in clinical trials as an adjunctive intervention to evidence-based treatments for persons with mood, anxiety, and trauma and stressor-related disorders, as well as more generally as an online resource to support self-regulation and well

  19. Using peer observers to assess the quality of cancer multidisciplinary team meetings: a qualitative proof of concept study

    Science.gov (United States)

    Harris, Jenny; Green, James SA; Sevdalis, Nick; Taylor, Cath

    2014-01-01

    Background Multidisciplinary team (MDT) working is well established as the foundation for providing cancer services in the UK and elsewhere. A core activity is the weekly meeting (or case conference/tumor boards) where the treatment recommendations for individual patients are agreed. Evidence suggests that the quality of team working varies across cancer teams, and this may impact negatively on the decision-making process, and ultimately patient care. Feedback on performance by expert observers may improve performance, but can be resource-intensive to implement. This proof of concept study sought to: develop a structured observational assessment tool for use by peers (managers or clinicians from the local workforce) and explore its usability; assess the feasibility of the principle of observational assessment by peers; and explore the views of MDT members and observers about the utility of feedback from observational assessment. Methods For tool development, the content was informed by national clinical consensus recommendations for best practice in cancer MDTs and developed in collaboration with an expert steering group. It consisted of ten subdomains of team working observable in MDT meetings that were rated on a 10-point scale (very poor to very good). For observational assessment, a total of 19 peer observers used the tool (assessing performance in 20 cancer teams from four hospitals). For evaluation, telephone interviews with 64 team members and all peer observers were analyzed thematically. Results The tool was easy to use and areas for refinement were identified. Peer observers were identified and most indicated that undertaking observation was feasible. MDT members generally reported that observational assessment and feedback was useful, with the potential to facilitate improvements in team working. Conclusion This study suggests that observation and feedback by peers may provide a feasible and acceptable approach to enhance MDT performance. Further tool

  20. Ciclosporin A proof of concept study in patients with active, progressive HTLV-1 associated myelopathy/tropical spastic paraparesis.

    Directory of Open Access Journals (Sweden)

    Fabiola Martin

    Full Text Available INTRODUCTION: Patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP become progressively impaired, with chronic pain, immobility and bladder, bowel and sexual dysfunction. Tested antiretroviral therapies have not been effective and most patients are offered a short course of corticosteroids or interferon-α, physiotherapy and symptomatic management. Pathogenesis studies implicate activated T-lymphocytes and cytokines in tissue damage. We therefore tested the hypothesis that inhibition of T-cell activation with ciclosporin A would be safe and clinically beneficial in patients with early and/or clinically progressing HAM/TSP. MATERIALS AND METHODS: Open label, proof of concept, pilot study of 48 weeks therapy with the calcineurin antagonist, ciclosporin A (CsA, in seven patients with 'early' (50% deterioration in timed walk during the preceding three months HAM/TSP. Primary outcomes were incidence of clinical failure at 48 weeks and time to clinical failure. RESULTS: All patients completed 72 weeks study participation and five showed objective evidence of clinical improvement after 3 months treatment with CsA. Two patients exhibited clinical failure over 6.4 person-years of follow-up to week 48. One patient had a >2 point deterioration in IPEC (Insituto de Pesquisa Clinica Evandro Chagas disability score at weeks 8 and 12, and then stopped treatment. The other stopped treatment at week 4 because of headache and tremor and deterioration in timed walk, which occurred at week 45. Overall pain, mobility, spasticity and bladder function improved by 48 weeks. Two patients recommenced CsA during follow-up due to relapse. CONCLUSIONS: These data provide initial evidence that treatment with CsA is safe and may partially reverse the clinical deterioration seen in patients with early/progressive HAM/TSP. This trial supports further investigation of this agent's safety and effectiveness in larger, randomised controlled studies in

  1. Design of a complex virtual reality simulation to train finger motion for persons with hemiparesis: a proof of concept study.

    Science.gov (United States)

    Adamovich, Sergei V; Fluet, Gerard G; Mathai, Abraham; Qiu, Qinyin; Lewis, Jeffrey; Merians, Alma S

    2009-07-17

    Current neuroscience has identified rehabilitation approaches with the potential to stimulate adaptive changes in the brains of persons with hemiparesis. These approaches include, intensive task-oriented training, bimanual activities and balancing proximal and distal upper extremity interventions to reduce competition between these segments for neural territory. This paper describes the design and feasibility testing of a robotic/virtual environment system designed to train the hand and arm of persons with hemiparesis. The system employs a simulated piano that presents visual, auditory and tactile feedback comparable to an actual piano. Arm tracking allows patients to train both the arm and hand as a coordinated unit, emphasizing the integration of both transport and manipulation phases. The piano trainer includes songs and scales that can be performed with one or both hands. Adaptable haptic assistance is available for more involved subjects. An algorithm adjusts task difficulty in proportion to subject performance. A proof of concept study was performed on four subjects with upper extremity hemiparesis secondary to chronic stroke to establish: a) the safety and feasibility of this system and b) the concurrent validity of robotically measured kinematic and performance measures to behavioral measures of upper extremity function. None of the subjects experienced adverse events or responses during or after training. As a group, the subjects improved in both performance time and key press accuracy. Three of the four subjects demonstrated improvements in fractionation, the ability to move each finger individually. Two subjects improved their aggregate time on the Jebsen Test of Hand Function and three of the four subjects improved in Wolf Motor Function Test aggregate time. The system designed in this paper has proven to be safe and feasible for the training of hand function for persons with hemiparesis. It features a flexible design that allows for the use and further

  2. The 15-Minute Audition: Translating a Proof of Concept into a Domain-Specific Screening Device for Mathematical Talent

    Science.gov (United States)

    Subotnik, Rena F.; Worrell, Frank C.; Olszewski-Kubilius, Paula

    2017-01-01

    In 2011, Subotnik, Olszewski-Kubilius, and Worrell proposed a conceptual model for talent development applicable to all domains. Although grounded in available psychological research, significant questions remain regarding practical applications of each tenet of the model. In this article, we highlight a method of implementing the model's focus on…

  3. A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults

    OpenAIRE

    Mason, Barbara J.; Crean, Rebecca; Goodell, Vivian; Light, John M.; Quello, Susan; Shadan, Farhad; Buffkins, Kimberly; Kyle, Mark; Adusumalli, Murali; Begovic, Adnan; Rao, Santosh

    2012-01-01

    There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence. A 12-week, randomized, double-blind, placebo-controlled clinical trial w...

  4. Using peer observers to assess the quality of cancer multidisciplinary team meetings: a qualitative proof of concept study

    Directory of Open Access Journals (Sweden)

    Harris J

    2014-08-01

    Full Text Available Jenny Harris,1 James SA Green,2,3 Nick Sevdalis,4 Cath Taylor1 1Florence Nightingale School of Nursing and Midwifery, King's College London, London, UK; 2Department of Urology, Whipps Cross University Hospital, London, UK; 3Department of Health and Social Care, London South Bank University, London, UK; 4Department of Surgery and Cancer, Imperial College London, London, UK Background: Multidisciplinary team (MDT working is well established as the foundation for providing cancer services in the UK and elsewhere. A core activity is the weekly meeting (or case conference/tumor boards where the treatment recommendations for individual patients are agreed. Evidence suggests that the quality of team working varies across cancer teams, and this may impact negatively on the decision-making process, and ultimately patient care. Feedback on performance by expert observers may improve performance, but can be resource-intensive to implement. This proof of concept study sought to: develop a structured observational assessment tool for use by peers (managers or clinicians from the local workforce and explore its usability; assess the feasibility of the principle of observational assessment by peers; and explore the views of MDT members and observers about the utility of feedback from observational assessment. Methods: For tool development, the content was informed by national clinical consensus recommendations for best practice in cancer MDTs and developed in collaboration with an expert steering group. It consisted of ten subdomains of team working observable in MDT meetings that were rated on a 10-point scale (very poor to very good. For observational assessment, a total of 19 peer observers used the tool (assessing performance in 20 cancer teams from four hospitals. For evaluation, telephone interviews with 64 team members and all peer observers were analyzed thematically. Results: The tool was easy to use and areas for refinement were identified. Peer

  5. Efficacy of intravenous immunoglobulin monotherapy in patients with cutaneous lupus erythematosus: results of proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Christa Ky

    2015-03-01

    Full Text Available Cutaneous lupus erythematosus (CLE is a chronic inflammatory autoimmune skin disease. Evidence-based therapy for CLE is lacking in the most part. Intravenous immunoglobulin (IVIg is being increasingly utilized as off-label therapy for a variety of autoimmune and inflammatory conditions, especially in dermatology. The usefulness of IVIg in CLE is not well established. The goal of the present study was to obtain the proof-of-concept evidence that IVIg can control acute CLE and thus replace current systemic immunosuppressive therapy that causes severe side effects and adverse reactions. Sixteen patients who tried and failed various systemic treatments for CLE were screened and consented to use IVIg as a monotherapy. The IVIg was administered at 500 mg/kg/day on 4 consecutive days up to a total of 2 g/kg/month for 3 months, and the subjects were monitored for additional 6 months off any drug for a possible relapse. The cumulative results revealed an overall improvement, as evinced by a decrease of both objective and subjective measures of disease activity. The most sensitive and specific objective and subjective instruments for assessment of the therapeutic effect of IVIg were CLASI-A (Cutaneous Lupus Erythematosus Disease Area and Severity Index measuring disease activity and Skindex-29 scores, respectively. The CLASI-A score dropped down from the initial value taken as 100%, and remained in the range of approximately 70% until the last visit. Three patients (18.8% had a temporary flare of CLE symptoms but recovered within a month from the relapse. No serious side effects and adverse reactions occurred. Thus, IVIg monotherapy in CLE allowed to achieve: i rapid and persistent decreased in disease activity; ii steady improvement of patients’ quality of life assessed by Skindex-29; iii low relapse rate; and iv mild nature and short duration of relapses. Since healing was maintained for months after IVIg treatment, it is possible that the IVIg

  6. Design of a complex virtual reality simulation to train finger motion for persons with hemiparesis: a proof of concept study

    Directory of Open Access Journals (Sweden)

    Qiu Qinyin

    2009-07-01

    Full Text Available Abstract Background Current neuroscience has identified rehabilitation approaches with the potential to stimulate adaptive changes in the brains of persons with hemiparesis. These approaches include, intensive task-oriented training, bimanual activities and balancing proximal and distal upper extremity interventions to reduce competition between these segments for neural territory. Methods This paper describes the design and feasibility testing of a robotic/virtual environment system designed to train the hand and arm of persons with hemiparesis. The system employs a simulated piano that presents visual, auditory and tactile feedback comparable to an actual piano. Arm tracking allows patients to train both the arm and hand as a coordinated unit, emphasizing the integration of both transport and manipulation phases. The piano trainer includes songs and scales that can be performed with one or both hands. Adaptable haptic assistance is available for more involved subjects. An algorithm adjusts task difficulty in proportion to subject performance. A proof of concept study was performed on four subjects with upper extremity hemiparesis secondary to chronic stroke to establish: a the safety and feasibility of this system and b the concurrent validity of robotically measured kinematic and performance measures to behavioral measures of upper extremity function. Results None of the subjects experienced adverse events or responses during or after training. As a group, the subjects improved in both performance time and key press accuracy. Three of the four subjects demonstrated improvements in fractionation, the ability to move each finger individually. Two subjects improved their aggregate time on the Jebsen Test of Hand Function and three of the four subjects improved in Wolf Motor Function Test aggregate time. Conclusion The system designed in this paper has proven to be safe and feasible for the training of hand function for persons with hemiparesis

  7. First-in-Human Proof-of-Concept Study: Intralesional Administration of BQ788, an Endothelin Receptor B Antagonist, to Melanoma Skin Metastases

    Science.gov (United States)

    Hunger, Robert E.; Garrod, Terence; Dubuis, Benoit; Hunziker, Thomas; van den Oord, Joost J.; Lahav-le Coutre, Ronit

    2015-01-01

    Lessons Learned Local tolerance of intralesional treatment of melanoma skin metastases with BQ788 is excellent. Hints of efficacy are observed, consisting of both direct effects (decreased expression of endothelin receptor B [EDNRB] and of survival factors, reduced proliferation) and indirect effects (enhanced immune cell infiltration and angiogenesis). Patients in future trials should be screened for EDNRB expression level prior to treatment because only patients with high EDNRB-expressing melanomas (four of five) responded to BQ788. Future studies should be performed for at least 2 weeks because reduced lesion growth was observed in the only patient that was treated for longer than 1 week. Background. This first-in-human proof-of-concept study aimed to check whether safety and preclinical results obtained by intratumoral administration of BQ788, an endothelin receptor B (EDNRB) antagonist, can be repeated in human melanoma patients. Methods. Three patients received a single intralesional BQ788 application of 3 mg. After 3–7 days, the lesions were measured and removed for analysis. The administered dose was increased to a cumulative dosage of 8 mg in patient 4 (4 × 2.0 mg, days 0–3; lesion removed on day 4) and to 10 mg in patient 5 (3 × 3.3 mg, days 0, 3, and 10; lesion removed after 14 days). Control lesions were simultaneously treated with phosphate-buffered saline (PBS). All samples were processed and analyzed without knowledge of the clinical findings. Results. No statistical evaluation was possible because of the number of patients (n = 5) and the variability in the mode of administration. No adverse events were observed, regardless of administered dose. All observations were in accordance with results obtained in preclinical studies. Accordingly, no difference in degree of tumor necrosis was detected between BQ788- and PBS-treated samples. In addition, both EDNRB and Ki67 showed decreased expression in patients 2 and 5 and, to a lesser extent, in

  8. Tracking of Listeria monocytogenes in meat establishment using Whole Genome Sequencing as a food safety management tool: A proof of concept.

    Science.gov (United States)

    Nastasijevic, Ivan; Milanov, Dubravka; Velebit, Branko; Djordjevic, Vesna; Swift, Craig; Painset, Anais; Lakicevic, Brankica

    2017-09-18

    Repeated Listeria outbreaks particularly associated with Ready-To-Eat (RTE) delicatessen meat products have been reported annually at global level. The most frequent scenario that led to foodborne outbreaks was the post-thermal treatment cross-contamination of deli meat products during slicing and modified atmosphere packaging (MAP). The precondition for such cross contamination is the previous introduction of Listeria into meat processing facilities and subsequent colonization of the production environment, associated with formation of biofilms resilient to common sanitation procedures regularly applied in meat establishments. The use of Whole Genome Sequencing (WGS) can facilitate the understanding of contamination and colonization routes of pathogens within the food production environment and enable efficient pathogen tracking among different departments. This study aimed to: a) provide a proof of concept on practical use of WGS in a meat establishment to define the entry routes and spread pattern of L. monocytogenes, and b) to consider the regular use of WGS in meat processing establishments as a strong support of food safety management system. The results revealed that Listeria spp. was present in slaughter line, chilling chambers, deboning, slicing, MAP, as well as in corridors and dispatch (53 positive samples, out of 240). Eight L. monocytogenes isolates (out of 53) were identified from the slaughterhouse, chilling chambers, deboning, MAP and dispatch. L. monocytogenes isolates were of three different serotypes (1/2a, 1/2c, 4b) and correspondingly of three MLST sequence types. Overall, two pairs of L. monocytogenes isolates were genetically identical, i.e. two serotype 4b isolates (ST1), isolated from water drain at dispatch unit and two isolates obtained from slaughterhouse (floorwall junction at the carcass wash point) and MAP (water drain). These findings indicated that L. monocytogenes isolates identified in meat processing units (MAP, chilling chamber

  9. The effects of different sensory augmentation on weight-shifting balance exercises in Parkinson's disease and healthy elderly people: a proof-of-concept study.

    Science.gov (United States)

    Lee, Beom-Chan; Thrasher, Timothy A; Fisher, Stanley P; Layne, Charles S

    2015-09-02

    Earlier versions of biofeedback systems for balance-related applications were intended primarily to provide "alarm" signals about body tilt rather than to guide rehabilitation exercise motion. Additionally, there have been few attempts to evaluate guidance modalities for balance rehabilitation exercises. The purpose of this proof-of-concept study is to evaluate the effects of guidance modalities during common dynamic weight-shifting exercises used in clinical settings. A motion guidance system providing visual biofeedback, vibrotactile biofeedback, or both, was used during weight-shifting exercises. Eleven people with idiopathic Parkinson's disease (PD) and nine healthy elderly people participated. Each participant wore a six-degree-of-freedom inertial measurement unit (IMU) located near the sacrum and four linear vibrating actuators (Tactors) attached to the skin over the front, back, and right and left sides of the abdomen. The IMU measured angular displacements and velocities of body tilt in anterior-posterior (A/P) and medial-lateral (M/L) directions. Participants were instructed to follow a slow moving target by shifting their weight in either the A/P or M/L direction up to 90 % of their limits of stability (LOS). Real-time position error was provided to participants in one of three sensory modalities: visual, vibrotactile, or both. Participants performed 5 trials for each biofeedback modality and movement direction (A/P and M/L) for a total of 30 trials in a random order. To characterize performance, position error was defined as the average absolute difference between the target and participant movements in degrees. Simultaneous delivery of visual and vibrotactile biofeedback resulted in significantly lower position error compared to either visual or vibrotactile biofeedback alone regardless of the movement direction for both participant cohorts. The pairwise comparisons were not significantly different between visual and vibrotactile biofeedback. The study

  10. Acute beetroot juice supplementation on sympathetic nerve activity: a randomized, double-blind, placebo-controlled proof-of-concept study.

    Science.gov (United States)

    Notay, Karambir; Incognito, Anthony V; Millar, Philip J

    2017-07-01

    exaggerated sympathetic outflow in clinical populations.NEW & NOTEWORTHY The hemodynamic benefits of dietary nitrate supplementation have been attributed to nitric oxide-mediated peripheral vasodilation. Here, we provide proof of concept that acute dietary nitrate supplementation using beetroot juice can decrease muscle sympathetic outflow at rest and during exercise in a normotensive population. These results have applications for targeting central sympathetic overactivation in disease. Copyright © 2017 the American Physiological Society.

  11. A novel geometry-dosimetry label fusion method in multi-atlas segmentation for radiotherapy: a proof-of-concept study

    Science.gov (United States)

    Chang, Jina; Tian, Zhen; Lu, Weiguo; Gu, Xuejun; Chen, Mingli; Jiang, Steve B.

    2017-05-01

    Multi-atlas segmentation (MAS) has been widely used to automate the delineation of organs at risk (OARs) for radiotherapy. Label fusion is a crucial step in MAS to cope with the segmentation variabilities among multiple atlases. However, most existing label fusion methods do not consider the potential dosimetric impact of the segmentation result. In this proof-of-concept study, we propose a novel geometry-dosimetry label fusion method for MAS-based OAR auto-contouring, which evaluates the segmentation performance in terms of both geometric accuracy and the dosimetric impact of the segmentation accuracy on the resulting treatment plan. Differently from the original selective and iterative method for performance level estimation (SIMPLE), we evaluated and rejected the atlases based on both Dice similarity coefficient and the predicted error of the dosimetric endpoints. The dosimetric error was predicted using our previously developed geometry-dosimetry model. We tested our method in MAS-based rectum auto-contouring on 20 prostate cancer patients. The accuracy in the rectum sub-volume close to the planning tumor volume (PTV), which was found to be a dosimetric sensitive region of the rectum, was greatly improved. The mean absolute distance between the obtained contour and the physician-drawn contour in the rectum sub-volume 2 mm away from PTV was reduced from 3.96 mm to 3.36 mm on average for the 20 patients, with the maximum decrease found to be from 9.22 mm to 3.75 mm. We also compared the dosimetric endpoints predicted for the obtained contours with those predicted for the physician-drawn contours. Our method led to smaller dosimetric endpoint errors than the SIMPLE method in 15 patients, comparable errors in 2 patients, and slightly larger errors in 3 patients. These results indicated the efficacy of our method in terms of considering both geometric accuracy and dosimetric impact during label fusion. Our algorithm can be applied to different tumor sites

  12. Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design.

    Science.gov (United States)

    Bastarrachea, Raul A; Chen, Jiaxi; Kent, Jack W; Nava-Gonzalez, Edna J; Rodriguez-Ayala, Ernesto; Daadi, Marcel M; Jorge, Barbara; Laviada-Molina, Hugo; Comuzzie, Anthony G; Chen, Shuyuan; Grayburn, Paul A

    2017-09-01

    Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue-specific gene delivery. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice. Our group recently demonstrated that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)-treated mice and baboons. We hypothesized that gene therapy with BMP7/PRDM16/PPARGC1A in skeletal muscle (SKM) of obese Zucker diabetic fatty (fa/fa) rats using UTMD technology would produce a brown adipose tissue (BAT) phenotype with UCP-1 overexpression. This study was designed as a proof of concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs encoding a gene cocktail with BMP7/PRDM16/PPARGC1A incorporated within microbubbles and intravenously delivered into their left thigh. Controls received UTMD with plasmids driving a DsRed reporter gene. An ultrasound transducer was directed to the thigh to disrupt the microbubbles within the microcirculation. Blood samples were drawn at baseline, and after treatment to measure glucose, insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry (IHC). Our IHC results showed a reliable pattern of effective UTMD-based gene delivery in enhancing SKM overexpression of the UCP-1 gene. This clearly indicates that our plasmid DNA construct encoding the gene combination of PRDM16, PPARGC1A, and BMP7 reprogrammed adult SKM tissue into brown adipose cells in vivo. Our pilot established POC showing that the administration of the gene cocktail to SKM in this rat model of genetic obesity using UTMD

  13. Post-exposure treatment of VX poisoned guinea pigs with the engineered phosphotriesterase mutant C23: a proof-of-concept study.

    Science.gov (United States)

    Worek, Franz; Seeger, Thomas; Reiter, Georg; Goldsmith, Moshe; Ashani, Yacov; Leader, Haim; Sussman, Joel L; Aggarwal, Nidhi; Thiermann, Horst; Tawfik, Dan S

    2014-11-18

    The highly toxic organophosphorus (OP) nerve agent VX is characterized by a remarkable biological persistence which limits the effectiveness of standard treatment with atropine and oximes. Existing OP hydrolyzing enzymes show low activity against VX and hydrolyze preferentially the less toxic P(+)-VX enantiomer. Recently, a phosphotriesterase (PTE) mutant, C23, was engineered towards the hydrolysis of the toxic P(-) isomers of VX and other V-type agents with relatively high in vitro catalytic efficiency (kcat/KM=5×10(6)M(-1)min(-1)). To investigate the suitability of the PTE mutant C23 as a catalytic scavenger, an in vivo guinea pig model was established to determine the efficacy of post-exposure treatment with C23 alone against VX intoxication. Injection of C23 (5mgkg(-1) i.v.) 5min after s.c. challenge with VX (∼2LD50) prevented systemic toxicity. A lower C23 dose (2mgkg(-1)) reduced systemic toxicity and prevented mortality. Delayed treatment (i.e., 15min post VX) with 5mgkg(-1) C23 resulted in survival of all animals and only in moderate systemic toxicity. Although C23 did not prevent inhibition of erythrocyte acetylcholinesterase (AChE) activity, it partially preserved brain AChE activity. C23 therapy resulted in a rapid decrease of racemic VX blood concentration which was mainly due to the rate of degradation of the toxic P(-)-VX enantiomer that correlates with the C23 blood levels and its kcat/KM value. Although performed under anesthesia, this proof-of-concept study demonstrated for the first time the ability of a catalytic bioscavenger to prevent systemic VX toxicity when given alone as a single post-exposure treatment, and enables an initial assessment of a time window for this approach. In conclusion, the PTE mutant C23 may be considered as a promising starting point for the development of highly effective catalytic bioscavengers for post-exposure treatment of V-agents intoxication.

  14. Mobile Health Medication Adherence and Blood Pressure Control in Renal Transplant Recipients: A Proof-of-Concept Randomized Controlled Trial.

    Science.gov (United States)

    McGillicuddy, John W; Gregoski, Mathew J; Weiland, Anna K; Rock, Rebecca A; Brunner-Jackson, Brenda M; Patel, Sachin K; Thomas, Beje S; Taber, David J; Chavin, Kenneth D; Baliga, Prabhakar K; Treiber, Frank A

    2013-09-04

    Mobile phone based programs for kidney transplant recipients are promising tools for improving long-term graft outcomes and better managing comorbidities (eg, hypertension, diabetes). These tools provide an easy to use self-management framework allowing optimal medication adherence that is guided by the patients' physiological data. This technology is also relatively inexpensive, has an intuitive interface, and provides the capability for real-time personalized feedback to help motivate patient self-efficacy. Automated summary reports of patients' adherence and blood pressure can easily be uploaded to providers' networks helping reduce clinical inertia by reducing regimen alteration time. The aim of this study was to assess the feasibility, acceptability, and preliminary outcomes of a prototype mobile health (mHealth) medication and blood pressure (BP) self-management system for kidney transplant patients with uncontrolled hypertension. A smartphone enabled medication adherence and BP self-management system was developed using a patient and provider centered design. The development framework utilized self-determination theory with iterative stages that were guided and refined based on patient/provider feedback. A 3-month proof-of-concept randomized controlled trial was conducted in 20 hypertensive kidney transplant patients identified as non-adherent to their current medication regimen based on a month long screening using an electronic medication tray. Participants randomized to the mHealth intervention had the reminder functions of their electronic medication tray enabled and received a bluetooth capable BP monitor and a smartphone that received and transmitted encrypted physiological data and delivered reminders to measure BP using text messaging. Controls received standard of care and their adherence continued to be monitored with the medication tray reminders turned off. Providers received weekly summary reports of patient medication adherence and BP readings

  15. Application of Nuclear Magnetic Resonance to Detect Toxigenic Clostridium difficile from Stool Specimens: A Proof of Concept.

    Science.gov (United States)

    Yang, Paul; Hash, Sara; Park, Katherine; Wong, Charlene; Doraisamy, Loganathan; Petterson, Jonas; Petti, Cathy A; Ward, Pamela M; Lee, Seung Heon; Menon, Suresh; She, Rosemary C

    2017-03-01

    We evaluated the performance of an early prototype core molecular mirroring nuclear magnetic resonance detection platform (Mentor-100) to detect toxigenic Clostridium difficile from stool. This technology uses customized nanoparticles bound to target specific oligonucleotide probes that form binaries in the presence of nucleic acid from the target microorganism. Liquid patient stool specimens were seeded with C. difficile or other Clostridium species to determine the analytical sensitivity and specificity. Samples underwent nucleic acid extraction and target amplification with probes conjugated with iron nanoparticles. Signal from nuclear magnetic resonance spin-spin relaxation time was measured to detect the presence or absence of toxigenic C. difficile. The limit of detection was difficile. No cross-reactivity was observed with nontoxigenic C. difficile, Clostridium sordellii, Clostridium perfringens, Bacillus subtilis, or Paenibacillus polymyxa at 10(8) colony forming units/mL. Correlation studies using frozen stool samples yielded a sensitivity of 88.4% (61 of 69) and a specificity of 87.0% (40 of 46) as compared with a commercial PCR assay for C. difficile. The area under the curve in the receiver operating characteristic curve analysis was 0.922. The prototype molecular mirroring platform showed promising performance for pathogen detection from clinical specimens. The platform design has the potential to offer a novel, low-cost alternative to currently available nucleic acid-based tests. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  16. A novel adaptive mixed reality system for stroke rehabilitation: principles, proof of concept, and preliminary application in 2 patients.

    Science.gov (United States)

    Chen, Yinpeng; Duff, Margaret; Lehrer, Nicole; Liu, Sheng-Min; Blake, Paul; Wolf, Steven L; Sundaram, Hari; Rikakis, Thanassis

    2011-01-01

    This article presents the principles of an adaptive mixed reality rehabilitation (AMRR) system, as well as the training process and results from 2 stroke survivors who received AMRR therapy, to illustrate how the system can be used in the clinic. The AMRR system integrates traditional rehabilitation practices with state-of-the-art computational and motion capture technologies to create an engaging environment to train reaching movements. The system provides real-time, intuitive, and integrated audio and visual feedback (based on detailed kinematic data) representative of goal accomplishment, activity performance, and body function during a reaching task. The AMRR system also provides a quantitative kinematic evaluation that measures the deviation of the stroke survivor's movement from an idealized, unimpaired movement. The therapist, using the quantitative measure and knowledge and observations, can adapt the feedback and physical environment of the AMRR system throughout therapy to address each participant's individual impairments and progress. Individualized training plans, kinematic improvements measured over the entire therapy period, and the changes in relevant clinical scales and kinematic movement attributes before and after the month-long therapy are presented for 2 participants. The substantial improvements made by both participants after AMRR therapy demonstrate that this system has the potential to considerably enhance the recovery of stroke survivors with varying impairments for both kinematic improvements and functional ability.

  17. Body-Machine Interface Enables People With Cervical Spinal Cord Injury to Control Devices With Available Body Movements: Proof of Concept.

    Science.gov (United States)

    Abdollahi, Farnaz; Farshchiansadegh, Ali; Pierella, Camilla; Seáñez-González, Ismael; Thorp, Elias; Lee, Mei-Hua; Ranganathan, Rajiv; Pedersen, Jessica; Chen, David; Roth, Elliot; Casadio, Maura; Mussa-Ivaldi, Ferdinando

    2017-05-01

    This study tested the use of a customized body-machine interface (BoMI) for enhancing functional capabilities in persons with cervical spinal cord injury (cSCI). The interface allows people with cSCI to operate external devices by reorganizing their residual movements. This was a proof-of-concept phase 0 interventional nonrandomized clinical trial. Eight cSCI participants wore a custom-made garment with motion sensors placed on the shoulders. Signals derived from the sensors controlled a computer cursor. A standard algorithm extracted the combinations of sensor signals that best captured each participant's capacity for controlling a computer cursor. Participants practiced with the BoMI for 24 sessions over 12 weeks performing 3 tasks: reaching, typing, and game playing. Learning and performance were evaluated by the evolution of movement time, errors, smoothness, and performance metrics specific to each task. Through practice, participants were able to reduce the movement time and the distance from the target at the 1-second mark in the reaching task. They also made straighter and smoother movements while reaching to different targets. All participants became faster in the typing task and more skilled in game playing, as the pong hit rate increased significantly with practice. The results provide proof-of-concept for the customized BoMI as a means for people with absent or severely impaired hand movements to control assistive devices that otherwise would be manually operated.

  18. Open access to Water Indicators for Climate Change Adaptation: proof-of-concept for the Copernicus Climate Change Service (C3S)

    Science.gov (United States)

    Lottle, Lorna; Arheimer, Berit; Gyllensvärd, Frida; Dejong, Fokke; Ludwig, Fulco; Hutjes, Ronald; Martinez, Bernat

    2017-04-01

    Copernicus Climate Change Service (C3S) is still in the development phase and will combine observations of the climate system with the latest science to develop authoritative, quality-assured information about the past, current and future states of the climate and climate dependent sectors in Europe and worldwide. C3S will provide key indicators on climate change drivers and selected sectorial impacts. The aim of these indicators will be to support adaptation and mitigation. This presentation will show one service already operational as a proof-of-concept of this future climate service. The project "Service for Water Indicators in Climate Change Adaptation" (SWICCA) has developed a sectorial information service for water management. It offers readily available climate-impact data, for open access from the web-site http://swicca.climate.copernicus.eu/. The development is user-driven with the overall goal to speed up the workflow in climate-change adaptation of water management across Europe. The service is co-designed by consultant engineers and agencies in 15 case-studies spread out over the continent. SWICCA has an interactive user-interface, which shows maps and graphs, and facilitates data download in user-friendly formats. In total, more than 900 open dataset are given for various hydrometeorological (and a few socioeconomical) variables, model ensembles, resolutions, time-periods and RCPs. The service offers more than 40 precomputed climate impact indicators (CIIs) and transient time-series of 4 essential climate variables ECVs) with high spatial and temporal resolution. To facilitate both near future and far future assessments, SWICCA provides the indicators for different time ranges; normally, absolute values are given for a reference period (e.g. 1971-2000) and the expected future changes for different 30-year periods, such as early century (2011-2040), mid-century (2041-2070) and end-century (2071-2100). An ensemble of model results is always given to

  19. Applying Pleck's Model of Paternal Involvement to the Study of Preschool Attachment Quality: A Proof of Concept Study

    Science.gov (United States)

    Kennedy, Mark; Betts, Lucy; Dunn, Thomas; Sonuga-Barke, Edmund; Underwood, Jean

    2015-01-01

    Recent re-conceptualisation of paternal involvement (Pleck, J. H. (2010). Paternal involvement: Revised conceptualization and theoretical linkages with child outcomes. In M. Lamb (Ed.), "The role of the father in child development" (5th ed., pp. 67-107). London: Wiley), while proving fruitful, has yet to be applied to investigations into…

  20. A Sustainable Model for Patient Follow-Up Following an International Cleft Mission: A Proof of Concept.

    Science.gov (United States)

    Wes, Ari M; Paul, Nadine; Gerety, Patrick A; Folsom, Nancy; Swanson, Jordan; Taylor, Jesse A; Weinstein, Mark H

    2017-01-13

      Patient follow-up after cleft missions is imperative if we are to critically assess the quality of care provided in these settings. The adoption of mobile telephones among disadvantaged families abroad may enable such an undertaking in a cost-effective manner. This project aimed to assess the efficacy of cellular phone-based follow-up in a developing country following a cleft mission to Thailand.   Changing Children's Lives Inc. performed a cleft surgical mission to Udon Thani, Thailand, in January 2013. Telephone numbers collected at that time were used to survey the patients or their parents 1.5 years postoperatively.   Of the 56 patients who underwent cleft lip and/or palate surgery during the mission, more than 50% (n = 30, 54%) were reachable by telephone; all chose to participate in the study. The cost for families was U.S. $124.92 (56.15); 26 families (87%) believed their money was well spent. Follow-up care was received by 22 (73%) patients, and all but one family (n = 29, 97%) felt that their child received all of the medical care and support required. All families (N = 30) would recommend similar cleft care to a friend. Of the patients younger than 18 years of age (n = 24, 80%), 20 (80%) families found their child more comfortable interacting with peers, more comfortable interacting with adults, and more confident postoperatively.   In one month, a survey response rate of more than 50% was obtained by leveraging the increased adoption of mobile phones in rural settings. Nearly all patients/families treated during the cleft mission were satisfied with the care that they received.

  1. Customized-Language Voice Survey on Mobile Devices for Text and Image Data Collection Among Ethnic Groups in Thailand: A Proof-of-Concept Study.

    Science.gov (United States)

    Jandee, Kasemsak; Lawpoolsri, Saranath; Taechaboonsermsak, Pimsurang; Khamsiriwatchara, Amnat; Wansatid, Peerawat; Kaewkungwal, Jaranit

    2014-03-06

    Public health surveys are often conducted using paper-based questionnaires. However, many problems are associated with this method, especially when collecting data among ethnic groups who speak a different language from the survey interviewer. The process can be time-consuming and there is the risk of missing important data due to incomplete surveys. This study was conducted as a proof-of-concept to develop a new electronic tool for data collection, and compare it with standard paper-based questionnaire surveys using the research setting of assessing Knowledge Attitude and Practice (KAP) toward the Expanded Program on Immunization (EPI) among 6 ethnic groups in Chiang Rai Province, Thailand. The two data collection methods were compared on data quality in terms of data completeness and time consumed in collecting the information. In addition, the initiative assessed the participants' satisfaction toward the use of a smartphone customized-language voice-based questionnaire in terms of perceived ease of use and perceived usefulness. Following a cross-over design, all study participants were interviewed using two data collection methods after a one-week washout period. Questions in the paper-based questionnaires in Thai language were translated to each ethnic language by the interviewer/translator when interviewing the study participant. The customized-language voice-based questionnaires were programmed to a smartphone tablet in six, selectable dialect languages and used by the trained interviewer when approaching participants. The study revealed positive data quality outcomes when using the smartphone, voice-based questionnaire survey compared with the paper-based questionnaire survey, both in terms of data completeness and time consumed in data collection process. Since the smartphone questionnaire survey was programmed to ask questions in sequence, no data was missing and there were no entry errors. Participants had positive attitudes toward answering the

  2. Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

    Directory of Open Access Journals (Sweden)

    Spadavecchia J

    2016-02-01

    Full Text Available Jolanda Spadavecchia,1,2,* Dania Movia,3,* Caroline Moore,3,4 Ciaran Manus Maguire,3,4 Hanane Moustaoui,2 Sandra Casale,1 Yuri Volkov,3,4 Adriele Prina-Mello3,4 1Laboratoire de Réactivité de Surface, Sorbonne Universités, UPMC Univ Paris VI, Paris, 2Centre National de la recherche française, UMR 7244, CSPBAT, Laboratory of Chemistry, Structures, and Properties of Biomaterials and Therapeutic Agents, Université Paris 13, Sorbonne Paris Cité, Bobigny, France; 3AMBER Centre, CRANN Institute, 4Department of Clinical Medicine, School of Medicine, Trinity College, Dublin, Ireland *These authors contributed equally to this work Abstract: The main objective of this study was to optimize and characterize a drug delivery carrier for doxorubicin, intended to be intravenously administered, capable of improving the therapeutic index of the chemotherapeutic agent itself, and aimed at the treatment of pancreatic cancer. In light of this goal, we report a robust one-step method for the synthesis of dicarboxylic acid-terminated polyethylene glycol (PEG-gold nanoparticles (AuNPs and doxorubicin-loaded PEG-AuNPs, and their further antibody targeting (anti-Kv11.1 polyclonal antibody [pAb]. In in vitro proof-of-concept studies, we evaluated the influence of the nanocarrier and of the active targeting functionality on the anti-tumor efficacy of doxorubicin, with respect to its half-maximal effective concentration (EC50 and drug-triggered changes in the cell cycle. Our results demonstrated that the therapeutic efficacy of doxorubicin was positively influenced not only by the active targeting exploited through anti-Kv11.1-pAb but also by the drug coupling with a nanometer-sized delivery system, which indeed resulted in a 30-fold decrease of doxorubicin EC50, cell cycle blockage, and drug localization in the cell nuclei. The cell internalization pathway was strongly influenced by the active targeting of the Kv11.1 subunit of the human Ether-à-go-go related gene

  3. Developing Bayesian networks from a dependency-layered ontology: A proof-of-concept in radiation oncology.

    Science.gov (United States)

    Kalet, Alan M; Doctor, Jason N; Gennari, John H; Phillips, Mark H

    2017-08-01

    Bayesian networks (BNs) are graphical representations of probabilistic knowledge that offer normative reasoning under uncertainty and are well suited for use in medical domains. Traditional knowledge-based network development of BN topology requires that modeling experts establish relevant dependency links between domain concepts by searching and translating published literature, querying domain experts, or applying machine learning algorithms on data. For initial development these methods are time-intensive and this cost hinders the growth of BN applications in medical decision making. Further, this approach fails to utilize knowledge representation in medical fields to automate network development. Our research alleviates the challenges surrounding BN modeling in radiation oncology by leveraging an ontology based hub and spoke system for BN construction. We implement a hub and spoke system by developing (a) an ontology of knowledge in radiation oncology (the hub) which includes dependency semantics similar to BN relations and (b) a software tool that operates on ontological semantics using deductive reasoning to create BN topologies (the spokes). We demonstrate that network topologies built using the software are terminologically consistent and form networks that are topologically compatible with existing ones. We do this first by merging two different BN models for prostate cancer radiotherapy prediction which contain domain cross terms. We then use the logic to perform discovery of new causal chains between radiation oncology concepts. From the radiation oncology (RO) ontology we successfully reconstructed a previously published prostate cancer radiotherapy Bayes net using up-to-date domain knowledge. Merging this model with another similar prostate cancer model in the RO domain produced a larger, highly interconnected model representing the expanded scope of knowledge available regarding prostate cancer therapy parameters, complications, and outcomes. The

  4. Exploring the Feasibility and Potential of Virtual Panels for Soliciting Feedback on Nutrition Education Materials: A Proof-of-Concept Study.

    Science.gov (United States)

    Norman, Cameron D; Haresign, Helen; Mehling, Christine; Bloomberg, Honey

    2016-01-01

    A changing and cluttered information landscape has put pressure on health organizations to produce consumer information materials that are not only factual but high quality and engaging to audiences. User-centered design methods can be useful in obtaining feedback from consumers; however, they are labor intensive and slow, which is not responsive to the fast-paced communication landscape influenced by social media. EatRight Ontario (ERO), a provincial nutrition and health support program of Dietitians of Canada, develops evidence-based resources for consumers and sought to increase user-centered design activities by exploring whether the standard approach to feedback could be replicated online. While online feedback has been used in marketing research, few examples are available in health promotion and public health to guide programming and policy. This study compared a traditional in-person approach for recruitment and feedback using paper surveys with an Internet-based approach using Facebook as a recruitment tool and collecting user feedback via the Web. The purpose of the proof-of-concept study was to explore the feasibility of the approach and compare an online versus traditional approach in terms of recruitment issues and response. An exploratory, two-group comparative trial was conducted using a convenience and purposive sampling. Participants reviewed a handout on healthy eating and then completed an 18-item survey with both forced-choice items and open-ended responses. One group viewed a hard-copy prototype and completed a paper survey and the other viewed a PDF prototype via Web links and completed a Web survey. The total days required to fulfill the sample for each group were used as the primary method of efficiency calculation. In total, 44 participants (22 per condition) completed the study, consisting of 42 women and 2 men over the age of 18. Few significant differences were detected between the groups. Statistically significant (P≤.05) differences

  5. Development of a new test for the easy characterization of the adhesion at the interface of bilayer tablets: proof-of-concept study by experimental design.

    Science.gov (United States)

    Busignies, Virginie; Mazel, Vincent; Diarra, Harona; Tchoreloff, Pierre

    2014-12-30

    Although, adhesion at the interface of bilayer tablets is critical for their design it is difficult to characterize this adhesion between layers. In view of this, a new test with an easy implementation was proposed for the characterization of the interface of bilayer tablets. This work is presented as a proof-of-concept study to investigate the reliability of this new test with regard to the effects of some critical process parameters (e.g., compaction pressure applied on each layer) and material attributes (e.g., elasticity of the layered materials) on the interfacial adhesion of bilayer tablets. This was investigated using a design of experiment approach and the results obtained were in good accordance with those obtained with other tests and thus, confirms the potential of such a method for the measurement of the interfacial adhesion of bilayer tablets. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Bifunctional Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Mechanism and Proof-of-Concept as a Novel Therapeutic Design Strategy

    Science.gov (United States)

    Bailey, Christopher M.; Sullivan, Todd J.; Iyidogan, Pinar; Tirado-Rives, Julian; Chung, Raymond; Ruiz-Caro, Juliana; Mohamed, Ebrahim; Jorgensen, William; Hunter, Roger; Anderson, Karen S.

    2013-01-01

    Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a major target for currently approved anti-HIV drugs. These drugs are divided into two classes: nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). This study illustrates the synthesis and biochemical evaluation of a novel bifunctional RT inhibitor utilizing d4T (NRTI) and a TMC-derivative (a diarylpyrimidine NNRTI) linked via a poly(ethylene glycol) (PEG) linker. HIV-1 RT successfully incorporates the triphosphate of d4T-4PEG-TMC bifunctional inhibitor in a base-specific manner. Moreover, this inhibitor demonstrates low nanomolar potency that has 4.3-fold and 4300-fold enhancement of polymerization inhibition in vitro relative to the parent TMC-derivative and d4T, respectively. This study serves as a proof-of-concept for the development and optimization of bifunctional RT inhibitors as potent inhibitors of HIV-1 viral replication. PMID:23659183

  7. Technology Assessment for Proof-of-Concept UF6 Cylinder Unique Identification Task 3.1.2 Report – Survey and Assessment of Technologies

    Energy Technology Data Exchange (ETDEWEB)

    Wylie, Joann; Hockert, John

    2014-04-24

    The National Nuclear Security Administration (NNSA) Office of Nonproliferation and International Security’s (NA-24) Next Generation Safeguards Initiative (NGSI) and the nuclear industry have begun to develop approaches to identify and monitor uranium hexafluoride (UF6) cylinders. The NA-24 interest in a global monitoring system for UF6 cylinders relates to its interest in supporting the International Atomic Energy Agency (IAEA) in deterring and detecting diversion of UF6 (e.g., loss of cylinder in transit) and undeclared excess production at conversion and enrichment facilities. The industry interest in a global monitoring system for UF6 cylinders relates to the improvements in operational efficiencies that such a system would provide. This task is part of an effort to survey and assess technologies for a UF6 cylinder to identify candidate technologies for a proof-of-concept demonstration and evaluation for the Cylinder Identification System (CIS).

  8. An Adaptive Treatment to Improve Positive Airway Pressure (PAP) Adherence in Patients With Obstructive Sleep Apnea: A Proof of Concept Trial.

    Science.gov (United States)

    Cvengros, Jamie A; Rodríguez, Vivian M; Snyder, Sarah; Hood, Megan M; Crawford, Megan; Park, Margaret

    2017-01-01

    Despite the benefits of positive airway pressure (PAP) treatment, rates of adherence to treatment are suboptimal. This proof-of-concept study assessed the feasibility, acceptability, and clinical significance of an adaptive treatment strategy to improve adherence to PAP. All participants first completed a brief educational intervention. Those who did not show at least a 25% increase in PAP use were randomized to receive a second, more intensive intervention, either motivational enhancement treatment or self-management treatment. Results suggested adequate feasibility and acceptability. In addition, participants demonstrated significant increases in objective PAP use, improvements in sleep quality, and decreases in daytime sleepiness. This study represents a first step in the development and validation of an adaptive treatment strategy to improve PAP adherence.

  9. An artificial intelligence tool to predict fluid requirement in the intensive care unit: a proof-of-concept study

    Science.gov (United States)

    Celi, Leo Anthony; Hinske, L Christian; Alterovitz, Gil; Szolovits, Peter

    2008-01-01

    Introduction The goal of personalised medicine in the intensive care unit (ICU) is to predict which diagnostic tests, monitoring interventions and treatments translate to improved outcomes given the variation between patients. Unfortunately, processes such as gene transcription and drug metabolism are dynamic in the critically ill; that is, information obtained during static non-diseased conditions may have limited applicability. We propose an alternative way of personalising medicine in the ICU on a real-time basis using information derived from the application of artificial intelligence on a high-resolution database. Calculation of maintenance fluid requirement at the height of systemic inflammatory response was selected to investigate the feasibility of this approach. Methods The Multi-parameter Intelligent Monitoring for Intensive Care II (MIMIC II) is a database of patients admitted to the Beth Israel Deaconess Medical Center ICU in Boston. Patients who were on vasopressors for more than six hours during the first 24 hours of admission were identified from the database. Demographic and physiological variables that might affect fluid requirement or reflect the intravascular volume during the first 24 hours in the ICU were extracted from the database. The outcome to be predicted is the total amount of fluid given during the second 24 hours in the ICU, including all the fluid boluses administered. Results We represented the variables by learning a Bayesian network from the underlying data. Using 10-fold cross-validation repeated 100 times, the accuracy of the model in predicting the outcome is 77.8%. The network generated has a threshold Bayes factor of seven representing the posterior probability of the model given the observed data. This Bayes factor translates into p < 0.05 assuming a Gaussian distribution of the variables. Conclusions Based on the model, the probability that a patient would require a certain range of fluid on day two can be predicted. In the

  10. An artificial intelligence tool to predict fluid requirement in the intensive care unit: a proof-of-concept study.

    Science.gov (United States)

    Celi, Leo Anthony; Hinske, L Christian; Alterovitz, Gil; Szolovits, Peter

    2008-01-01

    The goal of personalised medicine in the intensive care unit (ICU) is to predict which diagnostic tests, monitoring interventions and treatments translate to improved outcomes given the variation between patients. Unfortunately, processes such as gene transcription and drug metabolism are dynamic in the critically ill; that is, information obtained during static non-diseased conditions may have limited applicability. We propose an alternative way of personalising medicine in the ICU on a real-time basis using information derived from the application of artificial intelligence on a high-resolution database. Calculation of maintenance fluid requirement at the height of systemic inflammatory response was selected to investigate the feasibility of this approach. The Multi-parameter Intelligent Monitoring for Intensive Care II (MIMIC II) is a database of patients admitted to the Beth Israel Deaconess Medical Center ICU in Boston. Patients who were on vasopressors for more than six hours during the first 24 hours of admission were identified from the database. Demographic and physiological variables that might affect fluid requirement or reflect the intravascular volume during the first 24 hours in the ICU were extracted from the database. The outcome to be predicted is the total amount of fluid given during the second 24 hours in the ICU, including all the fluid boluses administered. We represented the variables by learning a Bayesian network from the underlying data. Using 10-fold cross-validation repeated 100 times, the accuracy of the model in predicting the outcome is 77.8%. The network generated has a threshold Bayes factor of seven representing the posterior probability of the model given the observed data. This Bayes factor translates into p < 0.05 assuming a Gaussian distribution of the variables. Based on the model, the probability that a patient would require a certain range of fluid on day two can be predicted. In the presence of a larger database, analysis

  11. Investigations of motor-cortex cortical plasticity following facilitatory and inhibitory transcranial theta-burst stimulation in schizophrenia: a proof-of-concept study.

    Science.gov (United States)

    Hasan, Alkomiet; Brinkmann, Caroline; Strube, Wolfgang; Palm, Ulrich; Malchow, Berend; Rothwell, John C; Falkai, Peter; Wobrock, Thomas

    2015-02-01

    Impaired neural plasticity has been proposed as an important pathophysiological feature underlying the neurobiology and symptomatology of schizophrenia. In this proof-of-concept study, we aimed to explore cortical plasticity in schizophrenia patients with two different transcranial theta-burst (TBS) paradigms. TBS induces Ca(2+)-dependent long-term-potentiation (LTP)-like and long-term-depression (LTP)-like plasticity in the human motor cortex. A total of 10 schizophrenia patients and 10 healthy controls were included in this study. Cortical excitability was investigated using transcranial magnetic stimulation in each study participant before and after TBS applied to the left primary motor-cortex on two different days. cTBS600 was used to induce LTD-like and cTBS300 was used to induce LTP-like plasticity in the absence of any prior motor-cortex activation. Repeated measures ANOVAs showed a significant interaction between the timecourse, the study group and the stimulation paradigm (cTBS600 vs. cTBS300) for the left, but not for the right hemisphere. Healthy controls showed an MEP amplitude decrease at a trend level following cTBS600 and a numeric, but not significant, increase in MEP amplitudes following cTBS300. Schizophrenia patients did not show an MEP amplitude decrease following cTBS600, but surprisingly a significant MEP decrease following cTBS300. The proportion of subjects showing the expected changes in motor-cortex excitability following both cTBS paradigms was higher in healthy controls. These preliminary results indicate differences in cortical plasticity following two different cTBS protocols in schizophrenia patients compared to healthy controls. However, the incomplete plasticity response in the healthy controls and the proof-of-concept nature of this study need to be considered as important limitations.

  12. A Phase II Multicentre, Open-Label, Proof-of-Concept Study of Tasquinimod in Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers.

    Science.gov (United States)

    Escudier, Bernard; Faivre, Sandrine; Van Cutsem, Eric; Germann, Nathalie; Pouget, Jean-Christophe; Plummer, Ruth; Vergote, Ignace; Thistlethwaite, Fiona; Bjarnason, Georg A; Jones, Robert; Mackay, Helen; Edeline, Julien; Fartoux, Laetitia; Hirte, Hal; Oza, Amit

    2017-08-10

    Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment. Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%). This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer. NCT01743469.

  13. IκB kinase inhibition as a potential treatment of osteoarthritis - results of a clinical proof-of-concept study.

    Science.gov (United States)

    Grothe, K; Flechsenhar, K; Paehler, T; Ritzeler, O; Beninga, J; Saas, J; Herrmann, M; Rudolphi, K

    2017-01-01

    This publication summarizes the clinical development of the compound SAR113945, an IκB kinase inhibitor injected intra-articularly in a slow-release formulation to treat patients with symptomatic osteoarthritis (OA) of the knee. In vitro experiments demonstrated a specific inhibition of the IκB kinase complex. Profiling of SAR113945 on kinases, enzymes and ion channels supported the initiation of a clinical development. Cellular assay systems also revealed an inhibition in the synthesis of interleukin 1β, tumor necrosis factor α (TNFα) and the prostaglandin E2 (PGE2). In vivo studies demonstrated positive effects of SAR113945 on thermal and mechanical hyperalgesia and even showed superiority in comparison with triamcinolone. Pharmacokinetic measurements showed a sustained release of dissolved SAR113945 locally supporting a comparably high exposure in the knee joint combined with a low systemic exposure. Three phase 1 studies with a dose-escalating design confirmed safety and tolerability of SAR113945. In those studies SAR113945 showed a positive trend on the WOMAC scores. The proof-of-concept or phase 2a study failed to show any effect in the overall group of recruited study participants for the primary endpoint, the WOMAC pain subscore at day 56, but showed a statistically significant difference in a subgroup of patients who had presented with effusion at baseline. Inhibiting the NFκB signaling pathway is an attractive method to treat patients with signs and symptoms of OA. The preclinical work and the results of the phase 1 studies appeared promising for a full clinical development, however, the proof-of-concept study failed to show efficacy in a larger patient sample size. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study.

    Science.gov (United States)

    Palm, Ulrich; Keeser, Daniel; Hasan, Alkomiet; Kupka, Michael J; Blautzik, Janusch; Sarubin, Nina; Kaymakanova, Filipa; Unger, Ina; Falkai, Peter; Meindl, Thomas; Ertl-Wagner, Birgit; Padberg, Frank

    2016-09-01

    Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (-36.1%) than after sham tDCS (-0.7%). PANSS sum scores decreased significantly more with active (-23.4%) than with sham stimulation (-2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. A multi-channel bioluminescent bacterial biosensor for the on-line detection of metals and toxicity. Part II: technical development and proof of concept of the biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Charrier, Thomas; Thouand, Gerald [UMR CNRS 6144 GEPEA, CBAC, Nantes University, PRES UNAM, Campus de la Courtaisiere-IUT, La Roche-sur-Yon cedex (France); Chapeau, Cyrille [Biolumine, Biokar Diagnostic, Rue des Quarante Mines ZAC de Ther-Allonne, Beauvais Cedex (France); Bendria, Loubna; Daniel, Philippe [UMR CNRS 6087 LPEC, Universite du Maine, Av Olivier Messiaen, Le Mans cedex 9 (France); Picart, Pascal [UMR CNRS 6613 IAM-LAUM, Ecole Nationale des Ingenieurs du Mans, Universite du Maine, Le Mans Cedex 9 (France)

    2011-05-15

    This research study deals with the on-line detection of heavy metals and toxicity within the context of environmental pollution monitoring. It describes the construction and the proof of concept of a multi-channel bioluminescent bacterial biosensor in immobilized phase: Lumisens3. This new versatile device, designed for the non-stop analysis of water pollution, enables the insertion of any bioluminescent strains (inducible or constitutive), immobilized in a multi-well removable card. The technical design of Lumisens3 has benefited from both a classical and a robust approach and includes four main parts: (1) a dedicated removable card contains 64 wells, 3 mm in depth, arranged in eight grooves within which bacteria are immobilized, (2) this card is incubated on a Pelletier block with a CCD cooled camera on top for bioluminescence monitoring, (3) a fluidic network feeds the card with the sample to be analyzed and finally (4) a dedicated computer interface, BIOLUX 1.0, controls all the elements of the biosensor, allowing it to operate autonomously. The proof of concept of this biosensor was performed using a set of four bioluminescent bacteria (Escherichia coli DH1 pBzntlux, pBarslux, pBcoplux, and E. coli XL1 pBfiluxCDABE) in the on-line detection of CdCl{sub 2} 0.5 {mu}M and As{sub 2}O{sub 3} 5 {mu}M from an influent. When considering metals individually, the ''fingerprints'' from the biosensor were as expected. However, when metals were mixed together, cross reaction and synergistic effects were detected. This biosensor allowed us to demonstrate the simultaneous on-line cross detection of one or several heavy metals as well as the measurement of the overall toxicity of the sample. (orig.)

  16. Early peripheral laser photocoagulation of nonperfused retina improves vision in patients with central retinal vein occlusion (Results of a proof of concept study).

    Science.gov (United States)

    Rehak, Matus; Tilgner, Eric; Franke, Annegret; Rauscher, Franziska G; Brosteanu, Oana; Wiedemann, Peter

    2014-05-01

    To evaluate the effect of combination of ranibizumab and laser photocoagulation to peripheral retinal areas of nonperfusion in patients with non-ischemic central retinal vein occlusion (CRVO) without neovascularizations. This prospective, proof of concept study randomized 22 CRVO patients into two arms. The RL group (ranibizumab + laser; n = 10) received ranibizumab with additive laser photocoagulation; the control R group (n = 12) was treated with ranibizumab only. All patients received three initial monthly ranibizumab injections followed by PRN regimen. Changes in best corrected visual acuity (BCVA) and in central retinal thickness (CRT) were documented over 6 months. Median of BCVA improved in the RL group from 65 ETDRS letters (interquartile range IQR = 10 letters) at baseline to 70 (IQR = 23.2) letters at month 6. In the control group BCVA remained stable [baseline: 61 (IQR = 19.5) and month 6: 61 (IQR = 22) letters]. CRT decreased between baseline and final visit in the RL group from 547 (IQR = 513) μm to 246.5 (IQR = 346.3) μm, and in the control group from 637.5 (IQR = 344) μm to 423 (IQR = 737) μm. More pronounced improvements in BCVA were seen in the RL group (medians = 14 vs. 6.5 letters) although the observed group differences were not statistically significant due to small samples. The selective laser photocoagulation of peripheral areas of nonperfusion seems to lead to additional visual improvement in patients with CRVO. A larger replication trial is necessary to confirm the results of this proof of concept study.

  17. A computational proof of concept of a machine-intelligent artificial pancreas using Lyapunov stability and differential game theory.

    Science.gov (United States)

    Greenwood, Nigel J C; Gunton, Jenny E

    2014-07-01

    This study demonstrated the novel application of a "machine-intelligent" mathematical structure, combining differential game theory and Lyapunov-based control theory, to the artificial pancreas to handle dynamic uncertainties. Realistic type 1 diabetes (T1D) models from the literature were combined into a composite system. Using a mixture of "black box" simulations and actual data from diabetic medical histories, realistic sets of diabetic time series were constructed for blood glucose (BG), interstitial fluid glucose, infused insulin, meal estimates, and sometimes plasma insulin assays. The problem of underdetermined parameters was side stepped by applying a variant of a genetic algorithm to partial information, whereby multiple candidate-personalized models were constructed and then rigorously tested using further data. These formed a "dynamic envelope" of trajectories in state space, where each trajectory was generated by a hypothesis on the hidden T1D system dynamics. This dynamic envelope was then culled to a reduced form to cover observed dynamic behavior. A machine-intelligent autonomous algorithm then implemented game theory to construct real-time insulin infusion strategies, based on the flow of these trajectories through state space and their interactions with hypoglycemic or near-hyperglycemic states. This technique was tested on 2 simulated participants over a total of fifty-five 24-hour days, with no hypoglycemic or hyperglycemic events, despite significant uncertainties from using actual diabetic meal histories with 10-minute warnings. In the main case studies, BG was steered within the desired target set for 99.8% of a 16-hour daily assessment period. Tests confirmed algorithm robustness for ±25% carbohydrate error. For over 99% of the overall 55-day simulation period, either formal controller stability was achieved to the desired target or else the trajectory was within the desired target. These results suggest that this is a stable, high

  18. Correlation of In Vivo Versus In Vitro Benchmark Doses (BMDs) Derived From Micronucleus Test Data: A Proof of Concept Study.

    Science.gov (United States)

    Soeteman-Hernández, Lya G; Fellows, Mick D; Johnson, George E; Slob, Wout

    2015-12-01

    In this study, we explored the applicability of using in vitro micronucleus (MN) data from human lymphoblastoid TK6 cells to derive in vivo genotoxicity potency information. Nineteen chemicals covering a broad spectrum of genotoxic modes of action were tested in an in vitro MN test using TK6 cells using the same study protocol. Several of these chemicals were considered to need metabolic activation, and these were administered in the presence of S9. The Benchmark dose (BMD) approach was applied using the dose-response modeling program PROAST to estimate the genotoxic potency from the in vitro data. The resulting in vitro BMDs were compared with previously derived BMDs from in vivo MN and carcinogenicity studies. A proportional correlation was observed between the BMDs from the in vitro MN and the BMDs from the in vivo MN assays. Further, a clear correlation was found between the BMDs from in vitro MN and the associated BMDs for malignant tumors. Although these results are based on only 19 compounds, they show that genotoxicity potencies estimated from in vitro tests may result in useful information regarding in vivo genotoxic potency, as well as expected cancer potency. Extension of the number of compounds and further investigation of metabolic activation (S9) and of other toxicokinetic factors would be needed to validate our initial conclusions. However, this initial work suggests that this approach could be used for in vitro to in vivo extrapolations which would support the reduction of animals used in research (3Rs: replacement, reduction, and refinement).

  19. Autologous temporomandibular joint reconstruction independent of exogenous additives: a proof-of-concept study for guided self-generation

    Science.gov (United States)

    Wei, Jiao; Herrler, Tanja; Han, Dong; Liu, Kai; Huang, Rulin; Guba, Markus; Dai, Chuanchang; Li, Qingfeng

    2016-01-01

    Joint defects are complex and difficult to reconstruct. By exploiting the body’s own regenerative capacity, we aimed to individually generate anatomically precise neo-tissue constructs for autologous joint reconstruction without using any exogenous additives. In a goat model, CT scans of the mandibular condyle including articular surface and a large portion of the ascending ramus were processed using computer-aided design and manufacturing. A corresponding hydroxylapatite negative mold was printed in 3D and temporarily embedded into the transition zone of costal periosteum and perichondrium. A demineralized bone matrix scaffold implanted on the contralateral side served as control. Neo-tissue constructs obtained by guided self-generation exhibited accurate configuration, robust vascularization, biomechanical stability, and function. After autologous replacement surgery, the constructs showed stable results with similar anatomical, histological, and functional findings compared to native controls. Further studies are required to assess long-term outcome and possible extensions to other further applications. The absence of exogenous cells, growth factors, and scaffolds may facilitate clinical translation of this approach. PMID:27892493

  20. Autologous temporomandibular joint reconstruction independent of exogenous additives: a proof-of-concept study for guided self-generation.

    Science.gov (United States)

    Wei, Jiao; Herrler, Tanja; Han, Dong; Liu, Kai; Huang, Rulin; Guba, Markus; Dai, Chuanchang; Li, Qingfeng

    2016-11-28

    Joint defects are complex and difficult to reconstruct. By exploiting the body's own regenerative capacity, we aimed to individually generate anatomically precise neo-tissue constructs for autologous joint reconstruction without using any exogenous additives. In a goat model, CT scans of the mandibular condyle including articular surface and a large portion of the ascending ramus were processed using computer-aided design and manufacturing. A corresponding hydroxylapatite negative mold was printed in 3D and temporarily embedded into the transition zone of costal periosteum and perichondrium. A demineralized bone matrix scaffold implanted on the contralateral side served as control. Neo-tissue constructs obtained by guided self-generation exhibited accurate configuration, robust vascularization, biomechanical stability, and function. After autologous replacement surgery, the constructs showed stable results with similar anatomical, histological, and functional findings compared to native controls. Further studies are required to assess long-term outcome and possible extensions to other further applications. The absence of exogenous cells, growth factors, and scaffolds may facilitate clinical translation of this approach.

  1. Ultra-High Gradient Channeling Acceleration in Nanostructures: Design/Progress of Proof-of-Concept (POC) Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Young Min [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Northern Illinois Univ., DeKalb, IL (United States). Northern Illinois Center for Accelerator & Detector Development; Green, A. [Northern Illinois Univ., DeKalb, IL (United States). Northern Illinois Center for Accelerator & Detector Development; Lumpkin, A. H. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Thurman-Keup, R. M. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Shiltsev, V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Zhang, X. [Shanhai Inst. of Optics and Fine Mechanics, Shanghai (China); Farinella, D. M. [Univ. of California, Irvine, CA (United States); Taborek, P. [Univ. of California, Irvine, CA (United States); Tajima, T. [Univ. of California, Irvine, CA (United States); Wheeler, J. A. [Univ. of Michigan, Ann Arbor, MI (United States). Center for Ultrafast Optical Science and FOCUS Center; Ecole Polytechnique, CNRS, Palaiseau (France). Lab. d' Optique Appliquee; Mourou, G. [Univ. of Michigan, Ann Arbor, MI (United States). Center for Ultrafast Optical Science and FOCUS Center; Ecole Polytechnique, CNRS, Palaiseau (France). Lab. d' Optique Appliquee

    2016-09-16

    A short bunch of relativistic particles or a short-pulse laser perturbs the density state of conduction electrons in a solid crystal and excites wakefields along atomic lattices in a crystal. Under a coupling condition the wakes, if excited, can accelerate channeling particles with TeV/m acceleration gradients in principle since the density of charge carriers (conduction electrons) in solids n0 = ~ 1020 – 1023 cm-3 is significantly higher than what can be obtained in gaseous plasma. Nanostructures have some advantages over crystals for channeling applications of high power beams. The dechanneling rate can be reduced and the beam acceptance increased by the large size of the channels. For beam-driven acceleration, a bunch length with a sufficient charge density would need to be in the range of the plasma wavelength to properly excite plasma wakefields, and channeled particle acceleration with the wakefields must occur before the ions in the lattices move beyond the restoring threshold. In the case of the excitation by short laser pulses, the dephasing length is appreciably increased with the larger channel, which enables channeled particles to gain sufficient amounts of energy. This paper describes simulation analyses on beam- and laser (X-ray)-driven accelerations in effective nanotube models obtained from Vsim and EPOCH codes. Experimental setups to detect wakefields are also outlined with accelerator facilities at Fermilab and NIU. In the FAST facility, the electron beamline was successfully commissioned at 50 MeV and it is being upgraded toward higher energies for electron accelerator R&D. The 50 MeV injector beamline of the facility is used for X-ray crystal-channeling radiation with a diamond target. It has been proposed to utilize the same diamond crystal for a channeling acceleration POC test. Another POC experiment is also designed for the NIU accelerator lab with time-resolved electron diffraction. Recently, a

  2. Ultra-High Gradient Channeling Acceleration in Nanostructures: Design/Progress of Proof-of-Concept (POC) Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Young min [Fermilab; Green, A. [NICADD, DeKalb; Lumpkin, A. H. [Fermilab; Thurman-Keup, R. M. [Fermilab; Shiltsev, V. [Fermilab; Zhang, X. [Shanghai, Inst. Optics, Fine Mech.; Farinella, D. M. [UC, Irvine; Taborek, P. [UC, Irvine; Tajima, T. [UC, Irvine; Wheeler, J. A. [U. Michigan, Ann Arbor; Mourou, G. [U. Michigan, Ann Arbor

    2016-09-16

    A short bunch of relativistic particles or a short-pulse laser perturbs the density state of conduction electrons in a solid crystal and excites wakefields along atomic lattices in a crystal. Under a coupling condition the wakes, if excited, can accelerate channeling particles with TeV/m acceleration gradients [1] in principle since the density of charge carriers (conduction electrons) in solids n0 = ~ 10 to the power of 20 – 10 to the power of 23 cm-3 is significantly higher than what was considered above in gaseous plasma. Nanostructures have some advantages over crystals for channeling applications of high power beams. The dechanneling rate can be reduced and the beam acceptance increased by the large size of the channels. For beam driven acceleration, a bunch length with a sufficient charge density would need to be in the range of the plasma wavelength to properly excite plasma wakefields, and channeled particle acceleration with the wakefields must occur before the ions in the lattices move beyond the restoring threshold. In the case of the excitation by short laser pulses, the dephasing length is appreciably increased with the larger channel, which enables channeled particles to gain sufficient amounts of energy. This paper describes simulation analyses on beam- and laser (X-ray)-driven accelerations in effective nanotube models obtained from Vsim and EPOCH codes. Experimental setups to detect wakefields are also outlined with accelerator facilities at Fermilab and NIU. In the FAST facility, the electron beamline was successfully commissioned at 50 MeV and it is being upgraded toward higher energies for electron accelerator R&D. The 50 MeV injector beamline of the facility is used for X-ray crystal-channeling radiation with a diamond target. It has been proposed to utilize the same diamond crystal for a channeling acceleration POC test. Another POC experiment is also designed for the NIU accelerator lab with time-resolved electron diffraction. Recently, a

  3. Proof of Concept: Development of Snow Liquid Water Content Profiler Using CS650 Reflectometers at Caribou, ME, USA

    Science.gov (United States)

    Pérez Díaz, Carlos L.; Muñoz, Jonathan; Lakhankar, Tarendra; Khanbilvardi, Reza; Romanov, Peter

    2017-01-01

    The quantity of liquid water in the snowpack defines its wetness. The temporal evolution of snow wetness’s plays a significant role in wet-snow avalanche prediction, meltwater release, and water availability estimations and assessments within a river basin. However, it remains a difficult task and a demanding issue to measure the snowpack’s liquid water content (LWC) and its temporal evolution with conventional in situ techniques. We propose an approach based on the use of time-domain reflectometry (TDR) and CS650 soil water content reflectometers to measure the snowpack’s LWC and temperature profiles. For this purpose, we created an easily-applicable, low-cost, automated, and continuous LWC profiling instrument using reflectometers at the Cooperative Remote Sensing Science and Technology Center-Snow Analysis and Field Experiment (CREST-SAFE) in Caribou, ME, USA, and tested it during the snow melt period (February–April) immediately after installation in 2014. Snow Thermal Model (SNTHERM) LWC simulations forced with CREST-SAFE meteorological data were used to evaluate the accuracy of the instrument. Results showed overall good agreement, but clearly indicated inaccuracy under wet snow conditions. For this reason, we present two (for dry and wet snow) statistical relationships between snow LWC and dielectric permittivity similar to Topp’s equation for the LWC of mineral soils. These equations were validated using CREST-SAFE in situ data from winter 2015. Results displayed high agreement when compared to LWC estimates obtained using empirical formulas developed in previous studies, and minor improvement over wet snow LWC estimates. Additionally, the equations seemed to be able to capture the snowpack state (i.e., onset of melt, medium, and maximum saturation). Lastly, field test results show advantages, such as: automated, continuous measurements, the temperature profiling of the snowpack, and the possible categorization of its state. However, future work

  4. Regional spore dispersal as a factor in disease risk warnings for potato late blight: A proof of concept

    NARCIS (Netherlands)

    Skelsey, P.; Kessel, G.J.T.; Holtslag, A.A.M.; Moene, A.F.; Werf, van der W.

    2009-01-01

    This study develops and tests a novel approach for including regional risk factors in operational disease risk warnings against potato late blight. The central premise is that fungicide inputs can be reduced by omitting applications on days when conditions are unsuitable for the atmospheric

  5. Regional spore dispersal as a factor in disease risk warnings for potato late blight : A proof of concept

    NARCIS (Netherlands)

    Skelsey, P.; Kessel, G. J. T.; Holtslag, A. A. M.; Moene, A. F.; van der Werf, W.

    2009-01-01

    This study develops and tests a novel approach for including regional risk factors in operational disease risk warnings against potato late blight. The central premise is that fungicide inputs can be reduced by omitting applications on days when conditions are unsuitable for the atmospheric

  6. Combining transrectal ultrasound and CT for image-guided adaptive brachytherapy of cervical cancer: Proof of concept.

    Science.gov (United States)

    Nesvacil, Nicole; Schmid, Maximilian P; Pötter, Richard; Kronreif, Gernot; Kirisits, Christian

    To investigate the feasibility of a treatment planning workflow for three-dimensional image-guided cervix cancer brachytherapy, combining volumetric transrectal ultrasound (TRUS) for target definition with CT for dose optimization to organs at risk (OARs), for settings with no access to MRI. A workflow for TRUS/CT-based volumetric treatment planning was developed, based on a customized system including ultrasound probe, stepper unit, and software for image volume acquisition. A full TRUS/CT-based workflow was simulated in a clinical case and compared with MR- or CT-only delineation. High-risk clinical target volume was delineated on TRUS, and OARs were delineated on CT. Manually defined tandem/ring applicator positions on TRUS and CT were used as a reference for rigid registration of the image volumes. Treatment plan optimization for TRUS target and CT organ volumes was performed and compared to MRI and CT target contours. TRUS/CT-based contouring, applicator reconstruction, image fusion, and treatment planning were feasible, and the full workflow could be successfully demonstrated. The TRUS/CT plan fulfilled all clinical planning aims. Dose-volume histogram evaluation of the TRUS/CT-optimized plan (high-risk clinical target volume D90, OARs D2cm³ for) on different image modalities showed good agreement between dose values reported for TRUS/CT and MRI-only reference contours and large deviations for CT-only target parameters. A TRUS/CT-based workflow for full three-dimensional image-guided cervix brachytherapy treatment planning seems feasible and may be clinically comparable to MRI-based treatment planning. Further development to solve challenges with applicator definition in the TRUS volume is required before systematic applicability of this workflow. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  7. Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT): e0143846

    National Research Council Canada - National Science Library

    Hendrik P N Scholl; Anthony T Moore; Robert K Koenekoop; Yuquan Wen; Gerald A Fishman; Ingeborgh van den Born; Ava Bittner; Kristen Bowles; Emily C Fletcher; Frederick T Collison; Gislin Dagnelie; Simona Degli Eposti; Michel Michaelides; David A Saperstein; Ronald A Schuchard; Claire Barnes; Wadih Zein; Ditta Zobor; David G Birch; Janine D Mendola; Eberhart Zrenner

    2015-01-01

    ...). Safety and visual outcomes of a once-daily oral dose of 40 mg/m2/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18...

  8. Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT)

    National Research Council Canada - National Science Library

    Scholl, Hendrik P N; Moore, Anthony T; Koenekoop, Robert K; Wen, Yuquan; Fishman, Gerald A; van den Born, L Ingeborgh; Bittner, Ava; Bowles, Kristen; Fletcher, Emily C; Collison, Frederick T; Dagnelie, Gislin; Degli Eposti, Simona; Michaelides, Michel; Saperstein, David A; Schuchard, Ronald A; Barnes, Claire; Zein, Wadih; Zobor, Ditta; Birch, David G; Mendola, Janine D; Zrenner, Eberhart

    2015-01-01

    ...). Safety and visual outcomes of a once-daily oral dose of 40 mg/m2/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18...

  9. Why people download the freeware AIDA v4.3a diabetes software program: a proof-of-concept semi-automated analysis.

    Science.gov (United States)

    Lehmann, Eldon D

    2003-01-01

    AIDA is a diabetes-computing program freely available at www.2aida.org on the Web. The software is intended to serve as an educational support tool and can be used by anyone who has an interest in diabetes, whether they be patients, relatives, health-care professionals, or students. In previous "Diabetes Information Technology & WebWatch" columns various indicators of usage of the AIDA program have been reviewed, and various comments from users of the software have been documented. The purpose of this column is to overview a proof-of-concept semi-automated analysis about why people are downloading the latest version of the AIDA educational diabetes program. AIDA permits the interactive simulation of plasma insulin and blood glucose profiles for teaching, demonstration, self-learning, and research purposes. It has been made freely available, without charge, on the Internet as a noncommercial contribution to continuing diabetes education. Since its launch in 1996 over 300,000 visits have been logged at the main AIDA Website-www.2aida.org-and over 60,000 copies of the AIDA program have been downloaded free-of-charge. This column documents the results of a semi-automated analysis of comments left by Website visitors while they were downloading the AIDA software, before they had a chance to use the program. The Internet-based survey methodology and semi-automated analysis were both found to be robust and reliable. Over a 5-month period (from October 3, 2001 to February 28, 2002) 400 responses were received. During the corresponding period 1,770 actual visits were made to the Website survey page-giving a response rate to this proof-of-concept study of 22.6%. Responses were received from participants in over 54 countries-with nearly half of these (n = 194; 48.5%) originating from the United States, United Kingdom, and Canada; 208 responses (52.0%) were received from patients with diabetes, 50 (12.5%) from doctors, 49 (12.3%) from relatives of patients, with fewer

  10. Use of the Blom Tracheotomy Tube with Suction Inner Cannula to Decontaminate Microorganisms from the Subglottic Space. A Proof of Concept.

    Science.gov (United States)

    Rabach, Lesley; Siegel, Mark D; Puchalski, Jonathan T; Towle, Dana; Follert, Michelle; Johnson, Kelsey M; Rademaker, Alfred W; Leder, Steven B

    2015-06-01

    Preventing pulmonary complications during mechanical ventilation via tracheotomy is a high priority. To investigate if the Blom tracheotomy tube with suction-above-the-cuff inner cannula reduced the quantity of normal flora and pathogens in supra- versus subglottic spaces. We enrolled 20 consecutive medical ICU adults requiring tracheostomy for mechanical ventilation in this proof-of-concept, prospective, single-center study. All participants received a Blom tracheotomy tube with suction-above-the-cuff inner cannula to decontaminate microorganisms from the supra- and subglottic spaces. Supra- and subglottic sputum samples were obtained for microbiologic analysis while an endotracheal tube was in place before tracheotomy and once per week for up to 4 weeks of mechanical ventilation after tracheotomy. Demographics, duration of endotracheal tube intubation, and duration of mechanical ventilation post-tracheotomy were recorded. There was a significant reduction for supraglottic (2.86 ± 1.11 [mean ± SD]) versus subglottic suction samples (2.48 ± 1.07) (paired t test, P = 0.048; Wilcoxon test, P = 0.045) when all data pairs for normal flora and pathogens were combined across times. There was a significant reduction of normal flora pooled across times in 19 data pairs for supraglottic (3.00 ± 1.05) versus subglottic suction samples (2.00 ± 0.94) (paired t test, P = 0.0004; Wilcoxon test, P = 0.0007). There was no significant reduction of pathogens pooled across times in 25 data pairs for supraglottic (2.76 ± 1.16) versus subglottic suction samples (2.84 ± 1.03) (paired t test, P = 0.75; Wilcoxon test, P = 0.83). Proof-of-concept was confirmed. The Blom tracheotomy tube with disposable suction-above-the-cuff inner cannula decontaminated microorganisms from the subglottic space when normal flora and pathogens were combined. Future research should investigate if decreased quantity of normal flora and pathogens in the subglottic space reduces the incidence of

  11. Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination.

    Science.gov (United States)

    Perez-Vilar, Silvia; Weibel, Daniel; Sturkenboom, Miriam; Black, Steven; Maure, Christine; Castro, Jose Luis; Bravo-Alcántara, Pamela; Dodd, Caitlin N; Romio, Silvana A; de Ridder, Maria; Nakato, Swabra; Molina-León, Helvert Felipe; Elango, Varalakshmi; Zuber, Patrick L F

    2017-05-27

    New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders'Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the

  12. Promotion of the mind through exercise (PROMoTE: a proof-of-concept randomized controlled trial of aerobic exercise training in older adults with vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    Davis Jennifer C

    2010-02-01

    Full Text Available Abstract Background Sub-cortical vascular ischaemia is the second most common etiology contributing to cognitive impairment in older adults, and is frequently under-diagnosed and under-treated. Although evidence is mounting that exercise has benefits for cognitive function among seniors, very few randomized controlled trials of exercise have been conducted in populations at high-risk for progression to dementia. Aerobic-based exercise training may be of specific benefit in delaying the progression of cognitive decline among seniors with vascular cognitive impairment by reducing key vascular risk factors associated with metabolic syndrome. Thus, we aim to carry out a proof-of-concept single-blinded randomized controlled trial primarily designed to provide preliminary evidence of efficacy aerobic-based exercise training program on cognitive and everyday function among older adults with mild sub-cortical ischaemic vascular cognitive impairment. Methods/Design A proof-of-concept single-blinded randomized trial comparing a six-month, thrice-weekly, aerobic-based exercise training group with usual care on cognitive and everyday function. Seventy older adults who meet the diagnostic criteria for sub-cortical ischaemic vascular cognitive impairment as outlined by Erkinjuntti and colleagues will be recruited from a memory clinic of a metropolitan hospital. The aerobic-based exercise training will last for 6 months. Participants will be followed for an additional six months after the cessation of exercise training. Discussion This research will be an important first step in quantifying the effect of an exercise intervention on cognitive and daily function among seniors with sub-cortical ischaemic vascular cognitive impairment, a recognized risk state for progression to dementia. Exercise has the potential to be an effective, inexpensive, and accessible intervention strategy with minimal adverse effects. Reducing the rate of cognitive decline among seniors

  13. Comparison of markerless and marker-based motion capture technologies through simultaneous data collection during gait: proof of concept.

    Directory of Open Access Journals (Sweden)

    Elena Ceseracciu

    Full Text Available During the last decade markerless motion capture techniques have gained an increasing interest in the biomechanics community. In the clinical field, however, the application of markerless techniques is still debated. This is mainly due to a limited number of papers dedicated to the comparison with the state of the art of marker based motion capture, in term of repeatability of the three dimensional joints' kinematics. In the present work the application of markerless technique to data acquired with a marker-based system was investigated. All videos and external data were recorded with the same motion capture system and included the possibility to use markerless and marker-based methods simultaneously. Three dimensional markerless joint kinematics was estimated and compared with the one determined with traditional marker based systems, through the evaluation of root mean square distance between joint rotations. In order to compare the performance of markerless and marker-based systems in terms of clinically relevant joint angles estimation, the same anatomical frames of reference were defined for both systems. Differences in calibration and synchronization of the cameras were excluded by applying the same wand calibration and lens distortion correction to both techniques. Best results were achieved for knee flexion-extension angle, with an average root mean square distance of 11.75 deg, corresponding to 18.35% of the range of motion. Sagittal plane kinematics was estimated better than on the other planes also for hip and ankle (root mean square distance of 17.62 deg e.g. 44.66%, and 7.17 deg e.g. 33.12%, meanwhile estimates for hip joint were the most incorrect. This technique enables users of markerless technology to compare differences with marker-based in order to define the degree of applicability of markerless technique.

  14. OCT Segmentation Survey and Summary Reviews and a Novel 3D Segmentation Algorithm and a Proof of Concept Implementation

    CERN Document Server

    Mokhov, Serguei A

    2012-01-01

    We overview the existing OCT work, especially the practical aspects of it. We create a novel algorithm for 3D OCT segmentation with the goals of speed and/or accuracy while remaining flexible in the design and implementation for future extensions and improvements. The document at this point is a running draft being iteratively "developed" as a progress report as the work and survey advance. It contains the review and summarization of select OCT works, the design and implementation of the OCTMARF experimentation application and some results.

  15. Virtual reality imaging with real-time ultrasound guidance for facet joint injection: a proof of concept.

    Science.gov (United States)

    Clarke, Collin; Moore, John; Wedlake, Christopher; Lee, Donald; Ganapathy, Su; Salbalbal, Maher; Wilson, Timothy; Peters, Terry; Bainbridge, Daniel

    2010-05-01

    Facet interventions continue to be used in pain management. Computed tomographic (CT) images can be registered into a virtual world that includes images generated by an ultrasound (US) probe tracked in real time, permitting guidance of tracked needles. We acquired CT-generated 3-dimensional (3D) images of 2 models and a cadaver. Three-dimensional representations of a US probe and needle were generated. A magnetic system tracked the needle and US probe. Using the US, 3D CT images were registered to the model/cadaver. Images were fused on a single interface. Facet injections were performed in the models and cadaver with radio-opaque markers. A postprocedure CT image determined appropriate placement. The virtual reality system described demonstrates technical innovations that may lead to future advancements in the area of percutaneous interventions in the management of pain.

  16. Knowledge-based expert systems and a proof-of-concept case study for multiple sequence alignment construction and analysis.

    Science.gov (United States)

    Aniba, Mohamed Radhouene; Siguenza, Sophie; Friedrich, Anne; Plewniak, Frédéric; Poch, Olivier; Marchler-Bauer, Aron; Thompson, Julie Dawn

    2009-01-01

    The traditional approach to bioinformatics analyses relies on independent task-specific services and applications, using different input and output formats, often idiosyncratic, and frequently not designed to inter-operate. In general, such analyses were performed by experts who manually verified the results obtained at each step in the process. Today, the amount of bioinformatics information continuously being produced means that handling the various applications used to study this information presents a major data management and analysis challenge to researchers. It is now impossible to manually analyse all this information and new approaches are needed that are capable of processing the large-scale heterogeneous data in order to extract the pertinent information. We review the recent use of integrated expert systems aimed at providing more efficient knowledge extraction for bioinformatics research. A general methodology for building knowledge-based expert systems is described, focusing on the unstructured information management architecture, UIMA, which provides facilities for both data and process management. A case study involving a multiple alignment expert system prototype called AlexSys is also presented.

  17. Pooling and Analysis of Published in Vitro Data: A Proof of Concept Study for the Grouping of Nanoparticles

    Directory of Open Access Journals (Sweden)

    Myrtill Simkó

    2015-11-01

    Full Text Available The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO2, TiO2, ZnO, CuO, CeO2 and carbon nanotubes, [CNT] nanoparticles (NP and to test the usefulness for grouping purposes. Publication selection was based on specific criteria regarding experimental conditions. Two relevant biological endpoints were selected; generation of intracellular reactive oxygen species (ROS and viability above 90%. The correlations of the ROS ratios with the NP parameters’ size, concentration, and exposure time were analysed. The obtained data sets were then analysed with multiple regression analysis of variance (ANOVA and the Tukey post-hoc test. The results show that this method is applicable for the selected metal oxide NP, but might need reconsideration and a larger data set for CNT. Several statistically significant correlations and results were obtained, thus validating the method. Furthermore, the relevance of the combination of ROS release with a cell viability test was shown. The data also show that it is advisable to compare ROS production of professional phagocytic with non-phagocytic cells. In conclusion, this is the first systematic analysis showing that pooling of available data into groups is a useful method for evaluation of data regarding NP induced toxicity in vitro.

  18. On-board B-ISDN fast packet switching architectures. Phase 2: Development. Proof-of-concept architecture definition report

    Science.gov (United States)

    Shyy, Dong-Jye; Redman, Wayne

    1993-01-01

    For the next-generation packet switched communications satellite system with onboard processing and spot-beam operation, a reliable onboard fast packet switch is essential to route packets from different uplink beams to different downlink beams. The rapid emergence of point-to-point services such as video distribution, and the large demand for video conference, distributed data processing, and network management makes the multicast function essential to a fast packet switch (FPS). The satellite's inherent broadcast features gives the satellite network an advantage over the terrestrial network in providing multicast services. This report evaluates alternate multicast FPS architectures for onboard baseband switching applications and selects a candidate for subsequent breadboard development. Architecture evaluation and selection will be based on the study performed in phase 1, 'Onboard B-ISDN Fast Packet Switching Architectures', and other switch architectures which have become commercially available as large scale integration (LSI) devices.

  19. Big Data Analysis of Contractor Performance Information for Services Acquisition in DoD: A Proof of Concept

    Science.gov (United States)

    2016-04-30

    and the F-22 Raptor . He was also a contracting squadron commander and the director of contracting for the Space Based Infrared Satellite program and...large archival data sets to model customer behavior , finding ways to represent the behavioral aspects of service design in quantitative and analytical...technology, banking, insurance, sports, and government. Big Data is used by computer scientists that feed computers volumes of data with hopes that

  20. Particle Image Velocimetry Used to Qualitatively Validate Computational Fluid Dynamic Simulations in an Oxygenator: A Proof of Concept.

    Science.gov (United States)

    Schlanstein, Peter C; Hesselmann, Felix; Jansen, Sebastian V; Gemsa, Jeannine; Kaufmann, Tim A; Klaas, Michael; Roggenkamp, Dorothee; Schröder, Wolfgang; Schmitz-Rode, Thomas; Steinseifer, Ulrich; Arens, Jutta

    2015-09-01

    Computational fluid dynamics (CFD) is used to simulate blood flow inside the fiber bundles of oxygenators. The results are interpreted in terms of flow distribution, e.g., stagnation and shunt areas. However, experimental measurements that provide such information on the local flow between the fibers are missing. A transparent model of an oxygenator was built to perform particle image velocimetry (PIV), to perform the experimental validation. The similitude theory was used to adjust the size of the PIV model to the minimal resolution of the PIV system used (scale factor 3.3). A standard flow of 80 mL/min was simulated with CFD for the real oxygenator and the equivalent flow of 711 mL/min, according to the similitude theory, was investigated with PIV. CFD predicts the global size of stagnation and shunt areas well, but underestimates the streamline length and changes in velocities due to the meandering flow around the real fibers in the PIV model. Symmetrical CFD simulation cannot consider asymmetries in the flow, due to manufacturing-related asymmetries in the fiber bundle. PIV could be useful for validation of CFD simulations; measurement quality however must be improved for a quantitative validation of CFD results and the investigation of flow effects such as tortuosity and anisotropic flow behavior.

  1. Labeling and preliminary in vivo assessment of niobium-labeled radioactive species: A proof-of-concept study.

    Science.gov (United States)

    Radchenko, Valery; Bouziotis, Penelope; Tsotakos, Theodoros; Paravatou-Petsotas, Mari; la Fuente, Ana de; Loudos, George; Harris, Adrian L; Xanthopoulos, Stavros; Filosofov, Dmitry; Hauser, Harald; Eisenhut, Michael; Ponsard, Bernard; Roesch, Frank

    2016-05-01

    The application of radionuclide-labeled biomolecules such as monoclonal antibodies or antibody fragments for imaging purposes is called immunoscintigraphy. More specifically, when the nuclides used are positron emitters, such as zirconium-89, the technique is referred to as immuno-PET. Currently, there is an urgent need for radionuclides with a half-life which correlates well with the biological kinetics of the biomolecules under question and which can be attached to the proteins by robust labeling chemistry. (90)Nb is a promising candidate for in vivo immuno-PET, due its half-life of 14.6h and low β(+) energy of Emean=0.35MeV per decay. (95)Nb on the other hand, is a convenient alternative for longer-term ex vivo biodistribution studies, due to its longer half-life of (t½=35days) and its convenient, lower-cost production (reactor-based production). In this proof-of-principle work, the monoclonal antibody bevacizumab (Avastin(®)) was labeled with (95/90)Nb and in vitro and in vivo stability was evaluated in normal Swiss mice and in tumor-bearing SCID mice. Initial ex vivo experiments with (95)Nb-bevacizumab showed adequate tumor uptake, however at the same time high uptake in the liver, spleen and kidneys was observed. In order to investigate whether this behavior is due to instability of (⁎)Nb-bevacizumab or to the creation of other (⁎)Nb species in vivo, we performed biodistribution studies of (95)Nb-oxalate, (95)Nb-chloride and (95)Nb-Df. These potential metabolite species did not show any specific uptake, apart from bone accumulation for (95)Nb-oxalate and (95)Nb-chloride, which, interestingly, may serve as an "indicator" for the release of (90)Nb from labeled biomolecules. Concerning the initial uptake of (95)Nb-bevacizumab in non-tumor tissue, biodistribution of a higher specific activity radiolabeled antibody sample did show only negligible uptake in the liver, spleen, kidneys or bones. In-vivo imaging of a tumor-bearing SCID mouse after injection

  2. Can smartphones measure momentary quality of life and participation? A proof of concept using experience sampling surveys with university students.

    Science.gov (United States)

    Liddle, Jacki; Wishink, Anna; Springfield, Liz; Gustafsson, Louise; Ireland, David; Silburn, Peter

    2017-08-01

    Understanding quality of life and participation is a key aspect of occupational therapy research. The use of smartphones to deliver experience-sampling surveys may provide an accessible way to monitor these outcomes. This study used smartphone-based experience sampling methods (ESM) to investigate factors influencing momentary quality of life (mQOL) of university students. A convenience sample of students at an Australian university participated. Using a custom smartphone application, ESM surveys were sent six to eight times, every second day, over a week. Participants indicated their mQOL, occupational participation, occupational enjoyment, social context and location via surveys and provided demographic and health information in a single self-report questionnaire. The relationship between mQOL and variables was analysed at the survey level using logistic regression. Forty students completed 391 surveys. Higher mQOL was significantly related to participation in productive occupations (z = 3.48; P = 0.001), moderate (z = 4.00; P sample, analysing at the individual level, and using ESM in conjunction with other methodologies is recommended. © 2017 Occupational Therapy Australia.

  3. Quantitative analysis of scapholunate diastasis using stress speckle-tracking sonography: a proof-of-concept and feasibility study.

    Science.gov (United States)

    Gondim Teixeira, Pedro Augusto; Badr, Sammy; Hossu, Gabriela; Lefebvre, Guillaume; Abou Arab, Waled; Blum, Alain; Cotten, Anne

    2017-06-27

    To evaluate the feasibility and potential clinical applicability of speckle-tracking sonography for the dynamic evaluation of the scapholunate diastasis during stress manoeuvres. Two readers used speckle tracking sonography to evaluate scapholunate diastasis during a clenching fist manoeuver in 30 normal wrists. Scapholunate peak strain, mean scapholunate diastasis and the diastasis variation coefficient were analysed. IRB exemption was granted for this study. Conventional and stress wrist radiographs of 26 patients with and without a scapholunate ligament tear were retrospectively analysed to ascertain the range of variation in scapholunate diastasis. Speckle-tracking parameters in normal wrists were similar between the two readers (p  > 0.2061). The maximal scapholunate peak strain during stress was relatively low (Speckle-tracking sonography could represent an interesting alternative for stress evaluation of the scapholunate ligament in patients with scapholunate diastasis. • Speckle-tracking sonography can assess scapholunate diastasis under stress testing. • Scapholunate gap shows little variation under stress in healthy volunteers. • Scapholunate gap measurements are influenced by grip strength. • Sex and BMI have a significant influence on strain measurements.

  4. Proof-of-Concept of a Zinc-Silver Battery for the Extraction of Energy from a Concentration Difference

    Directory of Open Access Journals (Sweden)

    Massimo Marino

    2014-06-01

    Full Text Available The conversion of heat into current can be obtained by a process with two stages. In the first one, the heat is used for distilling a solution and obtaining two flows with different concentrations. In the second stage, the two flows are sent to an electrochemical cell that produces current by consuming the concentration difference. In this paper, we propose such an electrochemical cell, working with water solutions of zinc chloride. The cell contains two electrodes, made respectively of zinc and silver covered by silver chloride. The operation of the cell is analogous to that of the capacitive mixing and of the “mixing entropy battery”: the electrodes are charged while dipped in the concentrated solution and discharged when dipped in the diluted solution. The cyclic operation allows us to extract a surplus of energy, at the expense of the free energy of the concentration difference. We evaluate the feasibility of such a cell for practical applications and find that a power up to 2 W per m2 of the surface of the electrodes can be achieved.

  5. List-mode PET motion correction using markerless head tracking: proof-of-concept with scans of human subject.

    Science.gov (United States)

    Olesen, Oline V; Sullivan, Jenna M; Mulnix, Tim; Paulsen, Rasmus R; Højgaard, Liselotte; Roed, Bjarne; Carson, Richard E; Morris, Evan D; Larsen, Rasmus

    2013-02-01

    A custom designed markerless tracking system was demonstrated to be applicable for positron emission tomography (PET) brain imaging. Precise head motion registration is crucial for accurate motion correction (MC) in PET imaging. State-of-the-art tracking systems applied with PET brain imaging rely on markers attached to the patient's head. The marker attachment is the main weakness of these systems. A healthy volunteer participating in a cigarette smoking study to image dopamine release was scanned twice for 2 h with (11)C-racolopride on the high resolution research tomograph (HRRT) PET scanner. Head motion was independently measured, with a commercial marker-based device and the proposed vision-based system. A list-mode event-by-event reconstruction algorithm using the detected motion was applied. A phantom study with hand-controlled continuous random motion was obtained. Motion was time-varying with long drift motions of up to 18 mm and regular step-wise motion of 1-6 mm. The evaluated measures were significantly better for motion-corrected images compared to no MC. The demonstrated system agreed with a commercial integrated system. Motion-corrected images were improved in contrast recovery of small structures.

  6. A New Coupled CFD/Neutron Kinetics System for High Fidelity Simulations of LWR Core Phenomena: Proof of Concept

    Directory of Open Access Journals (Sweden)

    Jorge Pérez Mañes

    2014-01-01

    Full Text Available The Institute for Neutron Physics and Reactor Technology (INR at the Karlsruhe Institute of Technology (KIT is investigating the application of the meso- and microscale analysis for the prediction of local safety parameters for light water reactors (LWR. By applying codes like CFD (computational fluid dynamics and SP3 (simplified transport reactor dynamics it is possible to describe the underlying phenomena in a more accurate manner than by the nodal/coarse 1D thermal hydraulic coupled codes. By coupling the transport (SP3 based neutron kinetics (NK code DYN3D with NEPTUNE-CFD, within a parallel MPI-environment, the NHESDYN platform is created. The newly developed system will allow high fidelity simulations of LWR fuel assemblies and cores. In NHESDYN, a heat conduction solver, SYRTHES, is coupled to NEPTUNE-CFD. The driver module of NHESDYN controls the sequence of execution of the solvers as well as the communication between the solvers based on MPI. In this paper, the main features of NHESDYN are discussed and the proof of the concept is done by solving a single pin problem. The prediction capability of NHESDYN is demonstrated by a code-to-code comparison with the DYNSUB code. Finally, the future developments and validation efforts are highlighted.

  7. Proof of concept of a zinc-silver battery for the extraction of energy from a concentration difference

    CERN Document Server

    Marino, M; Carati, A; Brogioli, D

    2014-01-01

    The conversion of heat into current can be obtained by a process with two stages. In the first one, the heat is used for distilling a solution and obtaining two flows with different concentrations. In the second stage, the two flows are sent to an electrochemical cell that produces current by consuming the concentration difference. In this paper, we propose such an electrochemical cell, working with water solutions of zinc chloride. The cell contains two electrodes, made respectively of zinc and silver covered by silver chloride. The operation of the cell is analogous to that of the capacitive mixing and of the "mixing entropy battery": the electrodes are charged while dipped in the concentrated solution and discharged when dipped in the diluted solution. The cyclic operation allows us to extract a surplus of energy, at the expense of the free energy of the concentration difference. We evaluate the feasibility of such a cell for practical applications, and find that a power up to 2 W per square meter of surfa...

  8. Definition of a family of tissue-protective cytokines using functional cluster analysis: a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Manuela eMengozzi

    2014-03-01

    Full Text Available The discovery of the tissue-protective activities of erythropoietin (EPO has underlined the importance of some cytokines in tissue protection, repair and remodeling. As such activities have been reported for other cytokines, we asked whether we could define a class of tissue-protective cytokines. We therefore explored a novel approach based on functional clustering. In this pilot study, we started by analyzing a small number of cytokines (30. We functionally classified the 30 cytokines according to their interactions by using the bioinformatics tool STRING (Search Tool for the Retrieval of Interacting Genes, followed by hierarchical cluster analysis. The results of this functional clustering were different from those obtained by clustering cytokines simply according to their sequence. We previously reported that the protective activity of EPO in a model of cerebral ischemia was paralleled by an upregulation of synaptic plasticity genes, particularly early growth response 2 (EGR2. To assess the predictivity of functional clustering, we tested some of the cytokines clustering close to EPO (interleukin-11, IL-11; kit ligand, KITLG; leukemia inhibitory factor, LIF; thrombopoietin, THPO in an in vitro model of human neuronal cells for their ability to induce EGR2. Two of these, LIF and IL-11, induced EGR2 expression. Although these data would need to be extended to a larger number of cytokines and the biological validation should be done using more robust in vivo models, rather then just one cell line, this study shows the feasibility of this approach. This type of functional cluster analysis could be extended to other fields of cytokine research and help design biological experiments.

  9. Definition of a Family of Tissue-Protective Cytokines Using Functional Cluster Analysis: A Proof-of-Concept Study.

    Science.gov (United States)

    Mengozzi, Manuela; Ermilov, Peter; Annenkov, Alexander; Ghezzi, Pietro; Pearl, Frances

    2014-01-01

    The discovery of the tissue-protective activities of erythropoietin (EPO) has underlined the importance of some cytokines in tissue-protection, repair, and remodeling. As such activities have been reported for other cytokines, we asked whether we could define a class of tissue-protective cytokines. We therefore explored a novel approach based on functional clustering. In this pilot study, we started by analyzing a small number of cytokines (30). We functionally classified the 30 cytokines according to their interactions by using the bioinformatics tool STRING (Search Tool for the Retrieval of Interacting Genes), followed by hierarchical cluster analysis. The results of this functional clustering were different from those obtained by clustering cytokines simply according to their sequence. We previously reported that the protective activity of EPO in a model of cerebral ischemia was paralleled by an upregulation of synaptic plasticity genes, particularly early growth response 2 (EGR2). To assess the predictivity of functional clustering, we tested some of the cytokines clustering close to EPO (interleukin-11, IL-11; kit ligand, KITLG; leukemia inhibitory factor, LIF; thrombopoietin, THPO) in an in vitro model of human neuronal cells for their ability to induce EGR2. Two of these, LIF and IL-11, induced EGR2 expression. Although these data would need to be extended to a larger number of cytokines and the biological validation should be done using more robust in vivo models, rather then just one cell line, this study shows the feasibility of this approach. This type of functional cluster analysis could be extended to other fields of cytokine research and help design biological experiments.

  10. Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study.

    Science.gov (United States)

    Tregellas, Jason R; Smucny, Jason; Legget, Kristina T; Stevens, Karen E

    2015-12-01

    Although the ketogenic diet has shown promise in a pilot study and case report in schizophrenia, its effects in animal models of hypothesized disease mechanisms are unknown. This study examined effects of treatment with the ketogenic diet on hippocampal P20/N40 gating in DBA/2 mice, a translational endophenotype that mirrors inhibitory deficits in P50 sensory gating in schizophrenia patients. As expected, the diet increased blood ketone levels. Animals with the highest ketone levels showed the lowest P20/N40 gating ratios. These preliminary results suggest that the ketogenic diet may effectively target sensory gating deficits and is a promising area for additional research in schizophrenia.

  11. The Milky Way: paediatric milk-based dispersible tablets prepared by direct compression - a proof-of-concept study.

    Science.gov (United States)

    Orubu, Samuel E F; Hobson, Nicholas J; Basit, Abdul W; Tuleu, Catherine

    2017-04-01

    Dispersible tablets are proposed by the World Health Organization as the preferred paediatric formulation. It was hypothesised that tablets made from a powdered milk-base that disperse in water to form suspensions resembling milk might be a useful platform to improve acceptability in children. Milk-based dispersible tablets containing various types of powdered milk and infant formulae were formulated. The influence of milk type and content on placebo tablet properties was investigated using a design-of-experiments approach. Responses measured included friability, crushing strength and disintegration time. Additionally, the influence of compression force on the tablet properties of a model formulation was studied by compaction simulation. Disintegration times increased as milk content increased. Compaction simulation studies showed that compression force influenced disintegration time. These results suggest that the milk content, rather than type, and compression force were the most important determinants of disintegration. Up to 30% milk could be incorporated to produce 200 mg 10-mm flat-faced placebo tablets by direct compression disintegrating within 3 min in 5-10 ml of water, which is a realistic administration volume in children. The platform could accommodate 30% of a model active pharmaceutical ingredient (caffeine citrate). © 2016 Royal Pharmaceutical Society.

  12. Rhenium-coated glass beads for intracolonic administration attenuate TNBS-induced colitis in mice: Proof-of-Concept Study.

    Science.gov (United States)

    Siczek, Krzysztof; Zatorski, Hubert; Pawlak, Wojciech; Fichna, Jakub

    2015-01-01

    In search for novel effective treatments in inflammatory bowel diseases, a new strategy employing glass beads coated with rhenium nanolayer has been developed and validated in the mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Briefly, mice were randomly divided into 5 experimental groups: control (vehicle alone, Group 1); control treated with rhenium-coated glass beads (Group 2); TNBS (Group 3); TNBS treated with rhenium-coated glass beads (Group 4); and TNBS treated with uncoated glass beads (Group 5). Mice from Group 2, 4 and 5 were treated with respective beads (once daily, 5 beads / animal, i.c.) between D3-D6 post-TNBS/vehicle and evaluation of colonic damage was performed on D7, based on macroscopic scoring and clinical parameters. Severe colonic inflammation developed in post-TNBS mice (Group 3) [P glass beads (Group 4) [P glass beads had any effect in control animals (Group 2), nor uncoated glass beads influenced TNBS-induced colitis (Group 5). In conclusion, a novel and attractive strategy for the treatment of colonic inflammation has been proposed; therapy with rhenium-coated glass beads already proved effective in the mouse model of TNBS-induced colitis, now requires further characterization in clinical conditions.

  13. In situ iron activated persulfate oxidative fluid sparging treatment of TCE contamination--a proof of concept study.

    Science.gov (United States)

    Liang, Chenju; Lee, I-Ling

    2008-09-10

    In situ chemical oxidation (ISCO) is considered a reliable technology to treat groundwater contaminated with high concentrations of organic contaminants. An ISCO oxidant, persulfate anion (S(2)O(8)(2-)) can be activated by ferrous ion (Fe(2+)) to generate sulfate radicals (E(o)=2.6 V), which are capable of destroying trichloroethylene (TCE). The property of polarity inhibits S(2)O(8)(2-) or sulfate radical (SO(4)(-)) from effectively oxidizing separate phase TCE, a dense non-aqueous phase liquid (DNAPL). Thus the oxidation primarily takes place in the aqueous phase where TCE is dissolved. A bench column study was conducted to demonstrate a conceptual remediation method by flushing either S(2)O(8)(2-) or Fe(2+) through a soil column, where the TCE DNAPL was present, and passing the dissolved mixture through either a Fe(2+) or S(2)O(8)(2-) fluid sparging curtain. Also, the effect of a solubility enhancing chemical, hydroxypropyl-beta-cyclodextrin (HPCD), was tested to evaluate its ability to increase the aqueous TCE concentration. Both flushing arrangements may result in similar TCE degradation efficiencies of 35% to 42% estimated by the ratio of TCE degraded/(TCE degraded+TCE remained in effluent) and degradation byproduct chloride generation rates of 4.9 to 7.6 mg Cl(-) per soil column pore volume. The addition of HPCD did greatly increase the aqueous TCE concentration. However, the TCE degradation efficiency decreased because the TCE degradation was a lower percentage of the relatively greater amount of dissolved TCE by HPCD. This conceptual treatment may serve as a reference for potential on-site application.

  14. Dual-frequency tissue harmonic suppression using phase-coded pulse sequence: proof of concept using a phantom.

    Science.gov (United States)

    Shen, Che-Chou; Wang, Hui-Ting

    2013-03-01

    The presence of tissue harmonic generation during acoustic propagation is one major limitation in nonlinear detection of microbubble contrast agents. However, conventional solutions for tissue harmonic suppression are not applicable in dual-frequency (DF) harmonic imaging. In DF harmonic imaging, the second harmonic signal at second harmonic (2f(0)) frequency and the inter-modulation harmonic signal at fundamental (f(0)) frequency are simultaneously generated for imaging and both need to be suppressed to improve contrast-to-tissue ratio (CTR). In this study, a novel phase-coded pulse sequence is developed to accomplish DF tissue harmonic suppression. Phase-coded pulse sequence utilizes multiple firings with equidistant transmit phase for harmonic cancellation in the sum of respective echoes. For the f(0) transmit component, the transmit phase comes from the equidistant set of {-2π/3, 0, 2π/3} to suppress the second harmonic signal at 2f(0) frequency. Moreover, in order to provide the inter-modulation harmonic suppression at f(0) frequency, the 2f(0) transmit phase has to be particularly manipulated for the corresponding f(0) transmit phase. The proposed three-pulse sequence can remove not only the second-order harmonic signal but also other higher-order counterparts at both f(0) and 2f(0) frequencies. Measurements were performed at f(0) equal to 2.25 MHz and using hydrophone in water and contrast agents in tissue phantom. Experimental results indicate that the sequence reduces the tissue harmonic magnitude by about 20 dB along the entire axial depths and the corresponding CTR improves at both frequencies. In DF harmonic imaging, the proposed phase-coded sequence can effectively remove the tissue harmonic background at both f(0) and 2f(0) frequencies for improvement of contrast detection. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Development of a new LAMP assay for the detection of CSFV strains from Cuba: a proof-of-concept study.

    Science.gov (United States)

    Postel, Alexander; Pérez, Lester J; Perera, Carmen L; Schmeiser, Stefanie; Meyer, Denise; Meindl-Boehmer, Alexandra; Rios, Liliam; Austermann-Busch, Sophia; Frias-Lepoureau, Maria T; Becher, Paul

    2015-06-01

    Classical swine fever (CSF) is a devastating animal disease of great economic impact worldwide. In many countries, CSF has been endemic for decades, and vaccination of domestic pigs is one of the measures to control the disease. Consequently, differentiating infected from vaccinated animals by antibody ELISA screening is not applicable. In some countries, such as Cuba, lack of molecular techniques for sensitive, rapid and reliable detection of virus genomes is a critical point. To overcome this problem, an easy-to-use one-tube assay based on the loop-mediated isothermal amplification (LAMP) principle has been developed for detection of the genome of CSF virus (CSFV) of endemic Cuban genotype 1.4 isolates. The assay reliably detected recent isolates from three different regions of Cuba with an analytical sensitivity 10-100 times lower than that of quantitative reverse transcription RT-qPCR. Diagnostic test sensitivity was examined using reference sera from two groups of pigs experimentally infected with Cuban virulent strain CSF0705 "Margarita" and the recent field isolate CSF1058 "Pinar del Rio". Differences in pathogenicity of the two viruses were reflected in the clinical course of disease as well as in virus loads of blood samples. Low viral RNA loads in samples from pigs infected with the field isolate caused serious detection problems in RT-LAMP as well as in RT-qPCR. Thus, it will be necessary in future research to focus on targeted sampling of diseased animals and to restrict diagnosis to the herd level in order to establish LAMP as an efficient tool for diagnosing CSF under field conditions.

  16. iPad technology for home rehabilitation after stroke (iHOME): a proof-of-concept randomized trial.

    Science.gov (United States)

    Saposnik, Gustavo; Chow, Chi-Ming; Gladstone, David; Cheung, Donna; Brawer, Edward; Thorpe, Kevin E; Saldanha, Avon; Dang, Alice; Bayley, Mark; Schweizer, Tom A

    2014-10-01

    Tablets are a novel line of computers controlled by a multitouch screen. Fine motor movements are captured on the tablet computer through electrical fields and can be qualitatively and quantitatively assessed. Evidence is limited on tablet use for stroke rehabilitation. iHOME is an investigator-initiated randomized controlled pilot trial with a single-blinded outcome assessment. The intervention consists of iPad use (investigational group) vs. usual care (control group) among patients receiving conventional outpatient rehabilitation. Eligibility includes aged 18-85 years who experienced a mild ischemic or hemorrhagic stroke (as diagnosed on neuroimaging and determined by the Chedoke-McMaster score ≥3. The STROKE REHAB® software for the iPad was specifically designed for patients with fine motor weakness and/or neglect. Of the total 30 patients, 20 will be in iHOME Acute (enrolled within three-months of stroke onset) and 10 patients in iHOME Chronic (enrolled more than six-months from onset). The primary feasibility outcome is the proportion of the scheduled iPad time used (more than 70% (≥140 mins) of the total 'dose' of intervention intended will be considered successful). Efficacy in fine motor movements will be assessed using the nine-hole peg test; time to magnify and pop the balloons in the iPad software application, and improvement in Wolf Motor Function Test. iHOME is a randomized controlled trial assessing the feasibility, safety, and efficacy of tablet technology for home use in stroke rehabilitation. The results of this study will serve as the basis for a larger multicenter trial. © 2014 World Stroke Organization.

  17. E. coli-Produced BMP-2 as a Chemopreventive Strategy for Colon Cancer: A Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Saravanan Yuvaraj

    2012-01-01

    Full Text Available Colon cancer is a serious health problem, and novel preventive and therapeutical avenues are urgently called for. Delivery of proteins with anticancer activity through genetically modified bacteria provides an interesting, potentially specific, economic and effective approach here. Interestingly, bone morphogenetic protein 2 (BMP-2 is an important and powerful tumour suppressor in the colon and is thus an attractive candidate protein for delivery through genetically modified bacteria. It has not been shown, however, that BMP production in the bacterial context is effective on colon cancer cells. Here we demonstrate that transforming E. coli with a cDNA encoding an ileal-derived mature human BMP-2 induces effective apoptosis in an in vitro model system for colorectal cancer, whereas the maternal organism was not effective in this respect. Furthermore, these effects were sensitive to cotreatment with the BMP inhibitor Noggin. We propose that prevention and treatment of colorectal cancer using transgenic bacteria is feasible.

  18. Use of Mixed Micelles for Presentation of Building Blocks in a New Combinatorial Discovery Methodology: Proof-of-Concept Studies

    Directory of Open Access Journals (Sweden)

    Istvan Toth

    2013-03-01

    Full Text Available We describe a new method of combinatorial screening in which building blocks, instead of being linked together chemically, are placed on the surface of nanoparticles. Two- or three-dimensional structures form on the surface of these particles through the close approach of different building blocks, with sufficient flexibility to be able to adapt and interact with putative binding sites in biological systems. The particles assemble without the need for formation of chemical bonds, so libraries comprised of many structures can be prepared rapidly, with large quantities of material available for testing. Screening methods can include solid and solution-phase binding assays, or tissue culture models, for example looking for structures which can change the behaviour of cells in a disease-modifying manner.

  19. Ultra-high-resolution 3D imaging of atherosclerosis in mice with synchrotron differential phase contrast: a proof of concept study

    Science.gov (United States)

    Bonanno, Gabriele; Coppo, Simone; Modregger, Peter; Pellegrin, Maxime; Stuber, Annina; Stampanoni, Marco; Mazzolai, Lucia; Stuber, Matthias; van Heeswijk, Ruud B.

    2015-07-01

    The goal of this study was to investigate the performance of 3D synchrotron differential phase contrast (DPC) imaging for the visualization of both macroscopic and microscopic aspects of atherosclerosis in the mouse vasculature ex vivo. The hearts and aortas of 2 atherosclerotic and 2 wild-type control mice were scanned with DPC imaging with an isotropic resolution of 15 μm. The coronary artery vessel walls were segmented in the DPC datasets to assess their thickness, and histological staining was performed at the level of atherosclerotic plaques. The DPC imaging allowed for the visualization of complex structures such as the coronary arteries and their branches, the thin fibrous cap of atherosclerotic plaques as well as the chordae tendineae. The coronary vessel wall thickness ranged from 37.4 ± 5.6 μm in proximal coronary arteries to 13.6 ± 3.3 μm in distal branches. No consistent differences in coronary vessel wall thickness were detected between the wild-type and atherosclerotic hearts in this proof-of-concept study, although the standard deviation in the atherosclerotic mice was higher in most segments, consistent with the observation of occasional focal vessel wall thickening. Overall, DPC imaging of the cardiovascular system of the mice allowed for a simultaneous detailed 3D morphological assessment of both large structures and microscopic details.

  20. Auditory-motor mapping training as an intervention to facilitate speech output in non-verbal children with autism: a proof of concept study.

    Directory of Open Access Journals (Sweden)

    Catherine Y Wan

    Full Text Available Although up to 25% of children with autism are non-verbal, there are very few interventions that can reliably produce significant improvements in speech output. Recently, a novel intervention called Auditory-Motor Mapping Training (AMMT has been developed, which aims to promote speech production directly by training the association between sounds and articulatory actions using intonation and bimanual motor activities. AMMT capitalizes on the inherent musical strengths of children with autism, and offers activities that they intrinsically enjoy. It also engages and potentially stimulates a network of brain regions that may be dysfunctional in autism. Here, we report an initial efficacy study to provide 'proof of concept' for AMMT. Six non-verbal children with autism participated. Prior to treatment, the children had no intelligible words. They each received 40 individual sessions of AMMT 5 times per week, over an 8-week period. Probe assessments were conducted periodically during baseline, therapy, and follow-up sessions. After therapy, all children showed significant improvements in their ability to articulate words and phrases, with generalization to items that were not practiced during therapy sessions. Because these children had no or minimal vocal output prior to treatment, the acquisition of speech sounds and word approximations through AMMT represents a critical step in expressive language development in children with autism.

  1. Proof of concept of a method that assesses the spread of microbial infections with spatially explicit and non-spatially explicit data

    Directory of Open Access Journals (Sweden)

    Smith Stephen D

    2008-11-01

    Full Text Available Abstract Background A method that assesses bacterial spatial dissemination was explored. It measures microbial genotypes (defined by electrophoretic patterns or EP, host, location (farm, interfarm Euclidean distance, and time. Its proof of concept (construct and internal validity was evaluated using a dataset that included 113 Staphylococcus aureus EPs from 1126 bovine milk isolates collected on 23 farms between 1988 and 2005. Results Construct validity was assessed by comparing results based on the interfarm Euclidean distance (a spatially explicit measure and those produced by the (non-spatial interfarm number of isolates reporting the same EP. The distance associated with EP spread correlated with the interfarm number of isolates/EP (r = .59, P r = .72, P r = .87, P Conclusion Findings supported both construct and internal validity. Because 3 EPs explained 12 times more isolates than expected and at least twice as many isolates as other EPs did, false negative results associated with the remaining EPs (those erroneously identified as lacking spatial dispersal when, in fact, they disseminated spatially, if they occurred, seemed to have negligible effects. Spatial analysis of laboratory data may support disease surveillance systems by generating hypotheses on microbial dispersal ability.

  2. Persistent Luminescence Nanophosphor Involved Near-Infrared Optical Bioimaging for Investigation of Foodborne Probiotics Biodistribution in Vivo: A Proof-of-Concept Study.

    Science.gov (United States)

    Liu, Yaoyao; Liu, Jing-Min; Zhang, Dongdong; Ge, Kun; Wang, Peihua; Liu, Huilin; Fang, Guozhen; Wang, Shuo

    2017-09-20

    Probiotics has attracted great attention in food nutrition and safety research field, but thus far there are limited analytical techniques for visualized and real-time monitoring of the probiotics when they are ingested in vivo. Herein, the optical bioimaging technique has been introduced for investigation of foodborne probiotics biodistribution in vivo, employing the near-infrared (NIR) emitting persistent luminescence nanophosphors (PLNPs) of Cr(3+)-doped zinc gallogermanate (ZGGO) as the contrast nanoprobes. The ultrabrightness, super long afterglow, polydispersed size, low toxicity, and excellent photostability and biocompatibility of PLNPs were demonstrated to be qualified as a tracer for labeling probiotics via antibody (anti-Gram positive bacteria LTA antibody) recognition as well as contrast agent for long-term bioimaging the probiotics. In vivo optical bioimaging assay showed that the LTA antibody functionalized ZGGO nanoprobes that could be efficiently tagged to the probiobics were successfully applied for real-time monitoring and nondamaged probing of the biodistribution of probiotics inside the living body after oral administration. This work presents a proof-of-concept that exploited the bioimaging methodology for real-time and nondamaged researching the foodborne probiotics behaviors in vivo, which would open up a novel way of food safety detection and nutrition investigation.

  3. A New Proof of Concept in Bacterial Reduction: Antimicrobial Action of Violet-Blue Light (405 nm in Ex Vivo Stored Plasma

    Directory of Open Access Journals (Sweden)

    Michelle Maclean

    2016-01-01

    Full Text Available Bacterial contamination of injectable stored biological fluids such as blood plasma and platelet concentrates preserved in plasma at room temperature is a major health risk. Current pathogen reduction technologies (PRT rely on the use of chemicals and/or ultraviolet light, which affects product quality and can be associated with adverse events in recipients. 405 nm violet-blue light is antibacterial without the use of photosensitizers and can be applied at levels safe for human exposure, making it of potential interest for decontamination of biological fluids such as plasma. As a pilot study to test whether 405 nm light is capable of inactivating bacteria in biological fluids, rabbit plasma and human plasma were seeded with bacteria and treated with a 405 nm light emitting diode (LED exposure system (patent pending. Inactivation was achieved in all tested samples, ranging from low volumes to prebagged plasma. 99.9% reduction of low density bacterial populations (≤103 CFU mL−1, selected to represent typical “natural” contamination levels, was achieved using doses of 144 Jcm−2. The penetrability of 405 nm light, permitting decontamination of prebagged plasma, and the nonrequirement for photosensitizing agents provide a new proof of concept in bacterial reduction in biological fluids, especially injectable fluids relevant to transfusion medicine.

  4. An open and flexible interface proposal and proof of concept implementation to support service orientated architectures and interoperability in the tactical environment

    Science.gov (United States)

    Peach, Nicholas

    2012-06-01

    The development of SOAs in the tactical domain has been hindered by a lack of interface standards suitable for the environment of unpredictable and low bandwidth communications, low powered computers and dynamic ad-hoc grouping of tactical participants. Existing commercial SOA standards have assumed reliable access to central servers and services and having relatively static participants. The proposal describes an open and published message-oriented interface created to support the aims of the upcoming MOD Generic Base Architecture1 (GBA) Defence Standard and the associated Land Open Systems Architecture2. The aims are; a) to support multiple open transport protocols, such as HTTP, SMTP, DDS and MQTT; b) to be suitable for integrating together low-level utility functions with their controlling systems (such as water, waste and power) and integrating together high-level mission-support functions (such as ISTAR and C2); c) reduce operator burden by using automated discovery and configuration where possible; d) dynamically integrate with MOD Generic Vehicle Architecture3 platforms to link base and vehicle mission and logistics systems over tactical radio links; e) extensible to support features such as security classification; f) to be lightweight in implementation and bandwidth and not dependent on central servers for operation. The paper will present the proposed interface and describe the features required for a military tactical rather than a commercial environment, and will report the outcome of a MOD-funded proof of concept that uses the proposed interface to interoperate several military systems.

  5. Enhancing the evaluation of pathogen transmission risk in a hospital by merging hand-hygiene compliance and contact data: a proof-of-concept study

    CERN Document Server

    Mastrandrea, Rossana; Brouqui, Philippe; Barrat, Alain

    2016-01-01

    Hand-hygiene compliance and contacts of health-care workers largely determine the potential paths of pathogen transmission in hospital wards. We explored how the combination of data collected by two automated infrastructures based on wearable sensors and recording (i) use of hydro-alcoholic solution and (ii) contacts of health-care workers provide an enhanced view of the risk of transmission events in the ward. We perform a proof-of-concept observational study. Detailed data on contact patterns and hand-hygiene compliance of health-care workers were collected by wearable sensors over 12 days in an infectious disease unit of a hospital in Marseilles, France. 10837 contact events among 10 doctors, 4 nurses, 4 nurses' aids and 4 housekeeping staff were recorded during the study. Most contacts took place among medical doctors. Aggregate contact durations were highly heterogeneous and the resulting contact network was highly structured. 510 visits of health-care workers to patients' rooms were recorded, with a low...

  6. First Human Use of a Radiopharmaceutical Prepared by Continuous-Flow Microfluidic Radiofluorination: Proof of Concept with the Tau Imaging Agent [18F]T807

    Directory of Open Access Journals (Sweden)

    Steven H. Liang

    2014-10-01

    Full Text Available Despite extensive preclinical imaging with radiotracers developed by continuous-flow microfluidics, a positron emission tomographic (PET radiopharmaceutical has not been reported for human imaging studies by this technology. The goal of this study was to validate the synthesis of the tau radiopharmaceutical 7-(6-fluoropyridin-3-yl-5H-pyrido[4,3-b]indole ([18F]T807 and perform first-in-human PET scanning enabled by microfluidic flow chemistry. [18F]T807 was synthesized by our modified one-step method and adapted to suit a commercial microfluidic flow chemistry module. For this proof of concept, the flow system was integrated to a GE Tracerlab FXFN unit for high-performance liquid chromatography purification and formulation. Three consecutive productions of [18F]T807 were conducted to validate this radiopharmaceutical. Uncorrected radiochemical yields of 17 ± 1% of crude [18F]T807 (≈ 500 mCi, radiochemical purity 95% were obtained from the microfluidic device. The crude material was then purified, and > 100 mCi of the final product was obtained in an overall uncorrected radiochemical yield of 5 ± 1% (n = 3, relative to starting [18F]fluoride (end of bombardment, with high radiochemical purity (≥ 99% and high specific activities (6 Ci/μmol in 100 minutes. A clinical research study was carried out with [18F]T807, representing the first reported human imaging study with a radiopharmaceutical prepared by this technology.

  7. A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults

    Science.gov (United States)

    Mason, Barbara J; Crean, Rebecca; Goodell, Vivian; Light, John M; Quello, Susan; Shadan, Farhad; Buffkins, Kimberly; Kyle, Mark; Adusumalli, Murali; Begovic, Adnan; Rao, Santosh

    2012-01-01

    There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence. A 12-week, randomized, double-blind, placebo-controlled clinical trial was conducted in 50 unpaid treatment-seeking male and female outpatients, aged 18–65 years, diagnosed with current cannabis dependence. Subjects received either gabapentin (1200 mg/day) or matched placebo. Manual-guided, abstinence-oriented individual counseling was provided weekly to all participants. Cannabis use was measured by weekly urine toxicology and by self-report using the Timeline Followback Interview. Cannabis withdrawal symptoms were assessed using the Marijuana Withdrawal Checklist. Executive function was measured using subtests from the Delis–Kaplan Executive Function System. Relative to placebo, gabapentin significantly reduced cannabis use as measured both by urine toxicology (p=0.001) and by the Timeline Followback Interview (p=0.004), and significantly decreased withdrawal symptoms as measured by the Marijuana Withdrawal Checklist (ptreatment of cannabis dependence that merits further study, and provides an alternative conceptual framework for treatment of addiction aimed at restoring homeostasis in brain stress systems that are dysregulated in drug dependence and withdrawal. PMID:22373942

  8. A New Proof of Concept in Bacterial Reduction: Antimicrobial Action of Violet-Blue Light (405 nm) in Ex Vivo Stored Plasma

    Science.gov (United States)

    Maclean, Michelle; Anderson, John G.; MacGregor, Scott J.; White, Tracy

    2016-01-01

    Bacterial contamination of injectable stored biological fluids such as blood plasma and platelet concentrates preserved in plasma at room temperature is a major health risk. Current pathogen reduction technologies (PRT) rely on the use of chemicals and/or ultraviolet light, which affects product quality and can be associated with adverse events in recipients. 405 nm violet-blue light is antibacterial without the use of photosensitizers and can be applied at levels safe for human exposure, making it of potential interest for decontamination of biological fluids such as plasma. As a pilot study to test whether 405 nm light is capable of inactivating bacteria in biological fluids, rabbit plasma and human plasma were seeded with bacteria and treated with a 405 nm light emitting diode (LED) exposure system (patent pending). Inactivation was achieved in all tested samples, ranging from low volumes to prebagged plasma. 99.9% reduction of low density bacterial populations (≤103 CFU mL−1), selected to represent typical “natural” contamination levels, was achieved using doses of 144 Jcm−2. The penetrability of 405 nm light, permitting decontamination of prebagged plasma, and the nonrequirement for photosensitizing agents provide a new proof of concept in bacterial reduction in biological fluids, especially injectable fluids relevant to transfusion medicine. PMID:27774337

  9. Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: A proof of concept study in healthy subjects.

    Science.gov (United States)

    de Gunzburg, Jean; Ducher, Annie; Modess, Christiane; Wegner, Danilo; Oswald, Stefan; Dressman, Jennifer; Augustin, Violaine; Feger, Céline; Andremont, Antoine; Weitschies, Werner; Siegmund, Werner

    2015-01-01

    During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial flora resulting in the emergence of resistance. To prevent these effects, we developed an enteric-coated formulated activated-charcoal based product, DAV132, meant to deliver its adsorbent to the ileum and neutralize antibiotic residues in the proximal colon. In a randomized, control, crossover study, the plasma pharmacokinetics of the probe drugs amoxicillin (500 mg) absorbed in the proximal intestine, and sulfapyridine (25 mg) metabolized from sulfasalazine in the cecum and rapidly absorbed, were compared after a single administration in 18 healthy subjects who had received DAV132, uncoated formulated activated charcoal (FAC) or water 16 and 8 hours before, concomitantly with the probe drugs, and 8 hours thereafter. The AUC0-96 h of amoxicillin was reduced by more than 70% when it was taken with FAC, but bioequivalent when it was taken with water or DAV132. By contrast, the AUC0-96 h of sulfapyridine was reduced by more than 90% when administered with either FAC or DAV132 in comparison with water. The results show that DAV132 can selectively adsorb drug compounds in the proximal colon, without interfering with drug absorption in the proximal small intestine, thereby constituting a proof of concept that DAV132 actually functions in humans.

  10. Using Video Conferencing to Deliver a Brief Motivational Intervention for Alcohol and Sex Risk to Emergency Department Patients: A Proof-of-Concept Pilot Study.

    Science.gov (United States)

    Celio, Mark A; Mastroleo, Nadine R; DiGuiseppi, Graham; Barnett, Nancy P; Colby, Suzanne M; Kahler, Christopher W; Operario, Don; Suffoletto, Brian; Monti, Peter M

    2017-01-01

    Brief motivational intervention (MI) is an efficacious approach to reduce heavy drinking and associated sexual risk behavior among Emergency Department (ED) patients, but the intensity of demands placed on ED staff makes the implementation of in-person MIs logistically challenging. This proof-of-concept pilot study examined the acceptability and logistic feasibility of using video-conferencing technology to deliver an MI targeting heavy drinking and risky sexual behavior to patients in an ED setting. Rigorous screening procedures were employed to ensure that the pilot sample represents the target portion of ED patients who would benefit from this multi-target MI. Mixed qualitative and quantitative data from a sample of seven ED patients (57% Female; Mage = 35 years) who received MI by video conference consistently demonstrated high levels of satisfaction, engagement, and acceptability. The observed completion rate supports logistic feasibility, and patient feedback identified methods to improve the experience by using high-definition hardware, ensuring stronger network connectivity, and effectively communicating information regarding protection of privacy. Post-intervention patient ratings and independent ratings of the audio-recorded sessions (using the Motivational Interviewing Skills Coding system) were very high, suggesting that intervention fidelity and MI adherence was not compromised by delivery modality. Collectively, these data suggest video conferencing is a viable technology that can be employed to implement brief evidence-based MIs in ED settings.

  11. A Proof of Concept to Bridge the Gap between Mass Spectrometry Imaging, Protein Identification and Relative Quantitation: MSI~LC-MS/MS-LF

    Science.gov (United States)

    Théron, Laëtitia; Centeno, Delphine; Coudy-Gandilhon, Cécile; Pujos-Guillot, Estelle; Astruc, Thierry; Rémond, Didier; Barthelemy, Jean-Claude; Roche, Frédéric; Feasson, Léonard; Hébraud, Michel; Béchet, Daniel; Chambon, Christophe

    2016-01-01

    Mass spectrometry imaging (MSI) is a powerful tool to visualize the spatial distribution of molecules on a tissue section. The main limitation of MALDI-MSI of proteins is the lack of direct identification. Therefore, this study focuses on a MSI~LC-MS/MS-LF workflow to link the results from MALDI-MSI with potential peak identification and label-free quantitation, using only one tissue section. At first, we studied the impact of matrix deposition and laser ablation on protein extraction from the tissue section. Then, we did a back-correlation of the m/z of the proteins detected by MALDI-MSI to those identified by label-free quantitation. This allowed us to compare the label-free quantitation of proteins obtained in LC-MS/MS with the peak intensities observed in MALDI-MSI. We managed to link identification to nine peaks observed by MALDI-MSI. The results showed that the MSI~LC-MS/MS-LF workflow (i) allowed us to study a representative muscle proteome compared to a classical bottom-up workflow; and (ii) was sparsely impacted by matrix deposition and laser ablation. This workflow, performed as a proof-of-concept, suggests that a single tissue section can be used to perform MALDI-MSI and protein extraction, identification, and relative quantitation. PMID:28248242

  12. A Proof of Concept to Bridge the Gap between Mass Spectrometry Imaging, Protein Identification and Relative Quantitation: MSI~LC-MS/MS-LF.

    Science.gov (United States)

    Théron, Laëtitia; Centeno, Delphine; Coudy-Gandilhon, Cécile; Pujos-Guillot, Estelle; Astruc, Thierry; Rémond, Didier; Barthelemy, Jean-Claude; Roche, Frédéric; Feasson, Léonard; Hébraud, Michel; Béchet, Daniel; Chambon, Christophe

    2016-10-26

    Mass spectrometry imaging (MSI) is a powerful tool to visualize the spatial distribution of molecules on a tissue section. The main limitation of MALDI-MSI of proteins is the lack of direct identification. Therefore, this study focuses on a MSI~LC-MS/MS-LF workflow to link the results from MALDI-MSI with potential peak identification and label-free quantitation, using only one tissue section. At first, we studied the impact of matrix deposition and laser ablation on protein extraction from the tissue section. Then, we did a back-correlation of the m/z of the proteins detected by MALDI-MSI to those identified by label-free quantitation. This allowed us to compare the label-free quantitation of proteins obtained in LC-MS/MS with the peak intensities obse